Age-related Decline In Kidney Function Research Articles

Elastin haploinsufficiency accelerates age-related structural and functional changes in the renal microvasculature and impairment of renal hemodynamics in female mice.

Age-related decline in functional elastin is associated with increased arterial stiffness, a known risk factor for developing cardiovascular disease. While the contribution of elastin insufficiency to the stiffening of conduit arteries is well described, little is known about the impact on the structure and function of the resistance vasculature, which contributes to total peripheral resistance and the regulation of organ perfusion. In this study, we determined how elastin insufficiency impinges on age-related changes in the structure and biomechanical properties of the renal microvasculature, altering renal hemodynamics and the response of the renal vascular bed to changes in renal perfusion pressure (RPP) in female mice. Using Doppler ultrasonography, we found that resistive index and pulsatility index were elevated in young Eln +/- and aged mice. Histological examination showed thinner internal and external elastic laminae, accompanied by increased elastin fragmentation in the medial layer without any calcium deposits in the small intrarenal arteries of kidneys from young Eln +/- and aged mice. Pressure myography of interlobar arteries showed that vessels from young Eln +/- and aged mice had a slight decrease in distensibility during pressure loading but a substantial decline in vascular recoil efficiency upon pressure unloading. To examine whether structural changes in the renal microvasculature influenced renal hemodynamics, we clamped neurohumoral input and increased renal perfusion pressure by simultaneously occluding the superior mesenteric and celiac arteries. Increased renal perfusion pressure caused robust changes in blood pressure in all groups; however, changes in renal vascular resistance and renal blood flow (RBF) were blunted in young Eln +/- and aged mice, accompanied by decreased autoregulatory index, indicating greater impairment of renal autoregulation. Finally, increased pulse pressure in aged Eln +/- mice positively correlated with high renal blood flow. Together, our data show that the loss of elastin negatively affects the structural and functional integrity of the renal microvasculature, ultimately worsening age-related decline in kidney function.

Thyroid function and age-related decline in kidney function in older Chinese adults: a cross-sectional study

BackgroundThyroid function may be a factor affecting kidney function in the general population. Kidney and thyroid function vary with age; therefore, the association between thyroid function and decreased kidney function in older adults may be different from that in younger adults and remains controversial. This study aimed to estimate the association between normal-range thyroid function and age-related decline in kidney function in older Chinese adults.MethodsA total of 15,653 adults, of whom 23.2% (N = 3624) were older adults (age≧65 years), were collected at the Health Management Center of the First Affiliated Hospital of Nanjing Medical University from January 2018 to January 2020. Basic demographic information was collected by a physician-administered questionnaire. The estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI formula. Trends in thyroid function with age were shown by means of free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) in subgroups every ten years. The association between kidney function and thyroid function was estimated by multiple linear regression using β value and by multivariable logistic regression models using odds ratios (OR) after adjusting for age, gender, body mass index, and serum urine acid.ResultsIn the older population, TSH tended to increase with age and FT3 tended to decrease, whereas FT4 was relatively stable. eGFR decreased significantly with increasing TSH (β = -0.081) and decreasing FT3 (β = 0.083) concentrations. Compared with those in the lowest quartile of FT3 (3.10–4.47 pmol/L), the prevalence of eGFR < 75 ml/min/1.73m2 decreased significantly by 22.0% for those with FT3 of 4.47–4.81 pmol/L, 27.6% for those with FT3 of 4.82–5.20 pmol/L, and 34.9% for those with FT3 of 5.21–6.8 pmol/L in older individuals (P for trend < .001). The OR was 1.315 (P: 0.025) in subjects with high-normal TSH, using low-normal TSH as a reference. The prevalence of reduced kidney function was not significantly associated with FT4 within the reference range. Similar results were found in association between the prevalence of eGFR < 60 ml/min/1.73m2 and thyroid function.ConclusionsThis study demonstrated a significant association between kidney function and thyroid function, particularly FT3, in the older population. Clinicians may need to pay more attention to the assessment and follow-up of kidney function in older individuals with low-normal FT3 and high-normal TSH.

Brd2 haploinsufficiency extends lifespan and healthspan in C57B6/J mice.

