Test Your Knowledge: Transplant Glomerulopathy

There is recent interest in understanding the cause of late allograft failure in kidney transplant recipients. One pathologic marker of poor allograft outcome is transplant glomerulopathy. A recent article by Husain and Sis published in the American Journal of Kidney Diseases reviews transplant glomerulopathy. The following questions will test your knowledge on transplant glomerulopathy:


A 44-year-old man with hepatitis C, hypertension, and type 2 diabetes mellitus who underwent a deceased donor kidney transplant one year ago presents with a slow rise in creatinine from a nadir of 1 mg/dL (eGFR 86 mL/min/1.73 m2) to 2 mg/dL (39 mL/min/1.73m2). He had donor specific antibody against HLA DR52 with an MFI of 4234 at the time of transplant. He received anti-thymocyte globulin induction and was maintained on tacrolimus and mycophenolic acid. His hepatitis C viral load is 1 million. A kidney biopsy is performed. The pathologist informs you the same day that he notices glomerular double contours on light microscopy (see below). The full report is expected in the next day or two.

1. Which of the following may be responsible for this light microscopy finding?

A. Membranoproliferative glomerulonephritis due to hepatitis C

B. Tacrolimus-associated thrombotic microangiopathy

C. Chronic antibody mediated rejection

D. All of the above

E. None of the above

Frequent double contours along the glomerular capillary loops (arrows). Methenamine silver; original magnification, ×400. Image courtesy of Dr. Tibor Nadasdy.

Frequent double contours along the glomerular capillary loops (arrows). Methenamine silver; original magnification, ×400. Image courtesy of Dr. Tibor Nadasdy.

 2. Which of the following clinical features is characteristic of transplant glomerulopathy?

A. Elevated creatinine

B. Proteinuria

C. Hypertension

D. All of the above


A 56-year-old multiparous African American woman with panel-reactive antibody of 84%, type 2 diabetes mellitus, hypertension, and hyperlipidemia received a deceased donor kidney transplant 8 months ago. At the time of transplant, the CDC crossmatch was negative but the B cell flow crossmatch was positive. She received anti-thymocyte globulin induction and was maintained on tacrolimus, mycophenolic acid, and prednisone. She has had good kidney function with a nadir creatinine of 1 mg/dL (eGFR 70 mL/min/1.73m2). She is adherent with her medications. Today you notice that her creatinine is 1.3 mg/dL (eGFR 51 mL/min/1.73 m2) and her urine protein-to-creatinine ratio is 1.5, increased from 0.4 at her last visit. Serum antibody analysis reveals a de novo donor specific antibody to HLA DR4 with a MFI of 6300. You decide to perform a kidney biopsy. Preliminary biopsy findings on light microscopy show only mild tubular damage, unremarkable glomeruli, and no active interstitial inflammatory infiltrate (no tubulitis). C4d staining of the peritubular capillaries is positive in 70% of the sample, and immunohistochemical staining for polyomavirus with SV40 antibody is negative.

 3. At this time, you decide to:

 A. Ask her to return in 2-3 months for possible repeat biopsy

B. Tell her the proteinuria is due to diabetes and hypertension, and that she should check her sugars and blood pressure regularly

C. Perform an electron microscopic examination of the tissue sample

D. Tell her she likely has focal segmental glomerulosclerosis that was probably the cause of her native kidney disease as well

  4. Electron microscopic examination of the sample shows glomeruli with widening of the subendothelial space, endothelial cell swelling, and loss of endothelial cell fenestrations (see below). There are also areas of multi-layering of the peritubular capillary basement membrane. You make a diagnosis of transplant glomerulopathy due to chronic antibody mediated rejection. Which of the following statements is most accurate?

A. Randomized controlled trials have conclusively demonstrated that the combination of anti-CD20 antibody, plasmapheresis, and intravenous immunoglobulin effectively treats transplant glomerulopathy

B. There is no proven effective treatment for transplant glomerulopathy

C. Proteasome inhibitors are a proven therapy for established transplant glomerulopathy

D. Eculizumab has been shown to be highly effective in preventing and treating transplant glomerulopathy

  5. The patient asks you what this means for her kidney function in the long term. You tell her:

 A. Transplant glomerulopathy has no effect on long term graft survival, and she has no reason to worry

B. At 5 years, she has about a 30% less likelihood of having a functioning graft than someone without transplant glomerulopathy

C. If she controls her blood pressure and hypertension with an ACE inhibitor, there should be no effect on graft survival

D. She should be more concerned about her survival rather than the kidney due to her co-morbidities

Post prepared by Dr. Sharad Sathyan, Transplant Nephrology Fellow from The Mount Sinai School of Medicine; Dr. Tibor Nadasdy, eAJKD Contributor; and Dr. Vinay Nair, eAJKD Advisory Board member.

To see answers, please click here.

To view the article abstract or full-text (subscription required), please visit AJKD.org.

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