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• W1611965846 abstract "Renal cystic diseases encompass a broad group of disorders with variable phenotypic expression. Cystic disorders can present during infancy, childhood, or adulthood. Often, but not always, they can be distinguished by the clinical features including age at presentation, renal imaging characteristics, including cyst distribution, and the presence/distribution of extrarenal manifestations. It is important to take the clinical context into consideration when assessing renal cystic disease in children and adults. For example, solitary kidney cysts may be completely benign when they develop during adulthood but may represent early polycystic kidney disease when observed during childhood. In this review, we have categorized renal cystic disease according to inherited single-gene disorders, for example, autosomal recessive polycystic kidney disease; syndromic disorders associated with kidney cysts, for example, tuberous sclerosis complex; and nongenetic forms of renal cystic disease, for example, simple kidney cysts. We present an overview of the clinical characteristics, genetics (when appropriate), and molecular pathogenesis and the diagnostic evaluation and management of each renal cystic disease. We also provide an algorithm that distinguishes kidney cysts based on their clinical features and may serve as a helpful diagnostic tool for practitioners. A review of Autosomal Dominant Polycystic Disease was excluded as this disorder was reviewed in this journal in March 2010, volume 17, issue 2. Renal cystic diseases encompass a broad group of disorders with variable phenotypic expression. Cystic disorders can present during infancy, childhood, or adulthood. Often, but not always, they can be distinguished by the clinical features including age at presentation, renal imaging characteristics, including cyst distribution, and the presence/distribution of extrarenal manifestations. It is important to take the clinical context into consideration when assessing renal cystic disease in children and adults. For example, solitary kidney cysts may be completely benign when they develop during adulthood but may represent early polycystic kidney disease when observed during childhood. In this review, we have categorized renal cystic disease according to inherited single-gene disorders, for example, autosomal recessive polycystic kidney disease; syndromic disorders associated with kidney cysts, for example, tuberous sclerosis complex; and nongenetic forms of renal cystic disease, for example, simple kidney cysts. We present an overview of the clinical characteristics, genetics (when appropriate), and molecular pathogenesis and the diagnostic evaluation and management of each renal cystic disease. We also provide an algorithm that distinguishes kidney cysts based on their clinical features and may serve as a helpful diagnostic tool for practitioners. A review of Autosomal Dominant Polycystic Disease was excluded as this disorder was reviewed in this journal in March 2010, volume 17, issue 2. Clinical Summary•Renal cystic diseases encompass a broad range of disorders that manifest in both children and adults with variable clinic features.•The identification of disease-causing genes has expanded our understanding of cystic disease pathogenesis and enhanced diagnostic accuracy. Autosomal recessive polycystic kidney disease (ARPKD, MIM 173900) is a severe hepatorenal fibrocystic disorder characterized by nonobstructive dilatation of the kidney collecting ducts and malformation of the portobiliary system. It occurs with an estimated frequency of 1 in 20,000 live births.1Hartung E.A. Guay-Woodford L.M. Autosomal recessive polycystic kidney disease: a hepatorenal fibrocystic disorder with pleiotropic effects.Pediatrics. 