Significant association between renal function and area of amyloid deposition evident in kidney biopsy specimens in both AA and AL amyloidosis

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<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.

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Significant association between renal function and amyloid-positive area in renal biopsy specimens in AL amyloidosis

BMC Nephrology ◽

10.1186/1471-2369-13-118 ◽

2012 ◽

Vol 13 (1) ◽

Cited By ~ 7

Author(s):

Takeshi Kuroda ◽

Naohito Tanabe ◽

Daisuke Kobayashi ◽

Yoko Wada ◽

Shuichi Murakami ◽

...

Keyword(s):

Renal Function ◽

Renal Biopsy ◽

Al Amyloidosis ◽

Biopsy Specimens

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Renal Involvement and Outcome In Monoclonal Lightchain Disease

Blood ◽

10.1182/blood.v116.21.4985.4985 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4985-4985

Author(s):

Raoul Bergner ◽

Michael J. Uppenkamp ◽

Martin Hoffmann

Keyword(s):

Renal Function ◽

Kidney Disease ◽

Renal Disease ◽

Light Chain ◽

Kidney Biopsy ◽

Renal Involvement ◽

The Other ◽

Renal Outcome ◽

Al Amyloidosis ◽

Light Chain Disease

Abstract Abstract 4985 Background: Renal involvement is very common in monoclonal light chain disease (mLCD). However, the types of renal disease are manifold. Also the prognosis and outcome is very different. We analysed the data and renal outcome of patients with monoclonal light chain disease and renal disease. Methods: We analysed the data of patients with monoclonal light chain disease, who underwent a kidney biopsy due to proteinuria and/or renal insufficiency of unclear origin, retrospectively. Data of renal function, proteinuria, the type of renal disease and the renal outcome were collected. The mLCD were subclassified in multiple myeloma (MM), AL-amyloidosis (ALA), monoclonal gammopathy of unclear significance (MGUS) and B-cell non hodgkin lymphona (B-NHL). The kidney biopsy findings were classified in cast nephropathy (CN), ALA, light chain deposit disease (LCDD) and other renal disease (ORD). Results: 88 patients were included in the analysis. 47 patients suffered from MM, 15 from systemic ALA, 21 from MGUS and 5 from B-NHL, respectively. In 17 patients the mLCD was not known before kidney biopsy but detected by typical kidney disease. Of the 47 patients with MM 24 had CN, 4 LCDD, 4 ALA and 15 ORD, respectively. All patients with ALA had renal amyloidosis except one, who had an IgA-glomerulonephritis. All patients with MGUS suffered from ORD only. Patients with B-NHL had CN one patient, LCDD one patient, ALA one patient and ORD two patients, respectively. The ORD were also associated with the mLCD in 21 cases (interstitial nephritis n=7, nephrocalcinosis n=7 and membranoproliferative glomerulonephritis n=4), the other patients had kidney disease independent from mLCD (e.g. diabetic nephropathy, focal segmental glomerulosclerosis, IgA-glomerulonephritits or nephroangiosclerosis). The mean follow up time was 20.4±24.8 month. Patients with CN had a significant worse renal function at time of kidney biopsy [serum creatinine [mg/dl]: CN 4.7±4.0; LCDD 3.36±1.38; ALA 1.46±1.0; ORD 2.0±2.3; p< 0.001 CN vs. ALA and ORD]. Patients with ALA had a significant greater proteinuria [g/d], than the other patients [CN 3.3±2.5; LCDD 1.7±0.9; ALA 5.6±5.2; ORD 2.1±1.9; p< 0.05 ALA vs. LCDD and CN; p<0.001 ORD vs. ALA]. 3.7 months after kidney biopsy 50% of patients with CN were on dialysis (HD). At 12 month 59% of patients with CN were on HD, compared to 37% of patients with ALA, 20% of patients with LCDD and 8% of patients with ORD (p=0.0004). Patients on HD had a significant worse survival compared to those without HD [50% survival 5.3 vs. 42 months; p=0.005]. Discussion: Our data demonstrate, that not all patients with mLCD suffered from a mLCD associated renal disease. The renal prognosis was very different between the types of renal disease. The worst renal outcome had patients with CN followed by patients with ALA. The best renal outcome had patients with ORD. Once on HD the survival is worse than without HD. Based on our data we would recommend to clarify the exact type of renal disease in all patients with mLCD and any evidence of renal disease by kidney biopsy. Disclosures: No relevant conflicts of interest to declare.

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Glomerular expression of matrix metalloproteinases in AL-amyloidosis and association with renal function at the time of kidney biopsy

Clinical Nephrology ◽

10.5414/cn108670 ◽

2016 ◽

Vol 85 (2016) (01) ◽

pp. 44-54 ◽

Cited By ~ 3

Author(s):

Evangelia Charitaki ◽

Efstathios Kastritis ◽

Constantina Petraki ◽

Konstantinos Liapis ◽

Konstantinos Adamidis ◽

...

