Estimating Residual Kidney Function in Hemodialysis Patients Using Serum Uromodulin

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.

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.

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.

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.