SGLT2 Inhibitors in Incremental Hemodialysis: Urine Output

Key Takeaways

• Among patients starting once- or twice-weekly incremental hemodialysis at two Spanish centers, urine output increased significantly within SGLT2 inhibitor users but not within nonusers; this was not a tested treatment contrast.
• Kidney urea and creatinine clearances moved upward among users and downward among nonusers, without significant within-group clearance changes.
• The authors reported that 80% of users versus 46.7% of nonusers remained on once-weekly hemodialysis at 12 months, although these percentages do not reconcile with the reported numbers completing follow-up.
• Cardiovascular events occurred in 6.7% of users versus 35.3% of nonusers, a descriptive comparison without formal between-group testing.
• Neither cohort recorded ketoacidosis, urinary tract infection, or genital infection.

For people beginning once- or twice-weekly hemodialysis, residual urine production can help determine how long a less frequent schedule remains feasible. Whether sodium-glucose cotransporter 2 (SGLT2) inhibitors affect residual kidney function after dialysis begins remains uncertain, particularly for patients who continue to produce urine.

Investigators retrospectively enrolled consecutive eligible patients starting incremental hemodialysis in Madrid and Cáceres, Spain, between January 2021 and December 2023. The two-center exploratory longitudinal incremental hemodialysis cohort in Medicina (Kaunas) included 32 patients: 15 users and 17 nonusers. At one center, patients started off-label empagliflozin, dapagliflozin, or canagliflozin within three months of beginning kidney replacement therapy; the other center did not prescribe these drugs. Initially, 86.7% of users versus 100% of nonusers began once-weekly dialysis, a baseline difference rather than a treatment outcome. Both groups received loop diuretics under the same incremental dialysis framework and post-dilution online hemodiafiltration. Quarterly measurements from baseline through 12 months assessed within-group changes in 24-hour urine output and residual kidney urea and creatinine clearances. Nonusers served as a descriptive reference; dialysis frequency and safety events were described without formal between-group tests.

Within SGLT2 inhibitor users, 24-hour urine output changed by +573.3 mL over 12 months (p < 0.001). The change within nonusers was not significant, and investigators did not formally test a difference between groups. Urea and creatinine clearances rose among users and fell among nonusers, but none of these within-group changes was significant. Nonusers began with higher urine output and urea clearance, complicating interpretation of the divergent trajectories.

The proportion remaining on once-weekly dialysis was higher among users at follow-up, while cardiovascular events were recorded less often in that cohort; neither comparison was formally tested. One participant in each cohort died before follow-up ended. The death among SGLT2 inhibitor users was cardiovascular; the death among nonusers was attributed to pulmonary sepsis–COVID-19. This left 14 users and 16 nonusers in the month-12 analysis. Neither cohort recorded euglycemic diabetic ketoacidosis, urinary or genital infections, amputations, or hypersensitivity reactions. Catheter infections and intradialytic hypotension occurred in both groups and were assessed descriptively, not as comparative safety outcomes.

Treatment exposure was inseparable from treatment center. Only the prescribing center combined bioimpedance with point-of-care ultrasound to manage dry weight, despite the shared dialysis framework. Nonusers also entered with higher urine output and urea clearance. Small cohorts, no randomization or matching, no multivariable adjustment, and no formal between-group tests prevent attribution of kidney-function, dialysis-schedule, or cardiovascular patterns to SGLT2 inhibition. Timed urine collections depend on volume status and completeness, while creatinine clearance can overestimate glomerular filtration. Few participants and limited follow-up restrict conclusions about uncommon adverse events and long-term safety. These observations come from Spanish centers and do not establish applicability elsewhere.

The authors characterized the within-user urine-output increase, nonsignificant clearance trajectories, and descriptive between-cohort signals as hypothesis-generating and called for dedicated randomized controlled trials. They did not establish a tested advantage in kidney function, dialysis frequency, cardiovascular events, or safety.

Clinician Questions

Which incident incremental hemodialysis patients were excluded from the SGLT2 inhibitor cohort?

In the Spanish cohort evaluating SGLT2 inhibitors during incident incremental hemodialysis, exclusions included anuria or very low urine output, urgent or unscheduled dialysis starts, prior failed kidney transplant, transfer after peritoneal dialysis technique failure, and type 1 diabetes. The observations do not cover these excluded patients.

How was residual kidney urea clearance measured in patients receiving incremental hemodialysis?

In the Spanish incremental hemodialysis cohort evaluating SGLT2 inhibitors, investigators collected urine during the last 24 hours of the interdialytic interval, ending before the next dialysis session. They calculated residual kidney urea clearance using urine urea concentration and volume together with the average plasma urea concentrations measured after and before consecutive dialysis sessions.

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