Pulse methylprednisolone therapy in idiopathic, rapidly progressive glomerulonephritis.

Idiopathic crescentic glomerulonephritis is associated with a 70% to 80% incidence of end-stage renal failure. Oral corticosteroid therapy in combination with immunosuppressive agents or anticoagulants has not altered the prognosis of this disease. We have seen five adults with idiopathic crescentic glomerulonephritis and treated them with intravenous methylprednisolone. Before therapy, the average serum creatinine concentration was 7.4 +/- 1.3 mg/dL (chi-square +/- SEM). This value declined to 2.0 +/- 0.48 mg/dL within 4 weeks. All patients continue to maintain stable renal function over an average follow-up period of 19 months (range 1.5 to 36 months). These data suggest that a prospective controlled trial of this therapy is warranted in the management of this entity.

Acute renal failure in legionnaires' disease: report of a case.

The renal insufficiency which has been described in some of Legionnaires' Disease, has not been characterized. We describe a patient who developed severe oligoanuric renal failure associated with Legionnaires' Disease. Renal biopsy revealed acute tubular necrosis.

Anticoagulation in renal vein thrombosis.

Long-term anticoagulation therapy was evaluated in two patients with renal vein thrombosis and the nephrotic syndrome. Neither patient exhibited peripheral thromboemboli. Moreover, the renal vein thrombus resolved in both cases after eight months on a regimen of oral anticoagulant therapy. Glomerular filtration rate remained stable despite persistence of the nephrotic syndrome. These results suggest that long-term anticoagulation may be of distinct value in nephrotic patients with renal vein thrombosis.

The effect of bumetanide on cation transport in human red blood cells.

Bumetanide, a sulfamyl-aminobenzoic acid derivative, is a new and highly effective diuretic agent. The present studies were designed to examine its effects on cation transport in human red cells. At a concentration of 10(-3) M, the drug inhibited both active and passive unidirectional sodium fluxes, as well as active potassium influx. It also caused a significant inhibition of glycolysis. The inhibition caused by bumetanide was less than that seen with ouabain alone, but a bumetanide effect was also present in ouabain-treated cells. Bumetanide had no effect on red cell Na-K adenosine triphosphatase activity and did not affect net transport of sodium in sodium-loaded cells. The data are consistent with a model in which the inhibition of monovalent cation movement in red cells by bumetanide is related to an effect of this compound in decreasing the permeability of the red cell membrane to sodium.

On the origin of urinary fibrin-fibrinogen-related antigen in glomerulonephritis.

A model of antiglomerular basement membrane nephritis in the rat was used to elucidate the origin of urinary fibrin-fibrinogen-related antigen (FRA). The intrarenal distribution and excretion of 125I-rat fibrinogen was examined to determine whether there was increased filtration of bibrinogen or fibrin degradation products (FDP) or lysis of intraglomerular fibrin. 125I-protein appeared in the urine immediately after injection of 125I-fibrinogen and fell in parallel with the fall in plasma 125I-fibrinogen. Renal retention of 125I-fibrin averaged less than 0.2 percent of the administered dose of 125I-fibrinogen. The infusion of epsilon aminocaproic acid (EACA) had no significant effect on either FRA excretion or 125I-protein excretion. Plasma FDP levels and the elution patteren of 125I-protein from the urine were not significantly changed by EACA infusion. These observations support the view that ruinary FRA excretion in glomerulonephritis is derived predominantly from increased filtration of plasma fibrinogen rather than from breakdown of intraglomerular fibrin.

Effect of albumin infusion on renal glucose reabsorption in the rat.

Clearance and micropuncture techniques were employed to assess the relationship between renal glucose and sodium reabsorption in the rat. Late proximal tubular fluid was collected from surface nephrons before and at two intervals after the infusion of hyperoncotic albumin by a double recollection technique. Plasma glucose levels were maintained at 28-44 mM throughout. Proximal tubular reabsorptive rates for both glucose and sodium were elevated 20 min after the start of the hyperoncotic infusion. Continued infusion of the hyperoncotic albumin resulted in a natriuresis and a parallel fall in proximal glucose and sodium reabsorption. Changes in maximal glucose reabsorption rates for the whole kidney paralleled changes in glucose reabsorption in surface nephrons. The addition of calcium and magnesium to the hyperoncotic infusate diminished the natriuresis but did not alter the relationship between sodium and glucose reabsorption. These observations indicate a close relationship between proximal tubular glucose reabsorption and sodium reabsorption during hyperoncotic infusion.

Heparin therapy in anti-basement membrane nephritis.

The effect of heparin on the development and progression of a form of antiglomerular basement membrane nephritis was examined in the rat. Animals which received heparin before and throughout the period of immunological insult developed lesions which were as severe, and perhaps more severe, than rats which did not receive heparin. Inulin clearances were lower in heparin-treated animals than in untreated rats. Animals in both groups exhibited renal fibrin-fibrinogen deposition and had increased rates of urinary fibrin-fibrinogen related antigen excretion. These results indicate that heparin per se has no beneficial effect on the development of this form of glomerulonephritis in this species.

Glomerulotubular relationships in glomerulonephritis.

Clearance techniques were employed to examine glomerulotubular relationships in a model of chronic glomerulonephritis in the rat. Clearance ratios were found to be equal in both kidneys in the same animals, indicating that the nephron population was functioning in a homogeneous manner. Glucose titration curves were normal and this finding also indicates that glomerulotubular relationships were intact for the composite nephron population. In contrast to models of chronic renal disease with nonglomerular lesions, nephron filtration rate was reduced in these animals. However, the animals still exhibited a capacity to respond to contralateral nephrectomy by increasing filtration rate in the residual nephrons.

On the influence of extracellular fluid volume expansion on bicarbonate reabsorption in the rat.

Bicarbonate reabsorption is classically regarded as a rate-limited process characterized by saturation kinetics. The tubular maximum (Tm), however, varies with glomerular filtration rate. Thus bicarbonate reabsorption, in common with sodium reabsorption, is characterized by glomerulo-tubular balance. The examination of bicarbonate reabsorption is accomplished using the bicarbonate titration technique; however, this method in its traditional form leads to marked expansion of extracellular fluid (ECF) volume. The possibility exists, therefore, that glomerulo-tubular balance for bicarbonate is altered by the volume expansion and thus that the classic pattern of reabsorption may actually reflect inhibited bicarbonate reabsorptive capacity. The present studies were performed in rats to examine this possibility. Bicarbonate titration studies were performed in two groups of animals: (a) those in which ECF volume expansion was minimized; and (b) those in which ECF volume expansion was exaggerated. In the first group, no Tm for bicarbonate was observed either in the majority of individual rats studied or in a group plot for all rats studied despite the fact that plasma bicarbonate concentrations were increased to values in excess of 60 mEq/liter. In the second group, a clear Tm was demonstrated both in individual animals and in group data and there was a lowered threshold for the excretion of bicarbonate. The data thus lend support to the view that the "normal" Tm for bicarbonate may actually represent an inhibited level of bicarbonate reabsorption induced by ECF volume expansion.