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BACKGROUND AND OBJECTIVES: The progression of polycystic liver disease is not well understood. The purpose of the study is to evaluate the associations of polycystic liver progression with other disease progression variables and classify liver progression on the basis of patient's age, height-adjusted liver cystic volume, and height-adjusted liver volume. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Prospective longitudinal magnetic resonance images from 670 patients with early autosomal dominant polycystic kidney disease for up to 14 years of follow-up were evaluated to measure height-adjusted liver cystic volume and height-adjusted liver volume. Among them, 245 patients with liver cyst volume >50 ml at baseline were included in the longitudinal analysis. Linear mixed models on log-transformed height-adjusted liver cystic volume and height-adjusted liver volume were fitted to approximate mean annual rate of change for each outcome. The association of sex, body mass index, genotype, baseline height-adjusted total kidney volume, and Mayo imaging class was assessed. We calculated height-adjusted liver cystic volume ranges for each specific age and divided them into five classes on the basis of annual percentage increase in height-adjusted liver cystic volume. RESULTS: The mean annual growth rate of height-adjusted liver cystic volume was 12% (95% confidence interval, 11.1% to 13.1%; P<0.001), whereas that for height-adjusted liver volume was 2% (95% confidence interval, 1.9% to 2.6%; P<0.001). Women had higher baseline height-adjusted liver cystic volume than men, but men had higher height-adjusted liver cystic volume growth rate than women by 2% (95% confidence interval, 0.4% to 4.5%; P=0.02). Whereas the height-adjusted liver cystic volume growth rate decreased in women after menopause, no decrease was observed in men at any age. Body mass index, genotype, and baseline height-adjusted total kidney volume were not associated with the growth rate of height-adjusted liver cystic volume or height-adjusted liver volume. According to the height-adjusted liver cystic volume growth rate, patients were classified into five classes (number of women, men in each class): A (24, six); B (44, 13); C (43, 48); D (28, 17); and E (13, nine). CONCLUSIONS: Compared with height-adjusted liver volume, the use of height-adjusted liver cystic volume showed greater separations in volumetric progression of polycystic liver disease. Similar to the Mayo imaging classification for the kidney, the progression of polycystic liver disease may be categorized on the basis of patient's age and height-adjusted liver cystic volume.
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Rim Policístico Autossômico Dominante , Cistos , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/diagnóstico por imagem , Rim/patologia , Fígado/diagnóstico por imagem , Fígado/patologia , Hepatopatias , Imageamento por Ressonância Magnética , Masculino , Rim Policístico Autossômico Dominante/complicações , Rim Policístico Autossômico Dominante/diagnóstico por imagem , Rim Policístico Autossômico Dominante/genética , Estudos ProspectivosRESUMO
RATIONALE & OBJECTIVE: Pain is a frequent complication of autosomal dominant polycystic kidney disease (ADPKD) and includes back and abdominal pain. We hypothesized that in adults with early- and late-stage ADPKD, overweight and obesity are independently associated with greater self-reported back, abdominal, and radicular pain at baseline and that weight loss would be associated with decreased pain over a follow-up period. STUDY DESIGN: Post hoc analysis of pooled data from 2 randomized trials. SETTING & PARTICIPANTS: Participants in the HALT-PKD study A or B. 867 individuals were included in a cross-sectional analysis. 4,248 observations from 871 participants were included in a longitudinal analysis. PREDICTOR: Overweight and obesity (cross-sectional); annual change in weight as a time-varying predictor (longitudinal). OUTCOME: Pain (Likert-scale responses; cross-sectional); annual change in pain (binary outcome of worsening pain or not worsening; longitudinal). ANALYTICAL APPROACH: Multivariable ordinal logistic regression (cross-sectional); generalized estimating equation analysis (longitudinal). RESULTS: Participants were aged 42±10 years and baseline estimated glomerular filtration rate was 71±26 mL/min/1.73 m2. Back, abdominal, and radicular pain were reported more frequently in individuals with increasing body mass index category (all P < 0.05 for trend). After multivariable adjustment, obesity was associated with increased odds of greater back and radicular pain, but not abdominal pain. Associations remained similar after further adjustment for baseline height-adjusted kidney and liver volume (study A only, n = 457); back pain: OR, 1.88 (95% CI, 1.15-3.08); and radicular pain: OR, 2.92 (95% CI, 1.45-5.91). Longitudinally (median follow-up, 5 years), weight loss (annual decrease in weight ≥ 4%) was associated with decreased adjusted odds of worsening back pain (OR, 0.87 [95% CI, 0.76-0.99]) compared with the reference group (stable weight). LIMITATIONS: Post hoc, associative analysis. CONCLUSIONS: In early- and late-stage ADPKD, obesity was associated with greater back and radicular pain independent of total kidney/liver volume. Mild weight loss was associated with favorable effects on back pain.
