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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2015  |  Volume : 26  |  Issue : 5  |  Page : 970-975
A case of primary renal allograft dysfunction due to myeloma cast nephropathy

1 Department of Nephrology, Institute of Nephro Urology, Bengaluru, Karnataka, India
2 Department of Pathology, Manipal Hospital, Bengaluru, Karnataka, India

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Date of Web Publication7-Sep-2015


We report a rare case of primary renal allograft dysfunction due to myeloma cast nephropathy in a patient with no overt clinical features of multiple myeloma preceding his transplantation. A 45-year-old man on hemodialysis for six months for end-stage kidney disease due to presumed chronic glomerulonephritis developed immediate graft dysfunction post-transplantation. The graft biopsy was diagnostic of myeloma cast nephropathy. Other criteria for lambda light chain multiple myeloma were fulfilled with immunofixation electrophoresis and bone marrow biopsy. He was treated with plasmapheresis, bortezomib and high-dose dexamethasone. However, the patient succumbed to septicemia on the 37 th post-operative day. This is probably the first report of primary renal allograft dysfunction due to myeloma cast nephropathy diagnosed within the first week posttransplanation in a patient with unrecognized multiple myeloma.

How to cite this article:
Lingaraj U, Vankalakunti M, Radhakrishnan H, Sreedhara C G, Rajanna S. A case of primary renal allograft dysfunction due to myeloma cast nephropathy. Saudi J Kidney Dis Transpl 2015;26:970-5

How to cite this URL:
Lingaraj U, Vankalakunti M, Radhakrishnan H, Sreedhara C G, Rajanna S. A case of primary renal allograft dysfunction due to myeloma cast nephropathy. Saudi J Kidney Dis Transpl [serial online] 2015 [cited 2023 Feb 6];26:970-5. Available from: https://www.sjkdt.org/text.asp?2015/26/5/970/164581

   Introduction Top

Common causes of primary renal allograft dysfunction include ischemic acute tubular necrosis and reperfusion injury, renal artery or vein thrombosis, ureteral obstruction and, rarely, hyperacute rejection in the recent era of immunosupression. [1] Herein, we report an exceptional case of primary renal allograft dysfunction due to myeloma cast nephropathy in a patient with no overt clinical clues of multiple myeloma prior to his transplantation.

   Case Report Top

A 45-year-old male patient was referred to our institute for renal transplantation. He was diagnosed to have end-stage kidney disease due to presumed chronic glomerulonephritis and was on maintenance hemodialysis through left arterio-venous fistula for six months prior to transplantation. His past medical history was significant for hypertension of two years duration prior to the diagnosis of chronic kidney disease. There was no history of systemic symptoms including backache or bone pain. Abdominal ultrasound showed highly echogenic kidneys. Kidney biopsy by the referring physician had been deferred due to high echogenicity of the kidneys.

Before admission to our hospital, the patient had hematemesis due to severe antral hemorrhagic gastritis. His hemoglobin was 4.6 g/dL. He was treated with packed cell transfusion and proton pump inhibitors. He responded to erythropoietin and intravenous iron supplementation and achieved hemoglobin of 12.4 g/dL. His erythropoietin dose was titrated to maintain a hemoglobin level of 10.6 g/dL immediately prior to transplantation.

On examination, he was a thin built adult with body mass index of 18.61 kg/m 2 . Vital signs were stable. Systemic examination was unremarkable. Laboratory evaluation included 2+ proteinuria, with no active sediments, total calcium of 7.8 mg/dL, phosphorus of 7.0 mg/dL, alkaline phosphatase of 95 IU/L, total protein of 8.0 g/dL and albumin of 4.1 g/dL. Ultrasound showed bilaterally echogenic kidneys with a thinned out cortex.

