Aldosterone synthase gene polymorphism and renal histopathologic changes in kidney transplant patients receiving a calcineurin inhibitor.

INTRODUCTION: Aldosterone participates in the pathogenesis of calcineurin inhibitor nephrotoxicity (CIN), producing renal vasoconstriction and transforming growth factor beta (TGFß) expression. The objective of this study was to assess aldosterone polymorphisms and relationships to plasma aldosterone levels and the development of renal histological lesions in kidney transplant patients. MATERIAL AND METHODS: Patients with kidney graft biopsy were divided according to the presence or absence of CIN. We determined aldosterone synthase (AS) -344 T/C and int 2 W/C gene polymorphisms and plasma aldosterone levels. Histological, biochemical and clinical variables were measured. RESULTS: Calcineurin inhibitor (CI) levels were significantly higher in patients with the int 2 WW genotype than in patients with WC or CC genotypes. There was a greater degree of interstitial fibrosis in patients with int 2 CC genotype. No relationship was found between the different polymorphisms and a higher degree and/or frequency of CIN. There was also no relationship with plasma aldosterone levels. CONCLUSION: The frequency of the different polymorphisms studied was not related to plasma aldosterone levels or the development of CIN; however, the int 2 CC genotype was related to a greater degree of interstitial fibrosis, whereas the WW genotype was related to higher CI serum levels.

[Clinical baseline and post-nephrectomy characteristics of renal donors with IgA nephropathy diagnosed by time-zero renal biopsy (T0-RBx) compared with donors with normal T0-RBx]. / Características clínicas basales y post-nefrectomía de donadores renales con nefropatía por IgA diagnosticada mediante biopsia "cero" comparados con donadores con biopsia "cero" normal.

BACKGROUND: The renal manifestations of IgA nephropathy are wide, including patients with asymptomatic disease. The probability of developing advanced renal disease after 20 years of diagnosis varies. The prevalence of mesangial deposits of IgA in otherwise healthy people has been studied previously and there are only 2 reports in which the diagnosis is made by time-zero renal biopsy (TO-RBx). MATERIAL AND METHODS: We compared clinical characteristics (baseline and at followup) of renal donors with IgA nephropathy diagnosed by TO-RBx compared with 20 donors with normal TO-RBx. RESULTS: From 1999 to 2006 151 T0-RBx were analyzed. Of these 10 cases (6.62%) had IgA nephropathy. There were two patients with stage II and 8 with stage I according to HASS classification of IgA nephropathy. All donors in both groups (n=30) had normal urinary tests, however urinary protein excretion was significantly higher in the IgA nephropathy group compared with the normal group from baseline to the end of follow-up (three years). The glomerular filtration rate at three years of follow-up was significantly higher in the normal group (80 +/- 14 vs. 65 +/- 8 mL/min, p = 0.001). CONCLUSIONS: Donors with IgA nephropathy on TO-RBx had no urinary abnormalities during pre donation screening. At three years of follow-up patients with IgA nephropathy showed a greater loss of renal function as well as increased urinary protein excretion.