Deciphering the impact of R324L Mutation in Polycystin-1PKD Domain associated with Autosomal Dominant Polycystic Kidney Disease(ADPKD): A Molecular Dynamics Perspective

Background: Autosomal dominant polycystic kidney disease (ADPKD) causes the development of renal cysts and leads to a decline in renal function. Limited guidance exists in clinical practice on the use of tolvaptan. A decision algorithm from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Working Groups of Inherited Kidney Disorders and European Renal Best Practice (WGIKD/ERBP) has been proposed to identify candidates for tolvaptan treatment; however, this algorithm has not been assessed in clinical practice. Methods: Eighteen-month cross-sectional, unicenter, observational study assessing 305 consecutive ADPKD patients. The ERA-EDTA WGIKD/ERBP algorithm with a stepwise approach was used to assess rapid progression (RP). Subsequently, expanded criteria based on the REPRISE trial were applied to evaluate the impact of extended age (≤55 years) and estimated glomerular filtration rate (eGFR; ≥25 mL/min/1.73 m2). Results: Historical eGFR decline, indicative of RP, was fulfilled in 26% of 73 patients who were candidates for RP assessment, mostly aged 31–55 years. Further tests including ultrasound and MRI measurements of kidney volume plus genetic testing enabled the evaluation of the remaining patients. Overall, 15.7% of patients met the criteria for rapid or likely RP using the algorithm, and the percentage increased to 27% when extending age and eGFR. Conclusions: The ERA-EDTA WGIKD/ERBP algorithm provides a valuable means of identifying in routine clinical practice patients who may be eligible for treatment with tolvaptan. The impact of a new threshold for age and eGFR may increase the percentage of patients to be treated.

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The impact of type II diabetes mellitus in patients with autosomal dominant polycystic kidney disease

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfr744 ◽

2011 ◽

Vol 27 (7) ◽

pp. 2862-2865 ◽

Cited By ~ 14

Author(s):

Berenice Reed ◽

Imed Helal ◽

Kim McFann ◽

Wei Wang ◽

Xiang-Dong Yan ◽

...

Keyword(s):

Diabetes Mellitus ◽

Kidney Disease ◽

Polycystic Kidney Disease ◽

Type Ii Diabetes ◽

Autosomal Dominant ◽

Type Ii Diabetes Mellitus ◽

Type Ii ◽

Polycystic Kidney ◽

Autosomal Dominant Polycystic Kidney ◽

The Impact

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Prevalence of nephrolithiasis in polycystic kidney disease

Open Medicine ◽

10.2478/s11536-011-0043-z ◽

2011 ◽

Vol 6 (4) ◽

pp. 497-501

Author(s):

Alma Idrizi ◽

Myftar Barbullushi ◽

Margarita Gjata ◽

Alketa Koroshi ◽

Enver Roshi ◽

...

Keyword(s):

Kidney Disease ◽

Polycystic Kidney Disease ◽

Autosomal Dominant ◽

Stone Formation ◽

Polycystic Kidney ◽

Metabolic Factors ◽

Survival Curves ◽

Autosomal Dominant Polycystic Kidney ◽

Tract Infections ◽

The Impact

AbstractWe aim to define the prevalence of nephrolithiasis, the impact of anatomic and metabolic factors to stone formation and prognosis of patients with autosomal dominant polycystic kidney disease in Albania. We included 200 patients with autosomal dominant polycystic kidney from 2002 to 2009. The patients underwent X-ray, renal ultrasonography. We performed the metabolic evaluation of blood and urine. Survival times were calculated as the time to dialysis, transplantation, or death. Kaplan-Meier product-limit survival curves were constructed. Log rank test was used to compare the survival curves. Nephrolithiasis was present in 116 of our patients with autosomal dominant polycystic kidney disease (58%), with a mean age 46.4±5.7 years. Sixty five patients with kidney stones (56%) were women. The stones were composed primarily of urate (47%) and calcium oxalate (39%), and other compounds 14%. In 40% of patients the presence of stones was associated with a history of urinary tract infections and flank pain. In our study the prevalence of nephrolithiasis is 58%, higher than it reported in literature. Except anatomic and metabolic factors, there are other contributor factors to stone formation in our patients such socioeconomic status of patients, geographic zones and dietary habits.

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Cardiovascular risk and quality of life in autosomal dominant polycystic kidney disease patients in therapy with tolvaptan: A pilot study

Current Vascular Pharmacology ◽

10.2174/1570161118999200918094809 ◽

2020 ◽

Vol 18 ◽

Author(s):

Silvia Lai ◽

Marco Mangiulli ◽

Adolfo M Perrotta ◽

Antonietta Gigante ◽

Ludovica Napoleoni ◽

...

Keyword(s):

