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The Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Management of Glomerular Diseases was published in 2021. Since then, the pace of drug development for glomerular diseases has accelerated, due in large part to rapidly accumulating insights into disease pathogenesis from genetic and molecular studies of afflicted patients. To keep the Glomerular Diseases Guideline as current as possible, KDIGO made a commitment to the nephrology community to provide periodic updates, based on new developments for each disease. After the 2021 guideline was published, two novel drugs received regulatory approval for the management of lupus nephritis, leading to the first KDIGO guideline update. Herein, an executive summary of the most important guideline changes from the Lupus Nephritis chapter is provided as a quick reference.
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Nefritis Lúpica , Nefrología , Humanos , Nefritis Lúpica/diagnóstico , Nefritis Lúpica/tratamiento farmacológico , Riñón , Desarrollo de MedicamentosRESUMEN
OBJECTIVES: Integrating clinical and histological parameters into prognostic scores may enhance the prediction of progression to kidney failure in anti-neutrophil cytoplasm antibodies-associated vasculitis (AAV). This study aimed to evaluate the prognostic performance of histological classifications and scoring systems for kidney survival in AAV. METHODS: This retrospective cohort study included 101 AAV patients with kidney involvement diagnosed by biopsy and followed for ≥12 months. The main outcome was the time to kidney failure. The prognostic performance of each histological and prognostic score was evaluated using Harrell's C statistic and Akaike's Information Criteria. RESULTS: Among the 101 patients, 37 progressed to kidney failure over a median follow-up of 75 months (IQR 39-123). The Harrell's C statistic was 0.702 (0.620-0.784), 0.606 (0.473-0.738), 0.801 (0.736-0.867), 0.782 (0.706-0.858), and 0.817 (0.749-0.885) for the EUVAS/Berden classification, Mayo Clinic Chronicity Score, Percentage of ANCA Crescentic Score (PACS), ANCA renal risk score (ARRS), and the improved ANCA kidney risk score (AKRiS), respectively. The AKRiS best discriminated the risk of kidney failure progression among subgroups. The AKRiS performance decreased with longer follow-up intervals. Adding the peak estimated glomerular filtration rate attained post-therapy improved the AKRiS performance at all follow-up intervals. Kidney relapses precipitated kidney failure in 71% of cases that progressed after the first year of follow-up. CONCLUSION: The novel AKRiS enhances the prediction of kidney failure in AAV with kidney involvement. As the prognostic yield of AKRiS decreases over time, a second calculation of AKRiS, including post-therapy kidney function, may improve its long-term performance.
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OBJECTIVES: To characterize the clinical presentation and outcomes of LN in a Hispanic cohort from Mexico. METHODS: We studied 440 subjects with systemic lupus erythematosus and biopsy-proven LN followed for >36 months. We obtained demographic, clinical, laboratory, histopathological and treatment variables. All outcomes were analysed by survival analysis and included response to therapy, renal relapses, progression of kidney disease (decline in eGFR ≥ 30%, doubling of serum creatinine, end-stage kidney disease) and patient survival. RESULTS: The median age of the study cohort was 29 years (IQR 23-37) and 96% were female. The median eGFR at inclusion was 81 mL/min/1.73m2 (IQR 48-118) and 24 h-uPCR was 3.4 g/g (IQR 1.9-5.6). Mixed class LN (III/IV+V) was the most frequently observed (69%). Over a median follow-up of 79 months, complete response rates were 22.3%, 40.5% and 51.6%, at 6, 12 and 24 months, respectively. Renal relapse rates were 32.3% and 50.6% at 3 and 5 years. By 3 and 5 years, 20.7% and 31.4% had decline in eGFR ≥30%, 14.4% and 22.5% doubled their serum creatinine, and 9.1% and 17.7% progressed to ESKD. The factors associated with loss of kidney function were age, eGFR at presentation, the histologic chronicity index in the kidney biopsy, and the type of response to therapy. Patient survival was 98.2% and 97.1% at 3 and 5 years. CONCLUSION: Although the response to treatment and patient survival in this Latin American cohort is comparable to that observed in other regions, there is still a high rate of renal relapses and progression to decline in kidney function.
