Year : 2019 | Volume
: 30 | Issue : 3 | Page : 719--722
Recurrence of membranoproliferative glomerulonephritis post transplant – Is this mere recurrence of pattern or recurrence of disease?
Umesh Lingaraj1, Shivanagouda Ramanagouda Patil1, Kishan Aralapuram1, Shivaprasad Sasivehalli Mallappa1, Sreedhara Chikkanayakanahalli Gurusiddaiah1, Mahesha Vankalakunti2,
1 Department of Nephrology, Institute of Nephro-Urology, Victoria Hospital Campus, Bengaluru, Karnataka, India
2 Department of Nephropathology, Manipal Hospital, Bengaluru, Karnataka, India
Department of Nephrology, Institute of Nephro-Urology, Victoria Hospital Campus, Bengaluru, Karnataka
Recurrence of membranoproliferative glomerulonephritis (MPGN) is seen in 1965% cases of postrenal transplant resulting in graft loss in up to 35-50% of cases. A 31-year-old female, after 1% years on maintenance hemodialysis, underwent ABO compatible deceased donor kidney transplantation with basiliximab induction. During the immediate posttransplant period, the patient had delayed graft function, but achieved nadir creatinine of 0.9 mg/dL by 10 days. Nine months posttransplant, the patient developed fever, anasarca, and decrease in urine output with albuminuria 3+, active sediments in urine, serum creatinine 3.5 mg/dL, 24-h urine protein 7.5 g, and low C3. The patient underwent graft biopsy. Subsequently, the patient received pulse steroid for three days and five sessions of plasmapheresis. Renal biopsy report was suggestive of MPGN with focal crescents and acute tubular necrosis. Immunofluorescence showed Ig G3+, C3 3+, к 3+, and negative for λ or other immunoglobulins or complements. As her native kidney disease was immune-complex-mediated MPGN with no light chain restriction, paraffin tissue of the native kidney was reexamined for light chain restrictions by immunoperoxidase method, but did not show light chain restriction. The patient underwent extensive workup for paraproteinemias, but results were negative. Subsequently, she received four doses of bortezomib. The patient’s serum creatinine got reduced to 0.8 mg/dL and proteinuria reduced to 800 mg/day. Our case is unique as we were not able to demonstrate monoclonal deposits in native kidney sample although there was recurrence of MPGN with monoclonal light chain deposits post transplant. Our findings emphasize the need for thorough evaluation of paraproteinemias in patients with idiopathic MPGN even in the absence of light chain deposition in biopsy.
|How to cite this article:|
Lingaraj U, Patil SR, Aralapuram K, Mallappa SS, Gurusiddaiah SC, Vankalakunti M. Recurrence of membranoproliferative glomerulonephritis post transplant – Is this mere recurrence of pattern or recurrence of disease?.Saudi J Kidney Dis Transpl 2019;30:719-722
|How to cite this URL:|
Lingaraj U, Patil SR, Aralapuram K, Mallappa SS, Gurusiddaiah SC, Vankalakunti M. Recurrence of membranoproliferative glomerulonephritis post transplant – Is this mere recurrence of pattern or recurrence of disease?. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2019 Aug 21 ];30:719-722
Available from: http://www.sjkdt.org/text.asp?2019/30/3/719/261356
Recurrence of membranoproliferative glome-rulonephritis (MPGN) is seen in 19%–65% cases of postrenal transplant and amounts for graft loss up to 35%–50% of cases. A newer schema of classification of MPGN was proposed by Sethi et al based on immunofluorescence (IF) findings, which provides better insight toward the pathogenesis of the disease. Recurrence after transplantation was found to be associated with the presence of monoclonal immunoglobulins, lower serum complement level, human leukocyte antigen B8, DR3, B49, and DR4, higher proteinuria, and the presence of crescents in the original biopsy. Here, we report a unique case of recurrence of MPGN pattern post transplant, however, with different subtype, from immune-complex (IC) to IC with light chain restriction.
A 31-year-old female patient diagnosed to have end-stage renal disease (ESRD) three years back was initiated on maintenance hemodialysis (HD) three times a week. One and half years post initiation of dialysis, she underwent deceased donor kidney transplantation. The donor was male, was 44 years old, was ABO compatible, and had brainstem death following road traffic accident. Serum creatinine on the day of retrieval was 1.4 mg/dL. The patient had received basiliximab induction. Transplant surgery was uneventful. Posttransplant, the patient had delayed graft function requiring two sessions of HD. Four days posttransplant, urine output was improved followed by gradual decline in serum creatinine and reached nadir value of 0.9 mg/dL by 10 days. Ten days later, the patient was discharged with triple immunosuppressive medications including tacrolimus, mycophenolate mofetil, and pred-nisolone. For subsequent nine months, the patient was apparently normal with good graft function. She had a past history of hypothyroi-dism on therapy for 10 years and diagnosed to have MPGN IC subtype five years back which progressed to ESRD two years later.