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Eighty primary renal allograft recipients, 61 living-related and 19 deceased donor, transplanted from 1963 through 1984 had continuous graft function for 30-47 years. They were treated with three different early immunosuppression programs (1963-1970: thymectomy, splenectomy, high oral prednisone; 1971-1979: divided-dose intravenous methylprednisolone; and 1980-1984: antilymphocyte globulin) each with maintenance prednisone and azathioprine, and no calcineurin inhibitor. Long-term treatment often included the anti-platelet medication, dipyridamole. Although both recipient and donor ages were young (27.2 ± 9.5 and 33.1 ± 12.0 years, respectively), six recipients with a parent donor had >40-year success. At 35 years, death-censored graft survival was 85.3% and death with a functioning graft 84.2%; overall graft survival was 69.5% (Kaplan-Meier estimate). Biopsy-documented early acute cellular and highly probable antibody-mediated rejections were reversed with divided-dose intravenous methylprednisolone. Complications are detailed in an integrated timeline. Hypogammaglobulinemia identified after 20 years doubled the infection rate. An association between a monoclonal gammopathy of undetermined significance and non-plasma-cell malignancies was identified. Twenty-seven azathioprine-treated patients tested after 37 years had extremely low levels of T1/T2 B lymphocytes representing a "low immunosuppression state of allograft acceptance (LISAA)". The lifetime achievements of these patients following a single renal allograft and low-dose maintenance immunosuppression are remarkable. Their success evolved as a clinical mosaic.
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Transplante de Rim , Ácido Micofenólico , Adolescente , Adulto , Aloenxertos , Soro Antilinfocitário , Azatioprina/uso terapêutico , Quimioterapia Combinada , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Humanos , Imunossupressores/uso terapêutico , Prednisona , Adulto JovemRESUMO
BACKGROUNDA treatment option for autosomal dominant polycystic kidney disease (ADPKD) has highlighted the need to identify rapidly progressive patients. Kidney size/age and genotype have predictive power for renal outcomes, but their relative and additive value, plus associated trajectories of disease progression, are not well defined.METHODSThe value of genotypic and/or kidney imaging data (Mayo Imaging Class; MIC) to predict the time to functional (end-stage kidney disease [ESKD] or decline in estimated glomerular filtration rate [eGFR]) or structural (increase in height-adjusted total kidney volume [htTKV]) outcomes were evaluated in a Mayo Clinic PKD1/PKD2 population, and eGFR and htTKV trajectories from 20-65 years of age were modeled and independently validated in similarly defined CRISP and HALT PKD patients.RESULTSBoth genotypic and imaging groups strongly predicted ESKD and eGFR endpoints, with genotype improving the imaging predictions and vice versa; a multivariate model had strong discriminatory power (C-index = 0.845). However, imaging but not genotypic groups predicted htTKV growth, although more severe genotypic and imaging groups had larger kidneys at a young age. The trajectory of eGFR decline was linear from baseline in the most severe genotypic and imaging groups, but it was curvilinear in milder groups. Imaging class trajectories differentiated htTKV growth rates; severe classes had rapid early growth and large kidneys, but growth later slowed.CONCLUSIONThe value of imaging, genotypic, and combined data to identify rapidly progressive patients was demonstrated, and reference values for clinical trials were provided. Our data indicate that differences in kidney growth rates before adulthood significantly define patients with severe disease.FUNDINGNIDDK grants: Mayo DK058816 and DK090728; CRISP DK056943, DK056956, DK056957, and DK056961; and HALT PKD DK062410, DK062408, DK062402, DK082230, DK062411, and DK062401.
