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Association of Intensive Blood Pressure Control and Kidney Disease Progression in Nondiabetic Patients With Chronic Kidney DiseaseA Systematic Review and Meta-analysis

Educational Objective
To compare intensive blood pressure control (<130/80 mm Hg) with standard blood pressure control (<140/90 mm Hg) on major renal outcomes in patients with chronic kidney disease without diabetes.
1 Credit CME
Key Points

Question  Does intensive blood pressure control provide better renoprotection for nondiabetic chronic kidney disease?

Findings  In this systematic review including 9 randomized clinical trials with 8127 patients and a median follow-up of 3.3 years, intensive and standard blood pressure control provided similar effects. However, nonblack patients and those with higher levels of proteinuria showed a trend of lower risk of kidney disease progression with intensive blood pressure–lowering treatments.

Meaning  Targeting blood pressure below the current standard is not consistently warranted, but may benefit nonblack patients or those with heavy proteinuria.

Abstract

Importance  The optimal blood pressure (BP) target remains debated in nondiabetic patients with chronic kidney disease (CKD).

Objective  To compare intensive BP control (<130/80 mm Hg) with standard BP control (<140/90 mm Hg) on major renal outcomes in patients with CKD without diabetes.

Data Sources  Searches of PubMed, MEDLINE, Embase, and Cochrane Library for publications up to March 24, 2016.

Study Selection  Randomized clinical trials that compared an intensive vs a standard BP target in nondiabetic adults with CKD, reporting changes in glomerular filtration rate (GFR), doubling of serum creatinine level, 50% reduction in GFR, end-stage renal disease (ESRD), or all-cause mortality.

Data Extraction and Synthesis  Random-effects meta-analyses for pooling effect measures. Meta-regression and subgroup analyses for exploring heterogeneity.

Main Outcomes and Measures  Differences in annual rate of change in GFR were expressed as mean differences with 95% CIs. Differences in doubling of serum creatinine or 50% reduction in GFR, ESRD, composite renal outcome, and all-cause mortality were expressed as risk ratios (RRs) with 95% CIs.

Results  We identified 9 trials with 8127 patients and a median follow-up of 3.3 years. Compared with standard BP control, intensive BP control did not show a significant difference on the annual rate of change in GFR (mean difference, 0.07; 95% CI, −0.16 to 0.29 mL/min/1.73 m2/y), doubling of serum creatinine level or 50% reduction in GFR (RR, 0.99; 95% CI, 0.76-1.29), ESRD (RR, 0.96; 95% CI, 0.78-1.18), composite renal outcome (RR, 0.99; 95% CI, 0.81-1.21), or all-cause mortality (RR, 0.81; 95% CI, 0.64-1.02). Intensive BP control reduced mortality (RR, 0.78; 95% CI, 0.61-0.99) in sensitivity analysis when the study populations were strictly restricted to those without diabetes. Nonblacks and patients with higher levels of proteinuria showed a trend of lower risk of kidney disease progression with intensive BP control.

Conclusions and Relevance  Targeting BP below the current standard did not provide additional benefit for renal outcomes compared with standard treatment during a follow-up of 3.3 years in patients with CKD without diabetes. However, nonblack patients or those with higher levels of proteinuria might benefit from the intensive BP-lowering treatments.

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Article Information

Corresponding Author: Hon-Yen Wu, MD, PhD, Department of Internal Medicine, Far Eastern Memorial Hospital, No. 21, Sec. 2, Nanya S Rd, Banciao District, New Taipei City 220, Taiwan (honyenwu@ntu.edu.tw).

Accepted for Publication: January 23, 2017.

Correction: This article was corrected on September 18, 2017, for omission of data and errors in the meta-analysis.

Published Online: March 13, 2017. doi:10.1001/jamainternmed.2017.0197

Author Contributions: Drs Wu and Chien had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Wu and Chien contributed equally as corresponding authors to this work.

Study concept and design: Tsai, Wu, Peng, Yang, Hung, Chien.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Tsai, Wu, Tu, Chien.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Tsai, Wu, Yang, Tu.

Obtained funding: Wu, Ko, Hung, Chien.

Administrative, technical, or material support: Chen, Chiu, Hsu, Pai.

Supervision: Wu, Peng, Hung, Chien.

Conflict of Interest Disclosures: None reported.

Funding/Support: This study was supported by research grants to Dr Wu from the National Health Research Institutes, Taiwan (NHRI-EX105-10510PC), and the Far Eastern Memorial Hospital, New Taipei City, Taiwan (FEMH-EX105-10510PC).

