Skip to main content

Advertisement

SpringerLink
Log in

Emerging Preventive Strategies in Chronic Kidney Disease: Recent Evidence and Gaps in Knowledge

  • Review
  • Published:
Current Atherosclerosis Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Chronic kidney disease (CKD) is increasingly prevalent worldwide and is associated with increased cardiovascular risk. New therapeutic options to slow CKD progression and reduce cardiovascular morbidity and mortality have recently emerged. This review highlights recent evidence and gaps in knowledge in emerging CKD preventive strategies.

Recent Findings

EMPA-Kidney trial found that empagliflozin, a sodium-glucose co-transporter 2 inhibitor (SGLT2i) led to 28% lower risk of progression of kidney disease or death from cardiovascular causes, compared to placebo. This reinforced the previous findings from DAPA-CKD and CREDENCE trials and led to inclusion of SGLT2i as the cornerstone of CKD preventive therapy in both diabetic and non-diabetic CKD. Finerenone, a selective nonsteroidal mineralocorticoid receptor antagonist, slowed diabetic kidney disease progression by 23% compared to placebo in a pool analysis of FIDELIO-DKD and FIGARO-DKD trials. Non-pharmacological interventions, including low protein diet, and early CKD detection and risk stratification strategies based on novel biomarkers have also gained momentum. Ongoing efforts to explore the wealth of molecular mechanisms in CKD, added to integrative omics modeling are well posed to lead to novel therapeutic targets in kidney care.

Summary

While breakthrough pharmacological interventions continue to improve outcomes in CKD, the heterogeneity of kidney diseases warrants additional investigation. Further research into specific kidney disease mechanisms will facilitate the identification of patient populations most likely to benefit from targeted interventions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. GBD. GBD 2019 diseases and injuries. Collaborators global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the global burden of disease study 2019. Lancet. 2020;396(10258):1204–22.

    Article  Google Scholar 

  2. Drawz PE, Beddhu S, Bignall ONR, 2nd, Cohen JB, Flynn JT, Ku E, Rahman M, Thomas G, Weir MR, Whelton PK (2022) KDOQI US commentary on the 2021 KDIGO clinical practice guideline for the management of blood pressure in CKD. Am J Kidney Dis. 2022;79(3):311–327. This commentary highlights the current controversies on the topic of blood pressure targets in CKD and highlights the uniform agreement accross all hypertension societies related to accurate blood pressure measurement and out of office assessment.

  3. United States Renal Data System. 2022 USRDS annual data report: epidemiology of kidney disease in the United States. Book 2022 USRDS annual data report: epidemiology of kidney disease in the United States.

  4. Pun PH, Al-Khatib SM, Han JY, Edwards R, Bardy GH, Bigger JT, Buxton AE, Moss AJ, Lee KL, Steinman R, Dorian P, Hallstrom A, Cappato R, Kadish AH, Kudenchuk PJ, Mark DB, Hess PL, Inoue LY, Sanders GD. Implantable cardioverter-defibrillators for primary prevention of sudden cardiac death in CKD: a meta-analysis of patient-level data from 3 randomized trials. Am J Kidney Dis. 2014;64(1):32–9.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Bansal N, Szpiro A, Reynolds K, Smith DH, Magid DJ, Gurwitz JH, Masoudi F, Greenlee RT, Tabada GH, Sung SH, Dighe A, Go AS. Long-term outcomes associated with implantable cardioverter defibrillator in adults with chronic kidney disease. JAMA Intern Med. 2018;178(3):390–8.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Matsushita K, Ballew SH, Wang AY, Kalyesubula R, Schaeffner E, Agarwal R. Epidemiology and risk of cardiovascular disease in populations with chronic kidney disease. Nat Rev Nephrol. 2022;18(11):696–707.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  8. Cheung AK, Rahman M, Reboussin DM, Craven TE, Greene T, Kimmel PL, Cushman WC, Hawfield AT, Johnson KC, Lewis CE, Oparil S, Rocco MV, Sink KM, Whelton PK, Wright JT Jr, Basile J, Beddhu S, Bhatt U, Chang TI, Chertow GM, Chonchol M, Freedman BI, Haley W, Ix JH, Katz LA, Killeen AA, Papademetriou V, Ricardo AC, Servilla K, Wall B, Wolfgram D, Yee J, Group, S.R. Effects of intensive BP control in CKD. J Am Soc Nephrol. 2017;28(9):2812–23.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Group SR, Lewis CE, Fine LJ, Beddhu S, Cheung AK, Cushman WC, Cutler JA, Evans GW, Johnson KC, Kitzman DW, Oparil S, Rahman M, Reboussin DM, Rocco MV, Sink KM, Snyder JK, Whelton PK, Williamson JD, Wright JT, Jr, Ambrosius WT (2021) Final report of a trial of intensive versus standard blood-pressure control. N Engl J Med 384(20):1921–1930.

