Dataset Information

Association Between Kidney Clearance of Secretory Solutes and Cardiovascular Events: The Chronic Renal Insufficiency Cohort (CRIC) Study.

ABSTRACT:

Rationale & objective

The clearance of protein-bound solutes by the proximal tubules is an innate kidney mechanism for removing putative uremic toxins that could exert cardiovascular toxicity in humans. However, potential associations between impaired kidney clearances of secretory solutes and cardiovascular events among patients with chronic kidney disease (CKD) remains uncertain.

Study design

A multicenter, prospective, cohort study.

Setting & participants

We evaluated 3,407 participants from the Chronic Renal Insufficiency Cohort (CRIC) study.

Exposures

Baseline kidney clearances of 8 secretory solutes. We measured concentrations of secretory solutes in plasma and paired 24-hour urine specimens using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Outcomes

Incident heart failure, myocardial infarction, and stroke events.

Analytical approach

We used Cox regression to evaluate associations of baseline secretory solute clearances with incident study outcomes adjusting for estimated GFR (eGFR) and other confounders.

Results

Participants had a mean age of 56 years; 45% were women; 41% were Black; and the median estimated glomerular filtration rate (eGFR) was 43 mL/min/1.73 m². Lower 24-hour kidney clearance of secretory solutes were associated with incident heart failure and myocardial infarction but not incident stroke over long-term follow-up after controlling for demographics and traditional risk factors. However, these associations were attenuated and not statistically significant after adjustment for eGFR.

Limitations

Exclusion of patients with severely reduced eGFR at baseline; measurement variability in secretory solutes clearances.

Conclusions

In a national cohort study of CKD, no clinically or statistically relevant associations were observed between the kidney clearances of endogenous secretory solutes and incident heart failure, myocardial infarction, or stroke after adjustment for eGFR. These findings suggest that tubular secretory clearance provides little additional information about the development of cardiovascular disease events beyond glomerular measures of GFR and albuminuria among patients with mild-to-moderate CKD.

SUBMITTER: Chen Y

PROVIDER: S-EPMC8260620 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association Between Kidney Clearance of Secretory Solutes and Cardiovascular Events: The Chronic Renal Insufficiency Cohort (CRIC) Study.

Chen Yan Y Zelnick Leila R LR Huber Matthew P MP Wang Ke K Bansal Nisha N Hoofnagle Andrew N AN Paranji Rajan K RK Heckbert Susan R SR Weiss Noel S NS Go Alan S AS Hsu Chi-Yuan CY Feldman Harold I HI Waikar Sushrut S SS Mehta Rupal C RC Srivastava Anand A Seliger Stephen L SL Lash James P JP Porter Anna C AC Raj Dominic S DS Kestenbaum Bryan R BR

American journal of kidney diseases : the official journal of the National Kidney Foundation 20210107 2

<h4>Rationale & objective</h4>The clearance of protein-bound solutes by the proximal tubules is an innate kidney mechanism for removing putative uremic toxins that could exert cardiovascular toxicity in humans. However, potential associations between impaired kidney clearances of secretory solutes and cardiovascular events among patients with chronic kidney disease (CKD) remains uncertain.<h4>Study design</h4>A multicenter, prospective, cohort study.<h4>Setting & participants</h4>We evaluated 3, ...[more]

PMID: 33421453

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Project description:We recently reported a linear association between higher systolic blood pressure (SBP) and risk of mortality in hemodialysis patients when SBP is measured outside of the dialysis unit (out-of-dialysis-unit-SBP), despite there being a U-shaped association between SBP measured at the dialysis unit (dialysis-unit-SBP) with risk of mortality. Here, we explored the relationship between SBP with cardiovascular events, which has important treatment implications but has not been well elucidated. Among 383 hemodialysis participants enrolled in the prospective CRIC study (Chronic Renal Insufficiency Cohort), multivariable splines and Cox models were used to study the association between SBP and adjudicated cardiovascular events (heart failure, myocardial infarction, ischemic stroke, and peripheral artery disease), controlling for differences in demographics, cardiovascular disease risk factors, and dialysis parameters. Dialysis-unit-SBP and out-of-dialysis-unit-SBP were modestly correlated (r=0.34; P<0.001). We noted a U-shaped association of dialysis-unit-SBP and risk of cardiovascular events, with the nadir risk between 140 and 170 mm Hg. In contrast, there was a linear stepwise association between out-of-dialysis-unit-SBP with risk of cardiovascular events. Participants with out-of-dialysis-unit-SBP ≥128 mm Hg (top 2 quartiles) had >2-fold increased risk of cardiovascular events compared with those with out-of-dialysis-unit-SBP ≤112 mm Hg (3rd SBP quartile: adjusted hazard ratio, 2.08 [95% confidence interval, 1.12-3.87] and fourth SBP quartile: adjusted hazard ratio, 2.76 [95% confidence interval, 1.42-5.33]). In conclusion, among hemodialysis patients, although there is a U-shaped (paradoxical) association of dialysis-unit-SBP and risk of cardiovascular disease, there is a linear association of out-of-dialysis-unit-SBP with risk of cardiovascular disease. Out-of-dialysis-unit blood pressure provides key information and may be an important therapeutic target.

