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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2016  |  Volume : 27  |  Issue : 4  |  Page : 816-820
Minimal change disease: A case report of an unusual relationship

1 Department of Medicine, Division of Nephrology, Washington University School of Medicine, Barnes Jewish Hospital, Saint Louis, MO, USA
2 Division of Renal Medicine, Saint Vincent Hospital; Reliant Medical Group, Worcester, MA, USA
3 Department of Hematology Oncology, Saint Vincent Hospital; Reliant Medical Group, Worcester, MA, USA
4 Department of Renal Pathology, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA

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Date of Web Publication5-Jul-2016


Kidney injury associated with lymphoproliferative disorders is rare, and the exact pathogenetic mechanisms behind it are still poorly understood. Glomerular involvement presenting as a nephrotic syndrome has been reported, usually secondary to membranoproliferative glomerulonephritis. We report a case of a 63-year-old male who presented with bilateral leg swelling due to nephrotic syndrome and acute kidney injury. A kidney biopsy showed minimal change disease with light chain deposition; however, no circulating light chains were present. This prompted a bone marrow biopsy, which showed chronic lymphocytic leukemia (CLL) with deposition of the same kappa monoclonal light chains. Three cycles of rituximab and methylprednisolone resulted in remission of both CLL and nephrotic syndrome, without recurrence during a three-year follow-up.

How to cite this article:
Edrees F, Black RM, Leb L, Rennke H. Minimal change disease: A case report of an unusual relationship. Saudi J Kidney Dis Transpl 2016;27:816-20

How to cite this URL:
Edrees F, Black RM, Leb L, Rennke H. Minimal change disease: A case report of an unusual relationship. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2022 Nov 27];27:816-20. Available from: https://www.sjkdt.org/text.asp?2016/27/4/816/185271

   Introduction Top

Minimal change disease (MCD) is the most common cause of nephrotic syndrome in children but it may occur in adults as well. Although nephrotic syndrome can be associated with a number of solid and hematological malignancies, [1],[2],[3],[4],[5] the association with chronic lymphocytic leukemia (CLL) is unusual. There are only 18 reported cases of MCD with CLL in the medical literature, [4],[5],[6],[7],[8] and only one of these patients had documented circulating monoclonal light chains, [6] we report a case of MCD with kappa light chain deposition in the mesangium without detectable urinary or serum light chains. The nephrotic syndrome responded to the treatment of CLL with rituximab and methylprednisolone.

   Case Report Top

The patient is a 63-year-old Caucasian male with a history of coronary artery disease, heart failure with preserved ejection fraction, hypertension, and chronic kidney disease with a baseline serum creatinine of 1.5 mg/dL. He presented to our hospital with shortness of breath and lower extremity edema. On initial examination, he was in no distress, blood pressure 187/95 mm Hg, pulse 90 beats/min, and O 2 saturation was 95% on 2 L nasal cannula. He had bilateral basal crackles and soft pitting pedal edema up to the knees. The remainder of the examination was unremarkable. Laboratory data showed a mild elevation of his creatinine to 1.74 mg/dL, mild thrombocytopenia 120,000 with a normal white blood cell count (WBC) of 7800/μL with normal differential count. Hemoglobin was 12.9 g/dL at this time. His urine dipstick showed 3+ protein. His serum albumin was 2.5 g/dL. His lipid profile was normal except for elevated triglycerides at 204 mg/dL. A random urine estimated his protein excretion to be 9.7 g/day. Renal ultrasound showed asymmetry with a small kidney on the right. As a result, a renal biopsy was canceled and he was placed on methylprednisolone 48 mg/day for the idiopathic nephrotic syndrome and discharged home. He had an initial response with a fall in urinary protein to 1.5 g/day and improvement in his edema.

