Urinary Biomarkers of Tubular Damage Are Associated with Mortality but Not Cardiovascular Risk among Systolic Blood Pressure Intervention Trial Participants with Chronic Kidney Disease

Background: Kidney tubulointerstitial fibrosis on biopsy is a strong predictor of chronic kidney disease (CKD) progression, and CKD is associated with elevated risk of cardiovascular disease (CVD). Tubular health is poorly quantified by traditional kidney function measures, including estimated glomerular filtration rate (eGFR) and albuminuria. We hypothesized that urinary biomarkers of tubular injury, inflammation, and repair would be associated with higher risk of CVD and mortality in persons with CKD. Methods: We measured urinary concentrations of interleukin-18 (IL-18), kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, monocyte chemoattractant protein-1, and chitinase-3-like protein-1 (YKL-40) at baseline among 2,377 participants of the Systolic Blood Pressure Intervention Trial who had an eGFR < 60 mL/min/1.73 m2. We used Cox proportional hazards models to evaluate biomarker associations with CVD events and all-cause mortality. Results: At baseline, the mean age of participants was 72 ± 9 years, and eGFR was 48 ± 11 mL/min/1.73 m2. Over a median follow-up of 3.8 years, 305 CVD events (3.6% per year) and 233 all-cause deaths (2.6% per year) occurred. After multivariable adjustment including eGFR, albuminuria, and urinary creatinine, none of the biomarkers showed statistically significant associations with CVD risk. Urinary IL-18 (hazard ratio [HR] per 2-fold higher value, 1.14; 95% CI 1.01–1.29) and YKL-40 (HR per 2-fold higher value, 1.08; 95% CI 1.02–1.14) concentrations were each incrementally associated with higher mortality risk. Associations were similar when stratified by randomized blood pressure arm. Conclusions: Among hypertensive trial participants with CKD, higher urinary IL-18 and YKL-40 were associated with higher risk of mortality, but not CVD.

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In the Wake of Systolic Blood Pressure Intervention Trial: New Targets for Improving Hypertension Management in Chronic Kidney Disease?

Nephron ◽

10.1159/000455130 ◽

2017 ◽

Vol 135 (4) ◽

pp. 287-290 ◽

Cited By ~ 2

Author(s):

Crystal C. Tyson ◽

Thomas M. Coffman

Keyword(s):

Blood Pressure ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Systolic Blood Pressure ◽

Hypertension Management ◽

Intervention Trial ◽

New Targets

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Hypertension in chronic kidney disease after the Systolic Blood Pressure Intervention Trial: targets, treatment and current uncertainties

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfw269 ◽

2017 ◽

Vol 32 (suppl_2) ◽

pp. ii219-ii223 ◽

Cited By ~ 5

Author(s):

Csaba P. Kovesdy

Keyword(s):

Blood Pressure ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Systolic Blood Pressure ◽

Intervention Trial

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Blood pressure targets in patients with chronic kidney disease: MDRD and AASK now confirming SPRINT

Clinical Kidney Journal ◽

10.1093/ckj/sfaa015 ◽

2020 ◽

Author(s):

Pantelis Sarafidis ◽

Charalampos Loutradis ◽

Alberto Ortiz ◽

Luis M Ruilope

Keyword(s):

Blood Pressure ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Systolic Blood Pressure ◽

Recent Analysis ◽

Intervention Trial ◽

Mortality Benefit ◽

Blood Pressure Targets ◽

Hypertension Guidelines ◽

All Cause Mortality

Abstract Recent American and European hypertension guidelines are not in agreement regarding blood pressure (BP) targets for persons with chronic kidney disease (CKD). Previous analyses from the African American Study on Kidney Disease (AASK) and Modification of Diet in Renal Disease (MDRD) trials suggested that strict BP control confers nephroprotection for patients with proteinuria, but a mortality benefit was not apparent. In contrast, an analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) subpopulation of CKD patients showed a mortality benefit with the systolic blood pressure (SBP) <120 mmHg versus the SBP <140 target. A recent analysis of the combined MDRD and AASK cohorts supports previous evidence on nephroprotection but also findings from the SPRINT trial on all-cause mortality benefits of intensive versus usual BP control in individuals with CKD.

