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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.

In a trial involving patients with later-stage ADPKD, the V 2 -receptor antagonist tolvaptan resulted in a slower decline than placebo in the estimated GFR over a 1-year period, which may slow the onset of end-stage kidney disease.

Key Points Intracranial aneurysms (IAs) are the most common vascular manifestation of autosomal dominant polycystic kidney disease (ADPKD) Individuals with ADPKD and increased risk of IA—including those with a family or personal history of IA or subarachnoid haemorrhage—should undergo screening Other vascular abnormalities in ADPKD include aneurysms and dissections of the thoracic aorta, coronary arteries and cervicocephalic arteries, aortic root dilatation and cerebral dolichoectasia; screening is not usually indicated Asymptomatic IAs detected by screening are frequently small and have a low risk of rupture Intervention, either surgical or endovascular, is indicated based on the size and location of the aneurysm The relationship between PKD1 and PKD2 mutations and the development of vascular abnormalities is undefined; modifier genes that increase TGF-β signalling might increase the risk of vascular complications in ADPKD Vascular abnormalities, particularly those associated with rupture of intracranial aneurysms (IAs) or arterial dissections are among the most serious complications of autosomal dominant polycystic kidney disease (ADPKD). In this article, the authors discuss the pathophysiological mechanisms that might be involved in the development of vascular complications in patients with ADPKD and review strategies for screening, diagnosis and treatment of IAs in this population. Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease. Relentless cyst growth substantially enlarges both kidneys and culminates in renal failure. Patients with ADPKD also have vascular abnormalities; intracranial aneurysms (IAs) are found in ∼10% of asymptomatic patients during screening and in up to 25% of those with a family history of IA or subarachnoid haemorrhage. As the genes responsible for ADPKD— PKD1 and PKD2 —have complex integrative roles in mechanotransduction and intracellular calcium signalling, the molecular basis of IA formation might involve focal haemodynamic conditions exacerbated by hypertension and altered flow sensing. IA rupture results in substantial mortality, morbidity and poor long-term outcomes. In this Review, we focus mainly on strategies for screening, diagnosis and treatment of IAs in patients with ADPKD. Other vascular aneurysms and anomalies—including aneurysms of the aorta and coronary arteries, cervicocephalic and thoracic aortic dissections, aortic root dilatation and cerebral dolichoectasia—are less common in this population, and the available data are insufficient to recommend screening strategies. Treatment decisions should be made with expert consultation and be based on a risk–benefit analysis that takes into account aneurysm location and morphology as well as patient age and comorbidities.

In patients with autosomal dominant polycystic kidney disease, the rate of increase in total kidney volume was not slowed by lisinopril and telmisartan, as compared with lisinopril and placebo, but was slowed with rigorous blood-pressure control. Autosomal dominant polycystic kidney disease (ADPKD) is characterized by gradual cyst enlargement over a period of decades before the loss of kidney function. 1 – 3 Total kidney volume in ADPKD is accurately measured with the use of magnetic resonance imaging (MRI). 4 – 6 Hypertension occurs early 6 , 7 and is associated with progression to end-stage renal disease (ESRD) and death from cardiovascular causes in patients with ADPKD. 8 , 9 Immunohistologic studies 10 , 11 and clinical studies 12 , 13 support a central role of the renin–angiotensin–aldosterone system (RAAS) in the pathogenesis of hypertension in patients with ADPKD. Activation of the RAAS may promote renal-cyst growth by means . . .

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.This Consensus Statement developed on behalf of the Network for Early Onset Cystic Kidney Disease provides guidance on counselling, diagnosing and monitoring children with autosomal dominant polycystic kidney disease based on current evidence and a multi-stakeholder discussion of ethical issues.

This trial tested single versus dual inhibition of the renin–angiotensin–aldosterone system in ADPKD. ACE-inhibitor monotherapy controlled blood pressure in most patients. Adding an angiotensin II–receptor blocker did not alter the decline in estimated GFR. Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the progressive development of kidney cysts. 1 Hypertension develops early in patients with ADPKD and is associated with the progression of disease. 2 The renin–angiotensin–aldosterone system (RAAS) is implicated in the pathogenesis of hypertension in patients with ADPKD. 2 – 7 Angiotensin-converting–enzyme (ACE) inhibitors slow the progression of renal dysfunction in nondiabetic kidney diseases. 8 , 9 On the basis of these data, the use of ACE inhibitors as first-line agents to treat hypertension in patients with ADPKD has become standard clinical practice, although no randomized, clinical trials of sufficient size and quality have shown their superiority . . .

