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1.
Klin Padiatr ; 232(5): 228-248, 2020 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-32659844

RESUMO

This consensus-based guideline was developed by all relevant German pediatric medical societies. Ultrasound is the standard imaging modality for pre- and postnatal kidney cysts and should also exclude extrarenal manifestations in the abdomen and internal genital organs. MRI has selected indications. Suspicion of a cystic kidney disease should prompt consultation of a pediatric nephrologist. Prenatal management must be tailored to very different degrees of disease severity. After renal oligohydramnios, we recommend delivery in a perinatal center. Neonates should not be denied renal replacement therapy solely because of their age. Children with unilateral multicystic dysplastic kidney do not require routine further imaging or nephrectomy, but long-term nephrology follow-up (as do children with uni- or bilateral kidney hypo-/dysplasia with cysts). ARPKD (autosomal recessive polycystic kidney disease), nephronophthisis, Bardet-Biedl syndrome and HNF1B mutations cause relevant extrarenal disease and genetic testing is advisable. Children with tuberous sclerosis complex, tumor predisposition (e. g. von Hippel Lindau syndrome) or high risk of acquired kidney cysts should have regular ultrasounds. Even asymptomatic children of parents with ADPKD (autosomal dominant PKD) should be monitored for hypertension and proteinuria. Presymptomatic diagnostic ultrasound or genetic examination for ADPKD in minors should only be done after thorough counselling. Simple cysts are very rare in children and ADPKD in a parent should be excluded. Complex renal cysts require further investigation.


Assuntos
Cistos/patologia , Neoplasias Renais , Rim Policístico Autossômico Dominante , Rim Policístico Autossômico Recessivo , Guias de Prática Clínica como Assunto , Criança , Feminino , Humanos , Recém-Nascido , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Masculino , Rim Policístico Autossômico Dominante/diagnóstico , Rim Policístico Autossômico Dominante/genética , Rim Policístico Autossômico Dominante/terapia , Rim Policístico Autossômico Recessivo/diagnóstico , Rim Policístico Autossômico Recessivo/genética , Rim Policístico Autossômico Recessivo/terapia , Gravidez , Sociedades Médicas
2.
J Stroke Cerebrovasc Dis ; 28(9): e129-e131, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31296478

RESUMO

Intracranial artery dissection secondary to autosomal dominant polycystic kidney disease is far less common than cerebral aneurysm. A 55-year-old man presented a sudden onset of headache and disturbed consciousness caused by ischemic stroke in the bilateral frontal lobes with minor subarachnoid hemorrhage. The bilateral anterior cerebral arteries were firstly occluded and re-perfused with irregular narrowing and dilation in 3 days after stroke onset, indicating dissection. He was diagnosed with autosomal dominant polycystic kidney disease by abdominal CT findings and by his family history though his renal function was almost normal. Dissection in the anterior cerebral artery has not been reported previously, while some cases with dissection in the vertebral and extracranial arteries were reported in autosomal dominant polycystic kidney disease. His family also had a history of aortic dissection and subarachnoid hemorrhage. Intracranial artery dissection may be a manifestation of systemic arteriopathy with familial clustering in autosomal dominant polycystic kidney disease. Strict antihypertensive treatment is needed in these cases.


Assuntos
Aneurisma Dissecante/etiologia , Aneurisma Intracraniano/etiologia , Rim Policístico Autossômico Dominante/complicações , Aneurisma Dissecante/diagnóstico por imagem , Aneurisma Dissecante/terapia , Angiografia Cerebral/métodos , Tratamento Conservador , Imagem de Difusão por Ressonância Magnética , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/terapia , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rim Policístico Autossômico Dominante/diagnóstico , Tomografia Computadorizada por Raios X
3.
Iran J Kidney Dis ; 13(3): 151-164, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31209188

RESUMO

The functional and structural disease with autosomal dominant inheritance (ADPKD) shows a poly cystic nature is described by the presence of epithelial cysts in the human renal parenchyma. There are no standard and reliable biomarkers for the detection of ADPKD in early stages which delays the therapeutic approaches. Ideal biomarkers of ADPKD, should have high sensitivity, specificity, and excellent association with disease pathogenesis and development. Both in vitro cellular and in vivo studies on animal models proved the significant roles of miRNAs in the course of ADPKD. In addition, different studies have explored miRNAs up or down regulation both in renal tissue and extracellular fluids in ADPKD which represent novel indicators applicable for diagnosis or targeted therapy. Since urine is a non-invasive, easily accessible sample for ADPKD, it could be the best sample for diagnosis. Additionally, due to early action of miRNAs for regulation the gene expression or because of their unique chemical properties, detectable urine miRNAs can be employed as appropriate biomarkers for timely diagnosis or intensive care of the progression of renal destruction or response to treatment. In this review, the specific microRNAs involved in the pathogenesis of PKD will be discussed with a particular focus on extracellular miRNAs with possibility for application as biomarkers.


