In one case microalbuminuria and in 3 patients early retinopathy were revealed. Linear correlation between eGFR and hearing threshold at 4, 6, 8 and 12 kHz was found. Patients with hearing impairment (n = 7) had lower eGFR 108.8 vs. 121.7 ml/min/1.73 m2, p = 0.047 compared to normal-hearing subjects. Also patients with absence of otoacoustic emissions in at least one ear had lower eGFR, 103.1 vs. 123.3 ml/min/1.73 m2, p < 0.001, compared to the remaining group. In auditory brainstem responses we found significant linear correlation between eGFR and wave III and interval I-III latencies, and between UAE and waves III, V and interval I-III latencies. This study suggests existence of relationship between hearing and kidney function in type 1 diabetic patients. Pathways directly linking hearing and renal function are unknown. Larger studies are necessary to further analyze these relationships.Type 1 diabetes can lead to impaired function of many organs and tissues. The aim of this study was to evaluate associations between hearing and kidney function in young adult type 1 diabetic patients. 31 patients (9 women) with type 1 diabetes, aged <45, with disease duration <10 years were included. Blood and urine samples for laboratory tests and urinary albumin excretion (UAE) assessment were obtained. eGFR was calculated with CKD-EPI formula. In all patients pure-tone audiometry, transient evoked otoacoustic emissions and auditory brainstem responses were evaluated, also eye fundus was examined. Mean patients’ age was 29.5 ± 7.0 years and disease duration 4.6 ± 2.6 years. All patients had eGFR > 60.0 ml/min/1.73 m Prevalence of type 1 diabetes mellitus in high income countries is estimated to consist 7–12% of all diabetes cases2. Poorly controlled type 1 diabetes can lead to development of a long-term diabetic complications. Diabetic retinopathy, nephropathy, neuropathy and cardiovascular disease are the most widely known consequences of diabetes3. However, type 1 diabetes can also affect function of other organs. Dysfunction of hearing organ is significantly more frequent in type 1 diabetic patients, compared to non-diabetic population, which was summarized in a recently published meta-analysis4. Abnormalities in hearing function, also subclinical, can be found even in a young adults with short-lasting diabetes, which was documented in our earlier published paper5.Incidence of type 1 diabetes continues to rise. In Podkarpackie Region in South-Eastern Poland, in population below 19 it reached almost 20 new cases per 100,000 children and adolescents in this age range in the year 2013 . However, type 1 diabetes can be diagnosed also in population above 30. In United Kingdom 42% of new cases of type 1 diabetes were diagnosed in this age group6. Otoacoustic emissions (OAEs) evaluation is used to determine cochlear micromechanics status, especially outer hair cells (OHC) function. The cochlear response is evoked by a click or pure-tone stimulus and its amplitude is expressed in dB. The higher is the amplitude of OAE’s, the better is the OHC function7. Evaluation of the auditory brainstem response (ABR) is the most commonly used non-invasive electrophysiological test to determine function of the retrocochlear part of the auditory pathway, up to the brainstem level8.The hearing function can be assessed using several audiological tests. The pure-tone audiometry (PTA) is the most common test used to evaluate hearing thresholds at different frequencies, which reflects the function of both peripheral and central auditory pathway9. In Norway it was even less prevalent in patients with childhood-onset type 1 diabetes: 0.7%, 2.9% and 5.3% after respectively 20, 30 and 40 years of type 1 diabetes duration10. Higher ESRD was observed in the Pittsburgh Epidemiology of Diabetes Complications (EDC) study with 5.5%, 14.5% and 26.5% affected after 20, 30 and 40 years of diabetes duration respectively11. Usually deterioration of kidney function was considered to be preceded by increased urinary albumin excretion (UAE). However, progressive decline of kidney function measured by estimated glomerular filtration rate (eGFR) is observed also in patients without albuminuria. And inversely, not always patients with overt proteinuria have progressive renal decline12. Diabetic complications frequently correlate to each other and, regardless of stage, diabetic nephropathy is almost exclusively seen in patients with co-existing diabetic retinopathy13.Diabetic kidney disease is one of the most common diabetic complications, which can finally lead to the end-stage renal disease (ESRD) requiring renal replacement therapy. Prevalence of ESRD in type 1 diabetes in Finland after 20 and 30 years of disease duration was 2.2% and 7.0% of patients respectively15.The primary objective of our cross-sectional study, was to evaluate whether auditory organ function, assessed by PTA, OAEs and ABR correlates to kidney function in a group of relatively young adult type 1 diabetic subjects with a short duration of the disease. The secondary objective was to evaluate other relationships between analyzed variables including lipid profile, blood pressure and presence of retinopathy. This study is a post-hoc analysis of our previously published data2, the rest had eGFR above 90.0 mL/min/1.73 m2. In one case UAE within microalbuminuria range was revealed (43.3 mg/L), however, in this patient urinary albumin/creatinine ratio (UACR) was <30 mg/g. In 3 patients early background retinopathy was found. Full characteristics of study participants are presented in Table The mean age of the study participants was 29.5 ± 7.0 years and mean type 1 diabetes duration 4.6 ± 2.6 years. In 3 patients eGFR was between 75.0 and 90.0 mL/min/1.73 m2, p = 0.047. However, they were also significantly older, 35.0 ± 7.8 vs. 27.9 ± 6.0 years respectively, P = 0.016. A significant negative linear correlation between eGFR and hearing threshold was revealed at frequencies 4 kHz , 6 kHz , 8 kHz  and 12 kHz  , P < 0.001. No relationship between UAE and lack of TEOAE was found, also no significant difference in age between these two groups was revealed. No linear correlation between eGFR and TEOAE amplitude was revealed, while an insignificant trend towards negative linear correlation between UAE and TEOAE amplitude was observed .In TEOAE evaluation absence of TEOAE in at least one ear was revealed in 7 patients. These subjects, compared to patients with preserved TEOAE, had significantly lower eGFR  and interval I-III  was revealed , p = 0.028. Retinopathy was also associated with presence of hearing impairment, P = 0.002 and with significantly higher hearing threshold at frequencies 1 kHz (P < 0.001), 2 kHz (P = 0.008) and 4 kHz (P = 0.030).Despite very low number of patients with retinopathy, eGFR in these subjects was significantly lower compared to patients without retinopathy, 102.8 ± 32.5 vs. 122.0 ± 18.2 mL/min/1.73 m1c level, r = 0.571, P < 0.001. No relationship between HbA1c and eGFR or retinopathy was found.UAE demonstrated strong linear correlation with HbA15. Significantly lower HDL cholesterol level , and significantly higher triglycerides  were also revealed in patients with retinopathy compared to subjects with normal eye fundus. No association was found between serum lipids, blood pressure or BMI and eGFR or UAE.Lipid parameters, blood pressure values and BMI were significantly associated with abnormalities in the audiological evaluations, which was described previously elsewhere16. Abnormalities in hearing organ function are also seen in OAEs and ABR evaluations15. Apart of age, among factors leading to impaired hearing function role of blood pressure, lipid abnormalities and elevated BMI are pointed out18.Sense of hearing is one of the most important tools of social communication. Hearing impairment assessed in PTA is significantly more prevalent among patients both with type 1 and type 2 diabetes, compared to non-diabetic populationet al. in their study on Hispanic/Latino population found significantly higher prevalence of hearing impairment in adult diabetic patients with moderate kidney impairment compared to subjects with normal eGFR19. In a large cross-sectional study conducted among 5,226 Korean adults, hearing impairment was strongly associated with eGFR < 60 mL/min/1.73 m2, systolic and diastolic blood pressure, while no association with microalbuminuria, diabetes, HbA1c, hypertension or dyslipidemia was revealed20. Also in another population-based study including 2,564 participants moderately decreased kidney function was associated with hearing impairment21.Data regarding associations between hearing impairment and kidney function in diabetic patients are scarce. Bainbridge 2 and none of them had eGFR < 75 mL/min/1.73 m2). Also positive linear correlation between eGFR and hearing threshold at high frequencies was revealed . However, after adjustment for age, lipid parameters and BMI this relationship lost its significance. Interestingly, similarly to Korean study20, no association between hearing impairment and microalbuminuria was found. We also did not find significant relationship between hearing thresholds at different frequencies and microalbuminuria.Our study suggests the existence of relationship between hearing and renal function in young adult type 1 diabetic patients. Mild to moderate hearing impairment was associated with lower eGFR at subclinical level  in patients with a lack of TEOAEs. The amplitude of OAEs tended to correlate with the level of microalbuminuria, but this relationship did not attain the level of statistical significance.Association between OAEs and renal function in type 1 diabetic patients was analyzed in only one study. Hou et al.22. They revealed significant relationship between ABR abnormalities and albuminuria but not with creatinine level. We also found association between UAE and ABR results: the higher was UAE, the longer was conduction time through auditory pathway . Interestingly, we found unexpected association between eGFR and ABR results – the higher (i.e. better) was eGFR, the longer (i.e. worse) was conduction time through the distal part of the auditory pathway .Correlation between ABR and renal function in diabetic patients was also analyzed by Hou 1c are divergent24. In diabetic kidney disease detrimental role of poor metabolic control is clear and also other mentioned above factors play a role in diabetic nephropathy development23. In our study, as it could be expected, microalbuminuria was strongly associated with HbA1c level and with longer conduction time in auditory pathway . However, UAE was not associated neither with hearing threshold, nor with lack of TEOAE. Inversely, lower eGFR was associated with the presence of hearing impairment, higher hearing threshold at high frequencies and with lack of TEOAE, while, unexpectedly, in ABR lower eGFR was associated with shorter conduction time in auditory pathway. These discrepancies are in fact not easy to explain and require further investigation. Nevertheless, they indicate possible different pathogenic pathways linking hearing organ function with albuminuria level and excretory kidney function measured by eGFR. Moreover, it is worth noting that all associations revealed in our study were present at sub-clinical level and none of the study participants had an overt impaired kidney function.Many genetic, metabolic, hemodynamic, environmental and inflammatory factors are involved in development