Population-based reference values for kidney function and kidney function decline in 25- to 95-year-old Germans without and with diabetes

Abstract

Understanding normal aging of kidney function is pivotal to help distinguish individuals at particular risk for chronic kidney disease. Glomerular filtration rate (GFR) is typically estimated via serum creatinine (eGFRcrea) or cystatin C (eGFRcys). Since population-based age-group-specific reference values for eGFR and eGFR-decline are scarce, we aimed to provide such reference values from population-based data of a wide age range. In four German population-based cohorts (KORA-3, KORA-4, AugUR, DIACORE), participants underwent medical exams, interview, and blood draw up to five times within up to 25 years. We analyzed eGFRcrea and eGFRcys cross-sectionally and longitudinally (12,000 individuals, age 25-95 years). Cross-sectionally, we found age-group-specific eGFRcrea to decrease approximately linearly across the full age range, for eGFRcys up to the age of 60 years. Within age-groups, there was little difference by sex or diabetes status. Longitudinally, linear mixed models estimated an annual eGFRcrea decline of -0.80 [95% confidence interval -0.82, -0.77], -0.79 [-0.83, -0.76], and -1.20 mL/min/1.73m2 [-1.33, -1.08] for the general population, “healthy” individuals, or individuals with diabetes, respectively. Reference values for eGFR using cross-sectional data were shown as percentile curves for “healthy” individuals and for individuals with diabetes. Reference values for eGFR-decline using longitudinal data were presented as 95% prediction intervals for “healthy” individuals and for individuals with diabetes, obesity, and/or albuminuria. Thus, our results can help clinicians to judge eGFR values in individuals seen in clinical practice according to their age and to understand the expected range of annual eGFR-decline based on their risk profile. Understanding normal aging of kidney function is pivotal to help distinguish individuals at particular risk for chronic kidney disease. Glomerular filtration rate (GFR) is typically estimated via serum creatinine (eGFRcrea) or cystatin C (eGFRcys). Since population-based age-group-specific reference values for eGFR and eGFR-decline are scarce, we aimed to provide such reference values from population-based data of a wide age range. In four German population-based cohorts (KORA-3, KORA-4, AugUR, DIACORE), participants underwent medical exams, interview, and blood draw up to five times within up to 25 years. We analyzed eGFRcrea and eGFRcys cross-sectionally and longitudinally (12,000 individuals, age 25-95 years). Cross-sectionally, we found age-group-specific eGFRcrea to decrease approximately linearly across the full age range, for eGFRcys up to the age of 60 years. Within age-groups, there was little difference by sex or diabetes status. Longitudinally, linear mixed models estimated an annual eGFRcrea decline of -0.80 [95% confidence interval -0.82, -0.77], -0.79 [-0.83, -0.76], and -1.20 mL/min/1.73m2 [-1.33, -1.08] for the general population, “healthy” individuals, or individuals with diabetes, respectively. Reference values for eGFR using cross-sectional data were shown as percentile curves for “healthy” individuals and for individuals with diabetes. Reference values for eGFR-decline using longitudinal data were presented as 95% prediction intervals for “healthy” individuals and for individuals with diabetes, obesity, and/or albuminuria. Thus, our results can help clinicians to judge eGFR values in individuals seen in clinical practice according to their age and to understand the expected range of annual eGFR-decline based on their risk profile. Lay SummaryKidney function, assessed as estimated glomerular filtration rate (eGFR), declines by age. In clinical practice, it is important to understand whether a person has an eGFR value as expected given the person’s age, or whether the value is lower than expected and potentially a reason for concern. Although chronic kidney disease is defined as eGFR <60 ml/min per 1.73 m2, the question arises whether a value of, for example, 58 ml/min per 1.73 m2 for an 80-year-old person is indicative of disease or age appropriate. We collected data from >12,000 individuals, aged 25 to 95 years, from population-based German studies. We provide age-specific reference values for eGFR usable in clinical practice to answer this question. Longitudinal information on eGFR decline was analyzed to also provide reference values for eGFR-decline by risk profile groups. Advanced regression models were applied for these analyses. Our results are interpretable and usable to help in clinical routine. Kidney function, assessed as estimated glomerular filtration rate (eGFR), declines by age. In clinical practice, it is important to understand whether a person has an eGFR value as expected given the person’s age, or whether the value is lower than expected and potentially a reason for concern. Although chronic kidney disease is defined as eGFR <60 ml/min per 1.73 m2, the question arises whether a value of, for example, 58 ml/min per 1.73 m2 for an 80-year-old person is indicative of disease or age appropriate. We collected data from >12,000 individuals, aged 25 to 95 years, from population-based German studies. We provide age-specific reference values for eGFR usable in clinical practice to answer this question. Longitudinal information on eGFR decline was analyzed to also provide reference values for eGFR-decline by risk profile groups. Advanced regression models were applied for these analyses. Our results are interpretable and usable to help in clinical routine. Kidney function undergoes a natural decline by aging. The number of nephrons, the smallest units of the kidney and responsible for the filtration process, starts decreasing at the age of 30 years.1Denic A. Lieske J.C. Chakkera H.A. et al.The substantial loss of nephrons in healthy human kidneys with aging.J Am Soc Nephrol. 2017; 28: 313-320Crossref PubMed Scopus (279) Google Scholar Glomerular filtration rate (GFR) is an established parameter to assess kidney function, typically estimated via serum creatinine (eGFRcrea), cystatin C (eGFRcys), or both (eGFRcrea-cys). Values of eGFR <60 ml/min per 1.73 m2 define chronic kidney disease (CKD).2Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work GroupKDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD).Kidney Int Suppl. 2009; 113: S1-S130PubMed Google Scholar,3Levey A.S. Coresh J. Bolton K. et al.K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification.Am J Kidney Dis. 2002; 39: S1-S266PubMed Google Scholar Approximately 10% of the world’s population4Cockwell P. Fisher L.-A. The global burden of chronic kidney disease.Lancet. 2020; 395: 662-664Abstract Full Full PubMed Scopus Google Scholar and 10% to in The of chronic kidney disease in 2020; Google Scholar are by individuals eGFR <60 ml/min per 1.73 m2 of natural kidney K. et kidney disease: global and Full Full PubMed Scopus Google The of chronic kidney disease to the global burden of Full Full PubMed Scopus Google Scholar a substantial on whether are P. A. et a for an Am Soc Nephrol. PubMed Scopus Google Scholar are typically with the question of whether an eGFR of, for example, 58 ml/min per 1.73 m2 is within the normal range for a healthy 80-year-old question is annual eGFR decline can expected for individuals with a risk profile for individuals with or with diabetes and Reference values for eGFR using cross-sectional data from general and longitudinal data to reference values for eGFR are provide reference values for et and reference values of estimated in the Full Full PubMed Scopus Google in decline in with age and reference data on of and in kidney PubMed Scopus Google A. J. et of estimated glomerular filtration rate and of age loss in a German population-based PubMed Scopus Google Scholar and individuals aged J. et of kidney function and in the 2017; Google et in healthy an data of in population-based Am Soc Nephrol. 2020; PubMed Scopus Google J. et of kidney in the Full Full PubMed Scopus Google et and the of in aged and J Am Soc Nephrol. PubMed Scopus Google Scholar German A. J. et of estimated glomerular filtration rate and of age loss in a German population-based PubMed Scopus Google et and the of in aged and J Am Soc Nephrol. 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