Assuntos
MicroRNAs/genética , MicroRNAs/urina , Rim Policístico Autossômico Dominante/genética , RNA Mensageiro/genética , Animais , Biomarcadores/urina , Modelos Animais de Doenças , Progressão da Doença , Humanos , Camundongos , Rim Policístico Autossômico Dominante/diagnóstico , Rim Policístico Autossômico Dominante/urina
4.
Br J Radiol ; 92(1098): 20190078, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31039325

RESUMO

Autosomal dominant polycystic kidney disease (ADPKD) is the most common renal genetic disorder and a leading cause of end stage renal failure (ESRF) affecting over 12 million people worldwide. Whilst the mainstay of diagnosis has historically favoured the imaging domain, the progression of disease was until very recently thought to be best monitored via biochemical analysis, i.e. measurement of estimated glomerular filtration rate. Imaging modalities such as sonography, CT and MRI have more recently proven to be key in monitoring disease progression. As much as half of the renal parenchyma can be lost with no real derangement in renal function. Tolvaptan, a vasopressin antagonist has been shown to slow disease progression and preserve renal function. Here we discuss at length the pathogenesis of ADPKD, the various diagnostic challenges surrounding its evaluation, new treatment options and monitoring of disease progression via serial imaging. We also propose monitoring of the efficacy of Tolvaptan at slowing the rate of deterioration in renal function in patients with ADPKD through MRI guided volumetric analysis of the kidneys.


Assuntos
Rim Policístico Autossômico Dominante/tratamento farmacológico , Antagonistas dos Receptores de Hormônios Antidiuréticos/uso terapêutico , Carcinoma de Células Renais/etiologia , Cistos/etiologia , Diagnóstico Diferencial , Diagnóstico por Imagem , Progressão da Doença , Humanos , Cálculos Renais/etiologia , Neoplasias Renais/etiologia , Rim Policístico Autossômico Dominante/diagnóstico , Rim Policístico Autossômico Dominante/etiologia , Tolvaptan/uso terapêutico
5.
Clin Exp Nephrol ; 23(9): 1130-1140, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31134465

RESUMO

BACKGROUND: Overweight and obesity were recently associated with a poor prognosis in patients with autosomal dominant polycystic kidney disease (ADPKD). Whether the metabolic consequences of obesity as defined by the metabolic syndrome (MS) are also linked with disease progression remains untested. METHODS: Eligible ADPKD patients with different stages of CKD (n = 105) and 105 non-diabetic controls matched for CKD stage were enrolled in the study. Groups were evaluated at baseline for presence of MS, blood markers of metabolism, homeostasis model assessment of insulin resistance (HOMA-IR) score, and biochemical markers of inflammation (hs-CRP, IL-1ß, IL-6, TNF-α and PON-1). MS was defined according to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III). Patients were followed for 12 months and progression defined as a decrease in baseline eGFR > 10%. RESULTS: MS and hypertension were more prevalent amongst ADPKD patients than in the control group. Meanwhile, markers of inflammation such as hs-CRP (3.63 [3.45-5.17] vs. 4.2 [3.45-8.99] mg/dL; p = 0.014), IL-6 (21.65 [14.1-27.49] vs. 24.9 [16.23-39.4] pg/mL; p = 0.004) and IL-1ß (21.33 [15.8-26.4] vs. 26.78 [18.22-35] pg/mL; p < 0.001) levels were all more elevated in ADPKD patients than in non-diabetic CKD subjects. In multivariate analysis having a truncating PKD1 mutation predicted (OR 1.25 [1.09-1.43]; p = 0.002) fulfilling the MS criteria. Finally, ADPKD patients fulfilling MS criteria had a significantly more rapid progression during 12 months of follow-up than did those that did not (OR 3.28 [1.09-9.87]; p = 0.035). CONCLUSIONS: Our data supports the notion that dysmetabolisms part of the ADPKD phenotype and associated with a poor outcome, especially in patients with a truncating PKD1 mutation.


Assuntos
Metabolismo Energético , Mediadores da Inflamação/sangue , Síndrome Metabólica/epidemiologia , Mutação , Rim Policístico Autossômico Dominante/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Canais de Cátion TRPP/genética , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Progressão da Doença , Feminino , Predisposição Genética para Doença , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/genética , Pessoa de Meia-Idade , Fenótipo , Rim Policístico Autossômico Dominante/diagnóstico , Rim Policístico Autossômico Dominante/genética , Prevalência , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/genética , Fatores de Risco , Fatores de Tempo , Turquia
6.
BMC Nephrol ; 20(1): 148, 2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-31039757

RESUMO

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is thought to affect about 1 in 1000 people in the UK. ADPKD causes a progressive decline in kidney function, with kidney failure tending to occur in middle age. Children and young people with ADPKD may not have any symptoms. However they may have high blood pressure, which may accelerate progression to later stages of chronic kidney disease.There is uncertainty and variation in how health professionals manage children and young people with confirmed or a family history of ADPKD, because of a lack of evidence. For example, health professionals may be unsure about when to test children's blood pressure and how often to monitor it in the hospital clinic or at the GP. They may have different approaches in recommending scanning or genetic testing for ADPKD in childhood, with some recommending waiting until the young person is mature enough to make this decision his or herself.This guideline is intended to help families affected by ADPKD by making sure that: health professionals with specialist knowledge in ADPKD offer you information on inheritance and potential benefits and harms of testing for ADPKD. the decision to test and the method of testing for ADPKD in children and young people is shared between you or your family and the health professionals blood pressure assessment is undertaken regularly in children and young people at risk of developing ADPKD.


