CTNS gene but also extends into the non-coding region upstream of the start codon of the TRPV1 gene, encoding the capsaicin- and heat-sensitive ion channel TRPV1. To evaluate the consequences of the 57-kb deletion on functional TRPV1 expression, we compared thermal, mechanical and chemical sensitivity of cystinosis patients with matched healthy controls. Whereas patients heterozygous for the 57-kb deletion showed normal sensory responses, homozygous subjects exhibited a 60% reduction in vasodilation and pain evoked by capsaicin, as well as an increase in heat detection threshold. Responses to cold, mechanical stimuli or cinnamaldehyde, an agonist of the related nociceptor channel TRPA1, were unaltered. We conclude that cystinosis patients homozygous for the 57-kb deletion exhibit a strong reduction of TRPV1 function, leading to sensory deficiencies akin to the phenotype of TRPV1-deficient mice. These deficits may account for the reported sensory alterations and thermoregulatory deficits in these patients, and provide a paradigm for life-long TRPV1 deficiency in humans.Cystinosis is a rare autosomal recessive disorder characterized by lysosomal cystine accumulation due to loss of function of the lysosomal cystine transporter (CTNS). The most common mutation in cystinosis patients of Northern Europe consists of a 57-kb deletion. This deletion not only inactivates the  CTNS) on chromosome 17p13.2CTNS gene but also removes the entire CARKL (carbohydrate kinase like) gene, which encodes a sedoheptulose kinase, and extends into the non-coding region of the TRPV1 gene. Freed et al.CARKL gene is known to result in increased concentrations of sedoheptulose in tissues, plasma and urine of patientsTRPV1 gene function are unknown.Cystinosis OMIM 219800) is rare autosomal recessive disorder , characterized by lysosomal cystine accumulation causing renal Fanconi syndrome, growth retardation, vomiting, periods of dehydration, constipation, and sometimes rickets. Lysosomal cystine accumulation is due to an impairment of the lysosomal membrane exodus of cystine, resulting from mutations in the cystinosin gene , a member of the TRP superfamily of cation channels, is highly expressed in a subset of primary sensory neurons, more specifically in terminals of small- to medium-diameter nociceptors, such as peptidergic and nonpeptidergic C fibers, as well as some Aδ fibersInterestingly, several cases of cystinosis patients with disturbances in thermoregulation, such as recurrent bouts of fever and heat intolerance, as well as craving for hot and spicy food have been reported, which could potentially be related to altered functional expression of TRPV11617To evaluate the potential influence of the 57-kb deletion on TRPV1 function, we compared chemical, mechanical and thermal sensitivity of cystinosis patients that were either homozygous or heterozygous for the deletion, with matched healthy controls. Detailed information on mutations in individual patients is provided in Comparison of demographics between these three groups is provided in 2/day) between patients with homo- or heterozygous 57 kb deletion. Both in the homozygous and the heterozygous groups, about half of the patients had a kidney graft and received immunosuppressive treatment. There were no significant differences between the two patient groups with respect to the use of anti-hypertensive drugs. All patients without kidney graft had renal Fanconi syndrome characterized by polyuria, proteinuria and urinary loss of several substances like glucose, amino acids, uric acid, phosphate and bicarbonate. All transplanted patients had a stable renal function. Body core temperature was normal in all patients. Comorbidities at the moment of the study are listed in All cystinosis patients took cysteamine to treat the cystine accumulation. No difference was found in cysteamine dose . In addition, the Numerical Rating Scale (NRS)-11 pain scale was used to quantify capsaicin-induced pain at these time points. In healthy volunteers, capsaicin induced a large increase in DBF during the first 40 minutes of application, as well as a clear pain response that peaked at 20 minutes. In contrast, capsaicin responses were blunted in cystinosis patients homozygous for the 57-kb deletion: the onset of the DBF response was delayed, and both the objective peak DBF response as well as the subjective pain levels were reduced by more than 60% compared to healthy volunteers. Notably, in heterozygous patients capsaicin-induced changes in DBF and pain responses were not significantly different from the healthy controls . The samCapsaicin-induced increases in DBF are the result of the release of vasoactive peptides such as CGRP from nerve terminals in the skin192021Since TRPV1 is a heat-activated channel, and has been implicated in heat sensing and thermoregulation in animal models and humans, we compared sensitivity to heating and cooling in the homo- and heterozygous patients to that in healthy volunteers. Analogous to earlier work in patients with persistent pain and healthy controlsThere are several, mostly anecdotal reports in the literature that cystinosis patients have a more frequent preference for spicy food or disturbances in thermoregulation than healthy subjects, but whether this is related to TRPV1 dysfunction is unknown. To address whether the objectively determined alterations in capsaicin sensitivity and thermosensation in the homozygous patients correlated with their subjective experiences in daily life, we performed a short structured interview in both hetero- and homozygous patients who were asked (1) whether they had a preference for spicy food, and (2) whether they had the feeling that the regulation of their body temperature was disturbed. Interestingly, 67% (6 out of 9) of the homozygous patients reported a strong preference for spicy food, compared to only 25% of the heterozygous patients . Likewise, 78% (7 out of 9) of the homozygous patients reported subjective thermosensory/thermoregulatory problems, such as hot flashes, difficulties in adapting to changes in temperature or difficulties in sensing temperature differences, compared to only 25% of the heterozygous patients .In this study, we provide evidence that homozygous deletion of the 57-kb fragment in cystinosis patients results in functional impairment of the TRPV1 receptor, as evidenced by a strongly reduced responsiveness to the selective TRPV1 activator capsaicin. The reduced capsaicin-induced vasodilation and pain responses in the homozygous patients recapitulate the reduced pain response and vasodilation reported both in TRPV1-deficient mice and in humans treated with TRPV1 antagonists924Trpv1−/− mice, Caterina et al. reported longer withdrawal latencies in the hot plate test, but only at temperatures exceeding 52 degrees, whereas Davis et al. reported unaltered nocifencive behavior in the hot plate assay9262829In addition to the strong deficiency in capsaicin sensitivity, we also measured milder alterations in heat sensitivity in the homozygous patients. In particular, these patients had a significantly higher threshold for detecting a heating stimulus. Their average threshold for heat pain was 46.7 ± 2.0 degrees compared to the threshold of healthy volunteers 44.7 ± 1.5 degrees, but no significant difference was found (p = 0.6), possibly due to the limited size of the patients group that we have access to, combined with the established inter-individual differences in heat pain thresholdsCTNS mutation on the other allele, did not exhibit any difference in capsaicin responses or heat sensitivity compared to healthy subjects, we can exclude that reduced capsaicin sensitivity represents a general effect of the disease cystinosis (or of the drugs taken to manage the disease and/or kidney transplant) on sensory processes or vascular responses. Instead, it suggests that the sensory deficit represents a direct consequence of homozygous 57-kb deletion on functional TRPV1 expression. The phenotype observed in our heterozygous patients is also in line with Trpv1+/− mice, which show no difference in their responses to capsaicin and temperature compared to the wild-type miceSince heterozygous cystinosis patients, who all lacked functional cystinosin due to the 57-kb deletion on one allele and another CARKL gene in the homozygous patients. The TRPV1 dependence of the sensory deficit is further supported by our finding that neither vasodilatation in response to the TRPA1 agonist cinnamaldehyde, nor responses to cold or mechanical stimuli were affected in the homozygous patients.The depletion of the sedoheptulose kinase CARKL is reportedly associated with increased immune responseTrpv1−/− mice also showed a normal core body temperature. Taken together, our and others’ data indicate that pharmacological or genetic reduction of TRPV1 activity in humans does not necessarily result in permanent alternations of body core temperature. Moreover, considering the role of TRPV1 in pathological pain conditions, the non-coding region upstream of the TRPV1 gene could be a possible target to reduce functional TRPV1 for therapeutic reasons. However, further evidence is required to validate whether homozygous patients have altered inflammatory pain experiences.In spite of the reduced TRPV1 functionality, the homozygous patients generally presented with a normal core body temperature. This may seem at odds with studies showing that healthy volunteers dosed with first generation TRPV1 antagonists exhibited mild to severe hyperthermia131431There have been anecdotal reports of cystinosis patients preferring hot and spicy food, or exhibiting disturbances in thermoregulation1617Our study did not unravel the exact genomic mechanism whereby the 57-kb deletion affects functional expression of TRPV1. A possible explanation is that the 57-kb deletion influences the interaction of transcription factors that regulate TRPV1 expression2834In conclusion, we demonstrate that cystinosis patients homozygous for the 57-kb deletion exhibit a significant reduction in capsaicin-induced dermal vasodilatation and pain, and thus provide a paradigm for life-long TRPV1 dysfunction in humans.CTNS gene. Healthy volunteers were recruited via the Center for Clinical Pharmacology, University Hospitals Leuven. The study was approved by the Ethics Committees of both hospitals  and conducted according to the declaration of Helsinki and International Guidelines on Clinical Trials of Medicinal Products (ICH/GCP Topic E6–July 1996) . All participants (or their parents when <18y) provided written informed consent prior to their participation in the study.Cystinosis patients were recruited from the University Hospitals Leuven, Belgium and the University Medical Center Radboud Nijmegen, the Netherlands. The diagnosis of cystinosis was based on the clinical presentation, measurement of elevated white blood cell cystine levels and confirmed by a molecular analysis of the Male and female participants were eligible if they were >8 years and did not have any abnormalities of the forearm skin or allergies to capsicum plants. All participants refrained from alcohol or caffeine for at least 12 hours and fasted for 3 hours before the study visit. Healthy volunteers had to be good health and took no medication. Patients and healthy volunteers were matched head-to-head based on age and sex.et al.CTNS coding exons and exon-intron boundaries was performed to detect other mutations.57 kb deletion was detected by PCR analysis as described by Heil Three O-shaped rubber rings  were placed on the volar site of the left arm of the subject. After 30 minutes of acclimatization, baseline DBF was measured and 10 minutes hereafter, capsaicin was applied in the two proximal rings (referred to as I1 and I2) and placebo in the distal ring (I3).et al.et al.Capsaicin powder and Trans-cinnamaldehyde oil were obtained from Sigma-Aldrich N.V. . Capsaicin was dissolved in a 3:3:4 mixture of ethanol 100%, Tween-20 and distilled water to obtain a 300 μg/20 μl (for subjects <18 years old) or 1000 μg/20 μl (>18 years old) concentration. The 1000 μg/20 μl dose of capsaicin was used in adults as previous studies reported that this dose produces the most robust responseThe pain level induced by the capsaicin was determined by asking the subject to score his pain with the numerical rating scale (NRS-11). Zero stood for ‘no pain at all’ and 10 ‘the worst pain you could imagine’. The pain level was determined at baseline (i.e. after 30 minutes of acclimatization) and 10, 20, 30 and 40 minutes after capsaicin application.A set of 17 monofilaments , marked 3 to 19 with different diameters (0.12–1 mm), was applied in ascending and descending sequence on the skin of the forearm on the area of capsaicin application with appropriate force (0.026–110 g) for it to obtain a U-shape. Each filament was applied 3 times to the skin with intervals of 1 second. The subjects were asked to report how many times they felt the application and how many times the application was painful.et al.37et al.The sensitivity of the skin for temperature, hot and cold, was determined using the advanced thermal stimulator (ATS) . The device uses a thermode (contact area of 27 mm diameter), with a baseline temperature of 32 °C, that was attached to the thenar eminence at the base of the thumb. The method used was the method of limits as described by Rolke A short, exploratory structured interview was performed by the investigator, during which the following two questions were asked (translated from Dutch): (1) “Do you have a preference for spicy food?”, and (2) “Do you have the feeling that the regulation of your body temperature is disturbed?”Values are expressed as means ± standard error of the mean.