In a recent study we demonstrated that low birth weight (LBW) was associated with increased risk of progressive IgA nephropathy (IgAN). In the present study we investigate whether this could be explained by differences in glomerular morphological parameters.2 at time of diagnosis were eligible for inclusion. Patients were included in a case-control manner based on whether or not they had LBW or were small for gestational age (SGA). Glomerular area, volume and density were measured using high resolution digital images and differences were compared between groups.The Medical Birth Registry of Norway has registered all births since 1967 and the Norwegian Kidney Biopsy Registry has registered all kidney biopsies since 1988. Patients diagnosed with IgAN, registered birth weight and estimated glomerular filtration rate above 60 ml/min/1.73m2, p-value 0.04). This was significant for total cohort and male but not female. On separate analysis by gender, glomerular area was significantly larger only in males . Glomerular density was not different between groups. In adjusted linear regression analysis, glomerular area was negatively associated with birth weight.We included 51 IgAN patients with a mean age of 23.6 years, 47.1% male. Compared to IgAN patients without LBW or SGA, IgAN patients with LBW and/or SGA had larger glomerular area  contains supplementary material, which is available to authorized users. Brenner and co-workers suggested that adverse intrauterine environment, for example due to placental insufficiency or maternal undernutrition, was associated with impaired nephron development and increased risk of hypertension and progressive kidney disease in adult life . BirthweIgA nephropathy (IgAN) is the most frequent primary idiopathic glomerulonephritis worldwide –12 and hSeveral previous autopsy-based stereological and histomorphometric studies have reported strong correlations between LBW and reduced glomerular numbers as well as increased glomerular volume –19. A prIn the present study we aimed to investigate how LBW and SGA in IgAN patients associate with specific glomerular morphological changes compared to IgAN without LBW and SGA. We hypothesized that LBW and SGA would be associated with fewer and larger glomeruli in line with the Brenner hypothesis but that the effects of LBW and SGA could be different. In our previous study cited above, associations were stronger in males, so gender differences were also investigated in the present study.Since 1967, the Medical Birth Registry of Norway has registered extensive medical data on all births in Norway  . The NorThe regional ethics committee of Western Norway gave clearance for the study (2013/553), participants were asked for consent by mail.LBW was defined as birth weight less than the 10th percentile for gender  in the study population of our previous study . From 19Maternal pregestational disease was defined as maternal rheumatic disease, renal disease, diabetes mellitus or hypertension diagnosed before pregnancy and reported at birth to the Medical Birth Registry . Materna2 were set to 150 ml/min/1.73m2. Proteinuria (grams/24 h), systolic and diastolic blood pressure measurements (mmHg) at time of biopsy were all used as continuous variables.The following clinical variables at the time of kidney biopsy were used in the present study; estimated glomerular filtration rate (eGFR), calculated using the IDMS-traceable CKD-EPI equation . All pat2 at time of biopsy and did not develop ESRD during follow-up . The last two criteria were chosen to ensure that during selection, our study population comprised of patients with lowest risk of progressive IgAN population at the time of biopsy . Power calculations were based on extrapolations from two human studies which had published measurements of glomerular size in relation to birth weight [2 as normal controls; this control group was age-and-sex matched with the group of IgAN cases without LBW or SGA; 19 patients in this control group had available tissue and were included.We selected cases and controls from patients registered in the described registries . The digital images were viewed in Imagescope . We recorded the total number of glomeruli, the number of glomeruli with mesangial hypercellularity, endocapillary hypercellularity, global sclerosis, segmental sclerosis and tubular atrophy as defined by the Oxford classification for IgAN and a MEST score was calculated . The ann3/2x β/d; where GV = glomerular volume, GA = glomerular tuft area, β = 1.38  and d is a size distribution coefficient that is used to adjust for the variation in glomerular size; we used d = 1.01 as adopted from other studies [For estimating glomerular volume we used the Weibel-Gomez formula expressed as GV = (GA) studies –31. The P < 0.05 was considered statistically significant, and all tests were 2 tailed. Analyses were performed using the SPSS version 21 .Birth weight related parameters were used as exposure variables whereas histopathological and histomorphometric parameters were used as outcome variables. In the primary analyses, outcome variables were compared between the four sub-groups with IgAN described above; in further analyses all groups with LBW and/or SGA were combined. Also, IgAN patients without LBW or SGA were compared to control patients. Continuous variables were tested for normal distribution  and compared using student t-tests while categorical variables were compared using Chi-square tests. Linear regression statistics were used to determine the association between glomerular area and birthweight-related variables and clinical variables. In the primary analysis (model 1) we adjusted for diagnostic group (IgA nephropathy vs control) as the study sample consisted of these two separate groups. In the secondary analysis (model 2) we further adjusted for gender and age at biopsy. If not otherwise stated, values are reported as mean ± standard deviation; 2. At the time of kidney biopsy, patients without LBW or SGA had comparable clinical characteristics to patients with LBW and/or SGA  were males. Mean age at biopsy was 23.6 years and mean eGFR was 95.3 ml/min/1.73m2, p-value 0.004). Further analyses stratified by gender showed that glomerular area was significantly larger only in males  but not in females . Glomerular density was not different between groups. In a sensitivity analysis, we tested whether including only patients with 9 glomeruli or more [2, p-value 0.04).As shown in Table N = 18) to a matched group of control patients with normal biopsies (N = 19). As shown in Table p-value 0.002). There were no significant differences between birth weight-related and glomerular histomorphometric characteristics observed between the two groups but there was a non-significant trend towards larger glomeruli in IgAN patients.To investigate whether development of IgAN altered glomerular area, we compared results for patients with IgAN who did not have LBW or SGA  but not in the primary model 1 analysis. Furthermore, maternal pre-eclampsia, gender and age at biopsy were significantly associated with glomerular area in both model 1 and 2 analyses, whereas body weight, BMI and eGFR at biopsy associated with glomerular area only in model 1 analysis


ABP) at brain level, change in the cerebral venous outflow path, lowered end‐tidal COP2 (ETCOP2), and intracranial pressure (ICP) modify cerebral blood flow (CBF). The question we undertook to answer is whether gravity‐induced blood pressure (BP) changes are compensated in CBF with the same dynamics as are spontaneous or induced ABP changes in a stable position. Twenty‐two healthy subjects  were subjected to 30° and 70° head‐up tilt (HUT) and sinusoidal tilts . Additionally, at those three tilt levels, they performed paced breathing at 6–15 breaths/min to induce larger than spontaneous cardiovascular oscillations. We measured continuous finger BP and cerebral blood flow velocity (CBFv) in the middle cerebral artery by transcranial Doppler to compute transfer functions (TFs) from ABP‐ to CBFv oscillations. SinTilt induces the largest ABP oscillations at brain level with CBFv gains strikingly lower than for paced breathing or spontaneous variations. This would imply better autoregulation for dynamic gravitational changes. We demonstrate in a mathematical model that this difference is explained by ICP changes due to movement of cerebrospinal fluid (CSF) into and out of the spinal dural sack. Dynamic cerebrovascular autoregulation seems insensitive to how BP oscillations originate if the effect of ICP is factored in. CSF‐movement in‐and‐out of the spinal dural space contributes importantly to orthostatic tolerance by its effect on cerebral perfusion pressure.Standing up elicits a host of cardiovascular changes which all affect the cerebral circulation. Lowered mean arterial blood pressure ( Standing up in the morning might be the most audacious deed of the day. It forces the circulation to adapt to the demands of gravity, most importantly to provide sufficient pressure for brain perfusion. Among the cardiovascular adaptations, the increased systemic vascular resistance (SVR) figures most prominently Rowell . In the The dynamics of the fast component of autoregulation is generally defined by measurement of the transfer function (TF) from blood pressure to cerebral flow changes. For this measurement, the subject is kept in one position in relation to gravity, for example, lower body negative pressure (LBNP)  spontaneous blood pressure to blood flow velocity oscillations in three body positions: supine, passive upright at 30° (0.5G), and tilted to 70° , (2) by paced breathing in those three positions, thereby inducing larger than normal blood pressure oscillations, and (3) by a series of sinusoidal tilt frequencies from supine to almost upright around the 30° position.Our test battery includes TF measurement from 2, and (2) the TF obtained by sinusoidal tilt is substantially different (in terms of gain and phase) due to the concurrent dynamic changes in hydrostatics of the venous and cerebrospinal fluid columns. Furthermore, we hypothesized that in the TF from sinusoidal tilt the lowest frequencies might deviate, since their time course would allow superimposed changes in activity of the autonomic nervous system and/or of pCO2 levels.We hypothesized that (1) the TF's from blood pressure to cerebral blood flow, measured in the three stable body positions, are similar, possibly differing by a scale factor due to the prevailing contractile state of the vasculature and concomitant changes in end‐tidal pCOFinally, in view of the clinical use of quantifying the TF from blood pressure to cerebral blood flow, we compared the various measures  and ways of measuring them for stability and reproducibility.In total, 22 healthy subjects  aged 40 ± 8 years, height 177 ± 9 cm, and weight 72 ± 11 kg participated in the study. Of the 22, seven were