Age-adapted percentiles of measured glomerular filtration in healthy individuals: extrapolation to living kidney donors over 65 years

Delanaye, Pierre; Weijden, Jessica van der; Mjøen, Geir; Ferhman-Ekholm, I.; Dubourg, Laurence; Ebert, Natalie; Schaeffner, Elke; Åkerfeldt, Torbjörn; Goffin, Karolien; Couzi, Lionel; Garrouste, Cyril; Rostaing, Lionel; Courbebaisse, Marie; Legendre, Christophe; Hourmant, Maryvonne; Kamar, Nassim; Weekers, Laurent; Bouquegneau, Antoine; Borst, Martin H. de; Mariat, Christophe; Pottel, Hans; Londen, Marco van

doi:10.1515/cclm-2021-1011

Cited by 8 publications

(4 citation statements)

References 27 publications

(55 reference statements)

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“…Kidney senescence has been well described at the cellular and microscopic levels, with a distinction between the microstructural changes observed in normal physiologic aging versus in diseases (1,2). The effect of kidney senescence on GFR has been relatively well described but mainly from cross-sectional data, which are not ideal from a methodologic point of view (1,3–5). After a period of kidney maturation in the first years of life, GFR remains constant until around 40 years.…”

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confidence: 99%

Physiology of the Aging Kidney

Delanaye

Pottel

Melsom

2022

CJASN

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Senescence could be defined as the gradual deterioration of functional characteristics in living organisms. The word senescence can refer to either cellular senescence or to senescence of the whole organism. Kidney senescence has been well described at the cellular and microscopic levels, with a distinction between the microstructural changes observed in normal physiologic aging versus in diseases (1,2). The effect of kidney senescence on GFR has been relatively well described but mainly from cross-sectional data, which are not ideal from a methodologic point of view (1,(3)(4)(5). After a period of kidney maturation in the first years of life, GFR remains constant until around 40 years. From the fourth decade, GFR is declining in line with the loss of nephrons (1). However, several important questions are still open. Is this decline observed in everyone? Is this physiologic decrease in GFR the same in men and women? Is this decline in GFR linear? Also, the evolution of GFR at the extremes of life is, by nature, difficult to study. Recently, Smeets et al.(6) assembled cross-sectional data from the literature to describe the evolution of GFR during the first 5 days after birth. On the other side of the age curve, data on GFR evolution in the elderly are scarce. Ideally, GFR slopes should be studied with longitudinal data using the measured GFR (exogenous clearance methods), but this is very challenging.In this issue of CJASN, Schaeffner et al. ( 7) studied the course of GFR with age in a longitudinal study of 2069 community-dwelling older persons (mean age of 8067 years old; the Berlin Initiative Study [BIS]) with eGFR and a follow-up time of 6.1 years. Study participants were members of the largest German statutory health insurance living in Berlin. The response rate in the BIS cohort has been reported to be relatively low (8%), but the loss to follow-up and the number of missing data were low in this study. The goal of the authors was double: "describe the crude and adjusted age-related course of eGFR in a population of individuals aged $70" and "define reference values for both sexes" (7). In our opinion, the population studied does not allow the authors to really "define" reference values. Indeed, although large and population based, their population may not be representative of the global German population over 70 years (and the authors never claimed such representativeness). Also, their population is obviously not a healthy one (e.g.,

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confidence: 99%

Physiology of the Aging Kidney

Delanaye

Pottel

Melsom

2022

CJASN

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“…Indeed, the significantly increased risk of physical frailty and mortality in older CKD patients [7,11,14,17,27,46,47,54,55]. However, the current KDIGO guidelines from 2012 do not take age into account when classifying the severity of CKD, although current research shows that from an age of about 45 years, the eGFR physiologically decreases by ~0.88 mL/min/1.73 m 2 /year [56]. This is particularly important because at the moment kidney aging is not relevantly differentiated from kidney disease, just as the severity of CKD in old age may be overestimated.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Signature of Chronic Kidney Disease in Advanced Age: Secondary Analysis from the InGAH Study with One-Year Follow-Up

