Update and review of adult polycystic kidney disease

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Abstract

Autosomal dominant polycystic kidney disease is a common cause of end stage kidney disease. It is a progressive and unfortunately incurable condition that can lead to significant morbidity and kidney failure. Many more patients are diagnosed with this disease without any symptoms as the population is increasingly undergoing imaging for other problems and diagnostic workup. Our understanding of the genetic variants has increased in recent years as research continues to improve. As well, therapeutic options have developed with the FDA approval of a new treatment medication, with many others underway. This review updates the clinician on the pathophysiology, clinical aspects, and therapeutic options for patients the is form of 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)

References (101)

  • S.A. Grampsas et al.

    Anatomic and metabolic risk factors for nephrolithiasis in patients with autosomal dominant polycystic kidney disease

    Am J Kidney Dis

    (2000)
  • Z. Farooq et al.

    Complex liver cysts in autosomal dominant polycystic kidney disease

    Clin Imaging

    (2017)
  • N. Vora et al.

    Reproductive issues for adults with autosomal dominant polycystic kidney disease

    Am J Kidney Dis

    (2008)
  • Y. Pirson

    Extrarenal manifestations of autosomal dominant polycystic kidney disease

    Adv Chronic Kidney Dis.

    (2010)
  • R.D. Perrone et al.

    Survival after end-stage renal disease in autosomal dominant polycystic kidney disease: contribution of extrarenal complications to mortality

    Am J Kidney Dis

    (2001)
  • M.D. Wagner et al.

    Selective, concurrent bilateral nephrectomies at renal transplantation for autosomal dominant polycystic kidney disease

    J Urol

    (2007)
  • G.J.E. Rinkel

    Natural history, epidemiology and screening of unruptured intracranial aneurysms

    J Neuroradiol

    (2008)
  • A. Lumiaho et al.

    Mitral valve prolapse and mitral regurgitation are common in patients with polycystic kidney disease type 1

    Am J Kidney Dis

    (2001)
  • A. Caroli et al.

    Effect of longacting somatostatin analogue on kidney and cyst growth in autosomal dominant polycystic kidney disease (ALADIN): a randomised, placebo-controlled, multicentre trial

    Lancet

    (2013)
  • A.B. Chapman et al.

    Autosomal-dominant polycystic kidney disease (ADPKD): executive summary from a kidney disease: improving global outcomes (KDIGO) controversies conference

    Kidney Int.

    (2015)
  • D. Ravine et al.

    Evaluation of ultrasonographic diagnostic criteria for autosomal dominant polycystic kidney disease 1

    Lancet

    (1994)
  • M.S. Zand et al.

    Screening a living kidney donor for polycystic kidney disease using heavily T2-weighted MRI

    Am J Kidney Dis

    (2001)
  • A. Alam et al.

    Management of ESRD in patients with autosomal dominant polycystic kidney disease

    Adv Chronic Kidney Dis

    (2010)
  • G. Mosconi et al.

    Renal transplant in patients with polycystic disease: the Italian experience

    Transplant Proc

    (2013)
  • K.W. Florijn et al.

    A century of mortality in five large families with polycystic kidney disease

    Am J Kidney Dis

    (1995)
  • P.A. Gabow et al.

    Renal structure and hypertension in autosomal dominant polycystic kidney disease

    Kidney Int

    (1990)
  • C. Patch et al.

    Use of antihypertensive medications and mortality of patients with autosomal dominant polycystic kidney disease: a population-based study

    Am J Kidney Dis

    (2011)
  • Z.H. Bajwa et al.

    Pain patterns in patients with polycystic kidney disease

    Kidney Int

    (2004)
  • E. Cornec-Le Gall et al.

    HALT progression of polycystic kidney disease group; consortium for radiologic imaging studies of polycystic kidney disease: monoallelic mutations to DNAJB11 cause atypical autosomal dominant polycystic kidney disease

    Am J Hum Genet

    (2018)
  • J.J. Grantham et al.

    Volume progression in polycystic kidney disease

    N Engl J Med

    (2006)
  • M.B. Lanktree et al.

    New treatment paradigms for ADPKD: moving towards precision medicine

    Nat Rev Nephrol

    (2017)
  • C.J. Willey et al.

    Prevalence of autosomal dominant polycystic kidney disease in the European Union

    Nephrol Dial Transpl

    (2017)
  • W.E. Braun

    Autosomal dominant polycystic kidney disease: emerging concepts of pathogenesis and new treatments

    Cleve Clin J Med

    (2009)
  • S.T. Reeders et al.

    A highly polymorphic DNA marker linked to adult polycystic kidney disease on chromosome 16

    Nature

    (1985)
  • The polycystic kidney disease 1 gene encodes a 14 kb transcript and lies within a duplicated region on chromosome 16

    Cell

    (1994)
  • L. Geng et al.

    Identification and localization of polycystin, the PKD1 gene product

    J Clin Invest

    (1996)
  • S. Rossetti et al.

    The position of the polycystic kidney disease 1 (PKD1) gene mutation correlates with the severity of renal disease

    J Am Soc Nephrol

    (2002)
  • T. Mochizuki et al.

    PKD2, a gene for polycystic kidney disease that encodes an integral membrane protein

    Science

    (1996)
  • K. Hajjar et al.

    Autosomal dominant polycystic kidney disease and minimal trauma: medical review and case report

    BMC Emerg Med

    (2018)
  • J.B. Wetmore et al.

    Polycystic kidney disease and cancer after renal transplantation

    J Am Soc Nephrol

    (2014)
  • S.K. Sogbein et al.

    A case of bilateral renal cell carcinoma in polycystic kidneys

    Can J Surg

    (1981)
  • C.A. Jilg et al.

    Autosomal dominant polycystic kidney disease: prevalence of renal neoplasias in surgical kidney specimens

    Nephron Clin. Pract

    (2013)
  • R. Dedi et al.

    Lesson of the week: causes of haematuria in adult polycystic kidney disease

    BMJ

    (2001)
  • T. Ecder et al.

    Hypertension in autosomal-dominant polycystic kidney disease: early occurrence and unique aspects

    J Am Soc Nephrol

    (2001)
  • M. Zeier et al.

    Elevated blood pressure profile and left ventricular mass in children and young adults with autosomal dominant polycystic kidney disease

    J Am Soc Nephrol

    (1993)
  • A.B. Chapman et al.

    The renin-angiotensin-aldosterone system and autosomal dominant polycystic kidney disease

    N Engl J Med

    (1990)
  • A.B. Chapman et al.

    Overt proteinuria and microalbuminuria in autosomal dominant polycystic kidney disease

    J Am Soc Nephrol

    (1994)
  • J.L. Nishiura et al.

    Evaluation of nephrolithiasis in autosomal dominant polycystic kidney disease patients

    Clin J Am Soc Nephrol

    (2009)
  • M.C. Hogan et al.

    Liver involvement in early autosomal-dominant polycystic kidney disease

    Clin Gastroenterol Hepatol

    (2015)
  • J.A. Kim et al.

    Pancreatic cysts in autosomal dominant polycystic kidney disease: prevalence and association with PKD2 gene mutations

    Radiology

    (2016)
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      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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