of diabetic complications. Some of them are modifiable, while other are non-modifiable. Many of them are common for both hearing impairment and diabetic kidney disease. Lipid abnormalities, elevated blood pressure and increased BMI are considered to be modifiable factors related to impaired hearing organ function in diabetes. Data regarding HbAcr formula can be influenced by body composition, e.g. high muscle mass. Nevertheless, our findings suggest the existence of association between hearing organ and kidney function in young adult type 1 diabetic patients with short duration of the disease. Obviously, larger, prospective studies are necessary to further analyze this relationship, to identify factors and pathogenic pathways directly linking these two complications of diabetes, and to determine whether they occur simultaneously or one of them predicts another.The main limitation of our study is a small number of participants, thus a random effect of our findings cannot be totally excluded. Another limitation is its cross-sectional design, which did not allow us to find causal relationship between analyzed variables. And finally, eGFR results calculated using CKD-EPIThe study group consisted of 31 patients (9 women) with type 1 diabetes. The inclusion criteria were: age below 45 (to avoid age-related hearing impairment) and diabetes duration less than 10 years (to avoid advanced diabetic complications). The exclusion criteria were: type 2 diabetes, clinically overt hearing impairment, occupational noise exposure or a history of ototoxic medications use.1c level from capillary blood sample and urinary albumin excretion (UAE) from the first morning urine sample were measured using certified DCA 2000® + analyzer  with the monoclonal antibody method. To calculate eGFR Chronic Kidney Disease Epidemiology Collaboration (CKD-EPIcr) equation, currently recommended by Diabetes Poland was used26:In all subjects body weight and height were measured and body mass index (BMI) was calculated. Blood pressure was measured in a sitting position after at least 5 minutes of rest using the automatic Omron 705 IT blood pressure monitor . Then fasting venous blood samples for laboratory tests (lipid profile and creatinine level) were obtained. They were measured in the certified laboratory using an Architect c8000 analyzer . HbAScr is serum creatinine (mg/dL), κ is 0.7 for females and 0.9 for males, α is −0.329 for females and −0.411 for males, min indicates the minimum of Scr/κ or 1, and max indicates the maximum of Scr/κ or 1.Then patients were referred to the audiological laboratory in the Otorhinolaryngology Department at the Regional Specialist Hospital in Rzeszów, Poland. After a detailed ENT examination by the same ENT specialist , audiological tests were performed.5. Mild and moderate hearing impairment were recognized at hearing thresholds exceeding 20 and 40 dB respectively, in at least one frequency27. The mean TEOAE amplitude below 6 dB in a band range 1.2–3.5 kHz was considered as a lack of otoacoustic emission28.In all patients pure-tone audiometry, transient evoked otoacoustic emissions (TEOAE) and auditory brainstem responses were evaluated. Detailed methodology of audiological tests was described elsewhereIn all but one patient eye fundus examination by an experienced ophthalmologist was performed within 3 months window from audiological evaluations.2 test. The linear correlations between analyzed variables were assessed using Pearson product moment correlation test after checking the normality of distribution by Shapiro-Wilk test. To assess the strength and independency of these associations, the multiple linear regression test was used. A P value of < 0.05 was considered statistically significant.Statistical analysis of the data was performed using SigmaPlot for Windows, version 12.5 . The continuous data are presented as mean ± SD (standard deviation). Differences between two groups were analyzed using a Student’s t-test or by a Mann-Whitney rank sum test where appropriate. The categorical data are presented as numbers and they were compared using χThe study was approved by the Bioethics Committee at the District Medical Chamber in Rzeszów and by the all appropriate administrative bodies. The study was conducted in accordance with ethical standards laid down in an appropriate version of the Declaration of Helsinki, and in Polish national regulations. All subjects signed informed consent form.


Idiopathic intracranial hypertension (IIH) is characterized by elevated intracranial pressure of unknown etiology and venous sinus stenting may be an optional treatment. We aimed to evaluate the effects of venous sinus stenting on visual function, intracranial pressure, and trans‐stenotic pressure gradient of the patients with IIH and to determine effects of baseline BMI or weight changes on subjective vision outcome and intracranial pressure.From July 2009 to Aug 2016, 88 eligible patients with IIH and venous sinus stenosis who underwent stenting were retrospectively studied.2. Here, 66 (75.9%) patients had papilledema, 39 had impaired vision before stenting; 57 patients were followed‐up, 48 (84.2%) showed significant subjective improvement or recovery in visual acuity, 4 (7.0%) patients reported no significant change in visual functions, and 5 (8.8%) suffered permanent vision loss. The cerebrospinal fluid opening pressure and trans‐stenotic pressure gradient were significantly decreased postoperatively. Baseline BMI was associated with pre‐and postoperative trans‐stenotic pressure gradients, as well as changes in cerebrospinal fluid opening pressure. However, baseline BMI and body weight changes during follow‐up were not necessarily associated with subjective visual outcomes after stenting. Stenting efficacy was limited in patients with severe preoperative optic symptoms.In this study, 67 women and 21 men were included with an average age of 39.01 (18–60) years. The average BMI was 26.75 kg/mVenous sinus stenting represented an effective treatment for resolving visual dysfunction and intracranial pressure associated with venous sinus stenosis. BMI seemed to be associated with intracranial pressure but not subjective visual outcomes after stenting. A time‐of‐flight venography was used to assess stenosis of the lateral sinus.Patients were considered for venous sinus stent implantation if they had one or more of the following conditions: refractory or intolerant‐to‐standard conservative therapy , failed surgical procedure, persistent or progressive papilledema, intractable headaches, significant IIH, or a diagnosis of venous sinus stenosis > 50% with a trans‐stenosis pressure gradient ≥ 7 mmHg. Baseline, intraprocedural, and postoperative clinical data for each recruited patient were collected from medical charts and neuroimaging. This study followed the principles outlined in the Declaration of Helsinki. Institutional review board approval was obtained from Chinese PLA General Hospital.2.2Detailed ophthalmologic examinations were performed on presentation, before stenting and in the follow‐up. Funduscopic examinations, visual acuity testing, and visual field testing were conducted to evaluate patients’ ophthalmological function. Funduscopic examination identified optic pathologic changes, such as papilledema, optic disc and retinal edema or hemorrhage, and blurred papillary boundary. Visual fields were assessed by manual kinetic Goldman perimetry. Visual acuity was measured using an international vision chart. Optic atrophy was assessed according to clinical symptoms and funduscopic examination and confirmed by visual electrophysiology. Optic tests were performed prior to stent implantation to establish diagnosis and to determine the degree of optic nerve impairment. Lumbar punctures at L3–L4 was performed within one week prior to and one week after the stenting procedure to determine the cerebrospinal fluid opening pressure.2.3A routine anti‐platelet therapy including a daily loading dose of 75 mg of clopidogrel and daily dose of 300 mg of aspirin were prescribed about 5 days prior the stent implantation. For patients with a history of arterial or deep venous thrombosis‐associated disease, an anticoagulated heparin combined with a single antiplatelet therapy was given before the procedure. All stenting procedures were performed under general anesthesia. Arterial femoral access was obtained, preprocedural high‐solution digital subtraction angiography (DSA) was performed to exclude vascular malformation or fistula and to identify general features of the stenosis, including location and degree of the stenosis, the presence of collateral vascular dilatation, arteriovenous circulation time, and filling duration. Meanwhile, venous femoral access was obtained, and a diagnostic venography was performed to further observe the morphological features of the stenosis. Intravenous heparin was maintained based on individual body weight. A guide catheter was advanced into the internal jugular vein ipsilateral to the stenosis and directed into the lateral sinus. A manometer was connected to guide the microcatheter and to determine the intravenous pressure in various venous sinus, ipsilateral, and contralateral jugular veins and in the stenotic segment. The trans‐stenotic pressure gradient was defined as the difference in pressure between the distal and proximal stenotic segments. Pressure was assessed and recorded before and after the procedure. Afterwards, a stent of appropriate size was deployed across the stenosis with the assistance of a guide wire. Angiography or venography was performed once more after releasing the stent to observe the improvement of blood flow in the lesioned sinus and determine if a balloon dilatation could be considered as necessary.2.4After the stenting procedure, the patients were given low‐molecular heparin for 3 days. They continued antiplatelet treatment (75 mg of clopidogrel daily and 300 mg of aspirin daily) for 3 months. Then, clopidogrel administration was discontinued and aspirin was reduced to 100 mg per day for another 6 months. For patients with thrombophilic disorder, long‐term anticoagulation therapy was recommended.2.5The recruited patients in this study were recontacted by telephone in July 2017. They were inquired about the following information: alternation of IIH‐associated symptoms ; having ophthalmic assessment or not and the corresponding results; whether radiographic examinations were performed and the recurrence of restenosis; recent body weight.2.6SD) with minimum and maximum values. Categorical variables are expressed as frequency or percentage (%). For continuous variables, a paired or unpaired t test was used to compare two groups. For multiple comparisons, a one‐way analysis of variance followed by LSD were performed. A Pearson's chi‐square test or Fisher's exact test was used to compare categorical variables. Pearson's correlation analyses were performed to evaluate the association between each two parameters of BMI, pressure gradient, and lumbar puncture pressure. A multivariate forward stepwise Logistic regression analysis was used to determine independent predictors for clinical outcome after stenting. A p value less than 0.05 was considered significant.All statistical analyses were performed using SPSS22.0 . Continuous variables are presented as means ± standard derivation  patients had normal BMIs, 44 (51.76%) were overweight and 18 (21.18%) patients were obese. Body weight or height data was not available for three patients. Here, 64 patients (72.7%) reported visual impairment, and 51 (58%) reported headaches. Comparable proportions of patients suffered from dizziness and tinnitus (15.9% and 13.6%). Eight patients experienced transient ischemic attack and five cases reported limb weakness. The mean medical duration of the symptoms with multiple presentations was 7.8 (0.4–84.0) months (Table The study comprised 88 eligible patients with an average age of 39.01 (18–60) years, 67 (76.1%) of whom were female. The mean BMI was 26.75 (18.59–40.58) kg/mSince visual impairment is a typical symptom of IIH, we then summarized the ophthalmological changes of the recruited patients. As shown in Table 3.2All patients in this study had venous sinus stenosis, located almost exclusively in the lateral venous sinus (98.9%), except for 1 (1.1%) in the sagittal sinus. Among them, 70 stenoses were in the transverse‐sigmoid (T‐S) sinus junction, 13 were in the transverse sinus, and 7 patients had bilateral stenoses at the T‐S junction. A variety of bare metal stents were used. The Precise nitinol carotid stent was used in approximately 80% of patients, followed by Xpert, Wallstent, Solitaire, and PROTÉGÉ stents. Stenting procedures were completed with a technique success rate of 100%. No neurological complications related to stent implantation were reported.3.3In the follow‐up, 57 (64.8%) patients were contacted and 40 of them reported headaches and 55 reported visual impairment prior the stenting. 