Assuntos
Monitorização Ambulatorial da Pressão Arterial , Testes Genéticos/métodos , Hipertensão , Anamnese/métodos , Rim Policístico Autossômico Dominante , Insuficiência Renal , Adolescente , Doenças Assintomáticas , Monitorização Ambulatorial da Pressão Arterial/métodos , Monitorização Ambulatorial da Pressão Arterial/normas , Criança , Humanos , Hipertensão/diagnóstico , Hipertensão/etiologia , Monitorização Fisiológica/métodos , Rim Policístico Autossômico Dominante/complicações , Rim Policístico Autossômico Dominante/diagnóstico , Insuficiência Renal/etiologia , Insuficiência Renal/prevenção & controle , Medição de Risco/métodos , Reino Unido
7.
Nat Rev Nephrol ; 15(11): 713-726, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31118499

RESUMO

These recommendations were systematically developed on behalf of the Network for Early Onset Cystic Kidney Disease (NEOCYST) by an international group of experts in autosomal dominant polycystic kidney disease (ADPKD) from paediatric and adult nephrology, human genetics, paediatric radiology and ethics specialties together with patient representatives. They have been endorsed by the International Pediatric Nephrology Association (IPNA) and the European Society of Paediatric Nephrology (ESPN). For asymptomatic minors at risk of ADPKD, ongoing surveillance (repeated screening for treatable disease manifestations without diagnostic testing) or immediate diagnostic screening are equally valid clinical approaches. Ultrasonography is the current radiological method of choice for screening. Sonographic detection of one or more cysts in an at-risk child is highly suggestive of ADPKD, but a negative scan cannot rule out ADPKD in childhood. Genetic testing is recommended for infants with very-early-onset symptomatic disease and for children with a negative family history and progressive disease. Children with a positive family history and either confirmed or unknown disease status should be monitored for hypertension (preferably by ambulatory blood pressure monitoring) and albuminuria. Currently, vasopressin antagonists should not be offered routinely but off-label use can be considered in selected children. No consensus was reached on the use of statins, but mTOR inhibitors and somatostatin analogues are not recommended. Children with ADPKD should be strongly encouraged to achieve the low dietary salt intake that is recommended for all children.


Assuntos
Rim Policístico Autossômico Dominante/diagnóstico , Rim Policístico Autossômico Dominante/terapia , Adolescente , Criança , Terapia Combinada , Aconselhamento Diretivo , Humanos , Programas de Rastreamento , Rim Policístico Autossômico Dominante/complicações , Rim Policístico Autossômico Dominante/psicologia , Encaminhamento e Consulta , Medição de Risco
8.
Pancreas ; 48(5): 698-705, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31091218

RESUMO

OBJECTIVES: Pancreatic lesions in autosomal dominant polycystic kidney disease (ADPKD) are primarily cysts. They are increasingly recognized, with isolated reports of intraductal papillary mucinous neoplasia (IPMN). METHODS: Retrospective study to determine prevalence, number, size, and location of pancreatic abnormalities using abdominal magnetic resonance imaging (MRI) of genotyped ADPKD patients (seen February 1998 to October 2013) and compared with age- and sex-matched non-ADPKD controls. We evaluated presentation, investigation, and management of all IPMNs among individuals with ADPKD (January 1997 to December 2016). RESULTS: Abdominal MRIs were examined for 271 genotyped ADPKD patients. A pancreatic cyst lesion (PCL) was detected in 52 patients (19%; 95% confidence interval, 15%-23%). Thirty-seven (71%) had a solitary PCL; 15 (28%) had multiple. Pancreatic cyst lesion prevalence did not differ by genotype. Intraductal papillary mucinous neoplasia was detected in 1% of ADPKD cases. Among 12 IPMN patients (7 branch duct; 5 main duct or mixed type) monitored for about 140 months, 2 with main duct IPMNs required Whipple resection, and 1 patient died of complications from small-bowel obstruction after declining surgical intervention. CONCLUSIONS: With MRI, PCLs were detected in 19% and IPMNs in 1% of 271 ADPKD patients with proven mutations, without difference across genotypes. Pancreatic cyst lesions were asymptomatic and remained stable in size.