2014; 134: e833-e845Crossref PubMed Scopus (82) Google Scholar ARPKD is typically diagnosed in utero or at birth and manifests as progressive renal insufficiency and portal hypertension. The typical kidney phenotype consists of enlarged echogenic kidneys with loss of corticomedullary differentiation because of fusiform dilatation of the collecting ducts. Affected fetuses often have oligohydramnios leading to fetal constraint and the “Potter sequence” that consists of characteristic dysmorphic facies, pulmonary hypoplasia, and limb defects. The estimated perinatal mortality rate is 30% because of respiratory insufficiency.2Bergmann C. Senderek J. Windelen E. et al.Clinical consequences of PKHD1 mutations in 164 patients with autosomal-recessive polycystic kidney disease (ARPKD).Kidney Int. 2005; 67: 829-848Crossref PubMed Scopus (228) Google Scholar, 3Guay-Woodford L.M. Desmond R.A. Autosomal recessive polycystic kidney disease: the clinical experience in North America.Pediatrics. 2003; 111: 1072-1080Crossref PubMed Scopus (293) Google Scholar In patients who survive the first month of life, 1-year survival rates of 92% to 95% have been reported.1Hartung E.A. Guay-Woodford L.M. Autosomal recessive polycystic kidney disease: a hepatorenal fibrocystic disorder with pleiotropic effects.Pediatrics. 2014; 134: e833-e845Crossref PubMed Scopus (82) Google Scholar The clinical course of infants who survive the neonatal period is characterized by severe systemic hypertension, progressive renal insufficiency, and portal hypertension. Although the pathophysiology of underlying hypertension is unclear, at least 1 study demonstrates intrarenal Renin-angiotensin-aldosterone system activation.4Guay-Woodford L.M. Bissler J.J. Braun M.C. et al.Consensus expert recommendations for the diagnosis and management of autosomal recessive polycystic kidney disease: report of an international conference.J Pediatr. 2014; 165: 611-617Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar Infants often have hyponatremia, presumably because of defects in free water excretion.4Guay-Woodford L.M. Bissler J.J. Braun M.C. et al.Consensus expert recommendations for the diagnosis and management of autosomal recessive polycystic kidney disease: report of an international conference.J Pediatr. 2014; 165: 611-617Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar Most ARPKD patients progress to ESRD, although the age of onset is variable. The kidney survival rate of 1 large cohort of neonatal survivors was 86% at 5 years and decreased to 42% at 20 years.2Bergmann C. Senderek J. Windelen E. et al.Clinical consequences of PKHD1 mutations in 164 patients with autosomal-recessive polycystic kidney disease (ARPKD).Kidney Int. 2005; 67: 829-848Crossref PubMed Scopus (228) Google Scholar Age of ESRD onset is somewhat correlated with age at ARPKD diagnosis.5Adeva M. El-Youssef M. Rossetti S. et al.Clinical and molecular characterization defines a broadened spectrum of autosomal recessive polycystic kidney disease (ARPKD).Medicine. 2006; 85: 1-21Crossref PubMed Scopus (187) Google Scholar Histologic liver involvement is invariably present in all ARPKD patients and is characterized by defective remodeling of the ductal plate with intrahepatic duct dilatation and progressive portal tract fibrosis.1Hartung E.A. Guay-Woodford L.M. Autosomal recessive polycystic kidney disease: a hepatorenal fibrocystic disorder with pleiotropic effects.Pediatrics. 2014; 134: e833-e845Crossref PubMed Scopus (82) Google Scholar Portal hypertension is the predominant clinical manifestation and may cause gastroesophageal varices and hypersplenism.1Hartung E.A. Guay-Woodford L.M. Autosomal recessive polycystic kidney disease: a hepatorenal fibrocystic disorder with pleiotropic effects.Pediatrics. 2014; 134: e833-e845Crossref PubMed Scopus (82) Google Scholar Splenomegaly may further result in thrombocytopenia, leukopenia, and anemia with the potential for splenic dysfunction and predisposition to bacterial infections. ARPKD patients with extensive dilatations of intrahepatic and extrahepatic bile ducts are at increased risk of ascending bacterial cholangitis.1Hartung E.A. Guay-Woodford L.M. Autosomal recessive polycystic kidney disease: a hepatorenal fibrocystic disorder with pleiotropic effects.Pediatrics. 2014; 134: e833-e845Crossref PubMed Scopus (82) Google Scholar Because hepatocytes are not involved, hepatocellular dysfunction is rare and liver enzymes are characteristically not increased. ARPKD is caused by mutations in the polycystic and hepatic disease gene 1 (PKHD1) that encodes fibrocystin-polyductin complex (FPC), a protein expressed in primary cilia of kidney and bile duct epithelial cells.3Guay-Woodford L.M. Desmond R.A. Autosomal recessive polycystic kidney disease: the clinical experience in North America.Pediatrics. 