RESUMO
COVID-19 causes morbid pathological changes in different organs including lungs, kidneys, liver, and so on, especially in those who succumb. Though clinical outcomes in those with comorbidities are known to be different from those without-not much is known about the differences at the histopathological level. To compare the morbid histopathological changes in COVID-19 patients between those who were immunocompromised (Gr 1), had a malignancy (Gr 2), or had cardiometabolic conditions (hypertension, diabetes, or coronary artery disease) (Gr 3), postmortem tissue sampling (minimally invasive tissue sampling [MITS]) was done from the lungs, kidney, heart, and liver using a biopsy gun within 2 hours of death. Routine (hematoxylin and eosin) and special staining (acid fast bacilli, silver methanamine, periodic acid schiff) was done besides immunohistochemistry. A total of 100 patients underwent MITS and data of 92 patients were included (immunocompromised: 27, malignancy: 18, cardiometabolic conditions: 71). In lung histopathology, capillary congestion was more in those with malignancy, while others like diffuse alveolar damage, microthrombi, pneumocyte hyperplasia, and so on, were equally distributed. In liver histopathology, architectural distortion was significantly different in immunocompromised; while steatosis, portal inflammation, Kupffer cell hypertrophy, and confluent necrosis were equally distributed. There was a trend towards higher acute tubular injury in those with cardiometabolic conditions as compared to the other groups. No significant histopathological difference in the heart was discerned. Certain histopathological features were markedly different in different groups (Gr 1, 2, and 3) of COVID-19 patients with fatal outcomes.
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COVID-19 , Trombose , Humanos , COVID-19/patologia , SARS-CoV-2 , Pulmão/patologia , CoraçãoRESUMO
BACKGROUND: Thrombotic microangiopathy (TMA) is usually caused due to dysregulation of the alternative complement pathway. Rarely, thrombotic microangiopathy is caused by non-complement mediated mutations in diacylglycerol kinase epsilon (DGKE); information about therapy and outcome of these patients is limited. METHODS: Medical records of patients, younger than 18 years, diagnosed with TMA and variants in DGKE were reviewed to include 12 patients from seven centers. Genetic studies included targeted exome sequencing and multiplex-ligation dependent probe amplification of CFH-CFHR5. RESULTS: Patients presented at a median age of 11 (7.5, 12.3) months; all were younger than 2 years. All patients had an infectious prodrome; enteroinvasive, enteropathogenic, and enterotoxigenic Escherichia coli were detected in two patients with diarrhea. Chief features included those of microangiopathic hemolysis (n = 11), microscopic hematuria (n = 10), nephrotic range proteinuria (n = 10), hypoalbuminemia (n = 6), elevated total cholesterol (n = 6), and hypocomplementemia (n = 4). Histopathology showed thrombotic microangiopathy (n = 4), overlapping with membranoproliferative pattern of injury (n = 1). At median 3.3 years of follow-up, significant hypertension and/or proteinuria (40%), relapses (66.7%), and death or progression to CKD (60%) were common. Genetic sequencing showed 13 homozygous and compound heterozygous variants (7 pathogenic, 3 likely pathogenic) located throughout DGKE; 11 variants were novel. CONCLUSIONS: This case series highlights the need to suspect DGKE nephropathy in young patients with TMA, especially those with severe proteinuria. Medium-term outcomes are unsatisfactory with risk of relapses, progressive kidney failure, and death. A higher resolution version of the Graphical abstract is available as Supplementary information.
Assuntos
Síndrome Hemolítico-Urêmica Atípica , Nefropatias , Microangiopatias Trombóticas , Humanos , Lactente , Síndrome Hemolítico-Urêmica Atípica/genética , Diacilglicerol Quinase/genética , Microangiopatias Trombóticas/genética , Mutação , ProteinúriaRESUMO
BACKGROUND: Vitamin D deficiency has been examined as a risk factor for severity and progression of kidney disease due to its immunomodulatory effects. There is paucity of data about its impact in IgA nephropathy (IgAN). METHODS: In a retrospective cohort study, 25 (OH) vitamin D assay was performed in bio-banked baseline serum samples collected during kidney biopsy of 105 adult patients with primary IgAN diagnosed between 2015 and 2019. A level of < 10 ng/mL was defined as Vitamin D deficiency. RESULTS: Mean age of patients was 34 ± 10.6 years, 69.5% were males. Mean baseline 25(OH) Vitamin D levels was 15.9 ± 11.9 ng/mL and 41(39%) patients had vitamin D deficiency. Serum albumin level was lower in vitamin D deficient patients compared to those who had higher vitamin D levels (3.7 ± 0.9 vs 4.1 ± 0.7 g/dl, p = 0.018)but there was no significant difference in baseline proteinuria and eGFR. Crescentic lesions were more frequent in vitamin D deficient group (19.5% vs 6.3%, p = 0.022). At median follow up of 21.5 months (6 - 56 months), there was no difference in remission (68.3% vs 65.6%, p = 0.777) and disease progression (12.5% vs 9.4%, p = 0.614) in those with and without Vitamin D deficiency respectively. On multivariate cox proportional hazard analysis, vitamin D deficiency was not a significant risk factor for renal survival (HR-1.79, 95% confidence interval:0.50-6.34, p = 0.368). CONCLUSION: There was no association between vitamin D deficiency and disease profile as well as renal outcome in Indian patients with IgAN.
