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Systolic blood pressure, low-density lipoprotein cholesterol levels, and adverse kidney outcome: results from KNOW-CKD

Hypertension Research volume 46, pages 1395–1406 (2023)Cite this article

Abstract

It is unknown whether intensive control of blood pressure (BP) and lipids can delay the progression of chronic kidney disease (CKD). This study examined the combined association of strict targets of systolic BP (SBP) and low-density lipoprotein cholesterol (LDL-C) levels with adverse kidney outcomes. In total, 2012 patients from the KoreaN Cohort Study for Outcomes in Patients With CKD (KNOW-CKD) were classified into four groups according to SBP of 120 mmHg and LDL-C of 70 mg/dl: group 1, <120 and <70; group 2, <120 and ≥70; group 3, ≥120 and <70; group 4, ≥120 and ≥70. We constructed time-varying models treating two variables as time-varying exposures. The primary outcome was the progression of CKD, defined as a ≥50% decrease in estimated glomerular filtration rate from the baseline or the onset of kidney failure requiring replacement therapy. The primary outcome events occurred in 27.9%, 26.7%, 40.3%, and 39.1% from groups 1 to 4. In the time-varying model, the hazard ratios (95% confidence intervals) for the primary outcome were 0.48 (0.33–0.69), 0.78 (0.63–0.96), and 0.96 (0.74–1.23) for groups 1 to 3, respectively, compared with group 4. When less stringent cut-offs of SBP of 130 mmHg and LDL-C of 100 mg/dl were used, this graded association was lost, while only SBP was associated with adverse kidney outcomes. In this study, the lower targets of SBP of <120 mmHg and LDL-C < 70 mg/dl were synergistically associated with a lower risk of adverse kidney outcomes.

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References

  1. GBD Chronic Kidney Disease Collaboration. Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2020;395:709–33.

    Article  Google Scholar 

  2. Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. KDIGO 2021 clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int. 2021;99:S1–s87.

    Article  Google Scholar 

  3. Kidney Disease: Improving Global Outcomes (KDIGO). Chapter 1: definition and classification of CKD. Kidney Int Suppl (2011). 2013;3:19–62.

  4. Webster AC, Nagler EV, Morton RL, Masson P. Chronic kidney disease. Lancet. 2017;389:1238–52.

    Article  PubMed  Google Scholar 

  5. Gupta R, Woo K, Yi JA. Epidemiology of end-stage kidney disease. Semin Vasc Surg. 2021;34:71–8.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Hanratty R, Chonchol M, Havranek EP, Powers JD, Dickinson LM, Ho PM, et al. Relationship between blood pressure and incident chronic kidney disease in hypertensive patients. Clin J Am Soc Nephrol. 2011;6:2605–11.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Tsuchida-Nishiwaki M, Uchida HA, Takeuchi H, Nishiwaki N, Maeshima Y, Saito C, et al. Association of blood pressure and renal outcome in patients with chronic kidney disease; a post hoc analysis of FROM-J study. Sci Rep. 2021;11:14990.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Olsen MH, Angell SY, Asma S, Boutouyrie P, Burger D, Chirinos JA, et al. A call to action and a lifecourse strategy to address the global burden of raised blood pressure on current and future generations: the Lancet Commission on hypertension. Lancet. 2016;388:2665–712.

    Article  PubMed  Google Scholar 

  9. Wu CY, Hu HY, Chou YJ, Huang N, Chou YC, Li CP. High blood pressure and all-cause and cardiovascular disease mortalities in community-dwelling older adults. Medicine. 2015;94:e2160.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Wright JT Jr, Williamson JD, Whelton PK, Snyder JK, Sink KM, Rocco MV, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373:2103–16.

    Article  CAS  PubMed  Google Scholar 

  11. Wright JT Jr, Bakris G, Greene T, Agodoa LY, Appel LJ, Charleston J, et al. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. JAMA. 2002;288:2421–31.

    Article  CAS  PubMed  Google Scholar 

  12. Collard D, Brouwer TF, Olde Engberink RHG, Zwinderman AH, Vogt L, van den Born BH. Initial estimated glomerular filtration rate decline and long-term renal function during intensive antihypertensive therapy: a post hoc analysis of the SPRINT and ACCORD-BP randomized controlled trials. Hypertension. 2020;75:1205–12.

