Monoclonal gammopathy of renal significance (MGRS)-related AL amyloidosis complicated by amyloid myopathy: a case report

Abstract Background Lately, monoclonal gammopathy of renal significance (MGRS) has been defined as a group of renal disorders that are strongly associated with monoclonal protein, including amyloid immunoglobulin light chain (AL) amyloidosis. Amyloid myopathy is rare (1.5% of all patients with amyloidosis) and the prognosis is poor. Furthermore, only approximately 20% of patients with amyloid myopathy are reported to have renal involvement, indicating a lack of data in the literature. Case presentation Here, we report a rare case of MGRS-related AL amyloidosis complicated by amyloid myopathy that presented with muscle weakness in the upper and lower limbs, neck and fingers, and nephrotic syndrome. Blood, urine, and bone marrow examination revealed monoclonal gammopathy of undetermined significance (MGUS) (Bence Jones protein-lambda). Muscle biopsy of the vastus lateralis muscle demonstrated amyloid proteins in the sarcolemma and in the blood vessel walls on Congo red staining, suggesting amyloid myopathy, and tiny inclusions in fibers on modified Gomori trichrome stain. Although we thought they were reminiscent of nemaline bodies, we could not confirm the nature of this structure. Renal biopsy demonstrated amyloid proteins in the mesangial region, part of the capillary walls, and the blood vessel walls on direct fast scarlet staining. As these amyloid proteins were positive for p-component staining and negative for amyloid A staining, β2-microglobulin, and pre-albumin, and as lambda light chains were positive in the mesangial region, we diagnosed the patient with MGRS-related AL amyloidosis. Although he was treated with melphalan and dexamethasone, his symptoms did not improve. Conclusions AL amyloidosis involving the kidneys and muscles has a poor prognosis, and a delayed diagnosis of amyloid myopathy is common because of its rarity and frequent misdiagnosis, which increases organ function deterioration. Therefore, early detection, therapeutic intervention, and careful follow-up are crucial.

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P0498CLINICAL PRESENTATION AND RENAL HISTOPATHOLOGICAL FINDINGS IN PATIENTS WITH MONOCLONAL GAMMOPATHY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0498 ◽

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

10.1101/2020.06.21.20136739 ◽

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.

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Effects of an Uphill Marathon on Running Mechanics and Lower-Limb Muscle Fatigue

International Journal of Sports Physiology and Performance ◽

10.1123/ijspp.2014-0602 ◽

2016 ◽

Vol 11 (4) ◽

pp. 522-529 ◽

Cited By ~ 27

Author(s):

Nicola Giovanelli ◽

Paolo Taboga ◽

Enrico Rejc ◽

Bostjan Simunic ◽

Guglielmo Antonutto ◽

...

Keyword(s):