  10. Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, DePalma SM, Gidding S, Jamerson KA, Jones DW, MacLaughlin EJ, Muntner P, Ovbiagele B, Smith SC Jr, Spencer CC, Stafford RS, Taler SJ, Thomas RJ, Williams KA Sr, Williamson JD, Wright JT Jr. J Am Soc Hypertens. 2018;12(8):579.e571-579.e573.

    Article  Google Scholar 

  11. Beddhu S, Chertow GM, Greene T, Whelton PK, Ambrosius WT, Cheung AK, Cutler J, Fine L, Boucher R, Wei G, Zhang C, Kramer H, Bress AP, Kimmel PL, Oparil S, Lewis CE, Rahman M, Cushman WC. Effects of intensive systolic blood pressure lowering on cardiovascular events and mortality in patients with type 2 diabetes mellitus on standard glycemic control and in those without diabetes mellitus: reconciling results from ACCORD BP and SPRINT. J Am Heart Assoc. 2018;7(18):e009326.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Dasgupta I, Zoccali C. Is the KDIGO systolic blood pressure target <120 mmHg for chronic kidney disease appropriate in routine clinical practice? Hypertension. 2022;79(1):4–11.

    Article  CAS  PubMed  Google Scholar 

  13. Drawz PE, Agarwal A, Dwyer JP, Horwitz E, Lash J, Lenoir K, McWilliams A, Oparil S, Rahbari-Oskoui F, Rahman M, Parkulo MA, Pemu P, Raj DS, Rocco M, Soman S, Thomas G, Tuot DS, Whelton PK, Pajewski NM. Concordance between blood pressure in the systolic blood pressure intervention trial and in routine clinical practice. JAMA Intern Med. 2020;180(12):1655–63.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Krist AH, Davidson KW, Mangione CM, Cabana M, Caughey AB, Davis EM, Donahue KE, Doubeni CA, Kubik M, Li L, Ogedegbe G, Pbert L, Silverstein M, Stevermer J, Tseng CW, Wong JB. Screening for hypertension in adults: US preventive services task force reaffirmation recommendation statement. JAMA. 2021;325(16):1650–6.

    Article  PubMed  Google Scholar 

  15. American Diabetes Association Professional Practice, C (2022) ‘3. Prevention or delay of type 2 diabetes and associated comorbidities: standards of medical care in diabetes-2022. Diabetes Care 45(Suppl 1):S39–S45.

  16. American Diabetes Association Professional Practice, C (2022) 6. Glycemic targets: standards of medical care in diabetes-2022. Diabetes Care 45(Suppl 1):S83–S96.

  17. de Boer IH, Khunti K, Sadusky T, Tuttle KR, Neumiller JJ, Rhee CM, Rosas SE, Rossing P, Bakris G. Diabetes management in chronic kidney disease: a consensus report by the American diabetes association (ADA) and kidney disease: Improving global outcomes (KDIGO). Diabetes Care. 2022;45(12):3075–90.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Kelly JT, Su G, Zhang L, Qin X, Marshall S, Gonzalez-Ortiz A, Clase CM, Campbell KL, Xu H, Carrero JJ. Modifiable lifestyle factors for primary prevention of CKD: A systematic review and meta-analysis. J Am Soc Nephrol. 2021;32(1):239–53.

    Article  CAS  PubMed  Google Scholar 

  19. Perez-Dominguez B, Casana-Granell J, Garcia-Maset R, Garcia-Testal A, Melendez-Oliva E, Segura-Orti E. Effects of exercise programs on physical function and activity levels in patients undergoing hemodialysis: a randomized controlled trial. Eur J Phys Rehabil Med. 2021;57(6):994–1001.