NASA astronauts destined for a shuttle flight and five ESA cosmonauts who would fly in the Soyuz capsule to the ISS for a short stay in Space. All participants were nonsmokers and were free of known cardiovascular and cerebrovascular disorders. Of the 22 subjects, eight underwent the whole protocol a second time after 12 months, enabling us to test the reproducibility over time of the various measurements.The procedures were explained in detail, in written form and orally, before each subject signed the informed consent form. The protocol was approved by the Medical Ethics Committee of the Academic Medical Center, University of Amsterdam and, where appropriate, by the NASA and/or ESA medical review boards.All experiments were conducted in our laboratory at the Academic Medical Center location of the University of Amsterdam. Subjects were in the postprandial state after a light meal and had refrained from alcohol and caffeine for more than 12 h. The room was quiet and dimly lit at a temperature around 22°C. The subject was lying on the tilt table for the whole protocol, supported by a footboard, which was conveniently angled to 98° rather than 90° to prevent overstretching the calf muscles or forcing the ankle in an uncomfortable position. The procedures started with a few test tilts and breathing procedures to familiarize the test subject with the tilt movement and paced breathing. Figure paced breathing (PB) at 10, 6, and 15 per min, in that order, each for 1 min plus two extra breaths. Pacing was by audio cue: tone going up for inspiration, going down for expiration (40/60) followed by a short expiratory pause; the subject was instructed to only adhere to the cue for inspiration, and not to hyper‐ or hypoventilate, by keeping a LED bar indicating end‐tidal pCO2 (PETCO2) within his/her normal limits.The first series of tests was in the supine position: 5‐min resting, then The second series was in the 30° head‐up tilted (HUT) position, 5‐min resting recording, then PB, followed by sinusoidal tilts (SinTilt) around 30° at 2.5, 4, 6, and 10 per min, moving between 0° and +60°, each for 2 min, followed by 1‐min rest. To avoid synchronization of respiration to the tilt maneuvers, breathing was paced by audio cue at 13 per min; this continued for the duration of the tilt and resting maneuvers. The tilt angle plotted in time describes a sine between 0° and 60° at the given frequencies. A version of the SinTilt‐protocol has been used in an earlier publication from this laboratory  was monitored (Hewlett Packard monitor 78345A). Carbon dioxide was sampled continuously from the nose and measured using a capnometer .Continuous noninvasive ABP was measured at the finger by a Finometer™ . The finger was held at the estimated level of the aortic valve throughout the procedures, the hand supported by a sling. Cerebral blood flow velocity (CBFv) was measured in the middle cerebral artery (MCA) by transcranial Doppler (TCD) . The probe was immobilized by a head band. The distance between aortic valve level and TCD probe was measured to calculate hydrostatic pressure‐corrected ABP at the brain level from the tilt angle: ABP2, and the tilt angle were analog‐to‐digital converted at 100 Hz. Offline, beat‐to‐beat values of systolic, diastolic, and mean blood pressure, as well as the corresponding systolic, diastolic, and mean CBFv values were calculated, after low‐pass filtering the raw CBFv signal to a frequency of 15 Hz. The mean ABP (MAP) and CBFv (mCBFv) were computed as the integral over one beat. During a posture change, hydrostatic arterial pressure at the brain level will change by an amount ρgh*sin(α), where ρ is the density of blood, g the gravitational acceleration, h the vertical distance to the position of the heart, and α denotes the angle of tilt. The distance h was measured individually. To compensate for differences in travel time of the pressure wave from the heart to the brain and from the heart to the finger, the finger pressure wave was shifted 60 ms back in time, and then the continuously computed hydrostatic pressure difference was subtracted to derive ABPbrain. PETCO2 was derived from the CO2 in‐ and expiration curve.Finger blood pressure, the envelope of the TCD spectral curve, ECG, expiratory COData segments of episodes of baseline rest, paced breathing, and tilting at each particular frequency were selected. At each tilt position, 3.5 min of recorded rest was used for spectral analysis. Ectopic beats were replaced by interpolation.for the rest periods standard Fourier Transform was used of beat‐to‐beat MAPbrain and mCBFv. For this, the 3.5 min of data were spline interpolated and resampled at 4 Hz; the resulting 840 points data segment was linearly detrended and Hanning‐windowed. Power spectra were then computed by a discrete Fourier Transform (Matlab® FFT routine). Resulting spectra were smoothed by a 7‐point triangular window. Linearity of the system and reliability of the transfer function estimation were evaluated by the coherence. Gain and phase relations for spontaneous oscillations were only included in further analysis for parts of the spectra with sufficiently high levels of coherence . To account for intersubject variability in mCBFv, the TF gain was normalized by dividing the transfer function gain (cm/sec per mmHg) of a data segment by its average mCBFv (cm/sec), expressing it as %/mmHg. Phase is defined as positive where mCBFv leads MAPbrain. The periods of paced breathing were introduced to force sufficient variability at a number of set frequencies to better define the cerebrovascular transfer function. Since paced breathing has a tendency to induce changes in PETCO2, we kept the periods as short as feasible, while on the other hand still getting sufficient data for a good spectral resolution.Two methods of transfer function analysis were applied: ETCO2 was not exactly constant during the forced oscillations (PB and SinTilt); therefore, gain and phase relations were computed for those cases by fitting an autoregressive (ARX) model with MAPbrain as input and PETCO2 as extra (exogenous) input , where ICP changes during tilt were estimated from the beat‐to‐beat estimated critical closing pressure using the method of “first harmonics” extrapolation of the pressure and flow signal  were calculated from ANOVA models using SPSS Statistics V24 and the method described by Shrout and Fleiss  are presented in Table ETCO2 is decreasing. CO decreases at +30° and remains unaltered at +70°, and SVR increases at +30° and still further at +70°.v during the SinTilt maneuvers. Figure brain to mCBFv in the three positions: supine, 30° HUT tilt, and 70° HUT tilt. The solid black line represents the overall averaged cross‐spectral results for those parts of the 3*22 spectra where coherence between MAPbrain and mCBFv was statistically significant. The open symbols are the results of the paced breathing and the closed symbols those of the SinTilt maneuvers. Striking is the similarity between the full spectral curves and how well the paced breathing data fit in. In the region from 0.05 Hz to 0.25 Hz, the curves behave as expected for a high‐pass dynamic autoregulation system . However, the SinTilt data do not fit this picture: the same phase behavior, but about two‐thirds of the gain. This would imply that the cerebral autoregulation (CAR) is somehow better able to filter out BP oscillations due to changes in gravitational load in the chosen frequency range. It was not explained by concurrent changes in PETCO2 . Second, the movement of cerebrospinal fluid (CSF) between the cerebral and spinal compartments was considered to cause ICP changes during a posture change. Incorporation of the ICP variations into the ARX model brought the SinTilt data (both for gain and phase) more or less in line with the other measurements as shown in Figure Figure cf. Fig. , since tcf. Fig. , resultecf. Fig.  model fobrain to CBFv, we have reduced the individual curves underlying Figure ETCO2 and ICP are summarized in Figure We have demonstrated three methods to define the dynamic autoregulatory capacity of a person's cerebral circulation. Which one is best to apply? This “best” method must fulfill at least two requirements: (1) it should give reproducible results over time and 2) it can be applied without much patient involvement. To make a good comparison for the three ways to define the transfer from ABP it can bOut of the 22 subjects, eight have participated in the whole procedure a second time, around 1 year after the first measurement. We have marked these eight in Figure Journal of Physiology, Drs. Simpson and Claassen defended the view that dynamic CAR should be quantified using induced blood pressure oscillations  cf. Figure Not many studies have used dynamic changes in gravitational load to study the effect on cerebral blood flow. In 2001, Hughson et al.  changes of body posture might shed more light on the individual capacity to autoregulate cerebral blood flow. The results of these studies were to help predict orthostatic intolerance after challenges like (short‐lasting) space flight. Part of this intolerance has been attributed , where other factors may come into play.We set out to test CAR during an orthostatic challenge and used dynamic tilt maneuvers as a novel method, expecting it to differ from more classical methods to define the transfer from ABPOf the methods that were tested for their use in the measurement of CAR, we found that sinusoidal tilt, relatively, gave the best reproducible results. Moreover, this technique can be applied without extensive subject cooperation and it lends itself to investigating very low frequencies with a high degree of precision.2 feedback, fixed respiration), still the CO2 levels were not exactly constant during SinTilt, contributing to the spread in results.The study has a limited (22) number of mainly male participants . This is explained by the study design, where the group of astronauts/cosmonauts  was to be complemented with a control group of roughly the same size and composition. In spite of the precautions which we took to get “ideal” responses (COETCO2 during tilt movements may not express the full extent of arterial CO2 (Immink et al. As in all studies where TCD of one main cerebral artery is used to estimate cerebral blood flow, we have to assume that the various interventions did not influence vessel diameter to such an extent that it would invalidate our interpretation. Furthermore, the observed changes in PIn the present paper, we focused on the reactions of CBFv to changes in cerebral perfusion pressure, taking the blood pressure, as it were, for granted. The analysis of how blood pressure was maintained in the various tests is outside the scope of this paper and requires a study of its own. However, the sympathetic part of blood pressure control may have influenced the cerebral vessels (Zhang et al. None declared.