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Fallo Renal Crónico , Nefritis Lúpica , Humanos , Femenino , Adulto Joven , Adulto , Masculino , Nefritis Lúpica/tratamiento farmacológico , México , Creatinina , Pronóstico , Estudios de Seguimiento , Estudios Retrospectivos , Riñón/patología , Fallo Renal Crónico/complicaciones , Hispánicos o LatinosRESUMEN
OBJECTIVES: To evaluate the effect of antimalarial drugs in response to therapy, incidence of LN flares, and progression of kidney disease in a large LN cohort. METHODS: We retrospectively studied 424 biopsy-proven LN patients followed for >3 years. We obtained demographic, clinical, laboratory, histopathological, and treatment variables. Antimalarial use was approached as 1) users versus no users, 2) according to prevalent vs incident use regarding the LN flare, and 3) according to the type of antimalarial. All outcomes were evaluated by time-to-event analyses. Adjusted hazard ratios were obtained by Cox regression. RESULTS: The cohort included 424 patients, median age of 29 years (IQR 23-37), 96% female, with a median eGFR of 81 ml/min/1.73m2 (IQR 48-118) and proteinuria of 3.4 g/g (IQR 1.9-5.5). Antimalarial use was associated with higher complete response (aHR 1.57, 1.08-2.27), lower incidence of kidney flares (aHR 0.63, 0.43-0.92), and lower progression to kidney failure (aHR 0.37, 0.23-0.53). The effect on these outcomes was modified by the presentation eGFR, histological class, and/or concomitant initial immunosuppressor. These protective effects were observed in patients with prevalent or incident use regarding the LN flare and patients using hydroxychloroquine. The incidence of toxic retinopathy was 1.7%, 5.7%, and 8.8% by 3-, 5-, and 7 years of continued antimalarial use. CONCLUSION: The use of antimalarial drugs is associated with increased response to therapy, lower incidence of kidney flares, and lower progression to kidney failure in LN patients. Conversely, this population is at high risk of toxic maculopathy, and yearly ophthalmologic examination is recommended.
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BACKGROUND: Repeated renal flares in lupus nephritis (LN) have been associated with worse long-term kidney function. This study aimed to assess the impact of repeated LN flares in response to therapy, kidney and patient prognosis. METHODS: All patients from a biopsy-proven LN cohort between 2008 and 2018 were segregated into three groups according to the number of LN flares when they entered our cohort: first LN flare, second LN flare or third LN flare. The following outcomes were evaluated by unadjusted and adjusted time-to-event analyses: complete and partial response, disease relapses, progression to decline of 30% of the estimated glomerular filtration rate (eGFR), doubling of serum creatinine, end-stage kidney disease and patient survival. RESULTS: A total of 441 patients were included: 257 (58%) in their first LN flare, 102 (23%) in their second LN flare and 82 (19%) in their third LN flare. There were significant differences in LN flare presentation in age, eGFR, serum albumin, pyuria and hematuria among groups. The National Institutes of Health chronicity indices and the percentage of patients with vascular lesions were higher in groups at progressive LN flares. In the adjusted analyses, complete and partial response rates decreased, as well as kidney and patient survival, at a progressive number of LN flares. No differences in the dynamic course of all surveillance laboratory parameters were observed in the first year after initial therapy among LN flare groups. CONCLUSIONS: A progressive number of LN flares is associated with a lower response to therapy and an adverse prognosis for kidney function and patient survival.
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Fallo Renal Crónico , Nefritis Lúpica , Humanos , Nefritis Lúpica/diagnóstico , Nefritis Lúpica/tratamiento farmacológico , Riñón/patología , Pronóstico , Fallo Renal Crónico/etiología , Fallo Renal Crónico/terapia , Fallo Renal Crónico/epidemiología , Biopsia , Estudios RetrospectivosRESUMEN
Over the past year, and for the first time ever, the US Food and Drug Administration approved 2 drugs specifically for the treatment of lupus nephritis (LN). As the lupus community works toward understanding how to best use these new therapies, it is also an ideal time to begin to rethink the overall management strategy of LN. In addition to new drugs, this must include how to use kidney biopsies for management and not just diagnosis, how molecular technologies can be applied to interrogate biopsies and how such data can impact management, and how to incorporate LN biomarkers into management paradigms. Herein, we will review new developments in these areas of LN and put them into perspective for disease management now and in the future.