At two months, he presented with worsening proteinuria and edema despite continuing the same dose of methylprednisolone with which he was compliant by history. Cyclosporine was added to his regimen. Serum creatinine increased to 5.2 mg/dL following one day of cyclosporine administration, which was markedly higher compared to 1.43 mg/dL three weeks earlier. Urine sediment showed lipid and abundant granular casts. Other abnormal tests included BUN 174 mg/dL, hemoglobin (Hgb) 9.3 g/dL, and platelet count 152,000 μL, which fell to 82,000 μL three days later. WBC remained normal. His renal function continued to worsen and hemodialysis was initiated. At this time, he underwent a percutaneous renal biopsy which on electron microscopy showed diffuse foot process effacement and scattered small electron dense deposits present within the mesangial matrix [Figure 1]a and b. Immunofluorescence microscopy showed the segmental granular deposition of IgM (2+/4+), kappa light chains (2+/4+), no lambda light chain reactivity, and trace C3 in the mesangial areas [Figure 1]c-e. Both serum and urine immunofixation performed on two separate occasions were negative. Free light chain ratio was normal at 0.89 (normal 0.26-1.65). Because of the IgM kappa deposits, he underwent a bone marrow biopsy. The bone marrow aspirate and biopsy showed a B-cell monoclonal population that was CD5, CD20, and CD23 positive [Figure 1]f and g with surface IgM kappa immunoglobulin, representing 34% of bone marrow cellularity, which was diagnostic of CLL. Cytogenetics and fluorescence in situ hybridization (FISH) studies showed that the B lymphocytes had a deletion of 13q and trisomy 12, characteristically associated with CLL.
Figure 1: (a) Diffuse effacement of foot processes, ×4000 (red arrows in a and b). (b) Mesangial electron dense deposits (asterix) ×6000. (c) Immunofluorescence positive for mesangial IgM deposits. (d and e) Immunofluorescence shows the deposits are reactive for kappa but not lambda light chains. (f and g) Bone morrow biopsy showing lymphocytes positive for CD20 and CD5.

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Based on these findings, treatment with rituximab 375 mg/m 2 once a week for four weeks and methylprednisolone 1 g/m 2 on the first 3 days of the week was initiated. After three cycles, his nephrotic syndrome improved (urine protein excretion below 500 mg/day) and his serum creatinine fell below 2 mg/dL; he no longer required dialysis [Figure 2]. The Hgb and platelets increased to 13.2 and 153,000, respectively. He has remained in remission from nephrotic syndrome and CLL for over three years without further treatment. However, he developed hypogammaglobulinemia most likely secondary to rituximab treatment with IgA 20 mg/dL (normal 81-463 mg/dL), IgG 125 mg/dL (normal 694-1618 mg/dL), and IgM <1 mg/dL (normal 48-271 mg/dL). This has resolved after two years of conservative management.
Figure 2: Protein/creatinine ratio over treatment course.

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   Discussion Top

This is an unusual case of MCD secondary to underlying CLL with no hematologic manifestations other than bone marrow and renal involvement. The main clue to a hematological disorder as the cause was the IgM kappa deposition in the mesangium on renal biopsy. While IgM nephropathy, evident by IgM mesangial deposits on kidney biopsy, is a common pattern of MCD, especially in children and is usually associated with steroid resistant or steroid dependent nephrotic syndrome. [9] Staining is usually positive for both kappa and lambda. In contrast to the case of Alzamora, [6] a monoclonal protein was not detected in the blood or urine of our patient. Identifying mesangial deposition of monoclonal light chains on renal biopsy in minimal chain disease should trigger a search for an underlying lymphoproliferative disorder. The acute kidney injury was attributed to acute tubular necrosis, which has been observed in MCD [10] and was unlikely to be due to one day of cyclosporine administration.

Of the 18 previously reported cases of CLL with MCD, treatment was reported on 13 of the patients [Table 1]. Most were treated with corticosteroids alone or in combination with chlorambucil. Two of the previous cases were treated with rituximab, one as initial treatment and the other as second line after steroid plus chlorambucil failed. [5] Resolution of the nephrotic syndrome occurred in the first case but not the second. While rituximab has been used successfully to treat idiopathic MCD, [16],[17] the deposition of monotypic immunoglobulin on biopsy supports a secondary form of the disease. The treatment of the underlying cause has been associated with resolution of the nephrotic syndrome in this setting. The combination treatment of rituximab with methylprednisolone is an effective treatment for CLL and is well tolerated. [18] A major side effect of rituximab is hypogammaglobulinemia, [19] which necessitates careful follow-up to detect infections early.
Table 1: Cases of chronic lymphocytic leukemia and minimal change disease that reported data about treatment and outcome (13 cases).

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   Conclusion Top

The major significance of our case is that it brings to light the importance of aggressively pursuing the etiology of MCD in patients with nephrotic syndrome with immunoglobulin deposition, even when serum and urine immune-fixation and the WBC are normal.

   Acknowledgment Top

We thank Dr. Joel Popkin for his time and comments that greatly improved the manuscript.

Conflict of interest: None declared.

