GFR Decline and Mortality Risk among Patients with Chronic Kidney Disease

Perkins, Robert M.; Bucaloiu, Ion D.; Kirchner, H. Lester; Ashouian, Nasrin; Hartle, James E.; Yahya, Taher

doi:10.2215/cjn.00470111

Cited by 105 publications

(138 citation statements)

References 18 publications

Supporting

Mentioning

118

Contrasting

Unclassified

Order By: Relevance

“…Alternatively, an antecedent decline in true GFR may simply reflect a more severe comorbidity profile. 12,14 For example, although we adjusted for diabetes and our findings were qualitatively similar after excluding subjects with diabetes, we did not adjust for severity of diabetes, a key determinant of both true GFR decline and mortality risk. 21,22 Similarly, episodes of acute coronary syndrome or congestive heart failure may increase the risk of death and also, cause true GFR decline.…”

Section: Discussionmentioning

confidence: 81%

“…Similar to previous work, in which adjustments were made for either the first or last eGFR in the antecedent period, we found a U-shaped relationship between eGFR slope and subsequent ACM risk. 11,[13][14][15][16] Direct, quantitative comparison between the results of these investigations and our own investigations are hampered by different indices of renal function change, different antecedent periods, and the use of rates, in some studies, rather than HRs to quantify mortality risk. However, Turin et al 12 found adjusted HRs for ACM of 1.14 and 1.68 for 4-ml/min per 1.73 m 2 per year declining and increasing slopes, respectively, compared with subjects with a stable eGFR value in a Canadian population-based study.…”

Section: Discussionmentioning

confidence: 99%

“…11,12 A surprising finding in previous studies was that an increase in eGFR was associated with an increased risk of mortality. Whether these observations are generalizable is uncertain, because they were on the basis of data from single centers 13,14 and/or cohorts with mean baseline eGFR values of $50 ml/min per 1.73 m 2 . [11][12][13][14][15][16] Improvement in eGFR in a CKD population might show different associations with mortality than that in a general population cohort.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Past Decline Versus Current eGFR and Subsequent Mortality Risk

Naimark

Grams

Matsushita

et al. 2015

JASN

View full text Add to dashboard Cite

A single determination of eGFR associates with subsequent mortality risk. Prior decline in eGFR indicates loss of kidney function, but the relationship to mortality risk is uncertain. We conducted an individual-level meta-analysis of the risk of mortality associated with antecedent eGFR slope, adjusting for established risk factors, including last eGFR, among 1.2 million subjects from 12 CKD and 22 other cohorts within the CKD Prognosis Consortium. Over a 3-year antecedent period, 12% of participants in the CKD cohorts and 11% in the other cohorts had an eGFR slope ,25 ml/min per 1.73 m 2 per year, whereas 7% and 4% had a slope .5 ml/min per 1.73 m 2 per year, respectively. Compared with a slope of 0 ml/min per 1.73 m 2 per year, a slope of 26 ml/min per 1.73 m 2 per year associated with adjusted hazard ratios for all-cause mortality of 1.25 (95% confidence interval [95% CI], 1.09 to 1.44) among CKD cohorts and 1.15 (95% CI, 1.01 to 1.31) among other cohorts during a follow-up of 3.2 years. A slope of +6 ml/min per 1.73 m 2 per year also associated with higher all-cause mortality risk, with adjusted hazard ratios of 1.58 (95% CI, 1.29 to 1.95) among CKD cohorts and 1.43 (95% CI, 1.11 to 1.84) among other cohorts. Results were similar for cardiovascular and noncardiovascular causes of death and stronger for longer antecedent periods (3 versus ,3 years). We conclude that prior decline or rise in eGFR associates with an increased risk of mortality, independent of current eGFR.

show abstract

Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Past Decline Versus Current eGFR and Subsequent Mortality Risk

Naimark

Grams

Matsushita

et al. 2015

JASN

View full text Add to dashboard Cite

show abstract

“…4,5 The mortality rate in ESKD patients maintained on dialysis is striking, with a life expectancy less than one-third that of their counterparts without ESKD, and a 5-year survival rate on dialysis of only 40%. 6 There is also a substantial healthcare cost associated with provision of ESKD care, currently estimated at $33 billion annually in the US, ABSTRACT equating to 6.3% of the Medicare Budget.…”

Section: Introductionmentioning

confidence: 99%

“…2,3 Even in its early stages, CKD is associated with accelerated cardiovascular disease and increased mortality, with an exponential increase in attributable risk as GFR declines to end-stage kidney disease (ESKD). 4,5 The mortality rate in ESKD patients maintained on dialysis is striking, with a life expectancy less than one-third that of their counterparts without ESKD, and a 5-year survival rate on dialysis of only 40%. 6 There is also a substantial healthcare cost associated with provision of ESKD care, currently estimated at $33 billion annually in the US,…”

