Renal hyperfiltration (RHF) may be independently associated with all-cause mortality and cardiovascular disease (CVD), according to a recent review.

The review included 19 studies (3 cross-sectional, 5 prospective, and 11 retrospective) that investigated the relationship between RHF and all-cause mortality, cardiovascular events (CVE), or CVD indicators. Of 15 studies that looked at the relationship between RHF and mortality, 13 found a significant correlation, Mehmet Kanbay, MD, of Koc University School of Medicine in Istanbul, Turkey, and colleagues reported in Diabetes, Obesity and Metabolism. Seven studies found that RHF predicted CVD.

The investigators concluded that “a better understanding of the relationship between RHF and CVD is important in order to better understand the cogent use of medications that reduce RHF and CVD, such as RAAS [renin-angiotensin-aldosterone system] inhibitors and SGLT2 [sodium-glucose co-transporter-2] inhibitors.”

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One study, published in Kidney International, was an investigation by Marcello Tonelli, MD, of the University of Alberta in Edmonton, and colleagues that included 920,985 patients. Dr Tonelli’s team demonstrated that an estimated glomerular filtration rate (eGFR) of 105 mL/min/1.73 m2 or higher was associated with a 3.7-fold increased risk of death compared with a reference eGFR of 60 to 74.9 mL/min/1.73 m2 in adjusted analyses. The review also included a study by Jula K. Inrig, MD, of Duke University Medical Center in Durham, North Carolina, and colleagues, which looked at 8941 patients with baseline atherosclerotic CVD. In a paper published in the Clinical Journal of the American Society of Nephrology, the investigators reported that among patients with an eGFR of 100 mL/min/1.73 m2 or higher, each 10 mL/min/1.73 m2 increase in eGFR was associated with a 9% increased risk for a composite end point of death, congestive heart failure, myocardial infarction, or stroke.

In addition, the review examined a study by Minseon Park MD, of Seoul National University Hospital in Seoul, South Korea, and colleagues that was published in the Journal of the American Society of Nephrology. The study, which included 43,503 adults who underwent voluntary health screening, demonstrated that RHF—defined as eGFR with residuals above the 95th percentile— was associated with a significant 37% increased risk of all-cause mortality and 30% and 17% increased risk of developing hypertension and CVD, respectively, in adjusted analyses.

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If the detrimental effects of RHF are confirmed, Dr Kanbay and colleagues wrote, “we could follow these patients more closely for timely intervention such as more strict blood pressure and blood glucose control.” In addition, GFR reducing therapy such as RAAS inhibitors and SGLT2 inhibitors could be used at earlier stages, according to the investigators.

Study limitations included the “ambiguity” of the RHF definition and lack of a consensus definition of RHF used by all studies, Dr Kanbay’s team stated. They cited a previous literature review of 405 studies showing the thresholds for defining RHF ranged from 90.7 to 175 mL/min/1.73 m2. In the current review, the range of RHF/high eGFR group thresholds varied from 90 to 130 mL/min/1.73 m2.


Kanbay M, Ertuglu LA, Afsar B, et al. Renal hyperfiltration defined by high estimated glomerular filtration rate: a risk factor of cardiovascular disease and mortality. Diabetes Obes Metab. 2019.

doi: 10.1111/dom.13831

Tonelli M, Klarenbach SW, Lloyd AM, et al. Higher estimated glomerular filtration rates may be associated with increased risk of adverse outcomes, especially with concomitant proteinuria. Kidney Int. 2011;80:1306-1314.

doi: 10.1038/ki.2011.280

Inrig JK, Gillespie BS, Patel UD, et al. Risk for cardiovascular outcomes among subjects with atherosclerotic cardiovascular disease and greater-than-normal estimated glomerular filtration rate. Clin J Am Soc Nephrol. 2007;2:1215-1222.

doi: 10.2215/CJN.00930207

Park M, Yoon E, Lim YH, et al. Renal hyperfiltration as a novel marker of all-cause mortality. J Am Soc Nephrol. 2015;26:1426-1433.