Natural History of Proteinuria in Renal Transplant Recipients Developing De Novo Human Leukocyte Antigen Antibodies

Abstract

Proteinuria is associated with DSA detection and is likely to be an important factor that determines rapid GFR decline and earlier graft failure in patients developing de novo HLA antibodies.

Donor-Specific HLA Antibodies in a Cohort Comparing Everolimus With Cyclosporine After Kidney Transplantation

“…On the other hand, proteinuria has been shown to be an early marker of AMR (15). In the light of the results of our study, development of proteinuria under immunosuppression with mTORi should prompt further diagnostics rather than routinely attributing this "side effect" to mTORi medication.…”

“…Chronic AMR is characterized by basement membrane abnormalities of glomerular and peritubular capillaries leading to chronic transplant glomerulopathy and nephron loss (11,12,14). Clinical signs of chronic AMR include proteinuria as hallmark of glomerular injury and a slow deterioration of allograft function (15,16).…”

Utility of HLA Antibody Testing in Kidney Transplantation

“…Despite this, when collectively examined, available studies do provide insights into the relationship of DSA with histopathology and impaired function, the prognostic utility of testing, and potential strategies for treatment and prevention. 113 Cumulative prevalence at 3 years post-transplant is similarly varied from 6% 116 to 38%, 113 with lifetime cumulative prevalence even more disparate. Class II antibodies predominate in most [115][116][117][118][119][120][121][122][123][124][125] but not all reports.…”

“…Class II antibodies predominate in most [115][116][117][118][119][120][121][122][123][124][125] but not all reports. [111][112][113][114] With differences in antibody MFI cutoffs, baseline immunosuppression, and frequency of testing, definitive conclusions remain elusive.…”

“…The timing of dnDSA occurrence to onset of graft dysfunction ranges from months to years, 111,113,114,116,118,123,[126][127][128][129][130] suggesting multiple pathways of injury and potentially diverse modifying factors. A comprehensive natural history study coupled to protocol and for-cause biopsies showed the mean time to dnDSA as 4.6 years, with the most important independent predictor being immunosuppressive nonadherence (60% cumulative prevalence versus 20% in adherent patients at 10 years; odds ratio, 8.75).…”