RENAL INVOLVEMENT IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA: A CASE SERIES

Abstract

Introduction: Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. It can infiltrate any organ, most commonly lymph nodes. When renal involvement occurs, it is usually asymptomatic, with clinical nephropathy being rare, and few cases reported. Here, we report a case series of renal involvement in CLL patients from the database of ICESP-USP. All cases had CLL diagnosis confirmed by flow cytometry. Cases: Case 1. A 66-year-old male presented with nephritic syndrome, severe acute kidney injury (AKI) (creatinine, Cr 6.25 mg/dL) and proteinuria of 1.7 g/24h. Complete blood count showed mild lymphocytosis (5,390/μL). Renal biopsy revealed membranoproliferative glomerulonephritis with B-lymphocyte infiltration. Treatment included cyclophosphamide, vincristine, and prednisone (CVP), followed by rituximab monotherapy. However, renal function did not improve, demanding chronic dialysis. Case 2. A 73-year-old male presented with nephrotic syndrome (proteinuria = 5.9 g/24h), mild AKI (Cr 1.42 mg/dL) and lymphocytosis (41,000/μL). Renal biopsy showed membranous glomerulopathy. Treatment with fludarabine and cyclophosphamide induced a partial response. Residual proteinuria persisted and he experienced a second exacerbation of proteinuria after 3 years, with a partial response to R-CVP regimen. Unfortunately, the patient succumbed to infectious complications during treatment. Case 3. A 75-year-old female, who had been treated previously with chlorambucil for CLL. She was admitted with AKI (Cr 7.11 mg/dL), without proteinuria or hematuria, and progressive CLL (lymphocytes = 52,950/μL). Abdominal CT revealed enlarged kidneys. The initial hypothesis was rapidly progressive glomerulonephritis, so she received methylprednisolone pulse therapy and required dialysis. Renal biopsy showed a dense B-lymphocytic infiltrate but was inconclusive for clonality. After that, weekly rituximab was initiated, with normalization of renal function. Case 4. A 68-year-old woman, after 10 years of CLL follow-up, developed AKI (Cr 3.28 mg/dL), without proteinuria, and lymphocytosis (80,000/μL). Renal biopsy showed renal infiltration with CD20+/CD5+/CD23+ lymphoid cells. CVP regimen was started with an initial improvement (Cr 1.8mg/dL), but was discontinued after C2 due to toxicity. Patient was lost to follow-up before starting an alternative strategy. Discussion: Renal disease is common among CLL patients, with a reported prevalence of 16%, but is usually related to comorbidities. Therefore, renal biopsy is rarely performed (approximately 1.2%) being reserved for patients with severe renal failure or nephritic/nephrotic presentation. In our cohort of 367 CLL patients, we retrieved 4 (1.1%) patients who underwent kidney biopsy and whose nephropathy was deemed secondary to CLL. The histological patterns were diverse, with cases of membranoproliferative and membranous glomerulonephritis, and interstitial infiltration. The response to treatment also varied. One patient with interstitial infiltration showed a good response, while the assessment of response of the other patient was limited, due to premature treatment discontinuation. The patients with glomerular lesions had partial improvement of kidney disease after immunochemotherapy. Due to the rarity of cases, the relationship between the type of histologic lesion and the response to treatment is unclear.