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Processamento de Imagem Assistida por Computador/métodos , Falência Renal Crônica/patologia , Rim/patologia , Mutação , Rim Policístico Autossômico Dominante/fisiopatologia , Canais de Cátion TRPP/genética , Adulto , Idoso , Estudos de Coortes , Progressão da Doença , Feminino , Genótipo , Taxa de Filtração Glomerular , Humanos , Rim/metabolismo , Falência Renal Crônica/diagnóstico por imagem , Falência Renal Crônica/genética , Masculino , Pessoa de Meia-Idade , Rim Policístico Autossômico Dominante/diagnóstico por imagem , Rim Policístico Autossômico Dominante/genética , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: The Mayo Clinic imaging classification of autosomal dominant polycystic kidney disease (ADPKD) uses height-adjusted total kidney volume (htTKV) and age to identify patients at highest risk for disease progression. However, this classification applies only to patients with typical diffuse cystic disease (class 1). Because htTKV poorly predicts eGFR decline for the 5%-10% of patients with atypical morphology (class 2), imaging-based risk modeling remains unresolved. METHODS: Of 558 adults with ADPKD in the HALT-A study, we identified 25 patients of class 2A with prominent exophytic cysts (class 2Ae) and 43 patients of class 1 with prominent exophytic cysts; we recalculated their htTKVs to exclude exophytic cysts. Using original and recalculated htTKVs in association with imaging classification in logistic and mixed linear models, we compared predictions for developing CKD stage 3 and for eGFR trajectory. RESULTS: Using recalculated htTKVs increased specificity for developing CKD stage 3 in all participants from 82.6% to 84.2% after adjustment for baseline age, eGFR, BMI, sex, and race. The predicted proportion of class 2Ae patients developing CKD stage 3 using a cutoff of 0.5 for predicting case status was better calibrated to the observed value of 13.0% with recalculated htTKVs (45.5%) versus original htTKVs (63.6%). Using recalculated htTKVs reduced the mean paired difference between predicted and observed eGFR from 17.6 (using original htTKVs) to 4.0 ml/min per 1.73 m2 for class 2Ae, and from -1.7 (using original htTKVs) to 0.1 ml/min per 1.73 m2 for class 1. CONCLUSIONS: Use of a recalculated htTKV measure that excludes prominent exophytic cysts facilitates inclusion of class 2 patients and reclassification of class 1 patients in the Mayo classification model.
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Rim/patologia , Rim Policístico Autossômico Dominante/classificação , Rim Policístico Autossômico Dominante/diagnóstico por imagem , Insuficiência Renal Crônica/etiologia , Adulto , Estatura , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Rim Policístico Autossômico Dominante/complicações , Rim Policístico Autossômico Dominante/patologia , Valor Preditivo dos Testes , Curva ROC , Medição de Risco/métodos , Adulto JovemRESUMO
INTRODUCTION: The high burden of cardiovascular morbidity and mortality in autosomal dominant polycystic kidney disease (ADPKD) is related to development of hypertension and left ventricular hypertrophy. Blood pressure reduction has been shown to reduce left ventricular mass in ADPKD; however, moderators and predictors of response to lower blood pressure are unknown. METHODS: This was a post hoc cohort analysis of HALT PKD study A, a randomized placebo controlled trial examining the effect of low blood pressure and single versus dual renin-angiotensin blockade in early ADPKD. Participants were hypertensive ADPKD patients 15 to 49 years of age with estimated glomerular filtration rate (eGFR) > 60 ml/min per 1.73 m2 across 7 centers in the United States. Predictors included age, sex, baseline eGFR, systolic blood pressure, total kidney volume, serum potassium, and urine sodium, potassium, albumin, and aldosterone. Outcome was left ventricular mass index (LVMI) measured using 1.5-T magnetic resonance imaging at months 0, 24, 48, and 60. RESULTS: Reduction in LVMI was associated with higher baseline systolic blood pressure and larger kidney volume regardless of blood pressure control group assignment (P < 0.001 for both). Male sex and baseline eGFR were associated with a positive annual slope in LVMI (P < 0.001 and P = 0.07, respectively). CONCLUSION: Characteristics associated with higher risk of progression in ADPKD, including higher systolic blood pressure, larger kidney volume, and lower eGFR are associated with improvement in LVMI with intensive blood pressure control, whereas male sex is associated with a smaller slope of reduction in LVMI.
