The Effect of Diffusive and Convective Sodium Balance During Hemodialysis on Interdialytic Weight Gain

Patients with end stage renal disease (ESRD) often require hemodialysis treatments in which blood’s water and dissolved solutes undergo diffusion and convection by exposure to an extracorporeal membrane. The leading cause of death in this population is cardiovascular, and how hemodialysis is prescribed alters total sodium balance, a critical determinant of cardiovascular health. We performed retrospective and prospective analysis of data from patients in the Southwestern Ontario Regional Hemodialysis Program. An increased Dialysate sodium (Dial-Na+) to Pre-dialysis plasma sodium (Pre- Na+) concentration difference (DPNa+) leads to adverse clinical outcomes in hemodialysis patients. The post- to pre-dialysis plasma sodium difference (PPNa+) predicts clinical outcomes equally well as DPNa+ so long as Dial-Na+ is within 3 mmol/L of Pre-Na+. Calculation of DPNa+ requires determination of the Pre-Na+, historically thought to be stable in hemodialysis patients and thus termed “setpoint” (SP). However, we determined that SP is modifiable by hemodialysis prescription. Finally, an equation to predict interdialytic weight gain was created, confirming Dial-Na+, dialysis frequency and duration to be modifiable factors affecting IDWG. Further research is required to validate this equation prospectively, and to determine the impact of changes of SP on cardiovascular morbidity and mortality

Narrative Review of Incremental Hemodialysis.

The prescription of hemodialysis (HD) in patients with incident end-stage kidney disease (ESKD) is fundamentally empirical. The abrupt transition from nondialysis chronic kidney disease (CKD) to thrice-weekly in-center HD of much the same dialysis intensity as in those with prevalent ESKD underappreciates the progressive nature of kidney disease whereby the decline in renal function has been gradual and ongoing-including at the time of HD initiation. Adjuvant pharmacologic treatment (i.e., diuretics, acid buffers, potassium binders), coupled with residual kidney function (RKF), can complement an initial HD regimen of lower intensity. Barriers to less intensive HD in incident ESKD include risk of inadequate clearance of uremic toxins due to variable and unexpected loss of RKF, lack of patient adherence to assessments of RKF or adjustment of HD intensity, increased burden for all stakeholders in the dialysis units, and negative financial repercussions. A stepped dialysis regimen with scheduled transition from time-delineated twice-weekly HD to thrice-weekly HD could represent an effective and safe strategy to standardize incremental HD in patients with CKD transitioning to early-stage ESKD. Patients' adherence and survival as well as other clinical outcomes should be rigorously evaluated in clinical trials before large-scale implementation of different incremental schedules of HD. This review discusses potential benefits of and barriers to alternative dialysis regimens in patients with incident ESKD, with emphasis on twice-weekly HD with pharmacologic therapy, and summarizes in-progress clinical trials of incremental HD schedules

Setting the dry weight and its cardiovascular implications

Volume overload is common and associated with adverse outcomes in the hemodialysis population including systemic hypertension, pulmonary hypertension, left ventricular hypertrophy, and mortality. Since the beginning of the era of maintenance dialysis, prescribing and maintaining a dry weight remains the standard of care for managing volume overload on hemodialysis. Reducing dry weight even by relatively small amounts has been shown to improve blood pressure and has been associated with reductions in left ventricular hypertrophy. Maintaining an adequately low dry weight requires attention to sodium intake and adequate time on dialysis, as well as a high index of suspicion for volume overload. Reducing dry weight can provoke decreased cardiac chamber filling and is associated with risks including intradialytic hypotension. The ideal method to minimize intradialytic morbidity is unknown, but more frequent dialysis should be considered. Experimental methods of assessing volume status may allow identification of patients most likely both to tolerate and to benefit from dry weight reduction, but further study is needed

Effect of frequent hemodialysis on residual kidney function.

