Study of pro-hepcidin level and renal functions in nephrotic syndrome, chronic renal failure and hemodialysis patients

Anemia is associated with worse outcomes in patients with chronic kidney disease [CKD]. Hepcidin is a recently discovered protein produced mainly by the hepatocytes as a pre-prohormone, pre-prohepcidin. It is a key regulator of iron metabolism in different iron disorders. To study serum pro-hepcidin levels in nephrotic syndrome [NS], chronic renal failure [CRF], and hemodialysis [HD] patients. The study included 4 groups. Group I: 20 patients with NS, group II: 20 patients with CRF on conservative treatment, group III: 20 patients on regular HD, and group IV: 20 healthy subjects as a control group. All groups were age and sex matched, and subjected to physical examination, abdominal ultrasound, and laboratory investigations including: Complete blood cell count, serum iron, iron indices, serum pro-hepcidin, serum high sensitivity C-reactive protein [hs-CRP], renal functions, liver functions, and other necessary tests. CRF and HD patients had a statistically significant higher mean serum pro-hepcidin than NS patients and controls [P <0.001], with no statistically significant difference between the NS and control groups. All patient groups had a statistically significant higher serum hs-CRP, and a significantly lower hemoglobin concentration, serum iron, and transferrin saturation compared with controls [P<0.001]. The mean serum ferritin was statistically significantly increased in the HD group only [P <0.001]. Serum pro-hepcidin showed a statistically significant positive correlation with serum hs-CRP [a marker of inflammation], serum ferritin, blood urea and serum creatinine in all patient groups, with serum uric acid in NS and CRE patients, and with serum albumin only in NS patients. It showed a statistically significant inverse correlation with serum iron and transferrin saturation in all patient groups, with hemoglobin concentration and creatinine clearance in NS and CRF patients [HD patients were anuric], and with urinary albumin excretion only in NS patients probably due to increased pro-hepcidin loss with the proteinuria. In patients with CKD, the presence of a chronic inflammatory status offsets the inhibitory effect of anemia on pro-hepcidin production with a net increase in serum pro-hepcidin levels. This inflammation related dysregulation of pro-hepcidin might result in a functional iron deficiency, thus aggravating the anemia. Pro-hepcidin is unlikely to be beneficial in monitoring anemia of CKD. However, it could be a future therapeutic target in managing anemia in these patients

Bone metabolism in dialysis patients assessed by biochemical markers and densitometry

A decrease in bone mineral density is common in patients with chronic renal failure. It is also a risk factor for fractures in this population. The aim of the study was to evaluate bone mineral density-BMD and some biochemical markers of bone metabolism in patients on chronic hemodialysis. The study was performed on 50 patients on chronic hemodialysis. Bone mineral density was measured using dual energy x-ray absorptiometry [DEXA] in the distal left forearm. Concentrations of iPTH and carboxy terminal propeptide of type I collagen [PICP] was measured by commercially available Kits. Mean T scores of the distal left forearm were -2.7 +/- 2.2 for men and -2.2 +/- 1.9 for women T scores in the range of osteopenia were present in 30% of patients, and in the osteoporosis range in 54% of patients. Patients with bone mass measurements in the osteoporosis range had significantly increased iPTH levels compared with patients with T scores in the osteopenic/normal range. There was statistically significant negative correlation between BMD T scores and iPTH [r=-0.63, P0.0032] and with PICP [r=-0.820, P=0.0001]. On the basis of our finding we conclude that bone loss is seen in patients on chronic hemodialysis. Bone turnover markers estimated in this population correlated well with BMD measurements at sites of pure cortical bone as the distal radius

Cytokine elimination during continuous hemofiltration. A feasible clinical modality for septic patients

Tumour necrosis factor a [TNF-alpha] and interleukin 6 [IL-6] arc important prognostic markers in intensive care unit [ICU] septic patients. The aim of the study was to determine whether continuous venovenous hemofiltration [CVVH]. using Fresenius hemofilter AV600s, leads to elimination of TNF-alpha and IL-6 in 20 septic patients with multi-organ failure. At the start of hemofiltration [o], 6 and 12 hours the mean afferent plasma concentration +/- SD of TNF-alpha [41.9 +/- 9.56, 30.85 +/- 6.2. 25.5 +/- 5.28 pg/ml] and that of IL-6 [890 +/- 183.96, 635 +/- 149.65, 410 +/- 168.27, pg/ml]. 'the different plasma concentrations were significantly lower than tile corresponding afferent concentrations. TNF-alpha and IL-6 were detectable in the ultra filtrate of all patients. The plasma clearance of TNF-alpha and IL-6 significantly decreased after 12 hours as a result of the adsorptive elimination of the mediators due to progressive membrane saturation. We demonstrated that CVVH could represent an appropriate tool to remove a broad spectrum of proinflammatory mediators, if such removal is required in septic patients

Evaluation study of tuberculosis risk in patients with end stage renal disease undergoing haemodialysis