    Article  PubMed  Google Scholar 

  20. Sheshadri A, Kittiskulnam P, Lai JC, Johansen KL. Effect of a pedometer-based walking intervention on body composition in patients with ESRD: a randomized controlled trial. BMC Nephrol. 2020;21(1):100.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Lyden K, Boucher R, Wei G, Zhou N, Christensen J, Chertow GM, Greene T, Beddhu S. Targeting sedentary behavior in CKD: A pilot and feasibility randomized controlled trial. Clin J Am Soc Nephrol. 2021;16(5):717–26.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Beetham KS, Krishnasamy R, Stanton T, Sacre JW, Douglas B, Isbel NM, Coombes JS, Howden EJ. Effect of a 3-year lifestyle intervention in patients with chronic kidney disease: A randomized clinical trial. J Am Soc Nephrol. 2022;33(2):431–41.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Bramlage P, Lanzinger S, Tittel SR, Hess E, Fahrner S, Heyer CHJ, Friebe M, Buschmann I, Danne T, Seufert J, Holl RW. Guidelines adherence in the prevention and management of chronic kidney disease in patients with diabetes mellitus on the background of recent European recommendations - a registry-based analysis. BMC Nephrol. 2021;22(1):184.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Tangri N, Grams ME, Levey AS, Coresh J, Appel LJ, Astor BC, Chodick G, Collins AJ, Djurdjev O, Elley CR, Evans M, Garg AX, Hallan SI, Inker LA, Ito S, Jee SH, Kovesdy CP, Kronenberg F, Heerspink HJ, Marks A, Nadkarni GN, Navaneethan SD, Nelson RG, Titze S, Sarnak MJ, Stengel B, Woodward M, Iseki K, Consortium, C.K.D.P. Multinational assessment of accuracy of equations for predicting risk of kidney failure: a meta-analysis. JAMA. 2016;315(2):164–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Coca SG, Nadkarni GN, Huang Y, Moledina DG, Rao V, Zhang J, Ferket B, Crowley ST, Fried LF, Parikh CR. Plasma biomarkers and kidney function decline in early and established diabetic kidney disease. J Am Soc Nephrol. 2017;28(9):2786–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJL, Charytan DM, Edwards R, Agarwal R, Bakris G, Bull S, Cannon CP, Capuano G, Chu PL, de Zeeuw D, Greene T, Levin A, Pollock C, Wheeler DC, Yavin Y, Zhang H, Zinman B, Meininger G, Brenner BM, Mahaffey KW, Investigators CT. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019;380(24):2295–306.

    Article  CAS  PubMed  Google Scholar 

  27. Heerspink HJL, Stefansson BV, Correa-Rotter R, Chertow GM, Greene T, Hou FF, Mann JFE, McMurray JJV, Lindberg M, Rossing P, Sjostrom CD, Toto RD, Langkilde AM, Wheeler DC, Committees, D.-C.T., and Investigators. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436–46.

    Article  CAS  PubMed  Google Scholar 

  28. The E-KCG, Herrington WG, Staplin N, Wanner C, Green JB, Hauske SJ, Emberson JR, Preiss D, Judge P, Mayne KJ, Ng SYA, Sammons E, Zhu D, Hill M, Stevens W, Wallendszus K, Brenner S, Cheung AK, Liu ZH, Li J, Hooi LS, Liu W, Kadowaki T, Nangaku M, Levin A, Cherney D, Maggioni AP, Pontremoli R, Deo R, Goto S, Rossello X, Tuttle KR, Steubl D, Petrini M, Massey D, Eilbracht J, Brueckmann M, Landray MJ, Baigent C, Haynes R. Empagliflozin in patients with chronic kidney disease. N Engl J Med. 2023;388(2):117–27.

    Article  Google Scholar 

  29. Heerspink HJL, Karasik A, Thuresson M, Melzer-Cohen C, Chodick G, Khunti K, Wilding JPH, Garcia Rodriguez LA, Cea-Soriano L, Kohsaka S, Nicolucci A, Lucisano G, Lin FJ, Wang CY, Wittbrodt E, Fenici P, Kosiborod M. Kidney outcomes associated with use of SGLT2 inhibitors in real-world clinical practice (CVD-REAL 3): a multinational observational cohort study. Lancet Diabetes Endocrinol. 2020;8(1):27–35.

    Article  CAS  PubMed  Google Scholar 

  30. Meraz-Munoz AY, Weinstein J, Wald R. eGFR decline after SGLT2 inhibitor initiation: the tortoise and the hare reimagined. Kidney360. 2021;2(6):1042–1047.

  31. DeFronzo RA, Reeves WB, Awad AS. Pathophysiology of diabetic kidney disease: impact of SGLT2 inhibitors. Nat Rev Nephrol. 2021;17(5):319–334. This is an excellent review on the role of SGLT312i in diabetic kidney disease.

  32. Davies MJ, Aroda VR, Collins BS, Gabbay RA, Green J, Maruthur NM, Rosas SE, Del Prato S, Mathieu C, Mingrone G, Rossing P, Tankova T, Tsapas A, Buse JB. Management of hyperglycemia in type 2 diabetes, 2022. A consensus report by the American diabetes association (ADA) and the European association for the study of diabetes (EASD). Diabetes Care. 2022;45(11):2753–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Marx N, Federici M, Schutt K, Muller-Wieland D, Ajjan RA, Antunes MJ, Christodorescu RM, Crawford C, Di Angelantonio E, Eliasson B, Espinola-Klein C, Fauchier L, Halle M, Herrington WG, Kautzky-Willer A, Lambrinou E, Lesiak M, Lettino M, McGuire DK, Mullens W, Rocca B, Sattar N, Group, E.S.C.S.D. 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. Eur Heart J. 2023;44:4043–140.

