RESUMEN
Autosomal dominant polycystic kidney disease is the most commonly inherited disease of the kidneys affecting an estimated 12,000,000 people in the world. Autosomal dominant polycystic kidney disease is a systemic disease, with a wide range of associated features that includes hypertension, valvular heart diseases, cerebral aneurysms, aortic aneurysms, liver cysts, abdominal hernias, diverticulosis, gross hematuria, urinary tract infections, nephrolithiasis, pancreatic cysts, and seminal vesicle cysts. The cardiovascular anomalies are somewhat different than in the general population and also chronic kidney disease population, with higher morbidity and mortality rates. This review will focus on cardiovascular diseases associated with autosomal dominant polycystic kidney disease and their management.
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Enfermedades Cardiovasculares , Quistes , Hipertensión , Riñón Poliquístico Autosómico Dominante , Humanos , Riñón Poliquístico Autosómico Dominante/complicaciones , Enfermedades Cardiovasculares/epidemiología , Hipertensión/complicaciones , Riñón , Quistes/complicacionesRESUMEN
BACKGROUND: Intensive BP lowering in the Systolic Blood Pressure Intervention Trial (SPRINT) produced acute decreases in kidney function and higher risk for AKI. We evaluated the effect of intensive BP lowering on long-term changes in kidney function using trial and outpatient electronic health record (EHR) creatinine values. METHODS: SPRINT data were linked with EHR data from 49 (of 102) study sites. The primary outcome was the total slope of decline in eGFR for the intervention phase and the post-trial slope of decline during the observation phase using trial and outpatient EHR values. Secondary outcomes included a ≥30% decline in eGFR to <60 ml/min per 1.73 m 2 and a ≥50% decline in eGFR or kidney failure among participants with baseline eGFR ≥60 and <60 ml/min per 1.73 m 2 , respectively. RESULTS: EHR creatinine values were available for a median of 8.3 years for 3041 participants. The total slope of decline in eGFR during the intervention phase was -0.67 ml/min per 1.73 m 2 per year (95% confidence interval [CI], -0.79 to -0.56) in the standard treatment group and -0.96 ml/min per 1.73 m 2 per year (95% CI, -1.08 to -0.85) in the intensive treatment group ( P < 0.001). The slopes were not significantly different during the observation phase: -1.02 ml/min per 1.73 m 2 per year (95% CI, -1.24 to -0.81) in the standard group and -0.85 ml/min per 1.73 m 2 per year (95% CI, -1.07 to -0.64) in the intensive group. Among participants without CKD at baseline, intensive treatment was associated with higher risk of a ≥30% decline in eGFR during the intervention (hazard ratio, 3.27; 95% CI, 2.43 to 4.40), but not during the postintervention observation phase. In those with CKD at baseline, intensive treatment was associated with a higher hazard of eGFR decline only during the intervention phase (hazard ratio, 1.95; 95% CI, 1.03 to 3.70). CONCLUSIONS: Intensive BP lowering was associated with a steeper total slope of decline in eGFR and higher risk for kidney events during the intervention phase of the trial, but not during the postintervention observation phase.
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Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by kidney cyst formation and progressive kidney function loss. Dietary interventions such as caloric restriction, intermittent fasting, and ketogenic diet have recently emerged as potential strategies to induce metabolic reprogramming and slow ADPKD progression. We review the available evidence supporting the efficacy and safety of these interventions in ADPKD. Dietary interventions show promise in managing ADPKD by improving metabolic health and reducing oxidative stress. However, while preclinical studies have shown favorable outcomes, limited clinical evidence supports their effectiveness. In addition, the long-term consequences of these dietary interventions, including their effect on adverse events in patients with ADPKD, remain uncertain. To optimize ADPKD management, patients are advised to follow a dietary regimen that aims to achieve or maintain an ideal body weight and includes high fluid intake, low sodium, and limited concentrated sweets. Caloric restriction seems particularly beneficial for patients with overweight or obesity because it promotes weight loss and improves metabolic parameters. Supplementation with curcumin, ginkgolide B, saponins, vitamin E, niacinamide, or triptolide has demonstrated uncertain clinical benefit in patients with ADPKD. Notably, ß -hydroxybutyrate supplements have shown promise in animal models; however, their safety and efficacy in ADPKD require further evaluation through well-designed clinical trials. Therefore, the use of these supplements is not currently recommended for patients with ADPKD. In summary, dietary interventions such as caloric restriction, intermittent fasting, and ketogenic diet hold promise in ADPKD management by enhancing metabolic health. However, extensive clinical research is necessary to establish their effectiveness and long-term effects. Adhering to personalized dietary guidelines, including weight management and specific nutritional restrictions, can contribute to optimal ADPKD management. Future research should prioritize well-designed clinical trials to determine the benefits and safety of dietary interventions and supplementation in ADPKD.
