Keller/eGFR ratio as a simple and useful tool to make a first differentiation between renal aging and chronic nephropathy in large populations

Background Chronic kidney disease (CKD) prevalence increases with age, but distinguishing physiological renal ageing from pathological CKD remains a major diagnostic challenge. Current CKD definitions based solely on estimated glomerular filtration rate (eGFR) often lead to overdiagnosis in elderly...

Full description

Autores:
Cristiano, Fabrizio
Aroca‑Martinez, Gustavo
Guido Musso, 4Carlos
Tipo de recurso:
Fecha de publicación:
2025
Institución:
Universidad Simón Bolívar
Repositorio:
Repositorio Digital USB
Idioma:
eng
OAI Identifier:
oai:bonga.unisimon.edu.co:20.500.12442/17166
Acceso en línea:
https://hdl.handle.net/20.500.12442/17166
https://doi.org/10.1007/s11255-025-04932-1
https://link.springer.com/article/10.1007/s11255-025-04932-1
Palabra clave:
Renal ageing
Chronic kidney disease
eGFR
Keller formula
CKD overdiagnosis
Population screening
Rights
openAccess
License
http://purl.org/coar/access_right/c_abf2
id USIMONBOL2_7f1f77f369c8e189ec4b78c525626543
oai_identifier_str oai:bonga.unisimon.edu.co:20.500.12442/17166
network_acronym_str USIMONBOL2
network_name_str Repositorio Digital USB
repository_id_str
dc.title.eng.fl_str_mv Keller/eGFR ratio as a simple and useful tool to make a first differentiation between renal aging and chronic nephropathy in large populations
title Keller/eGFR ratio as a simple and useful tool to make a first differentiation between renal aging and chronic nephropathy in large populations
spellingShingle Keller/eGFR ratio as a simple and useful tool to make a first differentiation between renal aging and chronic nephropathy in large populations
Renal ageing
Chronic kidney disease
eGFR
Keller formula
CKD overdiagnosis
Population screening
title_short Keller/eGFR ratio as a simple and useful tool to make a first differentiation between renal aging and chronic nephropathy in large populations
title_full Keller/eGFR ratio as a simple and useful tool to make a first differentiation between renal aging and chronic nephropathy in large populations
title_fullStr Keller/eGFR ratio as a simple and useful tool to make a first differentiation between renal aging and chronic nephropathy in large populations
title_full_unstemmed Keller/eGFR ratio as a simple and useful tool to make a first differentiation between renal aging and chronic nephropathy in large populations
title_sort Keller/eGFR ratio as a simple and useful tool to make a first differentiation between renal aging and chronic nephropathy in large populations
dc.creator.fl_str_mv Cristiano, Fabrizio
Aroca‑Martinez, Gustavo
Guido Musso, 4Carlos
dc.contributor.author.none.fl_str_mv Cristiano, Fabrizio
Aroca‑Martinez, Gustavo
Guido Musso, 4Carlos
dc.subject.keywords.eng.fl_str_mv Renal ageing
Chronic kidney disease
eGFR
Keller formula
CKD overdiagnosis
Population screening
topic Renal ageing
Chronic kidney disease
eGFR
Keller formula
CKD overdiagnosis
Population screening
description Background Chronic kidney disease (CKD) prevalence increases with age, but distinguishing physiological renal ageing from pathological CKD remains a major diagnostic challenge. Current CKD definitions based solely on estimated glomerular filtration rate (eGFR) often lead to overdiagnosis in elderly individuals with normal age-related decline. This study explores the use of the Keller/eGFR ratio as a simple and useful tool to differentiate normal renal ageing from true nephropathy in large populations. Methods Keller formula (GFR = 130—age) was applied to model the expected physiological GFR decline across the lifespan. The ratio between Keller-derived GFR and measured eGFR (CKD-EPI) was analyzed to distinguish physiological ageing (Keller/eGFR ≤ 1) from pathological decline (Keller/eGFR > 1). The approach was compared with classical biochemical, urinary, and imaging markers and validated using data from the Abruzzo cohort of older adults. Results Keller/eGFR ratio provided a clear separation between individuals with expected age-related GFR reduction and those with evidence of underlying CKD. In patients with Keller/eGFR ≤ 1, biochemical parameters (creatinine, urea, hemoglobin, calcium–phosphorus metabolism) and urinalysis remained within normal limits, and imaging findings were unremarkable. Conversely, Keller/eGFR > 1 was associated with typical CKD features, including anemia, mineral abnormalities, and structural renal alterations. Integrating this ratio with clinical and laboratory data significantly reduced CKD overdiagnosis in elderly subjects. Conclusions The Keller/eGFR ratio represents a practical, low-cost, and easily applicable index for the first-line screening of kidney function in older adults. When combined with biochemical and imaging markers, it enhances diagnostic accuracy and helps avoid excessive medicalization related to CKD misclassification. Wider implementation in population studies could improve epidemiological stratification and resource allocation in nephrology care.
