Acute Renal Failure Secondary to Chronic Lymphocytic Leukemia: A Case Report

Stephen I. Rifkin, MD, FACP, FASN


Medscape J Med. 2008;10(3):67 

Acute renal insufficiency associated with chronic lymphocytic leukemia (CLL) has a variety of causes. An extremely rare cause of renal dysfunction is dense leukemic infiltrate in the renal interstitium. This report describes a patient with CLL who developed acute renal failure secondary to leukemic infiltration and who had a partial response to chemotherapy. This diagnosis should always be considered when a patient with CLL, regardless of the clinical stage, presents with renal insufficiency because it appears to respond reasonably well to a variety of therapies. The finding of enlarged kidneys on renal ultrasound is suggestive of infiltrative disease, but is not always present. Proteinuria is generally mild. The literature is reviewed.

Leukemic infiltration of the kidneys is a common occurrence in chronic lymphocytic leukemia (CLL). However, it is an extremely rare cause of renal failure. This report describes a patient with CLL who developed acute renal failure believed to be secondary to massive leukemic infiltration of the kidney. He was treated with chemotherapy and had significant improvement in his renal function.

The patient is a 64-year-old, white man who was diagnosed with CLL stage I by classic criteria, with no evidence of splenomegaly and a minimal degree of lymphocytosis and lymphadenopathy. His bone marrow showed 80% atypical lymphocytes, and flow cytometry was typical of B-cell CLL being CD5-positive and co-expressing B-cell antigens. He was followed with observation alone.

He also had a long history of hypertension controlled on multiple medications.

A serum creatinine level 3 years later was 1.3 mg/dL and then 2.1 mg/dL the following year. In the fifth year after diagnosis, the serum creatinine level jumped to 5.0 mg/dL. Urinalysis and renal ultrasound done at that time were both unremarkable. Serum creatinine the next month was 7.0 mg/dL. A renal biopsy showed that the entire interstitium was densely infiltrated with a monomorphic population of lymphocytes (Figure). Immunofluorescence and electron microscopy were both negative for immune complexes. The patient was then started on a combination of fludarabine, rituximab, and prednisone. After 6 cycles of therapy, his serum creatinine stabilized at 2.8-3.0 mg/dL. Restaging studies revealed stable adenopathy. At that point, the patient moved out of town and was lost to further follow-up.

The entire interstitium is densely infiltrated with a monomorphic population of lymphocytes (hematoxylin and eosin stain, medium power).

Some degree of renal infiltration in CLL is common, occurring in up to 90% of cases at necropsy, but the incidence of marked infiltration is probably much less. Barcos and colleagues[1] reported on 109 patients with CLL and found a 63% incidence of renal involvement, but there is no quantitation of the degree of involvement. Schwartz and Shamsuddin[2] reported on 47 patients with CLL evaluated at autopsy. They found leukemic involvement in 90% of patients, but noted that the infiltration occurred in only 4 cases in a more diffuse, although still well-defined, manner. Of interest, they also noted a strong association between the areas of infiltrate and the presence of fibrosis in the same areas. Xiao and coworkers[3] noted renal involvement in 4 of 9 cases of CLL. However, when the degree of renal infiltration was evaluated semiquantitatively, only one of the 9 cases (11%) had marked infiltration. Norris and Wiener[4] noted renal infiltrates in 64% (41 of 64) of patients with CLL evaluated at necropsy. They divided the leukemic infiltrate into 2 gross forms. In the first type, nodules of varying size were found, usually in a cortical distribution. The second form was described as a rather diffuse infiltration. The frequency of each type was not quantified, but diffuse renal replacement by leukemic infiltrates was described as rare. Schwarze[5] noted renal infiltrates in 8 of 9 cases of CLL. However, infiltration was classified as only moderate in 5 cases and as low in the other 3 cases.

In addition, renal dysfunction attributable to leukemic infiltration is rare. When it does occur, it has been suggested that the diffuse infiltration compresses the renal tubules and microvasculature, resulting in intrarenal obstruction and ischemia. Norris and Wiener[4] found no association between renal infiltrates and renal dysfunction. Da'as and colleagues[6] reviewed 700 patients with documented lymphoma and CLL over 10 years and found 83 patients with acute renal insufficiency. Seventeen of these patients had CLL, but renal failure was believed to be related to CLL in only 3 patients, and renal failure wasn't found to be related to leukemic infiltration in any of these patients.

Renal failure in CLL attributable to leukemic infiltration has only been reported in a handful of patients. The reported patients have had a variety of presentations, clinical findings, and responses to different treatments. Several have presented with acute renal failure as the initial manifestation of CLL.[7,8,9,10] Several have had otherwise mild disease,[9,11,12] whereas others have had more aggressive disease along with their renal failure.[8,10,13,14] Kidney size can be either normal[7,8,11,14] or increased.[9,10,12,13] Proteinuria has generally been mild, and the nephrotic syndrome has not been reported. Response to treatment has varied from complete resolution[8] of the acute renal failure to more often a partial response[7,9,11,13,14] to no response.[10] Treatments have included irradiation of the kidneys, steroids, chlorambucil, vincristine, and cyclophosphamide. The present patient appears to be the first recipient of the combination of rituximab and fludarabine.

Thus, the present case is an example of a rare complication of CLL. It is extremely important to keep in mind the possibility of leukemic infiltrate causing acute renal insufficiency because renal biopsy is necessary to confirm the diagnosis, and this complication appears to respond reasonably well to a variety of treatments. The present patient had a partial response to fludarabine, rituximab, and prednisone -- a combination not previously reported.

Leukemic infiltration in CLL causing acute renal failure is an extremely rare condition. However, it should be prominently considered in the differential diagnosis because it appears to respond reasonably well to a variety of treatments.

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