The number of patients with type 2 diabetes has increased in Japan, and type 2 diabetes has attracted attention as a risk factor for asthma. However, the risk factors for the development of asthma in patients with type 2 diabetes have not been determined. This study was performed to clarify whether visceral fat accumulation (VFA) and insulin resistance are risk factors for the development of asthma in patients with type 2 diabetes.  A cross-sectional study was conducted. The study group comprised 15 patients with type 2 diabetes with asthma, and the control group comprised 145 patients with type 2 diabetes without asthma. Their fat distribution was evaluated by measuring the VFA by abdominal computed tomography at the umbilical level. Their glucose status was assessed by measuring the fasting plasma glucose (FPG) concentration, fasting immunoreactive insulin concentration, homeostasis model assessment (HOMA) index, and hemoglobin A1c concentration. P < 0.0001). The FPG concentration, fasting immunoreactive insulin concentration, and HOMA index were higher in patients with asthma than those without asthma . Multiple logistic regression analysis showed that VFA and the HOMA index were significantly associated with asthma in patients with type 2 diabetes .  Among patients with type 2 diabetes, VFA was significantly greater in patients with asthma than those without asthma ( Our data suggest that VFA and insulin resistance are associated with the development of asthma in patients with type 2 diabetes. The number of patients with type 2 diabetes has increased in Japan , and typBoth asthma and obesity are common clinical problems that often coexist in the same patient, and epidemiologic studies have consistently demonstrated that obesity is a risk factor for asthma , 4. IndiCentrally located body fat is now generally considered to be more important than regional or generalized obesity in the development of metabolic syndrome. Metabolic syndrome comprises several risk factors for cardiovascular disease, including insulin resistance, hyperinsulinemia, dyslipidemia, obesity, diabetes mellitus, and hypertension , 10.Although abdominal computed tomography (CT) can be used to precisely assess visceral fat accumulation (VFA), this technique is expensive; therefore, measurement of either the waist circumference or body mass index (BMI) is widely used . VFA is We hypothesized that the presence of asthma is associated with VFA and insulin resistance in patients with type 2 diabetes. To test this hypothesis, we measured the blood pressure (BP), lipid concentrations, metabolic profile, and degree of VFA  in Japanese patients with type 2 diabetes either with or without asthma. We then determined the independent predictors of asthma in these patients.We screened 282 Japanese patients with type 2 diabetes mellitus who were consecutively admitted to Oita Red Cross Hospital from April 2007 to March 2017. Of these, 160 patients (83 men and 77 women) with a mean age of 56 ± 7 years fulfilled the inclusion criteria and were enrolled in the study. The inclusion criteria were as follows: no underlying causes of secondary hypertension ; no history of chronic disease, such as renal failure (creatinine concentration of >1.5 mg/dl), pulmonary disease, liver dysfunction (aspartate aminotransferase concentration of >50 IU/l), arteriosclerosis obliterans, sleep apnea syndrome, or symptomatic cerebrovascular disease; not currently receiving treatment with insulin; and absence of organic heart disease according to treadmill exercise electrocardiography. Patients with an ST-T abnormality were also excluded.In total, 122 of the screened patients were excluded from further analysis. Of those excluded, 52 patients were being treated with insulin, 18 had renal failure, 12 had angina pectoris, 10 had symptomatic cerebrovascular disease, 9 had sleep apnea syndrome, 8 had secondary hypertension , 7 had arteriosclerotic obliterans, and 6 had liver dysfunction (3 with hepatitis B and 3 with hepatitis C). The remaining 160 patients were enrolled in the study.The study was conducted according to the principles in the Declaration of Helsinki. All patients provided written informed consent to participate in the study, and the study protocol was approved by the ethics committee of Oita Red Cross Hospital.β2 agonist. Nine of 15 patients were using salmeterol/fluticasone, and the remaining 6 were using budesonide/formoterol. Asthma attacks were well controlled using these inhaled corticosteroid/long-acting β2 agonist combinations. No patients had experienced severe asthma attacks within the previous few months, and none had been administered oral or systemic corticosteroids.Asthma was considered to be present if the medical records contained a diagnosis of asthma made by a pulmonary specialist, based on a history of intermittent wheezing in combination with bronchodilator and/or methacholine responsiveness . All 15 Essential hypertension was defined as a mean systolic BP of ≥140 mmHg, mean diastolic BP of ≥90 mmHg, or self-reported use of antihypertensive medication . BP was μU/ml) × FPG (mmol/l))/22.5.Blood was extracted from an antecubital vein with the patient in the recumbent position at 07:00, after an overnight fast. All patients underwent routine laboratory testing, including measurements of serum electrolytes, serum total cholesterol, serum triglycerides, serum high-density lipoprotein cholesterol (HDL-C), fasting plasma glucose (FPG), and fasting immunoreactive insulin (F-IRI). Dyslipidemia was defined as a fasting triglyceride level of ≥200 mg/dl or HDL-C concentration of <45 mg/dl for women and <35 mg/dl for men . InsulinAll patients underwent CT for cross-sectional measurement of abdominal VFA at the umbilical level, determined using Fat scan version 3 software  as previously described . This CTThe patients' anthropometry and body composition were evaluated using the following parameters: height, body mass, BMI, and waist circumference. BMI was calculated as weight in kg/squared height in m. Waist circumference was measured midway between the lower rib and the iliac crest on the midaxillary line at the end of a gentle expiration with the patients in a standing position.P < 0.05. Student's t-test was used for continuous variables, and the chi-square test was used for categorical variables. Logistic regression analysis was used to assess the influence of explanatory variables on asthma, where the explanatory variables were age, sex, BMI, VFA, waist circumference, duration of diabetes, hypertension, dyslipidemia, BP, heart rate, total cholesterol, triglycerides, HDL-C, FPG, F-IRI, HOMA index, hemoglobin A1c, uric acid, C-reactive protein (CRP), and creatinine. Sex, hypertension, and dyslipidemia were dichotomized as 1 (presence) or 0 (absence) by cut-off values defined in the previous section. The presence of asthma was represented as 1, and the absence of asthma was represented as 0. A backward elimination procedure was employed to identify the significant factors among all the explanatory variables considered. All statistical analyses were performed using a standard statistical package .All data are presented as mean ± standard deviation for two groups of patients: those with asthma and those without asthma . For eacPatients with type 2 diabetes mellitus were classified into two groups based on the presence or absence of asthma. Fifteen patients with type 2 diabetes (9.4%) had asthma and 145 (90.6%) did not.P < 0.0001). The BMI and waist circumference were also higher in patients with asthma than those without asthma . The mean ages of the patients in each group were similar, and there were no significant differences in sex, the duration of diabetes, or the medication administered between the two groups.As shown in P = 0.0232 and P < 0.0001, respectively), whereas the serum total cholesterol concentration was similar in the two groups. With regard to glucose metabolism, the FPG concentration, fasting insulin concentration, and HOMA index were higher in patients with asthma than those without asthma .With regard to lipid metabolism, the serum triglyceride concentration was higher and the serum HDL-C concentration was lower in patients with asthma than those without asthma (P = 0.0060). However, there were no significant differences in the CRP or hemoglobin A1c concentration. Regarding renal function, there was no significant difference in the serum creatinine concentration between the groups.The serum uric acid concentration was higher in patients with asthma than those without asthma (P = 0.0126), VFA , waist circumference , and triglyceride concentration ; a lower HDL-C concentration ; and a higher FPG concentration , F-IRI , HOMA index , and uric acid concentration . All of these were dependent lipid and glucose metabolic parameters in patients with type 2 diabetes , 1.23; 95% confidence interval (CI), 1.04–1.53; diabetes .P = 0.0115) and the HOMA index  as significant independent risk factors for asthma in patients with type 2 diabetes , and monocyte chemoattractant protein 1 (MCP-1) [α, and MCP-1) originate from obese adipose tissue and that the levels of these mediators are associated with the degree of insulin resistance [α in the bronchoalveolar lavage fluid of patients with asthma and elevated concentrations of plasma MCP-1 in patients with concurrent asthma and type 2 diabetes have been observed, and a relationship between these cytokines and asthma, including airway inflammation and remodeling, has been reported [The underlying pathophysiological mechanisms of the association between asthma and insulin resistance are not understood. In our opinion, several possible mechanisms exist. One is that both asthma and insulin resistance are derived from a generalized proinflammatory state. Data from animal and human studies have shown that obesity leads to a systemic proinflammatory state as indicated by higher plasma concentrations of various inflammatory markers, including CRP, interleukin 6 (IL-6), tumor necrosis factor  (MCP-1) –33. We p (MCP-1) . In addisistance , 36. Morreported , 38.1 is an important measure of asthma control [1, VFA, insulin resistance, and the presence of asthma in patients with type 2 diabetes. Finally, several reports have indicated that rhinitis, sinusitis, and gastroesophageal reflux disease are associated with the development or severity of asthma [The present study has several limitations. First, we studied a relatively small sample, and the study was cross-sectional in design. Sixty-three percent of the patients with asthma and 67% of the patients without asthma had been previously diagnosed with essential hypertension. All of these patients were being treated with one or more antihypertensive drugs, including angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and calcium channel antagonists, prior to enrollment. All three of these drug classes have been reported to ameliorate insulin resistance , 40; the control . Furtherf asthma . In the In conclusion, our findings suggest that asthma in patients with type 2 diabetes is associated with both abdominal VFA and insulin resistance. Large cohort studies, including studies of other populations, should be conducted in an attempt to corroborate these findings.


