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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2018  |  Volume : 29  |  Issue : 3  |  Page : 705-708
Recurrence of membranous nephropathy three weeks' postrenal transplant: A surprise in store

Department of Nephrology, Kerala Institute of Medical Sciences, Trivandrum, Kerala, India

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Date of Submission16-Jan-2017
Date of Decision11-Apr-2017
Date of Acceptance15-Apr-2017
Date of Web Publication28-Jun-2018


Membranous nephropathy (MN) may occur in the transplanted kidney, either as recurrent disease in patients who had MN as the cause of end-stage renal disease (ESRD) in the native kidney or de novo, in patients who had another cause of ESRD initially. The reported incidence of recurrent MN ranges between 10% and 45%. Clinical manifestations of recurrent MN are typically observed 13-15 months after transplantation, although they may be observed much earlier (within weeks). Our patient had a recurrence in three weeks. Recurrent disease can lead to loss of the allograft.

How to cite this article:
Kumar AN, Murlidharan P, Patil S, Balan S, Ramdas P. Recurrence of membranous nephropathy three weeks' postrenal transplant: A surprise in store. Saudi J Kidney Dis Transpl 2018;29:705-8

How to cite this URL:
Kumar AN, Murlidharan P, Patil S, Balan S, Ramdas P. Recurrence of membranous nephropathy three weeks' postrenal transplant: A surprise in store. Saudi J Kidney Dis Transpl [serial online] 2018 [cited 2022 May 18];29:705-8. Available from: https://www.sjkdt.org/text.asp?2018/29/3/705/235186

   Introduction Top

Membranous nephropathy (MN) is a common cause of the nephrotic syndrome (NS) in adults and can recur after kidney transplantation causing proteinuria, allograft dysfunction and graft failure.[1] MN may occur in the transplanted kidney, either as recurrent disease in patients who had MN as the cause of end-stage renal disease (ESRD) in the native kidneys, or de novo in patients who had another cause of ESRD. The incidence of recurrent MN is 10%-45%.[2],[3] Initial reports have suggested that patients with live-related donor kidney transplant (LRDKT) are at higher risk for recurrence than those who receive deceased donor renal transplantation (DDRT). Two series that included a total of 53 patients post-LRDKT were unable to confirm a higher risk associated with LRDKT.[4] Autoantibodies against PLA2R have been reported in patients with recurrent MN.[5]

   Case Report Top

Mr. M, a 31-year-old man presented with deranged renal function in 2011. On evaluation he had NS, renal failure, and creatinine of 1.6 mg/dL with accelerated systemic hypertension. Native kidney biopsy was performed in December 2011. Light microscopy (LM) and immunofluorescence (IF) showed features of MN. Electron microscopy (EM) was not performed. Anti-PLA2R could not be checked; however, he had low C3 at that time. Virology screening was negative. He was treated with pulse glucocorticoids 1 g intravenous (i.v.) for three days followed by oral 1 mg/kg predni-solone and cyclophosphamide seven cycles with 750 mg in each cycle once monthly, followed by alternate months, but there was no remission. His creatinine was persistently 1.6 mg/dL, and there was nephrotic range protei-nuria even after treatment with cyclophos-phamide. The patient was lost to follow-up. He was being treated by another nephrologist at a local hospital, where he was initiated on peritoneal dialysis (PD) with a Tenckhoff PD catheter. He had been on ESRD treatment for four years with PD.

The patient was worked up for LRDKT in late 2015 with mother as a willing donor. In February 2016, he underwent an LRDKT and the postoperative period was uneventful. The patient was on triple immunosuppression with steroids, mycophenolate, and tacrolimus. At discharge, his creatinine was 1.3 mg/dL.

On February 20, 2016, 15 days following transplantation, regular follow-up revealed a mild rise in creatinine to 1.6 mg/dL with urine examination showing 1+ proteinuria and no red blood cells. Infection and transplant renal artery stenosis were ruled out, and the patient was pulsed with injection methylprednisolone 500 mg i.v. suspecting acute rejection. His creatinine reduced to 1.3 mg/dL after pulse therapy. A week later, the creatinine again increased to 1.6 mg/dL. In the wake of progressive rise in creatinine even after adequate drug levels, transplant kidney biopsy was performed. LM showed thickened basement membranes [Figure 1] with spikes on silver stain [Figure 2]. IF showed 3+granular positivity along the loops for IgG, C3c, kappa, and lambda; staining for IgG subclasses was not done. EM study revealed electron-dense deposits in the basement membrane clinching the diagnosis of MN [Figure 3]. His urine protein-creatinine ratio was 300 mg/g. The patient has a creatinine of 1.6 mg/dL when last seen, and he is being followed-up regularly. He continues to be on triple immunosuppression and supportive measures.
Figure 1: Light microscopy of the allograft biopsy showing thickened basement membrane; ×400 PAS staining.

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Figure 2: Silver methenamine staining of the allograft biopsy showing thickened basement membrane with spikes; ×400.

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Figure 3: Electron microscopy of the allograft biopsy showing electron-dense deposits confirming the diagnosis of membranous nephropathy.

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   Discussion Top

Recurrent MN is suspected in the transplant patient who develops new and progressive proteinuria and/or an elevated serum creatinine level. The best data are from one study of 19 patients with MN who underwent surveillance biopsies after transplantation, of which recurrent MN was detected in eight (42%).[1]

Early reports have suggested that LRDKT patients are at higher risk for recurrent MN than those who underwent DDRT, though this has not been confirmed by larger studies.[1],[6],[7] Although the rate of recurrence was modestly higher among patients who had a LRDKT compared with those who received a DDRT (4 of 8, or 50%, vs. 8 of 27, or 30%, respectively), the difference was not significant. Two other series that included a total of 53 patients were also unable to confirm a higher risk associated with LRDKT for recurrent MN.

