Zeenat M. Nawab

Neutrophilic intracellular acidosis induced by conventional, lactate-containing peritoneal dialysis solutions.

Exposure of human neutrophils to a conventional, acidic, lactate-containing peritoneal dialysis solution (PDS) resulted in the development of a prompt and substantial intracellular acidosis. It is possible that this intracellular acidosis contributes to cellular dysfunction.

Treatment of acute methanol intoxication with hemodialysis using an ethanol-enriched, bicarbonate-based dialysate

A patient poisoned with methanol was successfully hemodialyzed with an ethanol-enriched, bicarbonate-based dialysate. Along with a concomitant intravenous infusion of ethanol, the ethanol-enriched dialytic procedure was able to maintain an intradialytic plasma ethanol level of 80 to 102 mg/dL. The patient recovered without any sequelae of methanol intoxication.

Demonstration of Fabry's disease deposits in placenta

Involvement of the placenta by glycosphingolipid deposits in Fabrys disease has not been previously reported. We describe the presence of such deposits in the maternal half of a placenta obtained from a heterozygous carrier of the disease.

Acetate relaxation of isolated vascular smooth muscle

The vasorelaxant effects of acetate in arginine vasopressin (AVP)-contracted rat tail artery strips were examined in order to study mechanism of action. Dose-dependent relaxation by acetate was found in the clinically important range of 4 to 16 mM. Relaxation was not due to complexing of ionized calcium, persisted after mechanical removal of the endothelium, and was not altered by pretreatment with indomethacin. Although acetate also inhibited contraction by alpha-1 and alpha-2 agonists, the relaxant effect was not altered by destruction of sympathetic nerve terminals using 6-hydroxydopamine. The degree of relaxation in this model by various anions correlated with their lyotropic properties; however, the vasorelaxant effect of acetate exceeded that which would be expected on the basis of its position in the lyotropic series. The vasorelaxant effect of acetate was shared by other short-chain fatty acids that can be conjugated with coenzyme A (CoA), such as propionate and malonate. In contrast, a much lesser or absent relaxant effect was found with nonfatty-acid precursors of acetyl CoA, such as pyruvate, lactate, and alanine. The vasorelaxant effect of acetate was abolished by pretreatment with DIDS, an inhibitor of organic anion uptake, suggesting that cellular uptake of acetate is essential to its vasorelaxant action. The results suggest that the relaxant effect of acetate in vascular smooth muscle is non-specific, is not mediated by prostaglandins, does not depend upon the presence of either endothelium or the sympathetic nervous system, and may be due to metabolism of acetate to acetyl CoA with attendant conversion of ATP to AMP.

Increasing plasma phosphorus values by enriching with phosphorus the "acid concentrate" of a bicarbonate-buffered dialysate delivery system.

Each of seven hypophosphatemic hemodialysis patients was dialyzed with a phosphorus-enriched, bicarbonate-buffered dialysate. The latter was prepared by the introduction of sodium phosphate salts to the “acid concentrate” of a bicarbonate-buffered dialysate delivery system. The patients tolerated the procedure well and their hypophosphatemia improved.

Use of Lactate as a Base in Hemodialysis

The purpose of our study was to investigate the feasibility of using lactate as a complete or partial substitute for acetate in hemodialysis solutions. Six patients, each serving as his own control, were dialyzed once against a dialysis solution containing 40 mM acetate, once against a dialysis solution containing 40 mM DL-lactate and once against a dialysis solution containing 20 mM each of acetate and DL-lactate. Six additional patients underwent hemodialysis using acetate + lactate for a 3-week period, and the blood acid-base values during this period were compared to those obtained during periods when acetate was used. All dialysis treatments were well tolerated without hypotension or other clinical manifestations. When acetate + lactate was used, only a slight delay in the correction of acidosis during dialysis occurred and the net change in the plasma bicarbonate value appeared to be comparable to that measured with acetate. On the other hand, when lactate was used, the increase in the plasma bicarbonate level during and immediately after dialysis was reduced. With acetate + lactate, intradialytic blood D-lactate levels remained between 1 and 2 mM and returned promptly to near baseline within 1 h after dialysis. During 3 weeks of dialysis using acetate + lactate, predialysis plasma bicarbonate values were similar to those achieved when using acetate, but with acetate + lactate, the intradialytic plasma acetate levels were reduced by 50%. The results suggest that DL-lactate merits further evaluation as a potential base for hemodialysis solutions, and that both the D- and the L-lactate isomers are metabolized in maintenance hemodialysis patients.

Failure of neutrophils to recover their ability to produce superoxide after stunning by a conventional, acidic, lactate-based peritoneal dialysis solution.

Exposure of human neutrophils to conventional, acidic, lactate-based peritoneal dialysis solutions for 5 minutes results in a depression of superoxide generation. In spite of restoration of extracellular pH to 7.4, these stunned cells failed to recover their ability to generate the anion after a period of an hour.

Heparin-associated thrombocytopenia in maintenance hemodialysis patients.

Thrombocytopenia associated with the presence of a heparin-dependent platelet aggregating factor developed in two patients after hemodialysis with heparin. It resolved in one patient after heparin was stopped; but persisted in the other during a two-week heparin-free period and intermittently thereafter. We suggest that when heparin causes thrombocytopenia in dialysis patients the heparin should be stopped whenever possible, but this may not be necessary in all patients.