Urinary retinol binding protein predicts renal outcome in systemic immunoglobulin light-chain (AL) amyloidosis

Renal risk stratification in systemic immunoglobulin light-chain (AL) amyloidosis is according to estimated glomerular filtration rate (eGFR) and urinary protein creatinine ratio (uPCR), the latter attributed to glomerular dysfunction, with proximal tubular dysfunction (PTD) little studied. Urinary retinol binding protein 4 (uRBP), a low molecular weight tubular protein and highly sensitive marker of PTD, was prospectively measured in 285 newly diagnosed, untreated patients with systemic AL amyloidosis between August 2017 to August 2018. At diagnosis, the uRBP/creatinine ratio (uRBPCR) correlated with serum creatinine (r = 0 center dot 618, P < 0 center dot 0001), uPCR (r = 0 center dot 422, P < 0 center dot 0001) as well as both fractional excretion of phosphate and urate (r = 0 center dot 563, P < 0 center dot 0001). Log uRBPCR at diagnosis was a strong independent predictor of end-stage renal disease {hazard ratio [HR] 2 center dot 65, [95% confidence interval (CI) 1 center dot 06-6 center dot 64]; P = 0 center dot 038}, particularly in patients with an eGFR >30 ml/min/1.73 m(2) [HR 4 center dot 11, (95% CI 1 center dot 45-11 center dot 65); P = 0 center dot 008] and those who failed to achieve a deep haematological response to chemotherapy within 3 months of diagnosis [HR 6 center dot 72, (95% CI 1 center dot 83-24 center dot 74); P = 0 center dot 004], and also predicted renal progression [HR 1 center dot 91, (95% CI 1 center dot 18-3 center dot 07); P = 0 center dot 008]. Elevated uRBPCR indicates PTD and predicts renal outcomes independently of eGFR, uPCR and clonal response in systemic AL amyloidosis. The role of uRBPCR as a novel prognostic biomarker merits further study, particularly in monoclonal gammopathies of renal significance.