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Lupus Eritematoso Sistémico , Nefritis Lúpica , Biomarcadores , Biopsia , Humanos , Riñón/patología , Nefritis Lúpica/diagnóstico , Nefritis Lúpica/tratamiento farmacológicoRESUMEN
Initial reports suggested that kidney involvement after coronavirus disease 19 (COVID-19) infection was uncommon, but this premise appears to be incorrect. Acute kidney injury can occur through various mechanisms and complicate the course of up to 25% of patients with COVID-19 hospitalized in our Institution, and of over 50% of those on invasive mechanical ventilation. Mechanisms of injury include direct kidney injury and predominantly tubular, although glomerular injury has been reported, and resulting from severe hypoxic respiratory failure, secondary infection, and exposure to nephrotoxic drugs. The mainstay of treatment remains the prevention of progressive kidney damage and, in some cases, the use of renal replacement therapy. Although the use of blood purification techniques has been proposed as a potential treatment, results to date have not been conclusive. In this manuscript, the mechanisms of kidney injury by COVID-19, risk factors, and the mainstays of treatment are reviewed.
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Lesión Renal Aguda , COVID-19 , Humanos , COVID-19/complicaciones , COVID-19/epidemiología , SARS-CoV-2 , Pandemias , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapia , RiñónRESUMEN
Background: A high incidence of acute kidney injury (AKI) has been reported in coronavirus disease 2019 (COVID-19) patients in critical care units and those undergoing invasive mechanical ventilation (IMV). The introduction of dexamethasone (DXM) as treatment for severe COVID-19 has improved mortality, but its effects in other organs remain under study. Objective: The objective of this study was to evaluate the association between DXM and AKI in COVID-19. Methods: In this prospective observational cohort study, we evaluated the incidence of AKI in critically ill COVID-19 patients undergoing mechanical ventilation, and the association of DXM treatment with the incidence, severity, and outcomes of AKI. The association between DXM treatment and AKI was evaluated by multivariable logistic regression. The association of the combination of DXM treatment and AKI on mortality was evaluated by Cox-regression analysis. Results: We included 552 patients. AKI was diagnosed in 311 (56%), of which 196 (63%) corresponded to severe (stage 2 or 3) AKI, and 46 (14.8%) received kidney replacement therapy. Two hundred and sixty-seven (48%) patients were treated with DXM. This treatment was associated to lower incidence of AKI (Odds Radio 0.34, 95% Confidence intervals [CI] 0.22-0.52, p < 0.001) after adjusting for age, body mass index, laboratory parameters, SOFA score, and vasopressor use. DXM treatment significantly reduced mortality in patients with severe AKI (HR 0.63, 95%CI 0.41-0.96, p = 0.032). Conclusions: The incidence of AKI is high in COVID-19 patients under IMV. DXM treatment is associated with a lower incidence of AKI and a lower mortality in the group with severe AKI.
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Lesión Renal Aguda , COVID-19 , Humanos , COVID-19/complicaciones , Respiración Artificial , Estudios Prospectivos , Tratamiento Farmacológico de COVID-19 , Cuidados Críticos , Unidades de Cuidados Intensivos , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , Lesión Renal Aguda/prevención & control , Enfermedad Crítica , Dexametasona , Estudios Retrospectivos , Factores de RiesgoRESUMEN
The Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Management of Glomerular Diseases is an update to the KDIGO 2012 guideline. The aim is to assist clinicians caring for individuals with glomerulonephritis (GN), both adults and children. The scope includes various glomerular diseases, including IgA nephropathy and IgA vasculitis, membranous nephropathy, nephrotic syndrome, minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), infection-related GN, antineutrophil cytoplasmic antibody (ANCA) vasculitis, lupus nephritis, and anti-glomerular basement membrane antibody GN. In addition, this guideline will be the first to address the subtype of complement-mediated diseases. Each chapter follows the same format providing guidance related to diagnosis, prognosis, treatment, and special situations. The goal of the guideline is to generate a useful resource for clinicians and patients by providing actionable recommendations based on evidence syntheses, with useful infographics incorporating views from experts in the field. Another aim is to propose research recommendations for areas where there are gaps in knowledge. The guideline targets a broad global audience of clinicians treating GN while being mindful of implications for policy and cost. Development of this guideline update followed an explicit process whereby treatment approaches and guideline recommendations are based on systematic reviews of relevant studies, and appraisal of the quality of the evidence and the strength of recommendations followed the "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) approach. Limitations of the evidence are discussed, with areas of future research also presented.
