Revised Hyperfiltration Formula Incorporates Age-Related Renal Function Decline

New research has yielded an updated definition of hyperfiltration to address age-related renal function decline in kidney donor candidates with obesity and glucose tolerance disorder.1

The revised formula uses both age and glomerular filtration rate (GFR) without body surface area correction to determine the threshold value for hyperfiltration, overcoming inherent limitations of the conventional method for detecting excessive filtration in patients with obesity and/or glucose tolerance disorder.1

“Since hyperfiltration is a precursor to diabetic nephropathy, we hope that using this new formula will more accurately diagnose the condition, leading to early detection and treatment,” lead investigator Akihiro Tsuda, a lecturer in the Department of clinical medical science at the Graduate School of Medicine at Osaka Metropolitan University in Japan, said in a press release.2

One of the earliest signs of kidney disease is when protein leaks into the urine, indicating the kidneys' filtering system, specifically the glomeruli, may be damaged and not functioning properly. Detecting kidney disease in its early stages is crucial for slowing the progression of kidney damage and improving outcomes.3,4

To facilitate early detection and prompt treatment, health care providers often turn to urine tests and GFR measurements to monitor kidney function. Individuals with diabetes are at a greater risk of developing kidney disease. According to the National Kidney Foundation, about 30% of those with type 1 diabetes and 10-40% of those with type 2 diabetes eventually suffer from kidney failure.5

In diabetic kidney disease, also known as diabetic nephropathy, albuminuria appears first, leading to excessive filtration and eventually a decrease in GFR. However, with older age, excessive filtration cannot be detected due to natural age-related GFR decline. Paired with the lack of a conclusive definition of hyperfiltration, the main pathogenesis of renal impairment in obesity and diabetes, investigators recognized the need for a new formula for determining the threshold value for hyperfiltration based on age and GFR values.1

To come up with such a definition, investigators conducted a study involving 180 kidney donor candidates with a mean age of 56.4 ± 11.3 years old who were predominantly (56%) female. In this cohort, they assessed GFR using inulin clearance and performed a 2-hour 75-g oral glucose tolerance test.1

Participants were then divided into 4 groups based on the presence or absence of glucose tolerance disorder and BMI, with normal glucose tolerance (NGT) and BMI < 25 kg/m2 defined as normal. Investigators defined hyperfiltration as the upper 95% confidence interval of the relationship between aging and GFR in normal cases, and compared this with GFR > 125 mL/min.1

Results showed GFR without body surface area correction and UAE in non-normal glucose tolerance subjects with obesity were greater than in other groups. However, GFR with body surface area correction did not show this relationship.1

In multiple regression analysis, BMI was independently associated with GFR without body surface area correction, but not with body surface area correction. Furthermore, aging was consistently associated with GFR.1

Investigators’ revised definition of hyperfiltration was as follows:

• GFR = −0.883 × Age + 167.398

By this definition, the prevalence of hyperfiltration was significantly increased relative to that measured by GFR > 125 mL/min (P <.0001).1

“Hyperfiltration in obesity and/or glucose tolerance disorder should be evaluated using GFR without BSA correction and including the decline of GFR due to aging,” investigators wrote.1

References

1. Tsuda A, Mori K, Uedono H, et al. Definition of hyperfiltration taking into account age-related decline in renal function in kidney donor candidates with obesity and glucose tolerance disorder. Hypertens Res. https://doi.org/10.1038/s41440-024-02020-y
2. Osaka Metropolitan University. Age matters: Kidney disorder indicator gains precision. EurekAlert! January 5, 2025. Accessed January 10, 2025. https://www.eurekalert.org/news-releases/1069163
3. US Centers for Disease Control and Prevention. Testing for Chronic Kidney Disease. Accessed January 10, 2024. https://www.cdc.gov/kidney-disease/testing/index.html
4. Mayo Clinic. Chronic Kidney Disease. September 6, 2023. Accessed January 10, 2025. https://www.mayoclinic.org/diseases-conditions/chronic-kidney-disease/symptoms-causes/syc-20354521
5. National Kidney Foundation. Diabetes - A Major Risk Factor for Kidney Disease. Accessed January 10, 2025. https://www.kidney.org/kidney-topics/diabetes-major-risk-factor-kidney-disease