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Progressive Renal Failure in a 24-Year-Old Man

Volume 63 - Issue 12 - December 2023

  • Treatment and management. As with many other renal diseases, modification of the renin-angiotensin-aldosterone axis leads to potential benefits in slowing the progression of CKD. In a 2020 study, Yamamura and colleagues examined renal survival in patients taking and not taking renin-angiotensin-aldosterone system inhibitor (RAASi) therapy.9 The median renal survival period of patients in this cohort was 35 years; the onset of ESRD in patients not taking RAASi was age 28 years, whereas in patients taking RAASi, the median age of onset was about age 50 years.9 With uncontrolled hypertension also contributing to declines in renal function, targeting aggressive blood pressure management is warranted. This may require additional agents in combination with RAASi. Even with progression slowed, ESRD remains a likely outcome. Therefore, other therapeutic options are essential for managing HN. These therapies can target areas such as:

    • Reducing proteinuria, adjunctive to the use of RAASi
    • Reducing tubular protein toxicity
    • Reducing tubulointerstitial fibrosis

    The CARDINAL trial examined bardoxolone, a semisynthetic drug that activates nuclear factor erythroid 2-related factor 2 (Nrf2).10 Nrf2 is important in expressing genes related to oxidative stress and inflammation. In this study, treatment with bardoxolone showed significant improvement in kidney function vs placebo the intent-to-treat population. This equated to a 7 to 8 mL/min improvement in estimated glomerular filtration rate (eGFR).10 Bardoxolone also demonstrated a significant improvement in eGFR a month after the medication was stopped.10 In 2021, bardoxolone is being submitted to the US Food and Drug Administration for potential treatment of CKD caused by HN.

    Patient outcome. He was started on dialysis and emergent hemodialysis for fluid overload and uremia. A renal biopsy was performed, results of which confirmed significant tubulointerstitial disease and fibrosis, as well as pathological findings consistent with HN. Once stable, the patient was converted to home hemodialysis and was referred for renal transplant evaluation. 

    References

    1. Wu KL, Shih CP, Chan JS, et al. Investigation of the relationship between sensorineural hearing loss and associated comorbidities in patients with chronic kidney disease: a nationwide, population-based cohort study. PLoS One. 2020;15(9):e0238913. https://doi.org/10.1371/journal.pone.0238913

    2. Kashtan CE. Alport syndrome: achieving early diagnosis and treatment. Am J Kidney Dis. 2021;77(2):272-279. https://doi.org/10.1053/j.ajkd.2020.03.026

    3. Savige J, Storey H, Watson E, et al. Consensus statement on standards and guidelines for the molecular diagnostics of Alport syndrome: refining the ACMG criteria. Eur J Hum Genet. 2021;10.1038/s41431-021-00858-1. https://doi.org/10.1038/s41431-021-00858-1

    4. Miner JH. Pathology vs. molecular genetics: (re)defining the spectrum of Alport syndrome. Kidney Int. 2014;86(6):1081-1083. https://doi.org/10.1038/ki.2014.326

    5. Sedaghat MR, Momeni-Moghaddam H, Haghighi B, Moshirfar M. Phacoemulsification in bilateral anterior lenticonus in Alport syndrome: a case report. Medicine (Baltimore). 2019;98(39):e17054. https://doi.org/10.1097/md.0000000000017054

    6. Kaipa R, Tether H. Speech, language, and hearing function in twins with Alport syndrome: a seven-year retrospective case report. J Otol. 2017;12(2):86-96. https://doi.org/10.1016/j.joto.2017.03.001

    7. Rumpelt HJ. Hereditary nephropathy (Alport syndrome): correlation of clinical data with glomerular basement membrane alterations. Clin Nephrol. 1980;13(5):203-207.

    8. Kashtan CE, Gross O. Clinical practice recommendations for the diagnosis and management of Alport syndrome in children, adolescents, and young adults-an update for 2020. Pediatr Nephrol. 2021;36(3):711-719. https://doi.org/10.1007/s00467-020-04819-6

    9. Yamamura T, Horinouchi T, Nagano C, et al. Genotype-phenotype correlations influence the response to angiotensin-targeting drugs in Japanese patients with male X-linked Alport syndrome. Kidney Int. 2020;98(6):1605-1614. https://doi.org/10.1016/j.kint.2020.06.038

    10. Reata announces positive results from year 2 of the pivotal phase 3 CARDINAL study of bardoxolone methyl in patients with Alport syndrome. News release. Reata; November 9, 2020; Accessed May 28, 2021. https://www.reatapharma.com/investors/news/news-details/2020/Reata-Announces-Positive-Results-From-Year-2-of-the-Pivotal-Phase-3-CARDINAL-Study-of-Bardoxolone-Methyl-in-Patients-with-Alport-Syndrome/default.aspx