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Background: Adjudication of inpatient AKI in the Systolic Blood Pressure Intervention Trial (SPRINT) was based on billing codes and admission and discharge notes. The purpose of this study was to evaluate the effect of intensive versus standard BP control on creatinine-based inpatient and outpatient AKI, and whether AKI was associated with cardiovascular disease (CVD) and mortality. Methods: We linked electronic health record (EHR) data from 47 clinic sites with trial data to enable creatinine-based adjudication of AKI. Cox regression was used to evaluate the effect of intensive BP control on the incidence of AKI, and the relationship between incident AKI and CVD and all-cause mortality. Results: A total of 3644 participants had linked EHR data. A greater number of inpatient AKI events were identified using EHR data (187 on intensive versus 155 on standard treatment) as compared with serious adverse event (SAE) adjudication in the trial (95 on intensive versus 61 on standard treatment). Intensive treatment increased risk for SPRINT-adjudicated inpatient AKI (HR, 1.51; 95% CI, 1.09 to 2.08) and for creatinine-based outpatient AKI (HR, 1.40; 95% CI, 1.15 to 1.70), but not for creatinine-based inpatient AKI (HR, 1.20; 95% CI, 0.97 to 1.48). Irrespective of the definition (SAE or creatinine based), AKI was associated with increased risk for all-cause mortality, but only creatinine-based inpatient AKI was associated with increased risk for CVD. Conclusions: Creatinine-based ascertainment of AKI, enabled by EHR data, may be more sensitive and less biased than traditional SAE adjudication. Identifying ways to prevent AKI may reduce mortality further in the setting of intensive BP control.
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Lesión Renal Aguda , Enfermedades Cardiovasculares , Hipertensión , Lesión Renal Aguda/epidemiología , Antihipertensivos/efectos adversos , Presión Sanguínea , Enfermedades Cardiovasculares/epidemiología , Creatinina/farmacología , Registros Electrónicos de Salud , Humanos , Hipertensión/complicaciones , Factores de Riesgo , Resultado del TratamientoRESUMEN
Importance: Low socioeconomic status (SES) in the form of educational level and income has been linked to greater cardiovascular risk across cohorts; however, associations have been inconsistent for African American individuals. Net worth, a measure of overall assets, may be a more relevant metric, especially for African American women, because it captures longer-term financial stability and economic reserve. Objective: To examine whether net worth is associated with increased ambulatory blood pressure (ABP), a marker of cardiovascular disease (CVD) risk, independent of educational level and income, in young to middle-aged African American women. Design, Setting, and Participants: A cross-sectional, community-based study conducted in the southeastern US was performed using 48-hour ambulatory BP monitoring. Participants included 384 African American women aged 30 to 46 years without clinical CVD recruited between December 16, 2016, and March 21, 2019; data analysis was performed from September 2020 to December 2021. Exposures: Self-reported net worth (total financial assets minus debts), self-reported educational level, and self-reported income. Main Outcomes and Measures: Mean daytime and nighttime BP levels, assessed via 48-hour ABP monitoring and sustained hypertension (ABP daytime and clinic BP ≥130/80 mm Hg). Results: The 384 African American women in this study represented a range of SES backgrounds; mean (SD) age was 38.0 (4.3) years. Excluding 66 women who were not receiving antihypertensive medications, in linear regression models adjusted for age, marital status, educational level, family income, and family size, women reporting a negative net worth (debt) had higher levels of daytime (ß = 6.7; SE = 1.5; P < .001) and nighttime (ß = 6.4; SE = 1.4; P < .001) systolic BP, compared with women reporting a positive net worth. Similar associations were observed with sustained hypertension: women reporting a negative net worth had 150% higher odds (odds ratio, 2.5; 95% CI, 1.3-4.7) of sustained hypertension than those reporting a positive net worth. Associations remained significant after additional adjustments for smoking, body mass index, psychosocial stress due to debt, and depressive symptoms and were similar, although attenuated, when women receiving antihypertensive medications were included and treatment was controlled for in all analyses. Conclusions and Relevance: In this cross-sectional study, having a negative net worth (ie, debt) was associated with elevated BP in African American women, independent of traditional indicators of SES. This finding suggests that limited assets or a lack of economic reserve may be associated with poor CVD outcomes in this at-risk group.