37 (92.5%) reported that their headaches significantly improved (17/40) or completely resolved (20/40) after the procedure. 28 of them reported significant relief of their symptoms immediately after stent deployment. Symptoms of the remaining patients (9/40) progressively improved over 2–7 weeks after the stent implantation. Besides, 48 (84.2%) patients reported significant improvement or recovery in visual acuity, 4 (7.0%) reported no significant change in visual functions and 5 (8.8%) suffered permanent vision loss, including three single left blindness and two binocular vision loss. All patients who lost their vision had preoperative papilledema, four of them had poor visual function with no or residual light perception before stenting that was complicated by initial optic atrophy. However, 39 patients had further ophthalmic examinations after discharge, all of them had papilledema resolved or almost completely resolved. The media acuity increased to 0.8 (range 0.02–1.25) and mean visual field defects were −9.35 dB and −7.28 dB in the left and right eyes in the follow‐up. Finally, two patients died during follow‐up, one from cerebral infarction and one from the advanced intracranial glioma diagnosed about one year after stenting. No recurrent stenosis was found in these patients.3.42O (ranging from 260–600). In the 53 patients for whom postoperative CSF opening pressure was available, it reduced to 221.08 ± 49.71 (ranging from 113–360). Moreover, opening pressure decreased after stenting in 52 patients, with only one patient experiencing a slight 10 mmH2O increase after stenting. The remaining patients did not receive lumbar punctures because of symptom improvement or lost to follow‐up, and no data were retrievable. The pre‐ and postpaired comparison of patients’ opening pressure shows a significant decrease after stenting   . A gradual increase of trans‐stenotic pressure gradient with elevated BMI was observed in patients with IIH both before and after stenting. For patients with normal BMI, no residual pressure gradient was indicated after treatment  and CSF opening pressure and trans‐stenotic pressure gradient was determined. Interestingly, we found that the normal weight patients presented slightly higher CSF opening pressure than the other two groups. However, they also had the most significant shifts after stenting, compared with the other two patient groups (p = 0.874). Besides, we noticed that all five patients who had vision loss were either overweight or obese. During the follow‐up, 48 patients were tracked for changes in body weight. Of those, 25 remained stable, 13 lost weight, and 10 gained. We then examined whether body weight change after stenting could markedly affect clinical outcomes. It was showed that postoperative body weight control or gain did not significantly alter the population outcomes   of ophthalmological symptoms using logistic regression analysis of stenting outcomes. The multivariate analysis showed that female gender, stent type, and papilledema and vision dysfunction were associated with an increased risk of poor prognosis. However, no significant differences were indicated in these variables Table .4Venous sinus stenosis is a relatively recent discovery observed in approximately 90% of patients with IIH, and thus venous sinus stenting is an alternative treatment modality. In this study, we summarized the effect of venous sinus stenting on patients with IIH and stenosis and further evaluated potential factors that affect the efficiency of stenting.It is considered that the obstructed venous outflow at venous stenosis will induce venous sinus hypertension and CSF reabsorption deficiency across the arachnoid villi. The elevated pressure derived from CSF compresses brain parenchyma and the compliant venous sinus system, in turn leading to increased intracranial hypertension which is responsible for the IIH symptoms and obstructed venous outflow . Cerebral stents can effectively treat high‐frequency venous sinus stenosis and the resultant intracranial pressure (Patsalides et al., 2 (Raper et al., Body weight is a well‐acknowledged risk factor that is experientially considered to be important for relieving symptoms of IIH. Even one study reported that as little as 6% reduction of the body weight was effective for relieving IIH symptoms (Wall et al., We traced body weight changes of patients after treatment and analyzed whether losing weight improved their symptoms. No significant impact of weight change on visual outcome was detected during follow‐up. Chagot et al. have suggested that weight gain, rather than initial weight, is a leading factor of poor visual outcome in patients with IIH using first‐line treatment (Chagot et al., 5Venous sinus stenting showed excellent efficiency in resolving vision impairment and suppressing CSF opening pressure and the trans‐stenotic pressure gradient caused by venous sinus stenosis. Baseline BMI was associated with the pre‐ and postoperative trans‐stenotic pressure gradient and with changes in CSF opening pressure. However, no association between baseline BMI or body weight changes during follow‐up and visual outcomes after stenting.All authors declare that they have no conflicts of interest.


Factors associated with left ventricular systolic dysfunction (LVSD) of peritoneal dialysis (PD) patients are limited. We aim to explore and quantify the associated factors of LVSD among PD patients.P value < 0.05 was considered significant.Participants from a PD clinic treated between 2012 and 2014 at the HRH Princess Maha Chakri Sirindhorn Medical Center, Srinakharinwirot University, Nakhon Nayok, Thailand were recruited and divided into 2 groups according to their left ventricular ejection fraction (LVEF) (< 50% vs. ≥ 50%) with LVEF < 50% considered as LVSD. Correlations among the clinical, laboratory and echocardiographic variables were analyzed. The factors associated with LVSD were explored with univariate and multivariate logistic regression analyses. Beta coefficient along with odds ratio and 95% confidence interval (CI) were calculated and the n = 18, 17.5%). The mean (SD) age was 59.3 (12.7) years, and nearly halves were males. Preexisting CAD, diabetes (DM) and current smoking were 20 (19.4%), 63 (61.2%) and 23 (22.3%) patients, respectively. The median time of dialysis vintage was 12  months. Factors associated with LVSD and corresponding ORs with 95% CI by multivariate analysis were prior coronary artery disease (CAD) [5.08 ], DM [6.36 ], smoking [10.62 ], neutrophil to lymphocyte ratio (NLR) > 3.6 [6.77 ], and high serum phosphate [9.39 ] were significantly associated with LVSD.Among 103 subjects stratified as LVSD  contains supplementary material, which is available to authorized users. Cardiovascular diseases (CVDs) are the leading causes of death in patients with end stage renal disease (ESRD) or on dialysis rather than progress to ESRD . AtherosThe inflammatory response is a key mechanism in the pathogenesis of atherosclerosis and its related clinical syndromes. Prior studies have proposed that inflammation may be responsible for LVSD and left ventricular diastolic dysfunction in PD patients , 16. TheAll PD patients treated between 2012 and 2014 from the PD clinic at the HRH Princess Maha Chakri Sirindhorn Medical Center, Srinakharinwirot University, Nakhon Nayok, Thailand were recruited. Our PD patients were prescribed only glucose-based PD solution. The most percentage of glucose-based PD solution was 1.5% dextrose. The 2.5 and 4.25% dextrose-based PD solution could be in a short term if patients had severe hypervolemia. The criteria for eligibility were patients at least 18 years of age without history of heart failure or pulmonary embolism, valvular heart disease, congenital heart disease, acute coronary syndrome, chronic lung and liver diseases, systemic lupus erythematosus, scleroderma, initiating PD treatment ≤2 weeks and infection during 3 months prior entry into this study. These data were verified by the physicians who were involved in our protocol. All patients have given their written, informed consent.2 (kg/m2).Baseline demographic and clinical data were collected. These include; age, gender, body mass index (BMI), body surface area (BSA), underlying diseases , duration of PD therapy , current medications, history of smoking and alcohol use, systolic blood pressure and diastolic blood pressure levels. CAD is defined as history of receiving angioplasty, coronary artery bypass graft surgery, myocardial infarction or angina. BMI was calculated as weight/heightTrans-thoracic echocardiography  was perfBy 2-D directed M-mode tracings, LV end-systolic diameter (LVESD) was estimated at end-systole, whereas LV posterior wall diastolic thickness, LV end-diastolic diameter (LVEDD) and interventricular septum diastolic thickness were determined at end-diastole. Left atrial (LA) volume and LA volume index (LAVI) were measured by biplane area-length method. Left ventricular mass was calculated by use of the Devereux formula . Left veIntra- and inter-observer reliability of TTE were analyzed prior to the initiation of this study. The continuous data was expressed as mean with standard deviation (SD) if normally distributed, or median with interquartile range if not. Subjects were divided into 2 groups of LVSD according to the cut off value of LVEF (< 50% vs. ≥ 50%). The categorical variables were presented as frequencies and percentages analyzed using Chi-square test or Fisher’s exact test. Comparisons between groups of patients on continuous variables were performed using the Student’s t-test or Mann-Whitney test. Pearson’s and Spearman’s rank correlation were applied to investigate the trend and strength of associations between LVSD and various risk factors. The univariate and multivariate logistic regression analyses were performed to determine significant factors associated with the categorical outcome variable of LVSD.P value < 0.05 was considered significant. All