Section: Introductionmentioning

confidence: 99%

Drug therapies to delay the progression of chronic kidney disease

2015

View full text Add to dashboard Cite

Chronic kidney disease (CKD) is associated with significant morbidity and mortality, impacted not alone by progression to end-stage kidney disease, but also by the high associated incidence of cardiovascular events and related mortality. Despite our current understanding of the pathogenesis of CKD and the treatments available, the reported incidence of CKD continues to rise worldwide, and is often referred to as the silent public healthcare epidemic. The significant cost to patient wellbeing and to the economy of managing the later stages of CKD have prompted efforts to develop interventions to delay the development and progression of this syndrome. In this article, we review established and novel agents that may aid in delaying the progression of CKD and improve patient outcomes. KEYWORDS: Chronic kidney disease, progression, drug therapy IntroductionChronic kidney disease (CKD), as defined by proteinuria or a reduced glomerular filtration rate (GFR) below 90 mL/min/1.73 m 2 persisting for greater than 3 months, is reported to affect 13% of US adults.1 There is a significantly higher prevalence in the elderly and those with hypertension or diabetes, and with these comorbidities increasing in prevalence and the population ageing, CKD is projected to affect up to 16% of adults by 2030.2,3 Even in its early stages, CKD is associated with accelerated cardiovascular disease and increased mortality, with an exponential increase in attributable risk as GFR declines to end-stage kidney disease (ESKD). 4,5 The mortality rate in ESKD patients maintained on dialysis is striking, with a life expectancy less than one-third that of their counterparts without ESKD, and a 5-year survival rate on dialysis of only 40%. 6 There is also a substantial healthcare cost associated with provision of ESKD care, currently estimated at $33 billion annually in the US, ABSTRACT equating to 6.3% of the Medicare Budget. 6 Hence, there may be significant healthcare and economic benefits to be garnered from halting or delaying CKD progression. In this article, we discuss recent evidence for established and emerging therapies that may alter the progression of CKD. Non disease-specific drug therapies Sodium bicarbonateCKD is associated with a metabolic acidosis, particularly at lower levels of GFR <25 mL/min/1.73 m 2 , which is predominantly attributed to reduced hydrogen ion excretion as titratable acids or ammonium in the urine. Chronic metabolic acidosis exacerbates CKD-related mineral bone disease, leads to muscle atrophy, and is associated with other complications such as abnormal albumin synthesis, thyroid dysfunction and insulin resistance. 7,8 Observational data demonstrate a strong risk of progression of CKD in those with a lower serum bicarbonate level, as well as an increased mortality risk. 9,10 Possible mechanisms for the deleterious effect of acidosis on GFR may be the inadvertent pro-fibrotic effects of inducing regulatory mechanisms in the kidney, such as increased renal ammonium production, endothelin-A receptor activation and pr...

show abstract

Age and Association of Kidney Measures With Mortality and End-stage Renal Disease

Hallan

Matsushita

Sang

et al. 2012

JAMA

532

408

View full text Add to dashboard Cite

Context Chronic kidney disease (CKD) is prevalent in older individuals, but the risk implications of low estimated glomerular filtration rate (eGFR) and high albuminuria across the full age range are controversial. Objective To evaluate possible effect modification (interaction) of age on the association of estimated GFR and albuminuria with clinical risk examining both relative and absolute risk. Design, Setting, Participants We investigated 2,051,244 participants from 33 general population or high-risk (of vascular disease) cohorts and 13 CKD cohorts from Asia, Australesia, Europe, and North/South America conducted during 1972–2011 with mean follow-up time of 5.8 years (range 0–31 years). Main Outcome Measures Hazard ratios (HRs) of mortality and end-stage renal disease (ESRD) according to eGFR and albuminuria were meta-analyzed across age categories after adjusting for sex, race, cardiovascular disease, diabetes, systolic blood pressure, cholestserol, body mass index, and smoking. Absolute risks were estimated using HRs and average incidence rates. Results Mortality (112,325 deaths) and ESRD (8,411 events) risk were higher at lower eGFR and higher albuminuria in every age category. In general/high-risk cohorts, relative mortality risk for reduced eGFR decreased with increasing age: e.g., adjusted HRs (95% CI) at eGFR 45 vs. 80 ml/min/1.73m2 were 3.50 (2.55–4.81), 2.21 (2.02–2.41), 1.59 (1.42–1.77), and 1.35 (1.23–1.48) in age categories 18–54, 55–64, 65–74 and 75+ years, respectively (P-values for age interaction <0.05). Absolute risk differences for the same comparisons were higher at older age (9.0 [95% CI, 6.0–12.8], 12.2 [10.3–14.3], 13.3 [9.0–18.6], and 27.2 [13.5–45.5] excess deaths per 1,000 person-years, respectively). For increased albuminuria, reduction of relative risk with increasing age were less evident, while differences in absolute risk were higher in the older age categories (7.5 [95% CI, 4.3–11.9], 12.2 [7.9–17.6], 22.7 [15.3–31.6], and 34.3 [19.5–52.4] excess deaths per 1,000 person-years, respectively by age category, at ACR 300 mg/g compared to 10 mg/g). In CKD cohorts, adjusted relative hazards of mortality did not decrease with age. In all cohorts, ESRD relative risks and absolute risk differences at lower eGFR or higher albuminuria were comparable across age categories. Conclusions Both low eGFR and high albuminuria were independently associated with mortality and ESRD regardless of age across a wide range of populations. Mortality showed lower relative risk but higher absolute risks differences at older age.

show abstract

GFR Decline and Mortality Risk among Patients with Chronic Kidney Disease

Cited by 105 publications

References 18 publications

Past Decline Versus Current eGFR and Subsequent Mortality Risk

Past Decline Versus Current eGFR and Subsequent Mortality Risk

Drug therapies to delay the progression of chronic kidney disease

Age and Association of Kidney Measures With Mortality and End-stage Renal Disease

Contact Info

Product

Resources

About