Aging in mammals is the gradual decline of an organism's physical, mental, and physiological capacity. Aging leads to increased risk for disease and eventually to death. Here, we show that Brd2 haploinsufficiency (Brd2+/-) extends lifespan and increases healthspan in C57B6/J mice. In Brd2+/- mice, longevity is increased by 23% (p<0.0001), and, relative to wildtype animals (Brd2+/+), cancer incidence is reduced by 43% (p<0.001). In addition, relative to age-matched wildtype mice, Brd2 heterozygotes show healthier aging including: improved grooming, extended period of fertility, and lack of age-related decline in kidney function and morphology. Our data support a role for haploinsufficiency of Brd2 in promoting healthy aging. We hypothesize that Brd2 affects aging by protecting against the accumulation of molecular and cellular damage. Given the recent advances in the development of BET inhibitors, our research provides impetus to test drugs that target BRD2 as a way to understand and treat/prevent age-related diseases.

Changes in kidney function follow living donor nephrectomy

Better understanding of kidney function after living donor nephrectomy and how it differs by donor characteristics can inform patient selection, counselling, and follow-up care. To evaluate this, we conducted a retrospective matched cohort study of living kidney donors in Alberta, Canada between 2002-2016, using linked healthcare administrative databases. We matched 604 donors to 2,414 healthy non-donors from the general population based on age, sex, year of cohort entry, urban residence and the estimated glomerular filtration rate (eGFR) before cohort entry (nephrectomy date for donors and randomly assigned date for non-donors). The primary outcome was the rate of eGFR change over time (median follow-up seven years; maximum 15 years). The median age of the cohort was 43 years, 64% women, and the baseline (pre-donation) eGFR was 100 mL/min/1.73 m2. Overall, from six weeks onwards, the eGFR increased by+0.35 mL/min/1.73 m2 per year (95% confidence interval+0.21 to+0.48) in donors and significantly decreased by -0.85 mL/min/1.73 m2 per year (-0.94 to -0.75) in the matched healthy non-donors. The change in eGFR between six weeks to two years, two to five years, and over five years among donors was+1.06,+0.64, and -0.06 mL/min/1.73 m2 per year, respectively. In contrast to the steady age-related decline in kidney function in non-donors, post-donation kidney function on average initially increased by 1 mL/min/1.73 m2 per year attributable to glomerular hyperfiltration, which began to plateau by five years post-donation. Thus, the average change in eGFR over time is significantly different between donors and non-donors.

SAT-214 DIETARY PLANT AND ANIMAL PROTEIN INTAKE AND DECLINE IN ESTIMATED GLOMERULAR FILTRATION RATE AMONG ELDERLY WOMEN: A 10-YEAR LONGITUDINAL COHORT STUDY

Current guidelines advise against high protein intake in people with chronic kidney disease (CKD) for fear of accelerating progression, but a differential impact of plant and animal-based proteins on kidney function may exist. We aimed to determine the association between plant and animal protein, and age-related decline in kidney function.

Progressive Decline in Estimated Glomerular Filtration Rate in Patients With Diabetes After Moderate Loss in Kidney Function-Even Without Albuminuria.

Persons with diabetes but no chronic kidney disease (CKD) and without albuminuria have the same age-related decline in kidney function as the background population. Whether this also applies following moderate loss in kidney function is unknown. We quantified the impact of albuminuria status on the development of estimated glomerular filtration rate (eGFR) trajectories following CKD stage 3 (CKD3) and assessed potential heterogeneous development patterns among the subgroup with normoalbuminuria. We used repeated clinical measures during up to 16 years of follow-up in 935 persons with type 1 diabetes and 1,984 with type 2 diabetes. Trajectories of eGFR by diabetes type and albuminuria status following CKD3 were estimated with spline mixed-effects models with adjustment for relevant confounders. Latent class trajectory modeling was used to find distinct patterns of eGFR development in the subgroups with normoalbuminuria. Mean annual declines in eGFR for normo-, micro- and macroalbuminuria the first 10 years following CKD3 were 1.9, 2.3, and 3.3 mL/min/1.73 m2 in type 1 diabetes and 1.9, 2.1, and 3.0 in type 2 diabetes, respectively. For normoalbuminuria, two distinct eGFR patterns were found, one with accelerated declining eGFR levels. This specific progression pattern was associated with less use of lipid-lowering treatment, renin-angiotensin system blockers, and other antihypertensive treatment. Our results support a diabetes-dependent decline in kidney function without albuminuria following CKD3, with a subgroup showing a progressive decline. Furthermore, this group seems to be undertreated in terms of cardioprotective and renal protective treatment and suggests that increased attention should be drawn to normoalbuminuric diabetic kidney disease.

Prevalence of chronic kidney disease in the elderly using the ASPirin in Reducing Events in the Elderly study cohort.