    Article  PubMed  Google Scholar 

  34. Heerspink HJL, Cherney DZI. Clinical Implications of an Acute Dip in eGFR after SGLT2 Inhibitor Initiation. Clin J Am Soc Nephrol. 2021;16(8):1278–80.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Cherney DZI, Cosentino F, Dagogo-Jack S, McGuire DK, Pratley R, Frederich R, Maldonado M, Liu CC, Liu J, Pong A, Cannon CP, Investigators VC. Ertugliflozin and slope of chronic eGFR: prespecified analyses from the randomized VERTIS CV trial. Clin J Am Soc Nephrol. 2021;16(9):1345–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Neuen BL, Oshima M, Perkovic V, Agarwal R, Arnott C, Bakris G, Cannon CP, Charytan DM, Edwards R, Gorriz JL, Jardine MJ, Levin A, Neal B, De Nicola L, Pollock C, Rosenthal N, Wheeler DC, Mahaffey KW, Heerspink HJL. Effects of canagliflozin on serum potassium in people with diabetes and chronic kidney disease: the CREDENCE trial. Eur Heart J. 2021;42(48):4891–901.

    Article  CAS  PubMed  Google Scholar 

  37. Krishnan A, Shankar M, Lerma EV, Wiegley N, GlomCon Editorial, T. Sodium glucose cotransporter 2 (SGLT2) inhibitors and CKD: are you a #Flozinator? Kidney Med. 2023;5(4):100608.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Blau JE, Bauman V, Conway EM, Piaggi P, Walter MF, Wright EC, Bernstein S, Courville AB, Collins MT, Rother KI, Taylor SI. Canagliflozin triggers the FGF23/1,25-dihydroxyvitamin D/PTH axis in healthy volunteers in a randomized crossover study. JCI Insight. 2018;3(8):e99123.

  39. Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, Shaw W, Law G, Desai M, Matthews DR, Group, C.P.C. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377(7):644–57.

    Article  CAS  PubMed  Google Scholar 

  40. Zhou Z, Jardine M, Perkovic V, Matthews DR, Mahaffey KW, de Zeeuw D, Fulcher G, Desai M, Oh R, Simpson R, Watts NB, Neal B. Canagliflozin and fracture risk in individuals with type 2 diabetes: results from the CANVAS program. Diabetologia. 2019;62(10):1854–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Cowan A, Jeyakumar N, Kang Y, Dixon SN, Garg AX, Naylor K, Weir MA, Clemens KK. Fracture risk of sodium-glucose cotransporter-2 inhibitors in chronic kidney disease. Clin J Am Soc Nephrol. 2022;17(6):835–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Silverii GA, Dicembrini I, Monami M, Mannucci E. Fournier’s gangrene and sodium-glucose co-transporter-2 inhibitors: A meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2020;22(2):272–5.

    Article  CAS  PubMed  Google Scholar 

  43. Green JB, Mottl AK, Bakris G, Heerspink HJL, Mann JFE, McGill JB, Nangaku M, Rossing P, Scott C, Gay A, Agarwal R. Design of the combination effect of finerenone and empagliflozin in participants with chronic kidney disease and type 2 diabetes using a UACR endpoint study (CONFIDENCE). Nephrol Dial Transplant. 2023;38(4):894–903.

    Article  CAS  PubMed  Google Scholar 

  44. Heerspink HJL, Vart P, Jongs N, Neuen BL, Bakris G, Claggett B, Vaduganathan M, McCausland F, Docherty KF, Jhund PS, Solomon SD, Perkovic V, McMurray JJV. Estimated lifetime benefit of novel pharmacological therapies in patients with type 2 diabetes and chronic kidney disease: a joint analysis of randomized controlled clinical trials. Diabetes Obes Metab. 2023;25:3327–36.

    Article  CAS  PubMed  Google Scholar 

  45. Bhatt DL, Szarek M, Pitt B, Cannon CP, Leiter LA, McGuire DK, Lewis JB, Riddle MC, Inzucchi SE, Kosiborod MN, Cherney DZI, Dwyer JP, Scirica BM, Bailey CJ, Diaz R, Ray KK, Udell JA, Lopes RD, Lapuerta P, Steg PG, Investigators S. Sotagliflozin in patients with diabetes and chronic kidney disease. N Engl J Med. 2021;384(2):129–39.

    Article  CAS  PubMed  Google Scholar 

  46. Muskiet MHA, Tonneijck L, Smits MM, van Baar MJB, Kramer MHH, Hoorn EJ, Joles JA, van Raalte DH. GLP-1 and the kidney: from physiology to pharmacology and outcomes in diabetes. Nat Rev Nephrol. 2017;13(10):605–28.

    Article  CAS  PubMed  Google Scholar 

  47. Mann JFE, Muskiet MHA. Incretin-based drugs and the kidney in type 2 diabetes: choosing between DPP-4 inhibitors and GLP-1 receptor agonists. Kidney Int. 2021;99(2):314–8.