2003; 111: 1072-1080Crossref PubMed Scopus (293) Google Scholar, 6Gunay-Aygun M. Avner E.D. Bacallao R.L. et al.Autosomal recessive polycystic kidney disease and congenital hepatic fibrosis: summary statement of a first National Institutes of Health/Office of Rare Diseases Conference.J Pediatr. 2006; 149: 159-164Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar, 7Onuchic L.F. Furu L. Nagasawa Y. et al.PKHD1, the polycystic kidney and hepatic disease 1 gene, encodes a novel large protein containing multiple immunoglobulin-like plexin-transcription-factor domains and parallel beta-helix 1 repeats.Am J Hum Genet. 2002; 70: 1305-1317Abstract Full Text Full Text PDF PubMed Scopus (384) Google Scholar PKHD1 is an exceptionally large gene that spans approximately 470 kb of genomic DNA and consists of 86 exons, with 67 exons included in the longest open-reading frame transcript.7Onuchic L.F. Furu L. Nagasawa Y. et al.PKHD1, the polycystic kidney and hepatic disease 1 gene, encodes a novel large protein containing multiple immunoglobulin-like plexin-transcription-factor domains and parallel beta-helix 1 repeats.Am J Hum Genet. 2002; 70: 1305-1317Abstract Full Text Full Text PDF PubMed Scopus (384) Google Scholar A number of alternatively spliced transcripts have been identified; however, the exact function and clinical significance of these isoforms have not been elucidated.8Boddu R. Yang C. O'Connor A.K. et al.Intragenic motifs regulate the transcriptional complexity of Pkhd1/PKHD1.J Mol Med (Berl). 2014; 92: 1045-1056Crossref PubMed Scopus (24) Google Scholar Almost 750 pathogenic PKHD1 mutations have been identified to date (http://www.humgen.rwth-aachen.de/), with approximately 44% classified as missense mutations.9Brüchle N.O. Zerres K. Mutation database autosomal recessive polycystic kidney disease (ARPKD/PKHD1). 2014Google Scholar, 10Gunay-Aygun M. Tuchman M. Font-Montgomery E. et al.PKHD1 sequence variations in 78 children and adults with autosomal recessive polycystic kidney disease and congenital hepatic fibrosis.Mol Genet Metab. 2010; 99: 160-173Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar A small number of relatively common mutations (eg, p.T36 M) account for ∼10% of all PKHD1 pathogenic variants.11Bergmann C. Kupper F. Dornia C. Schneider F. Senderek J. Zerres K. Algorithm for efficient PKHD1 mutation screening in autosomal recessive polycystic kidney disease (ARPKD).Hum Mutat. 2005; 25: 225-231Crossref PubMed Scopus (49) Google Scholar Most affected patients are compound heterozygotes, carrying 2 different mutant alleles.12Rossetti S. Harris P.C. Genotype-phenotype correlations in autosomal dominant and autosomal recessive polycystic kidney disease.J Am Soc Nephrol. 2007; 18: 1374-1380Crossref PubMed Scopus (140) Google Scholar Phenotype-genotype studies suggest that patients carrying a truncating mutation on both parental alleles have a more severe phenotype leading to perinatal demise.10Gunay-Aygun M. Tuchman M. Font-Montgomery E. et al.PKHD1 sequence variations in 78 children and adults with autosomal recessive polycystic kidney disease and congenital hepatic fibrosis.Mol Genet Metab. 2010; 99: 160-173Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar, 13Bergmann C. Senderek J. Schneider F. et al.PKHD1 mutations in families requesting prenatal diagnosis for autosomal recessive polycystic kidney disease (ARPKD).Hum Mutat. 2004; 23: 487-495Crossref PubMed Scopus (62) Google Scholar, 14Sharp A.M. Messiaen L.M. Page G. et al.Comprehensive genomic analysis of PKHD1 mutations in ARPKD cohorts.J Med Genet. 2005; 42: 336-349Crossref PubMed Scopus (77) Google Scholar However, there are notable exceptions, for example, a child homozygous for a large PKHD1 deletion who survived well past the neonatal period.15Zvereff V. Yao S. Ramsey J. Mikhail F.M. Vijzelaar R. Messiaen L. Identification of PKHD1 multiexon deletions using multiplex ligation-dependent probe amplification and quantitative polymerase chain reaction.Genet Test Mol Biomarkers. 