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Background: Patients with kidney failure treated with maintenance haemodialysis (HD) require appropriate small molecule clearance. Historically, a component of measuring 'dialysis adequacy' has been quantified using urea kinetic modelling that is dependent on the HD prescription. However, the impact of dialysate flow rate on urea clearance remains poorly described in vivo and its influence on other patient-important outcomes of adequacy is uncertain., Methods: We searched Embase, MEDLINE and the Cochrane Library from inception until April 2022 for randomized controlled trials and observational trials comparing a higher dialysate flow rate (800 ml/min) and lower dialysate flow rate (300 ml/min) with a standard dialysis flow rate (500 ml/min) in adults (age ≥18 years) treated with maintenance HD (>90 consecutive days). We conducted a random effects meta-analysis to estimate the pooled mean difference in dialysis adequacy as measured by Kt/V or urea reduction ratio (URR)., Results: A total of 3118 studies were identified. Of those, nine met eligibility criteria and four were included in the meta-analysis. A higher dialysate flow rate (800 ml/min) increased single-pool Kt/V by 0.08 [95% confidence interval (CI) 0.05-0.10, P  < .00001] and URR by 3.38 (95% CI 1.97-4.78, P  < .00001) compared with a dialysate flow rate of 500 ml/min. Clinically relevant outcomes including symptoms, cognition, physical function and mortality were lacking and studies were generally at a moderate risk of bias due to issues with randomization sequence generation, allocation concealment and blinding., Conclusion: A higher dialysate flow increased urea-based markers of dialysis adequacy. Additional high-quality research is needed to determine the clinical, economic and environmental impacts of higher dialysate flow rates., Competing Interests: P.K. is a consultant to Quanta Dialysis Technologies. C.B. has an ownership interest in Precision Advanced Digital Manufacturing. N.T. has equity in Quanta Dialysis Technologies and reports grants from Tricida, AstraZeneca, Janssen, Boehringer Ingelheim/Eli Lilly, Bayer, the Canadian Institutes for Health Research and the Kidney Foundation of Canada; personal fees from Tricida, AstraZeneca, Janssen, Boehringer Ingelheim/Eli Lilly, Bayer, Otsuka, Renibus, Roche, ClinPredict and Klinrisk; and other payments from ClinPredict, Klinrisk, Tricida and PulseData. ClinPredict and Klinrisk are engaged in efforts to develop and implement models for CKD progression in health systems. D.C. is funded by a KRESCENT New Investigator Award. Y.I., R.B., R.E., K.G. and R.W. report no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Previously, we demonstrated that removal of fetal bovine serum (FBS) from the medium of human skin fibroblasts resulted in an accelerated 86Rb+ washout, decreased cellular K+, and increased Na+ contents. In the present study we examined the mechanism underlying these changes. The efflux rate constant for 86Rb+, and the cellular contents of Na+ and K+ were measured. Verapamil (K1/2 = 15 microM) and chlorpromazine (K1/2 = 1 microM) reduced by approximately 70% the increased 86Rb+ washout evoked by FBS removal. The effect of the two drugs was additive at low, but not high, concentrations. Verapamil and chlorpromazine also attenuated the decrease in cellular K+ content and prevented the increase in cellular Na+ content associated with FBS depletion. Bumetanide (50 microM) was only partially effective in offsetting the enhanced 86Rb+ efflux and was completely without any effect on the cellular Na+ and K+ changes induced by FBS removal. In the presence of FBS, A-23187 produced a slight and transient increase of the 86Rb+ washout. The protein kinase C activator phorbol 12-myristate 13-acetate enhanced the 86Rb+ efflux in FBS-containing medium for a prolonged period but this increase was only a fraction of that caused by serum removal. Cellular Na+ and K+ contents were not changed by the phorbol ester. We conclude that FBS removal raises the cellular Na+ content, and enhances 86Rb+ efflux, through a calmodulin-dependent pathway activated by calcium influx.

To explore the etiology of altered Ca metabolism in essential hypertension, we studied parameters, i.e., maximal initial reaction velocity (Vmax) and Michaelis constant (Km), of Ca activation kinetics of Ca2(+)-ATPase in membrane fractions (isolated by a sucrose gradient) from platelets of blacks and whites, 27 of whom were essential hypertensives, 17 of whom were normotensives with a family history of essential hypertension, and 10 of whom were normotensives without a family history of the disease. The Vmax of hypertensives was significantly lower than in normotensives without a family history of essential hypertension (hypertensives, 14.99 +/- 1.71 nmol Pi.mg protein-1.min-1; normotensives, positive family history, 22.67 +/- 3.17 nmol Pi.mg protein-1.min-1; normotensives, negative family history, 27.54 +/- 4.37 nmol Pi.mg protein-1.min-1; overall, P = 0.0078). The Km was lower in both hypertensives and normotensives with a positive family history of essential hypertension as compared with normotensives with a negative family history of the disease (hypertensives, 1.70 +/- 0.23 microM; normotensives, positive family history, 1.38 +/- 0.2 microM; normotensives, negative family history, 2.79 +/- 0.58 microM; overall, P = 0.0251). Furthermore, the Km in whites was inversely related to plasma renin activity (r = 0.50; P less than 0.005). We propose that a lower Vmax for Ca2(+)-ATPase may play a role in the higher level of free Ca in platelets of essential hypertensives and that a higher affinity of the enzyme to Ca may reflect a process compensating for the lower Vmax. We also suggest that a higher Km for Ca2(+)-ATPase in juxtaglomerular cells of whites would result in blunting the release of renin.

Several reports indicate that erythrocytes (RBCs) from blacks and men have higher sodium concentrations than those from whites and women. One possible mechanism to explain this finding is a difference in the activity of Na+-K+-ATPase. To explore this possibility, we have studied the Na+ and K+ kinetics of RBC Na+-K+-ATPase and RBC Na+ and K+ concentrations in 37 normotensive blacks and whites, both males and females. The maximal initial reaction velocity (Vmax) values for RBC Na+-K+-ATPase were lower in blacks and men as compared with whites and women. Higher RBC Na+ levels were observed in blacks and males vs. whites and females. Significant inverse correlations were noted between the Na+-K+-ATPase activity and RBC Na+ concentrations. These findings indicate that cellular Na+ homeostasis is different in blacks and men as compared with whites and women. Since higher RBC Na+ concentrations have also been observed in patients with essential hypertension as compared with normotensive subjects, the higher intracellular Na+ concentrations in blacks and men may contribute to the greater predisposition of these groups to essential hypertension.