Management Of Autosomal Dominant Polycystic Kidney Disease Research Articles

Characterizing the impact of the Covid-19 pandemic on adults with autosomal dominant polycystic kidney disease: a cross-sectional study

BackgroundThe Covid-19 pandemic greatly affected those with chronic diseases, impacting healthcare access and healthcare seeking behaviors. The impact of the pandemic on adults with Autosomal Dominant Polycystic Kidney Disease (ADPKD) has not been investigated.MethodsParticipants were recruited from a cohort of 239 ADPKD patients enrolled in a longitudinal study at the University of Maryland. Patients on renal replacement therapy were excluded. N = 66 patients participated in a phone questionnaire from June 2022-December 2022 about ADPKD-related complications, concern about contracting Covid-19, healthcare-seeking behaviors, and telehealth utilization before and after March 2020.ResultsN = 34 (51.5%) of participants reported a positive Covid-19 test result. N = 29 (44%) expressed high concern of contracting Covid-19. Those who avoided medical care at least once (N = 17, 25.8%) had similar demographics and ADPKD severity to those who did not, but reported greater telehealth utilization (88.2% vs. 42.9%, p = 0.002), greater use of non-prescribed medication for Covid-19 treatment or prevention (35.3% vs. 8.2%, p = 0.01), and were more likely to contract Covid-19 (76.5% vs. 42.9%, p = 0.02). Among the N = 53 who reported very good or excellent ADPKD disease management pre-pandemic, N = 47(89%) reported no significant change during the pandemic.ConclusionsIn this highly educated, high-income cohort with a mean age of 46.1 years, most people reported well-managed ADPKD prior to the pandemic. This may explain why less than half of participants expressed high concern for contracting Covid-19. Overall, there was no significant pandemic-related decline in self-reported ADPKD management. This was likely due to this cohort’s excellent access to, and uptake of, telehealth services. Notably, 1 in 4 participants reported healthcare avoidant behavior, the effect of which may only be seen years from now. Future studies should investigate potential impacts of avoidant behaviors, as well as expand investigation to a more diverse cohort whose care may not have been as easily transitioned to telehealth.

Characterizing the Impact of the Covid-19 Pandemic on Adults with Autosomal Dominant Polycystic Kidney Disease: A Cross-Sectional Study.

The Covid-19 pandemic greatly affected those with chronic diseases, impacting healthcare access and healthcare seeking behaviors. The impact of the pandemic on adults with Autosomal Dominant Polycystic Kidney Disease (ADPKD) has not been investigated. Participants were recruited from a cohort of 239 ADPKD patients enrolled in a longitudinal study at the University of Maryland. Patients on renal replacement therapy were excluded. N = 66 patients participated in a phone questionnaire from June 2022-December 2022 about ADPKD-related complications, concern about contracting Covid-19, healthcare-seeking behaviors, and telehealth utilization before and after March 2020. N = 34 (51.5%) of participants reported a positive Covid-19 test result and N = 29 (44%) expressed high concern of contracting Covid-19. Those who avoided medical care at least once (N = 17, 25.8%) had similar demographics and ADPKD severity to those who did not, but reported greater telehealth utilization (88.2% vs. 42.9%, p = 0.002), greater use of non-prescribed medication for Covid-19 treatment or prevention (35.3% vs. 8.2%, p = 0.01), and were more likely to contract Covid-19 (76.5% vs. 42.9%, p = 0.02). Among the N = 53 who reported very good or excellent ADPKD disease management pre-pandemic, N = 47(89%) reported no significant change during the pandemic. In this highly educated, high-income cohort with a mean age of 46.1 years, most people reported well-managed ADPKD prior to the pandemic. This may explain why less than half of participants expressed high concern for contracting Covid-19. Overall, there was no significant pandemic-related decline in self-reported ADPKD management, like due to excellent access to, and uptake of, telehealth services. Notably, 1 in 4 participants reported healthcare avoidant behavior, the effect of which may only be seen years from now. Future studies should investigate potential impacts of avoidant behaviors, as well as expand investigation to a more diverse cohort whose care may not have been as easily transitioned to telehealth.

Additional renoprotective effect of the SGLT2 inhibitor dapagliflozin in a patient with ADPKD receiving tolvaptan treatment.

