The Aging Kidney: Physiological Changes

Weinstein, Jessica; Anderson, Sharon

doi:10.1053/j.ackd.2010.05.002

Cited by 523 publications

(434 citation statements)

References 57 publications

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“…Age is associated with reduction in renal function,21 and together with potentially longer duration of diabetes, older patients are likely to be at increased risk of microvascular complications22 including renal impairment and other co‐morbidities 23…”

Section: Discussionmentioning

confidence: 99%

A randomized clinical trial of the efficacy and safety of sitagliptin compared with dapagliflozin in patients with type 2 diabetes mellitus and mild renal insufficiency: The CompoSIT‐R study

Scott

Morgan

Zimmer

et al. 2018

Diabetes Obesity Metabolism

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AimTo compare the efficacy and safety of the dipeptidyl peptidase‐4 inhibitor sitagliptin with the sodium‐glucose transporter‐2 inhibitor dapagliflozin in patients with type 2 diabetes and mild renal insufficiency.Materials and MethodsPatients with HbA1c ≥7.0 to ≤9.5% (≥53 to ≤80 mmol/mol) and estimated glomerular filtration rate ≥60 to <90 mL/min/1.73m2 on metformin (≥1500 mg/d) ± sulfonylurea were randomized to sitagliptin 100 mg (n = 307) or dapagliflozin 5 mg titrated to 10 mg (n = 306) once daily for 24 weeks. A longitudinal data analysis model was used to test the primary hypothesis that sitagliptin is non‐inferior to dapagliflozin in reducing HbA1c at Week 24, with superiority to be tested if non‐inferiority is met. https://ClinicalTrials.gov NCT02532855.ResultsBaseline mean HbA1c (% [mmol/mol]) was 7.7 (60.9) and 7.8 (61.2), and mean eGFR (mL/min/1.73m2) was 79.4 and 76.9 for the sitagliptin and dapagliflozin groups, respectively. After 24 weeks, the between‐group difference in least squares mean (95% CI) changes from baseline in HbA1c was −0.15% (−0.26, −0.04) (−1.67 mmol/mol [−2.86, −0.48]), P = 0.006, meeting the prespecified criteria for declaring both non‐inferiority and superiority of sitagliptin versus dapagliflozin. The HbA1c goal of <7% (<53 mmol/mol) was met by 43% (sitagliptin) and 27% (dapagliflozin) of patients. No meaningful between‐group difference was observed in a pre‐specified analysis of 2‐hour incremental postprandial glucose excursion. A review of adverse events (AEs) was notable for a lower incidence of drug‐related AEs with sitagliptin compared with dapagliflozin.ConclusionsIn patients with type 2 diabetes, mild renal insufficiency and inadequate glycaemic control on metformin ± sulfonylurea, sitagliptin treatment resulted in greater improvement in glycaemic control compared with dapagliflozin and was generally well tolerated.

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Section: Discussionmentioning

confidence: 99%

A randomized clinical trial of the efficacy and safety of sitagliptin compared with dapagliflozin in patients with type 2 diabetes mellitus and mild renal insufficiency: The CompoSIT‐R study

Scott

Morgan

Zimmer

et al. 2018

Diabetes Obesity Metabolism

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“…The occurrence of age-related glucose intolerance due to defective insulin secretion, clearance and peripheral tissue responses to insulin, is also well documented (8). Kidney function is also known to significantly decline with age with an estimated average loss of glomerular filtration rate (GFR) of approximately 1 millilitre per year and an increased predisposition to glomerulosclerosis and interstitial fibrosis (9,10).…”