® and Graphpath Prism® was used.When comparing between 3 independent groups, one-way ANOVA was performed for continuous normally distributed variables  and Kruskall-Wallis test was performed for continuous non-normally distributed  or discrete variables . Shapiro-Wilk test was used to check for normality. Levene’s test was used to check equality of variances. Post-hoc Bonferroni or Dunn’s multiple comparison test was used to correct for multiple testing. When comparing two independent groups with small sample size , the Mann-Whitney test was used. For analysis of the data from the exploratory, structured interview, Barnard’s exact test was used. Statistical significance was taken at the 5% level . Statistical software of StatisticaHow to cite this article: Buntinx, L. et al. TRPV1 dysfunction in cystinosis patients harboring the homozygous 57 kb deletion. Sci. Rep.6, 35395; doi: 10.1038/srep35395 (2016).


Objective. Endothelial dysfunction plays a key role in atherosclerotic disease. Several methods have been reported to be useful for evaluating the endothelial dysfunction, and we investigated the endothelial dysfunction in patients with peripheral arterial disease (PAD) using peripheral arterial tonometry (PAT) test in this study. Furthermore, we examined the factors significantly correlated with PAT test. Methods. We performed PAT tests in 67 patients with PAD. In addition, we recorded the patients' demographics, including comorbidities, and hemodynamical status, such as ankle brachial pressure index (ABI). Results. In a univariate analysis, the ABI value  and a history of cerebrovascular disease  were found to significantly correlate with PAT test, which calculated the reactive hyperemia index (RHI). In a multivariate analysis, only the ABI value significantly and independently correlated with RHI . Conclusion. This study showed a significant correlation between RHI and ABI. The PAT test is a useful tool for evaluating not only endothelial dysfunction but also the hemodynamical state in patients with PAD. The impairment of endothelial function, which predisposes one to thrombosis, leukocyte adhesion, and smooth muscle cell proliferation, is centrally involved in the atherosclerotic disease process , 2. TherRecently, several noninvasive methods of assessing the endothelial dysfunction have been developed. Flow-mediated dilatation (FMD) is one such particularly useful technique, where the endothelial function is evaluated via ultrasound measurement of the brachial artery diameter during reactive hyperemia . FMD detPeripheral artery tonometry (PAT) is another noninvasive test for evaluating the endothelial function. In PAT, the pulse wave amplitude is assessed before and during reactive hyperemia, which is induced by occluding blood flow of the brachial artery using an inflatable cuff. The calculated index  between the flow in the arm with reactive hyperemia and the control arm represents a measure of the endothelial function , 11. PATWe herein evaluated the endothelial dysfunction of PAD patients using PAT and investigated the relationship between the endothelial dysfunction and various parameters.We recruited 67 patients with PAD due to atherosclerosis, from the outpatient clinic at Tokyo Medical and Dental University Hospital between May 2014 and July 2015. All of the recruited patients provided their informed consent, and approval was obtained from our Institutional Review Board for a retrospective review of the patients' medical records and images.We diagnosed PAD using such modalities as computed tomography angiography, magnetic resonance angiography, duplex ultrasound sonography, or digital subtraction angiography based on the presence of >50% vessel stenosis due to the lesions in the lower limbs. We excluded those patients who had received a recent intervention for PAD or coronary artery disease (CAD) (<6 months) and who had a recent history (<3 months) of unstable angina, myocardial infarction, or cerebrovascular disease (CVD), including stroke, decompensated heart failure, malignant disease, and systemic inflammatory disease, such as infectious diseases.2. Diabetes mellitus (DM) was defined as a fasting blood glucose > 126 mg/dL, hemoglobin A1c > 6.5%, or being medicated with antidiabetes drugs. The severity of PAD was assessed by measuring the ankle brachial pressure index (ABI), which was calculated as the ankle systolic blood pressure divided by the brachial systolic blood pressure using the VasoGuard P84™ system . The ABI for each patient was set as the lower of the ABI levels for each leg or nonrevascularized limb.We obtained the patients' demographics, medications, and medical histories using a dedicated database, retrospectively. The patients' medical records were reviewed as described below. Hypertension was defined as a systolic blood pressure of >130 mmHg, a diastolic blood pressure of >80 mmHg, or a history of treatment for hypertension. Dyslipidemia was defined as a serum LDL cholesterol level of >140 mg/dL, an HDL cholesterol level of <40 mg/dL, a triglyceride level of >150 mg/dL, or a history of treatment for dyslipidemia. CAD was defined as the presence of angina pectoris or myocardial infarction or both, as documented on coronary angiography or based on a history of any revascularization procedures of the coronary arteries. CVD was defined as a history of stroke, transient ischemic attacks, carotid artery revascularization, or cerebral hemorrhage. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 mAfter the patients had fasted for at least 12 hours, a venipuncture was made in the superficial vein of the upper limb for the collection of the blood samples. Complete blood cell counts, including hemoglobin; biochemistry examinations, including low-density lipoprotein and C-reactive protein; and coagulation tests, including fibrinogen, were conducted via standard laboratory methods.The endothelial function was measured by PAT using an EndoPAT 2000 device , which assessed the RHI as a measure of the microvascular endothelial function. Patients refrained from smoking, drinking caffeine-containing beverages, and eating for 12 hours before the PAT measurement. The patients also discontinued all drugs for 18 hours before the measurement and any food for 12 hours before the measurement.The patients were placed in a supine position with a specially designed finger probe on the index finger of each hand and a pressure cuff on one upper arm in a quiet room at a constant temperature of 20°C. After continuous recording of the PAT signal from both fingers during a 10-minute baseline period, the blood pressure cuff on the study arm was inflated to suprasystolic pressure for 5 minutes. The inflated cuff was then deflated, and recording of the PAT signal continued for 10 minutes. The pressure changes reflecting the pulse amplitude both before the inflation of cuff and after the deflation were transmitted to a computer, and the RHI was calculated automatically .t-test, and the correlations for the continuous variables were obtained using Pearson correlation, which reflected the degree of relationships between variables. These variables were evaluated in a univariate model, and variables with P < 0.15 were then entered into a multivariate regression analysis. P < 0.05 was defined as statistical significance. The statistical analyses were performed using the Stat View version 5 software program .The continuous variables are expressed as the mean ± standard deviation (SD), and the categorical variables are expressed as the frequencies and percentages. For the categorical variables, the significance was evaluated by 2. The documented comorbidities were smoking history (76.1%), hypertension (83.6%), dyslipidemia (56.7%), CAD (28.4%), CVD (14.9%), CKD (23.9%), and DM (56.7%). Thirty-seven patients (55.2%) used angiotensin II receptor blocker for hypertension, and 7 (10.4%) patients used angiotensin converting enzyme inhibitor. Thirteen patients (19.4%) used β-blockers, 32 (47.8%) used statin, and 2 (3.0%) did nitroglycerin. The findings on laboratory tests are also shown in We evaluated 67 patients  with PAD in this study. The mean age was 73.1 ± 8.1 years, and the mean body mass index was 22.3 ± 2.5 kg/mP = 0.143) and ABI  were defined as parameters correlated with RHI in the univariate analysis, we next evaluated the multivariate correlations between RHI and these parameters in β = 0.254, P = 0.041) and it was also an independent and significant variable associated with endothelial function as measured by RHI.The correlations between RHI and each of the parameters are shown in In this study, we examined the endothelial function in PAD patients using the PAT method. The endothelial dysfunction has been widely accepted as any form of abnormal activity of the endothelium. This dysfunction has been suggested to be associated with atherosclerotic disease and the risks of atherosclerosis –15. The PAT is recorded as the change in the pulse wave amplitude, which can indicate microvascular function . PAT refAlthough we were unable to detect any correlation between the endothelial dysfunction and atherosclerosis in the present study, we did reveal that the ABI was statistically correlated with the endothelial dysfunction measured using PAT. Brevetti et al.  reportedThough FMD might be promising for measuring endothelial dysfunction , we beliSeveral limitations associated with the present study warrant mention. First, this study had a small sample size, which might affect the statistical significance. Indeed, we noted no significant correlations between the endothelial dysfunction and atherosclerotic diseases, including CAD, which has shown a significant association with the endothelial dysfunction in other contexts . Future We herein demonstrated that the endothelial function measured by PAT significantly correlated with the ABI in PAD patients. However, the influence of several atherosclerotic-related conditions may have considerably affected these results. As such, the factors and conditions evaluated in the present study should be further examined in future studies in particular subgroups of subjects. In addition, further studies should be conducted to corroborate our findings regarding the endothelial function in patients with PAD and to confirm the PAT test as an appropriate method for determining the endothelial dysfunction of PAD patients.


