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Acute Renal Failure due to IgM-λ Glomerular Thrombi and MPGN-Like Lesions in a Patient With Angioimmunoblastic T-Cell Lymphoma

2006; Elsevier BV; Volume: 48; Issue: 1 Linguagem: Inglês

10.1053/j.ajkd.2006.03.084

1523-6838

Naoto Miura, Keisuke Suzuki, Masabumi Yoshino, Wataru Kitagawa, Harutaka Yamada, Hiroshi Ohtani, Kensuke Joh, Hirokazu Imai,

Chronic Lymphocytic Leukemia Research

A 70-year-old man with angioimmunoblastic T-cell lymphoma developed acute renal failure. Laboratory data showed decreased levels of serum C3, C4, and CH50, elevated immunoglobulin M (IgM) levels, and the presence of cryoglobulinemia (IgM-λ). Renal biopsy showed membranoproliferative glomerulonephritis–like lesions with azan-red–stained thrombi in the glomerular capillary lumen. Immunofluorescence showed that IgM-λ stained strongly in the glomerular capillary lumen, equal to the azan-red–stained thrombi, whereas C3 and C4 staining was negative. Electron microscopy showed electron-dense deposits in the subendothelial space and glomerular thrombi lacking fine fibrillar structure. These findings suggest that cryoglobulin, which consists of monoclonal IgM-λ, induced glomerular thrombi and acute renal failure in a patient with angioimmunoblastic T-cell lymphoma. A 70-year-old man with angioimmunoblastic T-cell lymphoma developed acute renal failure. Laboratory data showed decreased levels of serum C3, C4, and CH50, elevated immunoglobulin M (IgM) levels, and the presence of cryoglobulinemia (IgM-λ). Renal biopsy showed membranoproliferative glomerulonephritis–like lesions with azan-red–stained thrombi in the glomerular capillary lumen. Immunofluorescence showed that IgM-λ stained strongly in the glomerular capillary lumen, equal to the azan-red–stained thrombi, whereas C3 and C4 staining was negative. Electron microscopy showed electron-dense deposits in the subendothelial space and glomerular thrombi lacking fine fibrillar structure. These findings suggest that cryoglobulin, which consists of monoclonal IgM-λ, induced glomerular thrombi and acute renal failure in a patient with angioimmunoblastic T-cell lymphoma. IN 1974, FRIZZERA ET AL1Frizzera G. Moran E.M. Rappaport H. Angio-immunoblastic lymphadenopathy with dysproteinemia.Lancet. 1974; 1: 1070-1073Abstract PubMed Scopus (459) Google Scholar described “angioimmunoblastic lymphadenopathy with dysproteinemia” (AILD) as a new disease entity. Recently, AILD was recognized as a mature T-cell neoplasm termed “angioimmunoblastic T-cell lymphoma” (but the abbreviation AILD is still used) by the classification scheme of the World Health Organization.2Ferry J.A. Angioimmunoblastic T-cell lymphoma.Adv Anat Pathol. 2002; 9: 273-279Crossref PubMed Scopus (38) Google Scholar This disorder is known to occur in 1% to 2% of malignant lymphoma and includes polyclonal or monoclonal gammaglobulinemia and Coombs positive hemolytic anemia. However, in laboratory examinations, serum autoantibody, cold agglutinin, cryoglobulin, and circulating immune complexes are less common. We report a patient with AILD presenting with acute renal failure, cryoglobulinemia, and hypocomplementemia. A renal biopsy showed monoclonal immunoglobulin M-λ (IgM-λ) thrombi in the glomerular capillary lumen, similar to the nephropathy of Waldenström macroglobulinemia. A 70-year-old man was admitted to the Division of Neurology, Aichi Medical University Hospital, Aichi, Japan, because of paralysis of the left side of the body and speech disturbance, and a working diagnosis of right cerebral infarction had been made. Annual medical checkups had indicated high blood pressure, but no abnormal laboratory findings (such as serum creatinine) were ever found. Two months before he came to our hospital, he noticed transient muscle weakness of the left side and visited the Division of Neurology. Magnetic resonance imaging showed narrowing of the right middle cerebral artery, and treatment with antihypertensive drugs and anticoagulants was begun. On admission, the patient was of clear consciousness. His vital signs were blood pressure, 170/60 mm Hg; pulse rate, 70 beats/min regular; and body temperature, 37.0°C. Physical examination confirmed lower-limb paralysis, a