When kidneys get old: an essay on nephro-geriatrics / Quando os rins envelhecem: um ensaio em nefro-geriatria

Abstract Aging is a nearly universal phenomenon in biology only partially controlled by genetic endowment. Individuals and their organs age at varying rates. The kidneys manifest the aging process by steady loss of nephrons and a corresponding decrease in glomerular filtration rate (GFR) beginning about age 30 years. The mechanisms responsible for this observation is are elusive. However, defining chronic kidney disease based on arbitrary, fixed thresholds of GFR in the later phases of life can be problematical as it may over-diagnosis CKD in the elderly. A modest, persisting reduction of GFR (around 45-59 ml/min/1.73m2) without abnormal proteinuria does not seem to confer much of an adverse effect on mortality and remaining life expectancy in older adults and the development of end-stage renal disease in such subjects is very uncommon. Old kidneys should not be equated with "diseased" kidneys.

Resumo O envelhecimento é um fenômeno quase universal na biologia, apenas parcialmente controlado pela dotação genética. Os indivíduos e seus órgãos envelhecem em taxas variáveis. Os rins manifestam o processo de envelhecimento por perda constante de néfrons e uma diminuição correspondente na taxa de filtração glomerular (TFG) a partir dos 30 anos. Os mecanismos responsáveis por essa observação são elusivos. No entanto, a definição de doença renal crônica com base em limiares arbitrários e fixos de TFG nas últimas fases da vida pode ser problemática, pois pode levar a um excessivo diagnóstico de DRC em idosos. Uma modesta e persistente redução da TFG (cerca de 45-59 ml/min/1,73 m2) sem proteinúria anormal não parece conferir grande parte do efeito adverso sobre a mortalidade e expectativa de vida remanescente em adultos mais velhos; e o desenvolvimento de doença renal em fase terminal em tais indivíduos é muito incomum. Rins mais velhos não devem ser equiparados a rins "doentes".

El desempeño de las ecuaciones de estimación del índice de filtrado glomerular basado en cistatina-C y creatinina depende de las características del paciente / Performance of Cystatin C- and Creatinine-Based Estimated Glomerular / Filtration Rate Equations Depends on Patient Characteristics

Antecedentes: La guía Kidney Disease Improving Global Outcomes (KDIGO) recomienda el uso de un filtrado glomerular estimado (IFGe) basado en cistatina-C para confirmar un IFGe basado en creatinina entre 45 y 59 mL ∙ min-1 ∙ (1,73 m2)-1. Estudios anteriores han demostrado que comorbilidades tales como trasplantes de órganos sólidos influyen fuertemente en la relación entre el índice de filtrado glomerular (IFG) medido, creatinina y cistatina-C. Nuestro objetivo fue evaluar el desempeño de ecuaciones de IFGe basadas en cistatina-C en comparación con IFG medido e IFGe basada en creatinina en diferentes situaciones clínicas. Métodos: Comparamos el rendimiento de la ecuación CKD-EPI 2009, ecuación de IFGe basada en creatinina (IFGeCr), y las nuevas ecuaciones CKD-EPI 2012 basadas en cistatina-C (IFGeCys y IFGeCr-Cys), con el IFG medido (depuración renal de iotalamato) en poblaciones de pacientes totalmente definidas. Los pacientes (n=1.652) fueron clasificados como receptores de trasplantes (de riñón, n=568 u otro órgano, n=319), pacientes con enfermedad renal crónica (ERC) conocida (n=618), o potenciales donantes de riñón (n=147). Resultados: IFGeCr-Cys mostró el desempeño más consistente a través de diferentes poblaciones clínicas. Entre los potenciales donantes de riñón sin ERC [estadio 2 o superior; IFGe> 60 mL ∙ min-1 ∙ (1,73 m2)-1], IFGeCys y IFGeCr‑Cys demostraron significativamente menor sesgo que IFGeCr; sin embargo, las 3 ecuaciones subestimaron substancialmente IFG cuando IFGe fue <60 mL ∙ min-1 ∙ (1,73 m2)-1. Entre los receptores de trasplante con ERC estadio 3B o mayor [IFGe <45 mL ∙ min-1 ∙ (1,73 m2)-1], IFGeCys mostró un sesgo significativamente mayor que IFGeCr. No se observaron diferencias claras en el sesgo de IFGe entre las ecuaciones dentro del grupo de pacientes con ERC conocida independientemente del rango de IFGe o en cualquier grupo de pacientes con una IFG entre 45 y 59 mL ∙ min-1 ∙ (1,73 m2)-1. Conclusiones: El desempeño de las ecuaciones de IFGe depende de las características del paciente las cuales son evidentes en su presentación. Entre las 3 ecuaciones CKD-EPI, IFGeCr-Cys tuvo un desempeño más coherente en las poblaciones de pacientes estudiados.

Background: The Kidney Disease Improving Global Outcomes (KDIGO) guideline recommends use of a cystatin C-based estimated glomerular filtration rate (eGFR) to confirm creatinine-based eGFR between 45 and 59 mL ∙ min-1 ∙ (1.73 m2)-1. Prior studies have demonstrated that comorbidities such as solid-organ transplant strongly influence the relationship between measured GFR, creatinine, and cystatin C. Our objective was to evaluate the performance of cystatin C-based eGFR equations compared with creatinine-based eGFR and measured GFR across different clinical presentations. Methods: We compared the performance of the CKD-EPI 2009 creatinine-based estimated GFR equation (eGFRCr) and the newer CKD-EPI 2012 cystatin C-based equations (eGFRCys and eGFRCr-Cys) with measured GFR (iothalamate renal clearance) across defined patient populations. Patients (n = 1652) were categorized as transplant recipients (n = 568 kidney; n = 319 other organ), known chronic kidney disease (CKD) patients (n = 618), or potential kidney donors (n = 147). Results: eGFRCr-Cys showed the most consistent performance across different clinical populations. Among potential kidney donors without CKD [stage 2 or higher; eGFR >60 mL ∙ min-1 ∙ (1.73 m2)-1], eGFRCys and eGFRCr-Cys demonstrated significantly less bias than eGFRCr; however, all 3 equations substantially underestimated GFR when eGFR was <60 mL ∙ min-1 ∙ (1.73 m2)-1. Among transplant recipients with CKD stage 3B or greater [eGFR <45 mL ∙ min-1 ∙ (1.73 m2)-1], eGFRCys was significantly more biased than eGFRCr. No clear differences in eGFR bias between equations were observed among known CKD patients regardless of eGFR range or in any patient group with a GFR between 45 and 59 mL ∙ min-1 ∙ (1.73 m2)-1. Conclusions: The performance of eGFR equations depends on patient characteristics that are readily apparent on presentation. Among the 3 CKD-EPI equations, eGFRCr-Cys performed most consistently across the studied patient populations.