scholarly journals Clinical Presentation and Renal Histopathological Findings in Patients with Monoclonal Gammopathy and Kidney Disease

2020 ◽  
Author(s):  
Gaetano Alfano ◽  
Alice Delrio ◽  
Francesco Fontana ◽  
Annachiara Ferrari ◽  
Giacomo Mori ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Monoclonal Gammopathy ◽  
Renal Involvement ◽  
Lymphoproliferative Disorders ◽  
M Protein ◽  
Al Amyloidosis ◽  
Light Chain Deposition Disease ◽  
Monoclonal Gammopathies ◽  
Increased Risk ◽  
Kidney Involvement

AbstractMonoclonal gammopathies have been widely associated with renal lesions. Nephrotoxicity of the secreted monoclonal (M)-protein relies on a complex interplay between biological characteristics and serum concentration. Little is known about the prevalence and renal manifestations of the different types of monoclonal gammopathies in patients with kidney disease.We reviewed all renal biopsies in our Center during a 12-year period to characterize patients diagnosed with monoclonal gammopathy. Data about demographics, laboratory examinations, renal manifestations and histological lesions were collected retrospectively. Results were correlated with the different lymphoproliferative disorders to evaluate the relationship between renal involvement and monoclonal gammopathies.Monoclonal gammopathy was detected in 179 (13.4%) patients. The circulating M-protein was secreted by monoclonal gammopathy of undetermined significate (MGUS) (51.9%), myeloma multiple (MM) (25.7%), primary amyloidosis (AL) (8.9%), smoldering MM (5 %), non-Hodgkin lymphoma (NHL) (6.7%) and HL (1.7%). Documented renal involvement in benign disorders such as MGUS and SMM accounted for 7.5% and 11.1%, respectively. MM was associated with an increased risk of kidney involvement (adjusted odds ratio=36.4; P=<0.001) and manifested with higher serum creatinine compared to other disorders. AL amyloidosis was principally secondary to MGUS (75%) and presented with nephrotic proteinuria. NHL and HL patients had heterogeneous renal manifestations. MGRS manifested both with light chain deposition disease and membranoproliferative glomerulonephritis. Compared to the other lymphoproliferative disorders, MM and AL amyloidosis showed higher creatinine blood levels and proteinuria, respectively. MM was significantly associated with kidney disease in our cohort of patients.Monoclonal gammopathy is a frequent diagnosis in patients with kidney disease. An accurate diagnostic process including lab tests and kidney biopsy is necessary to identify if the secreted M-protein is associated with renal involvement.

P0498CLINICAL PRESENTATION AND RENAL HISTOPATHOLOGICAL FINDINGS IN PATIENTS WITH MONOCLONAL GAMMOPATHY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Gaetano Alfano ◽  
Alice Delrio ◽  
Francesco Fontana ◽  
Annachiara Ferrari ◽  
Andrea Solazzo ◽  
...  
Keyword(s):  
Renal Function ◽  
Monoclonal Gammopathy ◽  
Kidney Biopsy ◽  
Renal Involvement ◽  
M Protein ◽  
Histological Evaluation ◽  
Al Amyloidosis ◽  
Creatinine Ratio ◽  
Urine Protein ◽  
Cast Nephropathy

