Apelin is altered in subjects with autosomal dominant polycystic kidney disease and preserved kidney function.
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ABSTRACT:
SUBMITTER: Janssens P
PROVIDER: S-EPMC10387394 | biostudies-literature | 2023 Jul
REPOSITORIES: biostudies-literature
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Apelin is altered in subjects with autosomal dominant polycystic kidney disease and preserved kidney function.
Janssens Peter P Cools Wilfried W de Mota Nadia N Decuypere Jean-Paul JP Torres Vicente V Wissing Karl Martin KM Vennekens Rudi R Bammens Bert B Llorens-Cortes Catherine C Mekahli Djalila D
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 20230701 8
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Project description: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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Project description:Patients with autosomal dominant polycystic kidney disease benefit from specialized care over their lifetimes, starting with diagnosis of the condition with ongoing discussion of both the renal course and extra-renal issues. Both renal and extra-renal issues may continue to cause major morbidity even after successful kidney transplant or initiation of RRT, and extra-renal disease aspects should always be considered as part of routine management. In this review, we will focus on updates in pain/depression screening, cardiac manifestations, liver and pancreatic cysts, kidney stone management, and genetic counseling. In some instances, we have shared our current clinical practice rather than an evidence-based guideline. We anticipate more standardization of care after the release of the Kidney Disease Improving Global Outcomes guidelines for management in autosomal dominant polycystic kidney disease later this year.
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Project description:Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder affecting 1 in 1,000 people and responsible for 10% of cases of the end stage renal disease (ESRD). Apart from renal manifestations, changes in other organs may be present. In the absence of contraindications, patients with ADPKD and ESRD should be referred to renal transplantation. The ADPKD patient may also need liver transplantation, or combined liver and kidney transplantation. Also, the patient with ADPKD may become a potential organ donor. The aim of our paper is to review the problems that the physicians deal with in ADPKD patients in pre- and post-transplant period.
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Project description: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.
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Project description:BackgroundThe role of hyperuricemia in disease progression of autosomal dominant polycystic kidney disease (ADPKD) has not been defined well. We investigated the association of serum uric acid (sUA) with renal function and the effect of hypouricemic treatment on the rate of renal function decline.MethodsThis is a single-center, retrospective, observational cohort study. A total of 365 patients with ADPKD who had estimated glomerular filtration rate (eGFR)???15 mL/min/1.73 m2 and who were followed up for?>?1 year were included in our analysis. Hyperuricemia was defined by a sUA level of???7.0 mg/dL in male and???6.0 mg/dL in female or when hypouricemic medications were prescribed.ResultsHyperuricemia was associated with reduced initial eGFR, independent of age, sex, hypertension, albuminuria, and total kidney volume. During a median follow-up period of over 6 years, patients with hyperuricemia showed a faster annual decline in eGFR (-6.3% per year vs. -0.9% per year, p?=?0.008). However, after adjusting for age, sex, hypertension and initial eGFR, sUA was no longer associated with either annual eGFR decline or the development of ESRD. Among 53 patients who received hypouricemic treatment, the annual eGFR decline appeared to be attenuated after hypouricemic treatment (pretreatment vs. posttreatment: -5.3?±?8. 2 vs. 0.2?±?6.2 mL/min/1.73 m2 per year, p?=?0.001 by Wilcoxon signed-rank test).ConclusionsAlthough hyperuricemia was associated with reduced eGFR, it was not an independent factor for renal progression in ADPKD. However, the correction of hyperuricemia may attenuate renal function decline in some patients with mild renal insufficiency.
