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Published on: September 6, 2017
Association of HLA Typing and Alloimmunity With Posttransplantation Membranous Nephropathy: A Multicenter Case Series
Ibrahim Batal1, Elena-Rodica Vasilescu1, Darshana M Dadhania2
1Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY.
Rationale & Objectives:
Posttransplantation membranous nephropathy (MN) represents a rare complication of kidney transplantation that can be classified as recurrent or de novo. The clinical, pathologic, and immunogenetic characteristics of posttransplantation MN and the differences between de novo and recurrent MN are not well understood.
Study Design:
Multicenter case series.
Setting & Participants:
We included 77 patients from 5 North American and European medical centers with post-kidney transplantation MN (27 de novo and 50 recurrent). Patients with MN in the native kidney who received kidney allografts but did not develop recurrent MN were used as nonrecurrent controls (n = 43). To improve understanding of posttransplantation MN, we compared de novo MN with recurrent MN and then contrasted recurrent MN with nonrecurrent controls.
Findings:
Compared with recurrent MN, de novo MN was less likely to be classified as primary MN (OR, 0.04; P < 0.001) and had more concurrent antibody-mediated rejection (OR, 12.0; P < 0.001) and inferior allograft survival (HR for allograft failure, 3.2; P = 0.007). HLA-DQ2 and HLA-DR17 antigens were more common in recipients with recurrent MN compared with those with de novo MN; however, the frequency of these recipient antigens in recurrent MN was similar to that in nonrecurrent MN controls. Among the 93 kidney transplant recipients with native kidney failure attributed to MN, older recipient age (HR per each year older, 1.03; P = 0.02), recipient HLA-A3 antigen (HR, 2.5; P = 0.003), steroid-free immunosuppressive regimens (HR, 2.84; P < 0.001), and living related allograft (HR, 1.94; P = 0.03) were predictors of MN recurrence.
Limitations:
Retrospective case series, limited sample size due to rarity of the disease, nonstandardized nature of data collection and biopsies.
Conclusions:
De novo and recurrent MN likely represent separate diseases. De novo MN is associated with humoral alloimmunity and guarded outcome. Potential predisposing factors for recurrent MN include recipients who are older, recipient HLA-A3 antigen, steroid-free immunosuppressive regimen, and living related donor kidney.
Insights
De novo membranous nephropathy (MN) after kidney transplant is distinct from recurrent MN, often linked to antibody-mediated rejection and poorer outcomes. Recurrent MN may be predicted by older recipient age, HLA-A3 antigen, and specific immunosuppression.
Area of Science:
- Nephrology
- Transplantation Immunology
- Pathology
Background:
- Posttransplantation membranous nephropathy (MN) is a rare kidney transplant complication, presenting as recurrent or de novo forms.
- Understanding the distinct characteristics and clinical implications of de novo versus recurrent MN is crucial for patient management.
Purpose of the Study:
- To compare the clinical, pathological, and immunogenetic features of de novo and recurrent posttransplantation MN.
- To identify factors associated with MN recurrence in kidney transplant recipients.
Main Methods:
- A multicenter case series involving 77 patients with post-kidney transplantation MN (27 de novo, 50 recurrent).
- Comparison of de novo MN with recurrent MN, and recurrent MN with nonrecurrent controls (n=43).
- Analysis of recipient and donor factors, including HLA antigens and immunosuppressive regimens.
Main Results:
- De novo MN was less likely primary MN (OR, 0.04; P < 0.001) and associated with more concurrent antibody-mediated rejection (OR, 12.0; P < 0.001) and inferior allograft survival (HR, 3.2; P = 0.007).
- Recurrent MN showed higher frequencies of HLA-DQ2 and HLA-DR17 compared to de novo MN, but similar to nonrecurrent controls.
- Predictors of MN recurrence included older recipient age (HR, 1.03), HLA-A3 antigen (HR, 2.5), steroid-free immunosuppression (HR, 2.84), and living related allografts (HR, 1.94).
Conclusions:
- De novo and recurrent MN appear to be distinct entities.
- De novo MN is linked to humoral alloimmunity and carries a poorer prognosis.
- Older recipient age, HLA-A3, steroid-free immunosuppression, and living related donors are potential risk factors for recurrent MN.
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