Autosomal dominant polycystic kidney disease (ADPKD) is a major cause of end-stage kidney disease (ESKD). Vasopressin plays a pivotal role in ADPKD progression; therefore, the selective vasopressin V2 receptor antagonist tolvaptan is used as a key drug in the management of ADPKD. On the other hand, sodium-glucose cotransporter-2 inhibitors (SGLT2i), which may possibly stimulate vasopressin secretion due to the diuretic effect of the drug, have been shown to have both renal and cardioprotective effects in various populations, including those with non-diabetic chronic kidney disease. However, the effect of SGLT2i in patients with ADPKD have not been fully elucidated. Herein, we report the case of a patient with ADPKD on tolvaptan who was administered the SGLT2i dapagliflozin. The patient was a Japanese woman diagnosed with ADPKD at age 30. Despite the treatment with tolvaptan, eGFR was gradually declined from 79.8 to 50ml/min/1.73m2 in almost 5years and 10mg of dapagliflozin was initiated in the hope of renoprotective effects. Although a small increase in vasopressin levels was observed, eGFR decline rate was moderated after dapagliflozin initiation. This case suggested an additional renoprotective effect of dapagliflozin in patient with ADPKD receiving tolvaptan. Although there is no evidence about the renal protective effect of SGLT2i in patients with ADPKD, we hereby report a case successfully treated with dapagliflozin for approximately 2 years. Further research, including clinical trials, is needed to evaluate whether SGLT2i are effective in patients with ADPKD.

Evaluation of the Renal and Cardiovascular Effects of Long-Term Tolvaptan Treatment in Autosomal Dominant Polycystic Kidney Disease

Introduction: Cardiovascular diseases constitute a significant cause of morbidity and mortality in individuals with autosomal dominant polycystic kidney disease (ADPKD). This study aimed to assess the long-term effects of tolvaptan on the kidneys and heart in rapidly progressing ADPKD. Methods: Among 354 patients diagnosed with ADPKD, 58 meeting the eligibility criteria for tolvaptan were included in the study. The study comprised two groups with similar demographic and clinical characteristics: 29 patients receiving tolvaptan treatment and 29 in the control group. Several included genetic analysis, magnetic resonance imaging, and echocardiography. Clinical and cardiac changes were recorded in both groups after a 3-year follow-up. Results: Tolvaptan treatment demonstrated a significant reduction in the rate of eGFR decline compared to the control group. Furthermore, it was observed that tolvaptan could prevent the development of cardiac arrhythmias by inhibiting an increase in QTc interval and heart rate. Conclusion: These findings suggest that, in addition to slowing kidney progression in ADPKD management, tolvaptan may potentially benefit in preventing cardiac complications.

Update on the Application of Ultrasonography in Understanding Autosomal Dominant Polycystic Kidney Disease.

With an estimated prevalence of 1 in 1000 individuals globally, autosomal dominant polycystic kidney disease (ADPKD) stands as the most prevalent inherited renal disorder. Ultrasonography (US) is the most widely used imaging modality in the diagnosis and monitoring of ADPKD. This review discusses the role of US in the evaluation of ADPKD, including its diagnostic accuracy, limitations, and recent advances. An overview of the pathophysiology and clinical manifestations of ADPKD has also been provided. Furthermore, the potential of US as a noninvasive tool for the assessment of disease progression and treatment response is examined. Overall, US remains an essential tool for the management of ADPKD, and ongoing research efforts are aimed at improving its diagnostic and prognostic capabilities.

Polycystic Kidney Disease Diet: What is Known and What is Safe.

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, β -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.