    Article  CAS  PubMed  Google Scholar 

  48. Mann JFE, Orsted DD, Buse JB. Liraglutide and renal outcomes in type 2 diabetes. N Engl J Med. 2017;377(22):2197–8.

    PubMed  Google Scholar 

  49. Gerstein HC, Colhoun HM, Dagenais GR, Diaz R, Lakshmanan M, Pais P, Probstfield J, Botros FT, Riddle MC, Ryden L, Xavier D, Atisso CM, Dyal L, Hall S, Rao-Melacini P, Wong G, Avezum A, Basile J, Chung N, Conget I, Cushman WC, Franek E, Hancu N, Hanefeld M, Holt S, Jansky P, Keltai M, Lanas F, Leiter LA, Lopez-Jaramillo P, Cardona Munoz EG, Pirags V, Pogosova N, Raubenheimer PJ, Shaw JE, Sheu WH, Temelkova-Kurktschiev T, Investigators R. Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial. Lancet. 2019;394(10193):131–8.

    Article  CAS  PubMed  Google Scholar 

  50. Marso SP, Holst AG, Vilsboll T. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2017;376(9):891–2.

    PubMed  Google Scholar 

  51. Kristensen SL, Rorth R, Jhund PS, Docherty KF, Sattar N, Preiss D, Kober L, Petrie MC, McMurray JJV. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinol. 2019;7(10):776–85.

    Article  CAS  PubMed  Google Scholar 

  52. Tuttle KR, Lakshmanan MC, Rayner B, Busch RS, Zimmermann AG, Woodward DB, Botros FT. Dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease (AWARD-7): a multicentre, open-label, randomised trial. Lancet Diabetes Endocrinol. 2018;6(8):605–17.

    Article  CAS  PubMed  Google Scholar 

  53. Rosenstock J, Perkovic V, Johansen OE, Cooper ME, Kahn SE, Marx N, Alexander JH, Pencina M, Toto RD, Wanner C, Zinman B, Woerle HJ, Baanstra D, Pfarr E, Schnaidt S, Meinicke T, George JT, von Eynatten M, McGuire DK, Investigators C. Effect of linagliptin vs placebo on major cardiovascular events in adults with type 2 diabetes and high cardiovascular and renal risk: the CARMELINA randomized clinical trial. JAMA. 2019;321(1):69–79.

    Article  CAS  PubMed  Google Scholar 

  54. Rossing P, Baeres FMM, Bakris G, Bosch-Traberg H, Gislum M, Gough SCL, Idorn T, Lawson J, Mahaffey KW, Mann JFE, Mersebach H, Perkovic V, Tuttle K, Pratley R. The rationale, design and baseline data of FLOW, a kidney outcomes trial with once-weekly semaglutide in people with type 2 diabetes and chronic kidney disease. Nephrol Dial Transplant. 2023;38(9):2041–51.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Briet M, Schiffrin EL. Aldosterone: effects on the kidney and cardiovascular system. Nat Rev Nephrol. 2010;6(5):261–73.

    Article  CAS  PubMed  Google Scholar 

  56. Verma A, Vaidya A, Subudhi S, Waikar SS. Aldosterone in chronic kidney disease and renal outcomes. Eur Heart J. 2022;43(38):3781–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Chung EY, Ruospo M, Natale P, Bolignano D, Navaneethan SD, Palmer SC, Strippoli GF. Aldosterone antagonists in addition to renin angiotensin system antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2020;10(10):CD007004.

    PubMed  Google Scholar 

  58. Georgianos PI, Agarwal R. The nonsteroidal mineralocorticoid-receptor-antagonist finerenone in cardiorenal medicine: a state-of-the-art review of the literature. Am J Hypertens. 2023;36(3):135–143. Excellent, exhaustive and up-to-date review on the role of Finerenone in improving kidney and cardiac outcomes.

  59. Pitt B, Kober L, Ponikowski P, Gheorghiade M, Filippatos G, Krum H, Nowack C, Kolkhof P, Kim SY, Zannad F. Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94–8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: a randomized, double-blind trial. Eur Heart J. 2013;34(31):2453–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Bakris GL, Agarwal R, Chan JC, Cooper ME, Gansevoort RT, Haller H, Remuzzi G, Rossing P, Schmieder RE, Nowack C, Kolkhof P, Joseph A, Pieper A, Kimmeskamp-Kirschbaum N, Ruilope LM, Mineralocorticoid Receptor Antagonist Tolerability Study-Diabetic Nephropathy Study, G. Effect of finerenone on albuminuria in patients with diabetic nephropathy: a randomized clinical trial. Jama. 2015;314(9):884–94.