Keyword(s):

Renal Function ◽

Matrix Metalloproteinases ◽

Kidney Biopsy ◽

Al Amyloidosis

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Bone disease as the first manifestation of systemic AL-amyloidosis

Terapevticheskii arkhiv ◽

10.26442/00403660.2020.07.000775 ◽

2020 ◽

Vol 92 (7) ◽

pp. 85-89

Author(s):

L. P. Mendeleeva ◽

I. G. Rekhtina ◽

A. M. Kovrigina ◽

I. E. Kostina ◽

V. A. Khyshova ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Bone Disease ◽

Plasma Cells ◽

Interventricular Septum ◽

Bone Destruction ◽

Amyloid Deposition ◽

Bone Lesions ◽

Al Amyloidosis ◽

Linear Type

Our case demonstrates severe bone disease in primary AL-amyloidosis without concomitant multiple myeloma. A 30-year-old man had spontaneous vertebral fracture Th8. A computed tomography scan suggested multiple foci of lesions in all the bones. In bone marrow and resected rib werent detected any tumor cells. After 15 years from the beginning of the disease, nephrotic syndrome developed. Based on the kidney biopsy, AL-amyloidosis was confirmed. Amyloid was also detected in the bowel and bone marrow. On the indirect signs (thickening of the interventricular septum 16 mm and increased NT-proBNP 2200 pg/ml), a cardial involvement was confirmed. In the bone marrow (from three sites) was found 2.85% clonal plasma cells with immunophenotype СD138+, СD38dim, СD19-, СD117+, СD81-, СD27-, СD56-. FISH method revealed polysomy 5,9,15 in 3% of the nuclei. Serum free light chain Kappa 575 mg/l (/44.9) was detected. Multiple foci of destruction with increased metabolic activity (SUVmax 3.6) were visualized on PET-CT, and an surgical intervention biopsy was performed from two foci. The number of plasma cells from the destruction foci was 2.5%, and massive amyloid deposition was detected. On CT scan foci of lesions differed from bone lesions at multiple myeloma. Bone fragments of point and linear type (button sequestration) were visualized in most of the destruction foci. The content of the lesion was low density. There was no extraossal spread from large zones of destruction. There was also spontaneous scarring of the some lesions (without therapy). Thus, the diagnosis of multiple myeloma was excluded on the basis based on x-ray signs, of the duration of osteodestructive syndrome (15 years), the absence of plasma infiltration in the bone marrow, including from foci of bone destruction by open biopsy. This observation proves the possibility of damage to the skeleton due to amyloid deposition and justifies the need to include AL-amyloidosis in the spectrum of differential diagnosis of diseases that occur with osteodestructive syndrome.

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MO638ANEMIA IN DIABETIC PATIENTS REFLECTS SEVERE TUBULOINTERSTITIAL INJURY AND ASSISTS CLINICALLY IN PREDICTING DIAGNOSIS OF DIABETIC NEPHROPATHY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab094.006 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Soichiro Yokota ◽

Kenji Ito ◽

Maho Watanabe ◽

Koji Takahashi ◽

Naoko Himuro ◽

...

Keyword(s):

Renal Function ◽

Regression Analysis ◽

Diabetic Nephropathy ◽

Kidney Disease ◽

Confidence Interval ◽

Odds Ratio ◽

Kidney Biopsy ◽

Renal Pathology ◽

Diabetic Patients ◽

Pathological Findings

Abstract Background and Aims Diabetic nephropathy (DN) is currently a leading cause of end-stage kidney disease worldwide. Kidney biopsy is generally performed in diabetic patients to discriminate between DN and non-diabetic kidney disease (NDKD), and to provide more specific treatments. In addition to conventional predicting factors of DN, recent studies suggested the predictive value of anemia in the diagnosis of DN, however detailed pathophysiology and the significance of anemia in renal pathology are not fully understood. This study aimed to investigate the impact of anemia on renal pathology and clinical course in patients who underwent kidney biopsy. Method We reviewed 81 patients (60.4 ± 13.7 years, 54 men and 27 women) with type 2 diabetes who underwent percutaneous kidney biopsy in Fukuoka University Hospital from January 2001 through March 2020. DN was diagnosed by mesangial expansion or nodular glomerulosclerosis observed under a light microscope, and immunofluorescence assisted in differentiating NDKD from DN. Anemia was defined as hemoglobin level <13 g/dL in males and <12 g/dL in females in accordance with the World Health Organization standards. Laboratory and pathological findings, and clinical courses were investigated. Results According to their pathological findings, patients were classified into two groups: isolated DN (DN group, n=30) and NDKD alone or concurrent DN (NDKD group, n=51). There were 11 types of NDKD. Of these, membranous nephropathy was the most common (23.5%), followed by IgA nephropathy (17.6%), and crescentic glomerulonephritis (13.7%). In multiple logistic regression analysis, absence of severe hematuria (odds ratio (OR) 11.66, 95% confidence interval (CI) 1.68 - 89.9) and presence of anemia (OR 11.38, 95% CI 2.51 - 51.52) were significantly related with the diagnosis of DN. Akaike’s information criterion (AIC) and net reclassification improvement (NRI) analyses revealed improved predictive performance by adding anemia to the conventional factors (AIC 100.152 to 91.844; NRI 27.0%). The tissues of patients in the DN group demonstrated more severe interstitial fibrosis and tubular atrophy (IF/TA) than the NDKD group (p<0.05) regardless of the rate of global glomerulosclerosis (figure), and IF/TA was related to the prevalence of anemia (odds ratio: 7.31, 95% confidence interval: 2.33 - 23.00) in multivariate regression analysis. These results suggest DM-associated severe IF/TA (compared with NDKD) impaired erythropoietin production, resulting in earlier anemia, independent of glomerular injuries and renal function. Furthermore, the renal prognosis was significantly better in the NDKD group than in the DN group using Log-rank test (p<0.05). Conclusion DN is associated with anemia because of severe IF/TA regardless of renal function, and anemia helps clinician discriminate clinically between isolated DN and NDKD.

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