The prevalence of chronic kidney disease (CKD) in the elderly is controversial because age-related decline in kidney function may not truly reflect underlying kidney disease. We estimate the baseline prevalence and predictors of CKD using the CKD Epidemiology Collaboration (CKD-EPIeGFR ) and Berlin Initiative Study 1 (BIS1eGFR ) eGFR equations in the ASPirin in Reducing Events in the Elderly (ASPREE) trial cohort of healthy older participants. GFR was estimated using CKD-EPI and BIS1 equations. CKD was defined as eGFR <60 mL/min/1.73 m2 or ≥ 60 mL/min/1.73 m2 with urine albumin creatinine ratio (UACR) ≥ 3 mg/mmol. Logistic regression was used to identify predictors of CKD prevalence defined by each eGFR equation. Data for analysis were complete for 17,762 participants. Mean age was 75.1 years (SD 5); 56.4% were female, 76.4% had hypertension, 9% had diabetes mellitus. Mean CKD-EPIeGFR was 73.0 (SD 14.2), compared with mean BIS1eGFR of 62.7 (11.4). Median UACR was 0.8 (IQR 0.5, 1.5) mg/mmol. Prevalence of CKD by CKD-EPIeGFR was 27% (predominantly due to normoalbuminuric stage 3a CKD), substantially lower than 47.1% by BIS1eGFR ; the difference was predominantly driven by reclassification of individuals from G1 and G2 CKD to stage G3a without albuminuria. Increased prevalence of CKD by either equation was related to older age, hypertension, diabetes, or higher body mass index. Prevalence of CKD with CKD-EPIeGFR was 27%, and doubled using the elderly specific BIS1eGFR , with most participants reclassified from stage 2 to stage 3a. Increased prevalence of CKD was related older age, hypertension, diabetes, or increased body mass index.

Discovery of Potent, Selective, and Short-Acting Peptidic V2 Receptor Agonists.

The vasopressin analogue desmopressin (desamino-d-arginine8 vasopressin, dDAVP, 1) is a potent vasopressin 2 (V2) receptor (V2R) agonist approved in many countries for the treatment of diabetes insipidus, primary nocturnal enuresis, nocturia, and coagulation disorders. Since 1 is primarily excreted via the kidneys, an age-related decline in kidney function leads to slower elimination, prolonged antidiuresis, and hyponatremia. In search of novel, potent, selective, and short-acting peptidic V2R agonists, we synthesized a series of C-terminally truncated analogues of [Val4]dDAVP, 2, modified in positions 2, 3, and 7 and/or at the disulfide bridge. The peptides were evaluated for in vitro potency at the human V2 receptor, selectivity versus the related receptors (human vasopressin 1a receptor, human vasopressin 1b receptor, and human oxytocin receptor), and pharmacokinetic profiles in rodents and other higher species. The truncated analogues show excellent potency at the V2R, increased systemic clearance, and shorter half-life in rats. Two compounds 19 (c(Bua-Cpa-Thi-Val-Asn-Cys)-Pro-Agm) and 38 (c(Bua-Cpa-Thi-Val-Asn-Cys)-Pro-d-Arg-NEt2) have been selected for clinical development for nocturia.

Association between the age-related decline in renal function and lumbar spine bone mineral density in healthy Chinese postmenopausal women.

The relationship between the decline of renal function and bone mineral density (BMD) in healthy populations is not well-researched. The aim of this study was to investigate the association between the age-related decline in renal function and lumbar spine BMD (LBMD) in a community-based cross-sectional study of 390 healthy postmenopausal women (mean age 62.97 ± 8.79 years) from Shenyang, China. Dual-energy x-ray absorptiometry was used to measure LBMD. Estimated glomerular filtration rate (eGFR) was calculated using a modified Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for Asians and the CKD-EPI serum creatinine-cystatin c equation. Pearson's correlation analysis and binary logistic regression were used to evaluate associations. The eGFR-ASIA and eGFR-Scys were positively correlated with LBMD (r = 0.120 and r = 0.108, respectively). After adjustments for numerous potential confounders, the odds ratio for participants with LBMD decline in eGFR-ASIA quartile 3 group and 4 group were 2.45 (95% confidence interval [CI] 1.12-5.38, P < 0.05) and 3.89 (95% CI 1.55-9.76, P < 0.01), respectively, with P = 0.003 for the trend in eGFR-ASIA compared with the lowest quartile 1 group of eGFR-ASIA, where the odds ratio of eGFR-Scys for the quartile of 3 and 4 groups were 2.47 (95% CI 1.09-5.62, P < 0.05) and 2.63 (95% CI 1.10-6.29, P < 0.05), respectively, with P = 0.016 for the trend in eGFR-Scys compared with the lowest quartile 1 group of eGFR-Scys. The renal function decline was independently associated with decreased LBMD, and it was possible that the age-related decline in kidney function was an independent risk factor for decreased LBMD in healthy Chinese postmenopausal women.