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Negro o Afroamericano/estadística & datos numéricos , Presión Sanguínea/fisiología , Estados Financieros/estadística & datos numéricos , Adulto , Monitoreo Ambulatorio de la Presión Arterial , Estudios Transversales , Femenino , Humanos , Hipertensión/epidemiología , Persona de Mediana EdadRESUMEN
BACKGROUND: End-stage kidney disease patients on dialysis are particularly susceptible to COVID-19 infection due to comorbidities, age, and logistic constraints of dialysis making social distancing difficult. We describe our experience with hospitalized dialysis patients with COVID-19 and factors associated with mortality. METHODS: From March 1, 2020, to May 31, 2020, all dialysis patients admitted to 4 Emory Hospitals and tested for COVID-19 were identified. Sociodemographic information and clinical and laboratory data were obtained from the medical record. Death was defined as an in-hospital death or transfer to hospice for end-of-life care. Patients were followed until discharge or death. RESULTS: Sixty-four dialysis patients with COVID-19 were identified. Eighty-four percent were African-American. The median age was 64 years, and 59% were males. Four patients were on peritoneal dialysis, and 60 were on hemodialysis for a median time of 3.8 years, while 31% were obese. Fever (72%), cough (61%), and diarrhea (22%) were the most common symptoms at presentation. Thirty-three percent required admission to intensive care unit, and 23% required mechanical ventilation. The median length of stay was 10 days, while 11 patients (17%) died during hospitalization and 17% were discharged to a temporary rehabilitation facility. Age >65 years (RR 13.7, CI: 1.9-100.7), C-reactive protein >100 mg/dL (RR 8.3, CI: 1.1-60.4), peak D-dimer >3,000 ng/mL (RR 4.3, CI: 1.03-18.2), bilirubin >1 mg/dL (RR 3.9, CI: 1.5-10.4), and history of peripheral vascular disease (RR 3.2, CI: 1.2-9.1) were associated with mortality. Dialysis COVID-19-infected patients were more likely to develop thromboembolic complications than those without COVID-19 (RR 3.7, CI: 1.3-10.1). CONCLUSION: In a predominantly African-American population, the mortality of end-stage kidney disease patients admitted with COVID-19 infection was 17%. Age, C-reactive protein, D-dimer, bilirubin, and history of peripheral vascular disease were associated with worse survival.
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Negro o Afroamericano/estadística & datos numéricos , COVID-19/mortalidad , Fallo Renal Crónico/complicaciones , Anciano , COVID-19/sangre , COVID-19/complicaciones , COVID-19/etnología , Femenino , Georgia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Tromboembolia/virologíaRESUMEN
INTRODUCTION: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst growth and a loss of functioning renal mass, but a decline in glomerular filtration rate (GFR) and onset of end-stage renal disease (ESRD) occur late in the disease course. There is therefore a great need for early prognostic biomarkers in this disorder. METHODS: We measured baseline serum fibroblast growth factor 23 (FGF23) levels in 192 patients with ADPKD from the Consortium for Radiologic Imaging Studies of PKD (CRISP) cohort that were followed for a median of 13 years and tested the association between FGF23 levels and change over time in height-adjusted total kidney volume (htTKV), GFR, and time to the composite endpoints of ESRD, death, and doubling of serum creatinine. RESULTS: Patients in the highest quartile for baseline FGF23 level had a higher rate of increase in htTKV (0.95% per year, P = 0.0016), and faster rate of decline in GFR (difference of -1.03 ml/min/1.73 m2 per year, P = 0.005) compared with the lowest quartile, after adjusting for other covariates, including htTKV and genotype. The highest quartile of FGF23 was also associated with a substantial increase in risk for the composite endpoint of ESRD, death, or doubling of serum creatinine (hazard ratio [HR] of 2.45 in the fully adjusted model, P = 0.03). CONCLUSION: FGF23 is a prognostic biomarker for disease progression and clinically important outcomes in ADPKD, and has additive value to established imaging and genetic biomarkers.