Lower Limb ◽

Vastus Lateralis ◽

Reaction Force ◽

Lower Limbs ◽

Vastus Lateralis Muscle ◽

Leg Length ◽

Step Frequency ◽

Vertical Ground Reaction Force ◽

Finish Line ◽

Running Mechanics

Purpose:To investigate the effects of an uphill marathon (43 km, 3063-m elevation gain) on running mechanics and neuromuscular fatigue in lower-limb muscles.Methods:Maximal mechanical power of lower limbs (MMP), temporal tensiomyographic (TMG) parameters, and muscle-belly displacement (Dm) were determined in the vastus lateralis muscle before and after the competition in 18 runners (age 42.8 ± 9.9 y, body mass 70.1 ± 7.3 kg, maximal oxygen uptake 55.5 ± 7.5 mL · kg−1 · min−1). Contact (tc) and aerial (ta) times, step frequency (f), and running velocity (v) were measured at 3, 14, and 30 km and after the finish line (POST). Peak vertical ground-reaction force (Fmax), vertical displacement of the center of mass (Δz), leg-length change (ΔL), and vertical (kvert) and leg (kleg) stiffness were calculated.Results:MMP was inversely related with race time (r = –.56, P = .016), tc (r = –.61, P = .008), and Δz (r = –.57, P = .012) and directly related with Fmax (r = .59, P = .010), ta (r = .48, P = .040), and kvert (r = .51, P = .027). In the fastest subgroup (n = 9) the following parameters were lower in POST (P < .05) than at km 3: ta (–14.1% ± 17.8%), Fmax (–6.2% ± 6.4%), kvert (–17.5% ± 17.2%), and kleg (–11.4% ± 10.9%). The slowest subgroup (n = 9) showed changes (P < .05) at km 30 and POST in Fmax (–5.5% ± 4.9% and –5.3% ± 4.1%), ta (–20.5% ± 16.2% and –21.5% ± 14.4%), tc (5.5% ± 7.5% and 3.2% ± 5.2%), kvert (–14.0% ± 12.8% and –11.8% ± 10.0%), and kleg (–8.9% ± 11.5% and –11.9% ± 12%). TMG temporal parameters decreased in all runners (–27.35% ± 18.0%, P < .001), while Dm increased (24.0% ± 35.0%, P = .005), showing lower-limb stiffness and higher muscle sensibility to the electrical stimulus.Conclusions:Greater MMP was related with smaller changes in running mechanics induced by fatigue. Thus, lower-limb power training could improve running performance in uphill marathons.

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Is renal amyloidosis uncommon in Egypt? A-25-year study

Journal of Nephropathology ◽

10.15171/jnp.2019.05 ◽

2018 ◽

Vol 8 (1) ◽

pp. 5-5

Author(s):

Amal Labib ◽

Marwa M Shakweer ◽

Manal I Salman ◽

Elham I Seif

Keyword(s):

Inflammatory Diseases ◽

Renal Involvement ◽

Underlying Disease ◽

Renal Amyloidosis ◽

Al Amyloidosis ◽

Positive Staining ◽

Aa Amyloidosis ◽

University Hospitals ◽

Amyloid A ◽

Renal Biopsies

Background: Renal amyloidosis is a well-known disease. The forms of amyloidosis that are frequently associated with renal involvement are AL and AA amyloidosis. In Theodor Bilharz Institute, in Egypt, 2.5% of the total number of renal biopsies examined showed amyloidosis including secondary type in 80% and primary type in 20% of cases. Objectives: To investigate the prevalence of amyloidosis among Egyptian renal patients within 25 years and to screen the amyloid type whether AA or AL. Materials and Methods: Demographic and pathological data of archived renal biopsies presented to Ain Shams University hospitals in 25 years (1990-2015) were the material of this study. The diagnosis of all renal biopsies included in the study was confirmed by electron microscopy (EM). Immunohistochemical (IHC) staining of paraffin blocks for amyloid typing was carried out on archived material from (2010-2015). Results: Of a total number of 3962 biopsies examined; 118 were renal amyloidosis (2.97%). IHC typing of the screened samples revealed positive staining for amyloid A protein in 14 cases (73.68%). Light chain AL amyloidosis was found in 5 cases (26.3%). Conclusions: Renal amyloidosis is not uncommon in Egypt. AA amyloidosis represents the commonest type of renal amyloidosis in this study. The most common underlying disease was systemic inflammatory diseases, on top of familial Mediterranean fever (FMF).

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Ayurvedic management of Myositis Ossificans of Vastus Lateralis Muscle (Urusthamba) - A Case Study

Journal of Ayurveda and Integrated Medical Sciences (JAIMS) ◽

10.21760/jaims.v2i1.7523 ◽

2017 ◽

Vol 2 (1) ◽

Author(s):

Vishnu Mohan ◽

Gopikrishna BJ ◽

Avnish Pathak ◽

Mahesh Kumar ES ◽

Duradundi G

Keyword(s):

Heterotopic Ossification ◽

Myositis Ossificans ◽

Vastus Lateralis ◽

Treatment Protocol ◽

Vastus Lateralis Muscle ◽

Satisfactory Treatment ◽

Lateralis Muscle ◽

Ayurvedic Treatment

Myositis ossificansis characterized by heterotopic ossification (calcification) of muscle of various etiologies. It is most commonly affected in the quadriceps of the thighs. There are many tools available for diagnosis of Myositis ossificans, but lack of satisfactory treatment. So the development of a treatment protocol for Myositis ossificans is the need of today`s era. In Ayurveda, the same can be understood as Urusthamba. The present paper discusses a case of Myositis ossificans of right vastus lateralis muscle and its Ayurvedic treatment.