    Article  CAS  PubMed  Google Scholar 

  13. Beddhu S, Greene T, Boucher R, Cushman WC, Wei G, Stoddard G, et al. Intensive systolic blood pressure control and incident chronic kidney disease in people with and without diabetes mellitus: secondary analyses of two randomised controlled trials. Lancet Diabetes Endocrinol. 2018;6:555–63.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Baigent C, Landray MJ, Reith C, Emberson J, Wheeler DC, Tomson C, et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet. 2011;377:2181–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Wanner C, Krane V, März W, Olschewski M, Mann JF, Ruf G, et al. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med. 2005;353:238–48.

    Article  CAS  PubMed  Google Scholar 

  16. Fellström BC, Jardine AG, Schmieder RE, Holdaas H, Bannister K, Beutler J, et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med. 2009;360:1395–407.

    Article  PubMed  Google Scholar 

  17. Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372:2387–97.

    Article  CAS  PubMed  Google Scholar 

  18. Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376:1713–22.

    Article  CAS  PubMed  Google Scholar 

  19. Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R, et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018;379:2097–107.

    Article  CAS  PubMed  Google Scholar 

  20. Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139:e1082–143.

    PubMed  Google Scholar 

  21. Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41:111–88.

    Article  PubMed  Google Scholar 

  22. Lee JY, Park JT, Joo YS, Lee C, Yun HR, Yoo TH, et al. Association of blood pressure with the progression of CKD: findings from KNOW-CKD study. Am J Kidney Dis. 2021;78:236–45.

    Article  PubMed  Google Scholar 

  23. Lee C, Park JT, Chang TI, Kang EW, Nam KH, Joo YS, et al. Low-density lipoprotein cholesterol levels and adverse clinical outcomes in chronic kidney disease: results from the KNOW-CKD. Nutr Metab Cardiovasc Dis. 2022;32:410–9.

    Article  CAS  PubMed  Google Scholar 

  24. Chen SC, Hung CC, Kuo MC, Lee JJ, Chiu YW, Chang JM, et al. Association of dyslipidemia with renal outcomes in chronic kidney disease. PLoS ONE. 2013;8:e55643.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Beddhu S, Shen J, Cheung AK, Kimmel PL, Chertow GM, Wei G, et al. Implications of early decline in eGFR due to intensive BP control for cardiovascular outcomes in SPRINT. J Am Soc Nephrol. 2019;30:1523–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Rocco MV, Sink KM, Lovato LC, Wolfgram DF, Wiegmann TB, Wall BM, et al. Effects of intensive blood pressure treatment on acute kidney injury events in the systolic blood pressure intervention trial (SPRINT). Am J Kidney Dis. 2018;71:352–61.

    Article  PubMed  Google Scholar 

  27. Oh KH, Park SK, Park HC, Chin HJ, Chae DW, Choi KH, et al. KNOW-CKD (KoreaN cohort study for Outcome in patients With Chronic Kidney Disease): design and methods. BMC Nephrol. 2014;15:80.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Pickering TG, Hall JE, Appel LJ, Falkner BE, Graves J, Hill MN, et al. Recommendations for blood pressure measurement in humans and experimental animals: part 1: blood pressure measurement in humans: a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Circulation. 2005;111:697–716.

    Article  PubMed  Google Scholar 

  29. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–12.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Cheung AK, Chang TI, Cushman WC, Furth SL, Hou FF, Ix JH, et al. Executive summary of the KDIGO 2021 clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int. 2021;99:559–69.

    Article  PubMed  Google Scholar 

  31. Tonelli M, Wanner C, Cass A, Garg A, Holdaas H, Jardine A, et al. Kidney disease: improving global outcomes (KDIGO) lipid work group. KDIGO clinical practice guideline for lipid management in chronic kidney disease. Kidney Int Suppl. 2013;3:1–315.

