Drug Development in Pediatric Chronic Kidney Disease: A Review of Promising Treatments, Old Challenges, and New Strategies

Bowe B, Xie Y, Li T, Mokdad AH, Xian H, Yan Y, et al. Changes in the US burden of chronic kidney disease from 2002 to 2016: an analysis of the global burden of disease study. JAMA Netw Open. 2018;1(7): e184412-e. https://doi.org/10.1001/jamanetworkopen.2018.4412.

Article  Google Scholar 

Ogden CL, Carroll MD, Lawman HG, Fryar CD, Kruszon-Moran D, Kit BK, et al. Trends in obesity prevalence among children and adolescents in the United States, 1988–1994 through 2013–2014. JAMA. 2016;315(21):2292–9. https://doi.org/10.1001/jama.2016.6361.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Grubbs V, Lin F, Vittinghoff E, Shlipak MG, Peralta CA, Bansal N, et al. Body mass index and early kidney function decline in young adults: a longitudinal analysis of the CARDIA (Coronary Artery Risk Development in Young Adults) study. Am J Kidney Dis. 2014;63(4):590–7. https://doi.org/10.1053/j.ajkd.2013.10.055.

Article  PubMed  Google Scholar 

Long-term complications in youth-onset type 2 diabetes. N Engl J Med. 2021;385(5):416–26. https://doi.org/10.1056/NEJMoa2100165.

Blowey DL, Flynn JT, Warady BA. Are there consequences of adolescent blood pressure on kidney function in adulthood? Am J Kidney Dis. 2019;74(4):567–9. https://doi.org/10.1053/j.ajkd.2019.05.006.

Article  PubMed  Google Scholar 

Murray R, Zimmerman T, Agarwal A, Palevsky PM, Quaggin S, Rosas SE, et al. Kidney-related research in the united states: a position statement from the National Kidney Foundation and the American Society of Nephrology. Am J Kidney Dis. 2021;78(2):161–7. https://doi.org/10.1053/j.ajkd.2021.04.006.

Article  PubMed  PubMed Central  Google Scholar 

Skorecki K, Chertow GM, Marsden PA, Brenner BM, Rector FC. Brenner & Rector’s the kidney. Philadelphia: Elsevier; 2016.

Google Scholar 

de Boer IH, Alpers CE, Azeloglu EU, Balis UGJ, Barasch JM, Barisoni L, et al. Rationale and design of the Kidney Precision Medicine Project. Kidney Int. 2021;99(3):498–510. https://doi.org/10.1016/j.kint.2020.08.039.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Murray R, Kramer H. Realizing the goals of the advancing american kidney health initiative: toward a better future for kidney disease research funding. Adv Chronic Kidney Dis. 2022;29(1):76–82. https://doi.org/10.1053/j.ackd.2022.01.005.

Article  PubMed  Google Scholar 

Williams CEC, Lamond M, Marro J, Chetwynd AJ, Oni L. A narrative review of potential drug treatments for nephritis in children with IgA vasculitis (HSP). Clin Rheumatol. 2023;42(12):3189–200. https://doi.org/10.1007/s10067-023-06781-8.

Article  PubMed  PubMed Central  Google Scholar 

Perkovic V, Craig JC, Chailimpamontree W, Fox CS, Garcia-Garcia G, Benghanem Gharbi M, et al. Action plan for optimizing the design of clinical trials in chronic kidney disease. Kidney Int Suppl. 2017;7(2):138–44. https://doi.org/10.1016/j.kisu.2017.07.009.

Article  Google Scholar 

Levey AS, Gansevoort RT, Coresh J, Inker LA, Heerspink HL, Grams ME, et al. Change in albuminuria and GFR as end points for clinical trials in early stages of CKD: a scientific workshop sponsored by the National Kidney Foundation in Collaboration With the US Food and Drug Administration and European Medicines Agency. Am J Kidney Dis. 2020;75(1):84–104. https://doi.org/10.1053/j.ajkd.2019.06.009.

Article  CAS  PubMed  Google Scholar 

Braunwald E. SGLT2 inhibitors: the statins of the 21st century. Eur Heart J. 2021. https://doi.org/10.1093/eurheartj/ehab765.

Article  PubMed  PubMed Central  Google Scholar 

Li J, Tummalapalli SL, Mendu ML. Advancing American Kidney Health and the role of sodium-glucose cotransporter-2 inhibitors. Clin J Am Soc Nephrol. 2021;16(10):1584. https://doi.org/10.2215/CJN.05450421.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chao EC, Henry RR. SGLT2 inhibition—a novel strategy for diabetes treatment. Nat Rev Drug Discov. 2010;9(7):551–9. https://doi.org/10.1038/nrd3180.