statistical analysis was done using STATA 14.2  software.Data analysis was initiated with a univariate logistic regression analysis in order to screen for potential candidate variables and then added only these candidates; including NLR and PLR into the same model for multivariate analysis. Because of small sample size when compared with the number of variables needed, forward selection was used for considering which variables should or should not remain in the model. The backward elimination was not performed since it may force the model to over fit as for including all variables initially. Then the model selection was done by using “sw” command in STATA and keeping NLR and PLR as study factors in the model. Beta coefficient along with odds ratio and 95% confidence interval (CI) were calculated and the n = 85, 82.5%) and group 2 with LVEF < 50% or LVSD . The prevalence of LVSD was found 17.5% . Preexisting CAD, DM and current smoking were 20 (19.4%), 63 (61.2%) and 23 (22.3%) patients, respectively. The mean BMI was 24.2 ± 3.6 kg/m2 and the median time of dialysis vintage was 12  months. Prior CAD (p = 0.02), DM (p = 0.03), smoking (p = 0.01) were significantly high while Hb levels were low in the PD patients with LVSD  of PD adequacy was assessed by the total weekly Kt/V of urea was 1.7 . Dialysis efficiency data evaluated by total weekly Kt/V of urea was not analyzed with other factors in the final because 50% of this data was missing.Baseline clinical characteristics, laboratory and echocardiographic parameters are summarized in Table LVSD n = 8, 17.5%.p < 0.01), LAVI (p = 0.03), and right ventricular systolic pressure (RVSP) (p = 0.01) were significantly higher in group 2. The LVEF ≤40% was observed in only 7 of them (6.8%) and that ranged from 21 to 40% (data not shown). LV dilatation was found in 12(14.1%) and 13(72.2%) patients of group 1 and 2, respectively. All patients of group 2 and 52 (61.2%) patients of group 1 have met the criteria of elevated LV filling pressure and at least grade II of LV diastolic dysfunction . The left ventricular mass index (LVMI) (function : averagep = 0.03), Hb level  and serum calcium  showed a considerably positive correlation with LVEF. The serum phosphate , LVEDD , LAVI , LVMI  and RVSP  were significantly negative correlations . However, in multivariate analysis showed only that the underlying CAD , DM , smoking , NLR > 3.6 , and high serum phosphate  were significantly associated with LVSD , and PLR > 150 , were significant variable factors associated with LVEF ≤40% , high sensitivity CRP (hs-CRP) and other inflammatory markers are not included in our analysis as a result of the measurement of CRP and hs-CRP not widely used and rather expensive. NLR and PLR could be derived from a routine simple test; i.e., complete blood count. However, previous studies have illustrated the NLR could be a potential surrogate marker of systemic inflammation in its ability to predict hs-CRP  and CRP Prior history of CAD, DM, smoking, high NLR and serum phosphate levels were found to be associated with LVSD for our PD patients. The evidence from prospective study is needed to confirm the predictive value of these variables.Additional file 1:Table S1. Baseline characteristics and Laboratory parameters in group 1  and group 2 (LVSD). Table S2. Echocardiographic parameters in group 1  and group 2 (LVSD). (DOCX 21 kb)


To evaluate the association of pulse pressure (PP) with mortality and majoradverse cardiac events (MACE) in one-year period after anterior ST-elevationmyocardial infarction (A-STEMI).A total of 261 consecutive patients whose blood pressure was measured withthe aid of a catheter before primary percutaneous coronary intervention(PPCI) between August 2016 and February 2017 were included in the study. Thepatients were divided into three groups according to pulse pressure (PP).P=0.005 vs.P=0.042). The rates of MACE and mortality were higher inGroup 1. The predictive PP values were calculated to be 42.5 mmHg fordevelopment of MACE and 41.5 mmHg for mortality. One-year survival ratio wasworse in Group 1 than in the others according to Kaplan-Meier analysis(P<0.001).The mean age of the patients was 63.4±14.1 years, and 206 of them weremale. The groups were similar in terms of age and diastolic blood pressure(DBP). The ratio of female patients in Group 1 was higher, and theirsystolic blood pressure (SBP) was lower than those from the other groups(The values of PP which was measured intra-aortically in patients with A-STEMIwere associated with mortality and MACE in the one-year follow-upperiod. The most important cause of this condition is thedecline of cardiac functions after AMI. This decline's severity is associated withthe localization and size of the infarct region. The inadequacy ofcardiac functions causes acute changes in hemodynamic parameters, and eventually,cardiac output (CO) decreases. The neuroendocrine system is activated in response toan impaired CO. The secretory rhythm of vasopressor substances such as noradrenalineand angiotensinogen-II into the circulatory system changes. With the effect of thesevasopressors, changes occur in SBP and DBP compared to their baselinevalues.Acute myocardial infarction (AMI) is one of the leading causes of mortalityworldwide. For this reason, bloodpressure levels in risk scoring systems, which are used after ACS, rank as importantprognostic indicators. Pulse pressure (PP) is the difference between SBPand DBP. PP provides important information about the status of the arterialcirculation such as cardiac contraction and stiffness. It is suggested that thepower of PP for predicting cardiovascular events is higher than that of SBP andDBP.The PP of AMI patients, which is measured with the aid of a cuff from the arm at thetime of the first admission to the emergency service, is one of the determinants ofin-hospital and post-discharge long-term prognoses,8. However, the centralblood pressure measured from the aorta has a stronger association with early andlong-term outcomes of cardiovascular pathologies than the blood pressure measuredfrom the arm,10.The changes in blood pressure after acute coronary syndromes (ACS) were demonstratedto be associated with increased morbidity and mortalityIn our study, we measured intra-aortic blood pressures of patients in whom primarypercutaneous coronary intervention (PPCI) was planned due to anterior ST-elevationmyocardial infarction (A-STEMI) with the aid of a catheter before PPCI. In line withthe guidelines, we included patients who had normal blood pressure range. We aimedto evaluate the association of PP with mortality and major adverse cardiac events(MACE) in one-year period after A-STEMI.The patients of this study were gathered at a tertiary centre between August 2016 andFebruary 2017. The approval from the ethics committee was obtained prior to thestudy, and all researchers completed the study in accordance with the HelsinkiDeclaration.th percentile were considered as A-STEMI. Since ourcentre has a team on call for 24/7, the patients were quickly taken to theangiography laboratory after being diagnosed with A-STEMI.Patients in whom less than 12 hours has passed after the onset of ST-elevationmyocardial infarction (STEMI) and who were taken to the angiography laboratory forPPCI were evaluated. Those who had single vessel disease, age between 18 and 80years, and left ventricular ejection fraction (LVEF) more than 25% were included inour study. Since hypotensive periods were more frequent in inferior STEMIs, creatinga homogeneous group was aimed. Therefore, only patients with A-STEMI were includedin the study. Electrocardiographic examinations were performed during the periodwhen the patients were first admitted to the emergency department. Presence of STelevation ≥ 0.2 m in at least two of the precordial leads, newly developedleft bundle branch block, presence of chest pain with the typical onset and spread,and cardiac troponin-I (c-TnI) and creatinine kinase-myocardial band (CK-MB) valuesgreater than the 99Antiaggregant therapy of these patients  was initiated in the emergency service. Also,concurrently, unfractionated heparin was administered via intravenous (IV) route atthe dose of 100 IU/kg. An additional dose of IV unfractionated heparin wasadministered as needed so that the activated coagulation time would be >250.Beta-blockers, statins, and renin-angiotensin-aldosterone system (RAAS) blockerswere initiated after PPCI according to the hemodynamic state in the intensive careunit.2, chronic pulmonary disease, chronic liver disease,and presence of previous cerebrovascular disease. In addition to these, patientswith previously diagnosed hypertension and who were on antihypertensive medicationwere not included in the study. To minimise the effects of SBP and DBP levels on thestudy's outcome, the condition of having these values within normal limits (100-140mmHg for SBP and 60-90 mmHg for DBP) according to current hypertension guidelineswas applied. In our study, patients with hemodynamically unstable requirement ofinotropic agents and intra-aortic balloon pump (IABP) were excluded.The exclusion criteria included passing more the 12 hours after the onset of A-STEMI,previous AMI history, presence of known heart failure, presence of moderate to highheart valve insufficiency and/or stenosis, glomerular filtration rate (GFR) lessthan 30 ml/min/1.73 mBlood pressure measurements were performed using a 6F pigtail catheter which wasplaced in the ascending aorta just before coronary angiography. Before eachmeasurement, the pressure monitor was calibrated to zero. The system was rinsed withheparinised liquid, and it was paid attention not to leave any air inside. Thetransducer of the system to measure blood pressure was set at the same level withthe patient's heart. PP was calculated by subtracting DBP from SBP. The patientswere divided into three groups according to their PP: Group 1 included patients withPP <35 mmHg, Group 2 included patients with 35≤PP≤50 mmHg, andGroup 3 included patients with PP> 50 mmHg.The study's endpoints were accepted as all-cause mortality and MACE . Cardiogenic shock was defined as persistenthypotension which does not respond to IABP placement, inotropic support, and fluidsupport after PPCI and circulatory impairment. Re-MI was defined as recurring chestpain, new electrocardiogram (ECG) changes, and increase of cardiac enzymes comparedto previous values. Stroke was defined as the presence of focal neurological deficitwhich persists more than 24 hours and its confirmation with methods such as computedtomography (CT) and magnetic resonance imaging (MRI). The SYNTAX score (STXs) wascalculated to determine the prevalence of coronary artery disease(www.syntaxscore.com).Echocardiographic examinations are performed routinely on AMI patients in theemergency room of our centre; the patients are evaluated quickly, and images arerecorded. These examinations can be completed without a significant delay owing tothe presence of the angiography team and a cardiologist on call for 24/7 in theemergency. Cardiac function, valve function, and complications at admission wereevaluated with echocardiography. The LVEF of all patients was calculated by themodified Simpson method. Patients were followed-up for one year after A-STEMI; theywere called to outpatient clinics at 1, 3, 6, and 12 months.P values of which was found to beP<0.10 were evaluated by univariate analyses. Receiveroperating characteristic (ROC) analyses