Assuntos
Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Papilar/diagnóstico , Carcinoma Ductal Pancreático/diagnóstico , Cisto Pancreático/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Rim Policístico Autossômico Dominante/diagnóstico , Adenocarcinoma Mucinoso/diagnóstico por imagem , Adenocarcinoma Papilar/diagnóstico por imagem , Adulto , Carcinoma Ductal Pancreático/diagnóstico por imagem , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Mutação , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Cisto Pancreático/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Rim Policístico Autossômico Dominante/diagnóstico por imagem , Rim Policístico Autossômico Dominante/genética , Estudos Retrospectivos
9.
Clin Exp Nephrol ; 23(8): 1022-1030, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30989420

RESUMO

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD), one of the most common hereditary kidney diseases, causes gradual growth of cysts in the kidneys, leading to renal failure. Owing to the advanced technology of next-generation sequencing (NGS), genetic analyses of the causative genes PKD1 and PKD2 have been improved. METHODS: We performed genetic analyses of 111 Japanese ADPKD patients using hybridization-based NGS and long-range (LR)-PCR-based NGS. Additionally, genetic analyses in exon 1 of PKD1 using Sanger sequencing because of an extremely low coverage of NGS and those using multiplex ligation-dependent probe amplification (MLPA) were performed. RESULTS: The detection rate using NGS for 111 patients was 86.5%. One mutation in exon 1 of PKD1 and five deletions detected by MLPA were identified. When combined, the total detection rate was 91.9%. CONCLUSION: Although NGS is useful, we propose the addition of Sanger sequencing for exon 1 of PKD1 and MLPA as indispensable for identifying mutations not detected by NGS.


Assuntos
Análise Mutacional de DNA/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Reação em Cadeia da Polimerase Multiplex , Mutação , Rim Policístico Autossômico Dominante/genética , Canais de Cátion TRPP/genética , Grupo com Ancestrais do Continente Asiático/genética , Éxons , Predisposição Genética para Doença , Humanos , Japão , Rim Policístico Autossômico Dominante/diagnóstico , Rim Policístico Autossômico Dominante/etnologia , Valor Preditivo dos Testes , Fatores de Risco
10.
BMC Nephrol ; 20(1): 136, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31014270

RESUMO

BACKGROUND: The short-term efficacy of tolvaptan in patients with autosomal dominant polycystic kidney disease (ADPKD) has been demonstrated across several phase 3 trials, while the ADPKD Outcomes Model (ADPKD-OM) represents a validated approach to predict natural disease progression over a lifetime horizon. This study describes the implementation of a tolvaptan treatment effect within the ADPKD-OM and explores the potential long-term benefits of tolvaptan therapy in ADPKD. METHODS: The effect of tolvaptan on ADPKD progression was modelled by applying a constant treatment effect to the rate of renal function decline, consistent with that observed in the Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes trial (TEMPO 3:4; ClinicalTrials.gov identifier NCT00428948 ). Predictions generated by the ADPKD-OM were compared against aggregated data from a subsequent extension trial (TEMPO 4:4; ClinicalTrials.gov identifier NCT01214421 ) and the Replicating Evidence of Preserved Renal Function an Investigation of Tolvaptan Safety Efficacy in ADPKD trial (REPRISE; ClinicalTrials.gov identifier NCT02160145 ). Following validation, an application of the ADPKD-OM sought to estimate the benefit of tolvaptan therapy on time to end-stage renal disease (ESRD), in a range of ADPKD populations. RESULTS: Model validation against TEMPO 4:4 and REPRISE demonstrated the accuracy and generalisability of the tolvaptan treatment effect applied within the ADPKD-OM. In simulated patients matched to the overall TEMPO 3:4 trial population at baseline, tolvaptan therapy was predicted to delay the mean age of ESRD onset by five years, compared to natural disease progression (57 years versus 52 years, respectively). In subgroup and sensitivity analyses, the estimated delay to ESRD was greatest among patients with CKD stage 1 at baseline (6.6 years), compared to CKD 2 and 3 subgroups (4.7 and 2.7 years, respectively); and ADPKD patients in Mayo subclasses 1C-1E. CONCLUSIONS: This study demonstrated the potential for tolvaptan therapy to delay time to ESRD, particularly among patients with early-stage CKD and evidence of rapidly progressing disease. Data arising from this study highlight the value to be gained by early intervention and long-term treatment with tolvaptan, which may alleviate the economic and societal costs of providing care to patients who progress to ESRD.


Assuntos
Taxa de Filtração Glomerular/efeitos dos fármacos , Falência Renal Crônica , Rim Policístico Autossômico Dominante , Tolvaptan/uso terapêutico , Adulto , Antagonistas dos Receptores de Hormônios Antidiuréticos/uso terapêutico , Gerenciamento Clínico , Progressão da Doença , Feminino , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/tratamento farmacológico , Falência Renal Crônica/etiologia , Masculino , Rim Policístico Autossômico Dominante/diagnóstico , Rim Policístico Autossômico Dominante/tratamento farmacológico , Estudo de Prova de Conceito , Reprodutibilidade dos Testes , Tempo
11.
Int Urol Nephrol ; 51(7): 1191-1197, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31012038