2010; 14: 505-510Crossref PubMed Scopus (18) Google Scholar Although most missense mutations are associated with milder disease, a number of missense mutations result in severe phenotypes when present with a truncating mutation or in the homozygous form. FPC is a 4074-amino acid transmembrane protein predominantly expressed in kidney cortical and medullary collecting ducts and thick ascending loops of Henle and ductal structures in the liver and pancreas.16Ward C.J. Hogan M.C. Rossetti S. et al.The gene mutated in autosomal recessive polycystic kidney disease encodes a large, receptor-like protein.Nat Genet. 2002; 30: 259-269Crossref PubMed Scopus (583) Google Scholar FPC has been identified as a structural component of primary cilia in kidney tubular epithelial cells and cholangiocytes of bile ducts.7Onuchic L.F. Furu L. Nagasawa Y. et al.PKHD1, the polycystic kidney and hepatic disease 1 gene, encodes a novel large protein containing multiple immunoglobulin-like plexin-transcription-factor domains and parallel beta-helix 1 repeats.Am J Hum Genet. 2002; 70: 1305-1317Abstract Full Text Full Text PDF PubMed Scopus (384) Google Scholar, 17Menezes L.F. Cai Y. Nagasawa Y. et al.Polyductin, the PKHD1 gene product, comprises isoforms expressed in plasma membrane, primary cilium, and cytoplasm.Kidney Int. 2004; 66: 1345-1355Crossref PubMed Scopus (119) Google Scholar, 18Wang S. Luo Y. Wilson P.D. Witman G.B. Zhou J. The autosomal recessive polycystic kidney disease protein is localized to primary cilia, with concentration in the basal body area.J Am Soc Nephrol. 2004; 15: 592-602Crossref PubMed Scopus (124) Google Scholar, 19Masyuk T.V. Huang B.Q. Ward C.J. et al.Defects in cholangiocyte fibrocystin expression and ciliary structure in the PCK rat.Gastroenterology. 2003; 125: 1303-1310Abstract Full Text Full Text PDF PubMed Scopus (156) Google Scholar The specific functions of FPC remain to be fully characterized. However, numerous other proteins associated with other hepatorenal fibrocystic diseases (eg, autosomal dominant polycystic kidney disease [ADPKD], nephronophthisis [NPHP], Meckel-Gruber, Joubert, Bardet-Biedl, and other ciliary chondrodysplasias syndromes) also localize to the primary cilia/basal body (Fig 1), suggesting a role for primary cilium in the development and maintenance of kidney tubular architecture.1Hartung E.A. Guay-Woodford L.M. Autosomal recessive polycystic kidney disease: a hepatorenal fibrocystic disorder with pleiotropic effects.Pediatrics. 2014; 134: e833-e845Crossref PubMed Scopus (82) Google Scholar Sonographic features of ARPKD include enlarged, echogenic kidneys with poor corticomedullary differentiation. Dilated cortical collecting ducts just under the kidney capsule may be visible with high-resolution ultrasound (US). The cortex is often compressed to the periphery by the dilated medullary collecting ducts, forming a hypoechoic halo.20Chung E.M. Conran R.M. Schroeder J.W. Rohena-Quinquilla I.R. Rooks V.J. From the radiologic pathology archives: pediatric polycystic kidney disease and other ciliopathies: radiologic-pathologic correlation.Radiographics. 2014; 34: 155-178Crossref PubMed Scopus (30) Google Scholar Macrocysts are not routinely present at birth. Furthermore, kidney size in ARPKD stabilizes or may decrease over time and does not show progressive macrocystic enlargement as in ADPKD.1Hartung E.A. Guay-Woodford L.M. Autosomal recessive polycystic kidney disease: a hepatorenal fibrocystic disorder with pleiotropic effects.Pediatrics. 2014; 134: e833-e845Crossref PubMed Scopus (82) Google Scholar It can be difficult to differentiate ARPKD from ADPKD, in that a subset of ADPKD patients may present in infancy or early childhood with enlarged echogenic kidneys. Likewise, ARPKD can present in older children, who may demonstrate kidney macrocysts that can mimic the kidney cysts of ADPKD. ARPKD kidneys in utero are hyperechoic and display “decreased” corticomedullary differentiation because of the hyperechoic medulla. In comparison, ADPKD kidneys in utero tend to be moderately enlarged with a hyperechoic cortex and relatively hypoechoic medulla causing “increased” corticomedullary differentiation.20Chung E.M. Conran R.M. Schroeder J.W. Rohena-Quinquilla I.R. Rooks V.J. From the radiologic pathology archives: pediatric polycystic kidney disease and other ciliopathies: radiologic-pathologic correlation.Radiographics. 