Assuntos
Glomerulonefrite por IGA , Deficiência de Vitamina D , Adulto , Masculino , Humanos , Adulto Jovem , Feminino , Glomerulonefrite por IGA/diagnóstico , Vitamina D , Estudos Retrospectivos , Progressão da Doença , Vitaminas , Gravidade do PacienteRESUMO
Background: Digital clinical measures collected via various digital sensing technologies such as smartphones, smartwatches, wearables, and ingestible and implantable sensors are increasingly used by individuals and clinicians to capture the health outcomes or behavioral and physiological characteristics of individuals. Time series classification (TSC) is very commonly used for modeling digital clinical measures. While deep learning models for TSC are very common and powerful, there exist some fundamental challenges. This review presents the non-deep learning models that are commonly used for time series classification in biomedical applications that can achieve high performance. Objective: We performed a systematic review to characterize the techniques that are used in time series classification of digital clinical measures throughout all the stages of data processing and model building. Methods: We conducted a literature search on PubMed, as well as the Institute of Electrical and Electronics Engineers (IEEE), Web of Science, and SCOPUS databases using a range of search terms to retrieve peer-reviewed articles that report on the academic research about digital clinical measures from a five-year period between June 2016 and June 2021. We identified and categorized the research studies based on the types of classification algorithms and sensor input types. Results: We found 452 papers in total from four different databases: PubMed, IEEE, Web of Science Database, and SCOPUS. After removing duplicates and irrelevant papers, 135 articles remained for detailed review and data extraction. Among these, engineered features using time series methods that were subsequently fed into widely used machine learning classifiers were the most commonly used technique, and also most frequently achieved the best performance metrics (77 out of 135 articles). Statistical modeling (24 out of 135 articles) algorithms were the second most common and also the second-best classification technique. Conclusions: In this review paper, summaries of the time series classification models and interpretation methods for biomedical applications are summarized and categorized. While high time series classification performance has been achieved in digital clinical, physiological, or biomedical measures, no standard benchmark datasets, modeling methods, or reporting methodology exist. There is no single widely used method for time series model development or feature interpretation, however many different methods have proven successful.
Assuntos
Algoritmos , Aprendizado de Máquina , Humanos , Smartphone , Fatores de TempoRESUMO
BACKGROUND: Data on therapy and outcome of dense deposit disease (DDD), C3 glomerulonephritis (C3GN), and immune-complex MPGN (IC-MPGN) in children are limited. METHODS: In this retrospective single-center study from 2007 to 2019, kidney biopsies were reviewed to include patients aged <18-years with C3 glomerulopathy and IC-MPGN. Initial immunosuppression comprised prednisolone, mycophenolate mofetil (n = 51), tacrolimus (n = 11), and/or IV cyclophosphamide (n = 20). Clinicopathological features, response to therapy, and adverse outcome (eGFRcr < 15 mL/min/1.73 m2 or death) were evaluated. RESULTS: A total of 92 patients were classified as DDD (n = 48, 52.2%), C3GN (n = 26, 28.3%), and IC-MPGN (n = 18, 19.6%) by immunohistochemistry and electron microscopy; 8 patients with DDD were misclassified as IC-MPGN on immunofluorescence. At last follow-up (median 4.3 years), complete or partial remission occurred in 28.5, 36.1, and 16.7% patients with DDD, C3GN, and IC-MPGN, respectively. Serum albumin at onset < 2.5 g/dL (HR = 0.29, P = 0.005) and persistently low serum C3 (HR = 0.34, P = 0.02) were associated with lack of remission. The 5-year kidney survival was 62.6, 85.5, and 88.5% in patients with DDD, C3GN, and IC-MPGN, respectively (log-rank, P = 0.006). Presentation as rapidly progressive GN (HR = 11.2, P < 0.001), age > 10 years at onset (HR = 4.0, P = 0.004), and DDD (HR = 4.2, P = 0.02) were independently associated with adverse outcome; achieving remission was protective (HR = 0.04; P < 0.001). CONCLUSION: Outcome in patients with C3 glomerulopathy and IC-MPGN was unsatisfactory, and only a small proportion of patients achieved complete or partial remission. Patients with DDD were more likely to present with rapidly progressive GN and were at higher risk of adverse outcomes, including kidney failure.