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Project description:Background and objectivesIt is assumed that in autosomal dominant polycystic kidney disease (ADPKD), kidney function remains in the normal range for several decades because of hyperfiltration of remnant nephrons. In this study, we investigate the extent to which patients with ADPKD hyperfilter.Design, setting, participants, & measurementsIn this cross-sectional study, we measured GFR as urinary clearance using continuous infusion of 125I-iothalamate. Kidney function reserve capacity was determined as increase in measured GFR after adding a dopamine infusion of 4.4-6 mg/h. Potential kidney donors were used as healthy controls and matched by age and sex to patients with ADPKD for comparisons across age groups and CKD stages. Hyperfiltration was defined by a loss of kidney function reserve capacity compared with healthy controls.ResultsA total of 300 participants were studied. In the youngest age group (18-29 years), measured GFR was not different between patients with ADPKD and healthy controls (103±21 versus 111±9 ml/min per 1.73 m2; P=0.14). In this age group kidney function reserve capacity was higher compared with healthy controls (11.1%±8.3% versus 5.3%±6.5%; P=0.04). Moreover, kidney function reserve capacity was similar to healthy controls in patients with ADPKD with early-stage disease (eGFR≥60 ml/min per 1.73 m2), either overall or when divided into fast or slow progressors according to their Mayo height-adjusted total kidney volume class. However, in patients with ADPKD, lower measured GFR was associated with lower kidney function reserve capacity (β=1.0 [95% confidence interval, 0.5 to 1.5] % per 10 ml/min per 1.73 m2; P<0.001). Kidney function reserve capacity was therefore lower compared with healthy controls at older age and later CKD stages.ConclusionsPatients with early-stage ADPKD, either classified as having rapidly or slowly progressive disease, are able to increase their GFR in response to dopamine. Hyperfiltration, defined by a loss of kidney function reserve capacity, may therefore not be an early phenomenon in ADPKD.
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Project description:Autosomal dominant polycystic disease (ADPKD) is the most common form of inherited kidney disease that results in renal failure. The understanding of the pathogenesis of ADPKD has advanced significantly since the discovery of the 2 causative genes, PKD1 and PKD2. Dominantly inherited gene mutations followed by somatic second-hit mutations inactivating the normal copy of the respective gene result in renal tubular cyst formation that deforms the kidney and eventually impairs its function. The respective gene products, polycystin-1 and polycystin-2, work together in a common cellular pathway. Polycystin-1, a large receptor molecule, forms a receptor-channel complex with polycystin-2, which is a cation channel belonging to the TRP family. Both polycystin proteins have been localized to the primary cilium, a nonmotile microtubule-based structure that extends from the apical membrane of tubular cells into the lumen. Here we discuss recent insights in the pathogenesis of ADPKD including the genetics of ADPKD, the properties of the respective polycystin proteins, the role of cilia, and some cell-signaling pathways that have been implicated in the pathways related to PKD1 and PKD2.
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Project description:BackgroundThe clinical manifestations of autosomal dominant polycystic kidney disease (ADPKD) usually appear in adulthood, however pediatric series report a high morbidity. The objective of the study was to analyze the clinical characteristics of ADPKD in young adults.MethodsFamily history, hypertension, albuminuria, estimated glomerular filtration rate (eGFR) and imaging tests were examined in 346 young adults (18-30 years old) out of 2521 patients in the Spanish ADPKD registry (REPQRAD). A literature review searched for reports on hypertension in series with more than 50 young (age <30 years) ADPKD patients.ResultsThe mean age of this young adult cohort was 25.24 (SD 3.72) years. The mean age at diagnosis of hypertension was 21.15 (SD 4.62) years, while in the overall REPQRAD population was aged 37.6 years. The prevalence of hypertension was 28.03% and increased with age (18-24 years, 16.8%; 25-30 years, 36.8%). Although prevalence was lower in women than in men, the age at onset of hypertension (21 years) was similar in both sexes. Mean eGFR was 108 (SD 21) mL/min/1.73 m2, 38.0% had liver cysts and 3.45% of those studied had intracranial aneurysms. In multivariate analyses, hematuria episodes and kidney length were independent predictors of hypertension (area under the curve 0.75). The prevalence of hypertension in 22 pediatric cohorts was 20%-40%, but no literature reports on hypertension in young ADPKD adults were found.ConclusionsYoung adults present non-negligible ADPKD-related morbidity. This supports the need for a thorough assessment of young adults at risk of ADPKD that allows early diagnosis and treatment of hypertension.
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