#6060 A NOVEL CT-BASED RADIOMICS APPROACH FOR KIDNEY FUNCTION EVALUATION IN ADPKD

Abstract Background and Aims Clinical management of autosomal dominant polycystic kidney disease (ADPKD) might take advantage of the use of new tools to predict risk of progression towards end stage kidney disease (ESKD). The aim of this study is to develop and validate a model based on radiomic features to predict kidney function among patients with ADPKD obtained from CT scans performed for the determination of total kidney volume (TKV). Method We retrospectively selected a cohort of 58 patients with ADPKD who underwent CT scan from February 2020 to March 2021, including 30 patients with eGFR ≥ 60 mL/min/1.73 m2 and 28 with eGFR < 60 mL/min/1.73 m2 at baseline. An expert radiologist generated a region of interest (ROI) segmentation for cystic kidney compounds, obtaining 58 ROIs from which we extracted 217 radiomic features using a dedicated software. We built three different logistic regression models to predict kidney function based on different predictors: height-adjusted TKV (ht-TKV), a selected radiomic feature (F_cm_merged.clust.tend), and both. Area under the curve (AUC) of the receiver operating characteristic (ROC) and accuracy were employed to evaluate models’ performance in discriminating between the two eGFR groups. Internal 3-fold cross-validation (CV) was performed. Results The ht-TKV, radiomic and combined models presented respectively an AUC (95% confidence interval) of 0.79 (0.67, 0.91), 0.83 (0.72, 0.93), 0.84 (0.74, 0.94), confirmed by the CV. Mean (standard deviation) values of the accuracy over CV iterations were 0.67 (0.10), 0.77 (0.09), 0.77 (0.09) for the three models. A model combining ht-TKV with a radiomic feature based on CT images from polycystic kidneys resulted effective in the prediction of baseline kidney function in our cohort. Furthermore, a logistic regression model based on a different radiomic feature (F_cm.2.5Dmerged.info.corr.2) selected among a subcohort of 29 ADPKD patients with a clinical follow-up, predicted rapid progression with a AUC of 0.81, a sensitivity of 100% and a specificity of 53%. Conclusion This is among the first studies which aimed to investigate, in a clinical setting, radiomics potential ability in discriminating eGFR at baseline and to explore as well whether a reliable radiomic feature could be taken into account in predicting faster rapid kidney function impairment over time. Further studies should implement a model extension to predict kidney function slope in order to confirm the role of radiomics in ADPKD management.

#5882 BENEFIT OF LONG-TERM TOLVAPTAN ADMINISTRATION ON KIDNEY DISEASE PROGRESSION IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE: A SINGLE-CENTRE EXPERIENCE

Abstract Background and Aims Tolvaptan introduction in autosomal dominant polycystic kidney disease (ADPKD) treatment has significantly modified kidney disease progression in these patients. The efficacy and safety of tolvaptan in the management of ADPKD has already been demonstrated by TEMPO and REPRISE trials, however studies examining the long-term outcomes are limited. The aim of our study was to evaluate the long-term administration of tolvaptan in patients with ADPKD in our center. Method ADPKD patients treated with tolvaptan for at least one year were included in the study. Demographic, laboratory, and total kidney volume (TKV) data were collected. Kidney disease progression was assessed by comparing observed and predicted glomerular filtration rate (eGFR), based on the Mayo Clinic prediction model, at the last visit. Results Forty-one patients, 22 males, with ADPKD were studied. Median age at initial visit was 35 years (IQR 27-42), and median time on tolvaptan treatment was 24 months (IQR 18-33). Six (14.6%) patients discontinued tolvaptan after at least one year on treatment. Patients were classified according to the Mayo Clinic imaging classification into 1C (n = 8), 1D (n = 16) and 1E (n = 17). Those who received tolvaptan showed a lower eGFR decline from baseline compared to predicted (eGFR 66.7±32.7 vs 61.5±29.1, p<0.001), while a greater benefit was observed in Class 1E (eGFR 60.1±36.5 vs 52.4±29.5, p = 0.003) and in patients with eGFR>45ml/min (eGFR 79.4±28.8 vs 73±25.2, p = 0.001). Conclusion Our initial experience from long-term administration of tolvaptan in patients with ADPKD demonstrates benefit on kidney disease progression. The widespread use of tolvaptan in a larger number of patients and their long-term follow up are necessary to draw more secure conclusions.

Delay in funding of tolvaptan for polycystic kidney disease in Aotearoa New Zealand.

