Dataset Information

Change in Albuminuria and Risk of Renal and Cardiovascular Outcomes: Natural Variation Should Be Taken into Account.

ABSTRACT:

Introduction

Changes in urinary albumin-to-creatinine ratio (UACR) may affect the risk of advanced chronic kidney disease (CKD). How much the association changes after taking account for natural variation in UACR and the length of time taken to observe changes in UACR is unknown.

Methods

English Clinical Practice Research Datalink records (2000-2015) with linkage to secondary care and death certification were used to identify prospective cohorts with at least 2 measures of UACR within 1, 2, and 3 years. Adjusted Cox regression assessed the separate relevance of the baseline UACR and the UACR change to the risk of developing stages 4 to 5 CKD and end-stage renal disease (ESRD). Associations were compared before and after accounting for the effects of the natural variation in UACR (i.e., regression to the mean).

Results

A total of 212,810 individuals had baseline UACR measurements; 22% had a UACR ?3.4 mg/mmol, and 3% had UACR ?33.9 mg/mmol. During a median 4-year follow-up, 5976 developed stage 4 to 5 CKD, and 1076 developed ESRD. There were strong associations between baseline UACR and stage 4 to 5 CKD or ESRD risk, which doubled in strength after accounting for regression to the mean. Over 3 years, the hazard ratios (95% confidence intervals) for stage 4 to 5 CKD, relative to stable UACR, were 0.62 (0.50-0.77) for at least a halving of UACR and 2.68 (2.29-3.14) for at least a doubling of UACR. Associations were weaker for shorter exposure windows (and for cardiovascular disease or death), but strengthened after allowing for regression to the mean.

Conclusion

Baseline values and subsequent medium-term increases in albuminuria are both associated with substantially increased risk of developing advanced CKD. Standard analyses, not allowing for natural variation in UACR, may underestimate these associations.

SUBMITTER: Smith M

PROVIDER: S-EPMC6035156 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Publications

Change in Albuminuria and Risk of Renal and Cardiovascular Outcomes: Natural Variation Should Be Taken into Account.

Smith Margaret M Herrington William G WG Weldegiorgis Misghina M Hobbs Fd Richard FR Bankhead Clare C Woodward Mark M

Kidney international reports 20180416 4

<h4>Introduction</h4>Changes in urinary albumin-to-creatinine ratio (UACR) may affect the risk of advanced chronic kidney disease (CKD). How much the association changes after taking account for natural variation in UACR and the length of time taken to observe changes in UACR is unknown.<h4>Methods</h4>English Clinical Practice Research Datalink records (2000-2015) with linkage to secondary care and death certification were used to identify prospective cohorts with at least 2 measures of UACR wi ...[more]

PMID: 29988998

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Project description:Background and objectivesIn trials of people with type 2 diabetes, albuminuria reduction with renin-angiotensin system inhibitors is associated with lower risks of cardiovascular events and CKD progression. We tested whether progression or remission of microalbuminuria is associated with cardiovascular and renal risk in a well characterized cohort of type 1 diabetes.Design, setting, participants, & measurementsWe studied 1441 participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study. Albumin excretion rate (AER) was quantified annually or biennially for up to 30 years. For each participant, albuminuria status was defined over time as normoalbuminuria (AER continuously <30 mg/d), sustained microalbuminuria (AER, 30-299 mg/d on two consecutive visits), macroalbuminuria (AER≥300 mg/d), or remitted microalbuminuria (transition from sustained microalbuminuria to AER<30 mg/d on two consecutive visits). We tested associations of time-updated albuminuria status with adjudicated clinical cardiovascular events, the development of reduced GFR (<60 ml/min per 1.73 m2 on two consecutive visits), and subclinical cardiovascular disease.ResultsAt least one cardiovascular event occurred in 184 participants, and 98 participants developed reduced eGFR. Compared with normoalbuminuria, sustained microalbuminuria, remitted microalbuminuria, and macroalbuminuria were each associated with higher risk of cardiovascular events (adjusted hazard ratios [HRs] and 95% confidence intervals [95% CIs]: 1.79 [1.13 to 2.85], 2.62 [1.68 to 4.07], and 2.65 [1.68 to 4.19], respectively) and reduced eGFR (adjusted HRs [95% CIs], 5.26 [2.43 to 11.41], 4.36 [1.80 to 10.57], and 54.35 [30.79 to 95.94], respectively). Compared with sustained microalbuminuria, remission to normoalbuminuria was not associated with reduced risk of cardiovascular events (adjusted HR, 1.33; 95% CI, 0.68 to 2.59) or reduced eGFR (adjusted HR, 1.75; 95% CI, 0.56 to 5.49). Compared with normoalbuminuria, sustained microalbuminuria, remitted microalbuminuria, and macroalbuminuria were associated with greater carotid intima-media thickness, and macroalbuminuria was associated with a greater degree of coronary artery calcification.ConclusionsIn type 1 diabetes, microalbuminuria and macroalbuminuria are associated with higher risks of cardiovascular disease and reduced eGFR, but achieving a remission of established microalbuminuria to normoalbuminuria does not appear to improve outcomes.

Project description:BACKGROUND:If SGLT2 inhibitors protect the kidneys by reducing albuminuria as hypothesized, people with type 2 diabetes mellitus (T2DM) with higher albuminuria should benefit more. METHODS:We conducted a post-hoc analysis of data from the CANagliflozin cardioVascular Assessment Study (CANVAS) Program, which randomized 10,142 participants with T2DM and high cardiovascular risk to canagliflozin or placebo. We assessed effects of canagliflozin on renal, cardiovascular, and safety outcomes by baseline albuminuria. The trial included 2266 participants (22.3%) with moderately increased albuminuria (urinary albumin/creatinine ratio [UACR] 30-300 mg/g) and 760 (7.5%) with severely increased albuminuria (UACR >300 mg/g) at baseline. RESULTS:Canagliflozin lowered albuminuria with greater proportional reductions in those with moderately and severely increased albuminuria (P heterogeneity<0.001). After week 13, canagliflozin slowed the annual loss of kidney function across albuminuria subgroups, with greater absolute reductions in participants with severely increased albuminuria (placebo-subtracted difference 3.01 ml/min per 1.73 m2 per year; P heterogeneity<0.001). Heterogeneity for the renal composite outcome of 40% reduction in eGFR, ESKD, or renal-related death was driven by lesser effects in participants with moderately increased albuminuria (P heterogeneity=0.03), but no effect modification was observed when albuminuria was fitted as a continuous variable (P heterogeneity=0.94). Cardiovascular and safety outcomes were mostly consistent across albuminuria levels including increased risks for amputation across albuminuria subgroups (P heterogeneity=0.66). Greater absolute risk reductions in the renal composite outcome were observed in participants with severely increased albuminuria (P heterogeneity=0.004). CONCLUSIONS:The proportional effects of canagliflozin on renal and cardiovascular outcomes are mostly consistent across patients with different levels of albuminuria, but absolute benefits are greatest among those with severely increased albuminuria.

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Dataset Information

Change in Albuminuria and Risk of Renal and Cardiovascular Outcomes: Natural Variation Should Be Taken into Account.

Introduction

Methods

Results

Conclusion

Publications

Change in Albuminuria and Risk of Renal and Cardiovascular Outcomes: Natural Variation Should Be Taken into Account.

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