Abstract Background and Aims Monoclonal gammopathy is associated with renal lesions due to the toxic effect of M-protein. The aim of our study was to evaluate the prevalence and the clinical presentation of monoclonal gammopathy in patients who underwent kidney biopsy for renal impairment. Method We conducted a retrospective study at the Nephrology and Dialysis Unit of the University Hospital of Modena from 2005 to 2017. The diagnosis of renal disease was proved histologically. Results Monoclonal gammopathy was found in 179 out of 1334 patients (13.4%). Mean age was 66.1±13.4 years with a predominance of males (63.7%). There was no differences (P=0.16) between the age of patients with benign (64.9±14.3) and malignant lymphoproliferative diseases (67.6±12). The hematologic disorders involved in the production of M-protein were MGUS (51.9%), myeloma multiple (MM) (25.7%), amyloidosis (8.9%) smoldering MM (5 %), non-Hodgkin lymphoma (NHL) (6.7%) and HL (1.7%). The prevalence of MGUS was estimated to be 6.97% (93/1334). Mean serum creatinine was 2.68±2.12 mg/dl (eGFR of 35.24±29.32 ml/min) and urine protein/creatinine ratio of 5.1±6.5. None of the study subjects progressed to MM or other lymphoproliferative diseases. The most common kidney disease was membranoproliferative (GN) (19.3%). MGRS has been identified in five patients (5.4%). Mean age of MM was 66.84±13 years. Serum concentration M-protein was 1.47±0.98. Among patients with AKI (89.1%), 13 patients (28.2%) required urgent hemodialysis. Histological evaluation showed cast nephropathy (71.7%), MM-associated AL amyloidosis (15.2%), MM-associated-light chain deposition disease (4.3%) and interstitial nephritis (8.7%). Nine patients had a diagnosis of smoldering MM. Average age was 69.17±10.8 years old. At presentation, creatinine was 2.31±2.6 mg/dl (GFR of 41.35 ml/min). Evaluation of renal biopsies allowed us to identify different patterns of glomerular diseases, expression of an aspecific renal involvement of this hematological disease. AL amyloidosis was secondary to MGUS (75%) and smoldering MM (33%). Mean age was 66.04±11.7 years old. At presentation mean urine protein/creatinine ratio was 8.33±3.2 concomitant to a serum albumin level of 2.74±0.84 gr/dl. Mean creatinine was 1.4 mg/dl corresponding to eGFR= 56.5 ml/min. Average age of NHL patients was 72.6±9.6 years. Renal function was extremely variable at presentation; mean creatinine was 2.4±1.6 mg/dl (eGFR of 30.4±22.7 ml/min). Histological evaluation of biopsy specimen revealed amyloidosis (25%), cryoglobulinemic GN (25%), LCDD (16.6%), cast-nephropathy (8.3%), LCDD (8.3%) and other renal diseases (16.8%). Three patients (1.12%) had a diagnosis of HL at mean age of 69.04±5.3 years. At presentation, renal function was normal in all patients with a creatinine of 0.93±0.07mg/dl (eGFR of 62.7.3±7.4 ml/min). Urine protein/creatinine ratio was 0.3±0.2. Kidney biopsy revealed cryoglobulinemic GN (75%) and hypertensive nephrosclerosis (25%). ANOVA analysis did not found statistically significant differences in age (p=0.11) and serum concentration of M-protein (P=0.42) between groups. The differences in mean serum creatinine and mean urine protein/creatinine ratio were statistically significant between groups, (P&lt;0.0001) and (P=0.003), respectively. A post hoc Tukey test showed that proteinuria was higher in AL amyloidosis compared to MM and HL, whereas renal function was worse in MM patients compared to the others. Conclusion MGUS was the most common monoclonal gammopathy. Surprisingly, it is frequently associated with membranoproliferative glomerulonephritis. MGRS is a rare histopathological entity (5.4%). MM manifests frequently with AKI whereas AL amyloidosis with nephrotic syndrome. Renal function was extremely variable in NHL patients; on the other hand, the limited number of HL patients with renal involvement in our cohort does not allow generalization of our findings.

scholarly journals Clinical Presentation, Renal Histopathological Findings, and Outcome in Patients with Monoclonal Gammopathy and Kidney Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Gaetano Alfano ◽  
Alice Delrio ◽  
Francesco Fontana ◽  
Giacomo Mori ◽  
Silvia Cazzato ◽  
...  
Keyword(s):  
Kidney Disease ◽  
End Stage Renal Disease ◽  
Monoclonal Gammopathy ◽  
Kidney Biopsy ◽  
Clinical Manifestations ◽  
Kidney Injury ◽  
M Protein ◽  
Monoclonal Gammopathies ◽  
Stage Renal Disease ◽  
End Stage