We investigated the impact of short-acting and extended release nifedipine on sympathetic activity using radiotracer methodology in patients with stable coronary artery disease in order to more accurately document the response of the sympathetic nervous system to different formulations of this dihydropyridine calcium channel antagonist. Participants were randomized to placebo, short-acting or extended release nifedipine for 7–10 days. On the final day, systemic blood pressure, cardiac filling pressures, cardiac output, plasma norepinephrine (NE) and total body NE spillover were measured at baseline (time 0) and repeated at intervals for 6 hours. There were no differences in baseline measures between groups. Following the morning dose of study medication there were no changes in hemodynamics or sympathetic activity in the placebo group. However, there was a significant fall in blood pressure and a significant increase in total body NE spillover in both nifedipine groups. Importantly, the increase in sympathetic activity in response to short-acting nifedipine began earlier (30 minutes) and was much greater than that observed in the extended release group, which occurred later (270 minutes). These findings confirm that sustained therapy with nifedipine is associated with activation of the sympathetic nervous system which is dependent on the pharmacokinetics of the formulation. A number of studies have examined the impact of dihydropyridine calcium channel antagonists on the sympathetic nervous system using a variety of methods including plasma and/or urinary norepinephrine (NE) concentrations11, heart rate variability17, microneurography24 and, in a few cases, radiotracer measures of total body NE spillover26. Following acute dosing, a number of studies documented activation of the sympathetic nervous system29 but others have not31. In the setting of chronic therapy with dyhydropyridine calcium antagonists, some32, but not all33 studies reported continued sympathetic activation. Some studies documented differential effects on the sympathetic nervous system responses in young versus older patients34. This subject area was recently the subject of a detailed review35. Of note, the majority of these studies were carried out in normal volunteers or patients with hypertension. Only a small number of studies focussed on patients with known coronary artery disease38.Calcium channel antagonists play an important role in the management of hypertension and angina. Since their introduction into clinical practice there has been interest in their pharmacokinetic and pharmacodynamics related to the different dihydropyridines and effects on the sympathetic nervous system40. Although subsequent large scale clinical studies demonstrated the cardiovascular safety of these drugs42, there has been continued interest in their impact on sympathetic activity.Interest in the dihydropyridine calcium channel blockers for treating hypertension and angina is based on their potent vasodilatory activity. Interest in the autonomic responses to the dihydropyridine calcium channel antagonists stems from the known adverse effects of sympathetic activation in a number of disease states including heart failure and coronary artery disease. This interest was heightened after reports by Furberg and colleagues that therapy with calcium channel antagonists had adverse effects on clinical outcome in patients with coronary artery diseaseThe majority of studies have employed plasma concentrations of NE to assess the response of the sympathetic system with mixed results. The fundamental limitation of this approach is that changes in NE clearance as well as its release can alter plasma concentration of the amine. As such, changing plasma NE concentrations are not reliable as measures of sympathetic activity. Therefore, in the current study we employed radiotracer NE kinetic methods to examine the impact of therapy with short-acting nifedipine capsule and extended release nifedipine GITS, as compared to placebo, on sympathetic activity in a cohort of patients with coronary artery disease all of who were receiving concomitant therapy with a beta-blocker.This was a single-centre study designed to compare the pharmacokinetic, pharmacodynamic and sympathetic nervous system responses to two different formulations of the dihydropyridine calcium antagonist nifedipine. This protocol was approved by the Ethical Review Committee for Human Experimentation of the University of Toronto (Protocol Reference Number 1640). Written informed consent was obtained in all cases. This research was carried out in accordance with relevant guidelines including the International Council for Harmonization and the Declaration of Helsinki.Study participants included 40 patients with known coronary artery disease. and a history of stable angina. None had experienced an acute coronary syndrome or revascularization procedure within 3 months of their participation in the study. All patients had preserved left ventricular systolic dysfunction with an ejection fraction ≥45 percent by two-dimensional echocardiography and none had a history of congestive heart failure.All participants were taking either atenolol (25–50 mg daily) or metoprolol (25–75 mg twice daily). Patients previously treated with a calcium channel antagonist had those medications discontinued for at least 10 days prior to randomization. No patient was treated with long acting oral or transdermal nitrates. The use of sublingual nitroglycerin on an as needed basis was permitted but no patient received sublingual nitroglycerin on the day that study measurements were acquired.Patients were randomized to receive drug in a blinded manner using a double-dummy technique for allocation to placebo (n = 9), short-acting nifedipine 10 mg, TID (n = 16) or extended release nifedipine Gastrointestinal Therapeutic System (GITS) 60 mg, OD (n = 15). These medications were continued for 7–10 days. On the final day of the study, participants were admitted to the Cardiovascular Clinical Research Laboratory at 0800 hours prior to their morning dose of study medication.Study procedures were carried out without sedation. Instrumentation was as follows: (1) using a right femoral venous approach a Swan-Ganz catheter was placed in the pulmonary artery, and (2) an arterial line was place in the right femoral artery for monitoring of arterial pressure and blood sampling. The Fick method was used to estimate cardiac output. At each time point heart rate (determined from the electrocardiogram), right atrial, pulmonary artery and femoral artery pressure were recorded. For all pressure measurements an average of 15 cardiac cycles was determined and the results expressed as the mean value.3H]NE; New England Nuclear, Boston, MA) as previously described by Esler et al. and prior reports from our laboratory44. NE spillover rates were calculated from the following equations:Total body sympathetic activity was estimated using the NE spillover technique using a bolus followed by a constant infusion of tritiated NE  were then carried out. After control, hemodynamic and neurochemical measurements patients received their morning doses of double-blind study medication . Subsequently hemodynamics and cardiac output were repeated every 30 minutes for the next 6 hours. Blood sampling for catecholamines and plasma nifedipine concentrations were carried out at control (time 0) and at 30, 60, 90, 120, 270, 300, 330 and 360 minutes post study medication. Plasma atrial natriuretic peptide, the concentration of active plasma renin and endothelin-1 were measured at control as well as 60, 180 and 300 minutes post study medication.Baseline characteristics were compared using a two-way analysis of variance (ANOVA) with treatment  as factor for continuous variables while the Fisher’s exact test was used to compare categorical variables. Changes in hemodynamic, neurochemical and nifedipine concentrations within and between groups over time were assessed using a two-way repeated measures analysis of variance with treatment  as factor. This analysis allowed us to determine whether there was a significant change in measured variables over time and whether this time effect varied by treatment group . The relationship between plasma nifedipine concentrations, total body NE spillover and mean arterial blood pressure was assessed using simple linear regression. Statistical analyses were carried out in Prism 8, MacOS, version 8.2.1.Baseline characteristics of the 3 groups can be found in Table After administration of short-acting nifedipine there was a rapid increase in plasma nifedipine concentrations which peaked at the 30 minute time point and remained elevated for 120 minutes  formulation, is associated with sympathetic activation as compared to those treated with placebo. At baseline, following 7–10 days of therapy, total body NE spillover was similar in the 3 treatment groups. However, total body NE spillover rose immediately after the subsequent dose of short-acting nifedipine and this increase persisted for the next 6 hours. In contrast, after the morning dose of nifedipine GITS, total body NE spillover increased, although this increase did not begin until 3–4 hours following subsequent dosing. As such, this study demonstrates that both short-acting and extended release formulation of nifedipine GITS are associated with increases in total body NE spillover, the time course of which is dependent upon their individual pharmacokinetic and pharmacodynamic characteristics. Importantly, the magnitude of sympathetic activation in response to short-acting nifedipine is greater than that observed in the extended release preparation reflecting the very abrupt fall in blood pressure caused by the short-acting preparation.46, although others reported no change in this variable47. Some studies used measurement of peripheral muscle sympathetic nerve activity as a more direct measure of sympathetic responses. Some of these studies demonstrated an increase in muscle sympathetic activity in response to nifedipine24 although no change was observed on other reports18. These discordant results likely reflect differences in dose, formulation and study design.Prior studies examining the impact of therapy with nifedipine GITS on measures of the sympathetic nervous system have yielded contradictory results. Many of these studies involved patients with hypertension and there were significant differences in terms of study design, formulation of drug, dose and measures of sympathetic activity. Most of these studies used plasma NE as a marker for changes in sympathetic activity. Some demonstrated the plasma NE was increased during acute and/or sustained therapy with nifedipine GITS43.Importantly, this is the first report using radiotracer methodology to examine the impact of nifedipine on the activity of the sympathetic nervous system. This approach allows for measurement of total body NE spillover which is an integrated summation of sympathetic activity in all vascular beds. This approach provides a measurement which accounts for both changes in production and clearance of NE. As such, it provides a more specific estimate of changes in sympathetic activity than measures of plasma NE, the concentration of which can be changed by both changes in its production and clearance. Indeed, we have previously demonstrated that changes in NE clearance are directly proportional to changes in cardiac output and that plasma NE can remain unchanged despite an increase in total body NE spillover in situations where there is a concurrent increase in NE clearance24. Although the microneurographic technique does provide a direct measure of efferent nerve traffic to skeletal muscle, sympathetic activity to this vascular bed may not be representative of changes in sympathetic activity to other vascular beds. Further, measures of efferent post-ganglionic firing frequency cannot anticipate the prejunctional regulation of NE release from sympathetic nerve terminals.As mentioned above, some studies with various formulations of nifedipine have reported different effects of nifedipine on muscle sympathetic nerve activity38. To date, our observations represent the most comprehensive assessment of the effects of nifedipine in both short-acting and extended release formulations in patients with stable coronary artery disease. However, it is important to emphasize that patients in the current study were all receiving therapy with a beta-1 selective beta-blocker (either atenolol or metoprolol). In prior reports of the effects of nifedipine on sympathetic nervous system responses other vasoactive medications, including beta-blockers were either not given or withdrawn prior to study measurements. It is possible that ongoing adrenergic receptor blockade may explain the sympathetic activation observed in the current study. For example, by limiting the heart rate response to the vasodilator effect of nifedipine, ongoing beta-blockade could have enhanced arterial baroreceptor mediated increases in sympathetic responses. Nevertheless, since most patients with coronary artery disease receive beta-blockers, our observations are representative of the real-world use of nifedipine in this population. This was the case in the ACTION study where nifedipine GITS was shown to be safe in patients with stable coronary artery disease. In that study, 80 percent of patients were treated with concomitant beta-blockers41.The current observations were made in patients with stable coronary artery disease with well-preserved left ventricular systolic function and no history of congestive heart failure. There have been only limited prior reports of the sympathetic responses to nifedipine in patients with stable coronary artery disease. These studies used plasma NE as a marker of sympathetic responses with, as in studies with hypertension, inconsistent resultsThere was a significant positive correlation between the change in plasma nifedipine concentration and the change in total body sympathetic activity. This almost certainly results from the effect of increasing plasma concentrations on systemic arterial blood pressure. In fact, there was a highly significant negative correlation between increasing plasma concentrations of nifedipine and the resulting decrease in systemic arterial blood pressure. Of note, most of these changes were mediated by the large changes in plasma nifedipine concentrations that occurred following the administration of the short-acting formulation of nifedipine. Nevertheless, there was a significant correlation between absolute nifedipine concentrations  and total body sympathetic activity. These observations serve as an explanation for the observation that in the extended release nifedipine group, the decrease in blood pressure and an increase in total body NE spillover occurred at 270 minutes. These changes occurred in parallel with an increase in plasma nifedipine concentration that occurred over the same time period. Therefore, it appears that both the hemodynamic and neurochemical responses to nifedipine are closely linked to changes to changes in plasma concentrations of nifedipine.42. Finally, our study confirms that the use of short-acting nifedipine is associated with abrupt decreases in systemic arterial blood pressure and greater reflex increases in activity of the sympathetic nervous system which serve to emphasize that short-acting formulations of dihydropyridine antagonists should be avoided in patients with cardiovascular disease.Therefore, this study demonstrates that daily therapy with nifedipine, in both short-acting and extended release formulations is associated with evidence of increased generalized activity of the sympathetic nervous system as assessed the radiotracer NE kinetics. The time course of this activation varies in a manner which is consistent with the pharmacokinetics of the respective formulations. The clinical significance of these findings is unclear, as long-term outcome studies have documented the safety of extended release nifedipine in patients with both hypertension and chronic coronary artery disease. It should be noted that in the ACTION study, which demonstrated the safety of Nifedipine GITS in patients with stable coronary artery disease, 80 percent of enrolled patients were taking a beta-adrenergic blocker. Given the potential adverse effects of sustained increases in sympathetic activity in patients with cardiovascular disease, the current study suggests that when patients with coronary artery disease are treated with nifedipine, concurrent therapy with a beta-adrenergic blocking agent should be used whenever possible. Furthermore, less than 50 percent of these patients had concomitant hypertension and it is possible that the sympathetic responses to nifedipine would be different in a cohort of patients all of whom had hypertensionThe study protocol and data presented in this manuscript are available upon request from the corresponding author.


