Monoclonal gammopathy of renal significance: general review/start of art

Little is known about the rate and predictors of finding lesions of monoclonal gammopathy (MG) of renal significance (MGRS) on kidney biopsy specimens among patients with MG. We reviewed the medical records from 2013 to 2018 at the Mayo Clinic in Rochester, Minnesota, to identify patients with MG and whether they had undergone a kidney biopsy. In a more select group of patients with MG from 2017 to 2018, we conducted a review of records to determine how many had underlying CKD, which of those with CKD had undergone a kidney biopsy, and reasons for deferring a kidney biopsy. Between 2013 and 2018, we identified 6300 patients who had MG, 160 (2.5%) of whom had undergone a kidney biopsy. Of the 160 patients, 64 (40%) had an MGRS lesion; amyloid light chain amyloidosis, the most common finding, accounted for nearly half of these lesions. In the non-MGRS group comprising 96 patients, 23 had arteriosclerosis, the most common finding. In multivariate analysis, strong predictors of finding an MGRS lesion included the presence of an elevated free light chain ratio, proteinuria, and hematuria. Among 596 patients with CKD and MG from 2017 to 2018, 62 (10.4%) underwent a kidney biopsy. Kidney biopsy was deferred for 70 patients (20%); for 62 of the 70, the diagnosis was already known, and eight were not candidates for therapy. Younger age and higher proteinuria and serum creatinine levels increased the likelihood that the patient would undergo a kidney biopsy. Proteinuria ≥1.5 g/d, hematuria, and an elevated free light chain ratio increase the likelihood of finding MGRS, and a kidney biopsy should be highly considered in such patients.

INTRODUCTION:Renal injury associated with monoclonal gammopathies (MG) is an area of interest of practical onconephrology. Prevalence, spectrum and renal outcome as far as approaches to treatment in this pathological entity, particularly in Russian population, still remain unclear and need refinement. AIM: Analysis of the prevalence, spectrum, treatment approaches and renal outcome in kidney injury associated with monoclonal gammopathies (MG).PATIENTS AND METHODS:Patients with MG and renal injury proven by kidney biopsies from 01.01.2011 till 01.05.2018 were enrolled into this one-center prospective study (n=119). Cases of MG of undetermined significance and non-amyloid kidney lesions were estimated as MG of renal significance (MGRS). Treatment approaches, haematological and renal responses were analysed. Worsening of kidney function was estimated as eGFR decrease >25 % from initial value or initiation of renal replacement treatment (RRT), improving – as eGFR increase >25 % from the initial value or the discontinuation of RRT. Other cases were determined as stable kidney function. Kidney outcome was determined in RRT initiation or eGFR<15 ml/min/1,73m2 at the end of follow-up. Long-term kidney outcome was estimated by Kaplan-Meier survival analysis. The median follow-up period was 12 (2; 27) months.RESULTS.Prevalence of kidney injury associated with MG among all performed kidney biopsies was 7,5 %, MGRS – 0,94 %. Multiple myeloma (MM), AL-amyloidosis and lymphoproliferative disorder (LPD) were diagnosed in 39, 55 and 10 patients, respectively. Prevalence of kidney injury types was the following: Al-amyloidosis (53 %); cast nephropathy (12 %); light chain deposition disease (12 %); C3-glomerulopathy (3 %); proliferative glomerulonephritis (GN) with monoclonal immunoglobulin deposits (3 %); cryoglobulinemic GN (2 %); thrombotic microangiopathy (2 %); podocytopathy (2 %); acute tubular necrosis – 2 %; immunotactoid GN (1 %); fibrillary GN (1 %); proximal tubulopathy (1 %), combination of different types (6 %). Patients mostly were treated with bortezomib and dexamethasone. Autologous stem cell transplantation was performed in 13 patients. Haematological response was achieved in 48,8 %, 45,4 % and 46,7 % of patients with MM, AL-amyloidosis and MGRS, respectively. Worsening of kidney function was registered in 11,1 % of MM and in 37,2 % of AL-amyloidosis; improving or stable kidney function was in 88,9 % and 62,7 % MM and AL-amyloidosis patients, respectively. In MGRS improving (20 %) and stable kidney function (80 %) were detected. Four-years cumulative renal survival in MM, AL-amyloidosis, MGRS and LPD groups was 63 %, 54 %, 80 % and 39 %, respectively, and does not differ between 4 groups.CONCLUSION:MG-associated kidney disease represented by diverse clinical and morphological patterns is standard problem in routine clinical practice. It is associated with inferior renal outcome and requires a practical implementation of highly-specialized interdisciplinary approach to diagnostics and treatment.

Light Chain Podocytopathy Mimicking Recurrent Focal Segmental Glomerulosclerosis.