Monoclonal gammopathies are associated with acute and chronic kidney injury. Nephrotoxicity of the secreted monoclonal (M)-protein is related to its biological properties and blood concentration. Little is known about epidemiology, clinical manifestations, and outcome of monoclonal gammopathies in patients with kidney disease. We retrospectively collected data about demographics, clinical manifestations, and renal histological lesions of all patients (n = 1334) who underwent kidney biopsy between January 2000 and March 2017. Monoclonal gammopathy was detected in 174 (13%) patients with a mean age of 66.4 ± 13.1 years. The spectrum of monoclonal gammopathies comprised monoclonal gammopathy of undetermined significate (MGUS) (52.8%), multiple myeloma (MM) (25.2%), primary amyloidosis (AL) (9.1%), smoldering MM (SMM) (4%), non-Hodgkin lymphoma (NHL) (6.8%), and Hodgkin lymphoma (HL) (1.7%). Monoclonal gammopathy of renal significance (MGRS) accounted for 6.5% in patients with MGUS and 14.2% in patients with SMM. Evaluation of kidney biopsy revealed that M-protein was directly involved in causing kidney injury in MM (93.1%). MM was the only gammopathy significantly associated with an increased risk of kidney injury (odds ratio [OR] = 47.5, CI 95%, 13.7–164.9; P ≤ 0.001 ). While there were no significant differences in the progression toward end-stage renal disease or dialysis P = 0.776 , monoclonal gammopathies were associated with a different risk of death P = 0.047 at the end of the follow-up. In conclusion, monoclonal gammopathy was a frequent finding (13%) in patients who underwent kidney biopsy. M-protein was secreted by both premalignant (56.8%) and malignant (43.2%) lymphoproliferative clones. Kidney biopsy had a key role in identifying MGRS in patients with MGUS (6.5%) and SMM (14.2%). Among monoclonal gammopathies, only MM was significantly associated with biopsy-proven kidney injury. The rate of end-stage renal disease or dialysis was similar among monoclonal gammopathies, whereas NHL, MM, and SMM showed a higher rate of deaths.

P0257CLINICOPATHOLOGICAL SPECTRUM OF KIDNEY INVOLVEMENT IN MONOCLONAL GAMMOPATGY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Hadj Brahim Mayssa ◽  
Meriem Ben salem ◽  
Ouni Amal ◽  
Handous Insaf ◽  
Bensalah Manel ◽  
...  
Keyword(s):  
Renal Failure ◽  
Nephrotic Syndrome ◽  
Serum Proteins ◽  
Kidney Diseases ◽  
Renal Involvement ◽  
Chronic Hemodialysis ◽  
Al Amyloidosis ◽  
Monoclonal Gammopathies ◽  
Cast Nephropathy ◽  
Kidney Involvement