Assuntos
Glomerulonefrite Membranoproliferativa , Criança , Glomerulonefrite Membranoproliferativa/tratamento farmacológico , Humanos , Rim , Estudos RetrospectivosRESUMO
AIM: Pattern of kidney diseases varies across geographies due to multiple factors. There is a paucity of information from South Asia due to the absence of nationwide/regional biopsy registries. This study aimed to delineate the spectrum of renal parenchymal diseases in our region. METHODS: Records of kidney biopsies done in our nephrology department between 2006 and 2016 were analysed. Clinico-pathological correlation was done from the available records. RESULTS: Of the 3275 biopsy evaluated, 61.9% were males, and mean age was 33.2 ± 14.2 years. 6.2% patients were elderly (age ≥ 60 years). Nephrotic syndrome (60.3%) was the commonest indication for biopsy. On histology, 73.0% patients had primary glomerulonephritis (GN), 15.5% secondary GN, 5.3% tubulo-interstitial and 3.7% vascular disease. Focal segmental glomerulosclerosis (FSGS) was the commonest primary GN accounting for 18.2% of all GNs, followed by minimal change disease (16.8%), membranous nephropathy (MN) (16.0%) and IgA nephropathy (10.4%). Lupus nephritis (10.6%) and amyloidosis (3.7%) were the commonest secondary GN. The commonest cause of nephrotic syndrome was minimal change disease (22.9%), acute nephritic syndrome was lupus nephritis (30.6%), rapidly progressive renal failure was pauci-immune crescentic GN (24.5%). IgA nephropathy was the commonest etiology of asymptomatic urinary abnormalities (26.3%) and gross haematuria (50%). About 60.9% patients of undetermined chronic kidney disease had glomerular diseases, and 13.6% had chronic tubulointerstitial nephritis. Lupus nephritis and acute cortical necrosis were significantly more common in females compared with males. CONCLUSION: This is one of the largest cohorts of kidney biopsies from India, and it delineates the unique features and differences in the pattern of kidney disease in our population.
Assuntos
Glomerulonefrite Membranosa/patologia , Glomerulosclerose Segmentar e Focal/patologia , Rim/patologia , Nefrose Lipoide/patologia , Síndrome Nefrótica/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Feminino , Glomerulonefrite Membranosa/epidemiologia , Glomerulosclerose Segmentar e Focal/epidemiologia , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Nefrose Lipoide/epidemiologia , Síndrome Nefrótica/epidemiologia , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Tempo , Adulto JovemRESUMO
INTRODUCTION: BK polyomavirus is ubiquitous and remains dormant in the urothelial tract, reactivating and replicating in the immunocompromised state especially in the setting of post-renal transplantation where it is believed to be directly oncogenic based on recent reports. Its oncogenic role in the immunocompetent host is controversial. This study aimed to investigate the association of BK polyomavirus in Urothelial Carcinoma. MATERIAL AND METHODS: Patients with suspected urothelial carcinoma (UC) admitted under Department of Urology over a period of one year were recruited and transuretheral bladder tumor (TURBT) resection was performed, along with sampling of cystoscopically normal-appearing urothelium away from the tumor. In addition, cystectomy specimens with UC were included, with sampling of grossly normal-appearing urothelium away from the tumor. Immunohistochemistry (IHC) for SV40 T-Antigen and chromogenic in situ hybridization (CISH) using BK polyomavirus specific probe was performed on the paired samples (tumor and normal). RESULTS: Twenty-three TURBT and 14 cystectomy specimens were assessed. None of the cases showed evidence of BK polyomavirus infection in tumor or in surrounding mucosa by IHC. CISH performed in ten cases were also found to be negative. In comparison, one post-renal transplant urothelial carcinoma in our experience showed diffuse SV40 staining. CONCLUSIONS: This study suggests that BK polyomavirus infection is not associated with urothelial malignancy in the immunocompetent setting unlike in the immunocompromised setting where it should always be investigated for.