publishDate 2025
dc.date.accessioned.none.fl_str_mv 2025-12-04T20:03:38Z
dc.date.available.none.fl_str_mv 2025-12-04T20:03:38Z
dc.date.issued.none.fl_str_mv 2025
dc.type.coarversion.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.coar.fl_str_mv http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.driver.none.fl_str_mv info:eu-repo/semantics/article
dc.type.spa.none.fl_str_mv Artículo científico
dc.identifier.citation.none.fl_str_mv Cristiano, F., Aroca-Martinez, G. & Musso, C.G. Keller/eGFR ratio as a simple and useful tool to make a first differentiation between renal aging and chronic nephropathy in large populations. Int
dc.identifier.issn.none.fl_str_mv 1573-2584 (Electrónico)
0301-1623 (Impreso)
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/20.500.12442/17166
dc.identifier.doi.none.fl_str_mv https://doi.org/10.1007/s11255-025-04932-1
dc.identifier.url.none.fl_str_mv https://link.springer.com/article/10.1007/s11255-025-04932-1
identifier_str_mv Cristiano, F., Aroca-Martinez, G. & Musso, C.G. Keller/eGFR ratio as a simple and useful tool to make a first differentiation between renal aging and chronic nephropathy in large populations. Int
1573-2584 (Electrónico)
0301-1623 (Impreso)
url https://hdl.handle.net/20.500.12442/17166
https://doi.org/10.1007/s11255-025-04932-1
https://link.springer.com/article/10.1007/s11255-025-04932-1
dc.language.iso.none.fl_str_mv eng
language eng
dc.rights.coar.fl_str_mv http://purl.org/coar/access_right/c_abf2
dc.rights.accessrights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
rights_invalid_str_mv http://purl.org/coar/access_right/c_abf2
dc.format.mimetype.none.fl_str_mv pdf
dc.publisher.eng.fl_str_mv Springer
dc.source.spa.fl_str_mv Vol. 57  No. 12 Año 2025
dc.source.eng.fl_str_mv International Urology and Nephrology
institution Universidad Simón Bolívar
bitstream.url.fl_str_mv https://bonga.unisimon.edu.co/bitstreams/41cde4cf-dafa-44ac-a780-eb00120a4516/download
https://bonga.unisimon.edu.co/bitstreams/8c300728-e2e2-465a-ac56-99c7c3ff41e3/download
bitstream.checksum.fl_str_mv 4e39b4d10d1b40abaa6b60377c732de1
733bec43a0bf5ade4d97db708e29b185
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
repository.name.fl_str_mv Repositorio Digital Universidad Simón Bolívar
repository.mail.fl_str_mv repositorio.digital@unisimon.edu.co
_version_ 1858228177960173568
spelling Cristiano, Fabrizio333f291b-0e49-4297-846f-6ec918c709fd-1Aroca‑Martinez, Gustavoabf6dbf0-36d7-436c-b1ff-8a1154f50751-1Guido Musso, 4Carlos3db29e5f-8afd-4db6-a18a-139d322516b7-12025-12-04T20:03:38Z2025-12-04T20:03:38Z2025Cristiano, F., Aroca-Martinez, G. & Musso, C.G. Keller/eGFR ratio as a simple and useful tool to make a first differentiation between renal aging and chronic nephropathy in large populations. Int1573-2584 (Electrónico)0301-1623 (Impreso)https://hdl.handle.net/20.500.12442/17166https://doi.org/10.1007/s11255-025-04932-1https://link.springer.com/article/10.1007/s11255-025-04932-1Background Chronic kidney disease (CKD) prevalence increases with age, but distinguishing physiological renal ageing from pathological CKD remains a major diagnostic challenge. Current CKD definitions based solely on estimated glomerular filtration rate (eGFR) often lead to overdiagnosis in elderly individuals with normal age-related decline. This study explores the use of the Keller/eGFR ratio as a simple and useful tool to differentiate normal renal ageing from true nephropathy in large populations. Methods Keller formula (GFR = 130—age) was applied to model the expected physiological GFR decline across the lifespan. The ratio between Keller-derived GFR and measured eGFR (CKD-EPI) was analyzed to distinguish physiological ageing (Keller/eGFR ≤ 1) from pathological decline (Keller/eGFR > 1). The approach was compared with classical biochemical, urinary, and imaging markers and validated using data from the Abruzzo cohort of older adults. Results Keller/eGFR ratio provided a clear separation between individuals with expected age-related GFR reduction and those with evidence of underlying CKD. In patients with Keller/eGFR ≤ 1, biochemical parameters (creatinine, urea, hemoglobin, calcium–phosphorus metabolism) and urinalysis remained within normal limits, and imaging findings were unremarkable. Conversely, Keller/eGFR > 1 was associated with typical CKD features, including anemia, mineral abnormalities, and structural renal alterations. Integrating this ratio with clinical and laboratory data significantly reduced CKD overdiagnosis in elderly subjects. Conclusions The Keller/eGFR ratio represents a practical, low-cost, and easily applicable index for the first-line screening of kidney function in older adults. When combined with biochemical and imaging markers, it enhances diagnostic accuracy and helps avoid excessive medicalization related to CKD misclassification. Wider implementation in population studies could improve epidemiological stratification and resource allocation in nephrology care.pdfengSpringerVol. 57  No. 12 Año 2025International Urology and NephrologyKeller/eGFR ratio as a simple and useful tool to make a first differentiation between renal aging and chronic nephropathy in large populationsinfo:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/articleArtículo científicohttp://purl.org/coar/version/c_970fb48d4fbd8a85http://purl.org/coar/resource_type/c_2df8fbb1Renal ageingChronic kidney diseaseeGFRKeller formulaCKD overdiagnosisPopulation screeningZhou XJ, Rakheja D, Yu X, Saxena R, Vaziri ND, Silva FG (2008) The aging kidney. Kidney Int 74(6):710–720. https:// doi. org/ 10. 1038/ ki. 2008. 319Musso CG, Ricardo AC, Aroca-Martinez G (2024) The fourth wave in chronic kidney disease (CKD) classification: taking into account the aging kidney. Int Urol Nephrol 56(2):805–806. https:// doi. org/ 10. 1007/ s11255- 023- 03642-w. (Epub 2023 May 26 PMID: 37237099)Musso CG, MacíasNuñez JF, Oreopoulos DG (2007) Physiological similarities and differences between renal aging and chronic renal disease. J Nephrol 20(5):586–587Grubb A, Sundin PO, Eriksen BO, Melsom T, Rule AD, Berg U, Littmann K, Åsling-Monemi K, Hansson M, Larsson A, Courbebaisse M, Dubourg L, Couzi L, Gaillard F, Garrouste C, Jacquemont L, Kamar N, Legendre C, Rostaing L, Ebert N, Schaeffner E, Bökenkamp A, Mariat C, Pottel H, Delanaye P (2025) Enhancing individual glomerular filtration rate assessment: can we trust the equation? Development and validation of machine learning models to assess the trustworthiness of estimated GFR compared to measured GFR. BMC Nephrol 26(1):47. https:// doi. org/ 10. 1186/ s12882- 025- 03972-0changes. Adv Chronic Kidney Dis 17(4):302–307. https:// doi. org/ 10. 1053/j. ackd. 2010. 05. 002Denic A, Glassock RJ, Rule AD (2016) Structural and functional changes with the aging kidney. Adv Chronic Kidney Dis 23(1):19–28. https:// doi. org/ 10. 1053/j. ackd. 2015. 08. 004Hommos MS, Glassock RJ, Rule AD (2017) Structural and functional changes in human kidneys with healthy aging. J Am Soc Nephrol 28(10):2838–2844. https:// doi. org/ 10. 1681/ ASN. 20170 40421Corsonello A, Pedone C, Incalzi RA (2010) Age-related pharmacokinetic and pharmacodynamic changes and related risk of adverse drug reactions. Curr Med Chem 17(6):571–584. https:// doi. org/ 10. 2174/ 09298 67107 90416 326. (PMID: 20015034)Pottel H, Hoste L, Dubourg L, Ebert N, Schaeffner E, Eriksen BO, Melsom T, Lamb EJ, Rule AD, Turner ST, Glassock RJ, De Souza V, Selistre L, Mariat C, Martens F, Delanaye P (2016) An estimated glomerular filtration rate equation for the full age spectrum. Nephrol Dial Transplant 31(5):798–806. https:// doi. org/ 10. 