RESUMEN
Twice-weekly hemodialysis, as part of incremental initiation, has reported benefits including preservation of residual kidney function (RKF). To explore this, we initiated a randomized controlled feasibility trial examining 55 incident hemodialysis patients with urea clearance of 3 ml/min/1.73 m2 or more across four centers in the United Kingdom randomized to standard or incremental schedules for 12 months. Incremental hemodialysis involved twice-weekly sessions, upwardly adjusting hemodialysis dose as RKF was lost, maintaining total (Dialysis+Renal) Std Kt/V above 2. Standard hemodialysis was thrice weekly for 3.5-4 hours, minimum Dialysis Std Kt/V of 2. Primary outcomes were feasibility parameters and effect size of group differences in rate of loss of RKF at six months. Health care cost impact and patient-reported outcomes were explored. Around one-third of patients met eligibility criteria. Half agreed to randomization; 26 received standard hemodialysis and 29 incremental. At 12 months, 21 incremental patients remained in the study vs 12 in the standard arm with no group differences in the urea clearance slope. Ninety-two percent of incremental and 75% of standard arm patients had a urea clearance of 2 ml/min/1.73 m2 or more at six months. Serious adverse events were less frequent in incremental patients (Incidence Rate Ratio 0.47, confidence interval 0.27-0.81). Serum bicarbonate was significantly lower in incremental patients indicating supplementation may be required. There were three deaths in each arm. Blood pressure, extracellular fluid and patient-reported outcomes were similar. There was no signal of benefit of incremental hemodialysis in terms of protection of RKF or Quality of Life score. Median incremental hemodialysis costs were significantly lower compared to standard hemodialysis. Thus, incremental hemodialysis appears safe and cost-saving in incident patients with adequate RKF, justifying a definitive trial.
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Fallo Renal Crónico , Diálisis Renal/métodos , Estudios de Factibilidad , Humanos , Riñón , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/etiología , Fallo Renal Crónico/terapia , Calidad de VidaRESUMEN
INTRODUCTION: Preserving residual kidney function (RKF) may be beneficial to patients on haemodialysis (HD) and it has been proposed that commencing dialysis incrementally rather than three times a week may preserve RKF. In Incremental HD, target dose includes a contribution from RKF, which is added to HD dose, allowing individualisation of the HD prescription. We will conduct a feasibility randomised controlled trial (RCT) comparing incremental HD and conventional three times weekly treatments in incident HD patients. The study is designed also to provide pilot data to allow determination of effect size to power a definitive study. METHODS AND ANALYSIS: After screening to ensure native renal urea clearance >3 mL/min/1.73 m2, the study will randomise 54 patients within 3 months of HD initiation to conventional in-centre thrice weekly dialysis or incremental in-centre HD commencing 2 days a week. Subjects will be followed up for 12 months. The study will be carried out across four UK renal centres.The primary outcome is to evaluate the feasibility of conducting a definitive RCT and to estimate the difference in rate of decline of RKF between the two groups at 6 and 12 months time points. Secondary outcomes will include the impact of dialysis intensity on vascular access events, major adverse cardiac events and survival. Impact of dialysis intensity on patient-reported outcomes measures, cognition and frailty will be assessed using EQ-5D-5L, PHQ-9, Illness Intrusiveness Rating Score, Montreal Cognitive assessment and Clinical Frailty Score. Safety outcomes include hospitalisation, fluid overload episodes, hyperkalaemia events and vascular access events.This study will inform the design of a definitive study, adequately powered to determine whether RKF is better preserved after incremental HD initiation compared with conventional initiation. ETHICS AND DISSEMINATION: Ethics approval has been granted by Cambridge South Research Ethics Committee, United Kingdom(REC17/EE/0311). Results will be disseminated via peer-reviewed publication. TRIAL REGISTRATION NUMBER: NCT03418181.