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BACKGROUND: The HALT PKD trial in early autosomal dominant polycystic kidney disease (ADPKD) showed that intensive control of systolic blood pressure to 95-110 mmHg was associated with a 14% slower rate of kidney volume growth compared to standard control. It is unclear whether this result was due to greater blockade of the renin-angiotensin-aldosterone system (RAAS) by allowing the use of higher drug doses in the low blood pressure arm, or due to the lower blood pressure per se. METHODS: In this secondary analysis of HALT PKD Study A, we categorized participants into high and low dose groups based on the median daily equivalent dose of RAAS blocking drugs used after the initial dose titration period. Using linear mixed models, we compared the percent change in total kidney volume and the slope of estimated glomerular filtration rate (eGFR) between the 2 groups. We also assessed the effects of time-varying dose and time-varying blood pressure parameters on these outcomes. RESULTS: Subjects in the high dose group (n=252) did not experience a slower increase in total kidney volume than those in the low-dose (n=225) group, after adjustment for age, sex, genotype, and BP arm. The chronic slope of eGFR decline was similar in the 2 groups. Higher time-varying systolic blood pressure was associated with a steeper decline in eGFR. CONCLUSION: ADPKD progression (as detected by eGFR decline and TKV increase) was ameliorated by intense blood pressure control as opposed to pharmacologic intensity of RAAS blockade.
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Antagonistas de Receptores de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/prevenção & controle , Rim/efeitos dos fármacos , Rim Policístico Autossômico Dominante/tratamento farmacológico , Sistema Renina-Angiotensina/efeitos dos fármacos , Adolescente , Adulto , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Progressão da Doença , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Hipertensão/diagnóstico , Hipertensão/etiologia , Hipertensão/fisiopatologia , Rim/patologia , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Rim Policístico Autossômico Dominante/complicações , Rim Policístico Autossômico Dominante/diagnóstico , Rim Policístico Autossômico Dominante/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Previous clinical studies of autosomal dominant polycystic kidney disease (ADPKD) reported that loss of kidney function usually follows a steep and relentless course. A detailed examination of individual patterns of decline in estimated glomerular filtration rate (eGFR) has not been performed. STUDY DESIGN: Longitudinal post hoc analysis of data collected during the Halt Progression of Polycystic Kidney Disease (HALT-PKD) trials. SETTING & PARTICIPANTS: 494 HALT-PKD Study A participants (younger; preserved eGFR) and 435 Study B participants (older; reduced eGFR) who had more than 3 years of follow-up and 7 or more eGFR assessments. MEASUREMENTS: Longitudinal eGFR assessments using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation. PREDICTORS: Demographic, clinical, laboratory, and imaging features of participants. OUTCOMES: Probability of linear and nonlinear decline patterns or of stable eGFR calculated for each participant from a Bayesian model of individual eGFR trajectories. RESULTS: Most (62.5% in Study A and 81% in Study B) participants had a linear decline in eGFR during up to 8 years of follow-up. A proportion (22% in Study A and 13% in Study B) of progressors had a nonlinear pattern. 15.5% of participants in Study A and 6% in Study B had a prolonged (≥4.5 years) period of stable eGFRs. These individuals (Study A) had significantly smaller total kidney volumes, higher renal blood flows, lower urinary albumin excretion, and lower body mass index at baseline and study end. In Study B, participants with reduced but stable eGFRs were older than the progressors. Two-thirds of nonprogressors in both studies had PKD1 mutations, with enrichment for weak nontruncating mutations. LIMITATIONS: Relatively short follow-up of a clinical trial population. CONCLUSIONS: Although many individuals with ADPKD have a linear decline in eGFR, prolonged intervals of stable GFRs occur in a substantial fraction. Lower body mass index was associated with more stable kidney function in early ADPKD.