On the rationale of population screening for chronic kidney disease: a public health perspective.

Unlike opportunistic screening, population screening is accompanied by stringent quality control measures and careful programme monitoring. Sufficient evidence for benefit together with acceptable harms and costs to society are needed before launching a programme. A screening programme is a complex process organized at the population level involving multiple actors of the health care system that should ideally be supervised by public health authorities and evaluated by an independent and trustful body. Chronic kidney disease is defined by reduced glomerular filtration rate and/or presence of kidney damage for at least three months. Chronic kidney disease is divided into 5 stages with stages 1 to 3 being usually asymptomatic. Chronic kidney disease affects one in ten adults worldwide and its prevalence sharply increases with age. Kidney function is measured using serum creatinine-based, and/or cystatin C-based, equations. Markers of renal function show high intra-individual and inter-laboratory variabilities, highlighting the need for standardized procedures. There is also large inter-individual variability in age-related kidney function decline. Despite these limitations, chronic kidney disease, as currently defined, has been consistently associated with high cardiovascular morbidity and mortality and high risk of end-stage renal disease. Major modifiable risk factors for chronic kidney disease are diabetes, hypertension, obesity and cardiovascular disease. Several treatment options, ranging from antihypertensive and lipid-lowering treatments to dietary measures, reduce all-cause mortality and/or end-stage renal disease in patients with stages 1–3 chronic kidney disease. So far, no randomized controlled trial comparing outcomes with and without population screening for stages 1–3 chronic kidney disease has been published. Population screening for stages 1–3 chronic kidney disease is currently not recommended because of insufficient evidence for benefit. Given the current and future burden attributable to chronic kidney disease, randomized controlled trials exploring benefits and harms of population screening are clearly needed to prioritize resource allocations.

Is Chronic Kidney Disease in Older People a New Geriatric Giant?

The global population is aging, and the number of people above the age of 85 years is growing faster than any other age group. There is an age-related decline in kidney function; however, not all individuals will develop chronic kidney disease (CKD) with advancing age. Those who are genetically predisposed and exposed to lifetime cardiovascular risk factors are likely to develop systemic atherosclerosis and CKD as a part of its manifestation. CKD promotes poor health through its association with inflammation and oxidative stress. Malnutrition, weight loss and sarcopenia are common in CKD patients, leading to poor outcomes, such as physical and cognitive dysfunction, manifesting as major geriatric syndromes. Frailty is likely to be one of the underlying processes that leads to the clinical manifestations of geriatric syndromes in patients with CKD. Therefore, functional outcomes, such as cognition and physical functioning, might be more relevant outcomes to older patients with CKD. Interventions should be developed and assessed in terms of maintaining quality rather than quantity of life before disability develops.

Cardio-Kidney-Damage: a unifying concept

The perceived global rise in chronic kidney disease (CKD) has been met with apprehension and skepticism. It has been argued by some that we are facing a CKD 'epidemic' and by others that the high prevalence of CKD observed in different communities may be the result of flawed screening methods and tools. Both estimation of glomerular filtration rate and determination of microalbuminuria as markers of CKD have been criticized. Also, many commented that CKD, as currently defined, was primarily a disease of elderly people with reduced kidney function. Some described this as a physiological age-related decline in kidney function while others consider it to be pathological, warranting the label of a disease. In this review, an attempt is made to reconcile different views by examining some of the available evidence and to conclude that the high prevalence of 'CKD' in the elderly population is likely to reflect the underlying high prevalence of overt and subclinical atherosclerosis and cardiovascular disease. This leads to the conclusion that CKD is a reflection of diffuse and age-related Cardio-Kidney-Damage (C-K-D) that may not warrant the label of disease but certainly justifies attention with reduction of lifelong cardiovascular risks and careful evaluation and treatment.

