David Antoine Jaques

Key Points: Serum uromodulin identified patients with residual kidney function on hemodialysis (residual urea clearance ≥2 ml/min per 35 L) with high accuracy. Reflecting tubular mass, not filtration, uromodulin was orthogonal to β 2 microglobulin; combining both had higher discrimination. A two-threshold strategy reliably ruled in patients with the more-than-2 ml/min per 35 L residual urea clearance threshold, avoiding the need for urine collection in most patients. Background: Residual kidney function (RKF) monitoring is essential to safe incremental hemodialysis prescription. Yet the cumbersome nature of interdialytic urine collections represents a major barrier to routine implementation. We investigated serum uromodulin (UMOD), as a marker of functional renal mass, in identifying patients with clinically significant RKF on hemodialysis when used alone, or in combination with serum β 2 microglobulin, a traditional marker of glomerular filtration. Methods: We conducted a prospective observational study of 151 patients on hemodialysis at 2 centers in Geneva, Switzerland. Serum UMOD and β 2 microglobulin were measured on predialysis samples, and residual urea clearance (KRU) was determined by interdialytic timed urine collection. The discriminative performance of each biomarker for identifying patients with KRU ≥2 ml/min per 35 L was assessed by receiver operating characteristic analysis, and the 2 markers were then combined using logistic regression. We applied a two-threshold gray-zone strategy, defining a priori rule-out and rule-in cutoffs to achieve ≥90% sensitivity and specificity, respectively. Results: Of the 151 patients, 92 (61%) had KRU β 2 microglobulin (AUC 0.877; P = 0.66). Each marker contributed independent information: The combined model achieved an AUC of 0.923 (95% confidence interval, 0.883 to 0.964), superior to either alone (versus UMOD P = 0.03; versus β 2-microglobulin P = 0.01). Using the gray-zone strategy, UMOD alone classified 76% of patients without urine collection (negative predictive value 97%, positive predictive value 84%), while the combined model classified 85%. Restricting analysis to nonanuric patients modestly decreased discrimination (AUC 0.833) with preserved positive predictive value (84%), while avoiding the need for urine collection in 80% of this subgroup. Conclusions: Serum UMOD provides RKF information orthogonal to and nonredundant with conventional filtration markers. Their combination reliably identifies the KRU ≥2 ml/min per 35 L threshold relevant to incremental hemodialysis, sparing most patients from urine collection.

In dialysis, preservation of residual kidney function (RKF) is associated with a favorable prognosis. We aimed to identify differences in plasma metabolites depending on the presence of RKF and to evaluate whether a subset of biomarkers could assist in classifying RKF. A prospective study was conducted among chronic hemodialysis (HD) patients in Geneva, Switzerland. Presence of significant RKF was defined as residual clearance of urea (KRU) ≥ 2 mL/min on 24 h urine collection. A total of 89 a priori selected plasma metabolites were analyzed by liquid chromatography-mass spectrometry. We included 136 patients, 54 with KRU ≥ 2 mL/min (40%) and 82 (60%) with KRU < 2 mL/min. The overall metabolic profile strongly differed between patients with and without significant RKF, despite similar total (residual + dialytic) clearances. Classification based on the metabolic profile achieved a 93% accuracy to predict significant RKF at a 2 mL/min cut-off. A subset of 3 biomarkers allowed RKF classification with 87% accuracy. RKF has a decisive influence on the overall metabolic profile of HD patients, which may partly explain its clinical benefit. This provides a physiological rationale for RKF preservation in incremental HD programs, while a limited subset of metabolites could prove useful in monitoring RKF in this setting.

