Immunotactoid glomerulopathy: clinicopathologic and proteomic study

Nasr, Samih H.; Fidler, Mary E.; Cornell, Lynn D.; Leung, Nelson; Cosio, Fernando G.; Sheikh, Salwa S.; Amir, Abdulrazack; Vrana, Julie A.; Theis, Jason D.; Doğan, Ahmet; Sethi, Sanjeev

doi:10.1093/ndt/gfs348

Cited by 113 publications

(126 citation statements)

References 20 publications

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“…To date, most published series on glomerulopathy with monoclonal Ig deposits have been based on pathologic patterns [3,6,[12][13][14][15]. Because of the wide heterogeneity of treatments in these series (e.g., no treatment, steroids only, rituximab, or combined chemotherapy), no firm recommendations for iNHL treatment are available.…”

Section: Discussionmentioning

confidence: 99%

Rituximab–cyclophosphamide‐dexamethasone is highly effective in patients with monoclonal Ig deposit‐related glomerulopathy and indolent non‐Hodgkin lymphomas

et al. 2014

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Indolent non-hodgkin lymphomas (iNHL) are a rare cause of monoclonal immunoglobulin deposits-related glomerulopathy (mIgGN). In patients with iNHL-related mIgGN, whether treatment should include either single or a combination of drug(s) to target the malignant clone and renal inflammation remains elusive. In this retrospective study, we report a cohort of 14 patients with iNHL-related mIgGN (cryoglobulinemic glomerulonephritis [n 5 5], membranous nephropathy [n 5 3], membranoproliferative glomerulonephritis [n 5 3], AL or AL/AH amyloidosis [n 5 2], and Light Chain Deposits Disease [n 5 1]) and who received a treatment combining rituximab, cyclophosphamide, and dexamethasone (RCD). After a mean follow-up of 18 6 4 months, nine patients (63%) had complete haematological response. Renal response was observed in 12 of the 14 patients (86%; complete response: n 5 9; partial: n 5 3). Estimated glomerular filtration rate increased from 47 6 7 to 63 6 8 mL/min/1.73 m 2 , and proteinuria decreased from 6.5 6 0.7 to 1.4 6 0.8 g/24 hr at one year. Following hematological relapse, renal relapse occurred in two patients suggesting sustained clonal eradication offers the best renal protection. Tolerance of RCD was good and the most frequent adverse event was pneumonia (3/14, 21%). RCD is a promising regimen for patients with iNHL and mIgGN, irrespective of glomerular pathologic pattern. Whether steroids can be avoided or minimized remains to be addressed.

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Section: Discussionmentioning

confidence: 99%

Rituximab–cyclophosphamide‐dexamethasone is highly effective in patients with monoclonal Ig deposit‐related glomerulopathy and indolent non‐Hodgkin lymphomas

et al. 2014

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“…Immunotactoid GN is another glomerular disorder resulting from deposition of microtubules (53). By definition, cryoglobulinemic GN must be ruled out, because they are difficult to differentiate histopathologically.…”

Section: Immunotactoid Gnmentioning

confidence: 99%

“…Rarely, vasculitic skin lesions, immunotactoid corneal and liver deposits, and mononeuritis multiplex have been reported (54)(55)(56). Median age ranges from 57 to 61 years old, with a slight increased prevalence in men (53,54). Most patients present with nephrotic-range proteinuria, with a range of 6-11 g/d.…”

Section: Immunotactoid Gnmentioning

confidence: 99%

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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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“…Other conditions that have low rates of MM include light-chain Fanconi syndrome, which occurs in only 31% of patients (7). Rates are even lower in immunotactoid GN (.5%) and proliferative GN with monoclonal Ig deposits (PGNMID; 2%) and extremely low in monoclonal fibrillary GN (,1%) (8)(9)(10)(11). The presence of MM is not required for kidney disease, but when present, it does worsen the prognosis (12,13).…”

Section: The Role Of Monoclonal Proteins In Kidney Diseasesmentioning

confidence: 99%

A Patient with Abnormal Kidney Function and a Monoclonal Light Chain in the Urine

Leung

Nasr

2016

CJASN

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Monoclonal gammopathy is increasingly recognized as a cause of kidney injury. These renal conditions behave differently than ones without monoclonal gammopathy and require specific treatment. To avoid misdiagnosis, testing for paraprotein should be performed in addition to vasculitis and autoimmune diseases serologies in adults with unexplained AKI or proteinuria. Because the prevalence of monoclonal gammopathy is much more common than glomerular diseases, the nephrotoxicity of the monoclonal protein must be confirmed before cytotoxic therapy is initiated. This can only be done by a kidney biopsy. After a monoclonal gammopathy of renal significant is verified, the evaluation should then focus on the identification of the pathologic clone, because therapy is clone specific. We present this patient to illustrate the clinical presentation of a patient with renal dysfunction and a monoclonal gammopathy. This patient is also used to discuss the diagnostic process in detail when monoclonal gammopathy-associated renal disease is suspected.

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Immunotactoid glomerulopathy: clinicopathologic and proteomic study

Cited by 113 publications

References 20 publications

Rituximab–cyclophosphamide‐dexamethasone is highly effective in patients with monoclonal Ig deposit‐related glomerulopathy and indolent non‐Hodgkin lymphomas

Rituximab–cyclophosphamide‐dexamethasone is highly effective in patients with monoclonal Ig deposit‐related glomerulopathy and indolent non‐Hodgkin lymphomas

Dysproteinemias and Glomerular Disease

A Patient with Abnormal Kidney Function and a Monoclonal Light Chain in the Urine

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