Declining Estimated Glomerular Filtration Rate and Its Association with Mortality and Comorbidity Over 10 Years in Elderly Women

Abstract

Background/Aims: Renal function deteriorates with age, but a few studies have addressed this longitudinally in elderly women. Our objective was, using 5 estimated glomerular filtration rates (eGFR)-equations, to evaluate changes in renal function and association with adverse outcomes for a decade in 75-year-old women. Methods: Plasma creatinine was measured at ages 75 (n = 1,011), 78 (n = 827), 80 (n = 689) and 85 (n = 363). Glomerular filtration rates were estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI); Modification of Diet in Renal Disease (MDRD); revised Lund-Malmö (LM-rev); Berlin Initiative Study 1 (BIS1) and Cockcroft-Gault/body surface area (CG/BSA) equations. Mortality and comorbidity were investigated in women with chronic kidney disease (CKD) stage 3A and 3B-5. Results: Approximately, 95% of women had eGFR indicating CKD stage 2-3 and progression towards stage 3 was continuous. The women lost 22% of their eGFR during follow-up and loss accelerated between 80 and 85. Mean loss per decade was 16.6 ml/min/1.73 m². Women in CKD stage 3B-5 had an adjusted hazard ratio for death of 3.5 (95% CI 2.1-5.8) compared to stage 1-2 during follow-up and increased risk of diabetes, heart failure and hypertension. The CG/BSA, BIS1 and LM-rev equations continuously predicted lower eGFR than the MDRD and CKD-EPI equations. Conclusion: eGFR in women aged 75-85 ranges from 30 to 89 ml/min/1.73 m² (stage 2-3). Decline was 16.6 ml/min/1.73 m² per decade; accelerated with age and appeared nonlinear. Women with CKD 3B-5 demonstrate an over 3-fold risk of death. eGFR <45 ml/min/1.73 m² was associated with mortality, confirming the new KDIGO classification 3A and 3B, as clinically applicable in the elderly.

Key to Opening Kidney for In Vitro–In Vivo Extrapolation Entrance in Health and Disease: Part I: In Vitro Systems and Physiological Data

“…With respect to age, glomerular filtration rate (normalised to body surface area) increases rapidly after birth from around 20-30% of the adult value, reaching the adult level soon after 12 months of age (69). After the age of 30 years, glomerular filtration rate declines with ageing, although some uncertainties exist around the actual rate due to normal ageing, which has been reported at a loss of 7.5-16.6 mL/min/1.73 m 2 per decade (74,76). Glomerular filtration rate decreases in patients with renal impairment; in chronic kidney disease stages G1 (high and optimal), G2 (mild), G3a (mild-moderate), G3b (moderatesevere), G4 (severe) and G5 (kidney failure), glomerular filtration rates are >90, 60-90, 45-59, 30-44, 15-29 and <15 mL/min/1.73 m 2 , respectively (73).…”

Lifetime Risk of CKD

“…In a very recent study from Sweden, eGFR was followed in elderly women for 10 years between ages 75 and 85 years. This study also found that stage 3B CKD, but not stage 3A, was associated with mortality in 1011 women considered at baseline; however, large confidence intervals and a potential lack of statistical power do not fully exclude a clinically important higher risk even in stage 3A (22).…”

Reply to Letter to the Editor

“…Other longitudinal studies have not uniformly confirmed this observation. 5 We do not disagree that a "diagnosis" of CKD based on a stable or very slowly declining eGFR of 45-59ml/min/1.73m 2 without albuminuria in an elderly person might have some theoretical benefits, by bringing attention to potential risks of use of watersoluble nephrotoxic drugs, but is it necessary to label such patient with a "chronic disease" in order to accomplish this aim? Why not simply use the information about eGFR, with due recognition of its inaccuracies, to make appropriate clinical decisions without adding the anxiety provoking label of CKD?…”

“…More recently Malmgren et al 5 in longitudinal study of elderly women in Sweden found no increase in HR for ACM in a study of elderly women with an…”