RESUMO

PURPOSE: The decrease in kidney functions in autosomal dominant polycystic kidney disease (ADPKD) is strongly correlated with the severity and growth of kidney cysts. Total kidney volume (TKV) was shown to be an early marker of the severity of the disease and a predictor of reduction in kidney functions. New treatment approaches for ADPKD have led to a need for easily applicable strong biomarkers predicting progression of the disease. The profibrotic mediator of galectin-3 (Gal-3) is linked to development of renal fibrosis. METHODS: The study included 74 patients with ADPKD diagnosis and 40 healthy controls. The TKV of patients was calculated using the manual tracing method on MR images. The serum Gal-3 levels of patient and healthy control groups were measured with the ELISA method. The correlations between serum Gal-3 value with TKV and kidney function were assessed in patients. RESULTS: As the stage of chronic kidney disease (CKD) increased, serum Gal-3 and TKV values increased (p < 0.001, p = 0.049, respectively). Correlation analysis found a negative relationship between serum Gal-3 levels and eGFR (r: - 0.515, p < 0.001); however, there was no relationship between serum Gal-3 and TKV (r = 0.112, p = 0.344). Linear regression analysis showed the major parameter affecting Gal-3 was eGFR (p = 0.016). CONCLUSIONS: In our study, we showed that renal impairment is an important determinant of Gal-3, and there is no correlation of Gal-3 and TKV in ADPKD. As a result, there is an urgent clinical need for new biomarkers to identify individuals with the chance of treatment in the early stage among ADPKD patients.


Assuntos
Galectina 3/sangue , Rim , Rim Policístico Autossômico Dominante , Adulto , Biomarcadores/sangue , Correlação de Dados , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/diagnóstico por imagem , Rim/patologia , Rim/fisiopatologia , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Gravidade do Paciente , Rim Policístico Autossômico Dominante/sangue , Rim Policístico Autossômico Dominante/diagnóstico , Rim Policístico Autossômico Dominante/fisiopatologia , Índice de Gravidade de Doença
12.
BMJ Case Rep ; 12(4)2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30954962

RESUMO

Prostate cyst, as an extrarenal manifestation in patients with autosomal dominant polycystic kidney disease, although infrequent, nevertheless goes beyond tenuous concomitance and may rarely contribute to recurrent urinary tract infection or outflow obstruction and mostly remains asymptomatic. In this context, we report a case of incidentally detected, an asymptomatic prostatic cyst in a patient of autosomal dominant polycystic kidney disease.


Assuntos
Tratamento Conservador/métodos , Cistos/patologia , Rim Policístico Autossômico Dominante/diagnóstico , Doenças Prostáticas/patologia , Adulto , Cistos/diagnóstico por imagem , Humanos , Masculino , Rim Policístico Autossômico Dominante/congênito , Doenças Prostáticas/complicações , Doenças Prostáticas/diagnóstico por imagem , Ultrassonografia
13.
Lancet ; 393(10174): 919-935, 2019 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-30819518

RESUMO

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and one of the most common causes of end-stage kidney disease. Multiple clinical manifestations, such as enlarged kidneys filled with growing cysts, hypertension, and multiple extrarenal complications, including liver cysts, intracranial aneurysms, and cardiac valvular disease, show that ADPKD is a systemic disorder. New information derived from clinical research using molecular genetics and advanced imaging techniques has provided enhanced tools for assessing the diagnosis and prognosis for individual patients and their families. Phase 3 randomised, placebo-controlled clinical trials have clarified aspects of disease management and a disease-modifying therapeutic drug is now available for patients with high risk of rapid disease progression. These developments provide a strong basis on which to make clear recommendations about the management of affected patients and families. Implementation of these advances has the potential to delay kidney failure, reduce the symptom burden, lessen the risk of cardiovascular complications, and prolong life.


Assuntos
Rim Policístico Autossômico Dominante , Adulto , Idoso , Cistos/complicações , Progressão da Doença , Feminino , Testes Genéticos , Humanos , Hepatopatias/complicações , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mutação , Rim Policístico Autossômico Dominante/complicações , Rim Policístico Autossômico Dominante/diagnóstico , Rim Policístico Autossômico Dominante/fisiopatologia , Rim Policístico Autossômico Dominante/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Ultrassonografia
14.
Heart Surg Forum ; 22(1): E032-E034, 2019 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-30806618

RESUMO

A 78-year-old man who had been diagnosed with autosomal dominant polycystic kidney disease (ADPKD) and hypertension presented with chest pain. His family history was positive for ADPKD. Chest computed tomography (CT) revealed a type A aortic dissection with thrombotic occlusion of a false lumen and an ulcer-like projection in the ascending aorta, an aneurysm of the ascending aorta, and pericardial effusion. Abdominal CT showed multiple renal and hepatic cysts. At surgery, aortic dissection with thrombotic occlusion of the false lumen and an intimal tear in the distal ascending aorta were observed. Hemiarch replacement including the intimal tear was performed. The patient is doing well without requiring dialysis and without recurrence of aortic dissection or aneurysm under strict antihypertensive therapy 3 years after the operation. Pathological examination of aortic wall specimens revealed no degenerative abnormality. ADPKD should be kept in mind as one of the causative disorders of aortic dissection.


