RENAISSANCE

Kidney Transplant Outcomes Trial

RENAISSANCE

Cardiovascular and Renal Protection with SGLT2 Inhibition in Kidney Transplant Recipients.

Despite advances in immunosuppression, long-term transplant outcomes remain limited. RENAISSANCE is designed to answer whether sotagliflozin can safely reduce mortality, graft failure, and major cardiovascular and renal events in kidney transplant recipients.

900

Participants randomized 1:1

4.5 yrs

Maximum participant follow-up

25

Academic sites in US and Canada

Win Ratio

Hierarchical primary endpoint analysis

View ObjectivesInvestigator Login

Why This Study Now

Primary causes of late graft loss include recipient death and progressive renal dysfunction. Cardiovascular disease remains the leading cause of death despite functioning transplants.

Existing observational SGLT2i data in kidney transplant recipients suggest stable graft function, favorable metabolic effects, and low adverse event rates, but randomized evidence is still needed.

Current Safety Signals

  • More than 370 transplant recipients treated with SGLT2i
  • Review data across 9 observational studies
  • Minimal blood pressure impact with weight and glycemic benefit
  • Low adverse event rates similar to non-transplant populations
  • Propensity-matched retrospective data showed reduced composite risk (HR 0.43, 95% CI 0.24-0.78)

RENAISSANCE Objectives

Determine whether sotagliflozin is superior to placebo for major cardiovascular and kidney outcomes, while establishing an acceptable safety profile in kidney transplant recipients.

Primary Objective

Evaluate reduction in risk of death, kidney failure, significant decline in transplant function, stroke or non-fatal MI, and acute care for heart failure.

Secondary Objective

Compare safety events including serious adverse events, infections, ketoacidosis, acute kidney injury, rejection, hypotension, hypoglycemia, fracture, and treatment discontinuation.

Trial Type

Placebo-Controlled RCT

Population

Kidney Transplant Recipients

Scope

US + Canada Multicenter

Hierarchical Primary Outcome

The primary endpoint is analyzed using a win-ratio approach, comparing all treatment-control participant pairs by ordered outcome severity.

  1. All-cause mortality
  2. Transplant loss (chronic dialysis >90 days, retransplant, or eGFR <=15 ml/min/1.73m2 for >3 months)
  3. Non-fatal stroke or non-fatal myocardial infarction
  4. Sustained 40% decline in eGFR
  5. Hospitalization for heart failure or urgent HF treatment
  6. eGFR slope

Secondary and Tertiary Efficacy

  • Individual primary outcome components
  • Cardiovascular and kidney-specific hierarchical composites
  • Development of de novo diabetes
  • Percent weight change and albuminuria
  • AKI episodes and total eGFR slope
  • Study drug discontinuation

Safety Endpoints

  • Serious adverse events and discontinuation events
  • Mycotic genital and urinary infections
  • Any infection requiring emergency care or hospitalization
  • Amputation, fracture, ketoacidosis, hypotension, and hypoglycemia
  • Acute kidney injury, acute rejection, and diarrhea

Clinical Equipoise

This trial addresses both the promise and uncertainty of SGLT2i use in kidney transplantation with dedicated, prospective evidence.

Potential Advantages

  • High cardiovascular burden in transplant populations
  • Chronic kidney disease is universally present
  • Frequent diabetes, obesity, and hypertension
  • Chronic inflammation and fibrosis as ongoing risk drivers

Potential Concerns

  • Concomitant immunosuppression and infection burden
  • UTI and fungal infection risk
  • Single denervated kidney and DKA/sepsis concerns
  • Limited long-term randomized transplant-specific data

Who Can Participate

Inclusion Criteria

  • Adult kidney recipients (living or deceased donor), at least 6 months post-transplant
  • eGFR >=20 ml/min
  • At increased risk for worsening allograft function or cardiovascular events
  • Risk groups include Type 2 diabetes, BMI >=35 kg/m2, prior CHF hospitalization, albuminuria, or prior CV event
  • Additional CV risk pathway: men >=50 years or women >=60 years with at least two risk factors

Exclusion Criteria

  • SGLT2 inhibitor use in the last 3 months
  • Type 1 diabetes mellitus
  • Multi-organ or non-renal transplant
  • Recent ACS/TIA/stroke or acute rejection within 3 months
  • History of diabetic ketoacidosis within 5 years
  • Active high-risk infection setting, including BK/CMV/EBV activity
  • Severe hepatic impairment (Child-Pugh C), rifampicin use, or pregnancy/breastfeeding

Study Design Snapshot

  • Nine-hundred adult kidney transplant recipients randomized 1:1 to sotagliflozin or matched placebo
  • Stratification by center, diabetes status, and baseline eGFR (<45 vs >=45)
  • Visits every 3 months with a one-time safety lab approximately 1 month after initiation
  • Four-week washout before study completion with kidney function measured at discontinuation and end of study

Operational Context

Enrollment at approximately 25 academic sites across the US and Canada.

Key execution challenges include international coordination, pragmatic design constraints, limited budget, and interim monitoring with a relatively novel endpoint.