Autosomal dominant polycystic kidney disease (ADPKD) is the fifth most common cause of end stage kidney disease (ESKD) in Aotearoa New Zealand. Identification of two genes, PCKD1 and PCKD2, which cause the majority of this disease, has played a key role in the development of DNA-sequence molecular diagnostics. ADPKD is characterised by the formation and growth of multiple cysts within the kidney, with some but not all patients progressing to ESKD. The diagnosis of ADPKD is based on the presence of family history, and radiological imaging although increasingly genetic testing is being used for screening and diagnosis. Once diagnosed, standard management of ADPKD includes laboratory monitoring of chronic kidney disease (CKD) parameters, lowering of blood pressure, and a high fluid intake. Over the last decade much research has been undertaken for targeted therapies for ADPKD; however, despite funding of these medications overseas since May 2015, and applications to Te Pātaka Whaioranga, The Pharmaceutical Management Agency (PHARMAC), these therapies remain unavailable to New Zealanders resulting in an increased burden of disease to individuals and the whānau and financial cost to the health system.

Management of autosomal dominant polycystic kidney disease in the era of disease-modifying treatment options.

Autosomal dominant polycystic kidney disease (ADPKD) is the reported etiology in 10% of end-stage kidney disease (ESKD) patients and has an estimated prevalence of 12.5 million cases worldwide across all ethnicities. There have been major advancements over the last two decades in understanding the pathogenesis and development of disease-modifying treatment options for ADPKD, culminating in regulatory approval of tolvaptan for ADPKD patients at risk of rapid progression to kidney failure. This review highlights the genetic mutations associated with ADPKD, defines patients at risk of rapid progression to ESKD, and focuses on the management of ADPKD in the era of disease-modifying agents.

Incidental finding of autosomal dominant polycystic kidney disease in a 52-year-old man: a case report.

Background: Autosomal dominant polycystic kidney disease (ADPKD) also known as Adult Polycystic Kidney Disease (APKD) is one of the most common systemic hereditary diseases. The disease usually presents between 20 to 39 years of age, although milder forms may not present until over 60 years and absence of renal failure has been rarely observed in some patients up to 80 years of age. Three distinct gene defects have been implicated in the pathogenesis of APKD designated as PKD1, PKD2, and PKD3. Patients with APKD may be asymptomatic, or may usually present with hypertension (in 50-70% of cases), renal insufficiency, and the complications of multiple cysts (haematuria, pain and infection) or as an abdominal mass discovered on incidental clinical or imaging examination. APKD is said to be rare in Africans. Case report: We report a case of an incidental finding of autosomal dominant polycystic kidney disease (ADPKD) in a 52-year-old normotensive man with a normal renal function test. Haematuria, dysuria and low-grade fever were the presenting complaints. The role of radiology in the diagnosis and management of ADPKD was highlighted. Conclusion: Although APKD is rare in Africans, a high index of suspicion for the disease is essential for the diagnosis of the disease especially in elderly patients with a family history of APKD who present with haematuria associated with multiple renal cysts.

Incidental finding of autosomal dominant polycystic kidney disease in a 52-year-old man: a case report.

ABSTRACT Background: Autosomal dominant polycystic kidney disease (ADPKD) also known as Adult Polycystic Kidney Disease (APKD) is one of the most common systemic hereditary diseases. The disease usually presents between 20 to 39 years of age, although milder forms may not present until over 60 years and absence of renal failure has been rarely observed in some patients up to 80 years of age. Three distinct gene defects have been implicated in the pathogenesis of APKD designated as PKD1, PKD2, and PKD3. Patients with APKD may be asymptomatic, or may usually present with hypertension (in 50-70% of cases), renal insufficiency, and the complications of multiple cysts (haematuria, pain and infection) or as an abdominal mass discovered on incidental clinical or imaging examination. APKD is said to be rare in Africans. Case report: We report a case of an incidental finding of autosomal dominant polycystic kidney disease (ADPKD) in a 52-year-old normotensive man with a normal renal function test. Haematuria, dysuria and low-grade fever were the presenting complaints. The role of radiology in the diagnosis and management of ADPKD was highlighted. Conclusion: Although APKD is rare in Africans, a high index of suspicion for the disease is essential for the diagnosis of the disease especially in elderly patients with a family history of APKD who present with haematuria associated with multiple renal cysts. Keywords: Adult Polycystic Kidney Disease, Autosomal Dominant Polycystic Kidney Disease, Incidental finding, Normotensive.

Zebrafish Model as a Screen to Prevent Cyst Inflation in Autosomal Dominant Polycystic Kidney Disease.