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Fallo Renal Crónico , Diálisis Renal , Cognición , Estudios de Factibilidad , Humanos , Riñón , Fallo Renal Crónico/terapia , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Reino UnidoRESUMEN
BACKGROUND: Monoclonal immunoglobulin deposition disease (MIDD) is a rare condition accounting for < 1% of histopathological diagnoses made on kidney biopsy1. The best outcomes are seen in those diagnosed and treated promptly, but delay to diagnosis is common with the largest series reporting a median time from onset of renal impairment to diagnosis of 12 months2. Here, we report a case of the heavy chain subset of MIDD presenting with positive anti-glomerular basement membrane (anti-GBM) antibodies obscuring the true diagnosis. CASE PRESENTATION: Here, we present a challenging case presenting with oedema, haematoproteiuria, and new renal impairment. Anti-GBM antibodies were positive and prompted treatment as atypical anti-GBM disease. However, they were ultimately proven to be monoclonal and secondary to myeloma. The final diagnosis facilitated effective myeloma treatment which led to complete remission and independence from renal replacement therapy. CONCLUSIONS: This case reinforces the importance of comprehensive histopathological and haematological assessment in making the correct diagnosis. Here it facilitated effective treatment and recovery of renal function.
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Enfermedad por Anticuerpos Antimembrana Basal Glomerular/diagnóstico , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Glomerulonefritis/diagnóstico , Inmunoglobulina G/inmunología , Fallo Renal Crónico/terapia , Mieloma Múltiple/diagnóstico , Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Bortezomib/uso terapéutico , Dexametasona/uso terapéutico , Diagnóstico Diferencial , Edema/etiología , Glomerulonefritis/etiología , Glomerulonefritis/inmunología , Glomerulonefritis/patología , Hematuria/etiología , Humanos , Cadenas Pesadas de Inmunoglobulina/inmunología , Fallo Renal Crónico/etiología , Fallo Renal Crónico/patología , Masculino , Persona de Mediana Edad , Mieloma Múltiple/complicaciones , Mieloma Múltiple/inmunología , Mieloma Múltiple/terapia , Proteinuria/etiología , Inducción de Remisión , Diálisis Renal , Terapia de Reemplazo Renal , Trasplante de Células MadreRESUMEN
Unlike AL amyloid and cast nephropathy, the long-term outcomes of monoclonal gammopathy of renal significance (MGRS) patients with other renal histopathologies remain unclear. It is uncertain if early intervention improves renal outcomes, because of a lack of evidence from prospective studies. In this retrospective study, we examined outcomes of 41 MGRS patients treated between 2004 and 2017 across five centres: four in the UK and one in the Republic of Ireland. The primary outcome measure was renal survival estimated by Kaplan-Meier product-limit method. Thirty-three patients (80·5%) were kappa light chain (LC) restricted. Twenty-seven patients (65·9%) presented with LC deposition disease on renal histology. At 24 months follow-up, estimated renal survival was 81·6% for the whole cohort. The estimated overall survival was 80·3% at 48 months. At 24 months, patients who had chronic kidney disease (CKD) stage 2-3b at diagnosis showed an estimated renal survival of 100% compared to 80·7% in those with CKD stage 4-5 at diagnosis (P = 0·04). Poorer outcomes in MGRS patients were historically attributed to delayed diagnosis due to small plasma cell clones, as well as the need for renal biopsy.