Nine months posttransplant, the patient developed fever, swelling of lower limbs, puffiness of face, and decrease in urine output. On clinical evaluation, the patient had edema, raised jugular venous pressure, and ascites, and other systemic examinations were unremarkable. On laboratory evaluation, she was found to have 18–20 red blood cells (RBC) in microscopic examination of urine with albuminuria 3+; her serum creatinine was raised to 3.5 mg/dL from 0.8 mg/dL baseline, 24-h urine protein was 7.5 g, serum albumin was 2 g/dL, and serum C3 was reduced. In view of acute graft dysfunction with active urinary sediment and nephrotic range proteinuria, the patient was suspected to have recurrence of GN/de novo GN and underwent graft biopsy on May 26, 2017. Subsequently, the patient was started on pulse methylprednisolone 500 mg/day for three days and received five sessions of plasmapheresis. Maintenance immunosuppressive treatment was continued.
Later, renal biopsy report was suggestive of MPGN with focal crescents (6/20 glomeruli) and acute tubular injury with mild interstitial inflammation. IF showed Ig G3+, C3 3+, к 3+, and negative for λ or other immunoglobulins or complements. As her native kidney disease was IC-mediated MPGN with no light chain restriction seen on IF, paraffin tissue of the native kidney was reexamined for immuno-peroxidase stain for к and λ chains, which were positive for both, confirming the poly-clonality of immunoglobulin deposition in the native kidney.
In view of light chain restriction in tissue biopsy, the medical oncologist’s opinion was taken. The patient underwent bone marrow biopsy, serum electrophoresis, serum-free light chain assay, and serum β 2 microglobulin; however, results of these tests were negative for any clonal proliferation of plasma cells or monoclonal gammopathy in serum. The patient was started on injection bortezomib therapy. After four doses of bortezomib therapy, the patient’s serum creatinine reduced to 0.8 mg/dL, proteinuria reduced to 800 mg/day, and urine RBCs disappeared. In view of the development of severe polyneuropathy, borte-zomib was stopped after four doses.
Two months later, the patient on routine surveillance was found to have an increase in proteinuria and microscopic hematuria with no change in serum creatinine. The patient was reevaluated for paraproteinemias. However, serum electrophoresis was normal, bone marrow report was normal, and whole-body positron emission tomography scan was also normal. As per the medical oncologist’s opinion, the patient was restarted on injection bortezomib therapy via subcutaneous route in view of painful neuropathy that was developed following intravenous administration. Four doses post bortezomib therapy, the patient’s proteinuria reduced to previous baseline value, and microscopic hematuria resolved.
MPGN is the pathologic end result of multiple etiologies. The recurrence of MPGN is common and well described in literature. When MPGN pattern is associated with para-proteinemias, recurrence usually occurs within weeks, most of the cases within one year post transplant. There were two intriguing aspects in this case. One was the absence of light chain restriction in native kidneys and the second was absence of demonstrable monoclonal proliferation of light chains in serum in the background of the presence of monoclonal light chain deposition in tissue.
Regarding first aspect in our case i.e. absence of light chain restriction in native kidney, similar situation is described in a study by Larsen et al. In their study,16 cases of biopsy-proven MPGN which were either diagnosed as C3 GN or unclassified MPGN where IF was negative for light chain deposition, light chain deposition was reported on IF on formalin-fixed paraffin-embedded tissue after protease digestion. Based on these findings, we subjected native kidney biopsy specimen embedded in paraffin to protease digestion to look for masked deposits. However, we could not demonstrate monoclonal light chain deposits.
The second aspect in our case which is intriguing is the absence of consistently demonstrable monoclonal proliferation in serum and urine including free light chain assay and IF. Bhutani et al when they evaluated the hematologic characteristics of proliferative GN with unorganized monoclonal immunoglobulin deposits in a retrospective analysis of 60 cases, demonstrated nephro-pathic clone in serum and marrow in only 30% of cases. When they re-analyzed IgG subtype in those nondetectable cases, they found that IgG3 sub-type was predominant. This finding emphasizes that the presence of nephropathy clone in serum is not necessary in cases of MPGN with monoclonal light chain deposits.
Our case is unique as we were not able to demonstrate monoclonal deposits in native kidney sample although ecurrence of MPGN was with monoclonal light chain deposits post trans-plant. Our findings emphasize the need for thorough evaluation for paraproteinemias in patients with idiopathic MPGN even in the absence of light chain deposition in biopsy.
Conflict of interest: None declared.
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