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1.
Dig Dis Sci ; 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34655012

RESUMO

A patient with systemic amyloidosis developed portal hypertension, acute liver failure and multiorgan dysfunction. Extensive testing was unrevealing for paraproteinemia, plasma cell dyscrasia, infectious, or inflammatory conditions. He was transferred to our institution for orthotopic liver transplant evaluation but was ultimately declined given clinical instability and dysautonomia. Post-mortem evaluation revealed extensive amyloid deposition in multiple organs determined to be AL-lambda amyloidosis.

2.
Clin Nephrol Case Stud ; 9: 93-104, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34476173

RESUMO

Kidney allograft infarction is rare, but an urgent condition that requires prompt intervention to avoid allograft loss. Renal artery thrombosis is the leading cause of infarction. Apart from traditional risk factors for thrombosis, emerging SARS-CoV-2 predisposes patients to thrombotic diseases both in arterial and venous vasculatures. We report a case of kidney transplant recipient with known transplant renal artery stenosis (TRAS) status post angioplasty with severe COVID-19, complicated by oliguric acute kidney injury requiring continuous renal replacement therapy (CRRT). She did not have a history of thromboembolic disease. The hospital course was complicated by new-onset atrial and ventricular fibrillation and cardiac arrest requiring multiple rounds of cardiopulmonary resuscitation. She had no signs of renal recovery, and an abdominal CT scan showed evidence of allograft infarcts. She underwent an allograft nephrectomy. Pathology revealed diffuse thrombotic microangiopathy involving glomeruli, arterioles, and arteries associated with diffuse cortical infarction with negative SARS-CoV-2 immunostain and in situ hybridization. This is the first case of kidney allograft infarct with a history of TRAS in a COVID-19 patient. Underlying TRAS and COVID-19-associated thrombosis in this patient are unique and likely play a key role in allograft infarction from arterial thrombosis. Recognizing risk factors and early therapy for allograft infarction may improve transplant outcomes.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34366540

RESUMO

Histologic examination of interstitial fibrosis and tubular atrophy (IFTA) is critical to determine the extent of irreversible kidney injury in renal disease. The current clinical standard involves pathologist's visual assessment of IFTA, which is prone to inter-observer variability. To address this diagnostic variability, we designed two case studies (CSs), including seven pathologists, using HistomicsTK- a distributed system developed by Kitware Inc. (Clifton Park, NY). Twenty-five whole slide images (WSIs) were classified into a training set of 21 and a validation set of four. The training set was composed of seven unique subsets, each provided to an individual pathologist along with four common WSIs from the validation set. In CS 1, all pathologists individually annotated IFTA in their respective slides. These annotations were then used to train a deep learning algorithm to computationally segment IFTA. In CS 2, manual and computational annotations from CS 1 were first reviewed by the annotators to improve concordance of IFTA annotation. Both the manual and computational annotation processes were then repeated as in CS1. The inter-observer concordance in the validation set was measured by Krippendorff's alpha (KA). The KA for the seven pathologists in CS1 was 0.62 with CI [0.57, 0.67], and after reviewing each other's annotations in CS2, 0.66 with CI [0.60, 0.72]. The respective CS1 and CS2 KA were 0.58 with CI [0.52, 0.64] and 0.63 with CI [0.56, 0.69] when including the deep learner as an eighth annotator. These results suggest that our designed annotation framework refines agreement of spatial annotation of IFTA and demonstrates a human-AI approach to significantly improve the development of computational models.

4.
Nat Commun ; 12(1): 4884, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34385460

RESUMO

Pathology is practiced by visual inspection of histochemically stained tissue slides. While the hematoxylin and eosin (H&E) stain is most commonly used, special stains can provide additional contrast to different tissue components. Here, we demonstrate the utility of supervised learning-based computational stain transformation from H&E to special stains (Masson's Trichrome, periodic acid-Schiff and Jones silver stain) using kidney needle core biopsy tissue sections. Based on the evaluation by three renal pathologists, followed by adjudication by a fourth pathologist, we show that the generation of virtual special stains from existing H&E images improves the diagnosis of several non-neoplastic kidney diseases, sampled from 58 unique subjects (P = 0.0095). A second study found that the quality of the computationally generated special stains was statistically equivalent to those which were histochemically stained. This stain-to-stain transformation framework can improve preliminary diagnoses when additional special stains are needed, also providing significant savings in time and cost.