were performed to determine the PPvalues associated with mortality and MACE. The area under the curve (AUC),cut-off value, sensitivity, specificity, and confidence interval (CI) weredetermined by ROC analyses. The P values <0.05 were acceptedas statistically significant.In our study, the SPSS 17.0  program was used forstatistical analysis. Data distribution was checked by the Kolmogorov-Smirnovtest. Continuous variables were expressed as mean standard deviation (SD) ormedian (interquartile range), according to their distribution status. Continuousvariables with normal distribution were compared with the analysis of variance(ANOVA), those with non-normal distribution were compared with the Wilcoxon ranktest. Categorical variables were assessed with the chi-square test. Cumulativesurvival and MACE curves were plotted, and log-rank analysis was performed usingthe Kaplan-Meier method. Correlation analyses were performed to determine therelationship between PP and LVEF, c-TnI, CK-MB, and symptom-to-door (StD) time.Univariate analyses were performed with the variables, such as age, gender,diabetes mellitus, heart rate, smoking, hyperlipidemia, SBP, DBP, PP, STXs,LVEF, cTn-I, StD, door-to-balloon time (DtB), GFR, thrombolysis in myocardialinfarction (TIMI) flow grade, use of glycoprotein (GP) inhibitor, beta-blockers,and RAAS inhibitors in order to determine the predictors of MACE. Backwardstepwise multivariate regression analysis was performed with variables of thefemale gender, SBP, PP, LVEF, GFR, beta-blockers, RAAS inhibitors, and StD; theOf 297 patients who underwent PPCI with the diagnosis of A-STEMI in our clinic, 261completed a one-year follow-up. Thirty-six patients who could not come to theircontrol meetings for the study or who could not be contacted afterwards were notincluded in the statistical analysis. Of the studied patients, 206 were male and 55were female. The male patient ratio was lower in Group 1. Mean age was calculated as63.4±14.1 years. Means of smoking patients and SBP were higher in Groups 2and 3. General characteristics, laboratory data, and medical treatments of the studygroups are shown in Mortality, MACE, cardiogenic shock, and newly-onset atrial fibrillation were morefrequent in Group 1 compared to other groups. Re-MI, major stroke, mechanicalcomplication, ventricular tachycardia, major bleeding, and TIMI flow grade <IIIwere similar. The distribution of adverse events, which were seen during theone-year of follow-up, is shown in In the ROC analysis, the predictive PP value was calculated as 42.5 mmHg for MACEdevelopment and 41.5 mmHg for mortality . The patP=0.034 vs.HR 1.6 [1.1 to 3.1], P=0.041).After univariate and multivariate analyses carried out with the variables that couldaffect mortality, LVEF, inability to initiate beta-blockers in the acute period, PP,SBP, GFR, and STD were determined to be mortality predictors  and 4. AIn our study, it was determined that the PP measured in A-STEMI patientsintra-aortically before PPCI was significantly associated with MACE.. The studies in the following years suggested theidea that SBP is more important and it is not necessary to evaluate DBP forprognosis. Afterwards, the studies that evaluated therelationship between ACS and blood pressure were concluded. SBP < 90 mmHg afterAMI was generally considered to be a poor prognostic indicator. Various risk scoringsystems were developed as a result of this data. Blood pressure irregularity wasrated as a significant negative indicator. It is known that high blood pressure inpatients with ACS is associated with cardiovascular complications as much as lowblood pressure. AMI blood pressure studies usually assessed SBP levels. However, ina small number of studies, it was determined that the DBP not within the normallimits after ACS was associated with increase in mortality andmorbidity. All these evaluations showed that blood pressureout of the normal limits in AMI patients is a bad indicator. The changes in PPcalculated according to SBP and DBP are indicative of stiffness of vascular bed. Thedramatic decrease in CO and peripheral resistance in the patients with ACS, heartfailure, aortic stenosis, and septic shock were shown to cause a decrease in PP.Significant changes in PP were determined to increase morbidity andmortality.Many studies have discussed the relationship between blood pressure and prognosis formany years. The first blood pressure studies suggested that DBP is the maindeterminant of prognosisindicated that PP lower than 50 mm and higher than 70 mmHg increased the mortalityrates significantly in patients with ACS who were over 80 years old. Patients withPP between these two values had the best prognosis. In this study, no upper or lowerlimit was determined for blood pressure values. Patients with blood pressure valuesbetween 170/100 mmHg and 130/60 mmHg were considered similarly since their PP was 70mmHg.In our study, A-STEMI patients with normal SBP and DBP were followed according tothe recommendations of current guidelines. Thereby, the association of PP with theemerging cardiovascular events in patients with normal SBP and DBP intervals wasattempted to be determined. Patients in Group 1 who had PP lower than 35 mmHg werefound to have the worst prognosis. The highest mortality and MACE rates were also inthis group. Li et al. e El-Menyar et al. also showed that PPreduction in patients with ACS was associated with stroke and mortality. In bothstudies, PP was calculated according to the blood pressure values measured from thearm by experienced health personnel. Li et al. followed-up the patients with AMI whileEl-Menyar et al. followed-up all patients with ACS. As it is known,in all the ACS subgroups, CO does not fall to the same level, and the neuroendocrinesystem is not activated at the same degree. Additionally, cardiac functions do notchange at similar levels in all STEMIs. Blood pressure levels tend to be lower dueto decreased stroke volume and increased vagal stimulation in inferiorSTEMI,17. Therefore, only A-STEMI patients were accepted inorder to create a homogenous group.Li et al.,10, the central blood pressure obtained with the aidof aortic catheter was shown to have a stronger association with cardiovascularoutcomes than that measured from the arm. Thus, central blood pressure measurementsobtained from the ascending aorta with the aid of catheter before PPCI in thecoronary angiography laboratory were taken into consideration in our study. As aresult of one-year follow-up, an increased number of deaths, cardiogenic shocksafter PPCI, and total MACE ratios were detected in Group 1 compared to other groups.The prevalence of LVEF and coronary artery disease was similar among the groups. Therate of female patients in Group 1 was higher than in other groups. As it is known,the pain threshold is higher in women, and the microvascular circulation dynamicsand complication rates after AMI are increased compared to men,19. These findings aresupported by the high number of female patients in Group 1 with higher rates ofmortality and MACE in our study.In the previous studiesWhen the Kaplan-Meier curves were evaluated, the survival rate in Group 1 was worsethan in other groups. There was no difference in survival expectancy between Group 2and Group 3. The PP level limit, which could increase MACE rates, was determined as42.5 mmHg in the ROC analysis. The PP value, which could predict one-year mortality,was found to be 41.5 mmHg. The risk of developing cardiovascular events wasdetermined to be increased below these values. According to multivariate analysis,the predictors of mortality were determined to be PP, SBP, lower LVEF, inability toinitiate beta-blockers in the acute phase, lower GFR, and STD time.-22. Myocardial perfusion pressure decreases withthe decrease of PP. Even if SBP is decreased, the PP can maintain coronary perfusionby staying constant for a certain period. However, the reduction of PP reducescoronary perfusion. Myocardium recovery may be delayed after A-STEMI and sometimesmay not be possible due to decreased perfusion. The reduction in PP is an importantcondition which can increase cardiovascular complication rates due to thesereasons.Statistical analyses revealed that SBP and PP were associated with the complicationsthat could develop. However, the predictive power of PP was found to be higher thanthe one of SBP . This maIn our study, the inability to initiate beta-blockers in the acute phase of thedisease was one of the poor prognostic factors. The patients in whom beta-blockerscould not be initiated included those who generally had hemodynamic instability andwere unable to optimise medical treatments fully. Therefore, we think that there isa significant relationship between beta-blockers and prognosis.showed that there is a positive correlation between LVEF and PP. There was nosignificant difference between the groups in terms of the mean LVEF in our study.However, in the correlation analyses, it was determined that there was a lowpositive correlation between the decline in PP and LVEF and the prolongation of StDperiod. This condition suggests that cardiovascular complications following STEMIare associated with other variables apart from LVEF. It may be useful to considerthe changes in PP other than LVEF.Li et al.Our study's main limitation was the low number of patients. The study wasconducted in one centre. Blood pressure values are dynamic parameters especiallyin patients with STEMI, and sedation, agitation, and inotropic agents may affectthese values. In our study, patients with hemodynamically unstable requirementof inotropic agents and IABP were excluded. We can't extend this result'svalidity to hypotensive patients due to the fact that hemodynamically stablepatients were included in our study. The normalisation of PP with systolicarterial pressure (PAS) or diastolic arterial pressure (PAD) might be beneficialto predict the adequacy of coronary perfusion. PP has been registered with awater-filled catheter and not with high-fidelity catheters. This may reduce thequality of the measurement in patients with lower PP. Although poorlysignificant differences emerged between Group 2 and Group 3, patients weredivided into three groups to see the effect of the extreme values on theresults. Some of the recommended pharmacological treatments after STEMI in thecurrent guidelines could not be initiated in the patients with hemodynamicinstability at the same or in similar doses to the other patients. The leftventricular end-diastolic pressure (LVEDP) could not be calculated by enteringthe left ventricle to avoid time loss since the patients had A-STEMI. If LVEDPcould have been calculated, more accurate results could have been obtained byassessing perfusion pressure. These measurements can be performed in STEMIpatients whose general conditions are stable. In our study, there was asignificant difference between the groups in terms of means of SBP. Although SBPvalues were not the same, unlike other studies, they were in the rangeconsidered as normal by guidelines.In our study, the central PP measured intra-aortically before PPCI in patients withA-STEMI in the angiography laboratory was significantly associated with MACE.Therefore, even if the blood pressure of patients with A-STEMI is within normallimits, it is good to evaluate the changes in PP carefully while arranging follow-upand treatment. Including PP in the algorithms while calculating the risk levels ofpatients after AMI might be beneficial.