Asunto(s)
Enfermedades Renales/etiología , Gammopatía Monoclonal de Relevancia Indeterminada/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Riñón/patología , Enfermedades Renales/patología , Masculino , Persona de Mediana Edad , Gammopatía Monoclonal de Relevancia Indeterminada/patologíaRESUMEN
BACKGROUND AND OBJECTIVES: Large studies on long-term kidney outcome in patients with anti-glomerular basement membrane (anti-GBM) GN are lacking. This study aimed to identify clinical and histopathologic parameters that predict kidney outcome in these patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective analysis included a total of 123 patients with anti-GBM GN between 1986 and 2015 from six centers worldwide. Their kidney biopsy samples were classified according to the histopathologic classification for ANCA-associated GN. Clinical data such as details of treatment were retrieved from clinical records. The primary outcome parameter was the occurrence of ESRD. Kidney survival was analyzed using the log-rank test and Cox regression analyses. RESULTS: The 5-year kidney survival rate was 34%, with an improved rate observed among patients diagnosed after 2007 (P=0.01). In patients with anti-GBM GN, histopathologic class and kidney survival were associated (P<0.001). Only one of 15 patients with a focal class biopsy sample (≥50% normal glomeruli) developed ESRD. Patients with a sclerotic class biopsy sample (≥50% globally sclerotic glomeruli) and patients with 100% cellular crescents did not recover from dialysis dependency at presentation. In multivariable analysis, dialysis dependency at presentation (hazard ratio [HR], 3.17; 95% confidence interval [95% CI], 1.59 to 6.32), percentage of normal glomeruli (HR, 0.97; 95% CI, 0.95 to 0.99), and extent of interstitial infiltrate (HR, 2.02; 95% CI, 1.17 to 3.50) were predictors of ESRD during follow-up. CONCLUSIONS: Dialysis dependency, low percentage of normal glomeruli, and large extent of interstitial infiltrate are associated with poor kidney outcome in anti-GBM GN. Kidney outcome has improved during recent years; the success rate doubled after 2007. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017_11_21_CJASNPodcast_18_1_v.mp3.
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Enfermedad por Anticuerpos Antimembrana Basal Glomerular/inmunología , Autoanticuerpos/inmunología , Membrana Basal/inmunología , Glomérulos Renales/inmunología , Adulto , Anciano , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/diagnóstico , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/fisiopatología , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/terapia , Biopsia , Progresión de la Enfermedad , Femenino , Humanos , Fallo Renal Crónico/inmunología , Fallo Renal Crónico/patología , Fallo Renal Crónico/fisiopatología , Fallo Renal Crónico/terapia , Glomérulos Renales/patología , Glomérulos Renales/fisiopatología , Masculino , Persona de Mediana Edad , Pronóstico , Diálisis Renal , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: Patients with anti-glomerular basement membrane (GBM) disease are at increased risk of morbidity and mortality from renal failure, pulmonary haemorrhage or complications of treatment. One-third also have circulating anti-neutrophil cytoplasmic antibodies (ANCA). The aim of this study was to determine the clinicopathologic predictors of patient and renal outcomes in anti-GBM disease with or without ANCA. METHODS: Retrospective review of 43 patients diagnosed with anti-GBM disease over 20 years in two centres, including nine with dual anti-GBM and ANCA positivity. Renal biopsies from 27 patients were scored for the presence of active and chronic lesions. RESULTS: Dual-positive patients were almost 20 years older than those with anti-GBM positivity alone (P = 0.003). The overall 1-year patient and renal survivals were 88 and 16%, respectively. Oligoanuria at diagnosis was the strongest predictor of mortality; none of the 16 patients without oligoanuria died. In a Cox regression model excluding oligoanuria, age was the only other independent predictor of survival. Pulmonary haemorrhage and dialysis dependence did not influence mortality. Thirty-five of the forty-three (81%) patients required dialysis at presentation, including all nine dual-positive patients. Of them, only two (5.7%) regained renal function at 1 year. By logistic regression, oligoanuria at diagnosis and percentage of crescents were independent predictors of dialysis independence at 3 months. However, in biopsied patients, the presence of crescents (>75%) added little to the presence of oligoanuria in predicting dialysis independence. Histological activity and chronicity indices did not predict renal outcome. Two of the nine (22%) dual-positive patients relapsed compared with none of the anti-GBM alone patients. Seven patients received kidney transplants without disease recurrence. CONCLUSIONS: Oligoanuria is the strongest predictor of patient and renal survival while percentage of glomerular crescents is the only pathologic parameter associated with poor renal outcome in anti-GBM disease. Kidney biopsy may not be necessary in oligoanuric patients without pulmonary haemorrhage.
