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Case Report

Indian Pediatr 2012;49: 668-670

Chronic Myeloid Leukemia in a Child with IgA Nephropathy


Amish Udani, Vijayakumar Mahalingam, Prahlad Nageswaran and *Sudha Ekambaram

From the Department of Pediatric Nephrology and *Pediatrics, Mehta Children’s Hospitals, Chennai, India.

Correspondence to: Dr M Vijayakumar, Consultant Pediatric Nephrologist, Mehta Children’s Hospitals, No.2(e) Mc Nichols Road, 3rd Lane, Chetput, Chennai 600 031, Tamilnadu, India.
Email: [email protected] 

Received: September 5, 2011;
Initial review: September 30, 2011;
Accepted: February 27, 2012.

 


We report an 11 year old boy with IgA nephropathy developing chronic myeloid leukemia on follow-up. This association suggests that a B cell defect might be involved in the pathogenesis of these two conditions.

Key words: Chronic myeloid leukemia, IgA nephropathy.


There is increasing evidence of abnormal glycosylation of immunoglobulin A1 (IgA1) subclass due to B-cell defect in the pathogenesis of immune-complex mediated IgA nephropathy [1]. The occurrence of IgA nephropathy and leukemia has been reported rarely in children [2]. Here we report a child with IgA nephropathy developing chronic myeloid leukemia (CML) on follow-up.

Case Report

An 11-yr-old boy was diagnosed acute nephritic syndrome at 3 year back in view of hypertension, hematuria, proteinuria (spot urine protein to creatinine ratio 0.75), mild renal insufficiency (serum creatinine 1.1 mg/dL), and normal serum albumin and cholesterol. He had no anemia, leukocytosis or electrolyte disturbances. He was treated with salt and fluid restriction and oral nifedepine for hypertension. Serum complement C3 level was normal, anti nuclear antibody and anti double standard DNA was negative. In view of persistent hypertension, renal insufficiency, microscopic hematuria and proteinuria he was referred for evaluation. On examination, the patient was well nourished (weight 46 kg, and height 157 cm) with periorbital edema and blood pressure140/84 mm Hg. Systemic examination was normal. Urinalysis showed 2+ albumin, red blood cells and Up/Uc ratio of 0.33. Blood investigations showed a creatinine of 1.0 mg/dL, albumin 4.2 g/dL and potassium 5.1 mEq/L. Ultrasonogram of the kidneys showed normal size kidneys. Renal biopsy showed seven glomeruli of which two were completely sclerosed and one showed segmental sclerosis and proliferation. Remaining glomeruli were normal-sized with increase in mesangial cellularity and thin capillary walls; tubules, interstitium and blood vessels were unremarkable. Immuno-fluorescence examination showed mesangial granular deposits of IgA, and C3c and IgM. A diagnosis of class III IgA nephropathy was made [3]. The patient received treatment with angiotensin converting enzyme inhibitors and fish oil supplements without steroids. Later, he received therapy with an angiotensin receptor blocker. Ten months later, he was admitted with fever, generalized edema, anemia, hepatosplenomegaly and a soft systolic murmur. The blood pressure was 130/80 mm Hg. Investigations showed a serum creatinine level of 0.9 mg/dL, urea 28 mg/dL, uric acid 6.8 mg/dL, sodium 134 mEq/L, potassium 3.4 mEq/L and albumin 3.9 g/dL. The hemoglobin level was 8.5 g/dL, with leukocytes 237200/cu mm, and differential count of 6% polymorphs, 5% lymphocytes, 9% eosinophils, 10% basophils, 8% stab neutrophils, 6% myelocytes, 9% metamyelocytes, 10% promyelocytes, 32% myeloblasts and 5% nucleated red cells; platelets were normal. A diagnosis of CML with blast crisis was made (Fig 1), and the patient received intravenous and oral fluids of 3 L /day along with alkalization of urine and allopurinol. BCR-ABL translocation assay showed hybrid transcript in leukocytes suggesting chronic phase of CML. Genomic breakpoint observed at e14a2 corresponds to p210. The patient was treated with Imatinib 400 mg once a day [4, 5]. After 1 month follow-up, there was no hepatosplenomegaly, and leukocyte counts and renal functions were normal.

