Granulomatous interstitial nephritis secondary to chronic lymphocytic leukemia/small lymphocytic lymphoma

Nasr, Samih H.; Shanafelt, Tait D.; Hanson, Curtis A.; Fidler, Mary E.; Cornell, Lynn D.; Sethi, Sanjeev; Chaffee, Kari G.; Morris, J. S.; Leung, Nelson

doi:10.1016/j.anndiagpath.2015.03.003

Cited by 14 publications

(12 citation statements)

References 39 publications

(50 reference statements)

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“…The urinalysis showed no hematuria with mild proteinuria, and the markers for renal tubular injury were elevated, which was unusual for a pure interstitial nephritis and might represent a clinical feature specific to the ischemic changes induced by the diffuse infiltration of CLL cells. Compared with the two similar previous cases whose chronic renal function did not recover, there was no hematuria in the fifth case of Nasr et al [ 10 ], while the hematuria data were not available in the case of Kamat et al [ 8 ]. These findings suggested the absence of hematuria in cases wherein the progression of the diffuse infiltration of CLL cells occurred gradually.…”

Section: Discussionmentioning

confidence: 64%

“…Another study reported the case of a patient with GIN with CLL who was negative for CD5 and who received hemodialysis after 18 months [ 9 ]. There was also a report of five cases of GIN secondary to CLL in which the renal dysfunction improved after corticosteroid treatment with or without CLL-directed chemotherapy in four of the five cases [ 10 ]. Among these four cases, the extent of CLL cell infiltration was mild to moderate, while the fifth case, in which the renal dysfunction did not improve, showed diffuse infiltration similarly to the present case and that of Kamat et al [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

“…The infiltration of CLL cells was so diffuse in the present case that we considered treatment with corticosteroids unlikely to be effective. Indeed, the two similar previous cases who had progressive renal dysfunction due to the diffuse infiltration of CLL cells needed maintenance hemodialysis despite being treated with corticosteroids and chlorambucil or rituximab [ 8 , 10 ]. Unfortunately, the progressive renal failure in the present case did not improve with cyclophosphamide monotherapy.…”

Section: Discussionmentioning

confidence: 99%

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Granulomatous interstitial nephritis due to chronic lymphocytic leukemia: a case report

et al. 2017

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BackgroundRenal failure due to the infiltration of chronic lymphocytic leukemia (CLL) cells into the tubulointerstitial area of the kidney is uncommon. Furthermore, granulomatous interstitial nephritis (GIN) is a rare histological diagnosis in patients undergoing a renal biopsy. We herein report a case of GIN due to the diffuse infiltration of CLL cells in a patient who developed progressive renal failure.Case presentationThe patient was a 55-year-old man who had been diagnosed with CLL 4 years earlier and who had been followed up without treatment. Although his serum creatinine level had remained normal for three and a half years, it started to increase in the six months prior to his presentation. A urinalysis showed mild proteinuria without any hematuria at the time of presentation. A renal biopsy revealed the diffuse infiltration of CLL cells into the tubulointerstitial area with non-caseating epithelioid cell granulomas. Despite cyclophosphamide treatment, his renal function did not improve, and he ultimately required maintenance hemodialysis.ConclusionWhen progressive renal failure is combined with CLL, GIN due to the direct infiltration of CLL cells should be considered as a differential diagnosis.

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Granulomatous interstitial nephritis due to chronic lymphocytic leukemia: a case report

et al. 2017

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“…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%).…”

Section: Chronic Lymphocytic Leukemiamentioning

confidence: 99%

Dysproteinemias and Glomerular Disease

Leung

Drosou

Nasr

2017

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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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“…Indolent non‐Hodgkin's lymphomas (iNHL, i.e., Waldenström's macroglobulinemia or lymphoplasmacytic lymphoma [LPL], chronic lymphocytic leukemia [CLL], marginal zone lymphoma, indolent mantle‐cell lymphoma) and B‐cell monoclonal lymphocytosis are a group of monotypic B‐cell disorders that can be accompanied by renal disease, including renal infiltration, deposition of an entire or a truncated monoclonal immunoglobulin, or renal autoimmune disorders not related to a circulating monoclonal Ig (mIg) but induced by overproduction of specific patterns of cytokines or unbalanced lymphocyte sub‐populations …”

Section: Introductionmentioning

confidence: 99%

Bendamustine plus rituximab for indolent B‐cell lymphoma of renal significance

et al. 2017

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Treatment of indolent B-cell non-Hodgkin lymphomas (iNHL) of renal significance is challenging given the need for deep and prolonged hematological response to restore and control renal function overtime, yet to be balanced with the risk of adverse drug-related events. This prospective single-center study included 20 patients with iNHL of renal significance (tubulointerstitial presentation [n = 8], glomerulopathy with or without monoclonal Ig deposits [n = 12]) who received a steroid-sparing regimen of rituximab plus bendamustine (BR), with either no or<1 month of steroid intake (as a first line therapy in 80%). Seventeen patients (85%) achieved a complete (CHR, n = 12) or a partial (PHR, n = 5) hematological response. Nine out of the 12 patients (75%) with iNHL-related glomerulopathy had a complete (CRR) or a partial (PRR) renal response. Among the six patients with glomerulopathy and CHR, five had a CRR (83%) compared to 1/6 (17%) that did not reach CHR. eGFR increased from 38 to 58 mL/min/1.73 m , and returned to baseline in five patients. Among the eight patients with a tubulointerstitial presentation, six (75%) had a renal response (5 CRR), and eGFR increased from 29 to 48 mL/min/1.73 m . One patient with a PHR had a renal relapse. Mortality rate was 10% at 12 months. The BR regimen was well tolerated overall. Thus, despite severe renal disease at presentation, a relapsing iNHL in 20% of patients and several comorbidities, the BR regimen was efficient and safe in our series. It should be further assessed as a first line therapy for patients with iNHL of renal significance.

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Granulomatous interstitial nephritis secondary to chronic lymphocytic leukemia/small lymphocytic lymphoma

Cited by 14 publications

References 39 publications

Granulomatous interstitial nephritis due to chronic lymphocytic leukemia: a case report

Granulomatous interstitial nephritis due to chronic lymphocytic leukemia: a case report

Dysproteinemias and Glomerular Disease

Bendamustine plus rituximab for indolent B‐cell lymphoma of renal significance

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