Monoclonal Gammopathy of Renal Significance Causes C3 Glomerulonephritis Via Monoclonal IgG Kappa Inhibition of Complement Factor H

Monoclonal Gammopathies and Their Significance: A Retrospective Analysis of Monoclonal Gammopathy and Renal Disease

Patients with monoclonal gammopathy and concomitant kidney diseases are frequently found in clinical practice. Some of them are diagnosed with monoclonal gammopathy of renal significance (MGRS) due to the presence of monoclonal Ig-related kidney injuries. This study aimed to investigate the histopathologic spectrum and clinical characteristics associated with MGRS in a large cohort of patients with monoclonal gammopathy and biopsy-proven kidney diseases from a single Chinese nephrology referral center. Patients who presented with monoclonal gammopathy (monoclonal spike on serum and/or urine immunofixation tests) and underwent kidney biopsy in the Peking University First Hospital from January 1, 1999 to December 31, 2020 were enrolled in this retrospective study. Patients with malignant hematologic diseases were excluded. Clinical and laboratory data were collected from the electronic medical record system. Comparisons of patients with and without MGRS and with and without amyloidosis were performed. The clinical characteristics associated with MGRS were identified using multivariable logistic regression. A total of 700 patients with monoclonal gammopathy and kidney biopsy were identified. Thirteen patients with repeat kidney biopsies were analyzed separately. For the remaining 687 patients with one kidney biopsy, 261 patients (38%) had MGRS lesions, and the rest (426 patients, 62%) had non-MGRS kidney diseases. Ig-related amyloidosis accounted for the most MGRS cases (n=164, 63%), followed by monoclonal Ig deposition disease (n=23, 9%) and thrombotic microangiopathy (n=22, 8%). In the non-MGRS group, membranous nephropathy was the most common diagnosis (n=171, 40%). In the multivariable logistic regression model, the presence of abnormal serum free light chain ratio, older age, and greater proteinuria were independently associated with MGRS. Monoclonal Ig amyloidosis is the leading cause of MGRS in Chinese patients with monoclonal gammopathy. The presence of abnormal free light chain ratio, older age, and greater proteinuria were associated with MGRS.

SUN-007 MONOCLONAL GAMMOPATHY OF RENAL SIGNIFICANCE AND MONOCLONAL IMMUNOGLOBULIN RENAL DAMAGE IN MALIGNANT B-CELL DISORDERS: REAL CLINICAL PRACTICE – WHAT IS BEYOND MONOCLONAL IMMUNOGLOBULIN AMYLOIDOSIS?

Epidemiological Characteristics and Clinical Outcomes of Patients with Monoclonal Gammopathy of Renal Significance (MGRS) Diagnosed in a Large Safety-Net Hospital in the US

POS-499 CLINICAL AND PATHOLOGY SPECTRUM OF NON-AMYLOID MONOCLONAL GAMMOPATHY OF RENAL SIGNIFICANCE – ONE CENTER EXPERIENCE

Background: Monoclonal immunoglobulin–mediated kidney disease with various patterns of damage may occur in patients with B-cell malignancies and non-malignant monoclonal gammopathies, and the latter are actually merged under the umbrella of monoclonal gammopathy of renal significance. Amyloidosis is the most well-known monoclonal immunoglobulin–related kidney damage. We focused on the rarer conditions and aimed to evaluate the non-amyloid spectrum of monoclonal immunoglobulin–mediated patterns of renal damage in real clinical practice. Methods: A single-center non-interventional retrospective study included 45 patients with pathology-proven non-amyloid monoclonal immunoglobulin–mediated kidney disease, followed during 2002–2018. Disease duration, proteinuria, serum creatinine, need for dialysis at the time of kidney biopsy, clinical diagnosis, and kidney pathology findings were analyzed. Results: No significant differences in the median age, disease duration at the time of biopsy, or main clinical presentation of kidney disease were found between patients with monoclonal gammopathy of renal significance and patients with B-cell malignancies. Pathology patterns like proliferative glomerulonephritis with monoclonal immunoglobulin deposits, membranous nephropathy, C3 glomerulopathy, cryoglobulinemic glomerulonephritis, and combinations of light chain proximal tubulopathy with monoclonal immunoglobulin deposition disease, and of C3 glomerulopathy with light chain proximal tubulopathy were found in monoclonal gammopathy of renal significance setting only. In contrast, light chain proximal tubulopathy alone, anti-glomerular basement glomerulonephritis, and combinations of cast nephropathy with light chain proximal tubulopathy, and cast nephropathy with monoclonal immunoglobulin deposition disease were associated with multiple myeloma only. Monoclonal immunoglobulin deposition disease, intracapillary monoclonal immunoglobulin M deposits, and cast nephropathy alone were seen in both settings. Conclusion: The presence of monoclonal gammopathy in patients with proteinuria and/or impaired kidney function demands kidney biopsy. Neither duration of kidney disease nor its clinical presentation allows differentiating malignant and non-malignant causes of monoclonal immunoglobulin–mediated renal damage. Several pathology patterns, even cast nephropathy, can be found both in cases of monoclonal gammopathy of renal significance and in cases of B-cell malignancies. Dual patterns of damage, including combinations of organized and non-organized deposits, or organized deposits with monoclonal immunoglobulin–induced damage without monoclonal immunoglobulin deposition, constitute up to 9%, mostly in multiple myeloma cases.