    Google Scholar 

  32. Jellinger PS, Handelsman Y, Rosenblit PD, Bloomgarden ZT, Fonseca VA, Garber AJ, et al. American Association of Clinical Endocrinologists and American College of Endocrinology guidelines for management of dyslipidemia and prevention of cardiovascular disease. Endocr Pr. 2017;23:1–87.

    Article  Google Scholar 

  33. Zhang Z, Reinikainen J, Adeleke KA, Pieterse ME, Groothuis-Oudshoorn CGM. Time-varying covariates and coefficients in Cox regression models. Ann Transl Med. 2018;6:121.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Xie D, Yang W, Jepson C, Roy J, Hsu JY, Shou H, et al. Statistical methods for modeling time-updated exposures in cohort studies of chronic kidney disease. Clin J Am Soc Nephrol. 2017;12:1892–9.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Beddhu S, Rocco MV, Toto R, Craven TE, Greene T, Bhatt U, et al. Effects of intensive systolic blood pressure control on kidney and cardiovascular outcomes in persons without kidney disease: a secondary analysis of a randomized trial. Ann Intern Med. 2017;167:375–83.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Cushman WC, Evans GW, Byington RP, Goff DC Jr, Grimm RH Jr, Cutler JA, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010;362:1575–85.

    Article  PubMed  Google Scholar 

  37. Peterson JC, Adler S, Burkart JM, Greene T, Hebert LA, Hunsicker LG, et al. Blood pressure control, proteinuria, and the progression of renal disease. The Modification of Diet in Renal Disease Study. Ann Intern Med. 1995;123:754–62.

    Article  CAS  PubMed  Google Scholar 

  38. Berl T, Hunsicker LG, Lewis JB, Pfeffer MA, Porush JG, Rouleau JL, et al. Impact of achieved blood pressure on cardiovascular outcomes in the Irbesartan Diabetic Nephropathy Trial. J Am Soc Nephrol. 2005;16:2170–9.

    Article  CAS  PubMed  Google Scholar 

  39. Kovesdy CP, Lu JL, Molnar MZ, Ma JZ, Canada RB, Streja E, et al. Observational modeling of strict vs conventional blood pressure control in patients with chronic kidney disease. JAMA Intern Med. 2014;174:1442–9.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Navaneethan SD, Schold JD, Jolly SE, Arrigain S, Blum MF, Winkelmayer WC, et al. Blood pressure parameters are associated with all-cause and cause-specific mortality in chronic kidney disease. Kidney Int. 2017;92:1272–81.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Lee JY, Park JT, Joo YS, Lee C, Yun HR, Chang TI, et al. Association of blood pressure with cardiovascular outcome and mortality: results from the KNOW-CKD study. Nephrol Dial Transplant. 2021. https://doi.org/10.1093/ndt/gfab257.

  42. Wanner C, Tonelli M. KDIGO clinical practice guideline for lipid management in CKD: summary of recommendation statements and clinical approach to the patient. Kidney Int. 2014;85:1303–9.

    Article  CAS  PubMed  Google Scholar 

  43. Sandhu S, Wiebe N, Fried LF, Tonelli M. Statins for improving renal outcomes: a meta-analysis. J Am Soc Nephrol. 2006;17:2006–16.

    Article  CAS  PubMed  Google Scholar 

  44. Tonelli M, Isles C, Craven T, Tonkin A, Pfeffer MA, Shepherd J, et al. Effect of pravastatin on rate of kidney function loss in people with or at risk for coronary disease. Circulation. 2005;112:171–8.

    Article  CAS  PubMed  Google Scholar 

  45. Esmeijer K, Dekkers OM, de Fijter JW, Dekker FW, Hoogeveen EK. Effect of different types of statins on kidney function decline and proteinuria: a network meta-analysis. Sci Rep. 2019;9:16632.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Kamanna VS, Roh DD, Kirschenbaum MA. Atherogenic lipoproteins: mediators of glomerular injury. Am J Nephrol. 1993;13:1–5.

    Article  CAS  PubMed  Google Scholar 

  47. Kasiske BL. Relationship between vascular disease and age-associated changes in the human kidney. Kidney Int. 1987;31:1153–9.

