Glomerular Hyperfiltration Predicts Kidney Function Decline and Mortality in Type 1 and Type 2 Diabetes: A 21-Year Longitudinal Study

Abstract

OBJECTIVE To evaluate the prognostic value of glomerular hyperfiltration on long-term kidney-related outcomes and mortality in patients with diabetes. RESEARCH DESIGN AND METHODS We retrospectively analyzed 21-year longitudinal data from 314 patients with long-standing type 1 or type 2 diabetes. Glomerular hyperfiltration was identified based on the age- and sex-specific distribution of measured glomerular filtration rate (mGFR) by 99mTc-DTPA dynamic renal scintigraphy. The primary outcome was a composite of doubling of serum creatinine, end-stage kidney disease (ESKD), or cardiorenal death. The kidney-specific outcome was a composite of doubling of serum creatinine, ESKD, or renal death. RESULTS Over a median of 21.0 years, the primary composite outcome occurred in 25 (39.7%), 24 (38.1%), and 46 (24.5%) participants with high mGFR (H-mGFR) (n = 63), low mGFR (L-mGFR) (n = 63), or normal mGFR (N-mGFR) (n = 188), respectively. Compared with N-mGFR, the hazard ratio (HR) for the primary composite outcome was 2.09 (95% CI 1.25–3.49) in H-mGFR and 1.81 (1.05–3.16) in L-mGFR. The HR for the kidney-specific composite outcome was 4.95 (2.21–11.09) in H-mGFR and 3.81 (1.70–8.56) in L-mGFR. The HRs for doubling of serum creatinine and cardiorenal death were 4.86 (2.18–10.90) and 2.18 (1.24–3.83) in H-mGFR and 4.04 (1.77–9.20) and 2.26 (1.27–4.01) in L-mGFR, respectively. CONCLUSIONS Glomerular hyperfiltration, similar to hypofiltration, increases the combined risk of worsening kidney function and mortality from cardiovascular or renal causes in patients with diabetes. These findings encourage the active screening of these patients to optimize risk stratification and treatment of subclinical kidney disease.

Prevalence and risk factors of glomerular hyperfiltration in adults with type 2 diabetes: A population‐based study

“…However, the reported prevalence of glomerular hyperfiltration in that study fell to 0.3% when a more stringent eGFR cut point was used (130 mL/min/1.73 m 2 ), and remained below 5% using age‐ or age‐ and sex‐adjusted eGFR thresholds. Although there is a general agreement that an eGFR above 120 mL/min/1.73 m 2 identifies an inappropriately high GFR across all ages, 13,14 this threshold may be excessively conservative in the elderly, 5 considering a physiological ∼1 mL/min/1.73 m 2 GFR decline per year after 40–50 years of age. A lower prevalence of glomerular hyperfiltration than older studies can also be explained by improved management of metabolic risk factors and widespread implementation of renin‐angiotensin‐aldosterone system (RAAS) inhibitors 15–17 and SGLT‐2 inhibitors 18–20 .…”

“…Some limitations of this study should be acknowledged, mostly inherent to its retrospective design and ecological nature. First, the available data allowed the definition of glomerular hyperfiltration only based on a fixed eGFR threshold, which may be too stringent considering important age‐ and sex‐related differences in GFR, as well as the known limitations of eGFR in detecting high directly‐measured GFR values 5 . Second, aggregated center data did not allow for patient‐level analyses, which would be informative in risk factor assessment.…”

“…First, the available data allowed the definition of glomerular hyperfiltration only based on a fixed eGFR threshold, which may be too stringent considering important age-and sex-related differences in GFR, as well as the known limitations of eGFR in detecting high directlymeasured GFR values. 5 Second, aggregated center data did not allow for patient-level analyses, which would be informative in risk factor assessment. Third, data were automatically extracted from electronic clinical records, which are prone to errors and reporting bias.…”

“…1 The preclinical stage of diabetic nephropathy is characterised by an abnormal elevation in glomerular filtration rate (GFR), defined as glomerular hyperfiltration, which can contribute to kidney damage progression and albuminuria by increasing capillary pressure and tensile stress. 2 Glomerular hyperfiltration has been associated with worse kidney [3][4][5] and cardiovascular outcomes 6,7 and increased cardiovascular and allcause mortality, 5,8,9 which are only partly explained by its close association with poor glycaemic control, obesity, hypertension, and dyslipidemia. 2 The prevalence of glomerular hyperfiltration and its associated risk factors in the general population of individuals with T2D remains unknown.…”

Glomerular Hyperfiltration: A Marker of Fibrosis Severity in Metabolic Associated Steatotic Liver Disease in an Adult Population

“…Glomerular hyperfiltration was defined as eGFR ≥ the upper quartile of our population, as reported in previous studies [33].…”