disturbance in tongue movement, and left-side lower-leg edema. Laboratory studies showed the following data: white blood cell count, 9,500/μL (9,500 × 109/L); red blood cell count, 4.48 × 106/μL (4.48 × 1012/L); hemoglobin, 13.5 g/dL (135 g/L); hematocrit, 40.3%; platelet count, 272 × 103/μL (272 × 109/L); total protein, 7.7 g/dL (77 g/L); albumin, 4.7 g/dL (47 g/L); lactate dehydrogenase, 347 U/L (normal range, 104 to 224 U/L); blood urea nitrogen, 26.7 mg/dL (9.5 mmol/L); and serum creatinine, 1.2 mg/dL (106 μmol/L). Other values included sodium, 142 mEq/L (142 mmol/L); potassium, 4.4 mEq/L (4.4 mmol/L); chloride, 105 mEq/L (105 mmol/L); calcium, 10.1 mg/dL (2.52 mmol/L; normal range, 8.6 to 10.3 mg/dL); total cholesterol, 200 mg/dL (5.17 mmol/L); and C-reactive protein, 0.33 mg/dL. Hepatitis B antigen and hepatitis C virus antibody titers were negative. A brain computed tomographic scan showed cerebral infarction caused by occlusion of the right middle cerebral artery, and he began treatment with sodium ozagrel and edaravone. At day 23 in the hospital, the neurologist consulted with the Division of Nephrology because of an increase in serum creatinine level from 1.2 to 3.0 mg/dL (106 to 265 μmol/L). Physical examination showed lymph node swelling (without tenderness) on both sides of the neck and in both inguinal regions. Laboratory data showed proteinuria of 3+, urine occult blood reaction of 1+, and protein excretion of 1.7 g/d. Urinary β2-microglobulin level was 61 μg/L (normal range, <230 μg/L), and urinary N-acetyl-β-d-glucosaminidase was 33.8 U/L (normal range, 0.5 to 5.0 U/L). Urinary sedimentation tests also showed additional data: red blood cells, 25 to 30/high-power field (HPF); destructed red blood cells, 17/HPF; white blood cells, 1 to 2/HPF; hyaline casts, 2 to 3/HPF; granular casts, 8/HPF, and fat casts, 2 to 3/HPF. Assays for Bence-Jones protein were negative. Laboratory studies showed the following values: total protein, 6.1 g/dL (61 g/L); albumin, 3.4 g/dL (34 g/L); blood urea nitrogen, 53.0 mg/dL (18.9 mmol/L); creatinine, 2.8 mg/dL (248 μmol/L); uric acid, 7.8 mg/dL (464 μmol/L); total cholesterol, 197 mg/dL (5.09 mmol/L; normal range, 120 to 219 mg/dL); lactate dehydrogenase, 364 U/L (normal range, 104 to 224 U/L); C-reactive protein, 1.28 mg/dL; antistreptolysin O antibody, 18 IU/mL (normal range, <160 IU/mL); antistreptokinase antibody, 80 times (normal range, <1,280 times); and rheumatoid factor, 10.0 IU/mL (normal range, <20.0 IU/mL). Tests for antinuclear antibody, anti-DNA antibody, anti–glomerular basement membrane antibody, myeloperoxidase antineutrophil cytoplasmic antibody, and proteinase 3 antineutrophil cytoplasmic antibody were negative. IgG levels were 726 mg/dL (7.26 g/L; normal range, 870 to 1,700 mg/dL), IgA levels were 202 mg/dL (2.02 g/L; normal range, 110 to 410 mg/dL), and IgM levels were 1,048 mg/dL (10.48 g/L; normal range, 35 to 220 mg/dL). C3 levels were 51.7 mg/dL (0.52 g/L; normal range, 65 to 135 mg/dL), C4 levels were 2.0 mg/dL (0.02 g/L; normal range, 13.0 to 35.0 mg/dL), CH50 levels were 10.0 U/mL (normal range, 30 to 40 U/mL), and cryoglobulin was positive. Immunoelectrophoresis of cryoglobulinemia showed that the major immunoglobulin was IgM-λ, as well as small amounts of IgG and IgA. Serum-soluble interleukin 2 receptor level increased to 5,680 U/L (normal range, 220 to 530 U/L). Chest and abdominal computed tomographic scans showed systemic lymph node swelling, such as at the right and left lower chin, in the superficial and deep cervical regions, in the right and left axilla, around the aorta, and in both inguinal regions. Slight splenomegaly and hydrothorax also were apparent. However, there were no abnormal findings of the kidneys or ureters. Analysis of cell-surface markers during lymph node biopsy showed that CD3, CD4, CD20, and CD45RO were positive, and light microscopic examination with monoclonal antibody staining showed an AILD. Chromosomal analysis of lymph node biopsy specimens showed that 18 of 20 cells had such abnormalities as type A;47,XY,−2,der(2)add(2)(p13)ins(2;?)