Abstract Background and Aims The occurrence of kidney diseases associated with a monoclonal gammopathy is increasingly recognized.Renal biopsy and evaluation by light microscopy, electron microscopy and immunofluorescence,in association with adequate clinical examination are essential in accurate diagnosis. The objective of our study is to describe the types of kidney damage secodary to monoclonal gammopathies and to study its renal prognosis. Method It is a monocentric RETOSPECTIVE DESCRIPTIVE STUDY carried out in the nephrology department of CHU FATTOUMA BOURGUIBA MONASTIR spread over a period of 7 years from January 2012 to December 2018. Results we collected 40 cases of monoclonal gammopathies. The median age was 61 years.The sex ratio was 0,9. the circumstances of discovery were dominated by renal failure. it revealed the diagnosis in 77.5% of cases. the renal presentation proteinuria in 70%, microscopic hematuria in 12.5%, edematous syndrome in 27.5% and nephrotic syndrome in 37,5%. The mean creatinine level was 500 umol / L and proteinuria at 4,3 g / 24 h with a maximum rate of 17.5 g / 24h. the electrophoresis of serum proteins showed the presence of a monoclonal peak in 90% of the cases in the gamma zone. The plasmocytosis was less than 10% in 15% of cases and more than 60% in 22,5% of the cases. Radiology showed bone localizations in 32,5% of cases. These gammopathies were classified as Multiple myeloma in34 patients, POEMS in one case and 5 MGRS. Kidney biopsy was performed in 10 patients showing cast nephropathy, AL amyloidosis and vasculites(endocapillary glomerulonephritis with hyaline thrombi in all vessels and double contour appearance of the glomerular basement membrane) in respectively 12,5%, 7,5% and 2,5% of cases. the main indications were rapidly progressive renal failure, unexplained acute renal failure and nephrotic syndrome. The renal involvement retained was a myeloma tubulopathy in 28 patients, 3 of whom were confirmed histologically . AL amyloidosis was found in 5 patients and the confirmation was histological. Type 1 cryoglobulinemia was diagnosed in only one patient. Glomerular nephropathy remained undetermined in 6 patients whose PBR was indicated but not made in the presence of hemostasis disorders. The chemotherapy was started in 34 patients based on bortezomide-thalidomide-dexamethasone in 30% of cases. An autograft of the bone marrow was done in one patient. Hemodialysis was required in 15 patients. The renal function was improved in 42.5% of the cases and a passage on chronic hemodialysis in 10% of cases. 10% of patients have achieved complete hematological remission. Conclusion Patients with MG can develop a large variety of related renal lesions.Renal involvement darkens the prognosis hence the need for adequate care .

scholarly journals P0204PREVALENCE AND PREDICTIVE FACTORS OF BIOPSY-PROVEN NEPHROPATHY RELATED TO MONOCLONAL GAMMOPATHY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Arthur Roux ◽  
Helene Lazareth ◽  
Dominique Nochy ◽  
Anne-Sophie Jannot ◽  
Camille Nevoret ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Serum Creatinine ◽  
Monoclonal Gammopathy ◽  
Kidney Biopsy ◽  
Hematological Malignancy ◽  
Al Amyloidosis ◽  
Monoclonal Immunoglobulin ◽  
Lymphoid Leukemia ◽  
Predictive Values ◽  
Bence Jones Proteinuria