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Chronic Kidney Disease Classification in Systolic Blood Pressure Intervention Trial: Comparison Using Modification of Diet in Renal Disease and CKD-Epidemiology Collaboration Definitions

American Journal of Nephrology ◽

10.1159/000448722 ◽

2016 ◽

Vol 44 (2) ◽

pp. 130-140 ◽

Cited By ~ 6

Author(s):

Michael V. Rocco ◽

Arlene Chapman ◽

Glenn M. Chertow ◽

Debbie Cohen ◽

Jing Chen ◽

...

Keyword(s):

Blood Pressure ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Renal Disease ◽

Systolic Blood Pressure ◽

Disease Classification ◽

Intervention Trial ◽

Mdrd Equation ◽

Ckd Stage ◽

Lower Egfr

Background: Interventional trials have used either the Modification of Diet in Renal Disease (MDRD) or chronic kidney disease (CKD)-Epidemiology Collaboration (CKD-EPI) equation for determination of estimated glomerular filtration rate (eGFR) to define whether participants have stages 3-5 CKD. The equation used to calculate eGFR may influence the number and characteristics of participants designated as having CKD. Methods: We examined the classification of CKD at baseline using both equations in the Systolic Blood Pressure Intervention Trial (SPRINT). eGFR was calculated at baseline using fasting serum creatinine values from a central laboratory. Results: Among 9,308 participants with baseline CKD classification using the 4-variable MDRD equation specified in the SPRINT protocol, 681 (7.3%) participants were reclassified to a less advanced CKD stage (higher eGFR) and 346 (3.7%) were reclassified to a more advanced CKD stage (lower eGFR) when the CKD-EPI equation was used to calculate eGFR. For eGFRs <90 ml/min/1.73 m2, participants <75 years were more likely to be reclassified to a less advanced CKD stage; this reclassification was more likely to occur in non-blacks rather than blacks. Participants aged ≥75 years were more likely to be reclassified to a more advanced than a less advanced CKD stage, regardless of baseline CKD stage. Reclassification of baseline CKD status (eGFR <60 ml/min/1.73 m2) occurred in 3% of participants. Conclusions: Use of the MDRD equation led to a higher percentage of participants being classified as having CKD stages 3-4. Younger and non-black participants were more likely to be reclassified as not having CKD using the CKD-EPI equation.

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Pulse wave velocity and central aortic pressure in systolic blood pressure intervention trial participants

PLoS ONE ◽

10.1371/journal.pone.0203305 ◽

2018 ◽

Vol 13 (9) ◽

pp. e0203305 ◽

Cited By ~ 7

Author(s):

Mark A. Supiano ◽

Laura Lovato ◽

Walter T. Ambrosius ◽

Jeffrey Bates ◽

Srinivasan Beddhu ◽

...

Keyword(s):

Blood Pressure ◽

Pulse Wave Velocity ◽

Systolic Blood Pressure ◽

Wave Velocity ◽

Pulse Wave ◽

Aortic Pressure ◽

Intervention Trial ◽

Central Aortic Pressure ◽

Trial Participants

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Chronic Kidney Disease among Diabetes Patients in Ethiopia: A Systematic Review and Meta-Analysis

International Journal of Nephrology ◽

10.1155/2020/8890331 ◽

2020 ◽

Vol 2020 ◽

pp. 1-15

Author(s):

Wondimeneh Shibabaw Shiferaw ◽

Tadesse Yirga Akalu ◽

Yared Asmare Aynalem

Keyword(s):