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Progressão da Doença , Taxa de Filtração Glomerular/fisiologia , Rim Policístico Autossômico Dominante/complicações , Insuficiência Renal Crônica/diagnóstico , Adolescente , Adulto , Fatores Etários , Teorema de Bayes , Feminino , Humanos , Incidência , Testes de Função Renal , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Rim Policístico Autossômico Dominante/diagnóstico , Prognóstico , Insuficiência Renal Crônica/epidemiologia , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Adulto JovemRESUMO
BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) commonly results in end-stage renal disease (ESRD), yet a long-term treatment that is well tolerated is still lacking. In a small randomized trial in children and adolescents pravastatin administration for 3 years was associated with reduced renal cyst growth, but no large trial has tested the effect of statins in adults. METHODS: We performed a post-hoc analysis of the HALT PKD trials to compare outcomes of participants who never used statins with those who used statin for at least 3 years. Because statins were not randomly allocated, we used propensity score models with inverse probability of treatment weighting to account for imbalances between the groups. For subjects in Study A (preserved renal function, n=438) relevant outcomes were percent change in total kidney and liver volume and the rate of decline in estimated glomerular filtration rate (eGFR); for those in Study B (reduced renal function, n=352) we compared time to the composite endpoint of death, ESRD or 50% decline in eGFR. Follow-up was 5-8 years. RESULTS: There was no difference in any outcome between the 2 groups. However, limitations of this analysis are the small number of statin users in Study A, different statin drugs and doses used, non-randomized allocation and advanced disease stage in Study B. CONCLUSION: Although this post-hoc analysis of the HALT PKD trials does not demonstrate a benefit of statin therapy, conclusions remain preliminary. A larger randomized trial in young people with ADPKD is necessary to answer the question whether statins can slow renal cyst growth and preserve kidney function.
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Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Falência Renal Crônica/prevenção & controle , Rim/efeitos dos fármacos , Rim Policístico Autossômico Dominante/tratamento farmacológico , Adolescente , Adulto , Anti-Hipertensivos/uso terapêutico , Progressão da Doença , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Rim/patologia , Rim/fisiopatologia , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/etiologia , Falência Renal Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Rim Policístico Autossômico Dominante/complicações , Rim Policístico Autossômico Dominante/diagnóstico , Rim Policístico Autossômico Dominante/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Patients with mild autosomal dominant polycystic kidney disease (ADPKD) are less likely to be informative in randomized clinical trials (RCTs). We previously developed an imaging classification of ADPKD (typical diffuse cyst distribution Class 1A-E and atypical cyst distribution Class 2) for prognostic enrichment design in RCTs. We investigated whether using this classification would have increased the power to detect a beneficial treatment effect of rigorous blood pressure (BP) control on HALT-PKD participants with early disease (Study A). METHODS: Post hoc analysis of the early disease HALT-PKD study, an RCT that studied the effect of rigorous versus standard BP control on rates of total kidney volume (TKV) increase and estimated glomerular filtration rate (eGFR) decline in ADPKD patients with eGFR >60 mL/min/1.73 m2. RESULTS: Five hundred and fifty-one patients were classified by two observers (98.2% agreement) into Class 1A (6.2%), 1B (20.3%), 1C (34.1%), 1D (22.1%), 1E (11.8%) and 2 (5.4%). The TKV increase and eGFR decline became steeper from Class 1A through 1E. Rigorous BP control had been shown to be associated with slower TKV increase, without a significant overall effect on the rate of eGFR decline (faster in the first 4 months and marginally slower thereafter). Merging Classes 1A and 2 (lowest severity), 1B and 1C (intermediate severity) and 1D and 1E (highest severity) detected stronger beneficial effects on TKV increase and eGFR decline in Class 1D and E with a smaller number of patients. CONCLUSIONS: Strategies for prognostic enrichment, such as image classification, should be used in the design of RCTs for ADPKD to increase their power and reduce their cost.