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Enfermedad por Anticuerpos Antimembrana Basal Glomerular/diagnóstico , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Autoanticuerpos/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/inmunología , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/mortalidad , Biopsia , Femenino , Hemorragia/complicaciones , Humanos , Riñón/fisiopatología , Fallo Renal Crónico/mortalidad , Glomérulos Renales/inmunología , Trasplante de Riñón , Enfermedades Pulmonares/complicaciones , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Recurrencia , Diálisis Renal , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by recurrent arterial or venous thrombosis and/or pregnancy losses, in the presence of persistently elevated levels of anticardiolipin antibodies (aCL) and/or evidence of circulating lupus anticoagulant (LA). The kidney is a major target organ in both primary and secondary APS. With the expanding spectrum of renal diseases associated with APS, and the impact of APS in ESRD care, this subject is of increasing relevance to nephrologists. This review describes the various clinical manifestations and histological features of this syndrome, with reference to the kidney.
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Síndrome Antifosfolípido/complicaciones , Enfermedades Renales/etiología , Síndrome Antifosfolípido/tratamiento farmacológico , Síndrome Antifosfolípido/fisiopatología , Humanos , Hipertensión/etiología , Riñón/fisiopatología , Trasplante de Riñón , Nefritis Lúpica/etiología , Diálisis Renal , Trombosis/etiologíaRESUMEN
Membranoproliferative glomerulonephritis is an uncommon kidney disorder characterized by mesangial cell proliferation and structural changes in glomerular capillary walls. It can be subdivided into idiopathic and secondary forms, which are differentially diagnosed by a review of clinical features, laboratory data, and renal histopathology. Three types-I, II, and III-have been defined by pathologic features. All three types are associated with hypocomplementemia, but they manifest somewhat different mechanisms of complement activation. Type II, also known as "dense deposit disease", is associated with the presence of C3-nephritic factor. Membranoproliferative glomerulonephritis primarily affects children and young adults, with patients presenting with nephrotic or nephritic syndrome or with asymptomatic renal disease. This type of glomerulonephritis often progresses slowly to end-stage renal disease, and it tends to recur after renal transplantation, especially type II. The efficacy of various forms of treatment remains controversial; however, long-term steroid treatment seems to be effective in children with nephrotic-range proteinuria. Improvement in renal outcomes largely relies on the evaluation of more selective agents in carefully controlled studies.
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Glomerulonefritis Membranoproliferativa/tratamiento farmacológico , Glomerulonefritis Membranoproliferativa/patología , Adulto , Niño , Activación de Complemento , Factor Nefrítico del Complemento 3 , Glomerulonefritis/patología , Glomerulonefritis Membranoproliferativa/diagnóstico , Humanos , Riñón/patología , Enfermedades Renales/patología , Fallo Renal Crónico/patología , Glomérulos Renales/patología , Trasplante de RiñónRESUMEN
Renal amyloidosis is a rare and intractable disease that accounts for 0.2% of the original kidney diseases of dialysis patients in Japan. However, the number of patients with renal amyloidosis seems to be increasing in recent years. There have been some new concepts focusing on the mechanism of amyloidogenesis, such as molecular chaperones, seeding mechanism, and genetic polymorphisms of precursor protein. Clinical and histological features of renal amyloidosis vary according to the type. Significantly higher levels of urinary protein excretion are seen in the AL type, whereas microscopic haematuria is more prominent in the AA type. Histologically, amyloid deposition of AL type has stronger predilection for GBM than mesangium, and spicule formation is more frequently observed. In contrast, AA type has a higher affinity to TBM and interstitial area. For the histological diagnosis of renal amyloidosis, plural staining methods including Congo-red, Daylon and thioflavin-T stains are available. Combinations of these staining methods are necessary for establishing the precise diagnosis. The more recent and intensive treatments for renal amyloidosis are expected to improve patient outcome. For AL amyloidosis, high-dose melphalan plus high-dose dexamethasone or VAD, in conjunction with bone marrow stem cells transplantation, have shown a definitive effect on reducing urinary protein excretion. The biological agent, tumor necrosis factor (TNF alpha) blocker, improves the renal function in AA-type renal amyloidosis, as well as suppresses the inflammatory reactions in patients with rheumatoid arthritis. Clinical advances have been made in various aspects of renal amyloidosis.