(q31;?),+der(3)t(3;14) (p13;q11),−14,+18,+marl. These abnormalities were compatible with AILD. The patient was transferred to the Division of Nephrology to evaluate the causes of acute renal failure and begin treatment. Steroid pulse therapy with methylprednisolone (500 mg/d for 3 days) was administered before renal biopsy because oliguria occurred rapidly and blood urea nitrogen, creatinine, and IgM levels rapidly increased to 87.2 mg/dL (31.1 mmol/L), 5.6 mg/dL (495 μmol/L), and 2,080 mg/dL (20.80 g/L), respectively. Hypocomplementemia, including 35.0 mg/dL of C3 (0.35 g/L) and less than 2.0 mg/dL of C4 ( 2.0 g/d), whereas 3 of the 4 patients had acute renal failure. Harada et al19Harada Y. Ido N. Okada T. et al.Nephrotic syndrome caused by protein thrombi in glomerulocapillary lumen in Waldenström’s macroglobulinemia.Br J Haematol. 2000; 110: 880-883Crossref PubMed Scopus (12) Google Scholar reported a patient with Waldenström macroglobulinemia with nephritic syndrome with protein thrombi in the glomerular capillary lumen. Regarding IgM glomerular thrombi, except for cases of Waldenström macroglobulinemia, Oyama et al20Oyama Y. Komatsuda A. Ohtani H. et al.Extensive intraglomerular thrombi of monoclonal IgM-κ in a patient with malignant lymphoma.Am J Kidney Dis. 2000; 35: E1-E5Abstract Full Text Full Text PDF PubMed Google Scholar reported that a patient with CD5+ diffuse large B-cell lymphoma had monoclonal IgM-κ thrombi in glomerular lesions. The initial symptom in the present patient was acute renal failure, which differs from their patient. Waldenström macroglobulinemia typically is characterized by a B-cell monoclonal disorder, IgM monoclonal protein, bone marrow infiltration, and an immunophenotype of surface IgM+, CD19+, CD20+, CD22+, CD25+, CD27+, FMC7+, CD10−, CD23−, and CD103−.21Dimopoulos M.A. Kyle R.A. Anagnostopouls A. Treon S.P. Diagnosis and management of Waldenström’s macroglobulinemia.J Clin Oncol. 2005; 23: 1564-1577Crossref PubMed Scopus (185) Google Scholar Conversely, AILD is a mature T-cell neoplasm. Some patients with AILD lacked dominant T-cell clones, detected by using conventional polymerase chain reaction, single-cell polymerase chain reaction, or Southern blotting. Neoplastic T cells were found throughout the tissue, including areas dominated by B cells expressing CD20, as well as by follicular dendritic cells (CD21+).22Willenbrock K. Renne C. Gaulard P. Hansmann M.L. In angioimmunoblastic T-cell lymphoma, neoplastic T cells may be a minor cell population. A molecular single-cell and immunohistochemical study.Virchows Arch. 2005; 446: 15-20Crossref PubMed Scopus (23) Google Scholar A small number of an abnormal T-cell clone effectively activates B cells to produce IgM and other immunoglobulins. Chromosomal and immunophenotypic analyses of lymph nodes in the present case were compatible with AILD,23Lepretre S. Buchonnet G. Stamatoullas A. et al.Chromosomal abnormalities in peripheral T-cell lymphoma.Cancer Genet Cytogenet. 2000; 117: 71-79Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar and expression analysis of chemokine receptors showed that AILD has a T helper type 1–like phenotype, reacting with OX40/CD134 and CXCR3.24Tuchiya T. Ohshima K. Karube K. et al.Th1, Th2, and activated T-cell marker and clinical prognosis in peripheral T-cell lymphoma, unspecified Comparison with AILD, ALCL, lymphoblastic lymphoma, and ATLL.Blood. 2004; 103: 236-241Crossref PubMed Scopus (81) Google Scholar These data suggest that a small number of a malignant T-cell clone will influence benign B-cell clones, resulting in Waldenström macroglobulinemia–like symptoms (eg, monoclonal IgM gammopathy). In regard to therapy and prognosis, combination chemotherapy—such as CHOP—usually is the first attempted treatment for patients with AILD to induce complete remission, meaning hematologic and kidney improvement. Other approaches include plasmapheresis for hyperviscosity syndrome and administration of oral alkylating agents, such as chlorambucil, for 1 to 2 years. Recently, fludarabine and cladribine have been administered to patients with disease resistant to alkylating agents. The present patient showed a rapid response to CHOP therapy, which decreased serum creatinine levels. Thus, the present patient with acute renal failure caused by IgM-λ glomerular thrombi in AILD presents unique immunologic aspects and clinical features.