Assuntos
Aneurisma Dissecante/etiologia , Aorta/cirurgia , Aneurisma da Aorta Torácica/etiologia , Implante de Prótese Vascular/métodos , Rim Policístico Autossômico Dominante/complicações , Idoso , Aneurisma Dissecante/diagnóstico , Aneurisma Dissecante/cirurgia , Aorta/diagnóstico por imagem , Aneurisma da Aorta Torácica/diagnóstico , Aneurisma da Aorta Torácica/cirurgia , Humanos , Masculino , Rim Policístico Autossômico Dominante/diagnóstico , Tomografia Computadorizada por Raios X
15.
BMC Nephrol ; 20(1): 66, 2019 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-30803434

RESUMO

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and is characterized by gradual cyst growth and expansion, increase in kidney volume with an ultimate decline in kidney function leading to end stage renal disease (ESRD). Given the decades long period of stable kidney function while cyst growth occurs, it is important to identify those patients who will progress to ESRD. Recent data from our and other laboratories have demonstrated that metabolic reprogramming may play a key role in cystic epithelial proliferation resulting in cyst growth in ADPKD. Height corrected total kidney volume (ht-TKV) accurately reflects cyst burden and predicts future loss of kidney function. We hypothesize that specific plasma metabolites will correlate with eGFR and ht-TKV early in ADPKD, both predictors of disease progression, potentially indicative of early physiologic derangements of renal disease severity. METHODS: To investigate the predictive role of plasma metabolites on eGFR and/or ht-TKV, we used a non-targeted GC-TOF/MS-based metabolomics approach on hypertensive ADPKD patients in the early course of their disease. Patient data was obtained from the HALT-A randomized clinical trial at baseline including estimated glomerular filtration rate (eGFR) and measured ht-TKV. To identify individual metabolites whose intensities are significantly correlated with eGFR and ht-TKV, association analyses were performed using linear regression with each metabolite signal level as the primary predictor variable and baseline eGFR and ht-TKV as the continuous outcomes of interest, while adjusting for covariates. Significance was determined by Storey's false discovery rate (FDR) q-values to correct for multiple testing. RESULTS: Twelve metabolites significantly correlated with eGFR and two triglycerides significantly correlated with baseline ht-TKV at FDR q-value < 0.05. Specific significant metabolites, including pseudo-uridine, indole-3-lactate, uric acid, isothreonic acid, and creatinine, have been previously shown to accumulate in plasma and/or urine in both diabetic and cystic renal diseases with advanced renal insufficiency. CONCLUSIONS: This study identifies metabolic derangements in early ADPKD which may be prognostic for ADPKD disease progression. CLINICAL TRIAL: HALT Progression of Polycystic Kidney Disease (HALT PKD) Study A; Clinical www.clinicaltrials.gov identifier: NCT00283686; first posted January 30, 2006, last update posted March 19, 2015.


Assuntos
Rim , Rim Policístico Autossômico Dominante , Insuficiência Renal , Adulto , Creatinina/sangue , Progressão da Doença , Feminino , Humanos , Indóis/sangue , Rim/metabolismo , Rim/patologia , Testes de Função Renal/métodos , Testes de Função Renal/estatística & dados numéricos , Estudos Longitudinais , Masculino , Tamanho do Órgão , Gravidade do Paciente , Rim Policístico Autossômico Dominante/sangue , Rim Policístico Autossômico Dominante/diagnóstico , Rim Policístico Autossômico Dominante/fisiopatologia , Valor Preditivo dos Testes , Prognóstico , Pseudouridina/sangue , Insuficiência Renal/sangue , Insuficiência Renal/diagnóstico , Insuficiência Renal/etiologia , Ácido Úrico/sangue
16.
Indian J Pathol Microbiol ; 62(1): 95-98, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30706867

RESUMO

Glomerulocystic kidney disease (GCKD) is an uncommon type of cystic renal disease affecting children. It has both sporadic and familial occurrence and is characterized by cortical microcysts associated with dilatation of Bowman's spaces. In some instances, GCKD is an early manifestation of autosomal dominant polycystic kidney disease. Here, we present three cases of GCKD, two in infants and one in a perinatal postmortem. The first one is a case of GCKD with unilateral involvement, diagnosed on surgical biopsy. GCKD is a morphological expression of several hereditary and nonhereditary disorders that differ vastly in their management and long-term outcome. Hence, accurate morphological diagnosis of this entity is important for prognostication and genetic counseling.