He underwent live donor renal transplantation with a 38-year-old spousal donor. He had prolonged ischemia time due to anastomotic leak, he remained oliguric. Renal allograft ultrasound and Doppler were normal. His immunosuppression included intravenous methylprednisolone for three days followed by oral prednisolone, mycophenolate mofetil and low-dose tacrolimus. Hemodialysis was continued in view of persistent allograft dysfunction and a graft biopsy was planned. Renal allograft biopsy performed on the 3 rd post-operative day revealed presence of fractured and lamellated casts (Periodic acid-Schiff negative and fuchsinophilic) in the tubular lumen, suggestive of cast nephropathy with acute tubular injury and no evidence of rejection [Figure 1]. Multinucleated giant cells were not seen. Immunofluorescence showed intense staining for lambda light chain within the casts [Figure 2] and negative staining for kappa light chain and C4d in the peritubular capillaries. Subsequent serum protein electrophoresis revealed "M spike" in the gamma region and immunofixation electrophoresis revealed elevated free lambda light chains (31,400 mg/L against a normal value of 5.71-26.3 mg/L) and kappa:lambda ratio of 0.0003 (normal of 0.37-3.1), suggestive of free lambda light chain myeloma. Bone marrow biopsy revealed hypercellular marrow with 40% plasma cells, including binucleated and immature forms. Serum β2 microglobulin was elevated >27.20 mg/L (0.7-1.98mg/L). Radiological survey was negative for lytic lesions.
Figure 1: Renal allograft biopsy on POD 3 (Periodic acid–Schiff stain): Tubules show presence of PAS-negative lamellated and fractured casts with neutrophilic adherence at the periphery of the scalloped casts.

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Figure 2: Direct immunofluorescence showed intense staining for lambda light chain within the casts.

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After discussion with the patient's relatives and getting informed consent, he was started on bortezomib and oral dexamethasone 40 mg/day once weekly. He received four sessions of plasmapheresis for free light chain clearance. The tacrolimus and mycophenolate mofetil dose was reduced. The patient had developed hypercalcemia, which was treated with zolendronic acid. The patient received five doses of weekly bortezomib and high-dose dexamethasone. Further dose of bortezomib was withheld due to severe thrombocytopenia and painful peripheral neuropathy. The patient continued to be oliguric and dialysis dependent. After six weeks of his transplant surgery, the patient developed pneumonia and sepsis that did not respond to antibiotic treatment and he succumbed. Post-mortem graft biopsy showed multinucleated giant cell reaction [Figure 3] and mild degree of interstitial fibrosis, in addition to the findings observed in the first biopsy.
Figure 3: Post-mortem renal allograft biopsy on POD 37 (Periodic acid–Schiff stain): Tubules show presence of PAS-negative casts with surrounding giant cell reaction and interstitial infiltrates.

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   Discussion Top

Renal insufficiency is present in up to half of myeloma patients at presentation, contributes to excessive early mortality and diminishes eligibility and clinical outcomes after both systemic therapy and high-dose stem cell transplantation (SCT) as well as novel treatments. [2] Myeloma cast nephropathy is the most common cause of acute renal failure in patients with multiple myeloma. [3]

Although there are reported cases of recurrences in the literature, only limited number of cases (<50 cases) [4] have been in the <6 months of post-transplant period. The true role of renal transplantation in patients with renal failure and myeloma is not known. This is compounded by current advanced therapy including bortezomib, plasmapharesis, high-dose dexamethasone and hemopoetic stem cell transplantation. In the absence of control of excessive light chain production, outcomes are poor with reports of recurrent cast nephropathy as early as three months after transplantation. [5],[6] Renal transplantation is performed in selected patients who are in remission and have undergone successful hematopoietic stem cell transplantation. In addition, combined kidney and non-myeloablative marrow transplantation from HLA-identical siblings has been reported with excellent myeloma response and good renal allograft tolerance. [7]

There are only four reported cases of primary renal allograft dysfunction due to myeloma cast nephropathy in the literature [1],[8],[9],[10] [Table 1]. Geiger et al [8] reported a 55-year-old woman who was on hemodialysis for 15 months for end-stage renal disease of unknown etiology. The diagnosis of lambda light chain cast nephropathy was made on the fourth allograft biopsy on post-operative Day 81 with no recovery of renal function. Foster et al.[9] reported a case of a 63-year-old man with biopsy-proven diabetic glomerulosclerosis who was diagnosed with kappa light chain cast nephropathy on the second allograft biopsy performed five weeks post-transplantation. The patient was initially treated with a combination of high-dose dexamethasone and thalidomide and then with melphalan and prednisone. Despite excellent hematologic response, he remained dialysis dependent at four months.
Table 1: Comparison of other reported cases of primary renal allograft dysfunction due to myeloma cast nephropathy.

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Perkowska-Ptasinska et al [10] reported a 51year-old man who was on dialysis for one year for end-stage renal disease of unknown etiology. He was diagnosed with multiple myeloma cast nephropathy and mild thrombotic microangiopathy on his first graft biopsy on postoperative Day 21. He subsequently underwent allograft nephrectomy due to persistent dysfunction. Goel et al [1] reported a 72-year-old woman with end-stage renal disease on hemodialysis for four years who developed primary allograft dysfunction due to allograft myeloma cast nephropathy. The patient recovered renal function by Day 90 after treatment with bortezomib, dexamethasone and plasmapheresis. Hence, the same regimen was used in our patient.