    Article  CAS  PubMed  Google Scholar 

  61. Filippatos G, Anker SD, Bohm M, Gheorghiade M, Kober L, Krum H, Maggioni AP, Ponikowski P, Voors AA, Zannad F, Kim SY, Nowack C, Palombo G, Kolkhof P, Kimmeskamp-Kirschbaum N, Pieper A, Pitt B. A randomized controlled study of finerenone vs. eplerenone in patients with worsening chronic heart failure and diabetes mellitus and/or chronic kidney disease. Eur Heart J. 2016;37(27):2105–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Agarwal R, Kolkhof P, Bakris G, Bauersachs J, Haller H, Wada T, Zannad F. Steroidal and non-steroidal mineralocorticoid receptor antagonists in cardiorenal medicine. Eur Heart J. 2021;42(2):152–61.

    Article  CAS  PubMed  Google Scholar 

  63. Pitt B, Filippatos G, Agarwal R, Anker SD, Bakris GL, Rossing P, Joseph A, Kolkhof P, Nowack C, Schloemer P, Ruilope LM, Investigators F-D. Cardiovascular events with finerenone in kidney disease and type 2 diabetes. N Engl J Med. 2021;385(24):2252–63.

    Article  CAS  PubMed  Google Scholar 

  64. Bakris GL, Agarwal R, Anker SD, Pitt B, Ruilope LM, Rossing P, Kolkhof P, Nowack C, Schloemer P, Joseph A, Filippatos G, Investigators F-D. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med. 2020;383(23):2219–29.

    Article  CAS  PubMed  Google Scholar 

  65. Ruilope LM, Pitt B, Anker SD, Rossing P, Kovesdy CP, Pecoits-Filho R, Pergola P, Joseph A, Lage A, Mentenich N, Scheerer MF, Bakris GL. Kidney outcomes with finerenone: an analysis from the FIGARO-DKD study. Nephrol Dial Transplant. 2023;38(2):372–83.

    Article  CAS  PubMed  Google Scholar 

  66. Rossing P, Anker SD, Filippatos G, Pitt B, Ruilope LM, Birkenfeld AL, McGill JB, Rosas SE, Joseph A, Gebel M, Roberts L, Scheerer MF, Bakris GL, Agarwal R, Fidelio DKD, Investigators F-D. Finerenone in patients with chronic kidney disease and type 2 diabetes by sodium-glucose cotransporter 2 inhibitor treatment: the FIDELITY analysis. Diabetes Care. 2022;45(12):2991–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Moore LW, Byham-Gray LD, Scott Parrott J, Rigassio-Radler D, Mandayam S, Jones SL, Mitch WE, Osama Gaber A. The mean dietary protein intake at different stages of chronic kidney disease is higher than current guidelines. Kidney Int. 2013;83(4):724–32.

    Article  CAS  PubMed  Google Scholar 

  68. Addis T, Lew W. Diet and death in acute uremia. J Clin Invest. 1939;18(6):773–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Hostetter TH, Meyer TW, Rennke HG, Brenner BM. Chronic effects of dietary protein in the rat with intact and reduced renal mass. Kidney Int. 1986;30(4):509–17.

    Article  CAS  PubMed  Google Scholar 

  70. Ko GJ, Rhee CM, Kalantar-Zadeh K, Joshi S. The effects of high-protein diets on kidney health and longevity. J Am Soc Nephrol. 2020;31(8):1667–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Garneata L, Stancu A, Dragomir D, Stefan G, Mircescu G. Ketoanalogue-supplemented vegetarian very low-protein diet and CKD progression. J Am Soc Nephrol. 2016;27(7):2164–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Brunori G, Viola BF, Parrinello G, De Biase V, Como G, Franco V, Garibotto G, Zubani R, Cancarini GC. Efficacy and safety of a very-low-protein diet when postponing dialysis in the elderly: a prospective randomized multicenter controlled study. Am J Kidney Dis. 2007;49(5):569–80.

    Article  CAS  PubMed  Google Scholar 

  73. Ikizler TA, Burrowes JD, Byham-Gray LD, Campbell KL, Carrero JJ, Chan W, Fouque D, Friedman AN, Ghaddar S, Goldstein-Fuchs DJ, Kaysen GA, Kopple JD, Teta D, Yee-Moon Wang A, Cuppari L. KDOQI clinical practice guideline for nutrition in CKD: 2020 update. Am J Kidney Dis. 2020;76(3 Suppl 1):S1–107.

    Article  CAS  PubMed  Google Scholar 

  74. Oosterwijk MM, Soedamah-Muthu SS, Geleijnse JM, Bakker SJL, Navis G, Binnenmars SH, Gant CM, Laverman GD. High dietary intake of vegetable protein is associated with lower prevalence of renal function impairment: results of the Dutch DIALECT-1 cohort. Kidney Int Rep. 2019;4(5):710–9.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Lew QJ, Jafar TH, Koh HW, Jin A, Chow KY, Yuan JM, Koh WP. Red Meat intake and risk of ESRD. J Am Soc Nephrol. 2017;28(1):304–12.