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Amiloidosis/complicaciones , Enfermedades Renales/etiología , Riñón/patología , Amiloidosis/epidemiología , Amiloidosis/etiología , Amiloidosis/patología , Amiloidosis/terapia , Animales , Biopsia , Humanos , Enfermedades Renales/epidemiología , Enfermedades Renales/patología , Enfermedades Renales/terapia , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: This work aimed to examine the predictive value for death of various clinical variables after long-term hemodialysis (HD). DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: A total of 947 patients (597 men and 350 women, aged 21 to 93 yr) who were undergoing maintenance HD in Niigata, Japan, were stratified into two cohorts: Those with >10 yr of prior HD at study enrollment (n = 391) and those with < or =10 yr of previous therapy (n = 556). The survival of patients was examined for up to 40 mo (1999 to 2003) with the Cox proportional hazards model. Baseline clinical and dialysis data and serum biochemistries were used as independent variables. For adjustment for bias in patient selection, patient survival in either cohort was analyzed separately. RESULTS: In patients with >10 yr of HD, high pulse pressure, cerebrovascular disease, low serum creatinine, and low Kt/V values were the mortality risk predictors, whereas for those with < or =10 yr of HD, age and cerebrovascular disease were independent risk predictors for death. Diabetes, coronary artery disease, serum albumin, and C-reactive protein were NS predictors in those with long-term HD. CONCLUSIONS: Providing adequate dosage of dialysis and achieving a better control of pulse pressure may further improve survival in selected patients who had undergone HD for >10 yr.
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Diálisis Renal/mortalidad , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Factores de Riesgo , Factores de TiempoRESUMEN
BACKGROUND/AIMS: Our previous comprehensive analysis of the genes expressed in kidneys with anti-glomerular basement membrane (GBM) nephritis using DNA microarrays showed that SM22alpha was one of the highly expressed genes. SM22alpha is a 22-kDa cytoskeletal protein that is exclusively expressed in smooth muscle cells. We investigated the localization of SM22alpha at mRNA and protein levels, and its pathological significance in anti-GBM nephritis kidneys. METHODS: Northern blot analysis, in situ hybridization, immunohistochemistry and double immunofluorescence studies were performed. The specific antibody (Ab) against SM22alpha was obtained by immunization of rabbits with recombinant rat SM22alpha protein. RESULTS: SM22alpha mRNA expression was upregulated in kidneys and inducibly expressed in the parietal and visceral glomerular epithelial cells in anti-GBM nephritis kidneys. Immunohistochemistry with anti-SM22alpha Ab showed that SM22alpha protein was localized in the same series of cells. Double immunofluorescence with anti-SM22alpha and anti-glomerular cell markers demonstrated that SM22alpha might be expressed in epithelial cells of injured glomeruli. In visceral epithelial cells, SM22alpha might be expressed in cells in which podocyte specific markers, podocalyxin and nephrin were lost. CONCLUSION: The injured glomerular epithelial cells in anti-GBM nephritis might undergo structural and functional alterations, including the expression of a smooth muscle marker, SM22alpha.
