Hamad Dheir

The Impact of Membrane Permeability and Dialysate Purity on Cardiovascular Outcomes

The effects of high-flux dialysis and ultrapure dialysate on survival of hemodialysis patients are incompletely understood. We conducted a randomized controlled trial to investigate the effects of both membrane permeability and dialysate purity on cardiovascular outcomes. We randomly assigned 704 patients on three times per week hemodialysis to either high- or low-flux dialyzers and either ultrapure or standard dialysate using a two-by-two factorial design. The primary outcome was a composite of fatal and nonfatal cardiovascular events during a minimum 3 years follow-up. We did not detect statistically significant differences in the primary outcome between high- and low-flux (HR=0.73, 95% CI=0.49 to 1.08, P=0.12) and between ultrapure and standard dialysate (HR=0.90, 95% CI=0.61 to 1.32, P=0.60). Posthoc analyses suggested that cardiovascular event-free survival was significantly better in the high-flux group compared with the low-flux group for the subgroup with arteriovenous fistulas, which constituted 82% of the study population (adjusted HR=0.61, 95% CI=0.38 to 0.97, P=0.03). Furthermore, high-flux dialysis associated with a lower risk for cardiovascular events among diabetic subjects (adjusted HR=0.49, 95% CI=0.25 to 0.94, P=0.03), and ultrapure dialysate associated with a lower risk for cardiovascular events among subjects with more than 3 years of dialysis (adjusted HR=0.55, 95% CI=0.31 to 0.97, P=0.04). In conclusion, this trial did not detect a difference in cardiovascular event-free survival between flux and dialysate groups. Posthoc analyses suggest that high-flux hemodialysis may benefit patients with an arteriovenous fistula and patients with diabetes and that ultrapure dialysate may benefit patients with longer dialysis vintage.

Glycosylated hemoglobin levels are associated with cardiovascular events in nondiabetic peritoneal dialysis patients.

BACKGROUND High glycosylated hemoglobin (HbA1c) levels are recognized as a risk factor for cardiovascular disease in the diabetic dialysis population. However, it is not known whether this also applies to nondiabetic dialysis patients. We prospectively investigated the association between HbA1c levels and new cardiovascular events in nondiabetic patients treated with peritoneal dialysis. METHODS Eighty nondiabetic patients who had been on peritoneal dialysis treatment were prospectively followed for 5 years. HbA1c levels were measured at baseline and every 3 months. Fatal and nonfatal cardiovascular events were assessed during the follow-up. RESULTS Mean age was 48.5 ± 15.2 years; 51% were male. Baseline HbA1c level was 5.46% ± 0.41% (range 4.6%-6.3%). Mean HbA1c was 5.44% ± 0.31% (range 4.8%-6.3%) during the study, and positively correlated with age and high-sensitivity C-reactive protein. Twenty fatal and nonfatal cardiovascular events were observed during a mean 41.8 ± 7.1 months of follow-up. Event-free survival was better in patients with HbA1c levels <5.45%, compared with that for those with HbA1c levels =5.45% (p=0.01). In crude Cox regression analysis, an increase in HbA1c level of 0.1% was associated with a 1.22-fold increase in new cardiovascular events (p=0.007). In Cox analyses, HbA1c level was found as a significant predictor of cardiovascular events. CONCLUSION HbA1c levels predict fatal and nonfatal cardiovascular events in nondiabetic peritoneal dialysis patients.

Ventricular arrhythmia in dialysis patients: a link with higher hemoglobin levels?

We investigated the frequencies and associated risk factors of cardiac arrhythmias and heart rate variability (HRV) in hemodialysis (HD) patients. One hundred fifty prevalent HD patients underwent 48‐hour Holter monitoring. Holter monitoring was analyzed in 4 phases: early post‐HD phase (12 hours), late post‐HD phase (20 hours), pre‐HD phase (12 hours), and HD phase (4 hours). Echocardiography was applied to measure the left ventricular mass index in a subgroup of patients (n: 52). Patients with ventricular premature contraction (VPC) were significantly older, had a longer HD duration, and higher hemoglobin (Hb) levels. Left ventricular mass index was significantly correlated with the frequency of VPC, during the HD and pre HD phases (r: 0.435, 0.312, respectively). In logistic regression analysis, patients with Hb level >11.9 g/dL (high tertile) had a 4.5‐fold increased risk of VPC compared with those with Hb levels <10.8 g/dL (P: 0.04). In HRV analysis, age (P<0.001), and diabetes (P: 0.03) were found to be independent predictors of low standard deviation of all mean normal‐to‐normal RR intervals. Increased left ventricular mass index is associated with a high frequency of VPC in the pre‐HD and HD periods. The occurrence of VPC is predicted by older age, longer dialysis duration, and higher Hb levels, while older age and diabetes are the determinants of HRV. The relation between higher Hb levels and the frequency of VPC might provide a clue for the explanation of the detrimental effect of higher Hb levels on HD patients.