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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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Procesamiento de Imagen Asistido por Computador/métodos , Fallo Renal Crónico/patología , Riñón/patología , Mutación , Riñón Poliquístico Autosómico Dominante/fisiopatología , Canales Catiónicos TRPP/genética , Adulto , Anciano , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Genotipo , Tasa de Filtración Glomerular , Humanos , Riñón/metabolismo , Fallo Renal Crónico/diagnóstico por imagen , Fallo Renal Crónico/genética , Masculino , Persona de Mediana Edad , Riñón Poliquístico Autosómico Dominante/diagnóstico por imagen , Riñón Poliquístico Autosómico Dominante/genética , Tomografía Computarizada por Rayos XRESUMEN
Autosomal dominant polycystic kidney disease (ADPKD) is an inherited, progressive nephropathy accounting for 4-10% of end stage renal disease worldwide. PKD1 and PKD2 are the most common disease loci, but even accounting for other genetic causes, about 7% of families remain unresolved. Typically, these unsolved cases have relatively mild kidney disease and often have a negative family history. Mosaicism, due to de novo mutation in the early embryo, has rarely been identified by conventional genetic analysis of ADPKD families. Here we screened for mosaicism by employing two next generation sequencing screens, specific analysis of PKD1 and PKD2 employing long-range polymerase chain reaction, or targeted capture of cystogenes. We characterized mosaicism in 20 ADPKD families; the pathogenic variant was transmitted to the next generation in five families and sporadic in 15. The mosaic pathogenic variant was newly discovered by next generation sequencing in 13 families, and these methods precisely quantified the level of mosaicism in all. All of the mosaic cases had PKD1 mutations, 14 were deletions or insertions, and 16 occurred in females. Analysis of kidney size and function showed the mosaic cases had milder disease than a control PKD1 population, but only a few had clearly asymmetric disease. Thus, in a typical ADPKD population, readily detectable mosaicism by next generation sequencing accounts for about 1% of cases, and about 10% of genetically unresolved cases with an uncertain family history. Hence, identification of mosaicism is important to fully characterize ADPKD populations and provides informed prognostic information.
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Riñón Poliquístico Autosómico Dominante , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Mosaicismo , Mutación , Riñón Poliquístico Autosómico Dominante/diagnóstico , Riñón Poliquístico Autosómico Dominante/genética , Canales Catiónicos TRPP/genéticaRESUMEN
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by cyst and kidney growth, which is hypothesized to cause loss of functioning renal mass and eventually end-stage kidney disease. However, the time course of decline in glomerular filtration rate (GFR) is poorly defined. The Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease study is a 14-year observational cohort study of 241 adults with ADPKD. As an estimate of the rate of kidney growth, participants were stratified into 5 subclasses based on baseline age and magnetic resonance imaging measurements of total kidney volume (TKV) according to the method of Irazabal. GFR trajectories spanning over four decades of life were reconstructed and fitted using mixed polynomial models, which were validated using data from the HALT-PKD study. GFR trajectories were nonlinear, with a period of relative stability in most participants, followed by accelerating decline. The shape and slope of these trajectories were strongly associated with baseline Irazabal class. Patients with PKD1 mutations had a steeper GFR decline than patients with PKD2 mutations or with no detected mutation, largely mediated by the effect of genotype on Irazabal class. Thus, GFR decline in ADPKD is nonlinear, and its trajectory throughout adulthood can be predicted from a single measurement of kidney volume. These models can be used for clinical prognostication, clinical trial design, and patient selection for clinical interventions. Our findings support a causal link between growth in kidney volume and GFR decline, adding support for the use of TKV as a surrogate endpoint in clinical trials.