Blood Pressure ◽

Chronic Kidney Disease ◽

Diabetic Retinopathy ◽

Kidney Disease ◽

Glycemic Control ◽

High Density Lipoprotein ◽

Systolic Blood Pressure ◽

Meta Analysis ◽

Density Lipoprotein ◽

Diabetes Patients

Background. Though different primary studies have reported the burden of chronic kidney disease among diabetes patients, their results have demonstrated substantial variation regarding its prevalence in Ethiopia. Therefore, this study aimed to estimate the pooled prevalence of chronic kidney disease and its associated factors among diabetes patients in Ethiopia. Method. PubMed, African Journals Online, Google Scholar, Scopus, and Wiley Online Library were searched to identify relevant studies. The I2 statistic was used to check heterogeneity across the included studies. A random-effects model was applied to estimate the pooled effect size across studies. A funnel plot and Egger’s regression test were used to determine the presence of publication bias. All statistical analyses were performed using STATA™ version 14 software. Result. In this meta-analysis, a total of 12 studies with 4,075 study participants were included. The estimated prevalence of CKD among diabetes patients was found to be 35.52% (95% CI: 25.9–45.45, I2 = 96.3%) for CKD stages 1 to 5 and 14.5% (95% CI: 10.5–18.49, I2 = 91.1%) for CKD stages 3 to 5. Age greater than 60 years (OR = 2.99; 95% CI: 1.56–5.73), female sex (OR = 1.68; 95% CI: 1.04–2.69), duration of diabetes >10 years (OR = 2.76; 95% CI: 1.38–5.51), body mass index >30 kg/m2 (OR = 2.06; 95% CI: 1.41–3.00), type 2 diabetes (OR = 2.54; 95% CI: 1.73–3.73), poor glycemic control (OR = 2.01; 95% CI: 1.34–3.02), fasting blood glucose >150 mg/dl (OR = 2.58; 95% CI: 1.79–3.72), high density lipoprotein >40 mg/dl (OR = 0.48; 95% CI: 0.30–0.85–25), systolic blood pressure>140 mmHg (OR = 3.26; 95% CI: 2.24–4.74), and diabetic retinopathy (OR = 4.54; CI: 1.08–25) were significantly associated with CKD. Conclusion. This study revealed that the prevalence of chronic kidney disease remains high among diabetes patients in Ethiopia. This study found that a long duration of diabetes, age>60 years, diabetic retinopathy, female sex, family history of kidney disease, poor glycemic control, systolic blood pressure, overweight, and high level of high-density lipoprotein were associated with chronic kidney disease among diabetic patients. Therefore, situation-based interventions and context-specific preventive strategies should be developed to reduce the prevalence and risk factors of chronic kidney disease among diabetes patients.

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Modifying Effect of Statins on Fatal Outcomes in Chronic Kidney Disease Patients in the Systolic Blood Pressure Intervention Trial: A Post Hoc Analysis

American Journal of Nephrology ◽

10.1159/000499188 ◽

2019 ◽

Vol 49 (4) ◽

pp. 297-306 ◽

Cited By ~ 1

Author(s):

Manuel Rivera ◽

Leonardo Tamariz ◽

Maritza Suarez ◽

Gabriel Contreras

Keyword(s):

Blood Pressure ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Systolic Blood Pressure ◽

Statin Therapy ◽

Statin Group ◽

All Cause Mortality ◽

Modifying Effect ◽

Post Hoc ◽

Event Rates

Background: Management of chronic kidney disease (CKD) patients includes efforts directed toward modifying traditional cardiovascular risk factors. Such efforts include optimal management of hypertension together with the initiation of statin therapy. Methods: In this observational study, we determine the modifying effect of statins on the relationship of systolic blood pressure (SBP) goal with mortality and other outcomes in patients with CKD participating in a clinical trial. At baseline, 2,646 CKD patients (estimated glomerular filtration rate < 60 mL/min/1.73 m2) were randomized to an intensive SBP goal < 120 mm Hg or standard SBP goal <140 mm Hg. One thousand two hundred and seventy-three were not on statin, 1,354 were on a statin, and in 19 the use of statin was unknown. The 2 primary outcomes were all-cause mortality and cardiovascular disease (CVD) mortality. Results: The relationships of SBP goal with all-cause mortality (interaction p = 0.009) and cardiovascular (CV) mortality (interaction p = 0.021) were modified by the use of statin after adjusting for age, gender, race, CVD history, smoking, aspirin use, and blood pressure at baseline. In the statin group, targeting SBP to < 120 mm Hg compared to SBP < 140 mm Hg significantly reduced the risk of all-cause mortality (adjusted hazard ratio [aHR] 0.44 [0.28–0.71]; event rates 1.16 vs. 2.5 per 100 patient-years) and CV mortality (aHR 0.29 [0.12–0.74]; event rates 0.28 vs. 0.92 per 100 patient-years) after a median follow-up of 3.26 years. In the non-statin group, the risk of all-cause mortality (aHR 1.07 [0.69–1.66]; event rates 2.01 vs. 1.94 per 100 patient-years) and CV mortality (aHR 1.42 [0.56–3.59]; event rates 0.52 vs. 0.41 per 100 patient-years) were not significantly different in both SBP goal arms. Conclusion: The combination of statin therapy and intensive SBP management leads to improved survival in hypertensive patients with CKD.

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