Hepatorenal syndrome. Studies of the effect of vascular volume and intraperitoneal pressure on renal and hepatic function.

Eleven patients with well-documented hepatorenal syndrome were studied by measurement of blood volume, glomerular filtration rate, renal plasma flow, plasma aldosterone concentration, renin substrate concentration, and plasma renin activity. They were then given 750 ml of stored plasma, 750 ml of fresh frozen plasma, and then an infusion of angiotensin II, in random order on successive days. Infusion of fresh frozen plasma improved function more than did stored plasma and in addition returned a very low filtration fraction toward normal. Angiotensin II infusion increased filtration fraction, but decreased glomerular filtration rate, renal plasma flow, and urine flow sharply. Patients were then given a daily infusion of 1,000 ml of fresh frozen plasma for seven to 18 days to expand the blood volume to supranormal levels as assayed by serial measurement of blood volume. Plasma aldosterone levels decreased to a normal range, glomerular filtration rate and renal plasma flow both increased, and urinary excretion of sodium and potassium both returned toward normal. The effect of intraperitoneal pressure was then studied by measuring glomerular filtration rate, renal plasma flow, pressure in the vena cava, hepatic vein free flow, and hepatic vein wedged pressure before, during, and after paracentesis to reduce the intraperitoneal pressure from 30 to 40 cm H2O to 12 to 17 cm H2O. Venous pressures moved parallel to ascitic fluid pressures, and glomerular filtration rate, renal plasma flow, and urine flow all improved sharply; then, as ascitic fluid continued to form, reducing vascular volume, urine flow, glomerular filtration rate, and renal plasma flow all decreased slowly. Six patients then underwent placement of a LeVeen shunt. Improvement in glomerular filtration rate and renal plasma flow and clinical condition was dramatic. During postoperative observation of up to two years, progressive improvement in hepatic function has occurred.

Low dose, long-term treatment of rheumatoid arthritis with azathioprine.

Sixteen patients with classical rheumatoid arthritis which had been present for longer than two years, representing anatomic stages II-IV, were treated with azathioprine in doses of 50 to 175 mg/day. They were followed up for up to six years. Using the criterion of ability to work, 93% of the patients improved markedly during the time observed. Complement levels were low before treatment and tended to stabilize within the normal range as the disease became less active. Erythrocyte sedimentation rate (ESR) fell during therapy but changes in ESR did not correlate well with the patients' clinical states. Titers of rheumatoid agglutinins showed little change after as long as six years of therapy. When all patients were stable a double-blind cross-over study, using a placebo tablet, was instituted. Fifteen of 16 patients had a marked exacerbation of disease activity after receiving placebo for three to eight weeks. When azathioprine was reinstituted, gradual improvement again occurred so that all patients were back to their asymptomatic or mildly symptomatic state within seven months.

Immunoglobulin A glomerulonephritis: a clinicopathologic study.

Renal biopsies from 10 patients staining predominantly for immunoglobulin A are reviewed. Historically, nine of 10 patients were less than 32 years of age; they all presented with either microscopic or gross hematuria. The initial creatinine clearances demonstrated good function in all patients; only one patient experienced a progressive decline in the creatinine clearance. Similarly, proteinuria was mild. The light and electron microscopic findings presented a variable pattern, including a group with changes confined to the mesangium, another group also having glomerular basement membrane changes, and one patient with severe, progressive glomerular sclerosis. Immunogluorescence demonstrated large amounts of IgA predominantly within the mesangium but occasionally involving the peripheral capillary loops. Serum IgA levels were elevated in six of eight patients tested, and two of five patients had elevated nasal IgA concentrations. These data suggest that there is an immunologic entity, IgA glomerulonephritis, characterized by the above clincial findings in association with elevated serum and occasionally nasal IgA levels, but that the pathologic findings are highly variable. Neither the mechanism nor the particular pathogenetic significance of the raised IgA levels is presently known. The similarities of this entity to the reported findings in anaphylactoid purpura are mentioned.

On the mechanism of rhabdomyolysis in potassium depletion.

Rhabdomyolysis and myoglobinuria occur commonly in men who sustain environmental heat injury during intensive physical training in hot climates. These also occur in patients with potassium depletion. Since physical training in hot climates may be accompanied by serious losses of body potassium, the possibility was considered that performance of strenuous exercise when potassium deficient might enhance susceptibility to rhabdomyolysis. Potassium is released from contracting skeletal muscle fibers and its rising concentration in interstitial fluid is thought to dilate arterioles thereby mediating the normal rise of muscle blood flow during exercise. If potassium release from deficient muscle were subnormal, exercise would not be accompanied by sufficient muscle blood flow and rhabdomyolysis could occur by ischemia. This hypothesis was examined by comparing the effect of electrically stimulated exercise on muscle blood flow, potassium release, and histology of the intact gracilis muscle preparation in normal and potassium-depleted dogs. In normal dogs, muscle blood flow and potassium release rose sharply during exercise. In contrast, muscle blood flow and potassium release were markedly subnormal in depleted dogs despite brisk muscle contractions. Although minor histologic changes were sometimes observed in nonexercised potassium-depleted muscle, frank rhabdomyolysis occurred in each potassium-depleted animal after exercise. These findings support the hypothesis that ischemia may be the mechanism of rhabdomyolysis with exercise in potassium depletion.