Except for one patient reported by Goel et al, [1] the rest of the patients had graft loss [8],[9],[10] and two patients underwent graft nephrectomy. [8],[10] All other reported cases have received deceased donor allografts while our patient received live donor kidney transplantation. Another peculiar feature observed from our case and from those in the literature is that all cases except one are cases of lambda light chain-restricted myeloma.

All the four reported patients were diagnosed at varying intervals after transplantation, ranging from post-operative Day 21 to post-operative Day 81 requiring multiple biopsies, whereas our patient was diagnosed on post-operative Day 3. [8],[9],[10],[1] Hence, our case is probably the first case report of primary renal allograft dysfunction due to myeloma cast nephropathy diagnosed within the first week of transplantation. The probable precipitating factor for very early occurrence of myeloma cast nephropathy in our patient could be acute tubular injury due to prolonged ischemic time and sudden exposure of the tubules to a very high load of lambda light chains.

The other unusual features of this patient are relatively younger age of presentation for myeloma and absence of other clinical clues for multiple myeloma, like unintentional weight loss, bone pains, difficulty in achieving target hemoglobin despite iron and erythropoietin supplementation, hypercalcemia or altered albumin globulin ratio.

   Conclusion Top

We report a rare case of a 45-year-old man with end-stage renal disease who developed primary allograft dysfunction due to myeloma cast nephropathy. This case highlights the importance of establishing an etiological diagnosis for patients with renal failure of unknown etiology. This case also raises the question for the routine use of electrophoresis as part of the pre-transplantation evaluation.

   References Top

Goel SK, Granger D, Bellovich K, Marin M, Qu H, El-Ghoroury M. Myeloma cast nephropathy: A rare cause of primary renal allograft dysfunction. Transplant Proc 2011;43:2784-8.  Back to cited text no. 1
Heher EC, Goes NB, Spitzer TR, et al. Kidney disease associated with plasma cell dyscrasias. Blood 2010;116:1397-404.  Back to cited text no. 2
Pasquali S, Zucchelli P, Casanova S, et al. Renal histological lesions and clinical syndromes in multiple myeloma. Renal Immunopathology Group. Clin Nephrol 1987;27:222-8.  Back to cited text no. 3
Dagher F, Sammett D, Abbi R, Tomasula JR, Delaney V, Butt KM. Renal transplantation in multiple myeloma. Case report and review of the literature. Transplantation 1996;62:1577-80.  Back to cited text no. 4
Leung N, Lager DJ, Gertz MA, Wilson K, Kanakiriya S, Fervenza FC. Long-term outcome of renal transplantation in light-chain deposition disease. Am J Kidney Dis 2004;43:147-53.  Back to cited text no. 5
De Lima JJ, Kourilsky O, Meyrier A, MorelMaroger L, Sraer JD. Kidney transplant in multiple myeloma. Early recurrence in the graft with sustained normal renal function. Transplantation 1981;31:223-4.  Back to cited text no. 6
Fudaba Y, Spitzer TR, Shaffer J, et al. Myeloma responses and tolerance following combined kidney and nonmyeloablative marrow transplantation: In vivo and in vitro analyses. Am J Transplant 2006;6:2121-33.  Back to cited text no. 7
Geiger X, Harris D, Van Buren D, Goral S, Helderman JH, Fogo A. A middle-aged woman with refractory graft dysfunction in the early posttransplant period. Am J Kidney Dis 1999;33:998-1003.  Back to cited text no. 8
Foster K, Cohen DJ, D'Agati VD, Markowitz GS. Primary renal allograft dysfunction. Am J Kidney Dis 2004;44:376-81.  Back to cited text no. 9
Perkowska-Ptasinska A, Glyda M, Paczkowski M, Durlik M. Primary kidney allograft dysfunction due to myeloma-cast nephropathy: A case report. Transplant Proc 2007;39:1683-4.  Back to cited text no. 10

Correspondence Address:
Umesh Lingaraj
Department of Nephrology Institute of Nephro-Urology, Victoria Hospital Campus, Bengaluru, Karnataka - 560 002
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-2442.164581

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  [Figure 1], [Figure 2], [Figure 3]

  [Table 1]

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[Pubmed] | [DOI]


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