The effect of prostaglandin inhibition on the clinical course of chronic hemodialysis.

We studied the hypothesis that dialysis hypotension may be triggered by dialysis-induced release of prostaglandin/prostacyclin. Indomethacin (50 mg 5 X in 30 h) was given before dialysis to 10 stable, chronic hemodialysis patients, comparing it to placebo in a double-blind, crossover manner. Mean arterial blood pressure (MAP) before dialysis was 106.6 +/- 17.7 and 99.7 +/- 10.4 (SD) mm Hg for indomethacin and placebo, respectively. MAP after dialysis was 95.4 +/- 13.9 and 85.2 +/- 11.0 mm Hg for indomethacin and placebo, respectively. Ultrafiltration, expressed as a weight loss, was 1.82 +/- 1.1 kg for indomethacin and 1.38 +/- 1.29 kg for placebo dialysis. The amount of saline given during dialysis was 339 +/- 139 ml for indomethacin and 388 +/- 83 ml for placebo. Although indomethacin treatment resulted in more ultrafiltrate, less saline infusion, and higher MAP before and after dialysis, none of these differences were statistically significant. This preliminary trial indicates that prostaglandin/prostacyclin inhibition by indomethacin does not alter the clinical course of hemodialysis of chronic stable patients.

The glomerular mesangium: kinetics using radiolabeled ferritin and the effects of aggregated IgG.

A quantitative method for studying glomerular mesangial kinetics using radiolabeled native ferritin (125I-NF) is described. Groups of Sprague-Dawley rats were given injections of monomeric 125I-NF in a dose of 10 mg/100 g and sacrificed at 4, 16, and 36 hr. Radioactivity was measured in preparations of isolated glomeruli, spleen, and liver, and in blood. After initial uptake, a progressive decrease in the concentration of 125I-NF was observed in the mesangium and other organs. To examine the effect of one macromolecule on the mesangial kinetics of NF a separate group of animals was given aggregated human IgG (AHIgG) (40 mg/100 g) 4 hr prior to administration of 125I-NF. The administration of AHIgG did not alter the kinetics of 125I-NF in the mesangium, plasma, or spleen but the disappearance of 125I-NF from the liver was accelerated. Although the cellular mechanisms for uptake of NF and AHIgG are different, the presence of one macromolecule (AHIgG) within the mesangium did not affect the uptake and disappearance of another (NF). Thus, the glomerular mesangium has a relatively high capacity under normal circumstances.

Mannitol intoxication in patients with renal failure.

Eight patients with severe mannitol intoxication were treated during the last ten years. These patients had CNS involvement out of proportion to uremia, severe hyponatremia, a large osmolality gap (high measured minus calculated serum osmolality), and fluid overload. Six patients were treated with hemodialysis and one patient received peritoneal dialysis. One patient died before any treatment could be started. Mannitol had a half-life of approximately 36 hours during the intervals without treatment. The ideal treatment is hemodialysis that rapidly removes mannitol (half-life, six hours) and replaces it with sodium; peritoneal dialysis removed mannitol slowly (half-life, 21 hours).

Hypotension during acetate and bicarbonate dialysis in patients with acute renal failure.

Bicarbonate dialysate is claimed to be superior to acetate for both chronic and acute hemodialysis. We compared acetate and bicarbonate dialysates in 30 acute renal failure patients during 120 dialyses. 4 patients were diabetic and 2 had liver failure. Patients were dialyzed alternating acetate and bicarbonate dialysate in a double-blind cross-over manner; each patient was his own control. BUN, creatinine, Na+, K+, osmolality, delta osmolality, % ultrafiltration, arterial blood gases, pre, post and lowest dialysis mean arterial blood pressure, dialysis with hypotensive episodes and symptoms of hypotension were recorded. The measurements obtained for each patient during dialyses with acetate and bicarbonate were compared. There was no difference in predialysis chemistries, osmolality or osmolality fall, no change in mean arterial blood pressure or hypotensive episodes and symptoms and ultrafiltration. PCO2 and pH were slightly lower for the acetate group at the 2nd h but not at the end of dialysis. 4 patients had serum acetate determinations, all metabolized acetate normally. These findings contradict recent suggestions that severely ill patients should not be dialyzed against acetate. Since acetate is technically much easier to use and has no clinical drawbacks, it does not need to be replaced with bicarbonate in acute patients. Other factors must be more important than acetate in generating hypotension during acute dialysis.