In autosomal dominant polycystic kidney disease (ADPKD), kidney cyst growth requires the recruitment of CFTR (cystic fibrosis transmembrane conductance regulator), the chloride channel that is defective in cystic fibrosis. We have been studying cyst inflation using the zebrafish Kupffer’s vesicle (KV) as model system because we previously demonstrated that knocking down polycystin 2 (PC2) induced a CFTR-mediated enlargement of the organ. We have now quantified the PC2 knockdown by showing that it causes a 73% reduction in the number of KV cilia expressing PC2. According to the literature, this is an essential event in kidney cystogenesis in ADPKD mice. Additionally, we demonstrated that the PC2 knockdown leads to a significant accumulation of CFTR-GFP at the apical region of the KV cells. Furthermore, we determined that KV enlargement is rescued by the injection of Xenopus pkd2 mRNA and by 100 µM tolvaptan treatment, the unique and approved pharmacologic approach for ADPKD management. We expected vasopressin V2 receptor antagonist to lower the cAMP levels of KV-lining cells and, thus, to inactivate CFTR. These findings further support the use of the KV as an in vivo model for screening compounds that may prevent cyst enlargement in this ciliopathy, through CFTR inhibition.

Estimation of Changes in Kidney Volume Growth Rate in ADPKD

IntroductionIn the Mayo Imaging Classification (MIC) for autosomal dominant polycystic kidney disease (ADPKD), the height-adjusted total kidney volume (HtTKV) growth rate is estimated for classification. Estimated HtTKV slope, termed as eHTKV-α, is calculated by the equation [HtTKV at age t] = K(1+α/100)(t-A), where K = 150 and A = 0 are used in MIC. If eHTKV-α is nearly stable during a standard-of-care period, the change in eHTKV-α from baseline can be used for estimation of the treatment effect on the HtTKV slope.MethodsThe constancy of eHTKV-α (A = 0 and K = 150) was evaluated using 453 placebo-assigned subjects in the Tolvaptan Efficacy and Safety in Management of ADPKD and Its Outcomes (TEMPO) 3:4 trial. A and K were sought out respectively by a converged pattern of regression lines of log10(HtTKV) plotted against age for subgroups divided according to MIC, and by change in eHTKV-α from baseline. A total of 239 standard-of-care patients from the Kyorin University Cohort (KUC) served as validation. Changes in eHTKV-α from baseline were evaluated in 809 tolvaptan-treated subjects in TEMPO 3:4.ResultsIn placebo-assigned subjects, eHTKV-α (A = 0 and K = 150) changed significantly from baseline at the third year. As regression lines of placebo-assigned subgroups converged around age 0, A was set as 0, which was confirmed by KUC. K = 130 was selected because of minimal change in eHTKV-α from baseline. The KUC validated the constancy of eHTKV-α (A = 0 and K = 130) but not that of eHTKV-α (A=0 and K=150). In tolvaptan-treated subjects, eHTKV-α remained significantly lower than baseline for 3 years.ConclusionseHTKV-α (A = 0 and K = 130) was nearly stable from baseline through follow-up in standard-of-care adults. Treatment effects on the HtTKV slope can be estimated by changes in eHTKV-α from baseline.

Management of Autosomal Dominant Polycystic Kidney Disease (ADPKD) During Pregnancy: Risks and Challenges.

Autosomal dominant polycystic kidney disease (ADPKD) affects up to 1 in 1000 people. The disease is characterized by the progressive development of cysts throughout the renal parenchyma due to inherited pathogenic variants in genes including PKD1 or PKD2 and eventually leads to gradual loss of renal function, along with manifestations in other organ systems such as hepatic cysts and intracranial aneurysms. ADPKD management has advanced considerably in recent years due to genetic testing availability, pre-implantation genetic diagnosis technology and new therapeutic agents. Renal disease in pregnancy is recognised as an important risk factor for adverse maternal and fetal outcome. Women with ADPKD and health professionals face multiple challenges in optimising outcomes during the pre-pregnancy, pregnancy and post-partum periods.