Abstract Background and Aims The prevalence of monoclonal gammopathy (MG) and kidney disease increases with age. When a patient present with both conditions, it is often necessary to perform a kidney biopsy in order to rule out a Monoclonal Immunoglobulin-Related Nephropathy (MIRN) that may require a specific therapy that targets either an overt hematological malignancy or a MG or Renal Significance (MGRS). The aim of our study was to identify factors that predict the presence of MIRN in this setting. Method This retrospective monocentric study included all patients who underwent a kidney biopsy between 2007 and 2018 with concurrent presence of GM, as defined by positive serum immuno-electrophoresis and/or Bence-Jones proteinuria. Results 328 patients were included, representing 11.8% of all kidney biopsies performed in our center during this period. Indication of biopsy was renal failure (eGFR &lt;60ml/min/1.73m) in 77.4% of cases and/or proteinuria (urine protein-to-creatinine ratio &gt;0.5g/g) in 75.9% of them. Median (IQR) serum creatinine was 155 μmol/L (111-233), eGFR 37.5 (22-56) ml/min/1.73m, serum albumin 29.5 (24-35) g/l. Median age was 67 (57/75), the M/F ratio was 198/130, diabetes mellitus was present in 21.3% of cases, hypertension in 53.1%. Kidney biopsy revealed that nephropathy was related to MG in 91/328 patients (27.7%). Myeloma cast nephropathy and AL amyloidosis were the most common histopathological subtypes (36 and 34% respectively), followed by monoclonal immunoglobulin deposition disease (15%) and cryoglobulinemic glomerulonephritis (8%). Patients with MIRN had more severe renal function impairment with median (IQR) serum creatinine of 176 (119-307) vs 149 (108-216) μmol/l (p=0.003) and heavier proteinuria, 3.9 (2.2-8.2) vs 2.0 (0.9-5.2) g/g (p&lt; 0.001), when compared to non-MIRN patients. Hematological malignancy was diagnosed in 83 cases (25,3%) (Multiple Myeloma in 62, non-Hodgkin Lymphoma in 6, Waldenström Macroglobulinemia in 6, Chronic Lymphoid Leukemia in 6, Plasmocytoma in 3). Among them, MIRN was diagnosed in 51 (61%) cases but tumoral lympho-plasmocytic infiltration was observed in 9 (11%) cases. In this subgroup of patients, no laboratory test could predict the presence of a specific nephropathy. Among patients with no hematological malignancy (n=245), MIRN was diagnosed in 40 cases (16%) to confirm MGRS diagnosis. The markers that were most commonly associated with the presence of MGRS were positive Bence-Jones proteinuria (OR 4.7; 95%CI 2.2-10.3; p&lt; 0.001), abnormal serum Free Light Chain (FLC) ratio (OR 4.2; 95%CI 1.7-10.7; p&lt; 0.001), and serum electrophoresis spike &gt;1.5 g/l (OR 5.9; 95%CI 2.6-13.5; p&lt; 0.001). However, none of those markers had sufficient power to formally predict the result of the biopsy, as positive (PPV) or negative (NPV) predictive values were 36/41/45 % and 89/86/88 % respectively. Conclusion Almost one-third of patients with MG and kidney disease referred to our Department have biopsy-proven related nephropathy. Although negativity of Bence-Jones proteinuria and a normal serum FLC ratio are frequently associated with the absence of MGRS, kidney biopsy, beyond its diagnostic and prognostic interest, remains the most discriminating test.

scholarly journals Chronic kidney disease and undiagnosed atrial fibrillation in individuals with diabetes

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Nam Ju Heo ◽  
Sang Youl Rhee ◽  
Jill Waalen ◽  
Steven Steinhubl
Keyword(s):  
Atrial Fibrillation ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Clinical Symptoms ◽  
Screening Program ◽  
Renal Involvement ◽  
Newly Diagnosed ◽  
Mortality And Morbidity ◽  
Increased Risk

Abstract Background Diabetes is an independent risk factor for atrial fibrillation (AF), which is associated with increases in mortality and morbidity, as well as a diminished quality of life. Renal involvement in diabetes is common, and since chronic kidney disease (CKD) shares several of the same putative mechanisms as AF, it may contribute to its increased risk in individuals with diabetes. The objective of this study is to identify the relationship between CKD and the rates of newly-diagnosed AF in individuals with diabetes taking part in a screening program using a self-applied wearable electrocardiogram (ECG) patch. Materials and methods The study included 608 individuals with a diagnosis of diabetes among 1738 total actively monitored participants in the prospective mHealth Screening to Prevent Strokes (mSToPS) trial. Participants, without a prior diagnosis of AF, wore an ECG patch for 2 weeks, twice, over a 4-months period and followed clinically through claims data for 1 year. Definitions of CKD included ICD-9 or ICD-10 chronic renal failure diagnostic codes, and the Health Profile Database algorithm. Individuals requiring dialysis were excluded from trial enrollment. Results Ninety-six (15.8%) of study participants with diabetes also had a diagnosis of CKD. Over 12 months of follow-up, 19 new cases of AF were detected among the 608 participants. AF was newly diagnosed in 7.3% of participants with CKD and 2.3% in those without (P < 0.05) over 12 months of follow-up. In a univariate Cox proportional hazard regression analysis, the risk of incident AF was 3 times higher in individuals with CKD relative to those without CKD: hazard ratios (HR) 3.106 (95% CI 1.2–7.9). After adjusting for the effect of age, sex, and hypertension, the risk of incident AF was still significantly higher in those with CKD: HR 2.886 (95% CI 1.1–7.5). Conclusion Among individuals with diabetes, CKD significantly increases the risk of incident AF. Identification of AF prior to clinical symptoms through active ECG screening could help to improve the clinical outcomes in individuals with CKD and diabetes.