Assuntos
Vírus BK/isolamento & purificação , Carcinoma de Células de Transição/diagnóstico , Infecções por Polyomavirus/diagnóstico , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias Urológicas/diagnóstico , Carcinoma de Células de Transição/patologia , Humanos , Hospedeiro Imunocomprometido , Imuno-Histoquímica , Hibridização In Situ , Índia , Transplante de Rim/efeitos adversos , Infecções por Polyomavirus/patologia , Infecções por Polyomavirus/virologia , Centros de Atenção Terciária , Neoplasias da Bexiga Urinária/patologia , Neoplasias Urológicas/patologia , Urotélio/patologiaRESUMO
OBJECTIVE: The primary objective of this study was to compare triple-bolus dual-energy CT (DECT) against standard triple-phase MDCT in terms of appropriateness of patient treatment. SUBJECTS AND METHODS: One hundred twenty-four patients with suspected renal masses seen at ultrasound were randomized into triple-bolus DECT and triple-phase MDCT groups. Patients in the triple-bolus DECT group underwent synchronous corticomedullary nephrographic delayed-phase triple-bolus DECT. In the triple-phase MDCT group, single-energy triple-phase scans were acquired after an unenhanced scan. The primary outcome was appropriateness of treatment received at 1 year. The predefined noninferiority limit was 10%. Histopathologic analysis or follow-up confirmed the benign or malignant nature of the masses. Diagnostic accuracy to differentiate benign from malignant masses was calculated. Size-specific dose estimates were compared. RESULTS: After excluding six patients, 118 patients were analyzed (62 triple-bolus DECT; 56 triple-phase MDCT). Treatment appropriateness was not significantly different (p = 0.9397) between the two groups (61/62 [98.39%; 95% CI, 95.26-101.52%] for triple-bolus DECT vs 55/56 [98.21%; 95% CI, 94.74-101.68%] for triple-phase MDCT). The absolute difference was 0.18% (95% CI, -4.48% to 4.84%). Both techniques had similar diagnostic accuracy (sensitivity, 98.25% vs 96.67%; specificity, 98.17% vs 97.97%). The mean (± SD) size-specific dose estimate was significantly lower for triple-bolus DECT than for triple-phase MDCT (19.02 ± 4.07 vs 57.04 ± 15.17 mGy; p < 0.0001). CONCLUSION: Single-acquisition triple-bolus DECT is noninferior to triple-phase MDCT, with similar diagnostic accuracy but delivering significantly less radiation.
Assuntos
Neoplasias Renais/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Meios de Contraste/administração & dosagem , Diagnóstico Diferencial , Estudos de Equivalência como Asunto , Feminino , Humanos , Iohexol/administração & dosagem , Neoplasias Renais/terapia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Doses de Radiação , Interpretação de Imagem Radiográfica Assistida por Computador , Imagem Radiográfica a Partir de Emissão de Duplo Fóton , UltrassonografiaRESUMO
BACKGROUND: There is a paucity of data available about BK polyomavirus (BKPyV) infection after renal transplantation (RTX) in resource-limited countries with a predominantly living-donor, ABO-compatible RTX program. We aimed to assess BKPyV infection in such patients in a public hospital in India. METHODS: We prospectively evaluated plasma BKPyV replication in 62 patients at 1, 3, 6, 9, and 12 months after RTX. Sustained significant BK viremia (SSBKV) was defined as significant viremia (≥10 000 copies/mL) detected ≥2 times, and BKPyV-associated nephropathy (BKVAN) as histologic changes of BKVAN with BK viremia with/without graft dysfunction. RESULTS: All patients underwent RTX without requiring desensitization. Incidence of BK viremia was: 17.7%, 41.9%, 16.1%, 25.8%, and 17.7% at 1, 3, 6, 9, and 12 months, respectively. Of 62 patients, 64.5% had BKPyV viremia during the study, 32.2% had significant viremia, all except one detected in the first 6 months. Nine (14.5%) patients had SSBKV. There was no biopsy-proven BKVAN. At the end of 1 year, mean serum creatinine was higher and graft dysfunction was significantly more common in patients with SSBKV compared to those without SSBKV. CONCLUSION: Transient BK viremia is common in low/intermediate immunologic risk RTX recipients in India, with a peak occurring at 3-6 months. Most clear their viremia by 12 months. Graft dysfunction seems to be more frequent in patients with SSBKV, although BKVAN is uncommon on biopsy in these patients.