    Article  CAS  PubMed  Google Scholar 

  48. Diamond JR, Karnovsky MJ. Focal and segmental glomerulosclerosis: analogies to atherosclerosis. Kidney Int. 1988;33:917–24.

    Article  CAS  PubMed  Google Scholar 

  49. Abrass CK. Cellular lipid metabolism and the role of lipids in progressive renal disease. Am J Nephrol. 2004;24:46–53.

    Article  CAS  PubMed  Google Scholar 

  50. Kalantar-Zadeh K, Jafar TH, Nitsch D, Neuen BL, Perkovic V. Chronic kidney disease. Lancet. 2021;398:786–802.

    Article  CAS  PubMed  Google Scholar 

  51. Heerspink HJ, Perkins BA, Fitchett DH, Husain M, Cherney DZ. Sodium glucose cotransporter 2 inhibitors in the treatment of diabetes mellitus: cardiovascular and kidney effects, potential mechanisms, and clinical applications. Circulation. 2016;134:752–72.

    Article  CAS  PubMed  Google Scholar 

  52. Heerspink HJL, Kosiborod M, Inzucchi SE, Cherney DZI. Renoprotective effects of sodium-glucose cotransporter-2 inhibitors. Kidney Int. 2018;94:26–39.

    Article  CAS  PubMed  Google Scholar 

  53. Ueki K, Sasako T, Okazaki Y, Miyake K, Nangaku M, Ohashi Y, et al. Multifactorial intervention has a significant effect on diabetic kidney disease in patients with type 2 diabetes. Kidney Int. 2021;99:256–66.

    Article  CAS  PubMed  Google Scholar 

  54. Yusuf S, Lonn E, Pais P, Bosch J, López-Jaramillo P, Zhu J, et al. Blood-pressure and cholesterol lowering in persons without cardiovascular disease. N Engl J Med. 2016;374:2032–43.

    Article  CAS  PubMed  Google Scholar 

  55. Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13–115.

    CAS  PubMed  Google Scholar 

  56. Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension. J Hypertens. 2018;36:1953–2041.

    Article  CAS  PubMed  Google Scholar 

  57. Lawes CM, Bennett DA, Parag V, Woodward M, Whitlock G, Lam TH, et al. Blood pressure indices and cardiovascular disease in the Asia Pacific region: a pooled analysis. Hypertension. 2003;42:69–75.

    Article  PubMed  Google Scholar 

  58. Arima H, Murakami Y, Lam TH, Kim HC, Ueshima H, Woo J, et al. Effects of prehypertension and hypertension subtype on cardiovascular disease in the Asia-Pacific Region. Hypertension. 2012;59:1118–23.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank the clinical research coordinators of each participating center for their dedication during patient recruitment and data acquisition.

Funding

This work was supported by the Research Program funded by the Korea Disease Control and Prevention Agency (grants 2011E3300300, 2012E3301100, 2013E3301600, 2013E3301601, 2013E3301602, 2016E3300200, 2016E3300201, 2016E3300202, 2019E320100, 2019E320101, 2019E320102, 2022-11-007).

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Authors and Affiliations

  1. Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, Republic of Korea

    Kyung Won Kim, Hee Byung Koh, Hyung Woo Kim, Jung Tak Park, Tae-Hyun Yoo, Shin-Wook Kang & Seung Hyeok Han

  2. Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea

    Kook-Hwan Oh

  3. Division of Nephrology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

    Young Youl Hyun

  4. Division of Nephrology, Department of Internal Medicine, Gachon University of Gil Medical Center, Incheon, Republic of Korea

    Ji Yong Jung

  5. Department of Internal Medicine, Eulji Medical Center, Eulji University, Seoul, Republic of Korea

    Su Ah Sung

  6. Medical Research Collaborating Center, Seoul National University Hospital, Seoul, Republic of Korea

    Jayoun Kim

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Kim, K.W., Koh, H.B., Kim, H.W. et al. Systolic blood pressure, low-density lipoprotein cholesterol levels, and adverse kidney outcome: results from KNOW-CKD. Hypertens Res 46, 1395–1406 (2023). https://doi.org/10.1038/s41440-023-01230-0

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