scholarly journals Recommendations for use of Tumor Markers in Monoclonal Gammopathies

2007 ◽  
Vol 26 (2) ◽  
pp. 165-172
Author(s):  
Marijana Dajak
Keyword(s):  
Tumor Markers ◽  
Monoclonal Gammopathy ◽  
Clinical Biochemistry ◽  
M Protein ◽  
Monoclonal Gammopathies ◽  
Undetermined Significance

Preporuke za Primenu Tumorskih Markera Kod Monoklonskih GamapatijaMonoklonske gamapatije čine grupu poremećaja koji se karakterišu klonskom proliferacijom plazma ćelija. M protein je tumorski marker specifičan za monoklonske gamapatije jer odražava klonsku produkciju imunoglobulina. Monoklonske gamapatije uključuju: multipli mijelom,Waldenström-ovu makroglobulinemiju (WM), nesekretorni mijelom, prikriveni (smoldering) multipli mijelom, monoklonsku gamapatiju od neodređenog značaja (MGUS,Monoclonal gammopathy of undetermined significance), primarnu sistemsku amiloidozu i bolest teških lanaca. Dijagnoza multiplog mijeloma je zasnovana na detekciji M proteina u serumu i/ili urinu, infiltraciji plazma ćelija u koštanoj srži i litičkim koštanim lezijama na radiografiji skeleta. Prema NACB (National Academy of Clinical Biochemistry) preporukama, tumorski markeri za dijagnozu,screening, identifikaciju klonaliteta, praćenje bolesti i prognostičku evaluaciju kod monoklonskih gamapatija su: elektroforeza proteina u serumu i/ili urinu, imunofiksacija u serumu i/ili urinu, slobodni laki lanci (SLL) u serumu i/ili urinu, viskoznost seruma i β2-mikroglobulin. Imunofiksacija se koristi za identifikaciju klonaliteta (tipa) M proteina primećenog na elektroforezi i kada postoji sumnja bez obzira na normalan proteinski elektroforetogram. Posebno je korisna za prepoznavanje i razlikovanje biklonskih ili triklonskih gamapatija. Viskoznost seruma trebalo bi određivati ako pacijent ima znake i simptome sindroma hiperviskoznosti. WM je najčeŠći uzrok hiperviskoznosti, ali se takođe može pojaviti i kod pacijenata sa velikim nivoima monoklonskog IgA ili IgG. Automatizovana imunoodređivanja SLL u serumu su osetljivija od tradicionalne elektroforetske metode i imunofiksacije za detekciju mijeloma monoklonskih lakih lanaca, nesekretornog mijeloma i AL amiloidoze. Osim toga, odnos SLL u serumu je nezavisan faktor rizika za nastanak maligne progresije kod pacijenata sa MGUS. Određivanje SLL u serumu i elektroforeze proteina seruma kao testova prve linije za razmatranje prisustva mogućih poremećaja B ćelija daje dodatnu dijagnostičku informaciju.

scholarly journals Follow-up Care of Monoclonal Gammopathy of Undetermined Significance: A Guide for Primary Care Physicians

2021 ◽  
Vol 8 (5) ◽  
Author(s):  
Hammad Z ◽  
◽  
Hernandez E ◽  
Tate S ◽  
◽  
...  
Keyword(s):  
Plasma Cell ◽  
Primary Care Physicians ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Organ Damage ◽  
M Protein ◽  
Bone Lesions ◽  
Al Amyloidosis ◽  
End Organ Damage ◽  
Undetermined Significance