Assuntos
Nefropatias/epidemiologia , Transplante de Rim/efeitos adversos , Infecções por Polyomavirus/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Infecções Tumorais por Vírus/epidemiologia , Viremia/epidemiologia , Adulto , Vírus BK/isolamento & purificação , Biópsia , Monitoramento Epidemiológico , Feminino , Seguimentos , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/patologia , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/virologia , Humanos , Imunossupressores/uso terapêutico , Incidência , Índia/epidemiologia , Nefropatias/sangue , Nefropatias/patologia , Nefropatias/virologia , Transplante de Rim/métodos , Doadores Vivos , Masculino , Infecções por Polyomavirus/sangue , Infecções por Polyomavirus/patologia , Infecções por Polyomavirus/virologia , Complicações Pós-Operatórias/virologia , Estudos Prospectivos , Transplantados/estatística & dados numéricos , Infecções Tumorais por Vírus/sangue , Infecções Tumorais por Vírus/patologia , Infecções Tumorais por Vírus/virologia , Viremia/virologia , Adulto JovemRESUMO
Dense deposit disease is caused by fluid-phase dysregulation of the alternative complement pathway and frequently deviates from the classic membranoproliferative pattern of injury on light microscopy. Other patterns of injury described for dense deposit disease include mesangioproliferative, acute proliferative/exudative, and crescentic GN. Regardless of the histologic pattern, C3 glomerulopathy, which includes dense deposit disease and C3 GN, is defined by immunofluorescence intensity of C3c two or more orders of magnitude greater than any other immune reactant (on a 0-3 scale). Ultrastructural appearances distinguish dense deposit disease and C3 GN. Focal and segmental necrotizing glomerular lesions with crescents, mimicking a small vessel vasculitis such as ANCA-associated GN, are a very rare manifestation of dense deposit disease. We describe our experience with this unusual histologic presentation and distinct clinical course of dense deposit disease, discuss the pitfalls in diagnosis, examine differential diagnoses, and review the relevant literature.
Assuntos
Glomerulonefrite Membranoproliferativa/diagnóstico , Rim/irrigação sanguínea , Vasculite/diagnóstico , Criança , Diagnóstico Diferencial , Humanos , MasculinoRESUMO
BACKGROUND: IgA nephropathy (IgAN) is known to have an aggressive course in Asians. There is a paucity of data regarding the Oxford classification pattern of Indian patients with IgAN. This study aims to characterize the clinical and histopathologic profile of these patients. METHODS: All patients diagnosed to have primary IgAN by kidney biopsy in the nephrology department from July 2009 to July 2014 were included in this study. All kidney biopsies were reviewed and the MEST score was assigned as per the Oxford classification. The clinical features and Oxford classification score of patients were characterized. RESULTS: Nephrotic range proteinuria (NRP) (65/103, 63.1%) with or without edema was the commonest presentation. 67.0% patients had eGFR ≥ 60 mL/min and 16.5% patients had eGFR < 30 mL/min. Of the 103 patients, 80 (77.7%) had M1, 10 (9.7%) had E1, 45 (43.7%) had S1 and 41 (39.8%) had T1/T2 lesions by the Oxford criteria and 11 (10.7%) patients had crescents. 62 patients had eGFR ≥ 30 mL/min and follow up for at least 6 months (median -17.7 (6-65.1) months) of whom 52(83.9%) had received ACEi/ARBs and 38 (61.3%) had received immunosuppression. 11/62 (17.7%) patients developed renal worsening in this period of which 7 (11.3%) developed end stage kidney disease (ESKD). CONCLUSION: Indian patients with primary IgA nephropathy have a unique profile. They commonly present with nephrotic range proteinuria. A significant proportion of these patients have normal renal function despite heavy proteinuria. Mesangial proliferative lesions are predominant with a paucity of endocapillary proliferation and crescents compared to other Asian populations. Immunosuppressive use is more common in Indian patients.