Hypothyroidism is highly prevalent in patients with chronic kidney disease (CKD) and has been associated with poorer clinical outcomes, including faster decline of kidney function. However, there is no consensus whether low free thyroxin (LFT) affects the rate of estimated glomerular filtration rate (eGFR) decline and how the presence of proteinuria influences the progression of renal dysfunction in hypothyroidism.We assessed thyroid status, proteinuria, and progression of eGFR by Modification of Diet in Renal Disease equation and CKD-EPI equation in a cohort of CKD patients followed in general nephrology clinics. We estimated the association of LFT levels, and the degree of proteinuria on progression of eGFR. We adjusted for other covariables: age, gender, body mass index, diabetes, hypertension, HbA1c, uric acid, cholesterol, and triglycerides levels..2 in 479 (29.8%), 551(34.2%), and 580(36.0%) patients, respectively. LFT levels were available at initial evaluation in 288(17.9%) patients and 735(48.5%) had assessment of proteinuria . Median follow-up time was of 21 months, and 1223(76%) had at least 1 year of follow up. Overall, eGFR decline per month was − 0.05 ml/min/1.73m2, reaching 1.7 ml/min/1.73m2 by the end of study period. Similar results were obtained using CKD-EPI. Multivariable mixed linear analysis showed that proteinuria and age were independently associated with eGFR decline, with no effect of LFT, and no interaction between proteinuria and LFT. In patients without proteinuria, there was an improvement of eGFR despite the presence of LFT.One thousand six hundred ten patients  were included. At beggnining of follow up eGFR was between 45 and 60, 30–45 and 15-30 ml/min/1.73mWe confirmed a faster rate of eGFR declined in patients with proteinuria. However, despite the pathophysiological rational that hypothyroidism can lead to increased rate of CKD progression, we failed to demonstrate an association between LFT and rate of CKD progression. We conclude that the benefit of hypothyroidism treatment in CKD patients needs to be evaluate in prospective studies. During the embryonic period and after the maturation of the kidney, the thyroid gland influences the kidney’s growth and development. Thyroid hormones play an essential role in renal physiologic homeostasis through direct influence on the expression and activity of a number of ion channels and transporters .2 will receive this diagnosis ). We further classified patients according to eGFR decline/month above or below the cohort median decline as progressors and non-progressors.The rate of renal functional decline was calculated using the formula: slope =  - /months of follow up, and was expressed as the median slope decline eGFR  or as a percent, as appropriate. Normality distribution was verified by the Kolmogorov-Smirnov test. Comparison between patients with and without LFT as well as with and without proteinuria was done by unpaired t-test or Mann-Withney, for continuous variables and Chi-squared or Fisher for categorical variables, as appropriate. To compare longitudinal changes in eGFR across groups with and without proteinuria and with and without LFT, we performed a mixed linear model with repeated measures. The model was applied with a maximum likelihood estimation of variance components. The conditions evaluated were the presence of proteinuria, treated as a fixed factor, the presence of LFT also treated as a fixed factor and the interaction between these factors. Covariates in the model were age, gender, body mass index, and diabetes. The covariance was treated as AR (1) heterogeneous, which exhibited the lowest Akaikes’s Information Criterion (AIC).P values < 0.05 were considered to be statistically significant. Statistical analyses were performed using SPSS version 21.0 .In multivariable logistic regression analysis, we tested the factors associated with eGFR decline. Independent variables examined in the model were LFT, proteinuria, age, gender, BMI, presence of diabetes, and systolic blood pressure. 2 in 479 (29.8%), 551 (34.2%), and 580 patients (36.0%), respectively. Hypertension was highly prevalent, whereas diabetes mellitus was found in 25.3% of patients. Although mean levels of total cholesterol were within normal range, 37% of patients presented hyperlipidemia, and 61% had hyperuricemia.Clinical and biochemical characteristics of the patients are described in Table p = 0.0001) and presented high levels of total cholesterol  and triglycerides . There was no other clinical or biochemical difference between patients with and without LFT.Two hundred and eighty eight patients (17.9%) had LFT at baseline, and of these, 113 (39.2%) were receiving thyroid hormone replacement. Patients with LFT were younger .Albumin-creatinine ratio (ACR) was in 1514 patients, and it was above 0.3 g/g in 735 (48.5%). Proteinuria was more frequent among patients with LFT than without LFT . There was no difference in baseline eGFR in patients with and without LFT (p = 0.114).Fig. 2.The median follow up time was 21 months, and 1223 (76%) had at least 1 year of follow up. Overall, eGFR decline per month was − 0.05  ml/min/1.73 mResults of multivariable mixed linear analysis adjusted for age, gender, diabetes, and BMI are shown in Table Logistic regression on the independent risk factors for eGFR/month decline was buil with the first quartile (worse eGFR decline) as the dependent variable. Results showed that proteinuria but not LFT was independently associated with a greater decline in renal function. Figure CKD-EPI equation was calculated according to a previous report  and yielIn this retrospective analysis of CKD patients we failed to demonstrate an association between low thyroxin levels and rate of decline of kidney function. The sensitivity analysis, in patients with proteinuria was also negative, with no effect of LFT on eGFR decline, suggesting that LFT does not play a role on kidney function decline.Based on experimental data, hypothyroidism could impact renal function decline as it promotes significant alterations on cardiac and renal systems, affecting glomerular filtration and renal plasma flow –24. A feDespite this knowledge from experimental studies, clinical data demonstrating the association between LFT and loss of renal function is still controversial. Previous studies have shown that the decline in eGFR can be reversed, or at least attenuated, by exogenous thyroid hormone replacement, which indicates that kidney dysfunction could be the end result of functional changes rather than histological damage , 8. WhilIt is well accepted that proteinuria is associated with worse renal and clinical outcomes, including myocardial infarction, and all-cause mortality . ProteinThere are some limitations to our study. First, it is a retrospective study, and we did not control for the frequency of thyroid function and creatinne assessments, as they were measured at the discretion of health care providers. Secondly, we used creatinine-based estimates of eGFR and not assessed measured GFR; in aditiion we used Jaffé assay to measure creatinine, which is less accurate in the presence of glucose or protein. Patient adherence to thyroid hormone supplementation and dose were not available. We have focused on the final eGFR to calculate decline, and our follow-up was relatively short. Lastly, we did not have information on the coexisting medical conditions such as cardiac disease or neoplasia . NeverthOur study failed to demonstrated an association between low free thyroxine levels and CKD progression. The rate of progression of the CKD was greater in the presence of proteinuria, with no effect of thyroxine levels. Given the emerging literature on the association between LFT and loss of kidney function, our findings indicate the need for a prospective studies evaluating the impact of hypothyroidism treatment on CKD progression.


