Relationship between lymphocyte and clinical steroid responsiveness in focal segmental glomerulosclerosis

A remission in nephrotic proteinuria with steroid treatment appears to favorably alter the natural history of focal segmental glomerulosclerosis (FSGS). It is not known why some patients have a favorable response to steroid treatment whereas others do not. Considering the possibility that differences in the pharmacodynamic responsiveness to steroids among patients might be one factor, the authors examined the relationship between the pretreatment suppressive effect of steroids on lymphocyte proliferation (% inhibition) in vitro and the short- and intermediate-term responses of creatinine clearance (Cl-cr) and/or nephrotic proteinuria (urine protein/creatinine ratio = U-p/c) 13 patients with FSGS. There were significant correlations between % inhibition and the changes in Cl-cr at 3 (r = 0.92, p < 0.001) and 6 (r = 0.86 p < 0.01) months and the changes in U-p/c at 3 months (r = -0.74, p = 0.02). Thus, the greater the pretreatment lymphocyte steroid sensitivity the greater the increase in Cl-cr or decrease in U-p/c. The changes in these parameters could not be accounted for on the basis of steroid dose or histopathology. The in vitro sensitivity of FSGS patients' lymphocytes to steroids may be of value in anticipating their clinical response to treatment. Journal of Clinical Pharmacology, 2000;40:115-123 (C)2000 the American College of Clinical Pharmacology.