Cardiotoxic lipid peroxidation products in chronic renal failure in relation to severity of anemia and to left ventricular hypertrophy

To investigate the relationship between oxidative stress, anemia and cardiac injury in chronic renal failure [CRF] patients we measured two lipid peroxidation products [Malondialdehyde [MDA] and 4-hydroxynonenal [4-HNE]] by HPLC in 75 subject group I[15 apparently healthy volunteers as normal control], group II[15 CRF patients on conservative treatment], group III [15 CRF patients on regular haemodialysis [HD]] with Hb < 10g/dl], group IV [15 CRF patients on regular HD with Hb > 11g/dl]. group IV [15 anemic patients with normal kidney function]. [chocardiography was done to CRF patients and left ventricular mass index [LVMI] was estimated. Results of the study revealed that MDA and 4-HNE were significantly elevated in CRF patients [groups II, III, IV] and in non uremic anemic patients [group V] compared to control subjects [group I] [P < 0.001], [P < 0.001] for each group. Also significant increases in serum levels of these oxidative stress parameters in CRF patients under regular III] with Hb concentration < 10g/dl compared to those with Hb > 11g/dl [P < 0.001], [P < 0.001]. MDA and 4-HNE were elevated in group III [patients on regular HD with Hb < 10g/dl] compared to group II [conservatively treated group] but this difference was not statistically, significant [P > 0.05],[P > 0.05]. They were also elevated in CRF patient compared to anemic patients with normal kidney function [P < 0.001], [P < 0.001]. These parameters were significantly reduced after the HD session compared to before it in groups III and IV [P < 0.001], [P < 0.001] for each group. Serum MDA and 4-HNE showed significant negative correlations with Hb concentration [P < 0.001], [P < 0.001], and significant positive correlations with each of serum creatinine [P < 0.001], [P < 0.001], BUN [P < 0.001] [P < 0.001], and [[LVMI] [P < 0.001] [P < 0.001] in HD patients with Hb < 10g/dl. Similar correlation results were obtained in HD group with Hb > 11g/dl. These results lead to the conclusion that optimized correction of renal anemia as well as the use of biocompatible HD membranes may result in significant reduction of oxidative stress and therefore reduction of cardiac affection, reducing the co-morbidity of HD patients

Determinants of circulating soluble transferrin receptor level in chronic renal failure patiets

Anemia is a common problem in chronic renal failure [CRF] especially in patients under maintenance haemodialysis [HD] therapy. Soluble transferrin receptors [sTfR] is useful for quantitative assessment of erythropoiesis in HD patients but its specificity for detection of iron-defficient erythropoiesis in HD patients with recombinant human erythropoietin [rHuEpo] therapy is insufficient, even inconclusive and controversial. So the assessment of iron-deficient erythropoiesis is a hard task in HP patients during rHuEpo therapy. We designed this work aiming at identification of factors determining the sTfR level in CRF patients predialysis or on haemodialysis with and without rHuEpo therapy. Fifty CRF patients were studied who were divided into 3 groups:- Group I: 10 patients on conservative treatment.- Group II: 10 patients on regular HD but not on rHuEpo therapy.- Group III: 30 patients on regular HD and on rHuEpo therapy. We studied also two other groups, group IV: 10 anemic patients with normal kidney function and group V: 10 apperantly healthy control. We measured in all subjects sTfR level, s. Epo, transferrin saturation [TS%], s. ferritin, s. iron, TIBC, C-reactive protein, hypochrornic red cell percentage [HRC°/o] reticulocytic count and CBC. sTfR level was significantly raised in group III [dialysis with Epo] compared to group I [predialysis] [P < 0.01] and to group H [dialysis without Epo] [P < 0.0l]. sTfR was also significantly raised in group IV [anemic non uremic] compared to CRF groups [predialysis [P < 0.01], dialysis without Epo [P < 0.0l] and dialysis with Epo [P < 0.05]]. Haemodialysis patients with rHuEpo were stratified by less than 25. 25-75 and more than 75 percentiles of serum ferritin, by < 20 and > /= 20% of TS as well as by < 10 and > /= 10% of HRC%. The levels of sTfR in patients of lower quartile [mean +/- SD 4.9 +/- 1.5 micro g/l] was higher than those with upper quartile [mean +/- SD 2.23 +/- 0.78 micro g/l] and these with 25-75 percentile [mean +/- SD 2.48 +/- 0.69 micro g/l]. In CRF patients under dialysis with Epo there was significant positive correlation between sTfR versus basal Epo [P < 0.01], HRC% [P < 0.01], retics% [P < 0.01], Hct [P < 0.0l] and Hb [P < 0.01] but was significantly negative correlated versus TS [P < 0.01] and S.Ferritin [P < 0.01]. Multivariate regression analysis disclosed that HRC%, serum ferritin, Hct and TS% were the four independent predictors of sTfR levels and accounting for [68%] of the variability in sTfR. So, sTfR levels quantitatively reflects tile integrated effects of iron availability [HRC% and TS%], iron reserves [serum ferritin] and markers of erythropoiesis [Hct] and we conclude that sTfR levels is a good index of monitoring iron deficiency and erythropoietic activity in CRF especially those under HD therapy and receiving rHuEpo and it reflected the integrated effects of iron availability, iron reserves and erythropoietic stimulation