Assuntos
Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/tratamento farmacológico , Glomerulonefrite por IGA/patologia , Rim/patologia , Esteroides/uso terapêutico , Adolescente , Adulto , Biópsia , Feminino , Taxa de Filtração Glomerular , Humanos , Imunossupressores/uso terapêutico , Índia , Falência Renal Crônica/complicações , Falência Renal Crônica/patologia , Masculino , Pessoa de Meia-Idade , Proteinúria/diagnóstico , Proteinúria/tratamento farmacológico , Estudos Retrospectivos , Centros de Atenção Terciária , Adulto JovemRESUMO
BACKGROUND: Molecular stratification of prostate cancer (PCa) based on genetic aberrations including ETS or RAF gene-rearrangements, PTEN deletion, and SPINK1 over-expression show clear prognostic and diagnostic utility. Gene rearrangements involving ETS transcription factors are frequent pathogenetic somatic events observed in PCa. Incidence of ETS rearrangements in Caucasian PCa patients has been reported, however, occurrence in Indian population is largely unknown. The aim of this study was to determine the prevalence of the ETS and RAF kinase gene rearrangements, SPINK1 over-expression, and PTEN deletion in this cohort. METHODS: In this multi-center study, formalin-fixed paraffin embedded (FFPE) PCa specimens (n = 121) were procured from four major medical institutions in India. The tissues were sectioned and molecular profiling was done using immunohistochemistry (IHC), RNA in situ hybridization (RNA-ISH) and/or fluorescence in situ hybridization (FISH). RESULTS: ERG over-expression was detected in 48.9% (46/94) PCa specimens by IHC, which was confirmed in a subset of cases by FISH. Among other ETS family members, while ETV1 transcript was detected in one case by RNA-ISH, no alteration in ETV4 was observed. SPINK1 over-expression was observed in 12.5% (12/96) and PTEN deletion in 21.52% (17/79) of the total PCa cases. Interestingly, PTEN deletion was found in 30% of the ERG-positive cases (P = 0.017) but in only one case with SPINK1 over-expression (P = 0.67). BRAF and RAF1 gene rearrangements were detected in â¼1% and â¼4.5% of the PCa cases, respectively. CONCLUSIONS: This is the first report on comprehensive molecular profiling of the major spectrum of the causal aberrations in Indian men with PCa. Our findings suggest that ETS gene rearrangement and SPINK1 over-expression patterns in North Indian population largely resembled those observed in Caucasian population but differed from Japanese and Chinese PCa patients. The molecular profiling data presented in this study could help in clinical decision-making for the pursuit of surgery, diagnosis, and in selection of therapeutic intervention.
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Neoplasias da Próstata/genética , Proteínas Proto-Oncogênicas c-ets/genética , Proteínas de Transporte/genética , Deleção de Genes , Expressão Gênica , Perfilação da Expressão Gênica , Rearranjo Gênico/genética , Humanos , Imuno-Histoquímica , Hibridização In Situ , Hibridização in Situ Fluorescente , Índia , Masculino , PTEN Fosfo-Hidrolase , Prognóstico , Transativadores/genética , Regulador Transcricional ERG , Inibidor da Tripsina Pancreática de Kazal , Quinases raf/genéticaRESUMO
Patients with light-chain deposition disease (LCDD) frequently do not meet criteria for myeloma. In such cases, despite low tumor burden, the circulating monoclonal immunoglobulins cause renal damage, are responsible for post-transplant recurrence, and are rightly categorized as monoclonal gammopathy of renal significance (MGRS) requiring chemotherapy. A 65-year male with uncharacterized nodular glomerulopathy presented with proteinuria 3 years postrenal transplant. His allograft biopsies were diagnostic of light-chain deposition disease (likely recurrent), and in the absence of myeloma, he was labeled as MGRS. Based on the limited literature available, he was treated with bortezomib which resulted in normalization of serum-free light-chain ratios and resolution of proteinuria. He, however, later succumbed to complications of chemotherapy. This case highlights the diagnostic difficulties in LCDD, the importance of an accurate pretransplant diagnosis, and treatment of the malignant clone, in the absence of which post-transplant management of recurrence is challenging with poor outcomes.