The purpose of this study was to evaluate the association between the presence of clinical symptoms of peripheral artery disease and severe renal artery stenosis in patients referred for renal angiography.We included 82 patients with clinical suspicion of renovascular hypertension and performed an imaging investigation  for possible renal artery stenosis. All patients underwent renal arteriography and were examined for peripheral artery disease based on the presence of intermittent claudication and ankle-brachial index test results. Severe renal artery stenosis was defined as a lesion causing 70% obstruction.vs 56±12 years, p=0.006), had more intermittent claudication , and had a greater prevalence of an ankle-brachial index <0.9  than patients without severe renal artery stenosis. Multivariate logistic regression analysis showed that the presence of intermittent claudication was independently associated with renal artery stenosis ≥70% , unlike the ankle-brachial index, which showed no association .Severe renal artery stenosis was present in 32 of 82 (39%) patients. Patients with severe renal artery stenosis were older  in patients clinically suspected of having renovascular hypertension. Atherosclerotic renal stenosis is a significant cause of secondary arterial hypertension and is strongly associated with cardiovascular events Evidence has shown that RAS is a predictor of coronary artery disease (CAD) and a marker of diffuse atherosclerosis All subjects included in the study had established hypertension and suspicion of RAS based on clinical data. One or more of the following conditions were considered: resistant hypertension (sustained hypertension despite the use of 3 different classes of antihypertensive agents), previous hypertensive pulmonary edema, congestive heart failure, malignant hypertension or progressive renal failure. Subjects were referred to the Hypertension Unit of the Heart Institute (InCor) - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo over a 2-year period. The procedures were conducted in accordance with institutional guidelines, and the institutional review committee approved the protocol . All patients gave written informed consent.Patients were selected whose angiography would be useful for the diagnosis of significant RAS and according to the risk of RAS based on clinical data and additional diagnostic noninvasive imaging that suggested the presence of RAS as follows: decreased renal perfusion by renal scintigraphy, increased renal blood flow velocity (≥180 cm/s) observed on Doppler ultrasound of the renal arteries, and/or magnetic resonance angiography of renal arteries suggesting stenosis. Patients with known PAD  or RAS detected by prior renal angiography were excluded.Risk factors were measured at each clinical examination and included age, resting blood pressure, smoking status, presence of diabetes, and measurement of serum cholesterol levels. Blood tests were performed to measure total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and serum creatinine. The diagnosis of hypercholesterolemia was based on whether the patients had been prescribed cholesterol-lowering agents or had a fasting total cholesterol level >200 mg/dL. Patients were considered to have diabetes mellitus if dietary or pharmacological interventions were required to maintain normal blood glucose levels (<126 mg/dL) or if they were using specific medications. Blood pressure (BP) was measured using an automatic digital sphygmomanometer  after the patient had been in a resting position for 5 minutes. The classification of BP was based on the average of 2 readings taken by the examining physician and according to the recommendations of the Eighth Joint National Committee on High Blood Pressure Evaluation for the presence of IC was based on a structured history and questions from the Edinburgh Claudication Questionnaire 2 received a normal saline infusion (1 mL/kg/h) before and 24 h after the procedure plus 600 mg of oral N-acetyl-cysteine twice daily and low-osmolar contrast for the procedure, as previously described All patients underwent renal angiography after a detailed medical history and complete clinical examination were completed. For a statistical comparison of clinical and laboratory variables, the study population was divided into 2 groups, according to the presence ≥70%) or absence (<70%) of severe renal obstruction verified by renal angiography. Serum creatinine levels were determined twice during the evaluation, 1 day before the procedure and 3 days afterwards. The glomerular filtration rate (GFR) was estimated with the Modification of Diet in Renal Disease (MDRD) formula 0% or abst test for independent samples and the Mann-Whitney U test were used to compare quantitative variables of groups with and without significant RAS. A Chi-squared test was used to analyze qualitative variables, and the Fisher correction was used when necessary. Univariate and multiple logistic regression analyses were used to determine the factors associated with significant RAS in the entire population. Variables with a value of p<0.1 in the univariate analysis were included in multivariate models. A p value <0.05 was considered significant.Data were analyzed using SPSS 20.0 statistical software. Descriptive analysis was used to define the study population. Parametric data are expressed as the mean ± standard deviation, and nonparametric data are expressed as the median followed by the interquartile range or as percentages, when appropriate. Student’s vs 56±12, p=0.006) and had a greater prevalence of IC  and ABI <0.9 . No significant differences were observed between the 2 groups concerning diabetes, smoking status, angina, blood pressure, renal function, and dyslipidemia. The average contrast volume used in renal arteriography was 110 mL. Only 7 (8.5%) patients had a transient and mild/moderate increase in creatinine levels suggestive of contrast-induced nephropathy. Dialysis was not required, and no patient developed serious complications during renal arteriography. In the univariate analysis, the variables that were significantly correlated with the presence of severe RAS included age, ABI, and IC (p=0.04).We evaluated 82 patients with clinical suspicion of RAS, consisting of 62% females, with a mean age of 59±13 years. The main characteristics of the total sample and groups categorized by the presence or absence of severe RAS are shown in , and IC . In the vs 45%, p=0.027). IC has a significant effect on quality of life and is strongly associated with impaired functional capacity vs 20%, p=0.021) and is equally associated with an unfavorable prognosis as described in previous studies The present study produced the following important findings: a) in patients with hypertension who were referred for renal angiography under clinical suspicion of renovascular hypertension, the frequencies of IC and an ABI <0.9 were 35% and 28%, respectively; and b) a validated clinical parameter (presence of IC defined by a standardized questionnaire) was independently associated with severe RAS in patients with hypertension. Atherosclerotic RAS is a clinical condition frequently observed in patients with multiple cardiovascular risk factors and concomitant atherosclerosis in other arterial beds The clinical expression of severity in the group with RAS ≥70% can be verified by uncontrolled blood pressure (SBP median=149 mmHg) despite patients’ use of 4 different classes of antihypertensive medications . The preper se and could partially explain the high rate (35%) of IC in selected patients despite of prevalence of severe RAS in the total group.The main strength of the present investigation was the systematic evaluation of IC symptoms and PAD in consecutive patients diagnosed according to the gold standard method used for identifying RAS. We found a potential role for IC symptoms, which can be easily identified when the clinical history is obtained, for predicting severe RAS in high-risk patients. This finding may reinforce the indication of RAS investigation as important in patients with resistant hypertension. Some limitations should also be addressed. First, the sample size was small, which is primarily explained by our single-center study design, and we only investigated patients at high risk, suggesting the presence of RAS. Second, the selection of patients with hypertension at high risk for atherosclerotic RAS could overestimate the number of individuals affected by atherosclerosis in other vessels, including the peripheral arteries. However, both limitations are related to the standard indications for investigating RAS The presence of IC was independently associated with severe RAS in patients suspected of having renovascular hypertension based on clinical evidence.Macedo TA conceived and designed the work, wrote the draft and contributed to the correction of the manuscript, was responsible for the acquisition, analysis and interpretation of data for the work, managed the literature searches, conducted research procedures, supervised the work, agreed to be accountable for all aspects of the work and to answer questions related to the accuracy or integrity of any part of the work and approved the final version of the manuscript to be published. Drager LF conceived and designed the work, wrote the manuscript draft and contributed to the correction of the manuscript, supervised the work and approved the final version of the manuscript to be published. Muela HC, Pedrosa RP, Costa-Hong V and Kajita LJ were responsible for the acquisition, analysis and interpretation of data for the work, managed the literature searches, conducted research procedures and approved the final version of the manuscript to be published. Bortolotto LA conceived and designed the work, wrote the draft and contributed to the correction of the manuscript, was responsible for the acquisition, analysis and interpretation of data for the work, managed the literature searches, supervised the work, agreed to be accountable for all aspects of the work and to answer questions related to the accuracy or integrity of any part of the work, approved the final version of the manuscript to be published. All authors read and approved the final manuscript and have participated sufficiently in the work to take public responsibility for appropriate portions of the content.


