Update and review of adult polycystic kidney disease
Introduction
Autosomal dominant polycystic kidney disease (ADPKD) is an inherited multisystem disorder, characterized by progressive cystic enlargement of the kidneys. Considered as the fourth leading cause of ESKD in the United States it is noted for kidney (e.g., hypertension, progressive, CKD, fibrosis), as well as extra-kidney manifestations. Such extra-kidney manifestations can be subdivided into cystic (e.g., arachnoidal cysts, liver cysts, pancreatic cysts, etc.) as well as non-cystic complications (e.g., cerebral aneurysms, mitral valve prolapse, colonic diverticula, inguinal hernias, etc.)
In the past, management of patients with ADPKD was, for a long time, limited to supportive lifestyle measures. However, with recent understandings of various mechanistic pathways involved in the pathophysiology of ADPKD, there has been significant development in treatment options. As the first FDA approved treatment of ADPKD, the Vasopressin (V2) receptor blocking agent, tolvaptan, is a much awaited advance in the treatment of these patients. Here, we review ADPKD in its entirety, from epidemiology and genetics, to clinical manifestations and treatment advances.
Section snippets
Epidemiology
Polycystic kidney disease was first described in 1841 by Pierre Rayer and official coined "polycystic kidney disease" in 1888 by Felix Lejars.1 ADPKD is the most common of all the inherited cases of chronic kidney disease totaling 600,000–700,000 in the United States. World-wide around 12.5 million people suffer from ADPKD with a European Union prevalence of around 3.5/10,000 population on screening. ADPKD is more common than sickle cell disease, Down syndrome, cystic fibrosis, hemophilia and
Genetics
ADPKD is a genetically and phenotypically heterogeneous disease. It is most commonly attributed to mutations in one of two genes namely PKD1 and PKD2. Reeders et al. are credited with the discovery of link between PKD1 mutation and the most typical clinical form of the disease.5 They mapped the gene to the short arm of chromosome 16. Additionally, it was identified that a region the gene (exon 1–33) was duplicated at a few other sites on the same chromosome.6 Since these genes do not undergo
Presentation
ADPKD is a multisystem disorder presenting with many kidney and extra-kidney manifestations (Table 1). A careful medical history for kidney diseases, hypertension, stroke (or intracranial hemorrhage) or familial premature death may point out the type of gene mutation or the need for intracranial aneurysms screening. Less often, patients may present with various manifestations (flank pain, dysuria, hematuria or hypertension) which may lead to a new diagnosis of ADPKD.
Treatment
Hypertension is one of the most common clinical features in patients with ADPKD. HALT-PKD [Study A] was a ground-breaking trial which studied 558 young patients with ADPKD with a baseline eGFR of 60 ml/min/1.73m2 and greater, and identified that intensive blood pressure control (⪯ 110/75 mmHg) was associated with a slower annual increase in total kidney volume by 14.2% as compared to those achieving standard blood pressure control. Unfortunately, the benefit did not translate to a decrease in
Prognosis
Progression to ESKD is lower than other forms of chronic kidney disease with occurrence around 50% of patients. Screening tools mentioned above describe are currently the best predictors available for determining future progression. Unfortunately, the average age patients reach ESKD has not improved despite improved survival given higher kidney transplantation rates and better ESKD care.87 One predictive classification tool to determine future progression is the Mayo Clinic ADPKD classification
Future
Currently there is a lot of interest and research in studying the origins and treatments of ADPKD. Going forward there are many imaging studies undergoing surveillance to determine future prognostics. Four-dimensional flow MRI, blood oxygen level dependent diffusion-weighted and magnetization transfer MRI, arterial spin labeling, and magnetic resonance elastography are all being studied with hopes of increasing information in the early stages of cyst development. In addition to imaging
Disclaimers
Gates B Colbert: No related disclosures.
Mohamed E. Elrggal: No related disclosures.
Lovy Gaur: No related disclosures
Edgar Lerma: Astra Zeneca (Advisory Board)
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2022, Computers in Biology and MedicineCitation Excerpt :They include lumbar and abdominal pain, kidney stone production, urinary tract infections, proteinuria, haematuria, and arterial hypertension. ADPKD progression to end-stage renal disease (ESRD) occurs in more than 50% of patients by the age of 50–60, which accounts for 6% of ESRD cases in the US and makes ADPKD the fourth leading cause of ESRD in adult patients [2], with necessity of renal replacement therapy by haemodialysis or renal transplantation. Moreover, ADPKD can also affect other organs: its complications include aortic and cerebral aneurysms, and the growth of cysts in liver, pancreas, ovaries and spleen.
Adult dominant polycystic kidney disease: A prototypical disease for pharmanutrition interventions
2022, PharmaNutritionCitation Excerpt :Most of the ADPKD cases are due to loss of function mutations either in the PKD1 or in the PKD2 gene, which occur respectively in 78% and 15% of patients [1]. Mutations in additional genes such as GANAB and DNAJB11 are being discovered and may account for PKD1/PKD2 negative cases that were previously considered “genetically-unresolved” [5]. The present narrative review is not intended to provide a comprehensive overview of ADPKD, which the readers can find in recent excellent reviews on this topic [1,6–8], but has the aim to describe how and why ADPKD could represent an exemplificative case of a disease in which drug therapy and nutritional intervention may converge in achieving similar and potentially synergistic beneficial effects, in the context of a pharmanutrition approach.
Application of mesenchymal stem cell-derived exosomes in kidney diseases
2021, Cellular ImmunologyCitation Excerpt :In the body with urine G, the parathyroid cells are stimulated to produce a parathormone hormone, which increases the availability of calcium in the eggs. While polycystic kidney model rats possess a high level of white signal transcription factor 3 (the AGS), it is less efficient in therapy and is only present in the renal tubular cells late in people and is not useful early in patients with polycystic kidney disease, the latter lack higher levels of it [48–50]. Diabetic nephropathy is one of the major consequences of microvascular diabetes, which has a significant permanent impairment and mortality rate.
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