Estimating Residual Kidney Function in Hemodialysis Patients Using Serum Uromodulin

BACKGROUND: Residual kidney function (RKF) monitoring is essential to safe incremental hemodialysis (HD) prescription. Yet the cumbersome nature of interdialytic urine collections represents a major barrier to routine implementation. We investigated serum uromodulin, as a marker of functional renal mass, in identifying HD patients with clinically significant RKF when used alone, or in combination with serum β2-microglobulin, a traditional marker of glomerular filtration. METHODS: We conducted a prospective observational study of 151 HD patients at two centers in Geneva, Switzerland. Serum uromodulin and β2-microglobulin were measured on pre-dialysis 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/35L was assessed by receiver operating characteristic (ROC) analysis, and the two markers were then combined using logistic regression. We applied a two-threshold grey-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 <2 mL/min/35L and 59 (39%) had KRU ≥2 mL/min/35L. Serum uromodulin discriminated KRU ≥2 mL/min/35L with an area under the curve (AUC) of 0.891 (95% CI 0.839-0.944), statistically equivalent to β2-microglobulin (AUC 0.877; P=0.66). Each marker contributed independent information: the combined model achieved an AUC of 0.923 (95% CI 0.883-0.964), superior to either alone (vs uromodulin P=0.03; vs β2-microglobulin P=0.01). Using the grey-zone strategy, uromodulin alone classified 76% of patients without urine collection (negative predictive value (NPV) 97%, positive predictive value (PPV) 84%), while the combined model classified 85%. Restricting analysis to non-anuric patients modestly decreased discrimination (AUC 0.833) with preserved PPV (84%), while avoiding the need for urine collection in 80% of this sub-group. CONCLUSIONS: Serum uromodulin provides RKF information orthogonal to and non-redundant with conventional filtration markers. Their combination reliably identifies the KRU ≥2 mL/min/35L threshold relevant to incremental hemodialysis, sparing most patients from urine collection.