Enabling patients with asthma to obtain the knowledge, confidence and skills they need in order to assume a major role in the management of their disease is cost effective. It should be an integral part of any plan for long-term control of asthma. The modified Patient Enablement Instrument (mPEI) is an easily administered questionnaire that was adapted in the United Kingdom to measure patient enablement in asthma, but its applicability in Portugal is not known. Validity and reliability of questionnaires should be tested before use in settings different from those of the original version. The purpose of this study was to test the applicability of the mPEI to Portuguese asthma patients after translation and cross-cultural adaptation, and to verify the structural validity, internal consistency and reproducibility of the instrument. The mPEI was translated to Portuguese and back translated to English. Its content validity was assessed by a debriefing interview with 10 asthma patients. The translated instrument was then administered to a random sample of 142 patients with persistent asthma. Structural validity and internal consistency were assessed. For reproducibility analysis, 86 patients completed the instrument again 7 days later. Item-scale correlations and exploratory factor analysis were used to assess structural validity. Cronbach’s alpha was used to test internal consistency, and the intra-class correlation coefficient was used for the analysis of reproducibility. All items of the Portuguese version of the mPEI were found to be equivalent to the original English version. There were strong item-scale correlations that confirmed construct validity, with a one component structure and good internal consistency  as well as high test–retest reliability (ICC=0.85). The mPEI showed sound psychometric properties for the evaluation of enablement in patients with asthma making it a reliable instrument for use in research and clinical practice in Portugal. Further studies are needed to confirm its responsiveness. Assessment of patient enablement may prove to be an important component of effective asthma care, but it is important to know about the applicability of existing instruments in different cultural settings.1 In Portugal, the latest estimate of the prevalence of ‘current asthma’ is 6.8%, similar in both men and women,2 whereas the estimate for ‘lifelong asthma’ is between 10.24 and 10.5%.3Asthma is a chronic respiratory disease affecting 1–18% of the population.1–6 and national7 guidelines recommend the assessment of asthma control at every visit. The assessment should include symptom control and the risk of adverse outcomes, as well as a discussion of treatment issues, including inhaler technique, adherence, and the presence of adverse effects, and the management of comorbidities that contribute to the burden of symptoms and poorer quality of life.6International7–9 In Portugal it is estimated that 43% of patients have uncontrolled asthma,10 similar to results from recent studies in other countries.9Despite the availability of asthma management guidelines and asthma therapies of proven efficacy, the majority of patients do not achieve good asthma control.9–12The reasons for poor asthma control include errors in diagnosis, smoking, comorbid rhinitis, incorrect choice of inhalers, poor inhaler technique, individual variation in response to treatment, patient beliefs and concerns, treatment adherence, increased exposure to environmental allergens, decreased access to good care, suboptimal self-management and low socioeconomic status.8 Appropriate asthma self-management14 may be the most cost-effective way to reduce morbidity and mortality.16 This includes monitoring symptoms, controlling allergens, adhering to treatment and adjusting medicines when necessary.15Effective asthma management and improved outcomes require a partnership between the patient and healthcare providers.4Enabling the person with asthma to assume a major role in the management of their disease is cost effective and should be an integral component of any plan for long-term management of asthma, in accordance with international and national recommendations.17 The PEI is related to, but different from, measures of satisfaction.17 This is a widely accepted tool that has been validated in many cross-sectional studies. It has been translated and evaluated in several countries, including Portugal. It has high internal consistency and delivers consistent results.18–23The Patient Enablement Instrument (PEI) is a self-administered questionnaire that was developed in the United Kingdom.24 The mPEI demonstrated similar internal consistency and external validity to the original.24In 2006, the PEI was adapted by Haughney and collaborators for use in asthma management, creating the modified PEI (mPEI).24–26 In a Portuguese study, the instrument was translated and culturally adapted but no psychometric properties were assessed, hence the importance of the present study.26The mPEI has since been used in the United Kingdom and Portugal.The aim was to adapt the mPEI to Portuguese asthma patients and ensure it is a valid and reliable instrument. So, the objectives of this study were to test the applicability of the mPEI to Portuguese asthma patients after translation and cross-cultural adaptation, and to verify the structural validity, internal consistency and reproducibility.The study included a random sample without replacement of 150 patients, aged 18 years old and over, with a diagnosis of persistent asthma. Initially a random group of 302 patients were approached for participation in the study and screened for exclusion criteria. From this group 80 patients had intermittent asthma and were not currently under chronic treatment with inhaler devices, 36 patients were unwilling to participate, 20 patients missed the first appointment, 10 patients were improperly diagnosed, 4 patients had cognitive impairment and 2 patients were unable to independently complete the questionnaire. In addition, 8 patients could not be reached (due to emigration and/or cancelling of telephone accounts). Although 150 patients were eligible for the study, only 142 patients could be recruited in time to participate in the study, 86 (60.6%) of whom completed the mPEI in both T1 and T2.The sample consisted of 65 men and 77 women. The age of the participants ranged from 19 to 88. The demographic characteristics of the patients for both T1 and T2 are presented in The mean and s.d. of the mPEI  at T1 and T2 are presented in The suitability of data for factor analysis was assessed. Inspection of the correlation matrix revealed the presence of coefficients of 0.3 and above.χ2 (15)=402, P=0.000), which meant that the levels of correlation between the items of the instrument were high enough to perform factor analysis on the sample. PCA revealed the presence of 1 component with an initial eigenvalue of 3.68, explaining 61.3% of the variance, which consisted of all six items of the scale. Factor loadings are presented in At T1, the KMO value was 0.85 and Bartlett’s Test of Sphericity reached statistical significance (χ2 (15)=295, P=0.000), so the levels of correlation between the items of the instrument were enough to perform factor analysis on the sample. PCA revealed the presence of 1 component with eigenvalue exceeding 1, explaining 63.1% of the variance, which consisted of all six items of the scale. Factor loadings are presented in At T2, the KMO value was 0.82 and Bartlett’s Test of Sphericity reached statistical significance  to the underlying concept  being measured.28 To verify construct validity, the factorial design of the Portuguese version of the mPEI was analysed in a stepwise procedure. At both T1 and T2, two measures were used to assess sampling adequacy—Kaiser–Meyer–Olkin measure (KMO) and Bartlett’s test of sphericity. KMO is a measure of sampling adequacy calculated for both the entire correlation matrix and each variable individually. KMO values above 0.60 indicate that the sample is adequate for factor analysis.28 Bartlett’s test indicates the strength of the association between variables. It tests the null hypothesis that there is no association among the variables, only of each variable with itself. Factor analysis is only indicated when the null hypothesis is rejected. Assuming adequacy of the sample, a principal component analysis (PCA) with varimax rotation was also conducted. The number of factors extracted was determined using the Kaiser method, i.e., according to initial eigenvalues (retention if >1.0) and the visualisation of the Cattell’s scree plot in order to assess the amount of variance accounted for by a factor.28 All factor loadings  greater than 0.50 were considered relevant.28The internal construct validity of the scale was first evaluated by Spearman’s correlation coefficient between the item and the scale score. An item should be substantially linearly related  with values ranging from 0 (no stability) to 1 (perfect stability).23 Patients with cognitive impairment, kyphoscoliosis, absence of one lung, lung cancer, pregnancy and those unable to provide informed consent, or unable to independently complete the questionnaire were excluded before randomisation. Randomisation was performed using the number generator tool from SPSS. First, 10 patients were randomly selected to assess translation and cultural validation. These patients were later excluded from the randomisation. Second, 150 patients were randomly selected for interview. No financial compensation was provided for participation. The study was explained to each patient by telephone. The patients who agreed to participate were invited to come to the FHU at a time of their choosing for an interview in order to verify their eligibility to enter the study and to review the consent form. During the interview, demographic data, including gender, age and educational level, were collected on a form, identified with a unique number to preserve confidentiality. Each patient was scheduled for a second interview 7 days later (T2), at the FHU, at a time of their choosing.This study was conducted in two Family Health Units (FHU), in Matosinhos, Portugal during February and March 2015. The sample was randomly selected without replacement from the local database of 620 asthma patients. Asthma was classified as persistent according to the indication for chronic therapy with inhaled corticosteroids. The sample size was calculated to assure 20 observations per item.14 The translated version to Portuguese may be found in The mPEI is a six-item questionnaire. Each item is scored in a Likert-type scale from 0 (‘same or less’ or ‘not applicable’) to 2 (‘much better’). There is a minimum score of 0 and a maximum score of 12. A higher score reflects higher patient enablement. The mPEI has good internal consistency with a reported Cronbach’s alpha coefficient of 0.92.This study was approved by the Ethics Sub-committee for the Health and Life Sciences of University of Minho and by the Ethics Committee of the Local Health Authority in Matosinhos (053/CE/JAS).


