Continuous function of 80 primary renal allografts for 30-47 years with maintenance prednisone and azathioprine/mycophenolate mofetil therapy: A clinical mosaic of long-term successes

Clin Transplant. 2021 Jan;35(1):e14131. doi: 10.1111/ctr.14131. Epub 2020 Nov 27.

Abstract

Eighty primary renal allograft recipients, 61 living-related and 19 deceased donor, transplanted from 1963 through 1984 had continuous graft function for 30-47 years. They were treated with three different early immunosuppression programs (1963-1970: thymectomy, splenectomy, high oral prednisone; 1971-1979: divided-dose intravenous methylprednisolone; and 1980-1984: antilymphocyte globulin) each with maintenance prednisone and azathioprine, and no calcineurin inhibitor. Long-term treatment often included the anti-platelet medication, dipyridamole. Although both recipient and donor ages were young (27.2 ± 9.5 and 33.1 ± 12.0 years, respectively), six recipients with a parent donor had >40-year success. At 35 years, death-censored graft survival was 85.3% and death with a functioning graft 84.2%; overall graft survival was 69.5% (Kaplan-Meier estimate). Biopsy-documented early acute cellular and highly probable antibody-mediated rejections were reversed with divided-dose intravenous methylprednisolone. Complications are detailed in an integrated timeline. Hypogammaglobulinemia identified after 20 years doubled the infection rate. An association between a monoclonal gammopathy of undetermined significance and non-plasma-cell malignancies was identified. Twenty-seven azathioprine-treated patients tested after 37 years had extremely low levels of T1/T2 B lymphocytes representing a "low immunosuppression state of allograft acceptance (LISAA)". The lifetime achievements of these patients following a single renal allograft and low-dose maintenance immunosuppression are remarkable. Their success evolved as a clinical mosaic.

Keywords: B cell biology; azathioprine; biopsy; complication; immunosuppressant; malignancy; medical/metabolic.

MeSH terms

  • Adolescent
  • Adult
  • Allografts
  • Antilymphocyte Serum
  • Azathioprine / therapeutic use
  • Drug Therapy, Combination
  • Graft Rejection / drug therapy
  • Graft Rejection / etiology
  • Graft Rejection / prevention & control
  • Graft Survival
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Kidney Transplantation*
  • Mycophenolic Acid*
  • Prednisone
  • Young Adult

Substances

  • Antilymphocyte Serum
  • Immunosuppressive Agents
  • Mycophenolic Acid
  • Azathioprine
  • Prednisone