Endothelin-1 K198N Polymorphism Modifies Clinical and Histopathological Manifestations of IgA Nephropathy

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Endothelin 1 (ET-1) is a potent vasoconstrictor that plays an important role in the progression of renal injury. IgA nephropathy (IgAN), the most prevalent form of primary glomerulonephritis, is one of the major causes of end stage renal disease (ESRD) and the susceptibility to progressive renal dysfunction in this disease may be determined by genetic variations. In the present study, we investigated 308 patients with biopsy-proven IgAN for possible associations between ET-1 K198N polymorphism and clinical and histopathological manifestations. At the time of biopsy, the ET-1 198KK genotype was significantly associated with a higher incidence of hypertension and lower renal function, and the renal survival of patients with the ET-1 198KK genotype was significantly worse than those with other genotypes. Moreover, with respect to the histopathological characteristics of renal biopsy findings, the 198KK genotype was significantly associated with higher scores of global sclerosis, interstitial fibrosis, and arteriosclerosis of large arteries than other genotypes, whereas no difference was observed in other histological parameters including mesangial cell proliferation, mesangial matrix increase, the adhesion of glomerular tufts to Bowman's capsule, and crescent formation. The results of the present study indicate that the K198N polymorphism can be a marker for severe renal vascular injury and poor renal survival in patients with IgAN.

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