Valid detection of arthritis is essential in differential diagnosis of joint pain. Indocyanin green (ICG)-enhanced fluorescence optical imaging (FOI) is a new imaging method that visualizes inflammation in wrist and finger joints. Objectives of this study were to compare FOI with ultrasonography  and power Doppler (PD)) and clinical examination (CE) and to estimate the predictive power of FOI for discrimination between inflammatory and non-inflammatory juvenile joint diseases.FOI and GSUS/PDUS were performed in both hands of 76 patients with joint pain (53 with juvenile idiopathic arthritis (JIA), 23 with non-inflammatory joint diseases). Inflammation was graded by a semiquantitative score (grades 0–3) for each imaging method. Joints were defined clinically active if swollen or tender with limited range of motion. Sensitivity and specificity of FOI in three phases dependent on ICG enhancement (P1–P3) were analyzed with CE and GSUS/PDUS as reference.For JIA patients, FOI had an overall sensitivity of 67.3%/72.0% and a specificity of 65.0%/58.8% with GSUS/PDUS as reference; specificity was highest in P3 (GSUS 94.3%/PDUS 91.7%). FOI was more sensitive for detecting clinically active joints than GSUS/PDUS (75.2% vs 57.3%/32.5%). In patients with non-inflammatory joint diseases both FOI and US showed positive  findings (25% and 14% of joints). The predictive value for discrimination between inflammatory and non-inflammatory joint diseases was 0.79 for FOI and 0.80/0.85 for GSUS/PDUS.Dependent on the phase evaluated, FOI had moderate to good agreement with CE and US. Both imaging methods revealed limitations and should be interpreted cautiously. FOI may provide an additional diagnostic method in pediatric rheumatology.DRKS00012572. Registered 31 July 2017.Deutsches Register Klinischer Studien  Joint pain is a common complaint in children and adolescents, about 10–20% of school children being affected . DistingThe current International League of Associations for Rheumatology (ILAR) classification criteria of JIA and its treatment strategies and prognosis are, among other criteria, based on the number of inflamed joints involved  , 10, andIndocyanin green (ICG)-enhanced fluorescence optical imaging (FOI) is a novel technology utilizing near-infrared light to visualize altered microcirculation  in inflamed joints of the hands and wrists , 21. AdvComprehensive validation studies on adult patients with different arthritis have shown good agreement of FOI with GSUS, PDUS, and MRI as well as variable sensitivity and specificity dependent on FOI phase and joint, by comparison –24. ThesOur study was designed to determine the association and agreement of FOI with US  findings and physician assessment of clinical arthritic severity in joints of symptomatic children, as well as to estimate the predictive power of FOI to distinguish between inflammatory juvenile rheumatic diseases and non-inflammatory arthralgia.A total of 76 patients from three pediatric rheumatology centers in Berlin, Germany were recruited for this observational study. The patients were consecutively included. Inclusion criteria were joint pain (due to present JIA or without known reason), age of 6–18 years, and agreement of patient and parents. Exclusion criteria were allergy against ICG or iodine, hyperthyroidism, pregnancy, breast feeding, other known severe diseases, and chronic or active infection of the hands.The patients were categorized into three groups: group I included 29 JIA patients with clinically relevant active arthritis in the hand region at the time of examination (as determined by pediatric rheumatologist); group II included 23 patients with arthralgia ; and group III consisted of 53 JIA patients regardless of disease activity and affection of the hand region at the time of examination, and included all patients from group I. All JIA patients included fulfilled the ILAR criteria . In patiThe study was performed in compliance with the Declaration of Helsinki. The study protocol was approved by the local ethics committee of the Charité University Medicine Berlin, Germany (No. EA2/126/12). Written informed consent was obtained from all participants.For each patient, a detailed CE was performed in all 71 joints. Joints were defined as clinically active by the presence of either joint swelling or tenderness and limited range of motion. The assessment included a physician’s global disease activity score by a 21-point numerical rating scale (NRS), patient’s/parent’s global assessment of overall well-being by the same 21-point NRS, and an assessment of the patient’s functional capacity by the Childhood Health Assessment Questionnaire (CHAQ) score . The cliUltrasonographic examination of both hands was performed in a neutral position by gray-scale (GSUS) and power Doppler (PDUS) ultrasound with the following two machines and settings: Mylab Twice , GSUS 16-MHz frequency, linear probe and PDUS 9.1-MHz frequency, 750-Hz pulse repetition frequency (PRF); and Philips HD15, GSUS 12-MHz frequency, linear probe and PDUS 5.5-MHz frequency, 600-Hz PRF.The wrist, the interphalangeal joint of the thumb (IP), and the metacarpophalangeal (MCP I–V), proximal (PIP II–V), and distal interphalangeal (DIP II-V) joints were examined and scored semiquantitatively for presence of synovial thickening or joint effusion (combined as synovitis) in GSUS  and hyperperfusion in PDUS  .GSUS and PDUS were analyzed blinded to the clinical characteristics of the patient. For evaluation of interreader agreement between the two pediatric centers conducting sonographic examinations, a random sample survey of 11 static GSUS and PDUS images was taken from patients from center 1 and scored independently by the center 2 pediatric rheumatologist.FOI was performed in each patient with the Xiralite® X4 system  following a standardized procedure . Standarp < 0.05 was considered statistically significant.Data management and statistical analysis were performed using SAS 9.3 . Statistical analyses were performed on the patient and individual joint levels. The predictive value for discrimination between patients with inflammatory and non-inflammatory joint diseases by CE, GSUS, PDUS, and FOI was evaluated by calculating the area under receiver operating characteristics curve (AUC). The correlation of CE, GSUS, PDUS, and FOI scores was estimated by the standardized regression coefficient from univariable linear regression analyses. The standardized regression coefficient is reported as a measure of association and can be interpreted as the correlation. A robust variance estimator was used to account for the possible correlation of CE, GSUS, PDUS, FOI, and CE within the study sites . A sum sTwenty-nine JIA patients with clinically relevant active arthritis in the hand region were included in this group. Mean age at examination was 13.7 years (standard deviation (SD) = 3.3, median = 14.0); mean number of joints with clinically active arthritis in the hand region was 7.1 (SD = 5.2). Clinical parameters at study enrolment are presented in detail in Table FOI findings were compared with US findings Figs.  and 3 anPrevalence of joints with pathological findings was 206 (24%), 281 (32%), 118 (14%), and 395 (45%) by CE, GSUS, PDUS, and FOI, respectively. Most frequently affected joints in each method were the wrists as well as PIP joints. In FOI, the largest number of increased signal intensities was found in P2 (34% of joints). The number of joints with grading ≥ 2 was 87 (10%) in GSUS, 27 (3%) in PDUS, and 233 (26.8%) in FOI.The age-related distribution of FOI scores showed no relevant differences between patients aged < 13 and patients aged ≥ 13 years Fig. .Fig. 4CoOf the 206 joints rated as clinically active, 57.3%/32.5% were also positive by GSUS/PDUS and 75.2% by FOI. Of the 664 non-inflamed joints by CE, 75.5%/92.3% was negative in GSUS/PDUS and 63.9% was negative in FOI. With CE as reference, FOI sensitivity was highest in P2 (62.6%) and specificity was highest in P3 (93.1%).Taking GSUS as reference, CE had a sensitivity of 42.0% and a specificity of 85.1% and FOI had a sensitivity of 67.3% and a specificity of 65.0%. With PDUS as reference, CE had a sensitivity of 56.8% and a specificity of 81.5% while FOI had a sensitivity of 72.0% and a specificity of 58.8%. Specificity of FOI compared to US was high in PVM and P3 . However, corresponding sensitivities were low . Sensitivity of FOI was highest in P1  (Table Agreement of CE and US (GSUS and/or PDUS) was 71.6%. Agreement of CE and FOI ranged from 71.8 to 78.2% depending on the individual phases of FOI, agreement of GSUS and FOI ranged from 66.7 to 70.5%, and agreement of PDUS and FOI ranged from 67.9 to 81.9%. Highest agreement was found for P3 where mostly negative results were present, the lowest was found for P2 ; mean number of joints with arthralgia in the hand region was 5.2 (SD = 7.9). Clinical parameters are presented in detail in Table Figure Of the 690 wrists and finger joints evaluated, none had clinical signs of arthritis. However, 17 patients showed abnormalities in GSUS and/or PDUS suggestive of inflammatory activity in 96 joints (14%) , and 21 patients showed increased signal intensities in FOI in 172 joints (25%). The number of joints with grading ≥ 2 was 17 (2.4%) in GSUS, one (0.1%) in PDUS, and 53 (7.7%) in FOI. In FOI, P2 showed most increased signal intensities (16.8%), whereas P3 showed least signals and thus was most specific (98.2%). In US, most positive results were found in the wrists and MCP joints, and in FOI most positive results were found in the wrists and PIP joints.Again, the age-related distribution of FOI scores showed no relevant differences between patients aged < 13 and patients aged ≥ 13 years Fig. .Agreement of US and FOI was high, given the fact that most results were expected to be negative. With both GSUS and PDUS as reference, FOI had specificity up to 98.6% . However, overall sensitivity was relatively low . In 5.5% of joints both imaging methods showed positive findings.The predictive value for discrimination between inflammatory and non-inflammatory rheumatic diseases was calculated. The area under the curve (95% CI) was 0.85 (0.75–0.95) for PDUS, 0.80 (0.68–0.92) for GSUS, and 0.79 (0.67–0.91) for any FOI phase (P2 = 0.77 (0.64–0.89)).p < 0.001); PDUS, β = 0.69 (p < 0.001)), whereas correlation of FOI with clinically active arthritis was moderate (β = 0.32–0.54 (p < 0.001)). Correlation of FOI with US was moderate. P1 was