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

References
1.
Go  AS, Chertow  GM, Fan  D, McCulloch  CE, Hsu  CY.  Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization.  N Engl J Med. 2004;351(13):1296-1305.PubMedGoogle ScholarCrossref
2.
Tsai  WC, Wu  HY, Peng  YS,  et al.  Risk factors for development and progression of chronic kidney disease: a systematic review and exploratory meta-analysis.  Medicine (Baltimore). 2016;95(11):e3013.PubMedGoogle ScholarCrossref
3.
Wu  HY, Peng  YS, Chiang  CK,  et al.  Diagnostic performance of random urine samples using albumin concentration vs ratio of albumin to creatinine for microalbuminuria screening in patients with diabetes mellitus: a systematic review and meta-analysis.  JAMA Intern Med. 2014;174(7):1108-1115.PubMedGoogle ScholarCrossref
4.
Wen  CP, Cheng  TY, Tsai  MK,  et al.  All-cause mortality attributable to chronic kidney disease: a prospective cohort study based on 462 293 adults in Taiwan.  Lancet. 2008;371(9631):2173-2182.PubMedGoogle ScholarCrossref
5.
Jha  V, Garcia-Garcia  G, Iseki  K,  et al.  Chronic kidney disease: global dimension and perspectives.  Lancet. 2013;382(9888):260-272.PubMedGoogle ScholarCrossref
6.
Zhang  L, Wang  F, Wang  L,  et al.  Prevalence of chronic kidney disease in China: a cross-sectional survey.  Lancet. 2012;379(9818):815-822.PubMedGoogle ScholarCrossref
7.
Levey  AS.  Clinical practice. Nondiabetic kidney disease.  N Engl J Med. 2002;347(19):1505-1511.PubMedGoogle ScholarCrossref
8.
Kidney Disease; Improving Global Outcomes (KDIGO) Blood Pressure Work Group.  KDIGO clinical practice guideline for the management of blood pressure in chronic kidney disease.  Kidney Int Suppl. 2012;2(5):337-414.Google ScholarCrossref
9.
Kidney Disease Outcomes Quality Initiative (K/DOQI).  K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease.  Am J Kidney Dis. 2004;43(5)(suppl 1):S1-S290.PubMedGoogle ScholarCrossref
10.
Fukuma  S, Shimizu  S, Niihata  K,  et al.  Development of quality indicators for care of chronic kidney disease in the primary care setting using electronic health data: a RAND-modified Delphi method  [published online May 4, 2016].  Clin Exp Nephrol. 2016. doi:10.1007/s10157-016-1274-8PubMedGoogle Scholar
11.
Hayashi  M, Uchida  S, Kawamura  T, Kuwahara  M, Nangaku  M, Iino  Y; PROTECT-CKD Study Group.  Prospective randomized study of the tolerability and efficacy of combination therapy for hypertensive chronic kidney disease: results of the PROTECT-CKD study.  Clin Exp Nephrol. 2015;19(5):925-932.PubMedGoogle ScholarCrossref
12.
James  PA, Oparil  S, Carter  BL,  et al.  2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8).  JAMA. 2014;311(5):507-520.PubMedGoogle ScholarCrossref
13.
Dasgupta  K, Quinn  RR, Zarnke  KB,  et al; Canadian Hypertension Education Program.  The 2014 Canadian Hypertension Education Program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension.  Can J Cardiol. 2014;30(5):485-501.PubMedGoogle ScholarCrossref
14.
Mancia  G, Fagard  R, Narkiewicz  K,  et al.  2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).  Eur Heart J. 2013;34(28):2159-2219.PubMedGoogle ScholarCrossref
15.
Klahr  S, Levey  AS, Beck  GJ,  et al; Modification of Diet in Renal Disease Study Group.  The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease.  N Engl J Med. 1994;330(13):877-884.PubMedGoogle ScholarCrossref
16.
Wright  JT  Jr, Bakris  G, Greene  T,  et al; African American Study of Kidney Disease and Hypertension Study Group.  Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial.  JAMA. 2002;288(19):2421-2431.PubMedGoogle ScholarCrossref
17.
Ruggenenti  P, Perna  A, Loriga  G,  et al; REIN-2 Study Group.  Blood-pressure control for renoprotection in patients with non-diabetic chronic renal disease (REIN-2): multicentre, randomised controlled trial.  Lancet. 2005;365(9463):939-946.PubMedGoogle ScholarCrossref
18.
Ku  E, Gassman  J, Appel  LJ,  et al.  BP control and long-term risk of ESRD and mortality.  J Am Soc Nephrol. 2017;28(2):671-677.PubMedGoogle ScholarCrossref
19.
Lv  J, Ehteshami  P, Sarnak  MJ,  et al.  Effects of intensive blood pressure lowering on the progression of chronic kidney disease: a systematic review and meta-analysis.  CMAJ. 2013;185(11):949-957.PubMedGoogle ScholarCrossref
20.
Upadhyay  A, Earley  A, Haynes  SM, Uhlig  K.  Systematic review: blood pressure target in chronic kidney disease and proteinuria as an effect modifier.  Ann Intern Med. 2011;154(8):541-548.PubMedGoogle ScholarCrossref
21.