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Glomerulonefritis por IGA , Glomerulonefritis Membranosa , Glomerulonefritis , Nefrosis Lipoidea , Adulto , Niño , Glomerulonefritis/diagnóstico , Glomerulonefritis/terapia , Glomerulonefritis por IGA/diagnóstico , Glomerulonefritis por IGA/terapia , Glomerulonefritis Membranosa/diagnóstico , Glomerulonefritis Membranosa/tratamiento farmacológico , Humanos , RiñónRESUMEN
INTRODUCTION: Patients with acute respiratory distress syndrome (ARDS) secondary to COVID-19 frequently develop severe acute kidney injury (AKI). Although continuous renal replacement therapy is the standard of care for critically ill patients, prolonged intermittent renal replacement therapy (PIRRT) may be a feasible option. We aimed to describe the tolerability and security of PIRRT treatments in COVID-19 patients with ARDS who required mechanical ventilation and developed severe AKI. METHODS: We prospectively analyzed patients who underwent PIRRT treatments at a COVID-19 reference hospital in Mexico City. Intradialytic hypotension was defined as a systolic blood pressure decrease of ≥20 mm Hg or an increase of 100% in vasopressor dose. RESULTS: We identified 136 AKI cases (60.7%) in 224 patients admitted to the intensive care unit. Among them, 21 (15%) underwent PIRRT (130 sessions) due to stage 3 AKI. The median age of the cohort was 49 (range 36-73) years, 17 (81%) were male, 7 (33%) had diabetes, and the median time between symptoms onset and PIRRT initiation was 12 (interquartile range [IQR] 7-14) days. The median of PIRRT procedures for each patient was 5 (IQR 4-9) sessions. In 108 (83%) PIRRT sessions, the total ultrafiltration goal was achieved. In 84 (65%) PIRRT procedures, there was a median increase in norepinephrine dose of +0.031 mcg/kg/min during PIRRT (IQR 0.00 to +0.07). Intradialytic hypotensive events occurred in 56 (43%) procedures. Fifteen (12%) PIRRT treatments were discontinued due to severe hypotension. Vasopressor treatment at PIRRT session onset (OR 6.2, 95% CI 1.4-28.0, p: 0.02) and a pre-PIRRT lactate ≥3.0 mmol/L (OR 4.63, 95% CI 1.3-12.8, p: 0.003) were independently and significantly associated with the risk of hypotension during PIRRT. During follow-up, 11 patients (52%) recovered from AKI and respiratory failure and 9 (43%) died. Several adaptations to our PIRRT protocol during the COVID-19 outbreak are presented. CONCLUSIONS: PIRRT was feasible in the majority of COVID-19 patients with ARDS and severe AKI, despite frequent transitory intradialytic hypotensive episodes. PIRRT may represent an acceptable alternative of renal replacement therapy during the COVID-19 outbreak.
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Lesión Renal Aguda/terapia , COVID-19/complicaciones , Cuidados Críticos/métodos , Terapia de Reemplazo Renal Intermitente , Síndrome de Dificultad Respiratoria/etiología , SARS-CoV-2 , Lesión Renal Aguda/etiología , Adulto , Anciano , COVID-19/epidemiología , Comorbilidad , Terapia de Reemplazo Renal Continuo , Complicaciones de la Diabetes/epidemiología , Femenino , Humanos , Hipertensión/epidemiología , Hipotensión/etiología , Terapia de Reemplazo Renal Intermitente/efectos adversos , Masculino , Persona de Mediana Edad , Norepinefrina/uso terapéutico , Estudios Prospectivos , Respiración Artificial , Síndrome de Dificultad Respiratoria/terapia , Resultado del Tratamiento , Vasoconstrictores/uso terapéuticoRESUMEN
INTRODUCTION: Acute kidney injury (AKI) is common in coronavirus disease 2019 (COVID-19). It is unknown if hospital-acquired AKI (HA-AKI) and community-acquired AKI (CA-AKI) convey a distinct prognosis. METHODS: The study aim was to evaluate the incidence and risk factors associated with both CA-AKI and HA-AKI. Consecutive patients hospitalized at a reference center for COVID-19 were included in this prospective cohort study. RESULTS: We registered 349 (30%) AKI episodes in 1,170 hospitalized patients, 224 (19%) corresponded to CA-AKI, and 125 (11%) to HA-AKI. Compared to patients with HA-AKI, subjects with CA-AKI were older (61 years [IQR 49-70] vs. 50 years [IQR 43-61]), had more comorbidities (hypertension [44 vs. 26%], CKD [10 vs. 3%]), higher Charlson Comorbidity Index (2 points [IQR 1-4] vs. 1 point [IQR 0-2]), and presented to the emergency department with more severe disease. Mortality rates were not different between CA-AKI