The presence of comorbidity can be associated with poorer asthma outcomes. Previous prevalence studies focused on a limited selection of comorbid conditions in asthma only. We aimed to determine age- and sex-specific prevalence estimates for the full range of chronic comorbid conditions in adult asthma patients by performing a retrospective cohort study based on 32,787 medical records of patients aged ≥16 years with asthma from 179 general practices in the Netherlands. Age- and sex-specific prevalence estimates of 76 chronic comorbidities and 14 disease categories based on International Classification of Primary Care codes were determined. Chronic comorbidity was present in 65.3% of male asthma patients and 72.8% of female asthma patients, with female patients having a higher mean (SD) of 2.0 (2.1) comorbidities compared to male patients (1.7 (2.0)). This mean increased to 5.0 (2.7) conditions in the 75+ age group. Most prevalent comorbidities were hypertension (20.1%), osteoarthritis (11.5%), eczema (11.5%) and dyspepsia (10.7%). Compared to male asthma patients, female asthma patients showed higher odds for the presence of other chronic conditions in eight disease categories. Neurological , blood forming/lymphatics  and musculoskeletal diseases  showed the highest association with female sex. In conclusion, the presence of chronic comorbidity is the norm in adults with asthma and it is more prevalent in female than in male asthma patients. The odds of having a specific comorbid condition may differ between the sexes. Attention in guidelines on how to handle comorbidities may lead to a more targeted treatment for comorbidities and more patient-centred asthma management. In the Netherlands 31.8 per 1000 men and 40.5 per 1000 women consult a general practitioner (GP) with asthma complaints every year.2Bronchial asthma is a common chronic pulmonary disease, which is characterized by inflammation, obstruction and hyperresponsiveness of the bronchial tree.3 and the presence of this comorbidity can be associated with poorer asthma control, lower quality of life, higher morbidity and higher mortality.7 The identification and management of comorbidity is therefore increasingly recognized as an important part of asthma management.8Asthma frequently co-exists with other diseases9 Often these studies specifically included a hospital care population, thus representing patients in the more severe part of the asthma severity spectrum only.10 Other studies only focused on specific age groups like children or the elderly and are therefore not representative for the asthma population at large.12Several specific comorbidities like  rhinosinusitis, gastro-oesophageal reflux disease (GERD) and other respiratory diseases like chronic obstructive pulmonary disease (COPD) are known to be more prevalent in patients with asthma.17 Compared to non-asthma controls, asthma seems to be weakly associated with a higher prevalence of comorbidity in different disease categories like cardiovascular, other respiratory and mental diseases. However, these studies investigated only an a priori, limited selection of chronic conditions or major disease categories, or did not necessarily represent the asthma patient population that is managed in general practice. Therefore, comorbidity prevalence estimates from these studies may not reflect the true burden of comorbidity in the general practice asthma patient population. Therefore, the main aim of this study was to determine sex- and age-specific prevalence estimates for the full range of chronic comorbid conditions in adult asthma patients in real-life general practice. As our aim was not to look whether or not patients with asthma have an increased risk of other chronic conditions, we chose not to include a control group of non-asthma subjects in our study.Several previous studies have looked at the association between asthma and other chronic diseases in general population samples.n = 32,787). Just over 40%  were male patients. Mean (SD) age at the start of the study period (on 1 January 2012) was 46.3 (17.7) years. Eight percent  of patients were lost to follow-up before the end of the 2-year observation period. Reason for loss to follow-up was known for 44.9% of patients, with moving out of the practice being the predominant reason. Patients lost to follow-up were 38.3% male patients, had a mean age of 45.2 (standard deviation (SD) 19.0) years and were comparable with the patients with complete follow-up  years). Twelve percent  of patients entered the cohort after the start of the study period.Data from 40,050 patients aged ≥16 years with an asthma diagnosis were available. Of these patients, 7263 were excluded because they did not meet the criterion of having an ‘active’ diagnosis of asthma. Table p < 0.001), but this difference was no longer seen in the 75+ years age group.Table p < 0.001).Almost 35% (34.7%) of male patients and 27.2% of female patients had only asthma. For all ages combined, 40.4% of male patients and 47.9% of female patients had two or more chronic conditions next to their asthma , thus representing the ‘real’ prevalence of chronic comorbidity in the adult asthma patient population. The estimates of the most prevalent comorbid conditions in our study were comparable to other population-based and cohort studies, with hypertension being the most prevalent comorbid condition.16 Hypertension has been associated with poorer asthma control in previous studies.18 Other prevalent comorbidities in our study like GERD, eczema, COPD and sinusitis are also known to be associated with poorer asthma outcome.20 Prevalence of mental conditions in patients with asthma varies exceedingly in previous studies.24 Our prevalence estimates for depression (4.6%) and anxiety (4.9%) were in the lower range of this spectrum. This is probably due to the additional criterion to express chronicity in our study (recurrence of the depression episode within 24 months). Therefore, the prevalence estimates of these mental conditions as well as the other ‘conditionally chronic’ conditions in our study represent chronic instead of episodic conditions and are thus more clinically relevant.Our study confirms previous reports that chronic comorbidity is highly prevalent in patients with asthma.25 Sex differences in asthma severity have been described before.26 Cazzola et al.13 found that being female slightly increased the association between cardiovascular diseases, diabetes mellitus, dyslipidaemia, osteoporosis, mental diseases and GERD and asthma. Of these diseases, in our study only osteoporosis and mental diseases were associated with female sex, whereas GERD was associated with male sex. Our observation that cancer was associated with female sex and urogenital diseases with male sex should be interpreted with caution because these categories contain sex-specific diseases (i.e. ovarian cancer and prostate disorders).In our study, more women than men suffered from asthma, which is in agreement with earlier findings.This study’s major strength is the inclusion of almost 33,000 patients with asthma. Exclusion criteria were minimal, so this cohort can be considered as representative for the general adult asthma population. Moreover, we looked at the total range of chronic comorbid conditions as well as at ‘conditionally’ chronic and recurrent conditions without making an a priori selection. This results in more precise and real-life estimates of the prevalence of chronic comorbidity in adult patients with asthma compared to previous prevalence studies. Our additional analyses based on age groups and sex completed the comprehensive overview of the prevalence estimates of chronic comorbidity in patients with asthma in general practice.16This study also has some limitations, most of which are inherent to its observational and retrospective design. Firstly, because of the lack of a control group, it was only possible to determine the prevalence estimates of comorbid conditions in patients with asthma. However, the aim of our study was to determine the age- and sex-specific prevalence estimates of the ‘full range’ of chronic comorbid conditions in patients with asthma, not to find out whether or not patients with asthma have a higher risk of developing other chronic conditions, as this has already been investigated in several population-based studies.27 Regarding the prevalence estimates of the comorbid conditions in our study, underestimation may have occurred due to under-registration and under-diagnosis (i.e. patients with asthma who have another chronic condition might not consult their GP for it).28 In addition, some conditions (e.g. depression) are less clear cut in terms of diagnostic labels, and coding conventions are likely to have influenced our prevalence estimates for such conditions.Secondly, inclusion of subjects with a misdiagnosis of asthma could have occurred because data from lung function tests were not available in our database. For the same reason, we were not able to avoid asthma and COPD misclassification. In a recently published study, a positive predictive value of 86.4% was found for asthma diagnosis using an asthma code in a general practice database, and information of neither spirometry nor use of asthma medication did significantly improve accuracy.26, which will probably result in more comorbidity diagnoses. Finally, we used a study design with a dynamic cohort to determine period prevalence estimates of the chronic conditions. The strength of this type of cohort is a large, unbiased study population with minimal exclusion. However, patients lost to follow-up were included in the analysis and may have caused underestimation of the prevalence estimates, because these patients could have developed comorbidity between the moment of loss to follow-up and the end of the study period. Especially for gout, chronic sinusitis and recurrent urinary tract infection, this could have led to an underestimation, because these three conditions had an extra criterion of at least three episodes in 2011, 2012 and 2013 in order to be considered as chronic . But also the other way around, as asthma can interfere with the management of other comorbidities. For example, the use of inhaled corticosteroids may have a negative impact on diabetes control.30It would be interesting to study a possible influence of the presence of comorbid conditions on the use of asthma medication  and asthma outcomes (e.g. the risk of an asthma exacerbation). Regarding the presence of comorbidity in patients included in clinical trials, guideline and health policy makers should be careful in interpreting the generalizability of these trials, as there is a need for ‘real-life’ trials that include patients with comorbidity.In conclusion, this study showed that chronic comorbidity is highly prevalent in adult patients with asthma, even more in women than in men. It provides a comprehensive overview of the prevalence estimates of the full range of chronic comorbid conditions in patients with asthma. It is important that health care professionals who are involved in asthma care assess the role of comorbidity in a specific patient in order to achieve patient-centred asthma management.https://www.nhg.org/themas/publicaties/icpc-online), all contacts with the GP, and all medication prescriptions with start and end dates categorized using the Anatomical Therapeutic Chemical classification system.31We conducted a retrospective cohort study, using a general practice database from the Department of Primary and Community Care at the Radboud University Medical Centre, Nijmegen, The Netherlands. In the Netherlands the GP is the gatekeeper to secondary care. GPs are informed about any new diagnoses in their patients by the medical specialists they refer their patients to. Thus, a patient’s electronic medical record in general practice contains information regarding all of his diagnoses. De-identified electronic medical records of patients diagnosed with asthma from 179 general practices in the Eastern part of the Netherlands were available. For each registered subject, the following information was available: age, sex, all diagnoses coded according to the International