Hyperhomocysteinaemia in renal allograft recipients: could methylenetetrahydrofolate reductase gene polymorphism be a determinant risk factor for chronic allograft dysfunction?

The elevated plasma homocysteine could adversely influence long-term renal graft survival by promoting vascular sclerosis in the kidney allograft. This could be mediated through endothelial dysfunction. A polymorphism C677T in the gene coding for the enzyme methylenetetrahydrofolate reductase [MTHFR] was identified. The aim of the present work was to study the influence of the C677T MTHFR gene polymorphism on total plasma homocysteine and folate levels in renal graft recipients, and its impact on chronic graft dysfunction and the associated endothelial dysfunction. Thirty two stable renal allograft recipients were included in this study [group I] and compared with age and sex matched thirty control subjects [group II]. Plasma homocysteine level, plasma folic acid level, plasma van Willebrand factor [vWF] activity together with endothelial dependent and independent brachial artery vascular responses were done for all subjects. MTHFR genotype was determined by PCR in all renal recipients who were further classified accordingly into 3 subgroups: [group Ia] with homozygous TT type, [group Ib] with heterozygous CT type, and [group Ic] is wild CC type. Renal allograft recipients showed significant higher level of homocysteine as compared to control group [44.42 +/- 32.08 vs 11.62 +/- 2.57 respectively, p<0.001]. There was significant endothelial dysfunction in the transplant group as evidenced by the higher vWF [119.71 +/- 17.71 vs 67.60 +/- 28.65 p<0.001] and poorer endothelial dependent dilatation [EDD] of the brachial artery [7.84 +/- 1.08 vs 12.68 +/- 0.96 p<0.001] as compared to the control group. There was significant negative correlation between plasma homocysteine level and creatinine clearance [r=-0.55, p=0.001], suggesting the deleterious effect of hyperhomocysteinaemia on graft function. The homozygous subgroup [gpIa] showed significant higher level of homocysteine, vWF, lower folic acid, creatinine clearance and EDD as compared to the other two subgroups [gp Ib and Ic]. Our study identified that the presence of hyperhomocysteinemia in combination with unfavorable MTHFR genotypes contributes to an increased risk for development of chronic allograft dysfunction

Angiotensin-converting enzyme gene polymorphism in Egyptian patients with diabetic nephropathy

Background: Angiotensin converting enzyme [ACE] plays a key role in modulating vascular tone and electrolyte balance by hydrolyzing angiotensin II which is a potent vasopressor and aldosterone-stimulating peptide. The insertion/deletion polymorphism of ACE is a genetic determinant of plasma ACE levels and has been reported to be associated with diabetic microvascular or macrovascular complications

Aim: To contribute the ACE gene I/D polymorphism to the development ofdiabetic nephropathy in Egyptians

Methods: This study was carried on 30 Egyptian patients with diabetic nephropathy and 20 normal age-sex matched persons. All patients were subjected to thorough history taking, clinical examination and routine laboratory investigations. Determination of ACE genotype by PCR, quantitative determination of plasma ACE levels by colorimetric method and quantitative determination of angiotensin II levels using ELIZA technique

Results: There was significant increase in ACE and angiotensin levels in diabetic nephropathy patients than control persons. In diabetic nephropathy patients, ID and DD genotypes were present in 20% and 25% respectively as compared to 2% and 0% of control persons respectively. Thus D-allele was present in 45% of the patients as compared to 2% of normal controls

Conclusion: There is positive association between the D-allele [ID and DD] and development of diabetic nephropathy in Egyptians

Effect of oxidative stress on renal functions in traumatic rhabdomyolysis patients; effect of desferoxamine

Rhabdomyolysis is one of the leading causes of acute renal failure. The cytotoxic effect of myoglobin is one of the major injury pathways in developing of renal insufficiency in this clinical disorder. Oxidative stress plays a critical role in the development of this nephrotoxic effect. Because iron is incriminated as the critical initiator of heme induced proximal tubular cytotoxicity, it has been demonstrated that iron chelator, desferoxamine, can play a protective effect in this type of renal injury in experimental studies. The aim of this work was to study the effect of oxidative stress on renal functions in traumatic rhabdomyolysis patients and trying to evaluate the protective effect of desferoxamine [DFO] in these patients. Twenty patients with extensive muscle trauma and diagnosed as rhabdomyolysis by high serum CK and myoglobin were included in this study. Patients were classified into 2 groups: Group I that received desferoxamine plus conventional therapy in the form of fluids, mannitol, sodium bicarbonate and Group II that received conventional therapy alone. These 20 patients were compared to 10 normal subjects as a control group. All subjects were subjected to full history taking, complete clinical examination and scoring which is done for the patients only. Laboratory tests were done including blood urea, serum creatinine as well as estimation of serum CK, serum myoglobin, serum MDA and blood glutathione. Laboratory tests were done twice for the 20 patients, one on admission and another one 24 hours after treatment. Results revealed that oxidative stress developed in our twenty patients as evidenced by high MDA and reduced glutathione 24 hours after admission. This oxidative stress was less in the patients received desferoxamine when compared with those who did not receive desferoxamine. There were also better renal functions in the desferoxamine group in comparison to the non desferoxamine group. It was concluded that desferoxamine as an iron chelator, decreases the oxidative stress in traumatic rhabdomyolysis patients and recommended to be used on a larger scale before being standardized