et al. 2022

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The negative impact of chronic kidney disease (CKD) on health status and quality of life in older patients has been well documented. However, data on frailty trajectories and long-term outcomes of older CKD patients undergoing structured Comprehensive Geriatric Assessment (CGA) with multidimensional frailty evaluation are sparse. Here, we analysed records from 375 CKD patients admitted to our university hospital (mean age 77.5 (SD 6.1) years, 36% female) who had undergone a CGA-based calculation of the frailty score with the multidimensional prognostic index (MPI) as well as follow-up evaluations at 3, 6 and 12 months after discharge. Based on the MPI score at admission, 21% of the patients were frail and 56% were prefrail. MPI values were significantly associated with KDIGO CKD stages (p = 0.003) and rehospitalisation after 6 months (p = 0.027) and mortality at 3, 6 and 12 months (p = 0.001), independent of chronological age. Kidney transplant recipients (KTR) showed a significantly lower frailty compared to patients with renal replacement therapy (RRT, p = 0.028). The association between frailty and mortality after 12 months appeared particularly strong for KTR (mean MPI 0.43 KTR vs. 0.52 RRT, p < 0.001) and for patients with hypoalbuminemia (p < 0.001). Interestingly, RRT was per se not significantly associated with mortality during follow up. However, compared to patients on RRT those with KTR had a significantly lower grade of care (p = 0.031) and lower rehospitalisation rates at 12 months (p = 0.010). The present analysis shows that the large majority of older CKD inpatients are prefrail or frail and that the risk for CKD-related adverse outcomes on the long term can be accurately stratified by CGA-based instruments. Further studies are needed to explore the prognostic and frailty-related signature of laboratory biomarkers in CKD.

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“…It is true that, at the population level, median serum creatinine values only slightly increase with aging [ 31 ]. However, GFR is stable until 40 years of age and only physiologically declines with aging beyond 40 years, and thus, age in the CKD-EPI 2009 equation does not adequately reflect the way GFR evolves with age [ 12 , 32 ]. So, this method of modeling the association between creatinine, GFR and age in the CKD-EPI equation is an over-simplification [ 33–36 ].…”

Section: A Short History Of Creatinine-based Equationsmentioning

confidence: 99%

New and old GFR equations: a European perspective

Delanaye

Cavalier

Pottel

et al. 2023

Clinical Kidney Journal

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Glomerular filtration rate (GFR) is estimated in clinical practice from equations based on the serum concentration of endogenous biomarkers and demographic data. The 2009 creatinine-based CKD-EPI equation (CKD-EPI2009) was worldwide recommended until 2021, when it was recalibrated to remove the African-American race factor. The CKD-EPI2009 and CKD-EPIcr2021 equations overestimates GFR of adults aged 18 to 30 years, with a strong overestimation in eGFR at age 18. CKD-EPICr2021 does not perform better than CKD-EPI2009 in US population, overestimating GFR in non-black subjects, and underestimating it in black subjects with the same magnitude. CKD-EPICr2021 performed worse than the CKD-EPI2009 in White Europeans, and provides no or limited performance gains in Black European and Black African populations. The EKFC equation, which incorporates median normal value of serum creatinine in healthy population overcomes the limitations of the CKD-EPI equations: it provides a continuity of eGFR at the transition between pediatric and adult care, and performs reasonably well in diverse populations, assuming dedicated scaling of serum creatinine (Q) values is used. The new EKFC equation based on cystatin C (EKFCCC) shares the same mathematical construction, namely, it incorporates the median cystatin C value in the general population, which is independent of sex and ethnicity. EKFCCC is therefore a sex free and race free equation, which performs better than the CKD-EPI equation based on cystatin C. Despite advances in the field of GFR estimation, no equation is perfectly accurate, and GFR measurement by exogenous tracer clearance is still required in specific populations and/or specific clinical situations.

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Age-adapted percentiles of measured glomerular filtration in healthy individuals: extrapolation to living kidney donors over 65 years

Cited by 8 publications

References 27 publications

Physiology of the Aging Kidney

Physiology of the Aging Kidney

Prognostic Signature of Chronic Kidney Disease in Advanced Age: Secondary Analysis from the InGAH Study with One-Year Follow-Up

New and old GFR equations: a European perspective

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