Assuntos
Biópsia com Agulha de Grande Calibre/métodos , Aprendizado Profundo , Diagnóstico por Computador/métodos , Nefropatias/patologia , Rim/patologia , Coloração e Rotulagem/métodos , Algoritmos , Corantes/química , Corantes/classificação , Corantes/normas , Diagnóstico Diferencial , Humanos , Nefropatias/diagnóstico , Patologia Clínica/métodos , Patologia Clínica/normas , Padrões de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Coloração e Rotulagem/normas
5.
Pediatr Nephrol ; 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34292379

RESUMO

BACKGROUND: We propose a novel clinically significant finding, de novo lupus-like glomerulonephritis (DNLLGN), in patients with autoantibodies and kidney abnormalities in pediatric liver transplant (LT) and intestinal inclusive transplants (ITx). METHODS: We describe the clinical, serologic, and histopathologic presentation and kidney outcomes in eight patients from our center found to have DNLLGN on kidney biopsy. RESULTS: Pediatric recipients of non-kidney solid organ transplants developed an unusual de novo immune complex glomerulonephritis with morphologic similarity to lupus nephritis. Six had isolated LT (0.9% of all pediatric LT at our center) and two had ITx (2.1% of all ITx). Five (63%) presented with nephrotic syndrome. Five patients had autoantibodies. Patients underwent kidney biopsy at a mean of 11.5 years in LT and 2.8 years in ITx after the index transplant. Biopsies demonstrated changes similar to focal or diffuse active lupus. Follow-up eGFR at a mean of 6 years after biopsy showed a mean decrease of 30 ml/min/1.73 m2 in all patients (p = 0.11). CONCLUSIONS: DNLLGN has not been previously recognized in this clinical setting, yet 8 kidney biopsies from pediatric recipients of LT and ITx at our center in 25 years demonstrated this finding. DNLLGN appears to be an under-reported phenomenon of clinical significance. A higher resolution version of the Graphical abstract is available as Supplementary information.

6.
SAGE Open Med Case Rep ; 9: 2050313X211025145, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34221404

RESUMO

Non-steroidal anti-inflammatory drugs are not only potent analgesics and antipyretics but also nephrotoxins, and may cause electrolyte disarray. In addition to the commonly expected effects, including hyperkalemia, hyponatremia, acute renal injury, renal cortical necrosis, and volume retention, glomerular disease with or without nephrotic syndrome or nephritis can occur as well including after years of seemingly safe administration. Minimal change disease, secondary membranous glomerulonephritis, and acute interstitial nephritis are all reported glomerular lesions seen with non-steroidal anti-inflammatory use. We report a patient who used non-steroidal anti-inflammatory drugs for years without diabetes, chronic kidney disease, or proteinuria; he then developed severe nephrotic range proteinuria with 7 g of daily urinary protein excretion. Renal biopsy showed minimal change nephropathy, a likely secondary membranous glomerulonephritis, and acute interstitial nephritis present simultaneously in one biopsy. Cessation of non-steroidal anti-inflammatory drug use along with steroid treatment resulted in a moderate improvement in renal function, though residual impairment remained. Urine heavy metal screen returned with elevated levels of urine copper, but with normal ceruloplasmin level. Workup suggested that the elevated copper levels were due to cirrhosis from non-alcoholic fatty liver disease. The membranous glomerulonephritis is possibly linked to non-steroidal anti-inflammatory drug exposure, and possibly to heavy metal exposure, and is clinically and pathologically much less likely to be a primary membranous glomerulonephritis with negative serological markers.