2014; 34: 155-178Crossref PubMed Scopus (30) Google Scholar In addition, high-resolution US can detect the dilatations of branching collecting ducts that are readily distinguished from the round cysts of ADPKD.20Chung E.M. Conran R.M. Schroeder J.W. Rohena-Quinquilla I.R. Rooks V.J. From the radiologic pathology archives: pediatric polycystic kidney disease and other ciliopathies: radiologic-pathologic correlation.Radiographics. 2014; 34: 155-178Crossref PubMed Scopus (30) Google Scholar Renal US evaluation of the parents may be useful. Absence of cysts in the parents (particularly if they are >30 years) suggests ARPKD rather than ADPKD.20Chung E.M. Conran R.M. Schroeder J.W. Rohena-Quinquilla I.R. Rooks V.J. From the radiologic pathology archives: pediatric polycystic kidney disease and other ciliopathies: radiologic-pathologic correlation.Radiographics. 2014; 34: 155-178Crossref PubMed Scopus (30) Google Scholar, 21Sweeney Jr., W.E. Avner E.D. Diagnosis and management of childhood polycystic kidney disease.Pediatr Nephrol. 2011; 26: 675-692Crossref PubMed Scopus (83) Google Scholar However, it is important to note that in 5% to 10% of patients, ADPKD can result from spontaneous mutations. A number of commercial genetic testing laboratories offer gene-based testing for ARPKD. Most laboratories offer direct sequencing of the entire coding region, but the expected mutation detection rate with current technologies is only 80%. An additional challenge in establishing a molecular diagnosis is that several other diseases can mimic the clinical presentation of ARPKD. For example, patients with mutations in the ADPKD genes, PKD1 and PKD2, can present with early-onset renal cystic disease indistinguishable from ARPKD.4Guay-Woodford L.M. Bissler J.J. Braun M.C. et al.Consensus expert recommendations for the diagnosis and management of autosomal recessive polycystic kidney disease: report of an international conference.J Pediatr. 2014; 165: 611-617Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar Thus, mutational analysis of PKHD1 using current single-gene testing methodologies should not be considered as a first-line diagnostic approach for infants and children presenting with an ARPKD-like phenotype,4Guay-Woodford L.M. Bissler J.J. Braun M.C. et al.Consensus expert recommendations for the diagnosis and management of autosomal recessive polycystic kidney disease: report of an international conference.J Pediatr. 2014; 165: 611-617Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar and genetic testing should be largely reserved for prenatal testing and pre-implantation genetic diagnosis.1Hartung E.A. Guay-Woodford L.M. Autosomal recessive polycystic kidney disease: a hepatorenal fibrocystic disorder with pleiotropic effects.Pediatrics. 2014; 134: e833-e845Crossref PubMed Scopus (82) Google Scholar There are currently no specific therapies for ARPKD. Postnatal management of ARPKD infants should focus on respiratory support. Several small studies have advocated for nephrectomy to improve nutrition and enable weaning of ventilator support; however, there are no current guidelines for routine nephrectomy. Decision for nephrectomy must be made on a case-by-case basis understanding the risks of surgery and complications associated with neonatal dialysis.4Guay-Woodford L.M. Bissler J.J. Braun M.C. et al.Consensus expert recommendations for the diagnosis and management of autosomal recessive polycystic kidney disease: report of an international conference.J Pediatr. 2014; 165: 611-617Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar Hypertension should be aggressively managed and may require multiple antihypertensive agents. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are considered first-line therapy.4Guay-Woodford L.M. Bissler J.J. Braun M.C. et al.Consensus expert recommendations for the diagnosis and management of autosomal recessive polycystic kidney disease: report of an international conference.J Pediatr. 2014; 165: 611-617Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar Patients should be monitored for development of splenomegaly by abdominal examination, and annual complete blood and platelet counts should be obtained.4Guay-Woodford L.M. Bissler J.J. Braun M.C. et al.Consensus expert recommendations for the diagnosis and management of autosomal recessive polycystic kidney disease: report of an international conference.J Pediatr. 