Relationship between glucose exposure via peritoneal dialysis solutions and coronary artery calcification in non-diabetic peritoneal dialysis patients.

IntroductionVascular calcification is frequent in dialysis patients and is associated with increased mortality. Impaired glucose metabolism is proposed as a contributing factor for vascular calcification. We investigated whether glucose exposure via dialysate may have a role in vascular calcification in non-diabetic peritoneal dialysis patients.MethodWe measured coronary artery calcification by multi-slice computerized tomography in 50 prevalent non-diabetic peritoneal dialysis patients and assessed its relations with fasting blood glucose, homeostasis model assessment of insulin resistance (HOMA-IR), and glucose exposure from peritoneal dialysis fluid.ResultsTwenty-four patients (48%) had no coronary calcification. When patients were grouped according to the presence or absence of calcification, patients with calcification were mostly men and had higher burden of cardiovascular disease history, vitamin D dose intake, serum calcium, total glucose exposure from dialysis solution, and lower total weekly Kt/Vurea. In multivariate analysis, dialysate glucose exposure was an independent predictor of coronary artery calcification score, besides serum calcium and Kt/Vurea.ConclusionThese data suggest that high glucose exposure from dialysis solution, which is potentially correctable, is a risk factor for vascular calcification in non-diabetic PD patients.

Glycated hemoglobin predicts overall and cardiovascular mortality in non-diabetic hemodialysis patients.

AIMS Besides diabetic patients, glycated hemoglobin (HbA1c) levels have been reported to predict mortality in non-diabetics patients. However, the importance of HbA1c levels in non-diabetic hemodialysis patients still remains unknown. Thus, we aimed to prospectively investigate the impact of HbA1c on all-cause and cardiovascular mortality in a large group of prevalent non-diabetic hemodialysis patients. METHODS HbA1c was measured quarterly in 489 non-diabetic prevalent hemodialysis patients. Overall and cardiovascular mortality were evaluated over a 3 year follow-up. RESULTS Mean HbA1c level was 4.88 ± 0.46% (3.5 - 6.9%). During the 28.3 ± 10.6 months follow-up period, 67 patients (13.7%) died; 31 from cardiovascular causes. In Kaplan-Meier analysis, patients in the lowest (< 4.69%) and highest HbA1c (> 5.04%) tertiles had poorer overall survival compared to the middle HbA1c tertile (p < 0.001). Adjusted Cox-regression analysis revealed that the highest HbA1c tertile was associated with both overall (HR = 3.60, 95% CI 1.57 - 8.27, p = 0.002) and cardiovascular (HR = 6.66, 95% CI 1.51 - 29.4; p = 0.01) mortality. Also, low HbA1c levels tended to be associated with overall mortality (HR = 2.26, 95% CI 0.96 - 5.29, p = 0.06). CONCLUSION Upper normal HbA1c levels are independently associated with cardiovascular and overall mortality in non-diabetic hemodialysis patients, whereas lower HbA1c levels are not.

Congenital adrenal hyperplasia: a rare cause of renal failure and a successful renal transplantation.

Congenital adrenal hyperplasia belongs to a group of autosomal recessive disorders affecting steroid biosynthesis; a rare disease with a prevalence of 1 case per 16,000 population. A 30-year-old phenotypically male patient had been diagnosed with 11-β hydroxylase deficiency at the age of 16; presenting with ambiguous genitalia, growth retardation, presence of menstrual cycles, severe hypertension, hypokalemia and renal dysfunction. He developed endstage renal disease due to hypertension and was treated with hemodialysis for 3 y. After careful evaluation, he was approved to undergo renal transplantation. The patient has now finished 6th month after transplantation and is currently under follow-up at our outpatient clinic, having no problems related to the transplant. While early treatment to prevent hypertension is mandatory in patients with congenital adrenal hyperplasia, once renal failure occurs, renal transplantation may the best choice of treatment. In this study, we describe the first report of a successful renal transplantation in an adrenal hyperplasia.

A)typical (Extra) Pulmonary Tuberculosis in Kidney Patients

Tuberculosis is still a major health problem especially among immunocompromised hosts. Another problem is making diagnosis due to the unexpected presentation and localization of disease. Extrapulmonary disease may clinically and radiographically mimic other infectious or neoplastic diseases. In this report we presented three tuberculosis cases; a kidney allograft recipient and two patients with end stage renal disease including soft tissue abscess, lytic bony lesions and pathological fractures without any pulmonary symptoms. Tuberculosis should be kept in mind during atypical generalized inflammatory conditions especially in immunocompromised hosts. Atypical localization and symptomatology may arise due to the more potent immunosuppressive agents. Delay in diagnosis may cause significant mortality and morbidity in patients with high risk. Starting anti-tuberculosis treatment empirically in most cases due to the difficulties in establishing diagnosis is another problem. Classical anti-tuberculosis treatment is sufficient to control disease in most cases. Early management may be a life saving approach.