and HA-AKI (119 [53%] vs. 63 [50%], p = 0.66). In multivariate analysis, CA-AKI was strongly associated to a history of CKD (OR 4.17, 95% CI 1.53-11.3), hypertension (OR 1.55, 95% CI 1.01-2.36), Charlson Comorbidity Index (OR 1.16, 95% CI 1.02-1.32), and SOFA score (OR 2.19, 95% CI 1.87-2.57). HA-AKI was associated with the requirement for mechanical ventilation (OR 68.2, 95% CI 37.1-126), elevated troponin I (OR 1.95, 95% CI 1.01-3.83), and glucose levels at admission (OR 1.05, 95% CI 1.02-1.08). DISCUSSION/CONCLUSIONS: CA-AKI and HA-AKI portend an adverse prognosis in CO-VID-19. Nevertheless, CA-AKI was associated with a higher comorbidity burden (including CKD and hypertension), while HA-AKI occurred in younger patients by the time severe multiorgan disease developed.
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Lesión Renal Aguda/etiología , COVID-19/complicaciones , Lesión Renal Aguda/diagnóstico , Adulto , Factores de Edad , Anciano , COVID-19/diagnóstico , Femenino , Hospitalización , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Factores de Riesgo , SARS-CoV-2/aislamiento & purificaciónRESUMEN
BACKGROUND: Clinical distinction between patients with lupus nephritis who have active inflammation or chronic kidney damage is challenging. Studies have shown soluble CD163, which derives from cleavage of the CD163 M2c macrophage receptor and can be quantified in urine, correlates with active lupus nephritis. METHODS: We measured urine CD163 at lupus nephritis flares in patients from a Mexican cohort and cross-sectional and longitudinal United States cohorts. We also performed serial urine CD163 measurements during the treatment of flares in a subset of patients from the Mexican and longitudinal United States cohorts, and assessed response to therapy at 12 months. In addition, we evaluated urinary CD163 agreement with histologic activity in 19 patients from the Mexican cohort who had repeated kidney biopsies on follow-up. RESULTS: Urinary CD163 levels were significantly higher in patients with active lupus nephritis than in patients with active extrarenal SLE, inactive SLE, and other glomerular diseases, and correlated with disease clinical severity, histologic class, and the histologic activity index. Urinary CD163 increased from 6 months preflare to flare, diminishing progressively in complete and partial responders, whereas it remained elevated in nonresponders. Urinary CD163 <370 ng/mmol at 6 months predicted complete renal response at 12 months with >87% sensitivity and >87% specificity. Urinary CD163 <370 ng/mmol or >370 ng/mmol perfectly agreed (κ=1.0) with a histologic activity index ≤1 or >1 in repeated biopsies, respectively. Evaluation of urinary CD163 in patients with persistent proteinuria at 6 months improved the prediction of who would achieve complete renal response at 12 months. CONCLUSIONS: Urinary CD163 reflects histologic inflammation in lupus nephritis and is a promising activity biomarker that varies over time with lupus nephritis activity and treatment.
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Antígenos CD/orina , Antígenos de Diferenciación Mielomonocítica/orina , Nefritis Lúpica/orina , Adulto , Biomarcadores/orina , Femenino , Humanos , Nefritis Lúpica/diagnóstico , Nefritis Lúpica/patología , Masculino , Persona de Mediana Edad , Receptores de Superficie CelularRESUMEN
Amyloid light-chain (AL) amyloidosis represents the most common type of amyloid affecting the kidneys. As AL amyloidosis is frequently clinically manifested as nephrotic syndrome, this glomerular syndrome has been improperly linked to all other types of kidney amyloidosis. In this report, we highlight the importance of amyloid typing, as the deposition of several amyloidotic proteins in the kidneys is not associated with heavy proteinuria. We present two cases of patients who presented with sudden-onset nephrotic syndrome and kidney biopsies showing interstitial, vascular, and/or mesangial LECT2 amyloidosis. Further examination by electron microscopy demonstrated diffuse foot process effacement consistent with minimal change disease and no amyloid deposition in the glomerular basement membrane. Both patients had complete remission after glucocorticoid treatment. We conclude that the presence of nephrotic syndrome in a patient with LECT2 amyloidosis must alert for a potential concurrent podocytopathy.