7.
Heart Rhythm ; 18(10): 1745-1757, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34182169

RESUMO

BACKGROUND: Clinical trials for renal artery (RA) ablation have shown limited efficacy. OBJECTIVE: The purpose of this study was to investigate whether the aorticorenal ganglion (ARG) can be targeted for renal denervation. METHODS: Twenty-eight pigs were studied under isoflurane or alpha-chloralose to examine hemodynamic responses and catecholamine release in response to RA or ARG stimulation. To assess the efficacy of ARG ablation, we randomized 16 pigs to either sham, RA, or ARG ablation, followed by occlusion of the left anterior descending coronary artery (LAD). Hemodynamic responses, cardiac electrophysiological parameters, and arrhythmias/sudden cardiac death were assessed following LAD occlusion. Absent hemodynamic responses to stimulation confirmed ARG or RA ablation. In vivo stellate ganglion neural activity was recorded to assess cardiac sympathetic signaling. Cadaveric dissections were performed to localize the ARG in humans for comparison to swine. RESULTS: The ARG is a purely sympathetic ganglion with cholinergic inputs and pass-through sensory afferent fibers. Compared to RA stimulation, ARG stimulation yielded greater hemodynamic responses during alpha-chloralose anesthesia. However, neither site yielded significant responses under isoflurane. Radiofrequency ablation of the ARG eliminated responses to both RA and ARG stimulation, whereas RA ablation did not eliminate responses to ARG stimulation. Ablation of the ARG did not impact the kidneys or adrenal glands. Compared to control and RA ablation, ARG ablation was protective against ventricular arrhythmias and sudden death. Human and swine ARG are similarly located in the aorticorenal region. CONCLUSION: Our findings indicate that the ARG may be a novel target for renal neuromodulation. Further studies are warranted to validate these findings.

8.
Case Rep Nephrol Dial ; 11(1): 95-102, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33977097

RESUMO

Thrombotic microangiopathies (TMAs) involve multiple organ systems due to the presence of microangiopathic hemolysis. One such condition, atypical hemolytic uremic syndrome (aHUS), is a complement-mediated process that is part of a spectrum of disorders that have underlying complement dysfunction of the alternative pathway due to overactivity or decreased self-nonself discrimination by innate immunity. Complement-amplifying conditions such as pregnancy may unmask a diagnosis of aHUS. We present an important case of a pregnant 23-year-old Hispanic female who presented in mid-gestation (21 weeks) with an initial diagnosis of systemic lupus erythematosus (SLE) complicated by aHUS. She met clinical criteria for aHUS on presentation and was found to have a pathogenic CFHR1-3 homozygous deletion. She has been treated with intravenous and oral steroids, cyclophosphamide, subsequently also with plasma exchange, and finally with eculizumab with partial improvement in renal function. This case adds to the emerging literature showing that SLE and aHUS (or complement-mediated TMA) can be successfully treated with C5 blockade.

9.
Nephron ; 145(3): 275-279, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33601392

RESUMO

CONTEXT: Determining whether SARS-CoV-2 causes direct infection of the kidneys is challenging due to limitations in imaging and molecular tools. Subject of Review: A growing number of conflicting kidney biopsy and autopsy reports highlight this controversial issue. Second Opinion: Based on the collective evidence, therapies that improve hemodynamic stability and oxygenation, or dampen complement activation, are likely to ameliorate acute kidney injury in COVID-19. At this time, whether inhibition of viral infection and replication directly modulates kidney damage is inconclusive.