1093/ ndt/ gfv454O’Sullivan ED, Hughes J, Ferenbach DA (2017) Renal aging: causes and consequences. J Am Soc Nephrol 28(2):407–420. https:// doi. org/ 10. 1681/ ASN. 20151 21308Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group (2024) KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int 105(4S):S117–S314. https:// doi. org/ 10. 1016/j. kint. 2023. 10. 018Glassock RJ, Rule AD (2012) The implications of anatomical and functional changes of the aging kidney: with an emphasis on the glomeruli. Kidney Int 82(3):270–277. https:// doi. org/ 10. 1038/ ki. 2012. 65Shlipak MG, Matsushita K, Ärnlöv J, Inker LA, Katz R, Polkinghorne KR, Rothenbacher D, Sarnak MJ, Astor BC, Coresh J, Levey AS, Gansevoort RT, CKD Prognosis Consortium (2013) Cystatin C versus creatinine in determining risk based on kidney function. N Engl J Med 369(10):932–943. https:// doi. org/ 10. 1056/ NEJMo a1214 234Cristiano F, Posari C, d'Angelo B, Schiazza A, Gigante A, Caravelli L, Piano A, Fulle S, Cristiano J, di Matteo G, Rosa Diez G, Verratti V (2024). How to Assess the Glomerular Filtration Rate, and Which Method is Deemed Most Reliable? G Ital Nefrol 41(4):2024. https:// doi. org/ 10. 69097/ 41- 04- 2024- 02Shlipak MG, Sarnak MJ, Katz R, Fried LF, Seliger SL, Newman AB, Siscovick DS, Stehman-Breen C (2005) Cystatin C and the risk of death and cardiovascular events among elderly persons. N Engl J Med 352(20):2049–2060. https:// doi. org/ 10. 1056/ NEJMo a0431 61. (PMID: 15901858)Odden MC, Scherzer R, Bacchetti P, Szczech LA, Sidney S, Grunfeld C, Shlipak MG (2007) Cystatin C level as a marker of kidney function in human immunodeficiency virus infection: the FRAM study. Arch Intern Med 167(20):2213–2219. https:// doi. org/ 10. 1001/ archi nte. 167. 20. 2213Knight EL, Verhave JC, Spiegelman D, Hillege HL, de Zeeuw D, Curhan GC, de Jong PE (2004) Factors influencing serum cystatin C levels other than renal function and the impact on renal function measurement. Kidney Int 65(4):1416–1421. https:// doi. org/ 10. 1111/j. 1523- 1755. 2004. 00517.xLindeman RD, Tobin J, Shock NW (1985) Longitudinal studies on the rate of decline in renal function with age. J Am Geriatr Soc 33(4):278–285. https:// doi. org/ 10. 1111/j. 1532- 5415. 1985. tb071 17.x. (PMID: 3989190)Rutkowski M, Mann W, Derose S, Selevan D, Pascual N, Diesto J, Crooks P (2009) Implementing KDOQI CKD definition and staging guidelines in Southern California Kaiser Permanente. Am J Kidney Dis 53(3 Suppl 3):S86-99. https:// doi. org/ 10. 1053/j. ajkd. 2008. 07. 052Eriksen BO, Ingebretsen OC (2006) The progression of chronic kidney disease: a 10-year population-based study of the effects of gender and age. Kidney Int 69(2):375–382. https:// doi. org/ 10. 1038/ sj. ki. 50000 58Michels WM, Grootendorst DC, Verduijn M, Elliott EG, Dekker FW, Krediet RT (2010) Performance of the Cockcroft-Gault, MDRD, and new CKD-EPI formulas in relation to GFR, age, and body size. Clin J Am Soc Nephrol 5(6):1003–1009. https:// doi. org/ 10. 2215/ CJN. 06870 909Cirillo M, Laurenzi M, Mancini M, Zanchetti A, De Santo NG (2006) Low muscular mass and overestimation of microalbuminuria by urinary albumin/creatinine ratio. Hypertension 47(1):56– 61. https:// doi. org/ 10. 1161/ 01. HYP. 00001 97953. 91461. 95Hallan SI, Orth SR (2010) The conundrum of chronic kidney disease classification and end-stage renal risk prediction in the elderly--what is the right approach? Nephron Clin Pract 116(4):c307–c316. https:// doi. org/ 10. 1159/ 00031 9166Denic A, Lieske JC, Chakkera HA, Poggio ED, Alexander MP, Singh P, Kremers WK, Lerman LO, Rule AD (2017) The substantial loss of nephrons in healthy human kidneys with aging. J Am Soc Nephrol 28(1):313–320. https:// doi. org/ 10. 