Lack of independent relationship between age-related kidney function decline and carotid intima-media thickness in a healthy Chinese population

Ageing-related decline in kidney function is an independent predictor for cardiovascular events and death. However, the underlying mechanism is not clear. The purpose of this study was to identify the associations between ageing-related decline in kidney function and carotid intima-media thickness (IMT) in a healthy Chinese population with normal kidney function and with no cardiovascular disease. Methods. In cross-sectional study, we examined 852 participants (aged 30-98 years, 392 men) free from cardiovascular disease and with an estimated glomerular filtration rate (eGFR) >60 ml/min/1.73 m(2). Kidney function was estimated by using two markers: eGFR, which was evaluated by the creatinine-based Modification of Diet in Renal Disease (MDRD) Study equation, and cystatin C (CYSC) level. Participants were categorized into quartiles (I-IV) of eGFR and CYSC with quartile I representing the best kidney function (the highest eGFR quartiles and lowest CYSC). Carotid IMT was analysed using M-mode ultrasonography, and elevated carotid IMT was defined as measures above the 75th percentile of the sample distribution (0.9 mm). CYSC was significantly correlated with age in both males (r = 0.441, P < 0.001) and females (r = 0.634, P < 0.001). However, eGFR was only significantly related with age in females (r = -0.173, P < 0.001). CYSC was significantly associated with elevated carotid IMT in an unadjusted model in quartiles III and IV; the odds ratios (95% CI) were 3.64 (2.116-6.261) and 6.407 (3.786-10.84), respectively. However, this association was significantly attenuated by age adjustment and was lost after full adjustment of age and all other confounding variables including sex, body mass index, systolic blood pressure, diastolic blood pressure, triglyceride, total cholesterol, high-density lipoprotein, low-density lipoprotein, albumin, fasting blood glucose, log C-reactive protein, log interleukin-6 and fibrinogen. No significant association was found between quartiles of eGFR and higher IMT. Ageing is a major factor contributing to decline in kidney function in a healthy population. There is no independent relationship between ageing-related decline in kidney function and atherosclerosis in a population with normal kidney function.

Prediction, Progression, and Outcomes of Chronic Kidney Disease in Older Adults

Chronic kidney disease is a large and growing problem among aging populations. Although progression of chronic kidney disease to end-stage renal disease (ESRD) is a costly and important clinical event with substantial morbidity, it appears less frequently in aging people compared with cardiovascular mortality. The measurement of kidney function and management of kidney disease in older individuals remain challenging, partly because the pathophysiologic mechanisms underlying age-related decline in kidney function, the interactions between age and other risk factors in renal progression, and the associations of chronic kidney disease with other comorbidities in older people are understudied and poorly understood. The Association of Specialty Professors, the American Society of Nephrology, the American Geriatrics Society, the National Institute on Aging, and the National Institute of Diabetes and Digestive and Kidney Diseases held a workshop, summarized in this article, to review what is known about chronic kidney disease, identify research gaps and resources available to address them, and identify priority areas for future research. Answers to emerging research questions will support the integration of geriatrics and nephrology and thus improve care for older patients at risk for chronic kidney disease.

Renal Function, Erythropoietin, and Anemia of Older Persons

In the older population, anemia has been associated with poor outcomes including disability and mortality. Understanding the mechanisms leading to anemia is essential to plan better treatment and prevention strategies. We tested the hypothesis that the age-related decline in kidney function is associated with an increased prevalence of anemia and that such an increase is accompanied by a concomitant decrement in erythropoietin levels. Data were from the InCHIANTI study, a population-based study performed in a sample of community-dwelling older (> or = 65 years) persons living in Italy. This analysis included 1005 participants with complete data on hemoglobin and erythropoietin levels and markers of renal function. The prevalence of anemia according to the World Health Organization criteria (hemoglobin level < 12 g/dL for women and < 13 g/dL for men) was 12.0% and increased with age in both sexes. After adjusting for age, diseases, and other confounders, only participants with a creatinine clearance (CrCl) of 30 mL/min or lower (< or = 0.50 mL/s) had a higher prevalence of anemia compared with those with a CrCl higher than 90 mL/min (> 1.50 mL/s) (P<.01). Consistently, participants with a CrCl of 30 mL/min or lower (< or = 0.50 mL/s) had significantly lower age- and hemoglobin-adjusted erythropoietin endogenous levels. After excluding men and women with CrCl of 30 mL/min or lower (< or = 0.50 mL/s) and adjusting for confounders, we found a trend toward an increase in prevalence of anemia with decreasing renal function; however, it was not statistically significant. Severe age-related decline in renal function is associated with a reduced erythropoietin secretion and anemia. Whether moderate kidney impairment in older persons is associated with a progressively increasing risk of anemia remains to be determined.