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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT Table of Contents   
Year : 2010  |  Volume : 21  |  Issue : 4  |  Page : 738-741
Membranoproliferative glomerulonephritis secondary to chronic myeloid leukemia


1 Department of Medical Oncology, M.S. Ramaiah Medical College, Bangalore, India
2 Department of General Medicine, M.S. Ramaiah Medical College, Bangalore, India
3 Department of Pathology, M.S. Ramaiah Medical College, Bangalore, India

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Date of Web Publication26-Jun-2010
 

   Abstract 

The nephrotic syndrome (NS) is a well documented complication of hematological malignancies. However, chronic myeloid leukemia (CML) is rarely complicated by the NS, and it occurs usually after allogenic stem cell transplantation or interferon alpha therapy for CML. The NS as a complication of untreated CML is also rare. We report a 31-year-old patient who pre­sented with features of The NS. He was diagnosed to have CML one year ago and was on irre­gular treatment with imatinib mesylate. The renal biopsy and immunofluorescence revealed mem­branoproliferative glomerulonephritis type I. The patient was retreated with imatinib mesylate and the NS resolved gradually over three months. This maybe the third case in literature of mem­branoproliferative glomerulonephritis associated with CML.

How to cite this article:
Subramanian M, Kilara N, Manjunath R, Mysorekar V. Membranoproliferative glomerulonephritis secondary to chronic myeloid leukemia. Saudi J Kidney Dis Transpl 2010;21:738-41

How to cite this URL:
Subramanian M, Kilara N, Manjunath R, Mysorekar V. Membranoproliferative glomerulonephritis secondary to chronic myeloid leukemia. Saudi J Kidney Dis Transpl [serial online] 2010 [cited 2019 Oct 18];21:738-41. Available from: http://www.sjkdt.org/text.asp?2010/21/4/738/64664

   Introduction Top


The nephrotic syndrome (NS) is characte­rized by massive proteinuria, hypoalbumine­mia, edema, and high levels of serum choles­terol. Since 1922, when the link between the NS and malignancy was first elucidated, many case reports and reviews have analyzed their association. [1]

The occurrence of the NS is well documented in hematopoietic malignancies, especially Hodg­kin's lymphoma, non-Hodgkin's lymphoma and chronic lymphocytic leukemia. Chronic myeloid leukemia (CML) is a myeloprolifera­tive disease of hematopoietic stem cells that possess a reciprocal translocation between chro­mosome 9 and 22 i.e. Philadelphia chromosome t (9; 22). The NS in CML has been mainly reported as a complication of interferon alpha therapy or stem cell transplantation for CML. [2],[3]

The occurrence of NS in CML prior to any therapy has been reported in five cases, among which the NS responded to chemotherapy in two. [1],[2],[4] We present the third case in the me­ dical literature of membranoproliferative glo­merulonephritis complicating CML, which res­ponded to treatment with imatinib mesylate.


   Case Report Top


A 31-year-old man was diagnosed to have CML one year prior to development of the NS. Investigations at diagnosis revealed hemoglo­bin of 9.1 gm/dL, total count of 82.1 Χ 10 9 /L, platelet count of 620 Χ 10 9 /L and a peripheral smear blood picture of CML. Chromosomal analysis revealed Philadelphia chromosome t (9; 22). He was started on imatinib mesylate, but he was irregular on treatment and lost to follow-up.

He presented to us with complaints of swe­lling of the face and both lower limbs and dis­tension of the abdomen for the past 2 months. He had discontinued imatinib mesylate four months earlier. He was normotensive and had edema anasarca involving his face and lower limbs besides gross ascites and bilateral pleu­ral effusion. Investigations revealed hemoglo­bin of 10.9 gm/dL, total count of 10.1 Χ 10 9 /L, 83% being neutrophils, platelet count of 224 Χ 10 9 /L and a normocyitc normochromic blood picture. Serum creatinine was 100 umol/L. The liver function tests included a total serum pro­tein level of 41 g/L and serum albumin of 5 gm/L. Lipid profile revealed hypercholestero­lemia (12.21 mmol/L). Urinalysis showed 3(+) albuminuria. 24-hr urine protein was 9.8 gm/ day. Bilateral pleural effusion was noted on chest roentgenogram. 2-D echo was normal. Ultrasound of the abdomen and pelvis illus­trated the presence of splenomegaly of 14 cms, bilateral grade II nephropathy, and gross ascites. Light microscopy of the renal biopsy specimen revealed enlarged glomeruli with thickening of the glomerular basement membrane, mesangial hypercellularity, and mesangial matrix accumu­lation. The tubules and blood vessels were un­remarkable, while the interstitium showed mo­nonuclear cells with no leukemic infiltration [Figure 1] and [Figure 2].

These features were suggestive of membra­noproliferative glomerulonephritis type I. It was confirmed by immunofluorescence, which showed granular reaction for IgG (+++) and C3 (+) along the glomerular capillary walls [Figure 3].