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Bortezomib/uso terapêutico , Cadeias Leves de Imunoglobulina/metabolismo , Transplante de Rim/efeitos adversos , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Idoso , Antineoplásicos/uso terapêutico , Biópsia , Humanos , Rim/patologia , Falência Renal Crônica/cirurgia , Masculino , Gamopatia Monoclonal de Significância Indeterminada/etiologia , Gamopatia Monoclonal de Significância Indeterminada/terapiaRESUMO
Gain-of-function mutations in the calcium channel TRPC6 lead to autosomal dominant focal segmental glomerulosclerosis and podocyte expression of TRPC6 is increased in some acquired human glomerular diseases, particularly in membranous nephropathy. These observations led to the hypothesis that TRPC6 overactivation is deleterious to podocytes through pathological calcium signaling, both in genetic and acquired diseases. Here, we show that the effects of TRPC6 on podocyte function are context-dependent. Overexpression of TRPC6 alone did not directly affect podocyte morphology and cytoskeletal structure. Unexpectedly, however, overexpression of TRPC6 protected podocytes from complement-mediated injury, whereas genetic or pharmacological TRPC6 inactivation increased podocyte susceptibility to complement. Mechanistically, this effect was mediated by Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activation. Podocyte-specific TRPC6 transgenic mice showed stronger CaMKII activation, reduced podocyte foot process effacement and reduced levels of proteinuria during nephrotoxic serum nephritis, whereas TRPC6 null mice exhibited reduced CaMKII activation and higher levels of proteinuria compared with wild type littermates. Human membranous nephropathy biopsy samples showed podocyte staining for active CaMKII, which correlated with the degree of TRPC6 expression. Together, these data suggest a dual and context dependent role of TRPC6 in podocytes where acute activation protects from complement-mediated damage, but chronic overactivation leads to focal segmental glomerulosclerosis.
Assuntos
Proteínas do Sistema Complemento/metabolismo , Glomerulosclerose Segmentar e Focal/metabolismo , Podócitos/metabolismo , Canais de Cátion TRPC/metabolismo , Animais , Sinalização do Cálcio , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Ativação Enzimática , Glomerulonefrite Membranosa/metabolismo , Glomerulonefrite Membranosa/patologia , Glomerulosclerose Segmentar e Focal/patologia , Humanos , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Podócitos/patologia , Proteinúria/metabolismo , Canais de Cátion TRPC/genética , Canal de Cátion TRPC6Assuntos
Carcinoma de Células de Transição/diagnóstico , Neoplasias Renais/diagnóstico , Transplante de Rim/efeitos adversos , Infecções por Polyomavirus/diagnóstico , Infecções Tumorais por Vírus/diagnóstico , Aloenxertos/diagnóstico por imagem , Aloenxertos/patologia , Aloenxertos/virologia , Vírus BK/imunologia , Vírus BK/isolamento & purificação , Biópsia , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/virologia , Feminino , Fluordesoxiglucose F18/administração & dosagem , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Terapia de Imunossupressão/efeitos adversos , Rim/diagnóstico por imagem , Rim/patologia , Rim/virologia , Neoplasias Renais/patologia , Neoplasias Renais/virologia , Pessoa de Meia-Idade , Infecções por Polyomavirus/patologia , Infecções por Polyomavirus/virologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Insuficiência Renal Crônica/cirurgia , Infecções Tumorais por Vírus/patologia , Infecções Tumorais por Vírus/virologiaRESUMO
Antibodies to complement factor H are an uncommon cause of hemolytic uremic syndrome (HUS). Information on clinical features and outcomes in children is limited. In order to explore this we studied a multicenter cohort of 138 Indian children with anti-complement factor H antibody associated HUS, constituting 56% of patients with HUS. Antibody titers were high (mean 7054 AU/ml) and correlated inversely with levels of complement C3, but not complement factor H. Homozygous deletion of the CFHR1 gene was found in 60 of 68 patients. Therapies included dialysis in 119 children, 105 receiving plasma exchanges and 26 intravenous immunoglobulin. Induction immunosuppression consisted of 87 children receiving prednisolone with or without intravenous cyclophosphamide or rituximab. Antibody titers fell significantly following plasma exchanges and increased during relapses. Adverse outcome (stage 4-5 CKD or death) was seen in 36 at 3 months and 41 by last follow up, with relapse in 14 of 122 available children. Significant independent risk factors for adverse outcome were an antibody titer over 8000 AU/ml, low C3 and delay in plasma exchange. Combined plasma exchanges and induction immunosuppression resulted in significantly improved renal survival: one adverse outcome prevented for every 2.6 patients treated. Maintenance immunosuppressive therapy, of prednisolone with either mycophenolate mofetil or azathioprine, significantly reduced the risk of relapses. Thus, prompt use of immunosuppressive agents and plasma exchanges are useful for improving outcomes in pediatric patients with anti-complement factor H-associated HUS.
