A 79 year old man with chronic lymphocytic leukemia and nephrotic syndrome

Dr. Netti, Dr. Bruno A 79-year-old man was diagnosed with B-cell chronic lymphocytic leukemia (B-CLL) in another institution. During hospitalization, hematochemical examination revealed leukocytosis (30.8 9 10 cells/L) with inverted formula (neutrophils 26%, lymphocytes 64%) and chronic renal failure [serum creatinine 143.2 lmol/L; estimated glomerular filtration rate (eGFR), 54 mL/min/1.73 m according to the modification of diet in renal disease (MDRD) study equation], while hemoglobin level and platelet count were normal. At physical examination, no painful disease-related overgrowth of lymph nodes or spleen was observed. Only a few percentage of peripheral blood lymphocytes showed an undifferentiated phenotype (\10%). Because of the low grade disease (B-CLL RAI 0, Binet A), no treatment was carried out. Six months later, he developed pre-tibial oedema and asthenia. Blood analyses showed an increase in serum creatinine level to 230.7 lmol/L (eGFR, 31 mL/min/ 1.73 m), and urinalysis showed 100–150 red blood cells/ high-power field (hpf) and severe proteinuria (6.96 g/day). At this point, the patient was admitted to our hospital. Hematochemical examination showed leukocytosis (24 9 10 cells/L) with an inverted differential count (neutrophils 8.8%, lymphocytes 80.2%), while hemoglobin level, hematocrit, and platelet count were normal. International normalized ratio of prothrombin was 1.07; activated partial thromboplastin time was 36.1 s; and fibrinogen level was 375 mg/dL (11.025 lmol/L). Total protein level was 54 g/L, albumin level was 23 g/L, a-2-globulin level was increased, and c-globulin level was decreased. Serum levels of IgG and IgM were reduced (395 mg/dL and 8 mg/, respectively); IgA and complement levels were normal. Sedimentation rate was 4 mm/h with a C-reactive protein level of 3.39 mg/dL. Serum b-2-microglobulin was increased (0.1063 g/L). Serum creatinine level was 229.8 lmol/L (eGFR, 31 mL/min/1.73 m), and blood urea nitrogen level was 21.42 mmol/L. A 24-h urine collection had 4.16 g of proteins. Urine sediment contained many red blood cells (100–150/hpf) and leukocytes (50–100/hpf) with granular casts. Therefore, nephrotic syndrome was diagnosed. To stage the hematological disease, a peripheral blood cell morphology was examined, which confirmed an inverted differential leukocyte count (neutrophils 15.0%, lymphocytes 84.1%) and showed many Gumprecht ghosts. The flow-cytometric analysis of peripheral blood lymphocyte subsets revealed that the leukemic cells were positive for CD19 (88%), CD20 (83%), and CD23 (67%). Dr. Di Palma A kidney biopsy was performed. Light microscopy sections showed 11 glomeruli, four of which being fully sclerotic. Marked endocapillary proliferation with increased mesangial cellularity and matrix, and lobular simplification were present (Fig. 1a). Moreover, subendothelial deposits, resulting in a thickened capillary wall G. S. Netti M. Gigante G. Stallone L. Gesualdo Department of Biomedical Sciences and Research Centre ‘‘BioAgroMed’’, University of Foggia, Foggia, Italy