found to correlate most strongly with GSUS (β = 0.50 (p < 0.001) and P2 with PDUS (β = 0.51 (p < 0.001)) (Table p < 0.001); PDUS, β = 0.35 (p > 0.001)), as well as correlation of FOI with clinically active joints (up to β = 0.40 (p < 0.001) for any FOI phase). Correlation of FOI with GSUS was weak to moderate (up to β = 0.35 (p < 0.001) in P2); there was no correlation between FOI and PDUS on the joint level ; mean number of joints with arthritis in the hand region was 4.1 (SD = 5.1). Clinical parameters are presented in detail in Table Of 1590 joints evaluated, 218 (13.7%) were classified as clinically active. US was positive in 26% and FOI in 41.3% of all joints examined.p < 0.001)/β = 0.66 (p < 0.001)), as well as correlation with physician’s global assessment of disease activity (β = 0.51 (p < 0.001)/β = 0.55 (p < 0.001)). There was a weak correlation between GSUS/PDUS and CHAQ (β = 0.32 (p = 0.018)/β = 0.36 (p = 0.008)) and no correlation with the patient-reported outcome measurements pain and fatigue. GSUS/PDUS and inflammatory blood parameters did not show any correlation.Synovitis scores and FOIAS were compared with the cJADAS10, physician’s global assessment of disease activity, functional disability scores (CHAQ), and laboratory parameters  Table . Correlap = 0.002)), as well as correlations with physician’s global assessment of disease activity ). FOI PVM correlated moderately with CRP level (β = 0.48 (p = 0.0001)). There was no correlation between FOIAS and CHAQ or between FOIAS and patient-reported outcome measurements of pain and fatigue.Correlation between FOIAS and cJADAS10 was moderate  and substantial for PDUS , when considering the number of joints with any positive signal. The agreement rate for the grading was slightly lower for GSUS  and PDUS . The highest proportion of disagreement was found between grading 1 and 2 .In all subjects, the procedure was well tolerated. One patient presented circulatory problems due to peripheral IV insertion before the fluorescent compound was applied. The FOI examination could be performed after recovery. No adverse events were observed.ICG-enhanced FOI with the Xiralite® system is a novel imaging technique that has been shown to visualize inflammation in arthritis of wrist and finger joints and has been evaluated in various validation studies in adult rheumatology , 31, 32.Consistent with previous studies in adults –24, FOI Agreement of FOI and CE was comparable to agreement of GSUS/PDUS and CE, whereas FOI overall sensitivity for detecting clinically active arthritis was higher than GSUS/PDUS sensitivity (75.2% vs 57.3%/32.5%).. [Agreement of FOI and US was good, especially agreement with PDUS (up to 81.9%), which reflects the fact that both FOI and PDUS display acute inflammatory changes rather than chronic changes. Sensitivity of FOI compared to US was moderate. The highest values were reached if increased signal intensities in any phase were considered . Analyzing the phases separately, highest sensitivity was found for FOI P1 compared to hyperperfusion in PDUS in JIA patients with clinically active arthritis (59.8%) with corresponding high specificity (74.0%). This supports the theory by Werner et al.  that P1 . . However. –24.In accordance with adult studies, highest specificity compared to both GSUS and PDUS was found for P3 (94.3% and 91.7%). This was the phase showing least signal intensity increase; presumably it reflects increased capillary permeability with abnormal persistency of ICG and is therefore mostly found positive in osteoarthritis , 23, 34.Differences in the characteristics of the FOI phases compared to previous studies might result from the higher variation of ICG distribution patterns we observed in children and adolescents compared to adults. Defining the phases according to the standardized protocol was difficult in several cases, where the ICG distribution deviated from the known characteristic flow behavior. This is possibly due to growth-related vascular changes and might have had an influence on sensitivity and agreement rates of the individual phases. Therefore, the current standard of interpretation in adult rheumatology by Werner et al. , 23—in pBoth FOI and US detected a high number of positive results in clinically asymptomatic joints of JIA patients. In adult rheumatology, it is known that residual synovitis in patients with rheumatoid arthritis in clinical remission is frequent and predicts the risk of relapse and ongoing structural joint damage . Even thIn our study, agreement of US and FOI in clinically inactive joints that presented abnormalities in imaging was relatively low (up to 25.4%), showing that such preclinical/subclinical findings in children and adolescents have to be interpreted with caution. After all, validity of US in pediatric rheumatology has still not been fully established and preliminary standardized definitions of synovitis in US were established only recently . AdditioThis group served as a control group, because none of the patients presented clinical signs of an inflammatory joint disease. Previous examinations of healthy controls and individuals with arthralgia without any sign of inflammatory rheumatic disease showed a low rate of positive findings in FOI (0–5%) , 23. HowRemarkably, there was only moderate agreement between the positive results detected by US and FOI, suggesting that the mechanisms causing such findings differ between the two techniques. This is most likely due to the fact that FOI is based on different physical principles than US, such as light optics and microangiography. Thus, it should be considered a complementary rather than a competitive imaging method.The high number of positive signals in both US and FOI resulted from many joints being scored grade 1. Excluding those joints greatly minimized positive results and led to high specificities . For clinical use, this could mean that FOI tends to overestimate findings and that discreet findings with scores < 2, especially in P2, should be interpreted with caution in children with suspected inflammatory rheumatic diseases, as they might not be a sign of active arthritis but of mechanical stress or blood flow alterations. As discussed before, this possibility should also be considered for patients with inflammatory diseases with positive signals in clinically inactive joints. However, any finding in P3 should be taken seriously, as this highly specific phase might reflect the presence of inflammation.Most positive results in both US and FOI in patients with non-inflammatory diseases were found in the wrists. Interestingly, these results are compatible with observations in a healthy control group whose wrists were examined by MRI, where a high prevalence of increased volumes of joint fluid, signal changes similar to bone marrow edema, and bony depressions resembling erosions were found . Both MRThe predictive value for discrimination between active inflammatory and non-inflammatory conditions was calculated. We found it to be comparably high for both GSUS/PDUS and FOI (0.80/0.85 and 0.79) with slight advantages for US, showing that they are equally valid methods for differential diagnosis in children and adolescents with unclear joint pain.Our study has some limitations. Specific limitations of the technology include the lack of visualization of anatomic structures as well as the limited ability to assess palmar inflammation due to overlying structures reducing the depth of light penetration, most notably in the area of MCP joints. Also, FOI is currently available for examination of hands and wrists only, whereas the most common category of JIA—oligoarthritis—is often manifest in the knee or ankle joint. Therefore, the method might be more valuable for polyarticular-course JIA. Furthermore, it is limited to older children as the method’s fixed setup requires the patient’s capability to keep still for 6 minutes as well as a minimum arm’s length. The youngest patient examined in our study was 6.5 years old.FOI demonstrates any inflammation of the hand region including scratches or psoriatic plaques, which can result in signal enhancement similar to synovitis. Even though experienced readers are able to identify signals caused by such skin lesions, any clinical findings should be documented in order to be considered in image interpretation .FOI is a procedure that includes an IV injection with potential side effects, like circulatory problems and allergic reactions. In our study, FOI examination was tolerated well, with one report of circulatory problems due to peripheral IV insertion before the fluorescent compound was applied.The study population was rather inhomogeneous including several patients with unclear clinical findings at the time of examination. In hindsight, this limitation could be reduced by verifying every patient’s diagnosis approximately 1 year after the examination. Another limitation was the use of two different US machines with potential variance in resolution and display.Ultimately, we were confronted with the problem that there is no assured gold standard for detection of synovitis in children, which is why sensitivities and specificities should be regarded with reserve. Because of the fact that MRI is an invasive technique and not a routine procedure in pediatric rheumatology, we were not able to include it as a reference method in our study.ICG-enhanced FOI is a new imaging technique in rheumatology. It detects and excludes inflammatory changes in joints of children and adolescents in good agreement with sonography and CE.FOI had the highest rate of positive findings of all methods and showed signal enhancements in a majority of patients without known inflammatory rheumatic diseases, which is why discreet findings should always be put in a clinical context. Sonographic examination also showed limitations, proving that despite its value in clinical routine it cannot be regarded as an assured standard of reference in pediatric rheumatology. After all, both diagnostic methods need to be interpreted with caution in the use of children in order not to overestimate their findings. Diagnosis of patients with unclear clinical findings remains challenging. However, FOI is a simple, non-ionizing, and well-tolerated method that could serve as an additional diagnostic tool in pediatric rheumatology. In order to further evaluate the value of this method, and particularly its subclinical findings, more studies in pediatric rheumatology are needed.