Assuntos
COVID-19/complicações , Nefropatias/etiologia , Injúria Renal Aguda/etiologia , Autopsia , Biópsia , COVID-19/terapia , COVID-19/virologia , Humanos , Rim/patologia , Rim/virologia , Nefropatias/patologia , Nefropatias/terapia , Nefropatias/virologia , Nefrite Intersticial/etiologia
10.
Am J Kidney Dis ; 77(1): 82-93.e1, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33045255

RESUMO

RATIONALE & OBJECTIVE: Kidney biopsy data inform us about pathologic processes associated with infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We conducted a multicenter evaluation of kidney biopsy findings in living patients to identify various kidney disease pathology findings in patients with coronavirus disease 2019 (COVID-19) and their association with SARS-CoV-2 infection. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: We identified 14 native and 3 transplant kidney biopsies performed for cause in patients with documented recent or concurrent SARS-CoV-2 infection treated at 7 large hospital systems in the United States. OBSERVATIONS: Men and women were equally represented in this case series, with a higher proportion of Black (n=8) and Hispanic (n=5) patients. All 17 patients had SARS-CoV-2 infection confirmed by reverse transcriptase-polymerase chain reaction, but only 3 presented with severe COVID-19 symptoms. Acute kidney injury (n=15) and proteinuria (n=11) were the most common indications for biopsy and these symptoms developed concurrently or within 1 week of COVID-19 symptoms in all patients. Acute tubular injury (n=14), collapsing glomerulopathy (n=7), and endothelial injury/thrombotic microangiopathy (n=6) were the most common histologic findings. 2 of the 3 transplant recipients developed active antibody-mediated rejection weeks after COVID-19. 8 patients required dialysis, but others improved with conservative management. LIMITATIONS: Small study size and short clinical follow-up. CONCLUSIONS: Cases of even symptomatically mild COVID-19 were accompanied by acute kidney injury and/or heavy proteinuria that prompted a diagnostic kidney biopsy. Although acute tubular injury was seen among most of them, uncommon pathology such as collapsing glomerulopathy and acute endothelial injury were detected, and most of these patients progressed to irreversible kidney injury and dialysis.


Assuntos
Injúria Renal Aguda/etiologia , Injúria Renal Aguda/patologia , COVID-19/complicações , COVID-19/patologia , Proteinúria/etiologia , Proteinúria/patologia , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Rim/patologia , Masculino , Pessoa de Meia-Idade
11.
SAGE Open Med Case Rep ; 8: 2050313X20952650, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32913652

RESUMO

Scleroderma renal crisis is a serious complication that can develop in certain patients with systemic sclerosis. Some risks have been identified as potential triggers of scleroderma renal crisis, including the high-dose oral corticosteroids. Here, we present a patient who developed clinically severe systemic sclerosis and scleroderma renal crisis after exposure to oral corticosteroids and intravitreal vascular endothelial growth factor blockade with bevacizumab for cotton wool spots. The patient's scleroderma renal crisis was severe, progressive, and refractory to the standard of care therapy: oral captopril. Biopsy showed a diffuse thrombotic microangiopathy and findings consistent with scleroderma renal crisis. We hypothesize that depletion of systemic vascular endothelial growth factor with intravitreal anti-vascular endothelial growth factor injections likely contributed to the particularly severe presentation seen in this case. Though the finding of a monoclonal gammopathy of undetermined significance is another complicating factor, this case suggests that vascular endothelial growth factor inhibition may be a newly recognized trigger of scleroderma renal crisis.

12.
SAGE Open Med Case Rep ; 8: 2050313X20940510, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32699635

RESUMO

Idiopathic nodular glomerulosclerosis is an unusual histopathological finding that has commonly been observed in male smokers with hypertension. It has remained an enigmatic condition and is best described as a diabetic pattern of glomerular injury seen in non-diabetic patients. It is also one of the few nicotine (smoking)-associated/smoking-associated patterns of renal injury. We present an even more unusual manifestation of this pathological finding in a 59-year-old Hispanic female who presented with chronic kidney disease approaching need for renal replacement therapy. The patient had idiopathic nodular glomerulosclerosis on kidney biopsy, despite no prior history of diabetes, nor smoking history, including no secondhand smoking exposure. The patient did have hypertension. The renal biopsy also showed evidence of chronic thrombotic-microangiopathic changes within arteries and arterioles. Genetic testing of the alternative pathway revealed an unusual and likely pathological variant of thrombomodulin supporting complement dysfunction as having a role in the presentation.

