Focal segmental glomerulosclerosis in adult African Americans.

We have previously shown that idiopathic focal segmental glomerulosclerosis (FSGS) is the most common non-proliferative primary glomerulopathy in adult African Americans. In this report we present our experience with treated FSGS in 15 such patients followed over five years. They were all treated with prednisone 60 mg daily for three months, followed by a slow tapering. In addition, two patients later had cyclophosphamide, and five had enalapril. At entry hypertension was present in 73% of the patients, nephrotic syndrome in 87%, and elevated serum creatinine (> or = 1.4 mg/dl) in 40%. Five of the 15 patients (33%) developed end-stage renal failure (ESRF), one of them having a "malignant" course after the advent of pregnancy. Two patients (13%) have chronic renal insufficiency (CRI; serum creatinine > 2.5 mg/dl); three (20%) have mild renal insufficiency (serum creatinine 1.4-2.5 mg/dl), and five patients (33%) have normal renal function. The cumulative renal survival was 93% at five years, but only 26% at eight years. At last follow-up all the ten patients who did not develop ESRF were in partial remission (urinary protein of 1.3 g/day +/- 1.21), but 4 of the 5 patients who did not develop ESRF had no prolonged partial remission of nephrotic syndrome. Neither the initial clinical parameters not the use of enalapril correlated with the renal outcome (univariate analysis). However, 4 of the 5 patients who developed ESRF had elevated serum creatinine at entry, versus only 2 of the 10 not developing ESRF (p = 0.09 by two-sided, and 0.045 by one-sided Fisher's exact test). We conclude that the short-term renal outcome in nephrotic adult African Americans with treated FSGS is comparable to that of the non-African Americans, but their long-term prognosis may be poorer. Patients developing ESRF were more likely to present with elevated serum creatinine. Enalapril did not seem to modify the course of renal disease, but its utility and that of other ACE inhibitors in the treatment of FSGS must await prospective randomized studies.

Role of cocaine in end-stage renal disease in some hypertensive African Americans.

During a period of 1 year we observed 12 African American patients who had smoked or sniffed cocaine for several years and presented to inner city hospitals with accelerated hypertension and renal insufficiency. Ten required maintenance dialysis; 1 recovered partially after a brief period of dialysis, and 1 had moderate renal insufficiency. In the absence of striking proteinuria, cardiomegaly or renal shrinkage, the probable diagnosis in most of the patients was primary accelerated hypertension. The clinical history suggested that the habitual use of cocaine had worsened the hypertension, made it more difficult to control or triggered an accelerated phase resulting in renal shutdown. At a time when billions of dollars are being spent on the treatment of end-stage renal disease, the harmful role of cocaine in susceptible individuals requires due attention.

Possible role of calmodulin in renin secretion from isolated rat kidneys and renal cells: studies with trifluoperazine.

Trifluoperazine, an inhibitor of calmodulin and calmodulin-directed secretion, was used to examine a possible role of calmodulin in renin secretion from isolated perfused kidneys and renal cortical cells. In isolated perfused kidneys trifluoperazine stimulated basal renin secretion in a dose-dependent manner, with 10 microM causing no stimulation and 50 microM causing 167% increase. Trifluoperazine potentiated the elevated renin secretion induced by isoprenaline and low Ca in isolated kidneys. In renal cortical cells trifluoperazine increased basal renin secretion and potentiated the secretion induced by Ca omission. Cells homogenized immediately after 1 h exposure to trifluoperazine had a substantial reduction in soluble renin without any effect on the change in granular renin. In the absence of trifluoperazine, soluble renin increased with O Ca and decreased with 1.5 mM-Ca. It is concluded that trifluoperazine stimulates renin secretion by a cellular mechanism possibly at the level of the juxtaglomerular cell. It is suggested that the role of trifluoperazine, and by inference calmodulin, in the secretion of renin may be quite different from its role in secretion of several other substances.