2014; 165: 611-617Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar Abdominal US should be obtained at age 5, and if negative, follow-up is recommended every 2 to 3 years.4Guay-Woodford L.M. Bissler J.J. Braun M.C. et al.Consensus expert recommendations for the diagnosis and management of autosomal recessive polycystic kidney disease: report of an international conference.J Pediatr. 2014; 165: 611-617Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar Cholangitis should be considered in any ARPKD patient with unexplained fever.4Guay-Woodford L.M. Bissler J.J. Braun M.C. et al.Consensus expert recommendations for the diagnosis and management of autosomal recessive polycystic kidney disease: report of an international conference.J Pediatr. 2014; 165: 611-617Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar NPHP (MIM 256100) is an autosomal recessive tubulointerstitial disorder and one of the most common causes of inherited end-stage kidney disease in children and young adults.22Hildebrandt F. Otto E. Cilia and centrosomes: a unifying pathogenic concept for cystic kidney disease?.Nat Rev Genet. 2005; 6: 928-940Crossref PubMed Scopus (255) Google Scholar The initial features typically present between 4 and 6 years of age and include polydipsia and polyuria. Decreased urinary concentration is invariably present. Slowly progressive decline in kidney function is typical of NPHP. One-third of patients develop normocytic anemia before the onset of renal insufficiency.23Hildebrandt F. Zhou W. Nephronophthisis-associated ciliopathies.J Am Soc Nephrol. 2007; 18: 1855-1871Crossref PubMed Scopus (281) Google Scholar, 24Ala-Mello S. Kivivuori S.M. Ronnholm K.A. Koskimies O. Siimes M.A. Mechanism underlying early anaemia in children with familial juvenile nephronophthisis.Pediatr Nephrol. 1996; 10: 578-581Crossref PubMed Scopus (27) Google Scholar This early anemia may be secondary to impaired function or regulation of erythropoietin-producing cells.24Ala-Mello S. Kivivuori S.M. Ronnholm K.A. Koskimies O. Siimes M.A. Mechanism underlying early anaemia in children with familial juvenile nephronophthisis.Pediatr Nephrol. 1996; 10: 578-581Crossref PubMed Scopus (27) Google Scholar Growth retardation, out of proportion to the degree of renal impairment, is a common finding.25Guay-Woodford L. Other cystic diseases.in: Feehally RJaJ. Comprehensive Clinical Nephrology. 5th ed. Mosby, London, UK2014: 549-564Google Scholar An exception to this clinical presentation is the infantile variant, resulting primarily from mutations in the NPHP2 or NPHP3 genes, in which patients present in the first few months of life with kidney insufficiency and hypertension with rapid progression to ESRD.26Tory K. Rousset-Rouviere C. Gubler M.C. et al.Mutations of NPHP2 and NPHP3 in infantile nephronophthisis.Kidney Int. 2009; 75: 839-847Crossref PubMed Scopus (85) Google Scholar Extrarenal manifestations have been described in 10% to 20% of NPHP patients. The most frequently associated anomaly is retinal dystrophy because of tapetoretinal degeneration (Senior-Loken syndrome). Congenital hepatic fibrosis occurs in some NPHP patients, but the associated bile duct proliferation is mild and qualitatively different from that found in ARPKD.25Guay-Woodford L. Other cystic diseases.in: Feehally RJaJ. Comprehensive Clinical Nephrology. 5th ed. Mosby, London, UK2014: 549-564Google Scholar To date, 19 causative genes have been identified (NPHP1-19). Homozygous deletions in the NPHP1 gene account for 21% of all NPHP cases; however, causative genes are still unknown in approximately 70% of affected individuals. Disease expression seems to be exacerbated by oligogenic inheritance, that is, patients carrying 2 mutations in a single NPHP gene and a third mutation in an additional NPHP gene.25Guay-Woodford L. Other cystic diseases.in: Feehally RJaJ. Comprehensive Clinical Nephrology. 5th ed. Mosby, London, UK2014: 549-564Google Scholar Most of the protein products of the NPHP-associated genes, denoted “nephrocystins,” are expressed in primary cilia or the associated centrosome and play important roles in ciliogenesis and regulation of ciliary signaling.25Guay-Woodford L. Other cystic diseases.in: Feehally RJaJ. Comprehensive Clinical Nephrology. 5th ed. Mosby, London, UK2014: 549-564Google Scholar, 27Wolf M.T. Hildebrandt F. Nephronophthisis.Pediatr Nephrol. 