Performance of Glomerular Filtration Rate Estimation Formulae in Primary Aldosteronism

Objective: Glomerular hyperfiltration(GH), commonly featured in primary aldosteronism(PA), is an early marker of kidney damage and an independent risk factor for adverse cardio-renal outcomes. The performance of commonly used creatinine-based formulae for the estimation of glomerular filtration rate(eGFR) in conditions of GH, including the recently proposed European Kidney Function Consortium(EKFC) formula, remains uncertain. Design and method: In 34 consecutive patients with post-surgical confirmation of unilateral PA, we measured creatinine clearance(mCrCl), as the reference standard, and estimated GFR by Modification of Diet in Renal Disease(MDRD), CKD Epidemiology Collaboration(CKD-EPI) 2021 and EKFC formulae, at the time of diagnosis and 6 months after curative adrenalectomy. More than 6 weeks prior to testing, all renin-angiotensin-aldosterone system (RAAS)-confounding medications were discontinued. Results: After cure of the aldosteronism mCrCl significantly decreased (94.83±17.5 vs 115.1±32.1 ml/min/1.73m2, p=0.019), suggesting resolution of GH. At baseline, all three formulae underestimated mCrCl (δ mCrCl-eGFR = 20.43 ±6.63 for EKFC (p<0.001), 13.01 ±27.31 for CKD-EPI (p=0.0179), 14.17 ±26.25 (p=0.0081) for MDRD), with such bias being even larger for EKFC (p<0.01 vs both CKD-EPI and MDRD). The underestimation increased with increasing mCrCl for all formulae at diagnosis (at univariate linear regression: β=0.748 for EKFC, 0.769 for CKD-EPI, 0.648 for MDRD, p<0.001 for all), but not 6 months after surgery (p>0.1 for all). Of note, the change in glomerular filtration rate from diagnosis to cure was similar when assessed with mCrCl or with any eGFR formulae (18.53±27.24 ml/min/1.73m2 and 21.54±18.97 for MDRD, 18.62±15.37 for CKD-EPI, 16.70±13.10 for EKFC, respectively; p>0.1 for all vs mCrCl; δeGFR correlation with δmCrCl: r = 0.56, 0.56 and 0.68, respectively; p<0.05 for all). Conclusions: In PA, as a suitable model of reversible GH, commonly used formulae for eGFR underestimate GFR when compared with mCrCl, especially for higher GFRs. This may result in underdetection of GH and prevent early interventions; in this regard, the new EKFC did not prove superior to CKD-EPI or MDRD formulae. However, when GH is identified, they are all suitable to track its resolution. These conclusions may broadly apply to other diseases featuring GH across the spectrum of cardio-kidney-metabolic syndrome.