Classification of Primary Care first edition (ICPC-1) extended with Dutch ICPC sub-codes (32) with physician-diagnosed asthma (ICPC-1 code R96) were included if they were registered at any moment between 1 January 2012 and 31 December 2013 in one of the 179 general practices that provided data. To avoid inclusion of misdiagnosed patients (i.e. patients with a childhood diagnosis of asthma without confirmation of this diagnosis later in life), patients were excluded if they had not had at least one asthma-related contact with their GP or at least one prescription for asthma medication after 1 January 2011. The cohort was a dynamic cohort, that is, patients lost to follow-up or patients entering the cohort after 1 January 2012 were included in the analysis. Patients were classified in the following age groups, based on their age at 1 January 2012: 16–29, 30–44, 45–59, 60–74, and ≥75 years.Study subjects aged ≥16 years . Chronic comorbid conditions that had already been diagnosed before 2012 were also included in the analysis. We also investigated several recurrent conditions and applied criteria to define their chronicity based on Dutch general practice guidelines.32 Examples of these ‘conditionally’ chronic comorbidities are depression, anxiety, dyspepsia, urinary tract infection and gout. Specifications of these criteria can be found in Supplementary Appendix 36: cardiovascular, respiratory, endocrine, digestive, skin, musculoskeletal, mental health, eye/ear, urogenital, neurological, blood forming/lymphatics, infectious, non-pulmonary cancer and pulmonary cancer . Subgroups based on sex were analysed separately and ORs adjusted for age were calculated to analyse differences in the prevalence of chronic conditions and disease categories between male and female patients with asthma using logistic regression. A simple count of the number of comorbid chronic conditions was analysed per sex and age group using Poisson regression. Further information on research design is available in the AppendicesReporting Summary


Multivariate analysis demonstrated an independent association between AKI development and preoperative albuminuria, defined as a urinary Albumin to Creatinine ratio ≥ 30 mg·g−1  as well as perioperative chloride load > 500 mEq . Conclusion: Preoperative albuminuria, as well as a high intraoperative chloride load, were identified as predictors of postoperative AKI in patients undergoing major abdominal surgery.Background: Postoperative Acute Kidney Injury (AKI) is a common and serious complication associated with significant morbidity and mortality. While several pre- and intra-operative risk factors for AKI have been recognized in cardiac surgery patients, relatively few data are available regarding the incidence and risk factors for perioperative AKI in other surgical operations. The aim of the present study was to determine the risk factors for perioperative AKI in patients undergoing major abdominal surgery. Methods: This was a prospective, observational study of patients undergoing major abdominal surgery in a tertiary care center. Postoperative AKI was diagnosed according to the Acute Kidney Injury Network criteria within 48 h after surgery. Patients with chronic kidney disease stage IV or V were excluded. Logistic regression analysis was used to evaluate the association between perioperative factors and the risk of developing postoperative AKI. Results: Eleven out of 61 patients developed postoperative AKI. Four intra-operative variables were identified as predictors of AKI: intra-operative blood loss ( Postoperative acute kidney injury (AKI) represents a common, yet under-recognized, perioperative complication, with a reported incidence varying between 1% and 36%, depending on the type of surgery and the definition of kidney failure ,3,4. AKIThe aim of this prospective observational study was to determine the incidence and to identify the pre- and intra-operative risk factors associated with the development of postoperative AKI, using the Acute Kidney Injury Network (AKIN) criteria , in patiThis was a single-center, prospective cohort study conducted at a tertiary academic hospital. Between February 2012 and December 2016 all adult patients undergoing elective major abdominal (including vascular) surgery were enrolled. All subjects gave their informed consent for inclusion before they participated in the study. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the local institutional Ethics Committee −2 and a UACR value ≥ 30 mg·g−1 were considered abnormal. Serum and urine samples were centrifuged at 3000 rpm for 10 min and at 1500 rpm for 5 min, respectively, and stored at −80 °C until analysis. Exclusion criteria included: ASA 5 , chronic kidney disease (CKD) stage IV or V [On admission to hospital, the following patient variables were recorded: Age, sex, body mass index, preoperative medications, American Society of Anesthesiologists (ASA) physical status , and co- IV or V , preoperThe recorded intra-operative surgical and anesthetic parameters were: Type of surgery, volume and type of intravenous fluids, transfusions of red blood cells, fresh frozen plasma or platelets, vasopressor administration, mean arterial blood pressure, urine output, and blood loss. The total chloride ion content of intra-operatively administered crystalloids and colloids was estimated. Patients were followed until the 7th postoperative day or hospital discharge, whatever occurred first. Preoperative patient demographics, laboratory values and intra-operative variables were evaluated for their association with perioperative AKI development.The primary outcome of the study was the development of perioperative AKI, defined by the AKIN criteria using the maximal change in serum creatinine and eGFR within 48 h after surgery . The eGFt-test or the Mann-Whitney test. Numerical data, expressed as counts and % proportions, were analyzed using the Pearson’s chi-square or the Fisher’s exact test. Simple logistic regression models were applied to determine odds ratios (ORs) and 95% confidence intervals (CIs), for the perioperative risk factors associated with postoperative AKI development. Multiple logistic regression was applied to establish a model for AKI prediction with prediction variables UACR > 30 mg·g−1 and intraoperative chloride load > 500 mEq.Data were analyzed using SPSS for Windows . Continuous variables were expressed as medians with range or means ± SD and were analyzed using an independent p value < 0.05 was considered statistically significant.For graphical representation, data box and whisker plots were used. For all analyses, a Between February 2012 and December 2016, 61 patients  with a mean age of 67.1 ± 10.2 years underwent major elective abdominal surgery. Eleven patients (18%) developed postoperative AKI (AKI group), while 50 did not (Non-AKI group). The baseline clinical and demographic characteristics of both groups are presented in −1·m−2). However, in the AKI group, the eGFR was significantly lower in the recovery room  and remained so throughout the entire follow-up period . Four intra-operative variables were also identified as significant predictors of postoperative AKI (p = 0.033) had a sensitivity of 70% and a specificity of 77% in predicting the development of AKI. There was a strong correlation between blood losses and transfusion of RBCs and FFP. Thus, due to co-linearity, only the total amount of intraoperative fluids, along with chloride load and UACR were introduced in the multivariate model. Multivariate regression analysis confirmed that a UACR ≥ 30 mg·g−1  and chloride load > 500 mEq  were independent predictors of postoperative AKI. The remaining intra-operative variables did not differ significantly between the two groups.Univariate analysis showed that an abnormal tive AKI : intra-o−1) preoperative urine albumin to creatinine ratio. Furthermore, four intra-operative variables were identified as independent AKI predictors: Intra-operative blood loss, transfusion of red blood cells and fresh frozen plasma, and intraoperative chloride load >500 mEq. The present prospective study of postoperative acute kidney injury following elective major abdominal surgery showed an incidence of 18%. The development of AKI, defined by the AKIN creatinine criteria, was strongly associated with an abnormal . They found an AKI incidence of 0.8% and identified seven independent preoperative AKI risk factors: Age, body mass index, liver disease, peripheral vascular disease, chronic obstructive pulmonary disease, high-risk surgery, and emergent surgery. The low incidence of postoperative AKI in that study was probably related to the definition of AKI as a drop in estimated creatinine clearance below 50 mL·min−1, within the first 7 postoperative days. Biteker et al. [−1 for men and <1.4 mg·dL−1 for women, respectively). They found a postoperative AKI incidence of 6.7% and identified four independent AKI predictors  increases the sensitivity of AKI diagnosis. In fact, Joannidis et al.  showed tIt is noteworthy that in the AKI group, a significant decline in eGFR with a concomitant rise in serum creatinine and cystatin C was already evident at the recovery room, immediately following surgery. This finding is in line with previous observations in cardiac surgery patients , as well−1 resulted in a five-fold higher risk of AKI development. In recent years, albuminuria has been identified as a significant risk factor for AKI and adverse long-term outcomes, both in the general population [The most interesting finding of the present study was the significant association between an abnormal preoperative UACR and the development of postoperative AKI, regardless of preoperative renal function or other comorbidities. In fact, the presence of a UACR >30 mg·grpulation  and in cpulation ,33. Our pulation , showingpulation ,33. HoweCKD is the most consistent pre-existing condition associated with a high risk of AKI in almost every relevant study. While the definition of CKD includes many parameters, with the most prevalent being albuminuria, this parameter has been largely neglected in most studies where data on urine albumin were generally lacking . AlbuminBlood loss and the need for intraoperative transfusion of red blood cells and fresh frozen plasma were found to be associated with the development of postoperative AKI. These factors represent well-known risks for AKI . A meta-Regarding preservation of renal perfusion, intraoperative blood pressure management is regarded as a key element. Recent observational studies identified episodes of intraoperative hypotension as an independent risk factor for AKI development ,41. ThisAnother intraoperative factor significantly and independently associated with development of postoperative AKI was the intraoperative infusion of a high chloride load. This finding is in line with experimental, as well as clinical data, showing that chloride infusion-induced hyperchloremia causes renal vasoconstriction resulting in cortical hypoperfusion ,44. A gr−1, were significantly and independently associated with postoperative AKI development. However, since the study patients had several comorbidities and some degree of pre-existing renal dysfunction rendering them more susceptible to future renal injury, the implications of these results might be limited to patients with similar comorbidities and not be applicable to otherwise healthy surgical patients. Nevertheless, the presence of preoperative albuminuria seems to be a significant, yet neglected, independent risk factor for postoperative AKI. Bearing in mind that the strength of association and degree of external validity of this risk association needs further evaluation. We suggest that albuminuria should be included in the routine preoperative patient evaluation for major abdominal surgery and considered as a possible prognostic factor in future AKI risk prediction models.In conclusion, the present study showed that in patients developing postoperative AKI, a reduction of the eGFR can be detected very early in the postoperative period. An intraoperative chloride load higher than 500 mEq, as well as a pre-operative urine albumin to creatinine ratio >30 mg·g