Previous studies suggested the potential interactions between cerebrovascular diseases and impaired renal function. However, the relationship between renal function and white matter hyperintensity (WMH), marker of cerebral small vessel disease, in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) remains unknown.We consecutively enrolled 1632 subjects with AIS or TIA who underwent brain MRI for this analysis. The severity of WMH in both of periventricular (PVH) and deep subcortical white matter (SDWMH) was evaluated using Fazekas scale. Estimated glomerular filtration rate (eGFR) was calculated by the equation of the Modification Diet for Renal Disease. Multinomial logistic regression was performed to evaluate the association between the severity of WMH and eGFR.p < 0.001). There is a significantly inverse association between eGFR and PVH. Patients having each 30 ml/min/1.73 m2 increase in eGFR was associated with 75 % of risk of having degree 3 of WMH in periventricular areas compared with degree 0 . However this inverse association was not found between eGFR and SDWMH .Advanced age and hypertension were independently associated with the severity of both PVH and SDWMH  is independently associated with the severity of PVH but not SDWMH in patients with acute ischemic stroke. This results highlighted different pathological mechanism and risk factors of PVH and SDWMH. According to the eGFR, CKD stages were defined as follow: stage1:eGFR ≥ 90 ml/min per 1.73 m2, stage 2:60 ≤ eGFR < 90 ml/min per 1.73 m2, stage3: 30 ≤ eGFR < 60 ml/min per 1.73 m2, stage4: 15 ≤ eGFR < 30 ml/min per 1.73 m2, stage5: eGFR < 15 ml/min per 1.73 m2 [Diabetes mellitus (DM) was considered present when fasting blood glucose level ≥ 7.0 mmol/L, or antidiabetic drugs were taken or a current history of DM was reported. Hypertension was defined by high blood pressure (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg), or by use of antihypertensive drugs, or previous diagnosis. Hypercholesterolemia was defined as total cholesterol ≥ 5.2 mmol/L or lipid-lowing drugs were taken or a current history was documented. Smoking habits were categorized as nonsmokers and smokers (former or current). Admission serum creatinine was abstracted from the medical chart. Estimated glomerular filtration rate (eGFR) was calculated using the equation of the Modification Diet for Renal Disease modified by the Chinese coefficient [e (exp−1.4) × age The brain MRI scan had been performed on a 1.5-Tesla or 3.0-Tesla System due to different research centers, then MRI scans were converted from DICOM to analysis format by eZdicom software, and T2 fluid-attenuated inversion recovery (FLAIR) sequences were used to evaluate the degree of WMH. The Fazekas scale  was usedP value less than 0.2 was used to select variables to build the multinomial regression model. For multinomial logistic regression, with both PVH and SDWMH rated with a 4-degree score as the dependent variable, each response category was contrasted against the reference category (degree 0). Each model adjusted on age, gender and hypertension at least. Statistical significance level for all analyses was set at P value less than 0.05.The SPSS Version 19.0 was used for all analyses. The descriptive statistics on the baseline characteristics are presented as well as their crude distribution according to WMH degrees. The continuous variables were summarized as mean ± SD or median with interquartiles, and all the categorical variables were presented as number (percent). Univariate analysis was used to evaluate the relationship between WMH and other variables (data not shown), and a nominal 2 .Baseline characteristics of the study sample are shown in Table Of 1632 participants, 811(49.7 %) had no WMH (degree 0) in the subcortical area, 575 (35.2 %) had SDWMH of degree 1, leaving only 246 (15 %) with SDWMH of degree 2 or 3. By contrast, only 293 (18.0 %) participants had no visible WMH in the periventricular area, 749 (45.9 %) participants had PVH of degree 1, 590 (36.2 %) had PVH of degree 2 or 3  as compared with normotensive subjects  in our cohort than previous reported (28.1 % in one study and 40.2 % in another) [There are several limitations should be noted in our study. First, considered that it was a multicenter designed study and the serum creatinine concentration had been analyzed in different laboratories, there may be bias of measurement. However, the comparability of serum creatinine concentration detected in different lab was widely accepted in previous studies, and all of the involved centers have rigid quality control process of their clinical and biochemical tests, we think this may not change our results. Second, the WMH assessment had been performed using visual rating scale. Although also widely used, visual rating may be less precise or consistent than quantitative evaluation. Last, as we have excluded subjects with severe renal dysfunction, the proportion of patients with eGFR < 60 ml/min/1.73 manother) , which mIn conclusion, we demonstrated that kidney function is associated with WMH in patients having acute ischemic stroke or TIA. Furthermore, this association was found only in WMH located around ventricles. Further studies are needed to improve our understanding of this cerebro-renal coexisting impairment.


Sleeve gastrectomy may alter esophageal motility and lower esophageal sphincter pressure. To detect manometric changings in the esophagus and lower esophageal sphincter before and after sleeve gastrectomy in order to select patients who could develop postoperative esophageal motilitity disorders and lower esophageal sphincter pressure modifications. Seventy-three patients were selected. All were submitted to manometry before the operation and one year after. The variables analyzed were: resting pressure of the lower esophageal sphincter, contraction wave amplitude, duration of contraction waves, and esophageal peristalsis. Data were compared before and after surgery and to the healthy and non-obese control group. Exclusion criteria were: previous gastric surgery, reflux symptoms or endoscopic findings of reflux or hiatal hernia, diabetes and use of medications that could affect esophageal or lower esophageal sphincter motility. 49% of the patients presented preoperative manometric alterations: lower esophageal sphincter hypertonia in 47%, lower esophageal sphincter hypotonia in 22% and increase in contraction wave amplitude in 31%. One year after surgery, manometry was altered in 85% of patients: lower esophageal sphincter hypertonia in 11%, lower esophageal sphincter hypotonia in 52%, increase in contraction wave amplitude in 27% and 10% with alteration in esophageal peristalsis. Comparing the results between the preoperative and postoperative periods, was found statistical significance for the variables of the lower esophageal sphincter, amplitude of contraction waves and peristalsis. Manometry in the preoperative period of sleeve gastrectomy is not an exam to select candidates to this technique. The hypothesis was that surgical manipulation near the esophagogastric angle during the operation could affect LES function and esophageal motility.2 (35-46).This study was approved by the ethics and research committee of the State University of Londrina. It is a prospective cohort with a consecutive sample of the convenience of 87 obese subjects submitted to vertical gastrectomy from April 2012 to March 2014. The surgical indication obeyed the international criteria for performing bariatric surgery. Exclusion criteria were: previous gastric surgery, history of GERD or endoscopic finding of reflux esophagitis or hiatal hernia, diabetes and use of medications that could affect esophageal or lower esophageal sphincter motility. Patients who had postoperative complications that required surgical or endoscopic treatment, those who did not complete the study or those who refused to participate in the study were excluded from the analysis, so the data refer to 73 patients: 18 men and 55 women, with a mean age of 40.2 years (19-61) and mean body mass index (BMI) of 41.1 kg / mThe patients selected for the study were submitted to manometry before and one year after surgery. The variables analyzed were resting pressure of the LES in mmHg , contraction wave amplitude in mmHg , duration of contraction waves in seconds and esophageal peristalsis. The data were compared before and after the operation and the findings of the healthy and non-obese control group, composed of 10 volunteers, were also compared. The control group did not present gastrointestinal symptoms, previous abdominal operations and did not use any type of medication that could interfere in the esophageal motility or the LES pressure. All patients were operated by the same surgeon and the manometry performed by a single examiner. All obese participants in the study signed informed consent for the study.R software, USA, was used for data interpretation and analysis. Ten days before the study, drugs that could interfere with esophageal motility and proton pump inhibitors were discontinued. There were no complications during the exams.The test was performed with an eight-channel, water-infused device after an 8 h fast. The manometric data were obtained through 10 swallows of 5 ml of water with interval of 5 min. SyneticsVertical gastrectomy was performed with the surgeon between the patient’s legs. Initially, the vessels were released from the great gastric curvature from 4 cm of the pylorus until the gastric fundus was completely released and the diaphragmatic pillar was seen. After this surgical time a 32 F oro-gastric probe was introduced to the duodenum. The stomach was sectioned using a laparoscopic stapler along the gauge probe, starting 4 cm from the pylorus and continuing cranially to the esophagogastric angle. The last stapling was done 1 cm laterally to the esophagus. After removal of the stomach from the abdominal cavity, invaginating continuous suture was made with absorbable yarn of the staple line and methylene blue test was done. There was no intraoperative complication or need for conversion to laparotomy.p was less than or equal to 0.05.The variables were analyzed using non-parametric tests, Wilcoxon test for paired samples and Mann-Whitney for simple samples. Statistical significance was considered when Of the 73 patients, 36 (49%) presented manometric changes in the preoperative period. The alterations found in this group were: LES hypertonia in 17 (47%), eight LES hypotonia (22%) and 11 with an increase in contraction wave amplitude (31%). One year after the operation, manometry was altered in 62 patients (85%). The findings in this group were: LES hypertonia in seven (11%), 32 LES hypotonia (52%), 17 with an increase in contraction waves amplitude (27%) and six (10%) with alterations in esophageal peristalsis The control group did not present manometric alterations .Lower esophageal sphincter pressure before and after the operation was 26.5 9.1 mmHg and 12.6±8.7 mmHg, respectively. The amplitude of the contraction waves was 133.1±38.7 mmHg in the preoperative period and in the postoperative period was 146.5±37.7 mmHg. The duration of pre and postoperative contraction waves was 4.2±1.1 s and 5.7±1.1 s, respectively. Normal peristalsis occurred in 100% of the patients before the operation and in 90% after .Comparing the results of the preoperative period with the control group, statistical significance was not found for the variables analyzed. When comparing the postoperative results with the control, there was a significant difference in the LES pressure and the amplitude of the contraction waves. Comparing the results between the preoperative and postoperative periods, statistical significance was found for the variables LES pressure, amplitude of contraction waves and peristalsis .In this research we studied patients without GER because the objective was to evaluate the effects of vertical gastrectomy on esophageal motility and lower esophageal sphincter function. The absence of GER was defined by the absence of symptoms and normal endoscopic examination. The lack of esophageal phmetry in this population may be a bias in this research, since GER may be present in asymptomatic patients,,,A control group was constituted in this research, due to the fact that manometric changes in the esophagus can occur in non-obese asymptomatic individualsManometry is an important tool for the study of LES and esophageal body functionIn the studied population, we found preoperative manometric changes in 49% of the obese, with an increase in the amplitude of the contraction waves. A previous study by our team,,,,,,Several publications have shown that vertical gastrectomy is an effective method for weight loss and improvement of comorbidities,,Manometric studies after vertical gastrectomy showed a significant decrease in LES pressure,The worsening of esophageal motor function is most likely due to the increase in the pressure of the interior of the stomach after vertical gastrectomy and the decrease of the pressure of the LES possibly occurs due to the injury of the muscular fibers of the esophagogastric transitionData on manometric changes of the LES are controversial. Braghetto et al.Kleidi et al.,,Gastroesophageal reflux after vertical gastrectomy can vary from 2.8 to 13%This is also the opinion of the authors of this study and if we were able to select preoperatively those patients who could develop postoperative esophageal motor complications, the results would surely be better. This is why this study was carried out. We found alterations in the postoperative period of the vertical gastrectomy, but they were not correlated with the manometric findings in the preoperative period.It can not be concluded that the manometry in the preoperative period of vertical gastrectomy is a selection factor for the candidates for this operative technique.


