- Case Report
- Open Access
Concurrent nephrotic syndrome and acute renal failure caused by chronic lymphocytic leukemia (CLL): a case report and literature review
© Dou et al; licensee BioMed Central Ltd. 2011
- Received: 29 May 2011
- Accepted: 13 October 2011
- Published: 13 October 2011
Kidney injury associated with lymphocytic leukemia (CLL) is typically caused by direct tumor infiltration which occasionally results in acute renal failure. Glomerular involvement presenting as proteinuria or even nephrotic syndrome is exceptionally rare. Here we report a case of 54-year-old male CLL patient with nephrotic syndrome and renal failure. The lymph node biopsy confirmed that the patients had CLL with remarkable immunoglobulin light chain amyloid deposition. The renal biopsy demonstrated the concurrence of AL amyloidosis and neoplastic infiltration. Combined treatment of fludarabine, cyclophosphamide and rituximab resulted in remission of CLL, as well as the renal disfunction and nephrotic syndrome, without recurrence during a 12-month follow-up. To our knowledge, this is the first case of CLL patient showing the nephrotic syndrome and acute renal failure caused by AL amyloidosis and neoplastic infiltration. Though AL amyloidosis caused by plasma cell dyscrasia usually responses poorly to chemotherapy, this patient exhibited a satisfactory clinical outcome due to successful inhibition of the production of amylodogenic light chains by combined chemotherapy.
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- Chronic Lymphocytic Leukemia
- Nephrotic Syndrome
- Chronic Lymphocytic Leukemia Patient
- Monoclonal Immunoglobulin
- Plasma Cell Dyscrasia
AL amyloidosis is characterized by widespread, progressive deposition of amyloid fibrils derived from monoclonal immunoglobulin (Ig) light chains, leading to multi-system organ failure among which the kidneys and heart are most frequently affected . Although AL amyloidosis is typically caused by plasma cell proliferative disease especially multiple myeloma, it can also be caused by other lymphoproliferative disorders of B-cells such as lymphoplasmacytic lymphoma, of which the neoplastic B cells produce monoclonal immunoglobulin light chains . Only few cases of AL amyloidosis associated with chronic lymphocytic leukemia (CLL) have been reported [2–5]. Another relatively common injury caused CLL is the direct neoplastic cell infiltration as demonstrated by autopsy studies , but acute renal failure due to severe infiltration is rare [7–9].
In this report, we present a patient with nephrotic syndrome and renal failure associated with CLL. The patient completely recovered from the nephrotic syndrome and renal dysfunction after CLL was controlled with chemotherapy. We have reviewed the literature and discussed the relationship between CLL and amyloidosis and the pathological implications.
A 54-year-old male Chinese patient was admitted to the Shunde People's hospital on March 7, 2008, complaining of nocturia and edema of face and both lower extremities for more than two months. The patient had no history of any renal disease. Physical examinations revealed normal vital signs, moderate hypertension (162/96 mmHg) and pitting edema of the lower extremities. Enlargement of lymph nodes involving inguinal, axillary, submaxillary and supraclavicular fossa with a diameter of more than 1 cm was found. The remainder of the examination was unremarkable.
Treatment and following-up
Chemotherapy was given by combination of 44 mg fludarabine and 20 mg dexamethasone from July 24, 2008 to September 26, 2008 for 3 courses of treatment. After that, the lymph nodes size decreased and the edema was dramatically ameliorated with decreased serum Cr (200 μmol/L), increased serum albumin (39.96 g/L), declined serum IgM level (2.38 g/L) and slightly reduced 24-hour urinary protein excretion (4.22 g/24 h). However, the patient developed a severe bone marrow depression defined by markedly reduced blood cell count (erythrocytes: 1.66 × 1012/L, leukocytes: 0.62 × 109/L, platelet: 21 × 109/L). Then the chemotherapy regimen was adjusted (fludarabine 50 mg, CTX 0.3 g and rituximab 600 mg). After 3 courses of treatment from Nov 27, 2008 to Feb 19, 2009, the patient achieved a satisfactory hematologic response. His serum IgM concentration gradually decreased to the normal level and the monoclonal immunoglobulin was undetectable by serum immunofixation electrophoresis. At the same time, the patient experienced a gradual improvement in clinical status and decrease in the proteinuria and serum creatine. His renal function, urinary protein and serum C3 level were recovered entirely in Sept 2009 (24-hour urinary protein excretion: 139.20 mg/24 h, urine routine test: negative, serum Cr: 121.00 μmol/L, serum C3 level 0.96 g/L).