Wright  JT  Jr, Williamson  JD, Whelton  PK,  et al; SPRINT Research Group.  A randomized trial of intensive versus standard blood-pressure control.  N Engl J Med. 2015;373(22):2103-2116.PubMedGoogle ScholarCrossref
22.
Higgins  J, Green  S. Cochrane Handbook for Systematic Reviews of Interventions, version 5.1.0. Updated March 2011. The Cochrane Collaboration, 2011. http://handbook.cochrane.org. Accessed July 16, 2016.
23.
Borenstein  M, Hedges  LV, Higgins  JPT, Rothstein  HR.  Introduction to Meta-Analysis. Hoboken, NJ: John Wiley & Sons; 2009.Crossref
24.
Egger  M, Davey Smith  G, Schneider  M, Minder  C.  Bias in meta-analysis detected by a simple, graphical test.  BMJ. 1997;315(7109):629-634.PubMedGoogle ScholarCrossref
25.
Peters  JL, Sutton  AJ, Jones  DR, Abrams  KR, Rushton  L.  Contour-enhanced meta-analysis funnel plots help distinguish publication bias from other causes of asymmetry.  J Clin Epidemiol. 2008;61(10):991-996.PubMedGoogle ScholarCrossref
26.
Ku  E, Glidden  DV, Johansen  KL,  et al.  Association between strict blood pressure control during chronic kidney disease and lower mortality after onset of end-stage renal disease.  Kidney Int. 2015;87(5):1055-1060.PubMedGoogle ScholarCrossref
27.
Appel  LJ, Wright  JT  Jr, Greene  T,  et al; AASK Collaborative Research Group.  Intensive blood-pressure control in hypertensive chronic kidney disease.  N Engl J Med. 2010;363(10):918-929.PubMedGoogle ScholarCrossref
28.
Toto  RD, Mitchell  HC, Smith  RD, Lee  HC, McIntire  D, Pettinger  WA.  “Strict” blood pressure control and progression of renal disease in hypertensive nephrosclerosis.  Kidney Int. 1995;48(3):851-859.PubMedGoogle ScholarCrossref
29.
Schrier  R, McFann  K, Johnson  A,  et al.  Cardiac and renal effects of standard versus rigorous blood pressure control in autosomal-dominant polycystic kidney disease: results of a seven-year prospective randomized study.  J Am Soc Nephrol. 2002;13(7):1733-1739.PubMedGoogle ScholarCrossref
30.
Hayashi  K, Saruta  T, Goto  Y, Ishii  M; JATOS Study Group.  Impact of renal function on cardiovascular events in elderly hypertensive patients treated with efonidipine.  Hypertens Res. 2010;33(11):1211-1220.PubMedGoogle ScholarCrossref
31.
Schrier  RW, Abebe  KZ, Perrone  RD,  et al; HALT-PKD Trial Investigators.  Blood pressure in early autosomal dominant polycystic kidney disease.  N Engl J Med. 2014;371(24):2255-2266.PubMedGoogle ScholarCrossref
32.
Xie  X, Atkins  E, Lv  J,  et al.  Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: updated systematic review and meta-analysis.  Lancet. 2016;387(10017):435-443.PubMedGoogle ScholarCrossref
33.
Sarnak  MJ, Greene  T, Wang  X,  et al.  The effect of a lower target blood pressure on the progression of kidney disease: long-term follow-up of the modification of diet in renal disease study.  Ann Intern Med. 2005;142(5):342-351.PubMedGoogle ScholarCrossref
34.
Wühl  E, Trivelli  A, Picca  S,  et al; ESCAPE Trial Group.  Strict blood-pressure control and progression of renal failure in children.  N Engl J Med. 2009;361(17):1639-1650.PubMedGoogle ScholarCrossref
35.
Becherucci  F, Roperto  RM, Materassi  M, Romagnani  P.  Chronic kidney disease in children.  Clin Kidney J. 2016;9(4):583-591.PubMedGoogle ScholarCrossref
36.
Eckardt  KU, Coresh  J, Devuyst  O,  et al.  Evolving importance of kidney disease: from subspecialty to global health burden.  Lancet. 2013;382(9887):158-169.PubMedGoogle ScholarCrossref
37.
Wetmore  JB, Guo  H, Liu  J, Collins  AJ, Gilbertson  DT.  The incidence, prevalence, and outcomes of glomerulonephritis derived from a large retrospective analysis.  Kidney Int. 2016;90(4):853-860.PubMedGoogle ScholarCrossref
38.
Tarver-Carr  ME, Powe  NR, Eberhardt  MS,  et al.  Excess risk of chronic kidney disease among African-American versus white subjects in the United States: a population-based study of potential explanatory factors.  J Am Soc Nephrol. 2002;13(9):2363-2370.PubMedGoogle ScholarCrossref
39.
Hsu  CY, Lin  F, Vittinghoff  E, Shlipak  MG.  Racial differences in the progression from chronic renal insufficiency to end-stage renal disease in the United States.  J Am Soc Nephrol. 2003;14(11):2902-2907.PubMedGoogle ScholarCrossref
40.
Flack  JM, Neaton  JD, Daniels  B, Esunge  P.  Ethnicity and renal disease: lessons from the Multiple Risk Factor Intervention Trial and the Treatment of Mild Hypertension Study.  Am J Kidney Dis. 1993;21(4)(suppl 1):31-40.PubMedGoogle ScholarCrossref
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