Objectives. To determine the changes in blood pressure levels and antihypertensive medication use in the postrenal transplantation period compared to pretransplantation one. Methods. A comparative cross-sectional study was carried out on renal transplant recipients at the Kenyatta National Hospital, a national referral hospital in Kenya. Sociodemographic details, blood pressure levels, and antihypertensive medication use before and after renal transplantation were noted. Changes in mean blood pressure levels and mean number of antihypertensive medications after renal transplantation were determined using paired t-test. Results. 85 subjects were evaluated. Mean age was 42.4 (SD ± 12.2) years, with a male : female ratio of 1.9 : 1. Compared to the pretransplant period, significantly lower mean systolic and diastolic blood pressure levels after transplantation were noted . Mean number of antihypertensive medications also reduced significantly after transplantation, with an average of 3.3 (±1.6) versus 2.1 (±0.9) in the pre- and posttransplant periods, respectively (p < 0.001). Conclusion. There is a significant reduction in blood pressure levels and number of antihypertensive medications used after renal transplantation. The positive impact of renal transplantation on blood pressure control should be confirmed using prospective cohort studies of patients with end stage renal disease who then undergo renal transplantation. Renal transplantation remains the therapeutic modality of choice for patients with end stage renal disease, with improved quality of life compared to dialysis. Blood pressure levels in patients with end stage renal disease are often elevated and difficult to control. The pathophysiology of hypertension in this population of patients is multifactorial, including volume overload, increased renin activity, enhanced sympathetic outflow, and increased blood viscosity due to erythropoietin replacement therapy . ManagemThe blood pressure achieved after transplantation is inversely related to postoperative glomerular filtration rate (GFR). As a result of improved GFR after transplant, there is significant improvement in blood pressure control, with fewer antihypertensive medications required. However the prevalence of postrenal transplant hypertension still remains high, with multiple mechanisms implicated . In contUnfortunately, despite manipulation of immunosuppressants used (by use of the lowest effective dose), most transplant recipients continue to require one or more antihypertensive agents to achieve adequate blood pressure control. Małyszko et al., in a study conducted on 150 renal allograft patients in Poland found that 60% of them required 3 or more antihypertensive agents, with only 40% demonstrating target blood pressure levels of less than 130/80 mmHg [There may be increased, reduced, or stable antihypertensive medication requirements after renal transplantation. A study carried out in India showed that up to 52% of posttransplant patients required 3 or more antihypertensive drugs, with most (62%) having increased antihypertensive requirements. Only 13% had reduced antihypertensive requirements after renal transplantation, while 25% had stable requirements [In Norway, a study among nephrectomized renal transplant recipients showed that antihypertensive medication requirements reduced from a mean of 2.3 ± 0.5 drugs/day in the pretransplant period to 1.3 ± 0.9 drugs/day after renal transplantation .The situation in Kenya regarding changes in blood pressure and antihypertensive medications in the posttransplant period compared to the pretransplant period remains unknown. This study sought to document these changes.It is comparative cross-sectional study.It is conducted in Kenyatta National Hospital Renal Transplant Clinic. Kenyatta National Hospital is a tertiary referral hospital and runs a specialized renal transplant clinic.The entire cohort of renal transplant recipients was hypertensive, more than 2 months after transplant, 18 years of age, and above and not on dialysis due to nonfunctional grafts and gave informed written consent.All eligible patients attending the nephrology clinics and fulfilling the inclusion criteria were included.All eligible patients were consecutively sampled.First, it is to compare blood pressure levels in the pre- and postrenal transplant periods.Second, it is to compare number and type of antihypertensive medications used in the pre- and postrenal transplant periods.Hypertension was defined as either the use of antihypertensive therapy or systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg. Controlled blood pressure was defined as BP < 130/80 mmHg as per KDIGO guidelines [idelines .Antihypertensive medication use was defined as the number of different classes of antihypertensive medications used for management of blood pressure in both the pre- and posttransplant periods.Informed written consent was obtained prior to patient enrolment into the study. Participants' sociodemographic history and clinical history were then recorded in a predesigned questionnaire. Blood pressure measurement on the day of enrolment was done using standard procedure with duly calibrated machines . In addiFor the baseline characteristics, continuous variables were summarized into means and standard deviations (SD) or medians and interquartile ranges (IQR) while categorical variables were presented as proportions.t-test. Changes in blood pressure levels after transplantation were also determined by comparing the mean blood pressure before and after transplantation using paired t-test. All statistical tests were performed at 5% level of significance.Antihypertensive medication use was analyzed and presented as mean number of drugs used per patient. Changes in antihypertensive medication use after transplantation were determined by comparing the mean number of drugs before and after transplantation using paired Ethical approval was given by the KNH/UoN Ethics and Research Committee, and all procedures were in accordance with the institutional ethical standards. Patients gave informed written consent. Confidentiality of patient records was maintained at all times.Out of 100 documented renal transplant recipients attending the nephrology clinics, 85 were found to be eligible and recruited into the study. Data for all 85 study participants was subsequently analysed. This is presented in The average age of the renal transplant recipients was 42.4 (±12.2) years, with the donors being younger at a mean age of 33.2 (±8.5) years. Most recipients were male (65.9%), with a male to female ratio of 1.9 : 1. The male predominance was also noted among the donors, 54.1% of whom were male.In the pretransplant period, uncontrolled hypertension was noted in 87.1% of the patients , while in the posttransplant period 68.2%  had uncontrolled hypertension .p < 0.001)  .It was noted that in the pretransplant period more than a third of the patients (37.6%) had blood pressure levels greater than 160/110 mmHg. This was however reduced to 4.7% in the posttransplant period .In the pretransplant period most patients (70.7%) were on 3 or more classes of antihypertensive medications. In the posttransplant period the converse was noted, with most patients (70.4%) on 2 or less antihypertensive medications .p < 0.001). This is shown in There was a significant reduction in the mean number of antihypertensive agents used after transplantation, with an average of 3.3 (±1.6) drugs in the pretransplant period compared with 2.1 (±0.9) drugs in the posttransplant period  .Use of calcium channel blockers increased slightly in the posttransplant period from 71.8% to 80%, as did use of fixed dose combinations (2.4% to 7.1%). Beta-blocker and vasodilator use remained almost similar before and after transplantation.The most commonly used classes of antihypertensives were calcium channel blockers and beta-blockers.Blood pressure control in our renal transplant population still remains a challenge, with 68.2% of renal transplant recipients in our study having uncontrolled hypertension. In comparison, studies in the West showed much lower rates of uncontrolled hypertension, with figures of 50% in UK  and 58% As compared to the posttransplant period, there were higher rates of uncontrolled hypertension in the pretransplant period, with 87.1% of the patients not achieving target blood pressure goals. It is well established that higher blood pressure levels are seen with decreased or worsening renal function .Reasons for better rates of blood pressure control in the posttransplant period include the fact that blood pressure after renal transplantation is inversely related to the glomerular filtration rate. Many patients thus note a reduction in blood pressure levels with the improvement in renal function achieved after transplantation, as well as the reduced fluid overload status. Indeed, mean systolic and diastolic pressure were noted to decrease significantly from 144.5 (±18.2) mmHg to 131.8 (±16.6) mmHg and 103.6 (±37.7) mmHg to 83.5 (±12.9) mmHg in the pre- and posttransplant periods, respectively.In terms of antihypertensive medication use, it was noted that there was a significant reduction in mean number of antihypertensives used from 3.3 ±1.6) in the pretransplant period to 2.1 (±0.9) in the posttransplant period. This was also noted in a study carried out by Midtvedt et al. in Norway, where antihypertensive medication use reduced from 2.3 (±0.3) to 1.3 (±0.9) among renal transplant recipients who also underwent bilateral nephrectomy [ in the pThe most commonly used class of antihypertensive agents was calcium channel blockers in both the pre- and posttransplant period, followed by beta-blockers. Bulatova et al. in Jordan also had similar findings, with 58% of their patients on CCBs followed by beta-blockers at 33% . CalciumThere was a marked reduction in ACE inhibitor/angiotensin receptor blocker use from 56% in the pretransplant period to 14% in the posttransplant period. This reflects the fact that ACEi/ARBs are usually avoided in the immediate posttransplant period because they may cause a reduction in glomerular filtration rate that may mimic or mask rejection episodes. They may also precipitate renal failure in patients with transplant renal artery stenosis. Bulatova et al. also noted that only 19% of their renal transplant recipients were on ACE inhibitors . In addiOne of the limitations of this study is that pretransplant blood pressure levels were abstracted retrospectively from file records, which may be affected by interobserver variability in measurement of blood pressure during clinic visits.Uncontrolled hypertension remains highly prevalent at 68.2% in the postrenal transplant period, although there was an improvement in blood pressure control when compared to the pretransplant period.It was also noted that there was a reduction in mean number of antihypertensive medications used in the posttransplant period compared to the pretransplant period.Prospective cohort studies following up patients with end stage renal disease who then undergo renal transplantation will be best suited to confirm the positive impact of renal transplantation on antihypertensive medication requirements and blood pressure levels indicated in this comparative cross-sectional study.