Variants of alpha 1-proteinase inhibitor in black and white South African patients with focal glomerulosclerosis and minimal change nephrotic syndrome.

OBJECTIVE To determine the prevalence and biochemical characteristics of certain alleles of alpha 1-proteinase inhibitor in black and white South African patients with two common types of pathology causing the nephrotic syndrome. DESIGN A cross sectional study of black and white patients with focal glomerulosclerosis (FGS) or minimal change disease (MCNS) and black and white controls. SETTING The patients were drawn from the Paediatric Nephrology Units at the Johannesburg and Baragwanath Hospitals and the controls were drawn from the South African Blood Transfusion Service and the Paediatric Nephrology Clinic in Johannesburg. RESULTS There was a significant increase in the prevalence of the V allele in black patients with FGS (12%) as compared to black controls (1%) (p = 0.01). None of the white patients with FGS had the V allele but two out the five coloured (mixed race) patients had the V allele (20%). An increase in the prevalence of the S allele of alpha 1PI was found in white patients with FGS and MCNS (10%) as compared to white controls (2%). The plasma elastase inhibitory capacity (EIC) associated with the phenotypes (PI) M1 (Ala213)S, M1 (Ala213) V, and M1 (Ala213) M1 (Ala213) was significantly decreased as compared to the EIC associated with PI M1 (Val213) M1 (Val213) (p = 0.006, p = 0.004, and p = 0.025, respectively). Twelve of 13 patients with FGS and infected with tuberculosis had either the M1 (Ala213) V or F alleles and required transplantation owing to the severity of the disease. All of these patients were either black or coloured. However, eight of 12 patients with FGS who had the M1 (Ala213) V or S alleles but were PPD negative did not require transplantation. CONCLUSION It is possible that the combination of functionally less efficient alpha 1PI and an inflammatory challenge associated with an infection such as tuberculosis could predispose black and coloured nephrotic patients to more aggressive scarring in FGS.