Assuntos
Autoanticorpos/sangue , Proteínas Sanguíneas/imunologia , Proteínas Inativadoras do Complemento C3b/imunologia , Síndrome Hemolítico-Urêmica/terapia , Imunossupressores/uso terapêutico , Troca Plasmática , Tempo para o Tratamento , Fatores Etários , Anticorpos Monoclonais Murinos/uso terapêutico , Azatioprina/uso terapêutico , Biomarcadores/sangue , Proteínas Sanguíneas/genética , Estudos de Casos e Controles , Criança , Pré-Escolar , Terapia Combinada , Proteínas Inativadoras do Complemento C3b/genética , Ciclofosfamida/uso terapêutico , Quimioterapia Combinada , Feminino , Deleção de Genes , Síndrome Hemolítico-Urêmica/sangue , Síndrome Hemolítico-Urêmica/diagnóstico , Síndrome Hemolítico-Urêmica/genética , Síndrome Hemolítico-Urêmica/imunologia , Homozigoto , Humanos , Imunossupressores/efeitos adversos , Índia , Lactente , Masculino , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapêutico , Troca Plasmática/efeitos adversos , Prednisolona/uso terapêutico , Recidiva , Fatores de Risco , Rituximab , Fatores de Tempo , Resultado do TratamentoAssuntos
Doença das Cadeias Pesadas/diagnóstico , Doença das Cadeias Pesadas/terapia , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Paraproteinemias/diagnóstico , Paraproteinemias/terapia , Adulto , Aloenxertos , Biópsia , Bortezomib/uso terapêutico , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/cirurgia , Doença das Cadeias Pesadas/complicações , Humanos , Rim/patologia , Falência Renal Crônica/complicações , Falência Renal Crônica/imunologia , Doadores Vivos , Masculino , Paraproteinemias/complicações , Complicações Pós-Operatórias , Proteinúria/complicações , Indução de RemissãoRESUMO
INTRODUCTION: Chronic kidney disease of undetermined aetiology (CKDu) is an important public health problem. Indian data are mostly based on studies from rural regions in south and east India. We examined the burden and profile of CKDu in patients attending a tertiary care hospital in north India. METHODS: We assessed records of consecutive new CKD patients registered in a nephrology clinic from January 2015 to June 2022. Patients were classified as having CKDu based on predefined inclusion and exclusion criteria. Clinical and laboratory parameters at presentation and kidney biopsy when done were noted. RESULTS: Records of 32,369 patients with CKD were screened, and 29,663 were included (2,706 excluded due to inadequate data). A total of 370 (1.2%) patients were categorized as CKDu. Mean age was 41 ± 14.7 years, 58.1% being male. Of them, 158 (42.7%) patients were in CKD stage 3, 89 (24.1%) in stage 4, 84 (22.7%) in stage 5, and 39 (10.5%) were dialysis dependent at presentation; 232 (62.7%) patients had proteinuria <0.5 gm/day and 138 (37.3%) between 0.5 and 1 gm/day. Renal histology was available for 65 CKDu patients: 62 had chronic tubulointerstitial nephritis (CTIN) and 3 had non-specific changes. CONCLUSION: When defined using strict criteria with intensive diagnostic workup, burden of CKDu is low in our hospital-based cohort of CKD patients. CTIN is the predominant histopathological finding in kidney biopsy.
RESUMO
Smart portable devices- smartphones and smartwatches- are rapidly being adopted by the general population, which has brought forward an opportunity to use the large volumes of physiological, behavioral, and activity data continuously being collected by these devices in naturalistic settings to perform research, monitor health, and track disease. While these data can serve to revolutionize health monitoring in research and clinical care, minimal research has been conducted to understand what motivates people to use these devices and their interest and comfort in sharing the data. In this study, we aimed to characterize the ownership and usage of smart devices among patients from an expansive academic health system in the southeastern US and understand their willingness to share data collected by the smart devices. We conducted an electronic survey of participants from an online patient advisory group around smart device ownership, usage, and data sharing. Out of the 3021 members of the online patient advisory group, 1368 (45%) responded to the survey, with 871 female (64%), 826 and 390 White (60%) and Black (29%) participants, respectively, and a slight majority (52%) age 58 and older. Most of the respondents (98%) owned a smartphone and the majority (59%) owned a wearable. In this population, people who identify as female, Hispanic, and Generation Z (age 18-25), and those completing higher education and having full-time employment, were most likely to own a wearable device compared to their demographic counterparts. 50% of smart device owners were willing to share and 32% would consider sharing their smart device data for research purposes. The type of activity data they are willing to share varies by gender, age, education, and employment. Findings from this study can be used to design both equitable and cost-effective digital health studies, leveraging personally-owned smartphones and wearables in representative populations, ultimately enabling the development of equitable digital health technologies.