Monoclonal Gammopathy of Undetermined Significance (MGUS) is a condition in which M protein, an abnormal monoclonal immunoglobulin, is present in the blood at a nonmalignant level. Specifically, it is defined by: blood serum M protein concentration <3 g/dL (<30 g/L), <10% plasma cells in the bone marrow, and no evidence of end organ damage [1,2]. Evidence of end organ damage includes hypercalcemia, renal insufficiency, anemia, and bone lesions. These are indicative of MGUS progression and which can be attributed to the monoclonal plasma cell proliferative process [3]. MGUS occurs in 3% of the general population older than 50 years. Incidence increases with age and varies with sex with higher rates observered in males than females [1,4]. MGUS is the most common plasma cell disorder, with 60% of patients that present to the Mayo Clinic with a monoclonal gammopathy being diagnosed with MGUS [3]. While it is typically an asymptomatic condition, it is premalignant disorder to other monoclonal gammopathies. Multiple Myeloma (MM) is almost always preceded by MGUS and the majority of patients will have detectable levels of M protein for at least 5 years prior to MM diagnosis [5,6]. MGUS also precedes immunoglobulin light chain (AL) amyloidosis and Waldenstrom Macroglobulinemia (WM) and tends to progress to disorders at a fixed but unrelenting rate of 1% per year [4].

scholarly journals SARS-CoV-2 and Fabry nephropathy: potential risks and the pathophysiological perspective

2020 ◽  
Vol 9 (4) ◽  
pp. e36-e36 ◽  
Author(s):  
Hernán Trimarchi
Keyword(s):  
Kidney Disease ◽  
Replacement Therapy ◽  
Mesangial Cells ◽  
Late Onset ◽  
Kidney Injury ◽  
Pharmacological Chaperone ◽  
Enzyme Replacement ◽  
Increased Risk ◽  
Kidney Involvement ◽  
Fabry Nephropathy

Fabry disease is an X-linked disorder due to mutations in alpha-galactosidase A gene. It affects the kidney in virtually all patients with classical and some late onset variants. Podocytes, endothelial cells, vascular smooth muscle, tubular and mesangial cells are involved in different ways. Proteinuria and chronic kidney disease are the result of the progressive accumulation of the enzyme substrates globotriaosylceramide (GB3) and lyso-GB3 in the cytoplasm of these cells (mainly in lysosomes), which leads to cellular and organ dysfunction and eventually renal failure and end-stage kidney disease. Specific enzyme replacement therapy and pharmacological chaperone are at present the main therapeutic approach. After enzyme infusion, the delivered enzyme is differentially uptaken by kidney cells in three different ways: By Mannose-6-phosphate receptor, megalin and sortilin. The delivered enzyme gradually clears cells from the accumulation of the glycosphingolipids and contributes to a cellular healthier status. The recent pandemic caused by SARS-CoV-2 has led to the collapse of health systems around the world and to thousands of deaths. Kidney involvement has been reported to range from proteinuria to acute kidney injury, 30% of which may require renal replacement therapy. In this review the potential causes for which Fabry patients should be at increased risk and the necessity not to discontinue therapy are discussed.

scholarly journals Hepatitis B Associated Monoclonal Gammopathy That Resolved after Successful Liver Transplant

2009 ◽  
Vol 2009 ◽  
pp. 1-3
Author(s):  
P. Sreenivasan ◽  
S. Nair
Keyword(s):  
Multiple Myeloma ◽  
Liver Transplantation ◽  
Hepatitis B ◽  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Lymphoproliferative Disorders ◽  
M Protein ◽  
Kappa Light Chain ◽  
Hepatitis B Infection ◽  
Undetermined Significance