Our case underwent an LRDKT which may be the reason for the recurrence of the disease early in the transplant period. Recurrent MN is typically observed 13–15 months after transplantation, although they may be observed much earlier (within weeks).[6],[7] Our patient developed a progressive rise in creatinine in the 3rd week posttransplant with a protein creatinine ratio of 300 mg/g of creatinine. In one study of eight patients with recurrent MN diagnosed by surveillance biopsies, three had normal protein excretion, and five had protein excretion greater than 150 mg/day but <3 g/day at the time of biopsy.[6]

The association of the PLA2R antigen/autoantibody system in the majority of primary MN cases also holds true in recurrent MN. Occasionally, rapid recurrence of MN following transplantation suggests the presence of a circulating factor that may be present at the time of transplantation.[5] Autoantibody to the M-type PLA2R, has been implicated in the pathogenesis of MN.

In a study, 50% (5 of 10) of recurrent MN cases were seropositive for anti-PLA2R, and all five stained positively for the PLA2R antigen within immune deposits on biopsy of the allograft.[8] In another study, PLA2R staining within deposits had a sensitivity of 83% and a specificity of 92% for recurrent MN.[9],[10] Similar to findings in primary MN of the native kidney, IgG4 is the dominant or co-dominant IgG subclass in recurrent MN. These associations may be helpful in distinguishing recurrent MN from de novo MN. In our case, anti-PLA2R was negative, and serial anti-PLA2R was not done.

There is a report of one such patient in literature, who developed recurrent disease 13 days after LRDKT, and PLA2R and mono-typic IgG3 were co-localized in glomerular deposits.[11] This patient was also shown to have circulating anti-PLA2R antibodies of the same immunoglobulin G3 (IgG3) kappa subclass that was present in glomerular deposits of both the native kidney and the allograft, strongly suggesting that this antibody caused the glomerular disease.[12]

Other autoantibodies, such as those to throm-bospondin type-1 domain-containing 7A (THSD7A), have been identified in patients with primary MN, but not recurrent MN.[13]

   Conclusion Top

This case report shows an early recurrence of native kidney disease MN in an LRDKT recipient within a span of three weeks, being treated with triple immunosuppression and supportive measures. The patient has stable graft function after steroid pulse therapy, with a stable creatinine of 1.3 mg/dL and trace proteinuria.

Conflict of interest: None declared.

   References Top

Dabade TS, Grande JP, Norby SM, Fervenza FC, Cosio FG. Recurrent idiopathic membranous nephropathy after kidney transplantation: A surveillance biopsy study. Am J Transplant 2008;8:1318-22.  Back to cited text no. 1
Moroni G, Gallelli B, Quaglini S, et al. Longterm outcome of renal transplantation in patients with idiopathic membranous glomerulo-nephritis (MN). Nephrol Dial Transplant 2010; 25:3408-15.  Back to cited text no. 2
Obermiller LE, Hoy WE, Eversole M, Sterling WA. Recurrent membranous glomeruloneph-ritis in two renal transplants. Transplantation 1985;40:100-2.  Back to cited text no. 3
Stahl R, Hoxha E, Fechner K. PLA2R auto-antibodies and recurrent membranous nephropathy after transplantation. N Engl J Med 2010;363:496-8.  Back to cited text no. 4
Sprangers B, Lefkowitz GI, Cohen SD, et al. Beneficial effect of rituximab in the treatment of recurrent idiopathic membranous nephropathy after kidney transplantation. Clin J Am Soc Nephrol 2010;5:790-7.  Back to cited text no. 5
Ponticelli C, Glassock RJ. Posttransplant recurrence of primary glomerulonephritis. Clin J Am Soc Nephrol 2010;5:2363-72.  Back to cited text no. 6
Debiec H, Martin L, Jouanneau C, et al. Autoantibodies specific for the phospholipase A2 receptor in recurrent and de novo membranous nephropathy. Am J Transplant 2011; 11:2144-52.  Back to cited text no. 7
Larsen CP, Walker PD. Phospholipase A2 receptor (PLA2R) staining is useful in the determination of de novo versus recurrent membranous glomerulopathy. Transplantation 2013;95:1259-62.  Back to cited text no. 8
Kearney N, Podolak J, Matsumura L, Houghton D, Troxell M. Patterns of IgG subclass deposits in membranous glomerulonephritis in renal allografts. Transplant Proc 2011;43:3743-6.  Back to cited text no. 9
Choy BY, Chan TM, Lai KN. Recurrent glomerulonephritis after kidney transplantation. Am J Transplant 2006;6:2535-42.  Back to cited text no. 10
Debiec H, Hanoy M, Francois A, et al. Recurrent membranous nephropathy in an allograft caused by IgG3K targeting the PLA2 receptor. J Am Soc Nephrol 2012;23:1949-54.  Back to cited text no. 11
Beck LH Jr. Monoclonal anti-PLA2R and recurrent membranous nephropathy: Another piece of the puzzle. J Am Soc Nephrol 2012; 23:1911-3.  Back to cited text no. 12
Tomas NM, Beck LH Jr., Meyer-Schwesinger C, et al. Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy. N Engl J Med 2014;371:2277-87.  Back to cited text no. 13

Correspondence Address:
Dr. Arun Narayanan Kumar
Department of Nephrology, Kerala Institute of Medical Sciences, Trivandrum, Kerala
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-2442.235186

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