Patients with CKD have high rates of complications and comorbidities. Thus, they require the prescription of numerous medications, making the management of patients very complex. The prescription of numerous drugs associated with an altered renal- and non-renal clearance makes dose adjustment challenging in these patients, with frequent drug-related adverse events. However, the mechanisms involved in this abnormal drug clearance during CKD are not still well identified. We propose here that the transcription factor, aryl hydrocarbon receptor, which is the cellular receptor for indolic uremic toxins, could worsen the metabolism and the excretion of drugs in CKD patients.Chronic kidney disease (CKD) is a major public health problem, since 300,000,000 people in the world display a glomerular filtration rate (GFR) below 60 mL/min/1.73m A persistent GFR below 60 mL/min/1.73 m2 (stage 3) indicates a moderate loss of kidney function. In stage 5, GFR is lower than 15 mL/min/1.73m2, due to the kidney failure; these patients require chronic dialysis treatment or kidney transplantation .Chronic kidney disease (CKD) incidence has increased in recent years, and the global prevalence is estimated to be 8% to 16% . The gloCardiovascular disease (CVD) is the main cause of death in patients with CKD. The cardiovascular mortality rate is 10 to 30 times higher than in the general population ,9. KidneSince patients with CKD have high rates of complications and comorbidities, there is a relevant impact on medication administration. Specific and related complications of CKD increase the need fordrug intake, so the dose adequacy is difficult to identify and drug side effects are more frequent ,23,24. A2), and it plays an important role in controlling the drug’s biological activity. Reactions in phase I are mainly led by the cytochrome P450 (CYP) superfamily of microsomal enzymes. These DME are expressed abundantly in the liver, gastrointestinal tract, kidney, and lung ,UDP-glucuronosyltransferase 1A1 [UGT1A1], UGT1A3, UGT1A4, UGT1A7, UGT1A10, and glutathione S-transferase A1 [GSTA1]  ,132,133.d by AhR ,136,137.CYP1A2, whose activity is monitored by its probes—caffeine and theophylline—is among the major CYPs in the liver, and accounts for about 13% of the total CYP proteins in this organ ,139. In Colchicum autumnale) binds tubulin and inhibits the polymerization dynamics of microtubules. The taxane paclitaxel (from Taxus baccata) stabilizes microtubules by binding to polymeric tubulin. The resulting effect of these two molecules is to stop cell mitosis. Pheophorbide a, found in algae and plants, induces phototoxicity. Thus, these multidrug transporters were and are highly precious to preserve the hunter-gatherers that we were in the past. While these transporters are used to extrude mainly chemical compounds derived from plants, their very wide specificity lead them to handle drugs, and to be considered now as the main players of the multidrug resistance process (MDR) [About the drug transporters, MRP4, BCRP, and P-gp are increased upon AhR activation. They belong to the ABC-binding cassette transporters, which extrude from the cell a wide variety of chemical exogenous compounds, in order to fulfill detoxification functions and protect the organism against their toxic effects ,160,161.ss (MDR) ,162. Extss (MDR) , and couss (MDR) . Among tss (MDR) . LAT1 isss (MDR) . In vitrss (MDR) ,168,169,ss (MDR) , intestiss (MDR) , and plaIn conclusion, AhR, by its target genes, seems to play a role in drug metabolism, and could constitute a link between CKD and altered drug clearance. The modulation of its activity could be proposed as a possible and future potential target to modulate drug clearance in patients. Its level of activation in vivo, evaluated by a Callux assay, could help clinicians to adjust the dosage of some drugs. Further works are necessary to prove the usefulness of this approach in the care of patients with CKD.


Laparoscopic abdominal surgery has been widely used to reduce the length of hospital stay and complications from open abdominal surgery. During the operation, the creation of pneumoperitoneum is used for better visualization of the operating field. However, the effect of pneumoperitoneum on kidney function is unknown. We aimed to identify risk factors and predictors associated with AKI development following laparoscopic abdominal surgery.A single-center prospective cohort study of laparoscopic abdominal surgery patients between June 2012 and December 2013. Acute kidney injury (AKI) was identified by Kidney Disease Improving Global Outcome (KDIGO) criteria. Urinary neutrophil gelatinase associated lipocalin (uNGAL) was measured on the first 3 days after surgery as a surrogate marker of AKI.p = 0.045, and 2325.9 vs 1866.1 mmHg-minutes, p = 0.035). Operation time, mean intra-abdominal pressure, duration of intraoperative hypotension, amount of blood loss and intravenous fluid were not different between groups. In multivariable analysis adjusted for age, diabetes, baseline estimated glomerular filtration rate, and type of operation , exposure index was significantly associated with postoperative AKI, with odds ratio (95% CI) 1.47 (1.05–2.04), p = 0.024. By combining the intraoperative parameters with clinical model the area under the receiver operating characteristic curve was 0.71 (95% CI 0.58–0.84).Of the 64 patients, 23 (35%) developed postoperative AKI. The mean age, initial blood pressure, and initial glomerular filtration rate were not different between AKI and non-AKI groups. Inflation time and exposure index were significantly higher in the AKI group compared to non-AKI group  contains supplementary material, which is available to authorized users. This key process can induce many physiological changes especially in renal function [Laparoscopic abdominal surgery has been widely used in the past few decades. Compared to open surgery, it has various benefits such as small incision, less postoperative pain, reduced length of hospital stay, early mobilization, and shorter recovery period –3. One o2-induced pneumoperitoneum [2 insufflation and, after desufflation, renal blood flow returned to its pre-insufflated state. Further, a pig study from Kirsch and colleagues [2 pneumoperitoneum and renal function is still lacking.In animal experiments, different studies have found conflicting results when identifying physiological changes of renal function from COritoneum –7.Chiu aritoneum , in a salleagues  reportedlleagues  and Ali In this study, we aimed to examine the role of intraoperative parameters on predicting acute kidney injury (AKI) following laparoscopic abdominal surgery.This was a single-center prospective cohort study performed at King Chulalongkorn Memorial Hospital, Bangkok, Thailand between June 2012 and December 2013.2) and patients on non-steroidal anti-inflammatory drugs (NSAIDs) 1 week before surgery, because peri-operation kidney function might be affected. All patients received the standard treatment for postoperative care including fluid management and hemodynamic optimization). Every patient received standard dose of inhaled anesthetic agent with the maximum dose at 1.3 minimal alveolar concentration. We used age, dose of nitrous oxide, hemodynamic status, body temperature, and intraoperative opioid dose to adjust the dose of inhaled anesthetic agents. Intraoperative CO2 inflation was limited at 15 mmHg.Eligible participants were adults aged 18 years or older, with American Society of Anesthesiologist (ASA) status between I and III, who underwent laparoscopic abdominal surgery for at least 2 h, long enough to impact kidney function . ExclusiThe study was approved by The Institutional Review Board (IRB No. 393/55), Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. All participants accepted the protocol, and provided written informed consent.Blood samples for measurement of serum creatinine and urine samples for testing urine neutrophil gelatinase associated lipocalin levels (uNGAL) were serially obtained at five time points from the start of surgery: 0, 6, 24, 48 and 72 h. We measured uNGAL using ELISA technique . Furthermore, we collected and measured urine output (UO) every 30 min during the operation period, and on days 1, 2 and 3 after operation.2 inflation. Intra-abdominal pressure was the average pressure after the creation of pneumoperitoneum by CO2 inflation. Exposure index, the new parameter, was the product of inflation time and intra-abdominal pressure. Intraoperative hypotension was defined by the mean arterial pressure (MAP) < 65 mmHg during surgery.We collected patient demographic data, pre-operative clinical characteristics, co-morbid conditions  and ASA status. We also collected intraoperative data including type of operation , type of inhaled anesthetic agents, operation time, inflation time, intra-abdominal pressure, exposure index, duration of intraoperative hypotension, amount of blood loss, amount of intravenous fluid administered and UO. Operation time was defined as the duration of the procedure from the initiation of skin incision to the completion of skin closure according to anesthesia records. Inflation time was the time after the creation of pneumoperitoneum by COAKI was diagnosed using standard Kidney Disease Improving Global Outcomes (KDIGO) criteria . HoweverBody weight on admission was used for calculating the rate of urine flow per kilogram per hour. For AKI staging patients were assigned to their worst KDIGO category according to either serum creatinine or UO.p < 0.05. Comparisons between groups were performed with Fisher’s Exact test for categorical variables and using Student’s t-Test or Kruskal-Wallis one-way analysis of variance by ranks for continuous variables. Categorical data is summarized as counts and percent. Continuous data is summarized as mean (standard deviation) or median . For comparison of serum creatinine and urine NGAL between AKI and Non-AKI groups over the follow-up times , we used multivariable mixed model adjusted for age, diabetes status, urological surgery status and also the clustering effect from repeated measurements within patients.Statistical analyses were performed using STATA version 15.0, with statistical significance set at We used unadjusted and adjusted logistic regression to individually test the association between the three main exposure variables  and AKI development. Risk factors considered for adjustment were priori risk factors including age, diabetes, baseline eGFR and type of operation . For analyses of developing AKI prediction, Area under the receiver operating characteristic (AUC-ROC) curve and reclassification analyses were used to measure the predictive performances of each models. The optimal cutoff points were determined by the largest sum of sensitivity and specificity.2, and another was on NSAIDs 1 week before surgery. Therefore, 64 patients were included in the study  1.01 (0.41) vs 0.78 0.30) mg/dL, 0 mg/dL, p = 0.045. Similarly, mean exposure index was significantly higher in AKI as compared to non-AKI patients: 2325.9 (1083.5) vs. 1806.1 (827.7) mmHg-min, p = 0.035. However, intra-abdominal pressure was not different between groups. In addition, duration of intraoperative hypotension, amount of blood loss, intravenous fluid and intraoperative urine output were not different between groups , exposure index was the risk factors of AKI development with the OR of 1.47 per 500 exposure index increment, 95% CI 1.05–2.04, 48 Table . While t48 Table .Table 4A> 60%, respectively. We then compared the proportions of reclassified subjects across each of these three risk groups when intraoperative parameters was added to the clinical prediction model. Among 23 patients who had AKI, 26.1% were reclassified as increased risk of when intraoperative parameters was added to the clinical prediction model and 22.0% were reclassified as lower risk. Among 41 non-AKI patients, 12.2% were reclassified