Monoclonal gammopathy of undetermined significance (MGUS) has been most commonly associated with diseases like multiple myeloma, Waldenstrom's macroglobulinemia, primary systemic amyloidosis, HIV, and other lymphoproliferative disorders. There has been an isolated report of MGUS in patients coinfected with HIV and Hepatitis B, as the work by Amara et al. in 2006. Here, we report a case of IgA-kappa light chain gammopathy secondary to Hepatitis B infection, which resolved after liver transplantation. To our knowledge, this is the first reported case of M protein spike seen in the context of Hepatitis B infection only.

scholarly journals P0463KIDNEY INVOLVEMENT IN PARAPROTEINEMIC DISEASES - ANALYSIS OF THE SINGLE CENTER REGISTER OF KIDNEY BIOPSIES

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Nikola Zagorec ◽  
Ana Šavuk ◽  
Ivica Horvatić ◽  
Dino Kasumović ◽  
Ana Brechelmacher ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Nephrotic Syndrome ◽  
Kidney Disease ◽  
Plasma Cell ◽  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Kidney Biopsy ◽  
Kidney Injury ◽  
Al Amyloidosis ◽  
Monoclonal Immunoglobulin

Abstract Background and Aims Kidneys are often damaged in paraproteinemic conditions. Paraproteins are monoclonal immunoglobulins or immunoglobulin fractions that are produced by a clonal population of B- or plasma cell lineage and can cause a variety of histological patterns of kidney injury, such as light chain (AL) amyloidosis or light chain cast nephropathy (LCCN). Monoclonal gammopathy of renal significance (MGRS) represents a group of disorders in which a monoclonal immunoglobulin secreted by B- or plasma cell clone causes renal damage. By definition, these disorders do not meet diagnostic criteria for overt, symptomatic multiple myeloma or a lymphoproliferative disorder, but in contrast to monoclonal gammopathy of undetermined significance (MGUS) there is evidence of end-organ damage that can warrant therapy. Method All patients with paraproteinemic kidney disease were identified by retrospective review of the Hospital Register of kidney biopsies done at Department of Nephrology and Dialysis, in Dubrava University Hospital, Zagreb, from 2009 until 2018. Every kidney biopsy was analyzed by light, immunofluorescent and electron microscopy. Laboratory findings, including serum protein electrophoresis, serum free light chain level and immunofixation of serum proteins, were done for every patient. Clinical and histologic features of patients and features of underlying hematological conditions were analyzed. Results We identified 47 patients (3,28% of all biopsies that were done in that period) with kidney disease with clear hematological background. The mean patients' age at the time of the biopsy was 63 years and 27 of them were females. Two patients had signs of direct infiltration of kidneys with malignant lymphomic cells (non-Hodgkin lymphoma) and were excluded from the analysis. Clinical presentation of the patients at the time of biopsy were: proteinuria in 85% of patients, full nephrotic syndrome in 55%, azotemia in 66% of patients (80% had acute kidney injury of unclear etiology) and hematuria in 12,7%. Most common histologic patterns of kidney injury were AL amyloidosis (45%) and LCCN (30%) but additionally 7 different histological patterns were found: light chain depostion disease, light chain proxymal tubulopathy, fibrillary and imunotactoid glomerulopathy, proliferative glomerulonephritis with monoclonal immunoglobulin deposition, crioglobulinemic glomerulopathy type I and tubulointerstitial damage caused by immunoglobulin deposition. Figure 1 shows main features of patients with AL amyloidosis and cast LCCN. Conclusion Kidney disease can be initial presentation of an underlying paraproteinemia and, as our data showed, can clinicaly present with acute kidney injury, nephrotic or subnephrotic range proteinuria or full nephrotic syndrome. Variety of histologic patterns of kidney injury were described and AL amyloidosis and LCCN were the most common histological findings. Detailed hematologic workup should follow kidney biopsy in order to determine the exact nature and extension of the disease and therefore the most appropriate therapy.

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