ABSTRACT
BACKGROUND: It is unclear whether total serum homocysteine (tHcy) and the C677T mutation of methylenetetrahydrofolate reductase (MTHFR) are associated with cardiovascular disease (CVD) in patients with end-stage renal disease (ESRD). METHODS: A cross-sectional sample of 459 patients with ESRD on chronic dialysis was assessed to determine whether tHcy and the C677T mutation are associated with CVD prevalence in multiple logistic regression. As CVD mortality is high, we examined the relationship between homozygosity and duration of dialysis. RESULTS: Mean tHcy was higher in patients without a history of CVD (35.2 micromol/L vs. 30.4 micromol/L, P = 0.02). In multivariate models, CVD was negatively associated with tHcy and positively associated with TT genotype, male gender, and body mass index. Mean tHcy levels were higher among those with the TT genotype compared with those with the CC genotype when adjusted for age, folate, creatinine, and albumin (37.9 micromol/L vs. 31.9 micromol/L, P = 0.005). Among whites, the prevalence of the TT genotype was higher in those having undergone less than one year of dialysis (P = 0.002). CONCLUSIONS: The C677T genotype of MTHFR is associated with CVD in ESRD and may be a more meaningful marker than tHcy for abnormal homocysteine metabolism in ESRD. Prospective data from ongoing clinical trials are needed to improve our understanding of these findings. Screening for this polymorphism may help guide prevention measures.
Subject(s)
Cardiovascular Diseases/etiology , Hyperhomocysteinemia/complications , Kidney Failure, Chronic/complications , Oxidoreductases Acting on CH-NH Group Donors/blood , Body Mass Index , Cardiovascular Diseases/enzymology , Cardiovascular Diseases/genetics , Cross-Sectional Studies , Ethnicity , Female , Folic Acid/therapeutic use , Genotype , Humans , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/therapy , Male , Methylenetetrahydrofolate Reductase (NADPH2) , Middle Aged , Multivariate Analysis , Mutation , Oxidoreductases Acting on CH-NH Group Donors/genetics , Peritoneal Dialysis , Pyridoxine/therapeutic use , Renal Dialysis , Risk Factors , Sex Factors , Vitamin B 12/therapeutic useSubject(s)
Cardiovascular Diseases/epidemiology , Disease Outbreaks , Kidney Failure, Chronic/epidemiology , Cardiovascular Diseases/etiology , Cardiovascular Diseases/physiopathology , Heart/physiopathology , Humans , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/physiopathology , Risk Factors , Uremia/physiopathologyABSTRACT
HIV-associated nephropathy (HIVAN) is a clinicopathologic entity characterized by heavy proteinuria, absence of edema and an irreversible decline in renal function. Findings on renal biopsy include: collapsed glomerular capillaries; visceral glomerular epitheliosis; microcystic tubules; mesangial prominence; and endothelial tubuloreticular inclusions. Early in the AIDS epidemic, HIVAN was the predominant glomerular lesion observed in HIV-infected patients. It is being increasingly recognized, especially in Caucasian populations, that a variety of immune complex-mediated lesions such as membranoproliferative glomerulonephritis, proliferative glomerulonephritis and IgA nephropathy are associated with HIV infection. In this review we present two cases: one patient whose first presentation of AIDS was end-stage renal disease, who on biopsy was found to have HIVAN, and the second, who was infected with HIV, and on biopsy was found to have hepatitis C-related hepatitis C related membranoproliferative glomerulonephritis. We also review the current literature on HIVAN and HIV-associated immune complex diseases (HIVICDs). Each case illustrates an important clinical point. The first that renal disease can be the first manifestation of HIV infection and the second that HIV-infected patients may develop immune complex related renal diseases, some of which may be potentially treatable.
