albuminuria*GFR*proteinuria*CKD non-dialysis; Epidemiology; Critical Care and Intensive Care Medicine; Nephrology; Transplantation
Abstract :
[en] [en] KEY POINTS: GFR estimations are biased in patients with frank nephrotic syndrome, but the problem is uncharacterized in patients with non-nephrotic proteinuria. We investigated the bias and accuracy of eGFR formulas in patients with mild-to-moderate proteinuria participating in the ramipril in nondiabetic renal failure 1 and 2 trials. The CKD Epidemiology Collaboration 2009 and 2021 and European Kidney Function Consortium equations show no significant bias and sufficient accuracy in moderate-to-severe proteinuria.
BACKGROUND: Creatinine-based GFR formulas introduce a substantial bias in GFR estimations in patients with frank nephrotic syndrome. The bias and accuracy of creatinine-based GFR estimates (eGFR) in patients with non-nephrotic proteinuria need better characterization.
METHODS: We used data from the Ramipril in Nondiabetic Renal Failure (ramipril in nondiabetic renal failure [REIN] 1) and REIN 2 trials involving nondiabetic CKD patients with proteinuria to compare eGFRs derived from the CKD Epidemiology Collaboration formulas (with and without race) and the European Kidney Function Consortium equations with iohexol clearance (a gold-standard GFR measure, measured GFR [mGFR]). Bias was defined as the median difference between eGFR and mGFR while accuracy was assessed using P30 and P15 metrics, which represent the percentage of eGFR values within ±30% and ±15% of mGFR, respectively.
RESULTS: The median bias of the three formulas being compared did not differ, being minimal and in a strict range (0.04–0.05 ml/ml per min per 1.73 m2) in the REIN 1 trial and (−0.04 to 0.03 ml/min per 1.73 m2) in the REIN 2 trial. These findings were confirmed in analyses stratified by age and mGFR. The global accuracy of the three formulas regarding P30 % showed sufficient accuracy (P30 >75%) in the REIN 1 trial and all strata in the REIN 2 trial, but the mGFR stratum was <15 ml/min per 1.73 m2.
CONCLUSIONS: The CKD Epidemiology Collaboration (with and without race) and European Kidney Function Consortium equations show no significant bias and sufficient accuracy in patients with proteinuria. These formulas can be safely applied to nondiabetic CKD patients with moderate-to-severe proteinuria.
CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER:: This is a post hoc analysis of two trials, REIN 1 and 2, published about 20 years ago.
Disciplines :
Urology & nephrology
Author, co-author :
Zoccali, Carmine ; Renal Research Institute, New York, New York ; Institute of Molecular Biology and Genetics (Biogem), Ariano Irpino, Italy ; Associazione Ipertensione Nefrologia Trapianto Renale (IPNET), c/o Nefrologia, Grande Ospedale Metropolitano, Reggio Calabria, Italy
Provenzano, Pasquale Fabio; Research Unit of Clinical Epidemiology, CNR-IFC, Institute of Clinical Physiology, Pisa, Italy
Tripepi, Giovanni; Research Unit of Clinical Epidemiology, CNR-IFC, Institute of Clinical Physiology, Pisa, Italy
Carrara, Fabiola ; Instituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy
Mallamaci, Francesca; Research Unit of Clinical Epidemiology, CNR-IFC, Institute of Clinical Physiology, Pisa, Italy ; Unità Operativa di Nefrologia, Dialisi e Trapianto, Grande Ospedale Metropolitano, Reggio Calabria, Italy
Perna, Annalisa ; Instituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy
Delanaye, Pierre ; Université de Liège - ULiège > Département des sciences cliniques ; Department of Nephrology-Dialysis-Apheresis, Hôpital Universitaire Carémeau, Nîmes, France
Ruggenenti, Piero; Instituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy ; Unit of Nephrology and Dialysis, Azienda Socio-Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy
Remuzzi, Giuseppe ; Instituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy
Language :
English
Title :
Reliability of GFR Estimated by Creatinine-Based Formulas in Moderate-to-Severe Proteinuria.
Publication date :
2025
Journal title :
Clinical Journal of the American Society of Nephrology
C. Zoccali: Consiglio Nazionale delle Ricerche (345678910 2024). Because Francesca Mallamaci is an editor of the CJASN, she was not involved in the peer-review process for this manuscript. Another editor oversaw the peer-review and decision-making process for this manuscript.