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Membrana Basal/inmunología , Células Epiteliales/metabolismo , Glomerulonefritis/metabolismo , Glomérulos Renales/metabolismo , Proteínas de Microfilamentos/metabolismo , Proteínas Musculares/metabolismo , Animales , Biomarcadores/metabolismo , Modelos Animales de Enfermedad , Células Epiteliales/patología , Regulación de la Expresión Génica , Glomerulonefritis/inducido químicamente , Glomerulonefritis/patología , Inmunoglobulina G , Glomérulos Renales/patología , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Proteínas de Microfilamentos/genética , Proteínas Musculares/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Fenotipo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Distribución Aleatoria , Ratas , Ratas Endogámicas WKY , Sialoglicoproteínas/genética , Sialoglicoproteínas/metabolismoRESUMEN
We describe the case of a 44-year-old woman who presented with renovascular hypertension caused by primary leiomyosarcoma of the abdominal aorta that had metastasized into the renal arteries. Despite an extensive radiological evaluation, the diagnosis was mistaken first for Takayasu's arteritis and then for retroperitoneal hematoma or neoplasm. The patient developed renal failure due to bilateral renal infarction, and died 3 months after her initial presentation with ischemic colitis. Postmortem examination confirmed the diagnosis.
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Aorta Abdominal/patología , Hipertensión Renovascular/etiología , Leiomiosarcoma/complicaciones , Neoplasias Vasculares/complicaciones , Adulto , Diagnóstico Diferencial , Femenino , Humanos , Hipertensión Renovascular/diagnóstico , Hipertensión Renovascular/patología , Leiomiosarcoma/diagnóstico , Leiomiosarcoma/patología , Células Neoplásicas Circulantes/patología , Arteria Renal/patología , Neoplasias Vasculares/diagnóstico , Neoplasias Vasculares/patologíaRESUMEN
Collagenofibrotic glomerulopathy is an idiopathic glomerular disease characterized by massive accumulation of atypical type III collagen fibrils within the mesangial matrix and subendothelial space and marked increase in serum type III procollagen peptide levels. The disease is extremely rare, with most cases reported in Japan. The cause and pathogenesis are entirely elusive. Some cases were described in families; hence, a genetic mode of transmission, mostly by an autosomal recessive trait, has been assumed. Controversy exists about whether the glomerulopathy is a primary renal disease or manifestation of systemic disease. Proteinuria is a cardinal manifestation of this disease. Clinically, patients present with edema and hypertension and often progress to end-stage renal disease. A definite diagnosis can be established when typical histological findings are supported by immunohistochemistry for specific collagen types and electron microscopy with special staining methods. No specific treatment is available.
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Colágeno Tipo III/metabolismo , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Glomérulos Renales , Diagnóstico Diferencial , Fibrosis , Técnica del Anticuerpo Fluorescente , Mesangio Glomerular/metabolismo , Mesangio Glomerular/patología , Humanos , Enfermedades Renales/complicaciones , Enfermedades Renales/etiología , Microscopía Electrónica , Microscopía Fluorescente , Fragmentos de Péptidos/sangre , Procolágeno/sangre , Enfermedades RarasRESUMEN
A 48-year-old man presented with malignant hypertension and massive proteinuria. Renal angiography showed complete obstruction of the left renal artery and 99mTc-mercaptoacetylglycine (MAG3) renography showed a nonfunctioning left kidney. Percutaneous transluminal renal angioplasty of the left renal artery was unsuccessful; hence, the patient underwent left nephrectomy because of uncontrolled hypertension and proteinuria. Histological examination of a right kidney specimen revealed lesions of focal segmental glomerulosclerosis with benign nephrosclerosis. In contrast, histology of the left kidney showed typical ischemic kidney with hypertrophy of arteriolar smooth muscle cells. The patient responded favorably to the nephrectomy, as his blood pressure and urinary protein dramatically decreased with no antihypertensive medication. This case illustrates the heterogeneous effect of the renin-angiotensin system on either kidney in patients with renovascular hypertension due to unilateral renal artery stenosis.