On further evaluation, the patient was negative for anti-nuclear antibody, antinuclear cytoplas­mic antibody, hepatitis B, hepatitis C, VDRL, HIV 1 and 2 serologies. Complement C3 le­vels were normal (1.14 g/L). Final diagnosis of membranoproliferative glomerulonephritis type I secondary to CML was made. The patient was treated with diuretics and imatinib mesylate in the first week. Only imatinib mesylate was continued later on, which resulted in a gradual resolution of proteinuria over three months. Currently, the patient is asymptomatic, on imatinib mesylate and on regular follow-up.


   Discussion Top


The NS is a result of disease processes that damage the glomeruli and develop proteinuria. Membranoproliferative glomerulonephritis ac­counts for 7% of the NS in adults. Secondary membranoproliferative glomerulonephritis can be caused by chronic immune complex disea­ses such as systemic lupus erythematosus, he­patitis B infection, hepatitis C infection and human immunodeficiency viral infection. Ma­lignancies such as lymphoma, chronic lympho­cytic leukemia (CLL) and melanoma can also cause membranoproliferative glomeruloneph­ritis. The incidence of CML causing membra­noproliferative glomerulonephritis appears to be extremely rare. [1]

Different types of glomerulopathies have been associated with malignancies. However, mem­branoproliferative glomerulonephritis is more typical of lymphoproliferative malignancies. To date, 34 cases of membranoproliferative glo­merulonephritis associated with hematological malignancies have been reported. Among these the cause was CLL in 18 cases, non-Hodgkin's lymphoma in 12 cases, Hodgkin's lymphoma in two cases, AML in one case and CML in one case. [1],[4]

Possible contributory mechanisms for renal dysfunction in CML leading to the NS can be an autoimmune process or splenomegaly-asso­ciated predisposition to circulating infections and glomerular deposition of subsequent im­mune-complex formation. [1]

CML causing the NS has been reported in 5 cases [Table 1]. The renal pathologies were membranous glomerulonephritis in two cases and membranoproliferative glomerulonephritis in two cases and minimal change disease in one case. [2]

In the first reported case of CML causing membranoproliferative glomerulonephritis, the patient was simultaneously diagnosed to have the NS and CML at the initial presentation. He was treated with prednisolone, which margi­nally improved the proteinuria. The patient was then treated with busulfan (in the pre-imatinib era), which resulted in the disappearance of the myeloid cells in peripheral blood and gradual decrease in proteinuria. [5]

In the second case, the patient presented with features of nephrotic syndrome and was then diagnosed to have CML with membranopro­liferative glomerulonephritis and acute renal failure. Following the initiation of imatinib mesylate, proteinuria and renal function improved. [4]

Treatment with imatinib mesylate is often associated with fluid retention. Infrequently, pleural effusion, ascites and pulmonary edema can occur in CML patients treated with ima­tinib mesylate.

In our case, the patient was diagnosed to have CML one year before developing the NS and was started on imatinib mesylate. The patient was non-compliant to treatment and disconti­nued imatinib four months before the NS. He presented to us with features of NS and found to have membranoproliferative glomerulone­phritis. There were no other plausible causes for the NS except CML. The NS secondary to CML was confirmed from his clinical presen­tation, diagnostic findings, temporal relation­ship, discontinuance of imatinib mesylate be­fore the development of symptoms and res­ponse of the NS to imatinib mesylate therapy.

 
   References Top

1.Mallouk A, Pham PT, Pham PC. Concurrent FSGS and Hodgkin's lymphoma: case report and literature review on the link between nephrotic glomerulopathies and hematological malignancies. Clin Exp Nephrol 2006;10(4): 284-9.  Back to cited text no. 1      
2.Talwar R, Dash SC, Kucheria K. A case of chronic myeloid leukemia complicated with minimal change nephrotic syndrome. Acta Haematol 2003;109:101-3.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]  
3.Bee PC, Gan GG, Sangkar VJ, Haris AR. Nephrotic syndrome in a patient with relapsed of chronic myeloid leukemia after peripheral blood stem cell transplantation. Med J Malaysia 2008;63(1):71-2.  Back to cited text no. 3      
4.Dwyer JP, Yates KM, Sumner EL, et al. Chro­nic myeloid leukemia-associated membrano­proliferative glomerulonephritis that responded to imatinib mesylate therapy. Clin Nephrol 2007;67(3):176-81.  Back to cited text no. 4      
5.Yoshizaki N, Kohda K, Nakazawa O, et al. A case of chronic myelogenous leukemia com­plicated with nephrotic syndrome. Rinsho ketsueki 1989;30:691-6.  Back to cited text no. 5  [PUBMED]    

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Correspondence Address:
Murali Subramanian
Deptartment of Medical Oncology, M.S. Ramaiah Medical College, MSRIT Post, Bangalore-560054, Karnataka
India
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PMID: 20587884

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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1]

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