Assuntos
Doenças do Sistema Nervoso Central/diagnóstico , Esmalte Dentário/anormalidades , Diabetes Mellitus Tipo 2/diagnóstico , Doenças Renais Císticas/diagnóstico , Rim Policístico Autossômico Dominante/diagnóstico , Biópsia , Doenças do Sistema Nervoso Central/patologia , Esmalte Dentário/patologia , Diabetes Mellitus Tipo 2/patologia , Feminino , Humanos , Lactente , Recém-Nascido de muito Baixo Peso , Rim/diagnóstico por imagem , Rim/patologia , Doenças Renais Císticas/patologia , Doenças Renais Císticas/cirurgia , Masculino , Nefrectomia , Rim Policístico Autossômico Dominante/patologia , Rim Policístico Autossômico Dominante/cirurgia , Ultrassonografia
17.
Saudi J Kidney Dis Transpl ; 30(1): 175-184, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30804279

RESUMO

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease, which usually manifests in adulthood. It is characterized by the development of multiple cysts in the kidneys and many other extrarenal manifestations. We aimed to determine the factors that contribute to the progression of ADPKD to end-stage renal disease (ESRD). In a retrospective multicentric study, we reviewed the records of 569 patients with ADPKD, hospitalized at a nephrology department or followed up at the outpatient department of university and regional hospitals, covering the north and center of the country, during the period 1969-2016. The mean age of the study patients was 48.54 ± 13.68 years and 14% were young adults (<40 years). There were 272 female and 297 male patients (sex ratio: male/female = 1.09). A family history of ADPKD was found in 43.7% of cases. Renal symptoms were dominated by loin pain, renal failure, hypertension, and hematuria, seen in, respectively, 51.9%, 48.2%, 29.1%, and 24.6% of the patients. The median serum creatinine level was 459 µmol/L (range: 47-2454), and hypertension had preceded the onset of ADPKD in 28.8% of cases. Extrarenal manifestations consisted of urologic complications (54.6%), liver cysts (43.5%), cardiac involvement (31.9%), cerebral aneurysms (12.9%), and gastrointestinal involvement (9.4%). ESRD occurred in 43.1% after a mean follow-up of 47 months (range: 0-384). Risk factors for poor renal prognosis were age >40 years (P = 0.009), hematuria (P = 0.034), hemoglobin >14 g/dL (P = 0.0013), high uric acid level (P = 0.001), and leukocyturia (P = 0.02). Death occurred in 59 cases (10.3%), mostly caused by infections (44.1%). In our study, ADPKD was lately diagnosed in most cases. Family screening is important, which will enable early detection and management of the complications associated with ADPKD.


Assuntos
Rim Policístico Autossômico Dominante , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rim Policístico Autossômico Dominante/diagnóstico , Rim Policístico Autossômico Dominante/epidemiologia , Rim Policístico Autossômico Dominante/mortalidade , Rim Policístico Autossômico Dominante/fisiopatologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Tunísia/epidemiologia
18.
Nephrology (Carlton) ; 24(12): 1214-1224, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30663163

RESUMO

AIM: Patients with autosomal dominant polycystic kidney disease (ADPKD) are at increased risk of premature mortality, morbidities and complications, which severely impair quality of life. However, patient-centered outcomes are not consistently reported in trials in ADPKD, which can limit shared decision-making. We aimed to identify outcomes important to patients and caregivers and the reasons for their priorities. METHODS: Nominal group technique was adopted involving patients with ADPKD and caregivers who were purposively selected from eight centres across Australia, France and the Republic of Korea. Participants identified, ranked and discussed outcomes for trials in ADPKD. We calculated an importance score (0-1) for each outcome and conducted thematic analyses. RESULTS: Across 17 groups, 154 participants (121 patients, 33 caregivers) aged 19 to 78 (mean 54.5 years) identified 55 outcomes. The 10 highest ranked outcomes were: kidney function (importance score 0.36), end-stage kidney disease (0.32), survival (0.21), cyst size/growth (0.20), cyst pain/bleeding (0.18), blood pressure (0.17), ability to work (0.16), cerebral aneurysm/stroke (0.14), mobility/physical function (0.12), and fatigue (0.12). Three themes were identified: threatening semblance of normality, inability to control and making sense of diverse risks. CONCLUSION: For patients with ADPKD and their caregivers, kidney function, delayed progression to end-stage kidney disease and survival were the highest priorities, and were focused on achieving normality, and maintaining control over health and lifestyle. Implementing these patient-important outcomes may improve the meaning and relevance of trials to inform clinical care in ADPKD.


