Kidney Tubular Secretion Associated With Faster eGFR Decline

Faster decline in estimated glomerular filtration rate (eGFR) was found to be associated with lower estimated tubular secretion in participants with chronic kidney disease (CKD), according to a study published in Kidney Medicine. Tubular secretion was not found to be associated with progression of CKD or cardiovascular disease (CVD).

People with CKD have an increased risk of CVD. Kidney tubules have a central role in regulating blood pressure and drug secretion, but their pathology is not fully captured through the use of eGFR and albuminuria. The researchers aimed to assess if baseline estimated tubular secretion was associated with a faster decline of eGFR and greater risk of CKD progression, CVDs, and all-cause mortality.

This study used SPRINT trial participant data for analysis, which was an open-label clinical trial that “randomized participants with hypertension and high CVD risk to an ‘intensive’ systolic blood pressure (BP) target of [less than] 120 mm Hg vs a ‘standard’ BP target of [less than] 140 mm Hg.”

Participants (N = 2089) were included in the SPRINT trial if they were 50 years and older, had a systolic BP of 130 to 180 mm Hg, and had a high risk of CVD. Participants were enrolled from November 2010 to March 2013 and were followed-up monthly for the first 3 months after baseline and every 3 months after. The trial ended after a median follow-up of 3.26 years.

There were 10 endogenous secretion markers in plasma and urine at baseline measured for this study. Participants were excluded if they had unavailable specimens of plasma and urine biomarker measurements. Tubular secretion was calculated using the urine-to-plasma ratio (UPR) of each secretion marker and creating a summary score. Covariates such as age, sex, race, and past medical history were obtained using a questionnaire.

The annualized eGFR slope was the primary outcome of interest and was based on the serial serum creatinine measurements collected every 3 months.

There study participants had a baseline eGFR below 60 mL/min/1.73 m². The mean (SD) age of the participants was 73 (9) years, and 41% were women. Median (IQR) baseline eGFR was 48 mL/min/1.73 m² (38-55) and median baseline albuminuria was 15 mg/g (7-48). Participants in the highest secretion score quartile had the higher eGFR and lower albuminuria compared with the participants in the lowest quartile at baseline.

The mean secretion score for the participants was 59.3 (7.6). Baseline eGFR (r, 0.39) was positively correlated and albuminuria (r, –0.30) was inversely correlated with secretion score. UPRs were 2 to 3 times higher in participants with an eGFR of 45 to 59 mL/min/1.73 m² compared with the the UPRs of participants with an eGFR below 30 mL/min/1.73 m².

The mean annualized eGFR slope was –1.44% per year (95% CI, –1.60% to –1.27%) over a median 3.3 years of follow-up. The lowest secretion score quartile had the fastest annualized eGFR decline, and lower UPRs of 9 of the 10 secretion markers had an association with faster eGFR decline.

Multivariable models found that faster annualized eGFR decline was associated with lower secretion score (–0.65% less per year per 1-SD lower secretion score; 95% CI, –0.84% to –0.46%). Faster eGFR decline was found in the lowest compared with the highest quartile (–0.77% per year; 95% CI, –1.29% to –0.26%).

Faster eGFR decline in participants with a baseline eGFR of less than 45 mL/min/1.73 m² was found in participants with a lower secretion score (–1.17% per year; 95% CI, –1.49% to –0.86%) vs participants with a baseline eGFR of at least 45 mL/min/1.73 m².

Association between lower secretion score and risk of CKD or CVD was not statistically significant.

There were some limitations to this study. Direct measurements of tubular secretion are not available so tubular secretory function was estimated, and the urine samples in SPRINT were spot samples, which may have led to intraindividual variability.

The researchers concluded that lower estimated tubular secretion was associated with a faster decline in eGFR in patients with hypertension and CKD. This association was independent of baseline eGFR and albuminuria.

Reference

Ascher SB, Shlipak MG, Katz R, et al. Estimated kidney tubular secretion and kidney cardiovascular, and mortality outcomes in CKD: the systolic blood pressure intervention trial. Kidney Med. 2022;4(12):100546. doi:10.1016/j.xkme.2022.100546