SAT-463 ADPedKD: A Global Online Platform on the management of Children with Autosomal Dominant Polycystic Kidney Disease

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common monogenic cause of renal failure. For long, it was regarded as an adult-onset disease but over the last decade, literature on pediatric ADPKD is merging. In 2019, the first consensus statement on the diagnosis and management of ADPKD in childhood was published. However, most of these recommendations are based on small-cohort studies, lacking long-term follow-up and therefore rendering weak evidence quality. To fill this gap, we initiated the global ADPedKD project to establish a large international pediatric ADPKD cohort for a deep and long-term characterization. Global ADPedKD is an international multicenter observational web-based register study focusing on childhood-diagnosed ADPKD. Patients diagnosed with ADPKD, based on genetic analysis and/ or a positive familial history and with renal cysts on imaging, before the age of 19 years are eligible for inclusion. A major strength of ADPedKD is the collaboration of 6 regional and independent but uniformly organized chapters, namely Africa, Asia, Australia, Europe (United Kingdom), North America and South America. Australia and the United Kingdom already have their separate source databases, namely Australasian Registry of Rare and genetic Kidney disease (ARRK) and National Registry of Rare Kidney Diseases (RaDaR). In North America, the ADPedKD Registry will be implemented under the auspices of the NIH-funded Hepato-Renal Fibrocystic Disease (HRFD) Database. After written informed consent, clinical patient data including genetics, radiologic and laboratory findings as well as therapeutic interventions, are pseudonymously introduced in our secured web-based database (www.adpedkd.org), both retrospectively and prospectively. There are currently 73 centers (Figure 1) participating in the ADPedKD initiative, with an inclusion of 424 (205/219 male/female) children. The mean (+/- SD) age of the diagnosis was 5.9 +/- 5.4 years. Reasons for diagnosis were prenatal diagnosis, a postnatal accidental finding, family screening, a presenting feature or unknown in N (%): 24 (5.6), 103 (27.6%), 160 (42.9%), 66 (17.7%), 44 (11.8%) respectively. Presenting features were most frequently an abnormal prenatal ultrasound (42.4%), urinary tract infection (13.6%), hematuria (10.6%) and flank/back pain or hypertension (both 6.1%). In less than half (40.8%) of the population, genetic analysis was performed, showing in the vast majority a PKD1 mutation. The ADPedKD initiative is the first and the largest international pediatric ADPKD registry that will provide evidence for the development of unified diagnostic, follow-up and treatment recommendations regarding modifiable disease factors.

A Provincial Survey of the Contemporary Management of Autosomal Dominant Polycystic Kidney Disease

Background:Recent years have witnessed an encouraging expansion of knowledge and management tools in the care of patients with autosomal dominant polycystic kidney disease (ADPKD), including measurement of total kidney volume as a biomarker of disease progression, stringent blood pressure targets to slow cyst growth, and targeted treatments such as tolvaptan.Objectives:We sought to evaluate clinicians’ familiarity with, and usage of, novel evidence-based management tools for ADPKD.Design:On-line survey.Setting:British Columbia, Canada.Participants:Nephrologists in academic and community practice (excluding clinicians who practice exclusively in transplantation).Measurements:Participants answered multiple-choice questions in 6 domains: sources of information, self-identified needs for optimal care delivery, prognostication, imaging tests, blood pressure targets, and use of tolvaptan.Methods:An online survey was developed and disseminated via email to 65 nephrologists engaged in current clinical practice in British Columbia.Results:A total of 29 nephrologists (45%) completed the questionnaire. The most popular source of information was the primary literature (83% of respondents). While 86% of respondents reported assessing the risk of disease progression before the onset of kidney function decline, most were using traditional metrics such as blood pressure and proteinuria rather than validated prediction tools such as the Mayo Classification. Although 90% of respondents obtained additional imaging after diagnosis in some or all of their ADPKD patients, only 1 in 5 reported being confident in their ability to interpret kidney size. The recommended blood pressure (BP) target of <110/75 mmHg was sought by 17% of respondents. All respondents reported being familiar with the literature regarding tolvaptan; however, only half were confident in their ability to identify suitable patients for treatment. The top 3 needs identified by clinicians were better access to medications (69%), clear management protocols (66%), and easier access to imaging tests (59%).Limitations:Funding mechanisms for tolvaptan can vary; therefore, clinicians’ experience with the drug may not be generalizable. Although the response rate was acceptable, the survey is nonetheless subject to responder bias.Conclusion:This survey indicates that there is substantial variability in the usage of, and familiarity with, evidence-based ADPKD management tools among contemporary nephrologists, contributing to incomplete translation of evidence into clinical practice. Providing greater access to tolvaptan or imaging tests is unlikely to improve patient care without enhancing knowledge translation and education.Trial Registration:Not applicable as this was a survey.