Proteinuria caused by direct infiltration of neoplastic cells is generally mild. Severe proteinuria or even nephrotic syndrome often suggests glomerular involvement [7, 10]. Though CLL is rarely complicated with nephrotic syndrome, a spectrum of glomerular diseases including light chain deposition disease (LCDD), AL, membranoproliferative glomerulonephritis (MPGN) , membrane nephropathy (MN) and minimal change disease (MCD) have been reported, which suggests the presence of various pathogenesis pathways of CLL-associated nephrotic syndrome[2, 7, 11–13]. The glomerular injuries may be directly caused by the lymphoplasmacytic neoplasm through a paraprotein deposition process which finally results in amyloidosis or monoclonal immunoglobulin deposition disease or the indirect immune-mediated mechanisms may also be involved. In our case, the monoclonal Ig light chain detected in the sera was the same class as that found on the surface membrane of lymphocytes and the amyloid in the kidney and lymph node, indicating that the monoclonal Ig originated from the proliferating cells. Based on this finding as well as the histopathological observations, we made a diagnosis of CLL associated AL amyloidosis. The reason that we could not detect monoclonal Ig light chain in the lymphocytic cells by immunohistochemistry may be ascribed to the inaccessibility of epitope after tissue fixation.
Histologically, the leukaemic infiltratation in the kidney can be nodular or interstitial in CLL. In this patient, both patterns were observed. When the infiltration is nodular, especially when there are clusters of cells around sclerotic glomeruli or atrophic tubules, it is important to determine whether it is tumor infiltration leading to their destruction or is only local inflammation secondary to glomerular scelerosis and tubular atrophy caused by other glomerulopathies. The mixture of various inflammatory cells generally indicates the secondary local inflammatory response, while the monotonous appearance of the cells usually suggests tumor infiltration. But when it comes to a biopsy specimen, it is difficult to distinguish both situations due to the local distribution of the infiltration. In this regard, further immunohistochemical examinations should be applied. In general, leukemic infiltration in the kidney should be considered when a patient with CLL presents with renal impairment. This kind of patients usually responds well to chemotherapy as seen in our case [8, 14, 15].
AL amyloidosis can be complicated with any clonal B cell dyscrasia, especially plasma cell dyscrasia. The misfolded monoclonal free light chains deposited in the extracellular space in a fibrillar form which are very hard to be absorbed. Accumulation of these fibrils in the kidney causes progressive renal impairment with proteinuria, even renal failure. It is well known that most amyloid depositions associated with plasma disorders are lambda-light chains . On the contrary, in AL amyloid caused by CLL, the monoclonal light chains detected are predominantly kappa type as in our case [3, 5]. Though AL amyloidosis caused by plasma cell dyscrasia often has a poor prognosis with a median survival of 35.2 months from diagnosis due to the poor response to chemotherapy , CLL-associated AL amyloidosis were reported to be significantly alleviated and obtained a prolonged survival of more than 7 years . As with our patient, his proteinuria decreased very slowly and did not resolve until one year after he obtained hematologic remission. This is believed to be associated with the reduced production of amyloidogenic light chains so that the clearance of existing deposits exceeds the rate of deposition. Those deposited amyloids were gradually mobilized and cleared by the body.
Another interesting finding is that the serum concentration of C3 in our patient changed significantly after chemotherapy. It was in the lowest level when the patient was in acute phase and the serum IgM was high. With the decrease of serum IgM after treatment, it recovered to the normal level, indicating that impaired complement system might be involved in the pathogenesis of CLL and its complications .
We herein first reported a rare case of nephrotic syndrome combined with acute renal failure caused by CLL. From our patient and few cases reported in the literature, we suggest that AL amyloidosis should be considered in CLL patients presenting with proteinuria or nephrotic syndrome. AL amyloidosis associated with CLL may have a more favorable prognosis than those caused by multiple myeloma due to a better response to chemotherapy. Further investigations are needed to better clarify the clinical outcomes and prognosis of this unusual complication of CLL and to better understand the pathological and molecular mechanisms of CLL- induced nephrotic syndrome.
A written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
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