Potential role of thrombin-activatable fibrinolysis inhibitor [TAFI] in diabetic nephropathy and its relation to degree of albuminuria and to dialysis modality

Diabetic nephropathy has become the most prevalent cause of end-stage renal disease [ESRD] in many countries, and about one third of patients with diabetic nephropathy progress to end stage renal disease. Patients with end-stage renal disease dialyzed due to diabetic nephropathy are at higher risk of death due to cardiovascular complications than dialyzed non-diabetic patients. Hypofibrinolysis is a common finding in patients with diabetes mellitus and a risk factor for diabetic nephropathy and may play a role in the vascular complications in dialyzed diabetic patients. A new potent inhibitor of fibrinolysis, the thrombin-activatable fibrinolysis inhibitor [TAFI], has been isolated from human plasma. However, the relation between plasma TAFI level and diabetic nephropathy has not been well appraised. In the present study, we investigated the plasma levels of TAFI in 50 type 2 diabetic patients: 10 with normoalbuminuria, 10 with microalbuminuria, 10 with macroalbuminuria, 10 with ESRD on haemodialysis, and 10 with ESRD on peritoneal dialysis. Also, we assessed albumin/creatinine ratio in albumiuric patients, blood urea, serum creatinine, serum lipids, and ECG. The plasma level of TAFI in diabetic patients with macroalbuminuria was significantly higher than the level in diabetic patients with microalbuminuria [P < 0.00l], and higher in micro-albuminuric patients than in normolbuminuric patients[P < 0.00l]. Plasma TAFI level was correlated to albumin/craetinine ratio[P < 0.00l], blood urea[P < 0.00l] and serum creatinine[P < 0.00l] in patients with micro-albuminuria [non dialyzed patients]. Moreover, it was significantly higher in patients with diabetic nephropathy and on peritoneal dialysis than those on haemodialysis [P < 0.01] and it was correlated positively with triglycerides [P < 0.05] and negatively with HDL-c[P < 0.05]. These data suggest that TFAI level was increased by the progression of diabetic nephropathy as it was significantly higher in. patients reaching ESRD [haemodialysis and peritoneal dialysis groups]than in those still in the stages of micro and rnacro-albuminuria and higher in macroalbuminuric patients than in microalbuminuric patients. Also TAFI level was significantly positive correlated with tile indicators of decline in renal function [blood urea, serum creatinine, urinary albumin and urinary albumin/creatinine ratio]. So we can concluded that increased plasma level of TAFI may contribute to the pathogenesis and progression of diabetic nephropathy and may have role in tile cardiovascular complications of dialyzed diabetic patients, especially those under peritoneal dialysis