as increased risk for AKI whereas 22% were reclassified as lower risk for AKI. There was no overall significant improvement in reclassification among AKI and non-AKI when intraoperative parameters were combined with clinical model (net reclassification index (NRI) 14.1%, p = 0.41). However, using the relative IDI, the reclassification of risk of AKI improved by 1.8% when intraoperative parameters were combined with clinical model (p = 0.025).We also assessed the capability of intraoperative parameters , subjects were categorized into pre-specified ‘low’, ‘intermediate’, and ‘high’ risk of AKI Table  using cuThe present single-center prospective cohort study in patients who underwent laparoscopic abdominal surgery shows that AKI is a common condition. This study demonstrated the association between inflation time and exposure index with AKI following laparoscopic abdominal surgery. Our results indicate that high exposure index is a significant predictor for AKI in this setting.The incidence of AKI in our study was 35.9% which is higher than in previous studies. For example, Sharma et al. found th2 inflation time and intra-abdominal pressure in the occurrence of oliguria and AKI. Interestingly, prolonged time of CO2 inflation shown as exposure index and CO2 inflation time alone were associated with AKI  and patients with chronic kidney disease were excluded thus better isolating the effect of pneumoperitoneum on AKI occurrence.Admittedly, our study has some limitations. First, the study design was as a single-center prospective cohort study and generalizing the findings would require validation in a larger study. Second, the sample size was rather small. Therefore, the recommendation for further studies in larger populations is still warrant. Third, for an adjusted logistic regression to test the association between the three main exposure variables  and AKI development, we chose the priori risk factors for adjustment including age, diabetes, baseline eGFR and type of operation , not from the univariate analysis .AKI following laparoscopic abdominal surgery was a common condition which could occur transiently. By limiting the inflation time and exposure index perioperative renal dysfunction could be reduced. In our study, exposure index has been proposed as a novel predictor of laparoscopic abdominal surgery associated AKI. However, a large randomized controlled trial is needed to prove this concept.Additional file 1:Table S1. Diagnostic criteria for AKI in the AKI patients. (DOCX 18 kb)


Performing a kidney biopsy is necessary to accurately diagnose diseases such as glomerulonephritis and tubulointerstitial nephritis, among other such conditions. These conditions predispose patients to chronic kidney disease, as well as acute kidney injury (AKI). Notably, most epidemiological studies describing AKI have not investigated this patient population.Included patients admitted to the nephrology ward of a tertiary hospital who underwent percutaneous kidney biopsy. AKI was diagnosed based on the Kidney Disease: Improving Global Outcomes criteria.p = 0.048). Focal segmental glomerulosclerosis was the most prevalent primary disease . Multivariate analysis of risk factors associated with AKI showed hemoglobin levels , serum high-density lipoprotein cholesterol levels , and baseline serum creatinine levels  were significantly associated with AKI.Of the 223 patients investigated, 140 (62.8%) showed AKI. Of these, 91 (65%), 19 (13.6%), and 30 (21.4%) presented with AKI classified as stages 1, 2, and 3, respectively. The primary indication for performing biopsy was nephrotic syndrome or nephrotic proteinuria (73 [52.1%] in the AKI vs. 51 [61.4%] in the non-AKI group, We observed a high prevalence of AKI in hospitalized patients who underwent kidney biopsy to investigate their renal disease, particularly glomerulonephritis. Higher levels of hemoglobin and serum HDL-c were associated with a lower risk of AKI. Acute kidney injury (AKI) is a risk factor for the development of chronic kidney disease (CKD) and chronic end-stage renal disease (ESRD). AKI is also associated with increased short- and long-term mortality rates . AKI is In contrast, some kidney diseases such as glomerulonephritis and tubulointerstitial nephritis, among other such clinical conditions require histopathological analysis of kidney tissue specimens to accurately determine diagnosis, disease activity and chronicity , 4. NotaTherefore, we investigated the prevalence and risk factors associated with AKI in hospitalized patients who underwent kidney biopsy for histopathological diagnosis.This was a retrospective cohort study, included patients admitted to the Nephrology ward of Hospital São Paulo, Universidade Federal de São Paulo, São Paulo, Brazil. Patients were eligible if submitted to percutaneous kidney biopsy performed with aged ≥16 years as indicated by the nephrologists. Exclusion criteria were kidney transplant recipients. In our center, all percutaneous native kidney biopsies were performed in patients admitted exclusively to the nephrology ward. We did not perform native kidney biopsy in outpatient setting. Data were obtained, between January 2008 and December 2014, from patients’ medical records and the electronic hospital database. The follow-up period underwent 12-month after the kidney biopsy.We analyzed the following variables: age, sex, race, body mass index (BMI), major comorbidities such as hypertension, diabetes mellitus (DM), cancer, cardiovascular disease , and systemic lupus erythematosus (SLE).We evaluated the use of diuretics, antibiotics, statins, angiotensin-converting enzyme inhibitors (ACEI), and/or angiotensin receptor blockers (ARB), nonsteroidal anti-inflammatory drugs (NSAID), and contrast media . Previous use of corticosteroids was also recorded.Indications for renal biopsy were nephrotic syndrome , or nephrotic-range proteinuria (proteinuria ≥3.5 g/24 h), rapidly progressive glomerulonephritis , sub-nephrotic proteinuria (isolated proteinuria > 1.0 g/24 h), dysmorphic hematuria associated with some grade of proteinuria, renal dysfunction if unknown origin, and renal manifestations of systemic diseases.The following parameters were evaluated upon admission: hemoglobin, serum sodium, potassium, ionic calcium, phosphorus, and albumin levels, pH and bicarbonate levels, serum total cholesterol and its fractions, serum triglycerides, serum creatinine and urea levels, as well as 24-h urinary protein excretion. The glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease Study Group (MDRD) equation .All patients underwent kidney and urinary tract ultrasonography. The length of the kidneys was recorded in all patients.Optical microscopy analysis and immunofluorescence studies were performed for histopathological diagnostic confirmation as well electron microscopy, when indicated. All analysis was performed by a single renal pathologist.We evaluated the serum creatinine level upon admission, during hospitalization, and specific time-points after discharge until 12 months after the kidney biopsy. The reading that showed the lowest level during hospitalization was considered the baseline serum creatinine level because laboratory data prior to hospitalization were unavailable. The highest serum creatinine level during hospitalization was used to diagnose AKI.We defined and classified AKI observed during hospitalization based on the Kidney Disease: Improving Global Outcomes (KDIGO) criteria using only serum creatinine levels . AKI wasThe following outcomes were assessed: kidney function , need for dialysis initiation, and mortality within 12 months after kidney biopsy.Data were expressed as mean and standard deviation for normally distributed variables and as median and quartiles (25–75%) for variables showing non-normal distribution. Parametric distribution was confirmed using the Shapiro-Wilk test. We used the Student’s t-test or the Mann-Whitney test for numerical variables and the Chi-square test for comparison between nominal variables.For covariance analyze repeated measures of creatinine and for intergroup comparison of data, we used the Generalized Estimation Equations and applied the autoregressive structure correlation matrix  and gammp < 0.05) were subjected to multivariate logistic regression analysis for variables such as age and sex.Variables that were significantly associated with AKI on univariate analysis  was used for statistical analysis.A p = 0.508). Patients with AKI were older than patients without AKI  with similar BMI . Most patients were white in both groups .The study included 267 patients, of which 44 (16.5%) patients were diagnosed with ESRD during admission and were excluded from the study. Of the remaining patients (N = 223), 140 (62.8%) were diagnosed with AKI during hospitalization. No significant intergroup difference was observed in sex , patients with CVD , and patients with a history of cancer . DM was more prevalent in the AKI group .No statistically significant differences were observed between the AKI and non-AKI groups, respectively in the percentage of patients with hypertension . Additionally, a larger number of patients in the AKI group received a potentially nephrotoxic antibiotic . No statistically significant difference was observed between the AKI and non-AKI groups with respect to the use of diuretics , statins , NSAIDs , and corticosteroids . No patient underwent contrast examination during hospitalization.A lower percentage of patients in the AKI group used ACEIs/ARBs , renal dysfunction of undetermined etiology , and hematuria with non-nephrotic-range proteinuria . RPGN was an indication exclusively in the AKI group .The primary indications for renal biopsy were nephrotic-range proteinuria or nephrotic syndrome . The primary diagnoses were focal segmental glomerulosclerosis (FSGS)  and minimal change disease (MCD) . Secondary diseases predominated in the AKI group . SLE was the main cause of secondary renal disease, with classes III and IV being the most prevalent , serum urea , serum bicarbonate , and serum HDL-c . No statistically significant intergroup difference was observed in renal length.Laboratory data and measurements of renal length are presented in Table (p < 0.001) across the entire follow-up period. Compared with peak levels during admission, we observed a decrease in serum creatinine levels in the AKI group after 12 months (p < 0.05).Table Among patients diagnosed with AKI (62.8%), 91 (65.0%) were classified as showing stage I disease, 19 (13.6%) as stage 2, and 30 (21.4%) as stage 3 disease.Dialysis was performed in 19 (8.5%) patients in the AKI group and of these 19, 9 4.0%) remained dependent on dialysis therapy at the time of discharge. All patients were dialysis-free at the end of 12 months. Notably, 8 patients (3.6%) died and 5 of them died of infections during hospitalization. Table .0% remaiThis study showed a high prevalence of AKI in hospitalized patients who underwent kidney biopsy for renal disease primarily caused by glomerulonephritis. Most patients showed primary renal disease, and the most common indications for renal biopsy were nephrotic-range proteinuria or nephrotic syndrome. Among the primary diseases, FSGS showed the highest prevalence. Among all secondary diseases, lupus glomerulonephritis was the most common.2) based on KDIGO criteria may miss the occurrence of AKI in the community [Epidemiological studies investigating AKI should necessarily describe patients’ baseline serum creatinine levels. In this study, we defined the lowest serum creatinine level during hospitalization as an estimate of baseline renal function, given the lack of previous values. Retrospective baseline serum creatinine levels . Despite the long-term protective effect of ACEI/ARB in renal diseases in patients with proteinuria, their use may cause acute and reversible renal dysfunction, particularly when used concomitantly with diuretics and in