13.
Front Med (Lausanne) ; 7: 293, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32695788

RESUMO

C3 dominant immunofluorescence staining is present in a subset of patients with idiopathic immune complex membranoproliferative glomerulonephritis (iMPGN). It is increasingly recognized that iMPGN may be complement driven, as are cases of "typical" C3 glomerulopathy (C3G). In both iMPGN and C3G, a frequent membranoproliferative pattern of glomerular injury may indicate common pathogenic mechanisms via complement activation and endothelial cell damage. Dysregulation of the alternative complement pathway and mutations in certain regulatory factors are highly implicated in C3 glomerulopathy (which encompasses C3 glomerulonephritis, dense deposit disease, and cases of C3 dominant MPGN). We report three cases that demonstrate that an initial biopsy diagnosis of iMPGN does not exclude complement alterations similar to the ones observed in patients with a diagnosis of C3G. The first patient is a 39-year-old woman with iMPGN and C3 dominant staining, with persistently low C3 levels throughout her course. The second case is a 22-year-old woman with elevated anti-factor H antibodies and C3 dominant iMPGN findings on biopsy. The third case is a 25-year-old woman with C3 dominant iMPGN, dense deposit disease, and a crescentic glomerulonephritis on biopsy. We present the varied phenotypic variations of C3 dominant MPGN and review clinical course, complement profiles, genetic testing, treatment course, and peri-transplantation plans. Testing for complement involvement in iMPGN is important given emerging treatment options and transplant planning.

14.
Adv Chronic Kidney Dis ; 27(2): 149-154, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32553247

RESUMO

Thrombotic microangiopathy is characterized by the presence of thrombocytopenia and microangiopathic hemolytic anemia and can occur in up to 50% of patients with hypertensive emergency and 10-15% with scleroderma. This review discusses the emerging role of complement in these 2 clinical entities. Specifically, we evaluate the evidence linking complement dysregulation with the manifestation of thrombotic microangiopathy and its clinical course in these settings. We also explore the rationale for complement blockade in these complex clinical scenarios that often have poor outcomes.

15.
Proc Natl Acad Sci U S A ; 117(27): 15827-15836, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32571911

RESUMO

Bromine and peroxidasin (an extracellular peroxidase) are essential for generating sulfilimine cross-links between a methionine and a hydroxylysine within collagen IV, a basement membrane protein. The sulfilimine cross-links increase the structural integrity of basement membranes. The formation of sulfilimine cross-links depends on the ability of peroxidasin to use bromide and hydrogen peroxide substrates to produce hypobromous acid (HOBr). Once a sulfilimine cross-link is created, bromide is released into the extracellular space and becomes available for reutilization. Whether the HOBr generated by peroxidasin is used very selectively for creating sulfilimine cross-links or whether it also causes oxidative damage to bystander molecules (e.g., generating bromotyrosine residues in basement membrane proteins) is unclear. To examine this issue, we used nanoscale secondary ion mass spectrometry (NanoSIMS) imaging to define the distribution of bromine in mammalian tissues. We observed striking enrichment of bromine (79Br, 81Br) in basement membranes of normal human and mouse kidneys. In peroxidasin knockout mice, bromine enrichment of basement membranes of kidneys was reduced by ∼85%. Proteomic studies revealed bromination of tyrosine-1485 in the NC1 domain of α2 collagen IV from kidneys of wild-type mice; the same tyrosine was brominated in collagen IV from human kidney. Bromination of tyrosine-1485 was reduced by >90% in kidneys of peroxidasin knockout mice. Thus, in addition to promoting sulfilimine cross-links in collagen IV, peroxidasin can also brominate a bystander tyrosine. Also, the fact that bromine enrichment is largely confined to basement membranes implies that peroxidasin activity is largely restricted to basement membranes in mammalian tissues.