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Prevalence of the additional head of quadriceps femoris in the South Indian population: a cadaveric and radiological study

Scientific Reports ◽

10.1038/s41598-021-95374-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Femina Sam ◽

Madhavi Kandagaddala ◽

Ivan James Prithishkumar ◽

Koyeli Mary Mahata ◽

Mahasampath Gowri ◽

...

Keyword(s):

Indian Population ◽

Vastus Lateralis ◽

Femoral Nerve ◽

Quadriceps Femoris ◽

Lower Limbs ◽

South Indian Population ◽

The South ◽

South Indian ◽

Circumflex Femoral Artery ◽

Vastus Intermedius

AbstractQuadriceps femoris is an extensor muscle in the anterior compartment of thigh and is traditionally taught to be composed of four heads. Recently, there is an increased interest in the occurrence of an additional muscle head of quadriceps femoris. But scientific knowledge regarding its incidence is lacking in the South Indian population. This study was done to confirm the presence of the additional head by routine anatomic dissection and radiological imaging techniques. Forty-one formalin fixed human cadaveric lower limbs were dissected and the morphology of the additional head was noted. Retrospective analysis of 88 MRI images of patients was done. The additional muscle head was present in 43.9% of the cadaveric lower limbs and was consistently located between the vastus lateralis and vastus intermedius. It originated from variable portions of the greater trochanter, intertrochanteric line, lateral lip of linea aspera and lateral surface of the shaft of femur and inserted either as a muscle belly or as an aponeurosis into the vastus intermedius (55.6%), vastus lateralis (22.2%) or directly into the base of the patella. It received its vascular supply from branches of the lateral circumflex femoral artery and was innervated by branches from the posterior division of the femoral nerve. In addition, the additional muscle head was identified by MRI and its incidence was reported to be 30.68% for the first time in living subjects. The result of this study provides additional information in understanding the morphology of the quadriceps femoris muscle.

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Non-Coding RNAs in the Transcriptional Network That Differentiates Skeletal Muscles of Sedentary from Long-Term Endurance- and Resistance-Trained Elderly

International Journal of Molecular Sciences ◽

10.3390/ijms22041539 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1539

Author(s):

Paola De Sanctis ◽

Giuseppe Filardo ◽

Provvidenza Maria Abruzzo ◽

Annalisa Astolfi ◽

Alessandra Bolotta ◽

...

Keyword(s):

Exercise Training ◽

High Intensity ◽

Vastus Lateralis ◽

Mammalian Target Of Rapamycin ◽

Differentially Expressed ◽

Transcriptional Networks ◽

Vastus Lateralis Muscle ◽

Age Related ◽

Wide Range ◽

Non Coding Rnas

In a previous study, the whole transcriptome of the vastus lateralis muscle from sedentary elderly and from age-matched athletes with an exceptional record of high-intensity, life-long exercise training was compared—the two groups representing the two extremes on a physical activity scale. Exercise training enabled the skeletal muscle to counteract age-related sarcopenia by inducing a wide range of adaptations, sustained by the expression of protein-coding genes involved in energy handling, proteostasis, cytoskeletal organization, inflammation control, and cellular senescence. Building on the previous study, we examined here the network of non-coding RNAs participating in the orchestration of gene expression and identified differentially expressed micro- and long-non-coding RNAs and some of their possible targets and roles. Unsupervised hierarchical clustering analyses of all non-coding RNAs were able to discriminate between sedentary and trained individuals, regardless of the exercise typology. Validated targets of differentially expressed miRNA were grouped by KEGG analysis, which pointed to functional areas involved in cell cycle, cytoskeletal control, longevity, and many signaling pathways, including AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR), which had been shown to be pivotal in the modulation of the effects of high-intensity, life-long exercise training. The analysis of differentially expressed long-non-coding RNAs identified transcriptional networks, involving lncRNAs, miRNAs and mRNAs, affecting processes in line with the beneficial role of exercise training.

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