patients with other conditions causing hypovolemia , 9. InteProteinuria and low serum albumin levels are risk factors for AKI , 14. ThiPre-existing kidney dysfunction serves as an independent risk factor for AKI in conditions such as sepsis and contrast-induced nephropathy, as well as in patients undergoing cardiac surgery or solid organ transplantation, and in patients admitted to the ICU –22. ThisAnemia and AKI are occasionally associated. A few studies have shown anemia serves as an independent risk factor for AKI –28. PrevIn our study, we observed a higher level of serum hemoglobin was associated with a lower incidence of AKI. Several studies have shown an association between anemia and AKI; however, it is unclear whether higher levels of serum hemoglobin could reduce the incidence of AKI. It could be deduced that early intervention, for example, through the use of recombinant human erythropoietin, could reduce the risk of AKI in specific diseases, such as in glomerulonephritis. Previous studies have shown the role of erythropoietin in patients admitted to the ICU and in those undergoing cardiac surgery was controversial and in a few cases the benefit was independent of hematocrit and serum hemoglobin levels .Altered lipid metabolism is common in patients with renal disease, particularly in those with glomerulonephritis and nephrotic syndrome. Hypercholesterolemia and hypertriglyceridemia are the most common findings in such cases; however, low serum HDL-c levels may occur. Resolution of nephrotic syndrome usually tends to reverse these changes .HDL-c possesses antioxidant properties, thereby reducing endothelial damage and the risk of atherosclerosis . The MDRIn our cohort, we observed an association between higher levels of serum HDL-c and lower incidence of AKI. We inferred perhaps intensive drug therapy for dyslipidemia in addition to exercise and dietary strategies could improve patients’ lipid profile and consequently reduce the incidence of AKI, particularly in patients with glomerulonephritis.The following are the limitations of our study:  The lackWe observed a high prevalence of AKI in hospitalized patients who underwent kidney biopsy to investigate their renal disease, particularly glomerulonephritis. Higher levels of hemoglobin and serum HDL-c were associated with lower risks of AKI.


Lastly, being Korean versus Filipino reduced the odds of being in the highly active category . Based on predictive probabilities, Koreans and Filipinos with high blood pressure were more likely to belong in the low active PA category (52.31% and 46.33%). These findings highlight the need for culturally relevant PA interventions for promoting and increasing PA levels to prevent and manage hypertension among these populations.Physical activity (PA) serves a critical role in maintaining health and preventing chronic diseases, though its influence on high-risk Asian American populations is unclear. The purpose of this study was to determine PA levels among Filipino and Korean Americans at high risk of hypertension and to identify sociodemographic and health-related factors associated with PA levels in these populations. A cross-sectional survey was administered to 137 participants in the Greater Philadelphia Area. Data was collected on PA levels, sociodemographic factors, and health factors. Multinomial logistic regression was conducted to determine predictors associated with low, moderate, and high PA and predictive probabilities were calculated for interaction terms, incorporating ethnicity and blood pressure variables. Overall, 42.33% of participants belonged to the moderately active PA group and 21.90% belonged to the highly active group. In the final multinomial regression model, it was found that having gone to college increased the odds of being in the moderately active PA group (coef. = 1.96,  Filipinos and Korean Americans constitute two important Asian immigrant populations in the United States (U.S.). Within the last decade, due to increased awareness of disparities when disaggregating Asian Americans into subgroups, their health status has become a public health priority in the U.S. . HighligIt is well established that physical activity (PA) is a critical component of a healthy lifestyle and plays an important role in the prevention of chronic conditions, including cardiovascular disease, hypertension, specific cancers, hyperlipidemia, and type 2 diabetes . HoweverPhysical activity participation is viewed as an important component of maintaining weight and preventing obesity related chronic disease ,24. SubsThe purpose of this study was: (1) to determine PA levels among Filipinos and Korean Americans who are at high risk of hypertension, and (2) to determine what sociodemographic and health-related factors are associated with PA levels among Filipino and Korean Americans. This study presents baseline findings for interventions addressing sodium consumption and PA health education in Koreans and Filipinos in the Greater Philadelphia and Southern New Jersey Areas.The study data was collected through a cross-sectional survey that was administered to Filipino and Koreans living in the Greater Philadelphia and Southern New Jersey Areas who underwent an educational intervention to reduce sodium consumption and increase PA levels. Measures were taken at baseline and only reported in this paper. The baseline surveys were administered by staff members, with Korean participants receiving a survey in Korean. The survey took 15−20 minutes to complete. Inclusion criteria were: (1) self-identifying as Filipino or Korean, (2) being at least 18 years of age, (3) having resided in the Greater Philadelphia Area in the past year, and (4) not having previously participated in a health educational lifestyle or hypertension intervention.Participants were 71 Filipino−Americans and 66 Korean−Americans adults recruited through 5 community-based organizations (CBOs) and churches in the Greater Philadelphia Area from September 2016–May 2017. There was a total number of 137 participants. The mean average blood pressure taken at baseline among our participants for systolic was m = 133.24 mmHg, SD = 17.56 and for diastolic values m = 75.50 mmHg, SD = 9.85. We used the OMRON IntelliSense® Blood Pressure Monitor model HEM 907XL  to measure systolic blood pressure and diastolic blood pressure levels. The study coordinator placed the appropriately sized cuff around the bare upper right arm so that the midpoint of the length of the cuff laid over the brachial artery and the mid-height of the cuff was at heart level. Three blood pressure and pulse measurements were taken and the average of the three readings was recorded.Physical activity was measured using the International Physical Activity Questionnaire short form (IPAQ−short). The IPAQ−short is a 7-item self-administered questionnaire used to measure physical activity levels in young and middle-aged adults from various populations . The IPAIPAQ responses were collected and divided by amount of vigorous activity , amount of moderate activity , amount of time spent walking , and sitting time. Based on the amount of vigorous, moderate, and walking activity levels, calculations were expressed in metabolic equivalents (MET). Based on the MET-scoring, vigorous PA is equal to vigorous weekly PA expenditure × 8 METs, moderate PA is equal to moderate weekly PA expenditure × 4 METs, and walking PA is equal to walking weekly PA expenditure × 3.3 METs . ParticiThe sociodemographic characteristics that were assessed included age, gender, marital status, education level, employment status, and health insurance. Gender was expressed as male or female. Age was categorized as under 40, 40–64, and 65+ years old. Marital status was categorized as “married,” “never married,” or “divorced/separated/widowed.” Education level was categorized into “less than high school” and “some/completed college.” Employment status was categorized as “employed,” “unemployed,” and “not in labor force.” Lastly, participants checked off if they currently have health insurance and whether they have a regular physician to visit.The presence of high blood pressure was assessed by asking “have you ever been told by your doctor that you have high blood pressure?” Participants were also asked whether they monitored their blood pressure, which is an indicator of engaging in blood pressure control behaviors. 2) × 703. Asian BMI was used to categorize participants into two categories. A BMI cutoff of less than 22.9 indicated underweight or normal weight, while 23 and above indicated overweight or obese [BMI was calculated from self-reported height (inches) and weight (lb). The formula was used to determine BMI = weight (lb)/(height (in)or obese . p-value of <0.05 was selected for determining which variables were selected for the multinomial logistic regression and to determine the level of significance of variables. The sample size after list wise deletion was 113 participants. The coefficient (log odds), 95% confidence interval, log likelihood, pseudo r-square, and likelihood ratio (LR) Chi-square were reported. Furthermore, predicted probabilities of PA level among Filipinos and Koreans with and without high blood pressure as well as monitoring and non-monitoring of blood pressure were calculated when other variables were held at the mean value for each group.Data from the survey was entered into a statistical analysis program, STATA version 14 . Descriptive analyses were run for determining the differences in sociodemographic characteristics between physical activity categories. Chi-square tests or Fisher exact tests were ran to examine any differences of these sociodemographic, health, and BMI variables. Multinomial logistic regression was used to determine the sociodemographic and health related predictors of PA, based on three categories. The low active PA category served as the reference group. Four different multinomial regression models were created based on interaction terms between ethnicity and health indicators  that were each introduced separately in models 2 and 3 and together with other predictors in model 4. A Descriptive statistics of mean physical activity levels among the three groups are in Descriptive statistics are presented in p = 0.003) to belong to the low activity category (78.57%) versus those who did have health insurance (32.30%). Additionally, those who did not monitor their blood pressure (p = 0.007) were more likely to belong to the low active category (56.76%) versus those who did monitor their blood pressure (27.85%).Regarding health-related factors, slightly more than half of the study sample was in the underweight or normal weight category of Asian BMI (51.13%) and reported having high blood pressure (50.39%). The majority of participants had health insurance (89.39%) and were monitoring their blood pressure (72.39%). The three PA groups differed significantly on the specific health factors. Those who did not have health insurance were more likely  and highly active  compared to low active. Compared to the low activity group, having high blood pressure decreased the odds of being moderately active and this was statistically significant . In the second model, having gone to college  and monitoring blood pressure  increased the odds of being in the moderately active PA group, whereas having high blood pressure decreased the odds of being in the moderately active PA group . When introducing the interaction term into the second model, ethnicity and having/not having high blood pressure (Ethnic*High BP), Koreans who reported having high blood pressure had a higher odds of being in the moderately active PA group  versus Filipinos with high blood pressure. Among those in the highly active PA group, being Korean versus Filipino had a lower odds associated with belonging to this category . With respect to health indicators, having high blood pressure decreased the odds  and monitoring