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Rim Policístico Autossômico Dominante/diagnóstico por imagem , Rim Policístico Autossômico Dominante/terapia , Adulto , Pressão Sanguínea , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Interpretação de Imagem Assistida por Computador , Rim/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Rim Policístico Autossômico Dominante/fisiopatologia , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Adulto JovemRESUMO
The CRISP study of polycystic kidney disease (PKD) found that urinary sodium excretion associated with the rate of total kidney volume increase. Whether sodium restriction slows the progression of Autosomal Dominant PKD (ADPKD) is not known. To evaluate this we conducted a post hoc analysis of the HALT-PKD clinical trials of renin-angiotensin blockade in patients with ADPKD. Linear mixed models examined whether dietary sodium affected rates of total kidney volume or change in estimated glomerular filtration rate (eGFR) in patients with an eGFR over 60 ml/min/1.73 m2 (Study A) or the risk for a composite endpoint of 50% reduction in eGFR, end-stage renal disease or death, or the rate of eGFR decline in patients with an eGFR 25-60 ml/min/1.73 m2 (Study B) all in patients initiated on an under100 mEq sodium diet. During the trial urinary sodium excretion significantly declined by an average of 0.25 and 0.41 mEq/24 hour per month in studies A and B, respectively. In Study A, averaged and time varying urinary sodium excretions were significantly associated with kidney growth (0.43%/year and 0.09%/year, respectively, for each 18 mEq urinary sodium excretion). Averaged urinary sodium excretion was not significantly associated with faster eGFR decline (-0.07 ml/min/1.73m2/year for each 18 mEq urinary sodium excretion). In Study B, the averaged but not time-varying urinary sodium excretion significantly associated with increased risk for the composite endpoint (hazard ratio 1.08 for each 18 mEq urinary sodium excretion) and a significantly faster eGFR decline (-0.09 ml/min/1.73m2/year for each mEq 18 mEq urinary sodium excretion). Thus, sodium restriction is beneficial in the management of ADPKD.
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Dieta Hipossódica , Taxa de Filtração Glomerular , Rim/fisiopatologia , Rim Policístico Autossômico Dominante/dietoterapia , Cloreto de Sódio na Dieta/efeitos adversos , Adolescente , Adulto , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Progressão da Doença , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Pessoa de Meia-Idade , Natriurese , Rim Policístico Autossômico Dominante/diagnóstico , Rim Policístico Autossômico Dominante/fisiopatologia , Rim Policístico Autossômico Dominante/urina , Eliminação Renal , Sistema Renina-Angiotensina/efeitos dos fármacos , Cloreto de Sódio na Dieta/urina , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Reduction in operative trauma along with an improvement in endoscopic access has undoubtedly occupied surgical minds for at least the past 3 decades. It is not at all surprising that minimally invasive colon surgery has come a long way since the first laparoscopic appendectomy by Semm in 1981. It is common knowledge that the recent developments in video and robotic technologies have significantly furthered advancements in laparoscopic and minimally invasive surgery. This has led to the overall acceptance of the treatment of benign colorectal pathology via the endoscopic route. Malignant disease, however, is still primarily treated by conventional approaches. METHODS AND RESULTS: This review article is based on a literature search pertaining to advances in minimally invasive colorectal surgery for the treatment of malignant pathology, as well as on personal experience in the field over the same period of time. Our search was limited to level I and II clinical papers only, according to the evidence-based medicine guidelines. We attempted to present our unbiased view on the subject relying only on the evidence available. CONCLUSION: Focusing on advances in colorectal minimally invasive surgery, it has to be stated that there are still a number of unanswered questions regarding the surgical management of malignant diseases with this approach. These questions do not only relate to the area of boundaries set for the use of minimally invasive techniques in this field but also to the exact modality best suited to the treatment of every particular case whilst maintaining state-of-the-art oncological principles.
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Autosomal dominant polycystic kidney disease (ADPKD) often results in ESRD but with a highly variable course. Mutations to PKD1 or PKD2 cause ADPKD; both loci have high levels of allelic heterogeneity. We evaluated genotype-phenotype correlations in 1119 patients (945 families) from the HALT Progression of PKD Study and the Consortium of Radiologic Imaging Study of PKD Study. The population was defined as: 77.7% PKD1, 14.7% PKD2, and 7.6% with no mutation detected (NMD). Phenotypic end points were sex, eGFR, height-adjusted total kidney volume (htTKV), and liver cyst volume. Analysis of the eGFR and htTKV measures showed that the PKD1 group had more severe disease than the PKD2 group, whereas the NMD group had a PKD2-like phenotype. In both the PKD1 and PKD2 populations, men had more severe renal disease, but women had larger liver cyst volumes. Compared with nontruncating PKD1 mutations, truncating PKD1 mutations associated with lower eGFR, but the mutation groups were not differentiated by htTKV. PKD1 nontruncating mutations were evaluated for conservation and chemical change and subdivided into strong (mutation strength group 2 [MSG2]) and weak (MSG3) mutation groups. Analysis of eGFR and htTKV measures showed that patients with MSG3 but not MSG2 mutations had significantly milder disease than patients with truncating cases (MSG1), an association especially evident in extreme decile populations. Overall, we have quantified the contribution of genic and PKD1 allelic effects and sex to the ADPKD phenotype. Intrafamilial correlation analysis showed that other factors shared by families influence htTKV, with these additional genetic/environmental factors significantly affecting the ADPKD phenotype.