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Tasa de Filtración Glomerular/genética , Fallo Renal Crónico/fisiopatología , Riñón/fisiopatología , Modelos Biológicos , Riñón Poliquístico Autosómico Dominante/complicaciones , Adulto , Progresión de la Enfermedad , Femenino , Humanos , Fallo Renal Crónico/etiología , Masculino , Mutación , Riñón Poliquístico Autosómico Dominante/genética , Riñón Poliquístico Autosómico Dominante/patología , Canales Catiónicos TRPP/genética , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: Caffeine has been proposed, based on in vitro cultured cell studies, to accelerate progression of autosomal dominant polycystic kidney disease (ADPKD) by increasing kidney size. Since ADPKD patients are advised to minimize caffeine intake, we investigated the effect of caffeine on disease progression in the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP), a prospective, observational cohort study. METHODS: Our study included 239 patients (mean age = 32.3 ± 8.9 ys; 188 caffeine consumers) with a median follow-up time of 12.5 years. Caffeine intake reported at baseline was dichotomized (any vs. none). Linear mixed models, unadjusted and adjusted for age, race, sex, BMI, smoking, hypertension, genetics and time, were used to model height-adjusted total kidney volume (htTKV) and iothalamate clearance (mGFR). Cox proportional hazards models and Kaplan-Meier plots examined the effect of caffeine on time to ESRD or death. RESULTS: Caffeine-by-time was statistically significant when modeling ln(htTKV) in unadjusted and adjusted models (p < 0.01) indicating that caffeine consumers had slightly faster kidney growth (by 0.6% per year), but htTKV remained smaller from baseline throughout the study. Caffeine consumption was not associated with a difference in mGFR, or in the time to ESRD or death (p > 0.05). Moreover the results were similar when outcomes were modeled as a function of caffeine dose. CONCLUSION: We conclude that caffeine does not have a significant detrimental effect on disease progression in ADPKD.
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Cafeína/administración & dosificación , Progresión de la Enfermedad , Riñón/patología , Riñón Poliquístico Autosómico Dominante/patología , Riñón Poliquístico Autosómico Dominante/fisiopatología , Adulto , Cafeína/efectos adversos , Femenino , Tasa de Filtración Glomerular , Humanos , Estimación de Kaplan-Meier , Fallo Renal Crónico/etiología , Masculino , Estudios Observacionales como Asunto , Tamaño de los Órganos , Riñón Poliquístico Autosómico Dominante/complicaciones , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Tiempo , Adulto JovenRESUMEN
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/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Antihipertensivos/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Hipertensión/prevención & control , Riñón/efectos de los fármacos , Riñón Poliquístico Autosómico Dominante/tratamiento farmacológico , Sistema Renina-Angiotensina/efectos de los fármacos , Adolescente , Adulto , Antagonistas de Receptores de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Antihipertensivos/efectos adversos , Progresión de la Enfermedad , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Humanos , Hipertensión/diagnóstico , Hipertensión/etiología , Hipertensión/fisiopatología , Riñón/patología , Riñón/fisiopatología , Masculino , Persona de Mediana Edad , Riñón Poliquístico Autosómico Dominante/complicaciones , Riñón Poliquístico Autosómico Dominante/diagnóstico , Riñón Poliquístico Autosómico Dominante/fisiopatología , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
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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Progresión de la Enfermedad , Tasa de Filtración Glomerular/fisiología , Riñón Poliquístico Autosómico Dominante/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Adolescente , Adulto , Factores de Edad , Teorema de Bayes , Femenino , Humanos , Incidencia , Pruebas de Función Renal , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Riñón Poliquístico Autosómico Dominante/diagnóstico , Pronóstico , Insuficiencia Renal Crónica/epidemiología , Medición de Riesgo , Índice de Severidad de la Enfermedad , Factores Sexuales , Adulto JovenRESUMEN
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive enlargement of kidney cysts leading to chronic kidney disease (CKD) and end-stage renal disease (ESRD). Identification of an early biomarker that can predict progression of CKD is urgently needed. In an earlier Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) study (a prospective, multicenter, observational analysis of 241 patients with ADPKD initiated in 2000), baseline height-adjusted total kidney volume (htTKV) was shown to be associated with development of CKD stage 3 after eight years of follow-up. Here we conducted an extended study and found that in a multivariable logistic regression model, baseline htTKV was shown to be a strong, independent predictor for the development of CKD after a median follow-up of 13 years. The odds ratio of reaching each CKD stage per 100 mL/m increment in htTKV was 1.38 (95% confidence interval 1.19-1.60) for stage 3, 1.42 (1.23-1.64) for stage 4, and 1.35 (1.18-1.55) for stage 5 or ESRD. Baseline htTKV was also associated with relative decreases in the glomerular filtration rate of 30%, and 57% or more. Moreover, the rate of change in htTKV was negatively correlated with the slope of the glomerular filtration rate. While ADPKD genotype was also associated with CKD outcomes, it was not an independent prognostic factor after adjusting for htTKV. Thus, baseline total kidney volume and the rate of kidney growth are strongly associated with the development of advanced stages of CKD. These findings support the use of total kidney volume as a prognostic and potentially monitoring biomarker in ADPKD.