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Amiloidosis/complicaciones , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Síndrome Nefrótico/etiología , Podocitos/patología , Anciano , Femenino , Humanos , Riñón/patología , Riñón/ultraestructura , Masculino , Síndrome Nefrótico/patologíaRESUMEN
OBJECTIVE: To develop a score to predict the need for ICU admission in COVID-19. METHODS: We assessed patients admitted to a COVID-19 center in Mexico. Patients were segregated into a group that required ICU admission, and a group that never required ICU admission. By logistic regression, we derived predictive models including clinical, laboratory, and imaging findings. The ABC-GOALS was constructed and compared to other scores. RESULTS: We included 329 and 240 patients in the development and validation cohorts, respectively. One-hundred-fifteen patients from each cohort required ICU admission. The clinical (ABC-GOALSc), clinical+laboratory (ABC-GOALScl), clinical+laboratory+image (ABC-GOALSclx) models area under the curve were 0.79 (95%CI=0.74-0.83) and 0.77 (95%CI=0.71-0.83), 0.86 (95%CI=0.82-0.90) and 0.87 (95%CI=0.83-0.92), 0.88 (95%CI=0.84-0.92) and 0.86 (95%CI=0.81-0.90), in the development and validation cohorts, respectively. The ABC-GOALScl and ABC-GOALSclx outperformed other COVID-19 and pneumonia predictive scores. CONCLUSION: ABC-GOALS is a tool to timely predict the need for admission to ICU in COVID-19.
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COVID-19/epidemiología , Hospitalización/estadística & datos numéricos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Adulto , Área Bajo la Curva , Intervalos de Confianza , Femenino , Humanos , Modelos Logísticos , Masculino , México/epidemiología , Persona de Mediana Edad , Estudios Prospectivos , Factores de RiesgoRESUMEN
Leukocyte chemotactic factor 2 (LECT2) amyloidosis is a recently recognized entity that often affects the kidneys. Little information is available regarding kidney transplant outcomes in patients with LECT2 amyloidosis or who received kidney allografts containing LECT2 amyloid. We present clinical findings and allograft outcomes of 5 patients who received kidneys with donor-derived LECT2 amyloidosis. In all 5, LECT2 amyloidosis was discovered during protocol biopsies or in evaluation of suspected rejection. Less than 10% of kidney parenchyma was involved, with mostly interstitial and vascular deposits. Allograft function was not impaired and the amyloid deposits persisted for up to 8 years of follow-up. We conclude that kidneys with limited and localized LECT2 amyloid deposits that are otherwise suitable for transplantation need not be automatically discarded.
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Amiloidosis/diagnóstico , Amiloidosis/genética , Péptidos y Proteínas de Señalización Intercelular/genética , Trasplante de Riñón/métodos , Donantes de Tejidos , Adulto , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Up to 50% of lupus nephritis (LN) patients experience renal flares after their initial episode of LN. These flares contribute to poor renal outcomes. We postulated that intrarenal immune gene expression is different in flares compared with de novo LN, and conducted these studies to test this hypothesis. METHODS: Glomerular and tubulointerstitial immune gene expression was evaluated in 14 patients who had a kidney biopsy to diagnose LN and another biopsy at their first LN flare. Ten healthy living kidney donors were included as controls. RNA was extracted from laser microdissected formalin-fixed paraffin-embedded kidney biopsies. Gene expression was analyzed using the Nanostring nCounter® platform and validated by quantitative real-time polymerase chain reaction. Differentially expressed genes were analyzed by the Ingenuity Pathway Analysis and Panther Gene Ontology tools. RESULTS: Over 110 genes were differentially expressed between LN and healthy control kidney biopsies. Although there was considerable molecular heterogeneity between LN biopsies at diagnosis and flare, for about half the LN patients gene expression from the first LN biopsy clustered with the repeated LN biopsy. However, in all patients, a set of eight interferon alpha-controlled genes had a significantly higher expression in the diagnostic biopsy compared with the flare biopsy. In contrast, nine tumor necrosis factor alpha-controlled genes had higher expression in flare biopsies. CONCLUSIONS: There is significant heterogeneity in immune-gene expression of kidney tissue from LN patients. There are limited but important differences in gene expression between LN flares, which may influence treatment decisions.