Rovin BH, Ayoub IM, Chan TM, et al. Executive summary of the KDIGO 2024 clinical practice guideline for the management of lupus nephritis. Kidney Int. 2024;105(1):31–34. doi:10.1016/j. kint.2023.09.001
Inker LA, Eneanya ND, Coresh J, et al. New creatinine- and cystatin C–based equations to estimate GFR without race. N Engl J Med. 2021;385(19):1737–1749. doi:10.1056/ NEJMoa2102953
Fu EL, Coresh J, Grams ME, et al. Removing race from the CKD-EPI equation and its impact on prognosis in a predominantly White European population. Nephrol Dial Transplant. 2023; 38(1):119–128. doi:10.1093/ndt/gfac197
Pottel H, Björk J, Courbebaisse M, et al. Development and validation of a modified full age spectrum creatinine-based equation to estimate glomerular filtration rate: a cross-sectional analysis of pooled data. Ann Intern Med. 2021;174(2):183–191. doi:10.7326/M20-4366
Carrie BJ, Golbetz HV, Michaels AS, Myers BD. Creatinine: an inadequate filtration marker in glomerular diseases. Am J Med. 1980;69(2):177–182. doi:10.1016/0002-9343(80)90376-9
Löwenborg EKM, Berg UB. Influence of serum albumin on renal function in nephrotic syndrome. Pediatr Nephrol. 1999;13(1): 19–25. doi:10.1007/s004670050556
Branten AJW, Vervoort G, Wetzels JFM. Serum creatinine is a poor marker of GFR in nephrotic syndrome. Nephrol Dial Transplant. 2005;20(4):707–711. doi:10.1093/ndt/gfh719
Hofstra JM, Willems JL, Wetzels JFM. Estimated glomerular filtration rate in the nephrotic syndrome. Nephrol Dial Transplant. 2011;26(2):550–556. doi:10.1093/ndt/gfq443
Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9): 604–612. doi:10.7326/0003-4819-150-9-200905050-00006
Remuzzi G, Ruggenenti P, Perna A, et al. Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. Lancet. 1997;349(9069):1857–1863. PMID: 9217756
Ruggenenti P, Perna A, Gherardi G, et al. Renoprotective properties of ACE-inhibition in non-diabetic nephropathies with non-nephrotic proteinuria. Lancet. 1999;354(9176):359–364. doi:10.1016/S0140-6736(98)10363-X
Ruggenenti P, Perna A, Loriga G, et al. Blood-pressure control for renoprotection in patients with non-diabetic chronic renal disease (REIN-2): multicentre, randomised controlled trial. Lancet. 2005;365(9463):939–946. doi:10.1016/S0140-6736(05) 71082-5
Gaspari F, Perico N, Ruggenenti P, et al. Plasma clearance of nonradioactive iohexol as a measure of glomerular filtration rate. J Am Soc Nephrol. 1995;6(2):257–263. doi:10.1681/ASN. V62257
Bröchner-Mortensen J. A simple method for the determination of glomerular filtration rate. Scand J Clin Lab Invest. 1972;30(3): 271–274. doi:10.3109/00365517209084290
Coresh J, Bolton K, et al.; National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002; 39(2 suppl 1):1–266. PMID:11904577
Earley A, Miskulin D, Lamb EJ, Levey AS, Uhlig K. Estimating equations for glomerular filtration rate in the era of creatinine standardization: a systematic review. Ann Intern Med. 2012;156(11): 785–795. doi:10.7326/0003-4819-156-11-201203200-00391
De Jager DJ, De Mutsert R, Jager KJ, Zoccali C, Dekker FW. Reporting of interaction. Nephron Clin Pract. 2011;119(2): c158–c161. doi:10.1159/000327598
De Mutsert R, Jager KJ, Zoccali C, Dekker FW. The effect of joint exposures: examining the presence of interaction. Kidney Int. 2009;75(7):677–681. doi:10.1038/ki.2008.645
Pottel H, Björk J, Rule AD, et al. Cystatin C–based equation to estimate GFR without the inclusion of race and sex. New Engl J Med. 2023;388(4):333–343. doi:10.1056/NEJMoa2203769
Chen DC, Shlipak MG, Scherzer R, et al. Association of intraindividual differences in estimated GFR by creatinine versus cystatin C with incident heart failure. Am J Kidney Dis. 2022; 80(6):762–772.e1. doi:10.1053/j.ajkd.2022.05.011
Seegmiller JC, Burns BE, Schinstock CA, Lieske JC, Larson TS. Discordance between iothalamate and iohexol urinary clearances. Am J Kidney Dis. 2016;67(1):49–55. doi:10.1053/j.ajkd. 2015.08.020
Gaspari F, Perico N, Matalone M, et al. Precision of plasma clearance of iohexol for estimation of GFR in patients with renal disease. J Am Soc Nephrol. 1998;9(2):310–313. doi:10.1681/ ASN.V92310
Levey AS, Becker C, Inker LA. Glomerular filtration rate and albuminuria for detection and staging of acute and chronic kidney disease in adults: a systematic review. JAMA. 2015; 313(8):837–846. doi:10.1001/jama.2015.0602