Autosomal dominant polycystic kidney disease: updated perspectives.

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited multisystem disorder, characterized by renal and extra-renal fluid-filled cyst formation and increased kidney volume that eventually leads to end-stage renal disease. ADPKD is considered the fourth leading cause of end-stage renal disease in the United States and globally. Care of patients with ADPKD was, for a long time, limited to supportive lifestyle measures, due to the lack of therapeutic strategies targeting the main pathways involved in the pathophysiology of ADPKD. As the first FDA approved treatment of ADPKD, Vasopressin (V2) receptor blocking agent, tolvaptan, is an urgently awaited advance for ADPKD patients. In our review, we also shed some lights on what is beyond Tolvaptan as there are other medications in the pipeline and many medications have been or are currently being studied in clinical trials such as Tesevatinib, Metformin and Pravastatin, with the goal of slowing the rate of progression of ADPKD by reducing the increase in total kidney volume or maintaining eGFR. Here, we review updates in the perspectives and management of ADPKD.

Dietary Care for ADPKD Patients: Current Status and Future Directions.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic nephropathy, and tolvaptan is the only therapy available. However, tolvaptan slows but does not stop disease progression, is marred by polyuria, and most patients worldwide lack access. This and recent preclinical research findings on the glucose-dependency of cyst-lining cells have renewed interest in the dietary management of ADPKD. We now review the current dietary recommendations for ADPKD patients according to clinical guidelines, the evidence base for those, and the potential impact of preclinical studies addressing the impact of diet on ADPKD progression. The clinical efficacy of tolvaptan has put the focus on water intake and solute ingestion as modifiable factors that may impact tolvaptan tolerance and ADPKD progression. By contrast, dietary modifications suggested to ADPKD patients, such as avoiding caffeine, are not well supported and their impact is unknown. Recent studies have identified a chronic shift in energy production from mitochondrial oxidative phosphorylation to aerobic glycolysis (Warburg effect) as a contributor to cyst growth, rendering cyst cells exquisitely sensitive to glucose availability. Therefore, low calorie or ketogenic diets have delayed preclinical ADPKD progression. Additional preclinical data warn of potential negative impact of excess dietary phosphate or oxalate in ADPKD progression.

PUK16 - Reina (Retrospective Study on Italian ADPKD) Disease Management Cost Study

The aim of this study was to estimate the economic burden of autosomal dominant polycystic kidney disease (ADPKD) in Italy, analyzing direct costs according to progression stage of chronic kidney disease (CKD). The primary objective was the average annual cost per patient with ADPKD in Italy. The secondary objective was the average annual cost per patient suffering from ADPKD at CKD Stage I to CKD Stage V (not under dialysis), or receiving dialysis or at the post-transplant stage. This retrospective, observational study was carried out by gathering data through a pre-specified Case Report Form (CRF) in six Italian hospitals. Costs associated with ADPKD were estimated based on identified cost drivers (n of visits, n of hospitalization, treatment costs) and the analysis was performed using the Activity-Based Costing method. Inpatient and outpatient resource consumption was collected for each patient during the period 2012-2015. Direct costs were then calculated from the perspective of the Italian National Health Service (NHS). 191 patients were enrolled. The analysis estimated an average annual cost associated with ADPKD management of € 8,108. The average annual cost of patients under dialysis was € 28,279, followed by post-transplantation and CKD V patients (respectively € 22,793 and € 13,155), CKD IV (€ 7,413) and finally CKD III, CKD II, CKD I (respectively € 1,447.5, € 674.5, € 159.7). Costs increased with disease progression, except at the post-transplant stage. Outpatient specialist care (including dialysis) represented the highest impact on total costs, followed by pharmacological therapies and hospitalizations. The study underlined the relevant economic burden of ADPKD and its direct correlation with disease stage, suggesting the importance of slowing down disease progression vs ESRD, both for patient in terms of quality of life and the NHS budget