Uromodulin is a kidney‐specific protein that is excreted in the normal urine. Factors regulating its excretion are unknown. Conflicting studies suggest that water balance may influence uromodulin excretion which, in turn, may cooperate with vasopressin to increase water reabsorption in the distal nephron. We analyzed the interplay between uromodulin excretion and water balance in a healthy adult population. Participants were recruited in a population‐based study in Switzerland. The urine uromodulin excretion rate (UUER) (mg/24 h) was measured (ELISA) in parallel with urine osmolality and serum copeptin (pmol/L) (immune‐luminometric assay) as a surrogate for vasopressin. Mixed multi‐variate linear regression models were used. We included 937 participants with 497 (53.0%) women, median age 47.7 years (32.4–61.6) and 27 (2.8%) with eGFR 2 . In univariate analysis, UUER was positively associated with urine volume ( p < 0.001) and negatively with serum copeptin concentration ( p < 0.001). In fully adjusted analysis, UUER remained positively associated with urine volume ( p = 0.004) but not with serum copeptin concentration ( p = 0.224). In univariate analysis, urine osmolality was negatively associated with UUER ( p = 0.016). In fully adjusted analysis, namely accounting for serum copeptin and urine volume, urine osmolality was positively associated with UUER ( p = 0.001). These results indicate that, in a healthy population, urine uromodulin excretion strongly associates with urine volume and, once accounting for confounding factors, influences urine osmolality in addition to vasopressin/copeptin levels. These data substantiate the role of urine flow in regulating uromodulin excretion and suggest an additive effect of uromodulin on urine concentration, alongside vasopressin.

Introduction: Hyperphosphatemia is frequent in hemodialysis (HD) patients and associates with cardiovascular mortality. Parameters of online hemodiafiltration (OL‐HDF) prescription influencing phosphate removal are poorly understood in real‐world clinical settings. Methods: We conducted a prospective observational study including chronic HD patients dialyzed at a single UK university hospital between December 2021 and July 2023. Phosphate removal was quantified from spent dialysate during a midweek session. Results: Dialysate phosphate was measured during 161 dialysis sessions in 128 unique patients (19 on HD and 109 on OL‐HDF), with mean age 63.3 ± 16.2 years and 77 (60.1%) men. Mean intra‐dialytic phosphate removal was 25.6 ± 14.3 mmol per session. In multivariate analysis, pre‐HD serum phosphate concentration, session time, and urea distribution volume ( V ) were positively associated with intradialytic phosphate removal. A significant interaction between session time and pre‐HD serum phosphate concentration indicated that longer sessions provided greater benefit to patients with higher baseline phosphate levels. Conversely, dialysis modality (OL‐HDF vs. HD) and substitution volume were not significantly associated with phosphate removal. Conclusions: OL‐HDF and substitution flow do not demonstrate a measurable beneficial impact on phosphate removal in a real‐world setting. Session time, pre‐HD serum phosphate concentration, and urea distribution volume ( V ) are the most relevant determinants of phosphate clearance in real‐world clinical practice. Session duration emerges as the most effective modifiable factor for controlling phosphate burden in dialysis patients, particularly for those with higher pre‐HD phosphate levels.

Background: Mortality of patients > 75 years of age initiating dialysis is high. Late referral to a nephrologist prior to dialysis initiation is associated with poor outcomes. Herein, we report the outcomes of patients initiating dialysis according to their age and timing of referral. Methods: We reviewed a prospective cohort of patients initiating dialysis from 2000 to 2022 at a single university center. Primary outcome was one-year all-cause mortality. Secondary outcomes were overall all-cause mortality and one-year hospitalization days. Late referral was defined as dialysis initiation < 1 month after a first consultation with a nephrologist. Results: We included 906 patients, including 246 (27%) aged over 75 years. Late referral was more common in elderly patients compared to younger ones, with rates of 26% and 34%, respectively ( p = 0.027). Regarding one-year mortality, considering patients aged over 75 years with early referral as the reference, patients aged > 75 years with late referral were at higher risk (Hazard Ratio [HR] 2.30, p = 0.001), while patients aged < 75 years with either early or late referral were at similar risk. Regarding overall mortality, patients aged > 75 years with late referral were at higher risk (HR 1.56, p = 0.002), while patients aged < 75 years with either early (HR 0.65, p < 0.001) or late referral (HR 0.62, p = 0.001) were at lower risk. Finally, patients aged over 75 years with late referral had more hospitalization days per year (coef 0.09, p < 0.001), while patients < 75 years with either early (coef − 0.07, p < 0.001) or late referral (coef − 0.05, p < 0.001) had fewer hospitalization days per year. Conclusions: Late referral of elderly patients prior to dialysis initiation is common and adversely associated with short- and long-term mortality as well as hospitalization days. Conversely, early referral of elderly patients is associated with a favorable short-term prognosis that is comparable to that of younger patients. Graphical

