Effects of tacrolimus on proteinuria in Chinese and Indian patients with idiopathic membranous nephropathy: the results of machine learning study

Int Urol Nephrol. 2024 Sep;56(9):3047-3055. doi: 10.1007/s11255-024-04056-y. Epub 2024 Apr 20.

Abstract

Purpose: The present study aims to explore the effects of tacrolimus on proteinuria in patients with idiopathic membranous nephropathy (IMN) and recommend an appropriate dosage schedule via machine learning method.

Methods: The Emax model was constructed to analyze the effects of tacrolimus on proteinuria in patients with IMN. Data were mined from published literature and machine learning was built up with Emax model, among which the efficacy indicator was proteinuria change rates from baseline. 463 IMN patients were included for modeling, and tacrolimus therapeutic window concentrations were 4-10 ng/ml.

Results: In machine learning model, the Emax from tacrolimus effecting proteinuria in IMN patients was -72.7%, the ET50 was 0.43 months, and the time to achieving 25% Emax, 50% Emax, 75% Emax, and 80% (plateau) Emax of tacrolimus on proteinuria in patients with IMN were 0.15, 0.43, 1.29, and 1.72 months, respectively.

Conclusion: For achieving better therapeutic effects from tacrolimus on proteinuria in patients with IMN, tacrolimus concentration range need to be maintained at 4-10 ng/ml for at least 1.72 months.

Keywords: Idiopathic membranous nephropathy; Machine learning; Prediction; Proteinuria; Tacrolimus.

MeSH terms

  • Adult
  • China
  • East Asian People
  • Female
  • Glomerulonephritis, Membranous* / complications
  • Glomerulonephritis, Membranous* / drug therapy
  • Humans
  • Immunosuppressive Agents* / therapeutic use
  • India
  • Machine Learning*
  • Male
  • Middle Aged
  • Proteinuria* / drug therapy
  • Tacrolimus* / therapeutic use

Substances

  • Tacrolimus
  • Immunosuppressive Agents