Renal complications in chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis: the Mayo Clinic experience

Abstract

© F e r r a t a S t o r t i F o u n d a t i o ntent interstitial lymphocytic infiltration was observed. Standard processing of kidney biopsies evaluated at the Mayo Clinic included light microscopy, immunofluorescence, and electron microscopy. For light microscopy, biopsy specimens were stained with hematoxylin-eosin, periodic acid Schiff, Masson trichrome, and Jones methenamine silver. For immunofluorescence, 3-micron cryostat sections were stained with polyclonal fluorescein isothiocyanate-conjugated antibodies to IgG, IgM, IgA, C3, C1q, kappa and lambda light chains, fibrinogen, and albumin (Dako), as per routine clinical testing. Electron microscopy was performed as per clinical routine.Immunohistochemical stains for CD3, CD5, CD20, and CD23 were done in cases of interstitial lymphocytic infiltration (and for PAX5 and CD19 in selected cases) to help assess CLL/SLL involvement. Renal biopsy findings were further classified according to a potential causal relationship with CLL. Cases of membranoproliferative glomerulonephritis (MPGN), CLL infiltrate as primary etiology, minimal change disease (MCD), acute interstitial nephritis, amyloidosis, light chain cast nephropathy, membranous glomerulonephritis, and unclassified mesangial proliferative glomerulonephritis were considered directly related to CLL. Cases secondary to CLL-associated conditions, such as infections, autoimmune disease, and other cancers, or CLL treatment were considered potentially indirectly related to CLL. Cases secondary to non-CLL associated comorbidities or non-CLL treatment, such as diabetes, hypertension or obesity, were considered unrelated to CLL. Statistical analysisDescriptive statistics of baseline characteristics were calculated. The Mann-Whitney test was used for comparisons of medians. Overall survival was defined as time from diagnosis to death or last follow up. Survival curves were calculated using the Kaplan-Meier method, and comparisons were made using the log-rank test. All P-values were two-sided and considered statistically significant if ≤0.05. Statistical analyses were completed using SPSS 21. Results Baseline characteristicsBetween January 1 st , 1995 and June 30 th , 2014, 4,024 patients with CLL, SLL or MBL were followed at our institution. Of these patients, 49 (1.2%) had an ultrasound-guided kidney biopsy during follow-up to evaluate renal failure and/or nephrotic syndrome. Of these biopsies, 10% were performed before 2005, 49% between 2005 and 2010, and 41% after 2010. The indication for renal biopsy was renal insufficiency (without evidence of post-renal compression or tumor lysis) in 34 patients (69%; median creatinine 3.2 mg/dL, range 1.7-15) and nephrotic syndrome in 15 (31%; median proteinuria 11.3 g/24 hours, range 4-54.9). The pertinent baseline characteristics of these 49 patients at the time of CLL diagnosis are shown in Table 1.Kidney biopsy results are shown in Table 2. The distribution of renal pathology based on the indication for biopsy is shown in Figure 1. Of interest, among the five patie...

Dysproteinemias and Glomerular Disease

“…chronic lymphocytic leukemia infiltration was the most common histopathologic finding, accounting for 73% of patients (70). The chronic lymphocytic leukemia infiltration often coexisted with other lesions, and granulomatous reaction was noted in some (62,71). Cryoglobulinemia GN (20%) was the most common glomerular lesion followed by minimal change disease (13.3%).…”

“…A large study of 1043 patients newly diagnosed with chronic lymphocytic leukemia/small lymphocytic lymphoma found that 10% of patients had renal impairment, whereas another 14.5% developed renal impairment during the course of their disease (69). Another study from the same institution found that only 1.2% of all patients with chronic lymphocytic leukemia or MBL (n54024) underwent a kidney biopsy (62). Despite the lower prevalence, the variety of kidney diseases was similar to that of multiple myeloma and Waldenström macroglobulinemia.…”

“…The most common kidney disease in multiple myeloma is cast nephropathy, which has now become a myeloma-defining event (3). However, cast nephropathy can also be seen in patients with Waldenström macroglobulinemia and chronic lymphocytic leukemia (62,63). The most common glomerular lesion is AL amyloidosis, which is present in 3%-5% of patients with multiple myeloma during autopsy (64).…”

Renal insufficiency is an independent prognostic factor in patients with chronic lymphocytic leukemia

“…Up to 90% of pathology findings were either directly (infiltration) or indirectly (infection-associated) related to CLL, highlighting the apparent patho-biological relationship between CLL and renal function in some patients. 6 In the present cohort, RI was also acquired during the course of CLL follow up in an additional 151 patients. After adjusting for age and sex, factors associated with acquired RI during follow up included advanced Rai …”

“…However, some recent evidence suggests that, in some cases, RI may be a consequence of CLL rather than simply reflecting an aging individual. 6 We aimed to investigate the specific prognostic role of renal function in the haematologica 2017; 102:e22 Patients had to have a baseline pre-treatment creatinine clearance available within one year prior to or three months after CLL diagnosis. Glomerular filtration rate was calculated using the Cockroft-Gault formula.…”