blood pressure increased the odds  of belonging to the highly active PA group. In the third model, introducing the interaction terms ethnicity and monitoring blood pressure (Ethnic*Monitor BP) found that having high blood pressure remained a significant predictor in being moderately active . In the fourth model, having gone to college increased the odds of being in the moderately active PA group , while having high blood pressure reduced the odds of being in the moderately active PA group . Lastly, being Korean versus Filipino had reduced the odds of being in the high active category . Both interaction terms did not remain significant in the final model. In the final model, the log likelihood was −102.96, pseudo r-square was 0.1830 and the likelihood ratio was 46.13 (p = 0.0088).Results of the multinomial logistic regression on PA status are presented in Predictive probabilities of PA level are displayed in This study demonstrates the differences in sociodemographic and health related factors that influence PA levels among Koreans and Filipino Americans. We also investigated whether there were any interactive effects of ethnicity and health behaviors on physical activity level. In our final regression model, education level, ethnicity, and high blood pressure status were significant predictors of being moderately or highly active. Furthermore, predicted probabilities illustrated that those who had high blood pressure were more likely to belong to the low physical activity group. Overall, the percentage of participants in our study who reported engaging in moderately active (42.33%) and highly active 21.90%) PA levels was higher than the general U.S. population but similar to studies conducted among other Asian groups in the US .90% PA l. In our With regards to the multinomial regression analysis and ethnic differences in physical activity levels, Filipino Americans were more likely to be moderately to highly active compared to Koreans. In the few studies that disaggregated Asian Americans by groups, Korean Americans were generally less physically active compared to Filipinos ,39. A reAdditionally, participants with a higher education level indicated by having attended college were more likely to belong to the moderately active PA category. This is consistent with the literature where higher socioeconomic status, specifically with education being a proxy measure, is associated with higher levels of PA . Among AWith respect to health conditions, having high blood pressure decreased the odds of having moderate PA levels. Although our study was one of the first to investigate relationships between health factors and PA level among Filipino and Korean Americans, some studies have examined self-rated health, finding that Asian Americans with poor/fair self-rated health had a lower number of reported PA days and were half as likely to meet sufficient PA levels . PA has Our study faced limitations. First, our study was cross-sectional in nature, preventing causal conclusions to be drawn between the selected factors and their impact on PA levels among Filipino and Korean participants who are at risk of hypertension. Secondly, PA, hypertension status, and blood pressure monitoring was based on self-reports, which in the past have not been an accurate measure and can lead to over- or under-reporting. Future studies can incorporate more objective measures for PA in this population, such as accelerometers or pedometers that have reported high validity and reliability. Additionally, clinical measures administered by a health care professional can be taken to measure hypertension status and BMI. Furthermore, the study did not look at types of PA and leisure activities that these populations participate in, which are important indicators of PA perception. Lastly, future studies can assess the psychological and environmental factors which impact participation among Asian Americans, as these are important factors identified in the literature that were not collected in our study. For example, when examining specific barriers to Filipino and Korean Americans, previous studies have found that social isolation from one’s own ethnicity, presence of a chronic illness, low environmental resources/access, and low self-efficiency reduce the ability to participate in PA ,48,49,50This study demonstrated that for Filipino Americans, higher education levels and an absence of high blood pressure were predictors of meeting moderate/high physical activity levels. Future studies can be conducted to test the effectiveness of culturally relevant PA interventions that take sociodemographic factors into consideration. Targeted health education and cultural adaptation of PA can aid in increasing PA levels among these groups, facilitating the prevention and management of hypertension and other chronic diseases.


Understanding the risk factors of hypertension has led to a better understanding of the pathogenesis, prevention and reduction in morbidity of hypertension. It is well known that offsprings of hypertensive parents have an increased risk of developing hypertension. It is therefore necessary to explore the physiological differences between normotensive patients with and without a positive family history of hypertension with respect to their urinary excretion of sodium.This study was carried out at the University College Hospital, Ibadan Nigeria, to determine if normotensive patients with a positive family history of hypertension are different with respect to their urinary excretion of electrolytes and blood pressure. It examined the relationship between 24-hour urinary excretion of sodium, chloride and potassium, urea and creatinine and blood pressure in subjects with and without family history of hypertension. It was a case-control study of sixty-two subjects: normotensive patients’ first degree relatives of primary hypertensive patients and normotensive patients without positive family history.The mean (SD) systolic blood pressures for subjects with and without family history of hypertension were significantly different: 120.0(22.25) and 105.0(17.50) respectively, (p=0.001). The mean arterial blood pressures were significantly different: 86.4(10.2) mmHg and 80.1(8.1) mmHg respectively (p=0.010). The mean (SD) 24-hour urinary excretion of sodium for normotensive patients with and without positive family history of hypertension were 180.5 (45.50) mEq/L, and 156.0(36.25) mEq/L respectively. Systolic blood pressure and 24-hour urinary excretion of sodium was also higher in normotensive subjects with a positive family history of hypertension.Systolic blood pressure and twenty-four hour urinary excretion of sodium were higher in normotensive subjects with a positive family history of hypertension than in those without a family history of hypertension. Hypertension remains a major health problem in Africa, being the commonest cardiovascular cause of morbidity and mortality in adult patients -3. Under2 were excluded. The selection criteria for the normotensive groups followed the criteria specified by Watt [2)BMI = Weight (Kg)/Height, 30 normotensive patients without positive family history of hypertension (Group II). Subjects with pregnancy, diabetes mellitus, evidence of any renal disease, any endocrine disorder, use of traditional medicine, and Body Mass Index (BMI) greater than 30 kg/m by Watt . All subEach subject was asked to choose a convenient day when a 24-hour collection could be guaranteed. In most cases, Sunday morning 7.00 a.m. to Monday 7.00 a.m. was chosen so that subjects could still go work after bringing in their urine samples. At 7.00 a.m., the bladder was emptied whether the subject had the urge to void or not and the urine discarded. All urine passed subsequently till 7.00 a.m. next day was collected, and subjects were instructed to empty their bladder at 7.00 a.m. whether they felt the urge to void or not; this was the last urine collected. Only one 24-hour urine sample was collected as this has been shown to reflect the sodium and potassium intake over the previous 3 to 4 days . On the Statistical analysis: Data was entered into the Epi Info and then exported to R statistical package for analysis. The means, standard deviations (SD) were computed. The distribution of urinary variables was done by Shapiro-Wilk test for normality of data and t-test was thereafter used for analysis. Statistical significance was set at p< 0.05.Demographic and clinical data: There were 29 (46.8%) males and 33 (53.2%) females. The mean (SD) age were 39.0(9.75) and 36.0(11.25) years in the two study groups respectively (2 for groups I and II respectively. The mean (SD) 24-hour urinary excretion of sodium for normotensive patients with positive family history of hypertension was 180.5 (45.50) mEq/L, and 156.0(36.25) mEq/L for normotensive patients without a family history. There was no significant difference in urinary potassium and chloride between the two groups. Results for the serum and urine parameters are shown in ectively . The meaet al, have demonstrated that normotensive offsprings of hypertensive parents had increased BP and impaired compliance of small and large arteries [et al, concluded that the increased urinary output of salt may simply reflect intake rather than renal sodium handling abnormalities. Another explanation could be an inherent kidney abnormality even with a normal salt load. For increased salt intake to result in permanent changes in arterial pressure, renal function must be altered [The higher mean systolic blood pressure (SBP) and mean arterial pressure (MAP) in offsprings of hypertensive patients is comparable and this is consistent with findings of other studies which have suggested that there is a gradual increase in blood pressure in those with family history of hypertension. This may also imply that there is an impairment of arterial compliance and increased sympathetic activity -16. For arteries . Indeed,arteries , 19. Thearteries , 21. In arteries -23. The arteries . Thus Ob altered . An incr altered , 26, 27.Theories proposed to explain the blood pressure effect of salt loading on the blood pressure include an alteration of renal sodium handling. A sustained tendency to renal sodium and water retention leads to sustained long-term autoregulation eventually generating permanent elevation in peripheral vascular resistance with renal vascular lesions, and ultimately hypertension . The oveSystolic blood pressure and twenty-four hour urinary excretion of sodium was higher in normotensive subjects with a positive family history of hypertension than in those without a family history of hypertension. The possibility of using this finding as a screening tool needs to be explored further in this environment where scarce resources compel a need to emphasize prevention and anticipation of health problems rather than the curative aspects. Development of such a strategy affords the clinician an opportunity to intervene early (dietary and life style counselling) to delay or prevent the onset of high blood pressure in due course. Larger community-based studies are required to clarify more fully the relationship between sodium excretion, family history of hypertension and blood pressure.Offsprings of hypertensive parents have an increased risk of developing hypertension;Increased susceptibility is due to intake and abnormal salt handling by the kidney.The 24-hour urinary sodium excretion was higher in normotensive with a positive family history of hypertension than in those without;Systolic blood pressure and twenty-four hour urinary excretion of sodium was higher in normotensive subjects with a positive family;This study corroborates the theory of abnormal renal sodium handling in Black Nigerian individuals who are prone to developing hypertension perhaps through pressure natriuresis: that is, a higher blood pressure is required to excrete a given salt load.The authors declare no competing interests.