Fig.1 Peripheral smear showing features of chronic myeloid leukemia.

Discussion

IgA nephropathy is a common chronic primary glomerular disease, which rarely presents as acute nephritic syndrome. Systemic diseases with IgA deposits include systemic lupus erythematosus, Henoch-Schonlein purpura, cystic fibrosis, ankylosing spondylitis, dermatitis herpetiformis, inflammatory bowel disease, celiac disease, chronic liver disease, infections like mycoplasma, leprosy and toxoplasmosis, as well as neoplasms like non-Hodgkin lymphoma, monoclonal IgA gammopathy and carcinoma of the lung and colon [1]. Various hypotheses suggested in the pathogenesis of IgA nephropathy are predisposing genetic factors, IgA immune complex disease due to abnormal IgA glycosylation and adhesion molecules on mononuclear cells and lymphocyte subpopulation [1,6,7]. Chromosome aberrations identified by genome- wide linkage analysis in families with IgA nephropathy cases is suggested to be predisposing genetic factor for development of disease [1]. Abnormal galactosylation in the hinge region of IgA1 subclass results in formation of circulating immune complex and its deposition in mesangium. These deposits release cytokines, growth factors and adhesion molecules, which lead to proliferation of mesangial cells, inflammation and sclerosis [1,7]. The recognition of B-cell defect and the role of adhesion molecules/growth factors enables targeting treatment with bone marrow transplant or neutralizing antibodies [6,7]. Findings that predict progression to end stage renal disease include heavy proteinuria, diffuse mesangial proliferation, a high proportion of glomeruli showing sclerosis, crescents or capsular adhesions, and the presence of moderate or severe tubulointerstitial changes [8]. There are increasing reports of association between chronic glomerulo-nephritis and leukemia in adults [9,10]. Renal infiltration by leukemic cells is rare and presents with abdominal pain or hematuria with renal biopsy showing presence of abnormal cells as seen in peripheral blood. The present patient had acute nephritic syndrome, which was followed three years later by the occurrence of CML. This association suggests that a B-cell defect might be involved in the pathogenesis of IgA nephropathy and CML.

Acknowledgement: Histopathology Department of Apollo Hospitals, Chennai, India for preparation and reporting of renal biopsy, and Pediatric Hematology and Histopathology Departments of Mehta Hospitals, Chennai, India for preparation and reporting of peripheral smear.

Contributors: All the authors were involved in the case management. MVK, NP and AU were involved in review of literature and preparation of the manuscript. MVK will act as guarantor.

Funding: None;Competing interest: None stated.

References

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2. Motoyama O, Kojima Y, Ohara A, Tsukimoto I, Ishikawa Y, Iitaka K. IgA nephropathy associated with leukemia and lymphoma: report of two cases. Clin Exp Nephrol. 2008;12: 140-3.

3. Churg J, Bernstein J, Glassock R. In: Renal disease: classification and atlas of glomerular diseases 2nd ed. Tokyo: Igaku-Shion Medical Publishers 1995. p.86-8.

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9. Hu SL, Colvin GA, Rifai A, Suzuki H, Novak J, Esparza A, et al. Glomerulonephritis after hematopoietic stem transplant: IgA nephropathy with increased excretion of dn IgA1. Nephrol Dial Transplant. 2010;25:1708-13.

10. Iwata Y, Wada T, Uchiyama A, Miwa A, Nakaya I, Tohyama T, et al. Remission of IgA nephropathy after allogeneic peripheral blood stem cell transplantation followed by immunosuppression for acute lymphocytic leukemia. Intern Med. 2006;45:1291-5.

 

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