Sustained volume expansion and [Na,K]ATPase inhibition in chronic renal failure.

Hypotheses regarding the pathogenesis of volume-dependent hypertension have invoked an endogenous sodium pump inhibitor or digitalis-like factor (DLF) to link altered sodium homeostasis to the rise in blood pressure. Our goal was to develop a clinical protocol that achieved predictable, sustained volume expansion, with the premise that renal failure patients on peritoneal dialysis would increase intravascular volume, gain weight, and raise blood pressure (BP) in relation to measured increases in DLF. In a 5-day protocol, dialysis was kept constant but dietary NaCl and fluids were modified in 7 patients. DLF was measured as inhibition of [Na,K]ATPase. Likewise, the first 2 L of daily peritoneal dialysate (PD) was processed on HPLC and the eluate analyzed for DLF. The group achieved significant weight gain (WT) by day 3 (delta WT = 4.1 +/- 1.2 kg, P < .05). Likewise, mean arterial pressure (MAP) and plasma DLF activity increased significantly. All variables were highly correlated (DLF v WT: R = 0.88, P = .004; MAP v DLF: R = 0.82, P = .01; MAP v WT: R = 0.90, P = .003). Although a number of HPLC fractions contained agents that interacted with the assay, only one PD HPLC fraction (at 19.5 min) contained DLF activity that correlated with changes in MAP (R = 0.60, P = .002), and body weight (R = 0.67, P = .0003). We conclude that candidate DLF responds to sustained volume expansion and the relationship suggests that it could influence blood pressure. Moreover, the application of stringent criteria to the confusing array of factors in plasma that may affect assays for DLF appears to reduce the field dramatically, to a single candidate in this setting.

Late renal allograft failure secondary to thrombotic microangiopathy-human immunodeficiency virus nephropathy.

The case of a renal transplant recipient with a known history of iv drug abuse but unknown human immunodeficiency virus (HIV) status who presents after having a stable renal allograft function for 4 yr, with acute/subacute advanced renal failure, nephrotic syndrome, and hypertension, as well as clinical and histologic findings of thrombotic microangiopathy, is reported. He was subsequently found to have a positive serology for HIV-1 with a low CD4 count but no clinical manifestations of the acquired immunodeficiency syndrome. He was treated conservatively with zidovudine (AZT). The patient never regained graft function and was ultimately discharged from the hospital on maintenance dialytic therapy. This is, to our knowledge, the first report of thrombotic microangiopathy in an HIV-1-infected patient presenting late in the course as acute/subacute renal allograft failure.