Section: Introductionmentioning

confidence: 99%

Methionine restriction improves renal insulin signalling in aged kidneys

Grant

Lees

Forney

et al. 2016

Mechanisms of Ageing and Development

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Dietary methionine restriction (MR) leads to loss of adiposity, improved insulin sensitivity and lifespan extension. The possibility that dietary MR can protect the kidney from age-associated deterioration has not been addressed. Aged (10-month old) male and female mice were placed on a MR (0.172% methionine) or control diet (0.86% methionine) for 8-weeks and blood glucose, renal insulin signalling, and gene expression were assessed. Methionine restriction lead to decreased blood glucose levels compared to control-fed mice, and enhanced insulin-stimulated phosphorylation of PKB/Akt and S6 in kidneys, indicative of improved glucose homeostasis. Increased expression of lipogenic genes and downregulation of PEPCK were observed, suggesting that kidneys from MR-fed animals are more insulin sensitive. Interestingly, renal gene expression of the mitochondrial uncoupling protein UCP1 was upregulated in MR-fed animals, as were the anti-ageing and renoprotective genes Sirt1, FGF21, klotho, and β-klotho. This was associated with alterations in renal histology trending towards reduced frequency of proximal tubule intersections containing vacuoles in mice that had been on dietary MR for 190 days compared to control-fed mice, which exhibited a pre-diabetic status. Our results indicate that dietary MR may offer potential in ameliorating the renal functional decline related to ageing and other disorders associated with metabolic dysfunction by enhancing renal insulin sensitivity and renoprotective gene expression.

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“…The kidney weight declines with age, primarily due to loss of renal mass to the cortical, with a relative sparing of the medulla [44,45]. Degeneration of the cortical is based on a progressive sclerosis and hyalinosis of the glomeruli whose total number decreases, leading to a progressive atrophy [32]. In addition senescence of renal tissue is associated with impaired cellular repair mechanism [46].…”

Section: The Marginal Kidneymentioning

confidence: 99%

“…The aging causes a series of morphological and physiological changes to the kidneys leading to an increased glomerular, vascular, and tubular senescence [31,32]. Such morphological changes can result in significant functional changes including a decrease in renal blood flow and glomerular filtration rate, leading to an overall deterioration in renal function [6].…”

Section: The Marginal Kidneymentioning

confidence: 99%

“…Furthermore these changes may be aggravated by atherosclerosis [33], blood hypertension [34,35], smoking [33,34], dyslipidemia [34], obesity [36,37], and diabetes [6,38] which are highly prevalent in older [32,39,40]. Similar changes, with a decrease in renal blood flow by about 10 percent per decade, particularly to the renal cortex have been further documented [32,41]. Moreover animal studies suggest that another functional abnormality in aging is an increase in glomerular basement membrane permeability, leading to an increase in urinary excretion of proteins, including albumin [42].…”

Section: The Marginal Kidneymentioning

confidence: 99%

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Expanded Criteria Donors in Kidney Transplantation: The Role of Older Donors in a Setting of Older Recipients

Rosa

Muscogiuri

Sarno

2013

ISRN Transplantation

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Kidney transplantation (KT) is the therapy of choice for end-stage renal disease (ESRD). The ESRD population is aging and so are patients waiting for KT. New strategies have been made for increasing the donor and recipient pools, and as a consequence kidneys from older donors or donors with significant comorbidities, the so-called "expanded criteria donor" (ECD) kidneys, are used for transplantation. Although good outcomes have been achieved from ECD, several issues are still waiting for clarification and need to be discussed. The concept of age matching is accepted as a method to ameliorate utilization of these allografts, but an optimal and widely accepted strategy is still not defined. The development of machine perfusion and the dual kidney transplantation are techniques which further improve the outcome of transplants from ECD, but the described experiences are scarce or coming from small single institutional reports. Also due to age-related immune dysfunction and associated comorbidities, the elderly recipients are more susceptible to immunosuppression related complications (e.g., infections and malignancy), although a widely accepted and validated immunosuppressive regimen is still lacking. In this paper, we review the issues related to KT employing allografts from marginal donors with a particular interest for the elderly patients.

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The Aging Kidney: Physiological Changes

Cited by 523 publications

References 57 publications

A randomized clinical trial of the efficacy and safety of sitagliptin compared with dapagliflozin in patients with type 2 diabetes mellitus and mild renal insufficiency: The CompoSIT‐R study

A randomized clinical trial of the efficacy and safety of sitagliptin compared with dapagliflozin in patients with type 2 diabetes mellitus and mild renal insufficiency: The CompoSIT‐R study

Methionine restriction improves renal insulin signalling in aged kidneys

Expanded Criteria Donors in Kidney Transplantation: The Role of Older Donors in a Setting of Older Recipients

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