Assuntos
Membrana Basal/metabolismo , Bromo/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Peroxidase/metabolismo , Animais , Biópsia , Bromatos/metabolismo , Brometos , Células Cultivadas , Colágeno Tipo IV/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Iminas/metabolismo , Rim/citologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteômica
16.
Am J Physiol Renal Physiol ; 319(2): F229-F244, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32538150

RESUMO

Sepsis-associated acute kidney injury (s-AKI) has a staggering impact in patients and lacks any treatment. Incomplete understanding of the pathogenesis of s-AKI is a major barrier to the development of effective therapies. We address the gaps in knowledge regarding renal oxygenation, tubular metabolism, and mitochondrial function in the pathogenesis of s-AKI using the cecal ligation and puncture (CLP) model in mice. At 24 h after CLP, renal oxygen delivery was reduced; however, fractional oxygen extraction was unchanged, suggesting inefficient renal oxygen utilization despite decreased glomerular filtration rate and filtered load. To investigate the underlying mechanisms, we examined temporal changes in mitochondrial function and metabolism at 4 and 24 h after CLP. At 4 h after CLP, markers of mitochondrial content and biogenesis were increased in CLP kidneys, but mitochondrial oxygen consumption rates were suppressed in proximal tubules. Interestingly, at 24 h, proximal tubular mitochondria displayed high respiratory capacity, but with decreased mitochondrial content, biogenesis, fusion, and ATP levels in CLP kidneys, suggesting decreased ATP synthesis efficiency. We further investigated metabolic reprogramming after CLP and observed reduced expression of fatty acid oxidation enzymes but increased expression of glycolytic enzymes at 24 h. However, assessment of functional glycolysis revealed lower glycolytic capacity, glycolytic reserve, and compensatory glycolysis in CLP proximal tubules, which may explain their susceptibility to injury. In conclusion, we demonstrated significant alterations in renal oxygenation, tubular mitochondrial function, and metabolic reprogramming in s-AKI, which may play an important role in the progression of injury and recovery from AKI in sepsis.


Assuntos
Injúria Renal Aguda/patologia , Rim/lesões , Mitocôndrias/metabolismo , Sepse/complicações , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/metabolismo , Animais , Modelos Animais de Doenças , Rim/metabolismo , Túbulos Renais Proximais/metabolismo , Camundongos Endogâmicos C57BL , Sepse/metabolismo
18.
Nat Biomed Eng ; 3(6): 466-477, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31142829

RESUMO

The histological analysis of tissue samples, widely used for disease diagnosis, involves lengthy and laborious tissue preparation. Here, we show that a convolutional neural network trained using a generative adversarial-network model can transform wide-field autofluorescence images of unlabelled tissue sections into images that are equivalent to the bright-field images of histologically stained versions of the same samples. A blind comparison, by board-certified pathologists, of this virtual staining method and standard histological staining using microscopic images of human tissue sections of the salivary gland, thyroid, kidney, liver and lung, and involving different types of stain, showed no major discordances. The virtual-staining method bypasses the typically labour-intensive and costly histological staining procedures, and could be used as a blueprint for the virtual staining of tissue images acquired with other label-free imaging modalities.


Assuntos
Aprendizado Profundo , Processamento de Imagem Assistida por Computador , Coloração e Rotulagem , Algoritmos , Fluorescência , Humanos , Fígado/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Melaninas/metabolismo , Redes Neurais de Computação , Padrões de Referência
20.
Case Rep Pathol ; 2019: 6198380, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31929930

RESUMO

Kidney injury is a well-known sequelae of infectious endocarditis. Various types of kidney injury can be seen, including endocarditis-associated glomerulonephritis, and may affect nearly half of the patients with infectious endocarditis. Lactobacillus species are an infrequently documented cause of endocarditis. We present a case of Lactobacillus endocarditis-associated glomerulonephritis in a patient with a complex medical history including Lactobacillus infection of an artificial heart valve. To our knowledge, this is the first reported case of development of endocarditis-associated glomerulonephritis secondary to Lactobacillus species organisms. Furthermore, the patient's renal biopsy revealed several frequently overlooked concomitant findings including anti-coagulant nephropathy and renal amyloidosis.

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