While SARS-CoV-2 infection has direct obvious consequences on patients undergoing dialysis, the COVID-19 pandemic also had an indirect impact on health systems. Therefore, we aimed to determine whether the COVID-19 era itself was associated with adverse consequences in the Swiss dialysis population as compared to the pre-COVID-19 era, while accounting for direct impact of SARS-CoV-2 infection. We retrospectively included all patients recorded in the Swiss dialysis registry from January 2014 to December 2022. The pre-COVID-19 era and the COVID-19 era were defined based on the cut-off date of January 2020. Cox proportional hazard model was used with all-cause mortality as the primary outcome. The cohort consisted of 7′837 patients from 97 dialysis centres. Median age was 68.6 years with 66.1% men. Crude mortality rates were 11.6% (11.0% to 12.2%) and 14.2% (13.4% to 14.9%) person-years for the pre-COVID-19 era and the COVID-19 era, respectively. In multivariable analysis, SARS-CoV-2 infection was associated with an increased risk of mortality (HR 4.26, 95% CI 3.65 to 4.97, P < 0.001) while the COVID-19 era itself was not (HR 0.98, 95% CI 0.88 to 1.08, P = 0.687). The COVID-19 era was not associated with an excess of mortality in the Swiss dialysis population as compared to the pre-COVID-19 era when accounting for the direct effect of SARS-CoV-2 infection. This suggests that control measures established during the pandemic did not have a negative impact on dialysis patients at the national level. These results could inform health policy makers in the eventuality of future pandemics.

Introduction: Hyperkalemia is frequently encountered and associated with cardio‐vascular mortality in chronic hemodialysis (HD) patients. While online hemodiafiltration (OL‐HDF) is thought to offer clinical benefit over high‐flux HD, the impact of convective clearance on intra‐dialytic potassium removal is unknown.Methods: Chronic dialysis patients undergoing outpatient HD or OL‐HDF at a single center attached to a university hospital were recruited in a prospective observational study. Spent dialysate along with clinical and biological variables were collected during a single mid‐week session.Results: We included 141 patients, with 21 treated with HD and 120 with OL‐HDF. Mean age was 65.7 ± 15.6 years with 87 (61.7%) men. Mean intra‐dialytic potassium removal was 69.9 ± 34.2 mmol. Patients on OL‐HDF and HD have similar intra‐dialytic potassium removal, with mean values of 69.1 ± 34.2 and 74.3 ± 35.0, respectively. In multivariate analysis, factors associated with intra‐dialytic potassium removal were (decreasing order of effect size): dialysate potassium (β −15.5, p < 0.001), pre‐HD serum potassium (β 9.1, p < 0.001), and session time (β 7.8, p = 0.003). In OL‐HDF patients, substitution flow was not associated with potassium removal.Conclusion: In chronic dialysis patients, convective therapy provided by OL‐HDF does not affect potassium removal when compared with high‐flux HD. Moreover, the importance of convective volume is not associated with potassium clearance in OL‐HDF. Overall, session length and serum‐to‐dialysate potassium gradient are the main determinants of potassium clearance regardless of dialysis modality. Those results should inform clinicians on the optimal therapy in chronic dialysis patients in the era of OL‐HDF.