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Glomeruloesclerosis Focal y Segmentaria/complicaciones , Hipertensión Renovascular/complicaciones , Síndrome Nefrótico/etiología , Glomeruloesclerosis Focal y Segmentaria/diagnóstico , Humanos , Hipertensión Renovascular/diagnóstico , Hipertensión Renovascular/cirugía , Riñón/patología , Riñón/fisiopatología , Masculino , Persona de Mediana Edad , Nefrectomía , Nefroesclerosis/patología , Obstrucción de la Arteria Renal/patologíaRESUMEN
BACKGROUND: Complement 4d (C4d) deposition in the peritubular capillary (PTC) in the kidney allograft is a useful diagnostic marker for humoral rejection. C4d is produced not only by the classical pathway but also by the lectin pathway of the complement activation cascade. We have recently reported the in situ role of the later phase of the complement cascade in renal allografts with C4d deposition; however, the initial process prior to C4d deposition is yet to be resolved. METHODS: To clarify the early phases of the complement activation cascade, we evaluated the deposition of initial proteins of the above two pathways; IgG, IgM, mannose-binding lectin (MBL), H-ficolin, L-ficolin, MBL-associated serine protease (MASP)-1 and MASP-2 in kidney allografts with PTC C4d deposition. RESULTS: Sixty kidney allograft specimens were divided into two groups on the basis of the presence of C4d deposition in PTC. The C4d-positive group (n = 18) included nine ABO-identical and nine ABO-incompatible cases, and the C4d-negative group (n = 42) had 34 ABO-identical and eight ABO-compatible (but not identical) cases. In the C4d-positive group, 16 of 18 cases showed diffuse H-ficolin and IgM deposition in PTC. In contrast, H-ficolin and IgM were not detected in PTC in the C4d-negative group. Other initial proteins were not detected in all cases. CONCLUSIONS: Our study suggested for the first time that the lectin pathway activated by H-ficolin may be involved in C4d deposition on PTC in the kidney allograft.
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Complemento C4b/metabolismo , Rechazo de Injerto/metabolismo , Trasplante de Riñón/inmunología , Túbulos Renales/metabolismo , Lectina de Unión a Manosa/metabolismo , Fragmentos de Péptidos/metabolismo , Adulto , Biomarcadores/metabolismo , Biopsia , Femenino , Estudios de Seguimiento , Rechazo de Injerto/patología , Humanos , Inmunohistoquímica , Técnicas In Vitro , Trasplante de Riñón/patología , Túbulos Renales/patología , Masculino , Estudios Retrospectivos , Trasplante HomólogoRESUMEN
BACKGROUND: The etiology of encephalopathy in uremic patients is multiple. We recently encountered a novel type of encephalopathy which occurred exclusively in patients with chronic kidney diseases after ingestion of a mushroom called Sugihiratake. While the exact etiology of this encephalopathy remained mysterious, we aimed to describe its clinical features. METHODS: A total of 32 patients with chronic kidney diseases who had presented with encephalopathy following ingestion of Sugihiratake were enrolled from seven prefectures in Japan., with 24 of the 32 patients undergoing regular hemodialysis. The patient's clinical data were from surveillance by The Japanese Society of Nephrology. RESULTS: There was a significant association between Sugihiratake ingestion and the occurrence of encephalopathy in 524 hemodialysis patients questioned for a recent ingestion of this mushroom (P= 0.0006). The latent asymptomatic period before the onset of symptoms varied from 1 to 31 days (mean 9.1 +/- 7.3) days. The patient's symptoms consisted of disturbed consciousness in 30 patients (93.8%), convulsions in 25 (78.1%), myoclonus in 15 (46.9%), dysarthria in ten (31.3%), ataxia in eight (25.0%), paresis or paralysis in seven (21.9%), and skin parasthesia in two patients (6.3%). Nine (27.2%) patients died, mostly due to respiratory failure. The other patients were either discharged or still in hospitals with various degrees of clinical improvement. CONCLUSION: Patients with chronic kidney diseases are at risk of having serious encephalopathy following Sugihiratake ingestion and must refrain from eating it. Physicians, in those parts of the world, where this mushroom harvesting is common, should be aware of this complication.
