To the editor:Alport syndrome (AS) is a hereditary kidney disease characterized by progressive renal failure especially for patients with autosomal recessive and X-linked inheritance1Alport Syndrome: Achieving Early Diagnosis and Treatment.. At present, no preventive or curative therapies are available. Current treatment includes the use of renin-angiotensin-aldosterone system inhibitors which slow progression of kidney disease and prolong life expectancy2Chavez E. Rodriguez J. Drexler Y. Fornoni A. Novel Therapies for Alport Syndrome.. While the DAPA-CKD trial suggests a beneficial effect of sodium glucose cotransporter-2 inhibitors (SGLT2i) in CKD of non-metabolic origin3Heerspink H.J.L. Stefánsson B.V. Correa-Rotter R. et al.Dapagliflozin in Patients with Chronic Kidney Disease., whether the conclusion can be extrapolated for the treatment of rapidly progressive genetic kidney disease is unknown2Chavez E. Rodriguez J. Drexler Y. Fornoni A. Novel Therapies for Alport Syndrome.. Therefore, we explored the efficacy and safety of SGLT2i in adult autosomal recessive Alport syndrome (ARAS).This was a real-world study based on our dynamic cohort of AS (Supplementary Methods and Supplementary Table S1). With a follow-up of 4-6 months, proteinuria showed a decreasing trend in all the three ARAS cases, with 24-hour proteinuria decreasing by 0.17 (8.9%), 0.61 (39.9%), 0.69 (52.3%) g/24h respectively (Figure 1). Urinary albumin-creatinine ratio decreased by 374.92 (26.9%), 561.03 (44.0%), 234.33 (68.7%) mg/g respectively. Correspondingly, the serum albumin showed an increasement on the whole. Importantly, the serum creatinine and eGFR remained stable. No patient discontinued dapagliflozin due to safety concerns and no clinically adverse effect was observed.

Figure 1Changes in 24-hour urine protein (a), urinary albumin-creatinine ratio (b), plasma albumin (c), serum creatinine (d), eGFR (e) in the three cases with ARAS during dapagliflozin treatment. UTP: 24-hour urine protein; ACR: urinary albumin-creatinine ratio; Alb: serum albumin; Scr: serum creatinine; eGFR: estimated glomerular filtration rate.

In this report, the good efficacy of dapagliflozin is reported for the first time in ARAS patients with decreased renal function. Proteinuria was decreased steadily after administration of dapagliflozin. No patient discontinued SGLT2i therapy due to safety concerns during the follow-up period of 6 months. Limitations should be acknowledged. First, the included patients were with mild or moderate proteinuria, rather than nephrotic proteinuria. Second, this is just a pilot study, and more high-quality studies with a control arm are needed to verify our results.

In conclusion, the pilot study showed good efficacy and tolerance of half-dose dapagliflozin in AS patients. Application of SGLT2i as an add-on therapy may be considered. A high-quality study with a larger number of patients in full dose is needed in the future.

Acknowledgments

Support was provided by National Science Foundation of China (82022010); Beijing Natural Science Foundation (Z190023); CAMS Innovation Fund for Medical Sciences (2019-I2M-5-046). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Ethical Statement

The patients have given consent for their clinical information to be published in the journal.

Data Statement

The data will be available on request.

Supplementary DataReferences

Alport Syndrome: Achieving Early Diagnosis and Treatment.

Am J Kidney Dis. 77: 272-279Chavez E. Rodriguez J. Drexler Y. Fornoni A.

Novel Therapies for Alport Syndrome.

Front Med (Lausanne). 9848389Heerspink H.J.L. Stefánsson B.V. Correa-Rotter R. et al.

Dapagliflozin in Patients with Chronic Kidney Disease.

N Engl J Med. 383: 1436-1446Article InfoPublication History

Accepted: June 24, 2022

Received: June 21, 2022

Publication stageIn Press Journal Pre-ProofFootnotes

Disclosure

All the authors declared no conflict of interest.

Identification

DOI: https://doi.org/10.1016/j.ekir.2022.06.017

Copyright

© 2022 International Society of Nephrology. Published by Elsevier Inc.

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