The term monoclonal gammopathy of renal significance (MGRS) was introduced to describe renal damage caused by monoclonal immunoglobulin (MIg) secreted by small B-cell clones. By definition, patients with MGRS do not meet the diagnostic criteria of hematological malignancies such as multiple myeloma and lymphoma. MIg produced by these clones can result in permanent renal damage through its direct or indirect mechanisms. The spectrum of renal diseases in MGRS is wide, and early diagnosis is helpful for guiding the treatment and improving the prognosis. The diagnosis requires the combination of renal morphologic alterations from light microscopy, immunofluorescence (IF), and electron microscopy, with complete hematologic workup such as serum and urine protein electrophoresis, immunofixation, and serum light-chain assay. The treatment of MGRS includes conventional therapy, chemotherapy based on protease inhibitors, cytotoxic drugs, immunomodulators, and stem cell transplantation. The therapeutic strategy of MGRS targeting the causal B-cell clones is similar to the equivalent extrapolation treatments used for the overt malignancies. In addition, timely evaluation of the hematologic responses can be conducive to determining the efficacy of treatment, and prolonging the overall survival time. Key words: Monoclonal immunoglobulin; Renal damage; Diagnosis; Treatment; Hematological response

The Mayo MGRS Prediction Tool calculates the risk of finding monoclonal gammopathy of renal significance in a kidney biopsy in patients with monoclonal gammopathy.

Prevalence of MGCS Among Patients With Monoclonal Gammopathies.

Introduction: Monoclonal gammopathy of renal significance (MGRS) disorders are indolent B-cell or plasma cell lymphoproliferative neoplasms which do not meet the hematological criteria for malignancy, however they cause renal dysfunction as a result of production of nephrotoxic monoclonal immunoglobulin (MIg). Objectives: To study the clinical presentation, laboratory features, light microscopy and immunofluorescence (IF) characteristics of all cases of MGRS diagnosed at our hospital over a period of five years. Patients and Methods: A record of all renal biopsies performed at our hospital between 2014-2019 was accessed from the database. Out of 1356 kidney biopsies, 68 had evidence of MIg deposition on immunofluorescence. Only six cases met the criteria of MGRS. Histopathological and immunofluorescence characteristics were studied to classify the lesions as per International Kidney and Monoclonal Gammopathy (IKMG) Research Group classification. Results: All six cases presented with deranged renal function. Four had sub-nephrotic and one had nephrotic range proteinuria. MIg was identified in only one case on serum protein electrophoresis and free light chain assay. Using a conjunction of histomorphology of renal lesions, special stains and immunofluorescence all six cases of MGRS were categorized as per IKMG classification into monoclonal immunoglobulin deposition disease (two cases), AL amyloidosis, light chain cast nephropathy, proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) and light chain proximal tubulopathy (LCPT). Conclusion: MGRS presents as renal failure and proteinuria. MIg may not be detected on protein electrophoresis due to low-secretion in serum. A kidney biopsy is essential to study the morphology of renal lesions and identify MIg deposition.

Monoclonal gammopathy of renal significance (MGRS) results in kidney injury despite not meeting the hematological malignancy criteria necessitating treatment. Although kidney biopsy is crucial for diagnosis, it is an invasive procedure. Therefore, identifying patient characteristics associated with MGRS could aid in informing the decision to perform a biopsy. This cross-sectional multicenter study included participants with monoclonal gammopathy (MG) who underwent kidney biopsy between 2018 and 2022. We excluded patients diagnosed with hematological malignancies requiring treatment or those with vasculitis. Patient factors associated with MGRS were evaluated using a logistic regression model. Additionally, we describe monoclonal protein-related kidney diseases associated with hematological malignancies. A total of 2972 kidney biopsies were performed, of which 166 (5.6%) were associated with MG. Among these 166 patients, 57 had hematological malignancies. Of the remaining 98 patients, excluding those with vasculitis, 44 (45%) exhibited MGRS lesions. Among the MGRS cases, 71% had amyloid light-chain amyloidosis, whereas nephrosclerosis and diabetic nephropathy were more common in non-MGRS cases. Multivariate analysis revealed that the clinical predictors associated with MGRS lesions were the presence of proteinuria ≥ 1.5g/gCr, an abnormal free light chain (FLC) ratio, and the absence of diabetes. In hematological malignancy cases, monoclonal protein-related kidney diseases were observed in 49% of the cases, with kidney histology frequently exhibiting cast nephropathy or light chain deposition disease. Among patients with MG who underwent kidney biopsy, 45% were diagnosed with MGRS. Predictors of MGRS included proteinuria ≥ 1.5g/gCr, an abnormal FLC ratio, and the absence of diabetes.