Project description:Rationale & objectiveThe clinical significance of isolated diastolic hypertension in patients with chronic kidney disease (CKD) is unclear. We assessed the prevalence of isolated diastolic hypertension and its association with adverse kidney and cardiovascular outcomes in participants in the Chronic Renal Insufficiency Cohort (CRIC) study.Study designProspective cohort study.Setting & populationCRIC study participants with complete baseline data on systolic blood pressure (SBP) and diastolic BP (DBP) (N=5,621).ExposureIsolated diastolic hypertension defined as SBP ≤ 130 mm Hg and DBP >80 mm Hg.Reference groupNormotension, defined as SBP ≤ 130 mm Hg and DBP ≤ 80 mm Hg.OutcomesComposite kidney events (50% decline in estimated glomerular filtration rate or onset of kidney failure), composite cardiovascular events (myocardial infarction, heart failure, stroke, or peripheral arterial disease), and all-cause mortality.Analytical approachCox proportional hazards models adjusted for demographic, health behavior, and clinical covariates.ResultsOf the 5,621 participants, 347 (6.2%) had isolated diastolic hypertension. Among the 347 participants with isolated diastolic hypertension, there was no association between isolated diastolic hypertension and the composite kidney outcome (HR, 1.17; 95% CI, 0.93-1.47; P = 0.18), composite cardiovascular events (HR, 0.91; 95% CI, 0.65-1.27; P = 0.58), or all-cause mortality (HR, 0.82; 95% CI, 0.57-1.19; P = 0.30).LimitationsOlder age of cohort and low number of participants of Asian ethnicity limit generalizability of findings. A relatively small sample size is inadequate to detect modest associations with outcomes.ConclusionsIsolated diastolic hypertension was not associated with the risk of adverse kidney and cardiovascular events in participants with CKD.Plain language summaryClinicians frequently encounter patients with kidney disease who have controlled systolic blood pressure (BP) but high diastolic BP and do not know whether they should intensify BP treatment in an attempt to control the diastolic BP. We examined whether having controlled systolic BP but uncontrolled diastolic BP leads to worse heart and kidney outcomes in patients with chronic kidney disease. We did not find any such association. However, our study was relatively small and had a number of limitations. Till larger studies confirm or refute this finding, we recommend not increasing blood pressure medications to improve the diastolic BP control if the systolic BP is already well controlled in patients with chronic kidney disease.

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Project description:Rationale & objectiveMany adults with chronic kidney disease (CKD) and atherosclerotic cardiovascular disease (ASCVD) have high lipoprotein(a) levels. It is unclear whether high lipoprotein(a) levels confer an increased risk for recurrent ASCVD events in this population. We estimated the risk for recurrent ASCVD events associated with lipoprotein(a) in adults with CKD and prevalent ASCVD.Study designObservational cohort study.Setting & participantsWe included 1,439 adults with CKD and prevalent ASCVD not on dialysis enrolled in the Chronic Renal Insufficiency Cohort study between 2003 and 2008.ExposureBaseline lipoprotein(a) mass concentration, measured using a latex-enhanced immunoturbidimetric assay.OutcomesRecurrent ASCVD events (primary outcome), kidney failure, and death (exploratory outcomes) through 2019.Analytical approachWe used Cox proportional-hazards regression models to estimate adjusted HR (aHRs) and 95% CIs.ResultsAmong participants included in the current analysis (mean age 61.6 years, median lipoprotein(a) 29.4 mg/dL [25th-75th percentiles 9.9-70.9 mg/dL]), 641 had a recurrent ASCVD event, 510 developed kidney failure, and 845 died over a median follow-up of 6.6 years. The aHR for ASCVD events associated with 1 standard deviation (SD) higher log-transformed lipoprotein(a) was 1.04 (95% CI, 0.95-1.15). In subgroup analyses, 1 SD higher log-lipoprotein(a) was associated with an increased risk for ASCVD events in participants without diabetes (aHR, 1.23; 95% CI, 1.02-1.48), but there was no evidence of an association among those with diabetes (aHR, 0.99; 95% CI, 0.88-1.10, P comparing aHRs = 0.031). The aHR associated with 1 SD higher log-lipoprotein(a) in the overall study population was 1.16 (95% CI, 1.04-1.28) for kidney failure and 1.02 (95% CI, 0.94-1.11) for death.LimitationsLipoprotein(a) was not available in molar concentration.ConclusionsLipoprotein(a) was not associated with the risk for recurrent ASCVD events in adults with CKD, although it was associated with a risk for kidney failure.

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Dataset Information

Association Between Kidney Clearance of Secretory Solutes and Cardiovascular Events: The Chronic Renal Insufficiency Cohort (CRIC) Study.

Rationale & objective

Study design

Setting & participants

Exposures

Outcomes

Analytical approach

Results

Limitations

Conclusions

Publications

Association Between Kidney Clearance of Secretory Solutes and Cardiovascular Events: The Chronic Renal Insufficiency Cohort (CRIC) Study.

Similar Datasets

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