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 .