Frequent hemodialysis can alter volume status, blood pressure, and the concentration of osmotically active solutes, each of which might affect residual kidney function (RKF). In the Frequent Hemodialysis Network Daily and Nocturnal Trials, we examined the effects of assignment to six compared with three-times-per-week hemodialysis on follow-up RKF. In both trials, baseline RKF was inversely correlated with number of years since onset of ESRD. In the Nocturnal Trial, 63 participants had non-zero RKF at baseline (mean urine volume 0.76 liter/day, urea clearance 2.3 ml/min, and creatinine clearance 4.7 ml/min). In those assigned to frequent nocturnal dialysis, these indices were all significantly lower at month 4 and were mostly so at month 12 compared with controls. In the frequent dialysis group, urine volume had declined to zero in 52% and 67% of patients at months 4 and 12, respectively, compared with 18% and 36% in controls. In the Daily Trial, 83 patients had non-zero RKF at baseline (mean urine volume 0.43 liter/day, urea clearance 1.2 ml/min, and creatinine clearance 2.7 ml/min). Here, treatment assignment did not significantly influence follow-up levels of the measured indices, although the range in baseline RKF was narrower, potentially limiting power to detect differences. Thus, frequent nocturnal hemodialysis appears to promote a more rapid loss of RKF, the mechanism of which remains to be determined. Whether RKF also declines with frequent daily treatment could not be determined

The association between ultrafiltration rate and mortality in a co- hort of chronic hemodialysis patients with and without diabetes mellitus: a 7-year retrospective observational study.

Background: The ultrafiltration rate (UFR) is one of the important factors involved in long-term mortality in hemodialysis (HD) patients. Presence of diabetes mellitus often affects UFR due to abrupt hypotension during dialysis. In this study, we aimed to find the optimal UFR to improve the mortality in this population with and without diabetes mellitus (DM).Methods: The effect of the UFR on mortality was retrospectively evaluated in 707 patients un- dergoing regular HD from 1 June 2010 to 30 June 2017. The relationship between the UFR and mortality in patients in the non-DM group and those in the DM group was evaluated. Logistic regression analyses were used to select the determinants of mortality. Receiver operating char- acteristic (ROC) curve analyses and survival analysis were used to determine the optimal cutoff points of UFR for mortality.Results: The cutoff UFR values of the non-DM and DM groups were 12.07 ml/hr/kg and 9.66 ml/ hr/kg, respectively. A survival curve showed that in the non-DM group, the 7-year survival rate of patients with a UFR <12.07 ml/hr/kg was 72.6% and that in those with a UFR ≥12.07 ml/hr/kg was 19.6% (p<0.0001). In the DM group, the 7-year survival rate of those with a UFR <9.66 ml/ hr/kg was 66.7%, and it was 33.4% in those with a UFR ≥9.66 ml/hr/kg (p<0.0001).Conclusion: Lower UFR is essential for the long-term mortality of HD patients, and optimal UFR would be different between patients with and without DM

Blood pressure control in conventional hemodialysis

Hypertension among patients on hemodialysis is common, difficult to diagnose and often inadequately controlled. Although specific blood pressure (BP) targets in this particular population are not yet established, meta-analyses of randomized trials showed that deliberate BP-lowering with antihypertensive drugs improves clinical outcomes in hemodialysis patients. BP-lowering in these individuals should initially utilize nonpharmacological strategies aiming to control sodium and volume overload. Accordingly, restricting dietary sodium intake, eliminating intradialytic sodium gain via individualized dialysate sodium prescription, optimally assessing and managing dry-weight and providing a sufficient duration of dialysis are first-line treatment considerations to control BP. If BP remains uncontrolled despite the adequate management of volume, antihypertensive therapy is the next consideration. Contrary to nonhemodialysis populations, emerging clinical-trial evidence suggests that among those on hemodialysis, β-blockers are more effective than agents blocking the renin-angiotensin-system (RAS) in reducing BP levels and protecting from serious adverse cardiovascular complications. Accordingly, β-blockade is our first-line approach in pharmacotherapy of hypertension. Long-acting calcium-channel-blockers and RAS-blockers are our next considerations, taking into account the comorbidities and the overall risk profile of each individual patient. Additional research efforts, mainly randomized trials, are clearly warranted in order to elucidate aspects of management that remain elusive in hypertensive dialysis patients