Albuminuria Lowering Effect of Dapagliflozin, Spironolactone and Their Combination in Adult Patients with Alport Syndrome (COMBINE-ALPORT)

Inclusion Criteria: * Genetically proven Alport syndrome (AS) - defined as following: * gt;Men having hemizygous pathogenic/likely pathogenic variants involving COL4A5 gene - classified as X-linked AS involving men * gt;Women having heterozygous pathogenic/likely pathogenic variants involving COL4A5 gene - classified as X-linked AS involving women * gt;Both men and women with heterozygous pathogenic/likely pathogenic variants involving COL4A3 or COL4A4 genes - classified as autosomal dominant AS * gt;Both men and women with homozygous pathogenic/likely pathogenic variants involving COL4A3 or COL4A4 genes - classified as autosomal recessive AS * gt;Patients having variants of uncertain significance will be included if the fulfill at least 2 of the following criteria: (1) clinical features suggestive of AS, (2) positive family history suggestive of AS (i.e., at least one grade I relative having the same variant and presenting clinical features suggestive of AS) and (3) kidney biopsy showing the characteristic lesion of AS (i.e., structural defect of the glomerular basement membrane, "basket-wave" appearance of the basement membrane, lamination of the basement membrane) or for thin basement membrane disease (i.e., diffusely thin basement membrane) * Age between 18 and 70 years-old at the time of enrolment * Baseline estimated glomerular filtration rate (eGFR) over 10ml/min/1.73m2 at the time of enrolment * Stable kidney function: variation of eGFR under 25% from baseline in the last 6 weeks before randomization * 24-hours urine albumin-to-creatinine ratio greater than 30 mg/g after adjusting the dose of renin-angiotensin-system inhibitor * Stable renin-angiotensin-system inhibitor dose for at least 2 weeks before randomization Exclusion Criteria: * The need for kidney replacement therapy (i.e., hemodialysis, peritoneal dialysis, and kidney transplant) for more than 4 weeks in the last 12 months before enrollment * Treatment with Spironolactone or Dapagliflozin for more than 14 days in the last 28 days prior to enrollment * History of prior serious adverse event due to Spironolactone or Dapagliflozin * Active neoplasia * Autosomal dominant or recessive polycystic kidney disease * Type I diabetes * Patients with type II diabetes and diabetic nephropathy * Diagnosis of another concomitant distinct glomerulopathy (with the exception of concomitant IgA nephropathy on kidney biopsy) * Pregnancy and breastfeeding * History of solid organ transplant * Immunosuppressive treatment in the last 12 weeks prior to enrollment