Quality Of Life ◽

Kidney Disease ◽

Polycystic Kidney Disease ◽

Autosomal Dominant ◽

Clinical Laboratory ◽

Intima Media Thickness ◽

Polycystic Kidney ◽

Autosomal Dominant Polycystic Kidney ◽

The Impact

Introduction: ardiovascular (CV) complications are the most frequent cause of morbidity and mortality in autosomal dominant polycystic kidney disease (ADPKD) patients. In 2017, the Italian Medicines Agency authorised tolvaptan, a vasopressin V2 receptor antagonist, for the treatment of ADPKD, based on the Tolvaptan Phase 3 Efficacy and Safety Study in ADPKD (TEMPO 3: 4), TEMPO 4: 4 and Replicating Evidence of Preserved Renal Function: An Investigation of Tolvaptan Safety and Efficacy (REPRISE) studies. Aim of the study: To assess the impact of tolvaptan on CV risk and quality of life, evaluated by nutritional, inflammatory, metabolic, instrumental parameters and psychocognitive tests in ADPKD patients. Methods and Materials: We evaluated 36 patients with ADPKD; 10 patients (7 males, mean age 42.5±7.0 years) treated with tolvaptan and 26 controls (11 males, mean age 36.7±9.1 years). They underwent, at T0, monthly, and at T1 (1 year) clinical, laboratory and instrumental evaluation, in addition to psychocognitive tests. Results: In ADPKD patients treated with tolvaptan we found at T1 a decrease in carotid intima media thickness (p=0.048), epicardial adipose tissue thickness (p=0.002), C-reactive protein (p=0.026), sympathovagal balance during the night (p=0.045) and increases flow mediated dilation (p=0.023) with a reduction in depression (Hamilton and Beck tests, p=0.008 and p=0.002, respectively) compared with controls. Conclusions: These preliminary results suggest that treatment with tolvaptan could improve early atherosclerosis and endothelial dysfunction markers and improve the mood in ADPKD patients (probably by the acting on endothelial cell and adipocyte V2 receptors).

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The Kidney Genetics Clinic: delivering precision medicine for kidney patients

Portuguese Journal of Nephrology & Hypertension ◽

10.32932/pjnh.2021.10.139 ◽

2021 ◽

Vol 35 (3) ◽

Author(s):

Joaquim Calado ◽

◽

Rui Barata ◽

Rita Lucas ◽

Telma Francisco ◽

...

Keyword(s):

Genetic Testing ◽

Kidney Disease ◽

Tuberous Sclerosis ◽

Polycystic Kidney Disease ◽

Tuberous Sclerosis Complex ◽

Autosomal Dominant ◽

Molecular Testing ◽

Polycystic Kidney ◽

Autosomal Dominant Polycystic Kidney ◽

The Impact

Molecular genetic testing in human traits has traditionally relied on affiliated academic facilities, been focused on specific phenotypes and supported by research funding. We report the experience of the Kidney Genetics Clinic (“consulta de Doenças Renais Hereditárias”) for the past 5 years, a period during which we have outsourced genetic testing. We evaluated the impact of molecular testing in patients’ care, but we also assessed disease‑specific imaging procedures and medicines provided. During the study period, 293 individuals were evaluated. Autosomal Dominant Polycystic Kidney Disease was the most frequent diagnosis (61.8%). In 125 patients, a genetic test was available, and for 76 of these (60.8%) a pathogenic/likely pathogenic variant was identified. Depend‑ ing on the phenotype, the mutation detection rate ranged from 100% (Tuberous Sclerosis Complex) to 15.4% (Autosomal Dominant Tubuloint‑ erstitial Kidney Disease). The impact of genetic testing on patients’ diagnosis and treatments is discussed. Total kidney volume was calculated in 6 patients with Autosomal Dominant Polycystic Kidney Disease and the combined volume for selected angiomyolipoma monitored in 3 individuals with the Tuberous Sclerosis Complex. Currently, 4 patients are being treated with Everolimus/Votubia™, 3 with Eculizumab/Soliris™ and 2 with Tolvaptan/Jinarc™. Our results demonstrate the feasibility of genetic molecular testing in a clinical setting while relying on outsourced sites for gene testing. We emphasize that it was only because the Kidney Genetics Clinic was given the opportunity to look after several patients affected by the same specific orphan or rare diseases (cohort enrichment) that we were able to improve diagnostic skills and deliver personalized medicines.

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Cardiovascular risk factors and the impact on prognosis in patients with chronic kidney disease secondary to autosomal dominant polycystic kidney disease

BMC Nephrology ◽

10.1186/s12882-021-02313-1 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

José Luis Gorriz ◽

David Arroyo ◽

Luis D’Marco ◽

Roser Torra ◽

Patricia Tomás ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Risk ◽

Kidney Disease ◽

Cardiovascular Risk Factors ◽

Polycystic Kidney Disease ◽

Autosomal Dominant ◽

Atheromatous Plaque ◽

Polycystic Kidney ◽

Autosomal Dominant Polycystic Kidney ◽

The Impact

Abstract Background Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent hereditary renal disease. There is an increased rate of cardiovascular disease (CVD) in ADPKD. In this study, we evaluate the prevalence of cardiovascular risk factors, the achievement rates for treatment goals and cardiovascular events (CVE) in ADPKD and their relations with asymptomatic CVD in CKD from other etiologies (CKDoe) and controls. Methods We evaluated 2445 CKD patients (2010–2012). The information collected was: clinical, anthropometric and analytical parameters, treatments and CVD evaluation (intima-media thickness (IMT), atheromatous plaque presence and ankle-brachial index (ABI)). Laboratory, vital status, CVE and hospitalizations were collected for 4 years. Results ADPKD patients had a worse renal function and worst achievement of blood pressure, higher parathormone levels but lower proteinuria compared to CKDoe. ADPKD patients presented lower IMT values than other groups, however, an intermediate rate of pathologic ABI and atheromatous plaque was present. More than half of the patients received statins, achieving LDL-c levels < 100 only in 50 and 39.8% of them (ADPKD and CKDoe respectively). The number of CVE during the follow-up period was low. In adjusted Cox regression model, ADPDK had the lowest occurrence of CVE of all three groups (HR:0.422, 95%CI 0.221–0.808, p = 0.009). Conclusion ADPKD patients show intermediate control rates of CVD. A better control of CVD risk seems to be related with a lower load of CVD compared to other groups, which may lead in the long term to a better prognosis. Further investigation is necessary to determine cardiovascular prognosis in ADPKD.

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