ABSTRACT
Renal transplant patients receive several immunosuppressive drug regimens that are potentially nephrotoxic for treatment. Serum creatinine is the standard for monitoring kidney function; however, cystatin C (Cys C) and kidney injury molecule-1 (KIM-1) have been found to indicate kidney injury earlier than serum creatinine and provide a better reflection of kidney function. Here, we assessed Cys C and KIM-1 serum levels in renal transplant patients receiving mycophenolate mofetil, tacrolimus, sirolimus, everolimus, or cyclosporine to evaluate kidney function. We used both the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 equation, which is based on creatinine and combined creatinine with Cys C, and the CKD-EPI 2012 equation, which is based on Cys C alone, to estimate glomerular filtration rate (GFR). Then, we assessed the association between serum KIM-1 and GFR < 90 mL per minute per 1.73 m 2. We observed significantly higher serum Cys C levels in patients with the elevated serum creatinine, compared with those with normal serum creatinine. The estimated GFRs based on creatinine were significantly higher than those based on the other equations, while a significant positive correlation was observed among all equations. Serum KIM-1 levels were negatively correlated with the estimated GFRs by the CKD-EPI Cys C and the combined creatinine with Cys C equations. A serum KIM-1 level above 0.71 ng/mL is likely to indicate GFR < 90 mL per minute per 1.73 m 2. We observed a significant correlation between serum creatinine and Cys C in our renal transplant patients. Therefore, serum KIM-1 may be used to monitor renal function when using potentially nephrotoxic drugs in renal transplants.
ABSTRACT
BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) gene variants and hyperhomocysteinemia have been implicated in the pathogenesis of diabetic nephropathy (DN) in various ethnic groups. We investigated the association of C677T and A1298C MTHFR gene variants and altered homocysteine concentrations in Lebanese and Bahraini type 2 diabetes (T2DM) DN patients. METHODS: Bahraini subjects comprised 224 DN patients and 328 T2DM patients with normal urine albumin [diabetes without nephropathy (DWN)]. Lebanese subjects comprised 252 DN and 309 DWN patients. C677T and A1298C genotypes were determined by PCR-restriction fragment length polymorphism (RFLP) analysis, and homocysteine was measured by ELISA. RESULTS: A1298C allele and genotype distribution were comparable between DN and DWN patients in both communities. However, there was enrichment of the 677T allele, together with C/T and T/T genotypes in Lebanese but not Bahraini DN patients, thereby conferring DN susceptibility [odds ratio (OR) (95% CI)=2.43 (1.89-3.11) and OR (95% CI)=1.15 (0.83-1.61), respectively; heterogeneity Q=12.53, p=0.0004)]. CONCLUSIONS: The contribution of C677T single nucleotide polymorphism to increased risk of DN (presumably by increasing homocysteine concentrations) must be evaluated in the context of the ethnic background.