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Biopsia/métodos , Expresión Génica , Genes/genética , Inmunidad Innata/genética , Fallo Renal Crónico/patología , Riñón/patología , Nefritis Lúpica/genética , Adulto , Femenino , Humanos , Fallo Renal Crónico/etiología , Fallo Renal Crónico/genética , Nefritis Lúpica/complicaciones , Nefritis Lúpica/patología , Masculino , ARN/genéticaRESUMEN
AIM: To derive a simple risk score to predict the individual risk of major complications for patients undergoing a percutaneous renal biopsy procedure of native kidneys. METHODS: The risk score was derived from a cohort of 1205 adult patients subjected to percutaneous renal biopsy and assigned to training and validation datasets. Factors associated with major complications were derived from univariate analysis and then modelled by stepwise multivariate logistic regression. Based on the odds ratio, independent predictors were assigned a weighted integer. The risk score is calculated from the sum of the integers. RESULTS: The overall incidence of major complications was 3.2%. Independent factors associated with MC were lower pre-biopsy haemoglobin, lower platelets, higher blood urea nitrogen, documented chronic kidney disease features in pre-biopsy ultrasound (US) and the presence of haematoma in the post-biopsy US. A score for pre-biopsy evaluation included the first four predictors and stratified patients in three categories with increasing risk at higher scores (low-risk 0.1%, moderate-risk 3.0% and high-risk 26.1%). The score demonstrated good discriminative power (AUC = 0.872). The addition of post-biopsy US findings increased the discriminative power (AUC = 0.938). A higher post-biopsy risk score was also associated with a higher incidence of MC (low-risk 0.2%, moderate-risk 2.7%, high-risk 16.9%). CONCLUSION: The risk of major complications after a percutaneous renal biopsy can be assessed by a simple risk score calculated from readily available information.
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Biopsia/efectos adversos , Técnicas de Apoyo para la Decisión , Hemorragia/etiología , Enfermedades Renales/patología , Riñón/patología , Adulto , Área Bajo la Curva , Distribución de Chi-Cuadrado , Toma de Decisiones Clínicas , Bases de Datos Factuales , Femenino , Hemorragia/diagnóstico , Hemorragia/terapia , Humanos , Riñón/diagnóstico por imagen , Enfermedades Renales/diagnóstico por imagen , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Valor Predictivo de las Pruebas , Curva ROC , Reproducibilidad de los Resultados , Medición de Riesgo , Factores de Riesgo , Ultrasonografía , Adulto JovenRESUMEN
BACKGROUND: Renal thrombotic microangiopathy (TMA) may be associated with lupus nephritis. Its relationship to other disease factors and its specific effect on prognosis are not precisely known. Evidence regarding these aspects is controversial, and information focusing on kidney-limited TMA in systemic lupus erythematosus (SLE) patients is scarce. OBJECTIVES: The aims of this study were to identify risk factors for renal TMA in patients with lupus nephritis and to determine its impact on clinical outcomes. METHODS: A case-control study was performed. We studied 245 renal biopsies from SLE patients. We included patients with renal TMA, as well as control subjects adjusted for glomerulonephritis class, estimated glomerular filtration rate, activity and chronicity indices, and follow-up time. Serological and clinical features were measured at the time of the biopsy and during follow-up. RESULTS: Twenty-three patients with renal TMA and 21 control subjects were included. There were no differences in Systemic Lupus Erythematosus Disease Activity Index score, end-stage renal disease, or mortality between groups during follow-up. After multivariate analysis, lymphopenia (odds ratio, 10.69; 95% CI, 1.35-84.74) and anti-Ro antibody positivity (odds ratio, 8.96; 95% CI, 1.49-53.57) remained significantly associated with renal TMA. CONCLUSIONS: Lymphopenia and anti-Ro positivity are independent risk factors for renal TMA in SLE patients. This increased risk could be a consequence of the potential role of these factors in endothelial dysfunction and damage. Outcomes were similar for patients with the same estimated glomerular filtration rate and biopsy characteristics, regardless of the presence of TMA.