1681/ ASN. 20160 20154Malmgren L, McGuigan FE, Berglundh S, Westman K, Christensson A, Åkesson K (2015) Declining estimated glomerular filtration rate and its association with mortality and comorbidity over 10 years in elderly women. Nephron 130(4):245–255. https:// doi. org/ 10. 1159/ 00043 5790. (Epub 2015 Jul 15 PMID: 26184510)Eriksen BO, Palsson R, Ebert N, Melsom T, van der Giet M, Gudnason V, Indridason OS, Inker LA, Jenssen TG, Levey AS, Solbu MD, Tighiouart H, Schaeffner E (2020) GFR in healthy aging: an individual participant data meta-analysis of iohexol clearance in European population-based cohorts. J Am Soc Nephrol 31(7):1602–1615. https:// doi. org/ 10. 1681/ ASN. 20200 20151Cristiano F, Musso CG (2025) Reclassification of chronic kidney disease in the elderly: integrating age-adjusted GFR and frailty assessment in a regional Italian population (Abruzzo). Int Urol Nephrol. https:// doi. org/ 10. 1007/ s11255- 025- 04698-6Astley ME, Chesnaye NC, Gambaro G, Ortiz A, Hallan S, Carrero JJ, Ebert N, Eriksen BO, Faucon AL, Ferraro PM, Ittermann T, Jonsson AJ, Langlo KAR, Melsom T, Schaeffner E, Stracke S, Palsson R, Jager KJ, Stel VS (2025) Prevalence of reduced eGFR in European adults using KDIGO and age-adapted eGFR thresholds. Nephrol Dial Transplant. https:// doi. org/ 10. 1093/ ndt/ gfaf1 12Schaeffner ES, Ebert N, Delanaye P, Frei U, Gaedeke J, Jakob O, Kuhlmann MK, Schuchardt M, Tölle M, Ziebig R, van der Giet M, Martus P (2012) Two novel equations to estimate kidney function in persons aged 70 years or older. Ann Intern Med 157(7):471–481. https:// doi. org/ 10. 7326/ 0003- 4819- 157-7- 20121 0020- 00003. (PMID: 23027318)Kilbride HS, Stevens PE, Eaglestone G, Knight S, Carter JL, Delaney MP, Farmer CK, Irving J, O’Riordan SE, Dalton RN, Lamb EJ (2013) Accuracy of the MDRD (Modification of Diet in Renal Disease) study and CKD-EPI (CKD Epidemiology Collaboration) equations for estimation of GFR in the elderly. Am J Kidney Dis 61(1):57–66. https:// doi. org/ 10. 1053/j. ajkd. 2012. 06. 016Ebert N, Delanaye P, Shlipak M, Jakob O, Martus P, Bartel J, Gaedeke J, van der Giet M, Schuchardt M, Cavalier E, Schaeffner E (2016) Cystatin C standardization decreases assay variation and improves assessment of glomerular filtration rate. Clin Chim Acta 1(456):115–121. https:// doi. org/ 10. 1016/j. cca. 2016. 03. 002. (Epub 2016 Mar 3 PMID: 26947968)Cristiano F, Rosa-Diez G, Musso CG, Cristiano J (2025) Is Iohexol a Possible Method for Estimating Glomerular Filtration Rate? G Ital Nefrol 42(2):2025. https:// doi. org/ 10. 69097/ 42- 02- 2025- 03Devarajan P (2011) Biomarkers for the early detection of acute kidney injury. Curr Opin Pediatr 23(2):194–200. https:// doi. org/ 10. 1097/ MOP. 0b013 e3283 43f4ddMelk A, Schmidt BM, Takeuchi O, Sawitzki B, Rayner DC, Halloran PF (2004) Expression of p16INK4a and other cell cycle regulator and senescence associated genes in aging human kidney. Kidney Int 65(2):510–520. https:// doi. org/ 10. 1111/j. 1523- 1755. 2004. 00438.xORIGINALPDF.pdfPDF.pdfapplication/pdf900740https://bonga.unisimon.edu.co/bitstreams/41cde4cf-dafa-44ac-a780-eb00120a4516/download4e39b4d10d1b40abaa6b60377c732de1MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-8381https://bonga.unisimon.edu.co/bitstreams/8c300728-e2e2-465a-ac56-99c7c3ff41e3/download733bec43a0bf5ade4d97db708e29b185MD5220.500.12442/17166oai:bonga.unisimon.edu.co:20.500.12442/171662025-12-04 15:09:45.316open.accesshttps://bonga.unisimon.edu.coRepositorio Digital Universidad Simón Bolívarrepositorio.digital@unisimon.edu.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

Publicaciones similares