Chronic kidney disease is a worldwide public health problem with an increasing incidence and prevalence, poor outcomes, and high cost. Outcomes of chronic kidney disease include not only kidney failure but also complications of decreased kidney function and cardiovascular disease. Current evidence suggests that some of these adverse outcomes can be prevented or delayed by early detection and treatment. Unfortunately, chronic kidney disease is underdiagnosed and undertreated, in part as a result of lack of agreement on a definition and classification of its stages of progression. Recent clinical practice guidelines by the National Kidney Foundation 1) define chronic kidney disease and classify its stages, regardless of underlying cause, 2) evaluate laboratory measurements for the clinical assessment of kidney disease, 3) associate the level of kidney function with complications of chronic kidney disease, and 4) stratify the risk for loss of kidney function and development of cardiovascular disease. The guidelines were developed by using an approach based on the procedure outlined by the Agency for Healthcare Research and Quality. This paper presents the definition and five-stage classification system of chronic kidney disease and summarizes the major recommendations on early detection in adults. Recommendations include identifying persons at increased risk (those with diabetes, those with hypertension, those with a family history of chronic kidney disease, those older than 60 years of age, or those with U.S. racial or ethnic minority status), detecting kidney damage by measuring the albumin-creatinine ratio in untimed (\"spot\") urine specimens, and estimating the glomerular filtration rate from serum creatinine measurements by using prediction equations. Because of the high prevalence of early stages of chronic kidney disease in the general population (approximately 11% of adults), this information is particularly important for general internists and specialists.

Pain is a common symptom in people with autosomal dominant polycystic kidney disease (ADPKD), but it is assessed and reported inconsistently in research, and the validity of the measures remain uncertain. The aim of this study was to identify the characteristics, content, and psychometric properties of measures for pain used in ADPKD. We conducted a systematic review including all trials and observational studies that reported pain in people with ADPKD. Items from all measures were categorized into content and measurement dimensions of pain. We assessed the general characteristics and psychometric properties of all measures. 118 studies, we identified 26 measures: 12 (46%) measures were developed for a non-ADPKD population, 1 (4%) for chronic kidney disease, 2 (8%) for polycystic liver disease and 11 (42%) specifically for ADPKD. Ten anatomical sites were included, with the lower back the most common (10 measures [39%]), four measurement dimensions (intensity (23 [88%]), frequency (3 [12%]), temporality (2 [8%]), and sensory (21 [81%]), two pain types, nociceptive including visceral (15 [58%]) and somatic (5 [20%]), and neuropathic (2 [8%]), and twelve impact dimensions, where the most frequent was work (5 [31%]). The validation data for the measures were variable and only the ADPKD Impact Scale reported all psychometric domains. The measures for pain in ADPKD varied in terms of content and length, and most had not been validated in ADPKD. A standardized psychometrically robust measure that captures patient-important dimensions of pain is needed to evaluate and manage this debilitating complication of ADPKD.

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.

HALT PKD consists of two ongoing randomized trials with the largest cohort of systematically studied patients with autosomal dominant polycystic kidney disease to date. Study A will compare combined treatment with an angiotensin-converting inhibitor and receptor blocker to inhibitor alone and standard compared with low blood pressure targets in 558 early-stage disease patients with an eGFR over 60ml/min per 1.73m2. Study B will compare inhibitor-blocker treatment to the inhibitor alone in 486 late-stage patients with eGFR 25–60ml/min per 1.73m2. We used correlation and multiple regression cross-sectional analyses to determine associations of baseline parameters with total kidney, liver, or liver cyst volumes measured by MRI in Study A and eGFR in both studies. Lower eGFR and higher natural log-transformed urine albumin excretion were independently associated with a larger natural log–transformed total kidney volume adjusted for height (ln(HtTKV)). Higher body surface area was independently associated with a higher ln(HtTKV) and lower eGFR. Men had larger height-adjusted total kidney volume and smaller liver cyst volumes than women. A weak correlation was found between the ln(HtTKV) and natural log–transformed total liver volume adjusted for height or natural log liver cyst volume in women only. Women had higher urine aldosterone excretion and lower plasma potassium. Thus, our analysis (1) confirms a strong association between renal volume and functional parameters, (2) shows that gender and other factors differentially affect the development of polycystic disease in the kidney and liver, and (3) suggests an association between anthropomorphic measures reflecting prenatal and/or postnatal growth and disease severity.