Article  CAS  PubMed  Google Scholar 

Meng W, Ellsworth BA, Nirschl AA, McCann PJ, Patel M, Girotra RN, et al. Discovery of dapagliflozin: a potent, selective renal sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes. J Med Chem. 2008;51(5):1145–9. https://doi.org/10.1021/jm701272q.

Article  CAS  PubMed  Google Scholar 

Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117–28. https://doi.org/10.1056/NEJMoa1504720.

Article  CAS  PubMed  Google Scholar 

Wanner C, Inzucchi SE, Lachin JM, Fitchett D, von Eynatten M, Mattheus M, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016;375(4):323–34. https://doi.org/10.1056/NEJMoa1515920.

Article  CAS  PubMed  Google Scholar 

Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJL, Charytan DM, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019;380(24):2295–306. https://doi.org/10.1056/NEJMoa1811744.

Article  CAS  PubMed  Google Scholar 

Kula AJ. Considerations and possibilities for sodium-glucose cotransporter 2 inhibitors in pediatric CKD. Pediatr Nephrol. 2022;37(10):2267–76. https://doi.org/10.1007/s00467-022-05456-x.

Article  PubMed  Google Scholar 

Heerspink HJL, Stefánsson BV, Correa-Rotter R, Chertow GM, Greene T, Hou F-F, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436–46. https://doi.org/10.1056/NEJMoa2024816.

Article  CAS  PubMed  Google Scholar 

Wheeler DC, Toto RD, Stefansson BV, Jongs N, Chertow GM, Greene T, et al. A pre-specified analysis of the DAPA-CKD trial demonstrates the effects of dapagliflozin on major adverse kidney events in patients with IgA nephropathy. Kidney Int. 2021. https://doi.org/10.1016/j.kint.2021.03.033.

Article  PubMed  Google Scholar 

Empagliflozin in patients with chronic kidney disease. N Engl J Med. 2022. https://doi.org/10.1056/NEJMoa2204233

Mark PB, Sattar N. Implementation, not hesitation, for SGLT2 inhibition as foundational therapy for chronic kidney disease. Lancet. 2022;400(10365):1745–7. https://doi.org/10.1016/S0140-6736(22)02164-X.

Article  CAS  PubMed  Google Scholar 

Meraz-Muñoz AY, Weinstein J, Wald R. eGFR decline after SGLT2 inhibitor initiation: the tortoise and the hare reimagined. Kidney360. 2021;2(6):1042. https://doi.org/10.34067/KID.0001172021.

Article  PubMed  PubMed Central  Google Scholar 

Lava SAG, Laurence C, Di Deo A, Sekarski N, Burch M, Della PO. Dapagliflozin and empagliflozin in paediatric indications: a systematic review. Pediatr Drugs. 2024;26(3):229–43. https://doi.org/10.1007/s40272-024-00623-z.

Article  Google Scholar 

van den Belt SM, Heerspink HJL, Gracchi V, de Zeeuw D, Wühl E, Schaefer F, Group obotET. Early proteinuria lowering by angiotensin-converting enzyme inhibition predicts renal survival in children with CKD. J Am Soc Nephrol. 2018;29(8):2225–33. https://doi.org/10.1681/asn.2018010036.

Article  PubMed  PubMed Central  Google Scholar 

Cattran DC, Greenwood C, Ritchie S. Long-term benefits of angiotensin-converting enzyme inhibitor therapy in patients with severe immunoglobulin a nephropathy: a comparison to patients receiving treatment with other antihypertensive agents and to patients receiving no therapy. Am J Kidney Dis. 1994;23(2):247–54. https://doi.org/10.1016/S0272-6386(12)80980-2.

Article  CAS  PubMed  Google Scholar 

Levin A, Ahmed SB, Carrero JJ, Foster B, Francis A, Hall RK, et al. Executive summary of the KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease: known knowns and known unknowns. Kidney Int. 2024;105(4):684–701. https://doi.org/10.1016/j.kint.2023.10.016.

Article  PubMed  Google Scholar 

Maschio G, Alberti D, Janin G, Locatelli F, Mann JFE, et al. Effect of the angiotensin-converting–enzyme inhibitor benazepril on the progression of chronic renal insufficiency. N Engl J Med. 1996;334(15):939–45. https://doi.org/10.1056/NEJM199604113341502.

Article  CAS  PubMed  Google Scholar 

Coppo R, Peruzzi L, A

Comments (0)

No login
gif