   References Top

Audard V, Larousserie F, Grimbert P, et al. Minimal change nephrotic syndrome and classical Hodgkin's lymphoma: Report of 21 cases and review of the literature. Kidney Int 2006;69:2251-60.  Back to cited text no. 1
Lien YH, Lai LW. Pathogenesis, diagnosis and management of paraneoplastic glomerulonephritis. Nat Rev Nephrol 2011;7:85-95.  Back to cited text no. 2
Wagrowska-Danilewicz M, Danilewicz M. Nephrotic syndrome and neoplasia: our experience and review of the literature. Pol J Pathol 2011;62:12-8.  Back to cited text no. 3
Da'as N, Polliack A, Cohen Y, et al. Kidney involvement and renal manifestations in non-Hodgkin's lymphoma and lymphocytic leukemia: a retrospective study in 700 patients. Eur J Haematol 2001;67:158-64.  Back to cited text no. 4
Kofman T, Zhang SY, Copie-Bergman C, et al. Minimal change nephrotic syndrome associated with non-Hodgkin lymphoid disorders: a retrospective study of 18 cases. Medicine (Baltimore) 2014;93:350-8.  Back to cited text no. 5
Alzamora MG, Schmidli M, Hess U, Cathomas R, von Moos R. Minimal change glomerulonephritis in chronic lymphocytic leukemia: pathophysiological and therapeutic aspects. Onkologie 2006;29:153-6.  Back to cited text no. 6
Kowalewska J, Nicosia RF, Smith KD, Kats A, Alpers CE. Patterns of glomerular injury in kidneys infiltrated by lymphoplasmacytic neoplasms. Hum Pathol 2011;42:896-903.  Back to cited text no. 7
Poitou-Verkinder AL, Francois A, Drieux F, et al. The spectrum of kidney pathology in B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma: a 25-year multicenter experience. PLoS One 2015;10:e0119156.  Back to cited text no. 8
Swartz SJ, Eldin KW, Hicks MJ, Feig DI. Minimal change disease with IgM+ immunofluorescence: a subtype of nephrotic syndrome. Pediatr Nephrol 2009;24:1187-92.  Back to cited text no. 9
Tavares MB, Chagas de Almeida Mda C, Martins RT, de Sousa AC, Martinelli R, dos-Santos WL. Acute tubular necrosis and renal failure in patients with glomerular disease. Ren Fail 2012;34:1252-7.  Back to cited text no. 10
Kerkhoven P, Briner J, Blumberg A. Nephrotic syndrome as the 1st manifestation of malignant lymphoma. Schweiz Med Wochenschr 1973;103:1706-9.  Back to cited text no. 11
Seney FD Jr., Federgreen WR, Stein H, Kashgarian M. A review of nephrotic syndrome associated with chronic lymphocytic leukemia. Arch Intern Med 1986;146:137-41.  Back to cited text no. 12
Farrant JM, Taylor CG, Beer SF. Nephrotic syndrome in chronic lymphocytic leukaemia. Br J Haematol 1988;69:419.  Back to cited text no. 13
Vivaldi P, Frizzi R, Rovati C, Pedrazzoli M. Nephrotic syndrome in chronic lymphocytic leukemia. Haematologica 1992;77:438-9.  Back to cited text no. 14
Spalding EM, Watkins S, Warwicker P. Minimal-change glomerulonephritis and chronic lymphocytic leukaemia. Nephron 2001;88:283-4.  Back to cited text no. 15
Takei T, Itabashi M, Moriyama T, et al. Effect of single-dose rituximab on steroid-dependent minimal-change nephrotic syndrome in adults. Nephrol Dial Transplant 2013;28:1225-32.  Back to cited text no. 16
Munyentwali H, Bouachi K, Audard V, et al. Rituximab is an efficient and safe treatment in adults with steroid-dependent minimal change disease. Kidney Int 2013;83:511-6.  Back to cited text no. 17
Castro JE, James DF, Sandoval-Sus JD, et al. Rituximab in combination with high-dose methylprednisolone for the treatment of chronic lymphocytic leukemia. Leukemia 2009;23:1779-89.  Back to cited text no. 18
Makatsori M, Kiani-Alikhan S, Manson AL, et al. Hypogammaglobulinaemia after rituximab treatment-incidence and outcomes. QJM 2014;107:821-8.  Back to cited text no. 19

Correspondence Address:
Fahad Edrees
Washington University School of Medicine, Barnes Jewish Hospital, St. Louis, MO 63110
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-2442.185271

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