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Fallo Renal Crónico/etiología , Riñón/diagnóstico por imagen , Imagen por Resonancia Magnética , Riñón Poliquístico Autosómico Dominante/diagnóstico por imagen , Insuficiencia Renal Crónica/etiología , Adolescente , Adulto , Progresión de la Enfermedad , Femenino , Tasa de Filtración Glomerular , Humanos , Riñón/crecimiento & desarrollo , Riñón/patología , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/fisiopatología , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Riñón Poliquístico Autosómico Dominante/complicaciones , Riñón Poliquístico Autosómico Dominante/patología , Riñón Poliquístico Autosómico Dominante/fisiopatología , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/fisiopatología , Factores de Riesgo , Factores de Tiempo , Estados Unidos , Adulto JovenRESUMEN
The association of overweight/obesity with disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD) remains untested. We hypothesized that overweight/obesity associates with faster progression in early-stage ADPKD. Overall, 441 nondiabetic participants with ADPKD and an eGFR>60 ml/min per 1.73 m2 who participated in the Halt Progression of Polycystic Kidney Disease Study A were categorized on the basis of body mass index (BMI; calculated using nonkidney and nonliver weight) as normal weight (18.5-24.9 kg/m2; reference; n=192), overweight (25.0-29.9 kg/m2; n=168), or obese (≥30 kg/m2; n=81). We evaluated the longitudinal (5-year) association of overweight/obesity with change in total kidney volume (TKV) by magnetic resonance imaging using linear regression and multinomial logistic regression models. Among participants, mean±SD age was 37±8 years, annual percent change in TKV was 7.4%±5.1%, and BMI was 26.3±4.9 kg/m2 The annual percent change in TKV increased with increasing BMI category (normal weight: 6.1%±4.7%, overweight: 7.9%±4.8%, obese: 9.4%±6.2%; P<0.001). In the fully adjusted model, higher BMI associated with greater annual percent change in TKV (ß=0.79; 95% confidence interval [95% CI], 0.18 to 1.39, per 5-unit increase in BMI). Overweight and obesity associated with increased odds of annual percent change in TKV ≥7% compared with <5% (overweight: odds ratio, 2.02; 95% CI, 1.15 to 3.56; obese: odds ratio, 3.76; 95% CI, 1.81 to 7.80). Obesity also independently associated with greater eGFR decline (slope) versus normal weight (fully adjusted ß =-0.08; 95% CI, -0.15 to -0.02). In conclusion, overweight and, particularly, obesity are strongly and independently associated with rate of progression in early-stage ADPKD.
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Riñón/patología , Obesidad/epidemiología , Riñón Poliquístico Autosómico Dominante/fisiopatología , Adulto , Índice de Masa Corporal , Progresión de la Enfermedad , Femenino , Tasa de Filtración Glomerular , Humanos , Riñón/diagnóstico por imagen , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Sobrepeso/epidemiología , Factores de TiempoRESUMEN
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.
Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Fallo Renal Crónico/prevención & control , Riñón/efectos de los fármacos , Riñón Poliquístico Autosómico Dominante/tratamiento farmacológico , Adolescente , Adulto , Antihipertensivos/uso terapéutico , Progresión de la Enfermedad , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Riñón/patología , Riñón/fisiopatología , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/etiología , Fallo Renal Crónico/mortalidad , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Riñón Poliquístico Autosómico Dominante/complicaciones , Riñón Poliquístico Autosómico Dominante/diagnóstico , Riñón Poliquístico Autosómico Dominante/mortalidad , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
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.