The Spectrum of Kidney Pathology in B-Cell Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma: A 25-Year Multicenter Experience

Poitou-Verkinder, Anne-Laure; Audigier, François; Drieux, Fanny; Leprêtre, Stéphane; Legallicier, B.; Moulin, Anne‐Marie; Godin, Michel; Guerrot, Dominique

doi:10.1371/journal.pone.0119156

Cited by 49 publications

(60 citation statements)

References 44 publications

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“…31 Similar mechanisms were described in the majority of the 27 cases reported in the literature. 11,13,15,16,19,25,26 Treatment of CLL with concomitant renal abnormalities is challenging. In fact, creatinine clearance is one of the strongest predictors of fludarabine toxicity, a mainstay of CLL therapy.…”

Section: © F E R R a T A S T O R T I F O U N D A T I O Nmentioning

confidence: 99%

“…Although reported in up to 90% of CLL patients in autopsy series, only ten cases of CLL infiltration of the kidney causing clinical sequelae have been reported to date. 3,4,11 Accordingly, great care must be taken to determine whether CLL cells infiltrating the kidney are or are not the etiology of renal pathology. This determination requires close collaboration between hematologists, nephrologists and pathologists expert in the care of patients with CLL and its effects on the kidney.…”

Section: © F E R R a T A S T O R T I F O U N D A T I O Nmentioning

confidence: 99%

“…[2][3][4][5] Although interstitial CLL infiltration of the kidney can have clinical manifestations, only ten cases of acute renal failure secondary to CLL infiltration have been reported in the literature. 2,[6][7][8][9][10][11] Collectively, 81 cases of biopsy-proven glomerular or interstitial renal abnormalities due to CLL have been reported in the literature to date, whereas no cases associated with monoclonal B-cell lymphocytosis (MBL) have been described. Most of these CLL-associated cases are single patient case reports or small case series, with the largest report to date including 15 patients.…”

Section: Introductionmentioning

confidence: 99%

“…Most of these CLL-associated cases are single patient case reports or small case series, with the largest report to date including 15 patients. [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] Here we report the pathological findings and outcomes of a series of 49 patients with CLL and MBL followed at a single institution, who underwent a kidney biopsy during the course of their disease to evaluate renal insufficiency and/or nephrotic syndrome.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

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© 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...

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Section: © F E R R a T A S T O R T I F O U N D A T I O Nmentioning

confidence: 99%

Section: © F E R R a T A S T O R T I F O U N D A T I O Nmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

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“…Despite the lower prevalence, the variety of kidney diseases was similar to that of multiple myeloma and Waldenström macroglobulinemia. 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).…”

Section: Chronic Lymphocytic Leukemiamentioning

confidence: 99%

Dysproteinemias and Glomerular Disease

Leung

Drosou

Nasr

2017

CJASN

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Dysproteinemia is characterized by the overproduction of an Ig by clonal expansion of cells from the B cell lineage. The resultant monoclonal protein can be composed of the entire Ig or its components. Monoclonal proteins are increasingly recognized as a contributor to kidney disease. They can cause injury in all areas of the kidney, including the glomerular, tubular, and vascular compartments. In the glomerulus, the major mechanism of injury is deposition. Examples of this include Ig amyloidosis, monoclonal Ig deposition disease, immunotactoid glomerulopathy, and cryoglobulinemic GN specifically from types 1 and 2 cryoglobulins. Mechanisms that do not involve Ig deposition include the activation of the complement system, which causes complement deposition in C3 glomerulopathy, and cytokines/growth factors as seen in thrombotic microangiopathy and precipitation, which is involved with cryoglobulinemia. It is important to recognize that nephrotoxic monoclonal proteins can be produced by clones from any of the B cell lineages and that a malignant state is not required for the development of kidney disease. The nephrotoxic clones that do not meet requirement for a malignant condition are now called monoclonal gammopathy of renal significance. Whether it is a malignancy or monoclonal gammopathy of renal significance, preservation of renal function requires substantial reduction of the monoclonal protein. With better understanding of the pathogenesis, clone-directed strategies, such as rituximab against CD20 expressing B cell and bortezomib against plasma cell clones, have been used in the treatment of these diseases. These clone-directed therapies been found to be more effective than immunosuppressive regimens used in nonmonoclonal protein-related kidney diseases.

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Unusual complications in the management of chronic lymphocytic leukemia

Gordon

Ferrajoli

2022

American J Hematol

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Chronic lymphocytic leukemia (CLL) is a common, indolent disease that typically presents with a proliferation of mature, immunologically dysfunctional CD5+ B-cells which preferentially occupy the bone marrow, peripheral blood and lymphoid organs.Immune dysfunction leads to an increase in autoimmune diseases which occur in approximately 10% of patients with CLL. Autoimmune cytopenias are the most common, but other organs may be affected as well. The treatment of these conditions typically depends on the extent of CLL and severity of symptoms, but generally consists of CLL-directed therapies, immunosuppression or both. CLL may also infiltrate extranodal sites in the body. Symptomatic extranodal CLL or extranodal disease which threatens normal organ function is an indication for initiation of CLL-directed therapy. The following review summarizes autoimmune and extranodal complications that can occur in patients with CLL and our suggested approach to their treatment.

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The Spectrum of Kidney Pathology in B-Cell Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma: A 25-Year Multicenter Experience

Cited by 49 publications

References 44 publications

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

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

Dysproteinemias and Glomerular Disease

Unusual complications in the management of chronic lymphocytic leukemia

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