Assuntos
Efeitos Psicossociais da Doença , Falência Renal Crônica , Estilo de Vida , Avaliação de Resultados da Assistência ao Paciente , Rim Policístico Autossômico Dominante , Qualidade de Vida , Atitude Frente a Saúde , Austrália , Cuidadores/psicologia , Progressão da Doença , Estudos de Avaliação como Assunto , Feminino , França , Humanos , Falência Renal Crônica/etiologia , Falência Renal Crônica/mortalidade , Testes de Função Renal/psicologia , Masculino , Pessoa de Meia-Idade , Rim Policístico Autossômico Dominante/diagnóstico , Rim Policístico Autossômico Dominante/epidemiologia , Rim Policístico Autossômico Dominante/fisiopatologia , Rim Policístico Autossômico Dominante/psicologia , Intervalo Livre de Progressão , República da Coreia
19.
Nephrology (Carlton) ; 24(6): 638-646, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29952039

RESUMO

BACKGROUND: Complications related to peritoneal dialysis (PD) in patients with autosomal-dominant polycystic kidney disease (ADPKD), including intraperitoneal rupture of renal cyst, hernia, membrane failure and peritonitis, have been reported. However, long-term clinical outcomes of ADPKD patients on PD remain unclear. We performed this meta-analysis to assess the risks of death, technique failure and peritonitis in ADPKD patients on PD. METHODS: A systematic review was conducted using MEDLINE, EMBASE and Cochrane databases from inception to October 2017 to identify studies that evaluated the outcomes of ADPKD patients on PD, including the risks of death, technique failure and peritonitis. Non-ADPKD patients on PD were used as controls. Effect estimates from the individual study were extracted and combined using the random-effect, generic inverse variance method of DerSimonian and Laird. RESULTS: Twelve cohort studies with a total of 14 673 patients on PD (931 ADPKD and 13 742 non-ADPKD patients) were enrolled. Compared with non-ADPKD status, ADPKD was associated with significantly decreased mortality risk with pooled odds ratio (OR) of 0.68 (95% confidence interval (CI), 0.53-0.86; I2 = 0). There were no associations of ADPKD with the risks of technique failure of PD and peritonitis with pooled OR of 0.93 (95% CI, 0.79-1.10; I2 = 0) and 0.88 (95% CI, 0.75-1.05; I2 = 0), respectively. We found no publication bias as assessed by Egger's regression asymmetry test, with P = 0.90, 0.28 and 0.60 for the risks of mortality, technique failure and peritonitis in ADPKD patients on PD, respectively. CONCLUSION: Compared with non-ADPKD patients on PD, our study demonstrates that ADPKD patients on PD have 0.68-fold decreased mortality risk. There are no associations of ADPKD status with the risks of technique failure or peritonitis.


Assuntos
Falência Renal Crônica/terapia , Diálise Peritoneal , Rim Policístico Autossômico Dominante/terapia , Progressão da Doença , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/genética , Falência Renal Crônica/mortalidade , Diálise Peritoneal/efeitos adversos , Diálise Peritoneal/mortalidade , Peritonite/epidemiologia , Rim Policístico Autossômico Dominante/diagnóstico , Rim Policístico Autossômico Dominante/genética , Rim Policístico Autossômico Dominante/mortalidade , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
20.
J Nephrol ; 32(1): 83-91, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30022320

RESUMO

BACKGROUND: The prominent features of autosomal dominant polycystic kidney disease (ADPKD) are early development of hypertension, chronic kidney disease and cardiovascular problems. Thus, we aimed to investigate the role of endothelin, a vascular biomarker, in the clinical course of ADPKD, including renal and cardiovascular survival. METHODS: In 138 patients with ADPKD and 28 healthy controls, we measured serum endothelin-1 (ET-1) levels by enzyme-linked immunosorbent assay (ELISA). Endothelium-dependent vasodilatation (flow-mediated dilatation, FMD) and endothelium-independent vasodilatation (nitroglycerin-mediated dilatation, NMD) of the brachial artery were assessed non-invasively with high-resolution ultrasound. Magnetic resonance imaging (MRI) was performed with a 1.5-T system, and total kidney volumes were calculated using mid-slice technique. To determine PKD1 and PKD2 genotype, we performed molecular and genetic tests involving the following steps: DNA isolation, next-generation sequencing (NGS) and data analysis. RESULTS: Endothelin levels and height-adjusted total kidney volumes (hTKV) significantly increased while the estimated glomerular filtration rate (eGFR) decreased across CKD stages 1-4. Hypertension was more frequent in ADPKD patients with high serum endothelin. At multivariate Cox analysis, endothelin level, PKD1 truncating mutation, hTKV, high-sensitive C reactive protein (hs-CRP) level and the presence of diabetes mellitus were associated with the risk of overall survival. Moreover, endothelin level, PKD1 truncating mutation, hTKV, age and presence of hypertension were associated with the risk of renal survival. Additionally, body mass index (BMI), FMD, PKD1 truncating mutation, endothelin and triglyceride levels were independently associated with hypertension. CONCLUSIONS: Increased serum endothelin levels independently predict hypertension in ADPKD. Serum endothelin levels are also associated with both renal and overall survival in patients with ADPKD.


Assuntos
Endotelina-1/sangue , Hipertensão/etiologia , Rim Policístico Autossômico Dominante/sangue , Insuficiência Renal Crônica/etiologia , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Hemodinâmica , Humanos , Hipertensão/sangue , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Rim Policístico Autossômico Dominante/complicações , Rim Policístico Autossômico Dominante/diagnóstico , Rim Policístico Autossômico Dominante/fisiopatologia , Prognóstico , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco , Fatores de Tempo , Regulação para Cima
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