    Article  PubMed  Google Scholar 

  76. Carrero JJ, Gonzalez-Ortiz A, Avesani CM, Bakker SJL, Bellizzi V, Chauveau P, Clase CM, Cupisti A, Espinosa-Cuevas A, Molina P, Moreau K, Piccoli GB, Post A, Sezer S, Fouque D. Plant-based diets to manage the risks and complications of chronic kidney disease. Nat Rev Nephrol. 2020;16(9):525–42.

    Article  PubMed  Google Scholar 

  77. Kwon YJ, Lee HS, Park G, Kim HM, Lee JW. Association of dietary fiber intake with all-cause mortality and cardiovascular disease mortality: A 10-year prospective cohort study. Nutrients. 2022;14(15):3089.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Lattimer JM, Haub MD. Effects of dietary fiber and its components on metabolic health. Nutrients. 2010;2(12):1266–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Sullivan VK, Appel LJ, Anderson CAM, Kim H, Unruh ML, Lash JP, Trego M, Sondheimer J, Dobre M, Pradhan N, Rao PS, Chen J, He J, Rebholz CM, Investigators CS. Ultraprocessed foods and kidney disease progression, mortality, and cardiovascular disease risk in the CRIC study. Am J Kidney Dis. 2023;82(2):202–12.

    Article  CAS  PubMed  Google Scholar 

  80. Rhee CM, Wang AY, Biruete A, Kistler B, Kovesdy CP, Zarantonello D, Ko GJ, Piccoli GB, Garibotto G, Brunori G, Sumida K, Lambert K, Moore LW, Han SH, Narasaki Y, Kalantar-Zadeh K. Nutritional and dietary management of chronic kidney disease under conservative and preservative kidney care without dialysis. J Ren Nutr. 2023;33(6S):S56–S66.

  81. Nangaku M, Kanda H, Takama H, Ichikawa T, Hase H, Akizawa T. Randomized clinical trial on the effect of bardoxolone methyl on GFR in diabetic kidney disease patients (TSUBAKI study). Kidney Int Rep. 2020;5(6):879–90.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Nangaku M, Takama H, Ichikawa T, Mukai K, Kojima M, Suzuki Y, Watada H, Wada T, Ueki K, Narita I, Kashihara N, Kadowaki T, Hase H, Akizawa T. Randomized, double-blind, placebo-controlled phase 3 study of bardoxolone methyl in patients with diabetic kidney disease: design and baseline characteristics of the AYAME study. Nephrol Dial Transplant. 2023;38(5):1204–16.

    Article  CAS  PubMed  Google Scholar 

  83. Heerspink HJL, Parving HH, Andress DL, Bakris G, Correa-Rotter R, Hou FF, Kitzman DW, Kohan D, Makino H, McMurray JJV, Melnick JZ, Miller MG, Pergola PE, Perkovic V, Tobe S, Yi T, Wigderson M, de Zeeuw D, Committees, S., and Investigators. Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial. Lancet. 2019;393(10184):1937–47.

    Article  CAS  PubMed  Google Scholar 

  84. de Boer IH, Alpers CE, Azeloglu EU, Balis UGJ, Barasch JM, Barisoni L, Blank KN, Bomback AS, Brown K, Dagher PC, Dighe AL, Eadon MT, El-Achkar TM, Gaut JP, Hacohen N, He Y, Hodgin JB, Jain S, Kellum JA, Kiryluk K, Knight R, Laszik ZG, Lienczewski C, Mariani LH, McClelland RL, Menez S, Moledina DG, Mooney SD, O’Toole JF, Palevsky PM, Parikh CR, Poggio ED, Rosas SE, Rosengart MR, Sarwal MM, Schaub JA, Sedor JR, Sharma K, Steck B, Toto RD, Troyanskaya OG, Tuttle KR, Vazquez MA, Waikar SS, Williams K, Wilson FP, Zhang K, Iyengar R, Kretzler M, Himmelfarb J, Kidney Precision Medicine, P. Rationale and design of the kidney precision medicine project. Kidney Int. 2021;99(3):498–510.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Genovese G, Friedman DJ, Ross MD, Lecordier L, Uzureau P, Freedman BI, Bowden DW, Langefeld CD, Oleksyk TK, Uscinski Knob AL, Bernhardy AJ, Hicks PJ, Nelson GW, Vanhollebeke B, Winkler CA, Kopp JB, Pays E, Pollak MR. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science. 2010;329(5993):841–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Lipkowitz MS, Freedman BI, Langefeld CD, Comeau ME, Bowden DW, Kao WH, Astor BC, Bottinger EP, Iyengar SK, Klotman PE, Freedman RG, Zhang W, Parekh RS, Choi MJ, Nelson GW, Winkler CA, Kopp JB, Investigators SK. Apolipoprotein L1 gene variants associate with hypertension-attributed nephropathy and the rate of kidney function decline in African Americans. Kidney Int. 2013;83(1):114–20.