2011; 26: 181-194Crossref PubMed Scopus (127) Google Scholar Kidneys appear to be normal in size or hypoplastic, except in the infantile form, where nephromegaly is present.27Wolf M.T. Hildebrandt F. Nephronophthisis.Pediatr Nephrol. 2011; 26: 181-194Crossref PubMed Scopus (127) Google Scholar Cysts can be observed at the corticomedullary junction. Genetic testing may be helpful in establishing the diagnosis; however, it must be noted that defects in these genes only account for 30% to 40% of NPHP patients.27Wolf M.T. Hildebrandt F. Nephronophthisis.Pediatr Nephrol. 2011; 26: 181-194Crossref PubMed Scopus (127) Google Scholar Given the large number of NPHP-related genes, single-gene analysis is cost prohibitive. Newer strategies using next-generation sequencing technologies in the context of commercially available gene panels currently allows high-throughput mutation detection for 9 to 12 of the known NPHP genes.28Renkema K.Y. Stokman M.F. Giles R.H. Knoers N.V. Next-generation sequencing for research and diagnostics in kidney disease.Nat Rev Nephrol. 2014; 10: 433-444Crossref PubMed Scopus (73) Google Scholar Current treatment of NPHP is entirely supportive. Glomerulocystic kidney disease (GCKD) is not a single disorder but a histologic designation that involves cystic dilatation of Bowman's space in the context of multiple clinical disorders. GCKD has both sporadic and familial occurrence. The clinical presentation of GCKD can be variable, and the appearance of the kidneys on US may be similar to other renal cystic diseases. Kidneys are echogenic and may be small, normal sized, or enlarged. Small renal volumes have typically been reported in cases of hereditary GCKD. Kidney cysts are not always evident on US. Hyperuricemia and an autosomal dominant inheritance pattern may be present in patients with UMOD mutations. Glomerulocystic disease can be divided into 5 major categories: (1) an early manifestation of ADPKD (PKD1 mutations); (2) hereditary GCKD associated with other single-gene defects (eg, hepatocyte nuclear factor-1 beta [HNF1B] and UMOD); (3) GCKD associated with syndromic disorders (eg, Bardet-Biedl syndrome, orofacial digital syndrome, and tuberous sclerosis complex [TSC]); (4) obstructive GCKD with or without kidney dysplasia; and (5) isolated, sporadic cases.29Lennerz J.K. Spence D.C. Iskandar S.S. Dehner L.P. Liapis H. Glomerulocystic kidney: one hundred-year perspective.Arch Pathol Lab Med. 2010; 134: 583-605PubMed Google Scholar, 30Bissler J.J. Siroky B.J. Yin H. Glomerulocystic kidney disease.Pediatr Nephrol. 2010; 25 (quiz 2056–2049): 2049-2056Crossref PubMed Scopus (41) Google Scholar Hereditary forms involve mutations in genes whose proteins are expressed in renal tubular primary cilia or the centrosome.30Bissler J.J. Siroky B.J. Yin H. Glomerulocystic kidney disease.Pediatr Nephrol. 2010; 25 (quiz 2056–2049): 2049-2056Crossref PubMed Scopus (41) Google Scholar GCKD is typically transmitted as an autosomal dominant trait. The diagnosis of GCKD is often based on clinical suspicion, with findings of echogenic kidneys on US with or without glomerular cysts. The cysts may be difficult to define at US, and cortical hyperechogenicity may be seen instead of the typical anechoic appearance of simple cysts.31Wood III, C.G. Stromberg III, L.J. Harmath C.B. et al.CT and MR imaging for evaluation of cystic renal lesions and diseases.Radiographics. 2015; 35: 125-141Crossref PubMed Scopus (69) Google Scholar MRI may be more reliable for diagnosis and demonstrates small kidney cysts with a predominant cortical and subcapsular distribution.31Wood III, C.G. Stromberg III, L.J. Harmath C.B. et al.CT and MR imaging for evaluation of cystic renal lesions and diseases.Radiographics. 2015; 35: 125-141Crossref PubMed Scopus (69) Google Scholar Histopathology shows glomerular cysts defined as Bowman space dilatation greater" @default.
• W1611965846 created "2016-06-24" @default.
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• W1611965846 date "2015-07-01" @default.
• W1611965846 modified "2023-09-24" @default.
• W1611965846 title "Cystic Kidney Disease: A Primer" @default.
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• W1611965846 doi "https://doi.org/10.1053/j.ackd.2015.04.001" @default.
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