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Mutação , Rim Policístico Autossômico Dominante/genética , Canais de Cátion TRPP/genética , Adulto , Feminino , Previsões , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , FenótipoRESUMO
BACKGROUND: The aim of this paper was to study the effects of Nordic ski training on post-exercise blood glucose (BG) regulation. METHODS: Twenty-one (male N.=10; female N.=11) competitive college Nordic skiers (age 19.14±1.3 yrs; body fat percentage 14.9±6.2) completed two ski training conditions (high intensity [HI] and easy volume [MOD]) and one resting control (CON) condition on separate days. At rest on the control day and upon completion of ski training, a 75 g oral glucose tolerance test (OGTT) was administered. BG was measured prior to the OGTT and at 20-minute intervals for 80 minutes of passive rest. Hunger was assessed prior to the OGTT and at 40 and 80 minutes of rest via Visual Analog Scale. Data were analyzed using a two-way ANOVA with repeated measures and one-way ANOVA (SPSS v. 19). RESULTS: Significant time effects were present for BG. BG area under the curve (AUC) was significantly smaller (P<0.05) following HI (8825±149 arbitrary units [a.u.]) vs. CON (9493±168 a.u.), but not different from MOD (9087±227 a.u.). MOD AUC tended to be smaller than CON (P=0.064). Mean CON hunger was lower than MOD (P<0.05) and tended to be lower than HI (P=0.064). CONCLUSIONS: High-intensity Nordic skiing appears to enhance glycemic control when provided with an OGTT following acute exercise. The role that active muscle volume plays in this response should be investigated.
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Glicemia/metabolismo , Fome , Condicionamento Físico Humano/fisiologia , Esqui/fisiologia , Adolescente , Área Sob a Curva , Feminino , Teste de Tolerância a Glucose , Humanos , Masculino , Esforço Físico/fisiologia , Descanso/fisiologia , Escala Visual Analógica , Adulto JovemRESUMO
With the rapid development of the knowledge and techniques in bariatric surgery, as well as extensive expansion of indications for metabolic operations, surgeons have started to realize that the procedures they choose are not always suited to the needs and behavior of patients. Second and very frequently third revisional procedures are thus necessary in order to achieve desired outcomes and fulfill patients' expectations. Restoration of restriction is commonly the first procedure, but not all may benefit from it. We hence want to illustrate the decision-making process by presenting a patient with the background of initial Rouxen-Y gastric bypass (RYGB) and redo-RYGB, who then underwent a further revision by a 2-stage approach due to weight regain. The first stage involved shortening of the common channel and the second one reconstruction of his gastric pouch with duodenal switch (DS). Consequently we wish to focus here on a discussion about operative techniques and strategies to improve outcomes in such patients.
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BACKGROUND: The HALT Polycystic Kidney Disease Trials Network consisted of two randomized, double blind, placebo-controlled trials among patients with autosomal dominant polycystic kidney disease. The trials involved 5-8years of participant follow-up with interventions in blood pressure and antihypertensive therapy. We provide a framework for designing and implementing closeout near the end of a trial while ensuring patient safety and maintaining scientific rigor and study morale. METHODS: We discuss issues and resolutions for determining the last visit, tapering medications, and unblinding of participants to study allocation and results. We also discuss closure of clinical sites and Data Coordinating Center responsibilities to ensure timely release of study results and meeting the requirements of regulatory and funding authorities. RESULTS: Just over 90% of full participants had a 6-month study visit prior to their last visit preparing them for trial closeout. Nearly all patients wanted notification of study results (99%) and treatment allocation (99%). All participants were safely tapered off study and open label blood pressure medications. Within 6months, the trials were closed, primary papers published, and 805 letters distributed to participants with results and allocation. DCC obligations for data repository and clinicaltrials.gov reporting were completed within 12months of the last study visit. CONCLUSIONS: Closeout of our trials involved years of planning and significant human and financial resources. We provide questions for investigators to consider when planning closeout of their trials with focus on (1) patient safety, (2) dissemination of study results and (3) compliance with regulatory and funding responsibilities.