    Article  CAS  PubMed  Google Scholar 

  87. Freedman BI, Moxey-Mims MM, Alexander AA, Astor BC, Birdwell KA, Bowden DW, Bowen G, Bromberg J, Craven TE, Dadhania DM, Divers J, Doshi MD, Eidbo E, Fornoni A, Gautreaux MD, Gbadegesin RA, Gee PO, Guerra G, Hsu CY, Iltis AS, Jefferson N, Julian BA, Klassen DK, Koty PP, Langefeld CD, Lentine KL, Ma L, Mannon RB, Menon MC, Mohan S, Moore JB, Murphy B, Newell KA, Odim J, Ortigosa-Goggins M, Palmer ND, Park M, Parsa A, Pastan SO, Poggio ED, Rajapakse N, Reeves-Daniel AM, Rosas SE, Russell LP, Sawinski D, Smith SC, Spainhour M, Stratta RJ, Weir MR, Reboussin DM, Kimmel PL, Brennan DC. APOL1 long-term kidney Transplantation outcomes network (APOLLO): design and rationale. Kidney Int Rep. 2020;5(3):278–88.

    Article  PubMed  Google Scholar 

  88. Egbuna O, Zimmerman B, Manos G, Fortier A, Chirieac MC, Dakin LA, Friedman DJ, Bramham K, Campbell K, Knebelmann B, Barisoni L, Falk RJ, Gipson DS, Lipkowitz MS, Ojo A, Bunnage ME, Pollak MR, Altshuler D, Chertow GM, Group, V.X.S. Inaxaplin for Proteinuric Kidney Disease in Persons with Two APOL1 Variants. N Engl J Med. 2023;388(11):969–79.

    Article  CAS  PubMed  Google Scholar 

  89. Parsa A, Kanetsky PA, Xiao R, Gupta J, Mitra N, Limou S, Xie D, Xu H, Anderson AH, Ojo A, Kusek JW, Lora CM, Hamm LL, He J, Sandholm N, Jeff J, Raj DE, Boger CA, Bottinger E, Salimi S, Parekh RS, Adler SG, Langefeld CD, Bowden DW, Consortium F, Groop PH, Forsblom C, Freedman BI, Lipkowitz M, Fox CS, Winkler CA, Feldman HI, and the Chronic Renal Insufficiency Cohort Study I. Genome-wide association of CKD progression: The chronic renal insufficiency cohort study. J Am Soc Nephrol. 2017;28(3):923–934.

  90. Kelly TN, Raj D, Rahman M, Kretzler M, Kallem RR, Ricardo AC, Rosas SE, Tao K, Xie D, Hamm LL, He J, Investigators CS. The role of renin-angiotensin-aldosterone system genes in the progression of chronic kidney disease: findings from the Chronic Renal Insufficiency Cohort (CRIC) study. Nephrol Dial Transplant. 2015;30(10):1711–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Puthumana J, Thiessen-Philbrook H, Xu L, Coca SG, Garg AX, Himmelfarb J, Bhatraju PK, Ikizler TA, Siew ED, Ware LB, Liu KD, Go AS, Kaufman JS, Kimmel PL, Chinchilli VM, Cantley LG, Parikh CR. Biomarkers of inflammation and repair in kidney disease progression. J Clin Invest. 2021;131(3):e139927.

Download references

Acknowledgements

MD is supported by a grant from the NIH (R01HL141846).

Author information

Authors and Affiliations

  1. Division of Nephrology and Hypertension, University Hospitals Cleveland Medical Center, 11100 Euclid Ave, Cleveland, OH, 44106, USA

    Nishigandha Pradhan & Mirela Dobre

  2. School of Medicine, Case Western Reserve University, Cleveland, OH, USA

    Nishigandha Pradhan & Mirela Dobre

Authors
  1. Nishigandha Pradhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mirela Dobre
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

NP wrote the original draft. MD and NP contributed to the design and critical review of the manuscript.

Corresponding author

Correspondence to Mirela Dobre.

Ethics declarations

Conflict of Interest

MD reports consulting fees from Care Dx. NP has no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pradhan, N., Dobre, M. Emerging Preventive Strategies in Chronic Kidney Disease: Recent Evidence and Gaps in Knowledge. Curr Atheroscler Rep 25, 1047–1058 (2023). https://doi.org/10.1007/s11883-023-01172-5

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11883-023-01172-5

Keywords

Search

Navigation