CV, Non-CV Mortality Risks Rise as Residual Kidney Function Declines

Lower residual kidney function and loss of residual kidney function (RFK) both correlate with increased risks for cardiovascular and non-cardiovascular mortality in patients receiving thrice-weekly maintenance hemodialysis, a new study suggests.

Kamyar Kalantar-Zadeh, MD, MPH, PhD, of the Harold Simmons Center for Kidney Disease Research and Epidemiology at the University of California Irvine, and colleagues examined baseline RKF in 39,623 patients as well as RKF decline over 6 months in a subset of 12,169 patients. They collected data on renal urea clearance and urine volume.

A significant trend toward higher cardiovascular and non-cardiovascular mortality risk was observed across low RKF categories, starting at a baseline renal urea clearance threshold (in mL/min/1.73m²) of less than 6, the investigators reported in Kidney International Reports. In subgroup analyses, non-cardiovascular death risk significantly increased 79%, 31%, and 22% when baseline renal urea clearance was less than 1.5, 1.5 to less than 3, and 3.0 to less than 4.5, respectively, compared with 6 or higher (reference). The risk for sudden cardiac death significantly increased 63% and 27% at renal urea clearances of less than 1.5 and1.5 to less than 3, respectively. The risk for other cardiovascular deaths significantly increased 59% at a renal urea clearance less than 1.5. The investigators adjusted for case-mix, ultrafiltration rate, and multiple laboratory values.

Adjustment for ultrafiltration rate slightly attenuated the association between low renal urea clearance and high cause-specific mortality, Dr Kalantar-Zadeh’s team reported. The highest serum potassium level reached did not explain the excess mortality.

The faster RKF declined, the greater the mortality risks. In case-mix adjusted analyses, the risk for sudden cardiac death, other cardiovascular mortality, and non-cardiovascular mortality significantly increased by 14%, 24%, and 19%, respectively, when renal urea clearance declined by 3.0 compared with 1.5 over 6 months.

The investigators used urine output as another measure of RKF. Mortality risk trended higher across urine volume categories lower than 900 mL/d. Faster decline in urine volume over 6 months correlated with increased risks for sudden cardiac death and non-cardiovascular mortality, respectively.

“Future clinical trials are warranted to demonstrate the benefits of interventions to preserve RKF, such as an incremental hemodialysis and/or emerging renoprotective pharmacotherapies, and whether these interventions improve high mortality in patients undergoing hemodialysis,” Dr Kalantar-Zadeh’s team wrote.

In an accompanying editorial, John T. Daugirdas, MD, of the University of Illinois College of Medicine in Chicago,  commented that the study provides “important and useful new insights.” He noted that infection-related mortality would have been a valuable addition.

“The exact mechanism whereby RKF is associated with a lower death risk remains incompletely defined, but it is most likely related to reduced serum levels of potential uremic toxins rather than to lower ultrafiltration rates or to lower incidence rates of severe hyperkalemia,” Daugirdas wrote. “Even small amounts of RKF can substantially lower serum levels of higher molecular weight toxins such as beta-2-microglobulin5 and protein-bound uremic toxins, which are not well removed by hemodialysis. Future exploration of the role of RKF and urine volume on hard outcomes should ideally include measurement of serum levels of such uremic toxins.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

References

Okazaki M, Obi Y, Shafi T, Rhee CM, Kovesdy CP, Kalantar-Zadeh K. Residual kidney function and cause-specific mortality among incident hemodialysis patients. Kidney Int Rep. Published online August 3, 2023. doi:10.1016/j.ekir.2023.07.020

Daugirdas JT. Residual kidney function and cause-specific mortality. Kidney Int Rep. Published online August 24, 2023. doi:10.1016/j.ekir.2023.08.024