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BACKGROUND & AIMS: Polycystic liver disease (PLD), the most common extrarenal manifestation of autosomal-dominant polycystic kidney disease (ADPKD), has become more prevalent as a result of increased life expectancy, improved renal survival, reduced cardiovascular mortality, and renal replacement therapy. No studies have fully characterized PLD in large cohorts. We investigated whether liver and cyst volumes are associated with volume of the hepatic parenchyma, results from liver laboratory tests, and patient-reported outcomes. METHODS: We performed a cross-sectional analysis of baseline liver volumes, measured by magnetic resonance imaging, and their association with demographics, results from liver laboratory and other tests, and quality of life. The data were collected from a randomized, placebo-controlled trial underway at 7 tertiary-care medical centers to determine whether the combination of an angiotensin I-converting enzyme inhibitor and angiotensin II-receptor blocker was superior to the inhibitor alone, and whether low blood pressure (<110/75 mm Hg) was superior to standard blood pressure (120-130/70-80 mm Hg), in delaying renal cystic progression in 558 patients with ADPKD, stages 1 and 2 chronic kidney disease, and hypertension (age, 15-49 y). RESULTS: We found hepatomegaly to be common among patients with ADPKD. Cysts and parenchyma contributed to hepatomegaly. Cysts were more common and liver and cyst volumes were greater in women, increasing with age. Patients with advanced disease had a relative loss of liver parenchyma. We observed small abnormalities in results from liver laboratory tests, and that splenomegaly and hypersplenism were associated with PLD severity. Higher liver volumes were associated with a lower quality of life. CONCLUSIONS: Hepatomegaly is common even in early stage ADPKD and is not accounted for by cysts alone. Parenchymal volumes were larger, compared with liver volumes of patients without ADPKD or with those predicted by standardized equations, even among patients without cysts. The severity of PLD was associated with altered biochemical and hematologic features, as well as quality of life. ClinicalTrials.gov identifier: NCT00283686.
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Hepatomegalia/epidemiologia , Hepatomegalia/patologia , Rim Policístico Autossômico Dominante/complicações , Rim Policístico Autossômico Dominante/diagnóstico , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Fígado , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto JovemRESUMO
BACKGROUND: Hypertension develops early in patients with autosomal dominant polycystic kidney disease (ADPKD) and is associated with disease progression. The renin-angiotensin-aldosterone system (RAAS) is implicated in the pathogenesis of hypertension in patients with ADPKD. Dual blockade of the RAAS may circumvent compensatory mechanisms that limit the efficacy of monotherapy with an angiotensin-converting-enzyme (ACE) inhibitor or angiotensin II-receptor blocker (ARB). METHODS: In this double-blind, placebo-controlled trial, we randomly assigned 486 patients, 18 to 64 years of age, with ADPKD (estimated glomerular filtration rate [GFR], 25 to 60 ml per minute per 1.73 m(2) of body-surface area) to receive an ACE inhibitor (lisinopril) and placebo or lisinopril and an ARB (telmisartan), with the doses adjusted to achieve a blood pressure of 110/70 to 130/80 mm Hg. The composite primary outcome was the time to death, end-stage renal disease, or a 50% reduction from the baseline estimated GFR. Secondary outcomes included the rates of change in urinary aldosterone and albumin excretion, frequency of hospitalizations for any cause and for cardiovascular causes, incidence of pain, frequency of ADPKD-related symptoms, quality of life, and adverse study-medication effects. Patients were followed for 5 to 8 years. RESULTS: There was no significant difference between the study groups in the incidence of the composite primary outcome (hazard ratio with lisinopril-telmisartan, 1.08; 95% confidence interval, 0.82 to 1.42). The two treatments controlled blood pressure and lowered urinary aldosterone excretion similarly. The rates of decline in the estimated GFR, urinary albumin excretion, and other secondary outcomes and adverse events, including hyperkalemia and acute kidney injury, were also similar in the two groups. CONCLUSIONS: Monotherapy with an ACE inhibitor was associated with blood-pressure control in most patients with ADPKD and stage 3 chronic kidney disease. The addition of an ARB did not alter the decline in the estimated GFR. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; HALT-PKD [Study B] ClinicalTrials.gov number, NCT01885559.).