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Encefalopatías/etiología , Fallo Renal Crónico/complicaciones , Intoxicación por Setas , Agaricales , Anciano , Anciano de 80 o más Años , Encefalopatías/diagnóstico , Encefalopatías/mortalidad , Cryptomeria , Femenino , Humanos , Japón/epidemiología , Fallo Renal Crónico/mortalidad , Masculino , Persona de Mediana Edad , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
To clarify the compensatory hemodynamic alterations in the interstitium of renal allograft biopsies with chronic rejection, we evaluated the morphological changes in the peritubular capillary (PTC) network. Seven renal biopsy specimens from recipients with chronic rejection presenting with elevation of serum creatinine of 1.9 +/- 0.5 mg/dL were examined. Renal biopsy specimens from their counterpart donors were used as normal controls. In each specimen, non-pathological interstitial areas without fibrosis, tubular atrophy or cell infiltration were compared with pathological areas (PA) showing fibrosis and/or tubular atrophy using a computer image analysis. Morphological measurements revealed that the mean cut surface area of the PTC in the non-pathological and pathological interstitial areas in the recipient biopsies were significantly larger than that of the normal controls (p < 0.001 and 0.001, respectively). In the recipient biopsies, both of the mean cut surface areas of the tubules and PTC in the non-pathological areas were significantly higher than those in the PA (p < 0.001). The mean glomerular diameter in the recipient biopsies was also significantly higher than that of the donors (p < 0.01). In this study, we provided pathological evidence for the compensatory interstitial and glomerular hemodynamic alterations in kidney graft with chronic rejection and the condition as single kidney.
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Rechazo de Injerto/patología , Rechazo de Injerto/fisiopatología , Trasplante de Riñón/inmunología , Túbulos Renales/irrigación sanguínea , Circulación Renal/fisiología , Adulto , Anciano , Capilares/patología , Estudios de Casos y Controles , Enfermedad Crónica , Espacio Extracelular/fisiología , Humanos , Procesamiento de Imagen Asistido por Computador , Persona de Mediana EdadAsunto(s)
Cadenas Ligeras de Inmunoglobulina , Cadenas gamma de Inmunoglobulina , Trasplante de Riñón/efectos adversos , Paraproteinemias/etiología , Amiloidosis/diagnóstico , Amiloidosis/etiología , Amiloidosis/terapia , Humanos , Masculino , Persona de Mediana Edad , Paraproteinemias/diagnóstico , Paraproteinemias/terapia , RecurrenciaRESUMEN
BACKGROUND: Osteopontin (OPN) is a potent chemoattractant for mononuclear cells that is up-regulated in various inflammatory states of the kidney. The role of OPN and its expression in human renal allograft rejection are unknown. METHODS: We examined by immunohistochemistry and in situ hybridization, renal biopsies from patients with acute rejection (N= 22), protocol biopsies without rejection (N= 9), and perioperative donor biopsies (N= 35) for intrarenal expression of OPN, and its correlation with clinical, laboratory, and histopathologic parameters. In the rejection biopsies, interstitial monocyte/macrophage infiltration, tubulointerstitial cell proliferation/regeneration and apoptosis were investigated. RESULTS: In the majority of rejection biopsies, OPN expression by proximal tubular epithelium was widespread, and tended to be enhanced in the tubules surrounded by numerous inflammatory cells. Conversely, in patients that did not experience episodes of rejection and in donor biopsies, OPN expression by proximal tubules was nil or weak. OPN mRNA was colocalized with its translated protein in the renal tubular epithelium. OPN expression positively correlated with the degree of interstitial inflammation (P < 0.05), CD68+ monocyte infiltration (P < 0.01), Ki-67+ regenerating tubular and interstitial cells (P < 0.05 and P < 0.005, respectively), but not with terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL)-positive apoptotic tubular cells. CONCLUSION: These data suggest that inducible expression of OPN in the tubular epithelium may have a pathogenic role in acute renal allograft rejection by mediating interstitial monocyte infiltration and possibly tubular regeneration.