Because of Immunity defect patients with end stage renal disease [ESRD] are at increased risk of developing infections, tuberculosis [TB] in particular. The incidence of TB is higher in dialysis patients than in general population, the aim of this study was to evaluate the prevelance of TB among ESRD patients undergoing haemodialysis and to assess its risk factors and clinical features. The present study controlled 203 patient: on haemodialysis. They were subjected to history taking clinical examination chest x-ray routine laboratory investigations, mycobacteriological examination, BACTEC culture, PCR for a valuable samples. The results showed that the prevalence of tuberculosis in patients undergoing haemodialysis was 10.96%. Total tuberculin positivity was detected in [13.6%] with [75.1%] positive in tuberculous cases versus [7.2%] in non tuberculous patients. This difference was statistically significant [P < 0.05]. The sensitivity and specificity of tuberculin test was [75.12%], [78%] respectively, while for ZN stain it was [85.7%], [100%] respectively, anti for PCR it was [95.24%]. [96%] respectively Diabetus mellitus as found to be the aetiology of renal failure in patients who developed tuberculosis in [47.69%], Hepatitis B was found in [28.56%], and hepatitis C in 42.86%. TB screening of patient population's undergoing dialysis is advisable. The ESRD population has an increased risk of TB with a greater frequency of extrapulmonary presentations and fever. Enhanced a awareness of TB in the ESRD population, early diagnosis and treatment are very important in order to improve the outcomes

Inflammatory status in patients on chronic hemodialysis

All chronic renal failure patients show clinical and/or laboratory manifestations of inflammation. Prevalence of infection in chronic renal failure [CRF] patients is high due to immune dysfunction, also repeated cannulation and central venous catheters are probably responsible for the high incidence of infection. Detection of these pro-inflammatory cytokines in the plasma allow to detect patients with high risk of endotoxemia and also it was noticed that there is high degree of correlation between the inflammation, malnutrition and atherosclerotic process. The aim of the present study was to detect the level of plasma alpha-MSH as immunomodulator which counter acts the pro-inflammatory cytokines such as TNF-alpha, neopterin, nitric oxide [NO], C-reactive protein [CRP] and eridotoxins. This study was conducted on 40 subjects divided into three groups, 15 patients on maintenance hemodilaysis [GI], 15 patients with chronic renal failure not yet on dialysis [GII], and 10 healthy subjects as a control group [GIII]. Plasma alpha-MSH was measured using a double antibody radioimmunoassay, TNF-alpha and neopterin using specific enzyme-linked immunosorbent assays. Plasma nitrites were determined by a colorimetric method and endotoxin with the quantitative chromogenic method. The present study showed that most of the chronic renal failure patients show laboratory evidence of inflammation especially before starting dialysis. alpha-MSH was found to he elevated in both groups. Also, the levels of the proinflammatory cytokines, TNF-alpha, neopterin, nitric oxide, iNOS, C-reactive protein and plasma endotoxin were found to he elevated in both group I and group II. There was a positive correlation between alpha-MSH and endotoxemia. Also, there was a positive correlation between the level of endotoxins and the level of other pro-inflammatory cytokines suggesting the role of endotoxemia in stimulating the formation and release of the proinflammatory cytokines

Role of the kidney in removing circulating leptin in humans

To assess the role of the kidney in removing circulating leptin in humans by studying the leptin metabolism across the renal bed of normal human kidney and also studying the circulating leptin levels in end stage renal disease [ESRD] patients maintained on hemodialysis [HD]. The study included 14 human subjects with intact renal functions and who were scheduled for elective cardiac catheterization. Aortic, renal vein, peripherial arterial and urine samples were withdrawn from each subject. A separate cohort of 32 patients with ESRD maintained on HD were also included in the study. A blood sample was taken from the arterial limb of the vascular access of each patient before and after the HD session. For all samples, leptin levels were determined by radioimmunoassay [RIA]. In subjects with intact renal functions, plasma leptin concentrations were significantly increased in the aorta than in the renal vein [11.3 +/- 3.1 vs. 10.1 +/- 2.9 ng/ml] indicating net renal leptin uptake [RU]. The calculated RU was 849 +/- 184 ng/min which accounted for 65% of all leptin removed from the circulation. The calculated renal leptin fractional extraction [Fx] was 15.6 +/- 2%. Lineweaver-Burk analysis indicated that RU followed saturation kinetics with an apparent Michaelis-Menten constant of 10.7ng/ml and maximal velocity of 1700 ng/min. Leptin was generally undetectable in urine. In ESRD patients on HD, the peripheral arterial leptin levels standardized for body mass index were increased by fourfold as compared to control subjects with intact renal function. In addition, plasma leptin is not cleared by hemodialysis with a modified cellulose membrane. Human kidney plays a substantial role in leptin removal from the circulation by taking up and degrading the peptide. ESRD patients have higher levels of circulating leptin which are not cleared by hemodialysis using modified cellulose membrane