Autosomal dominant polycystic kidney disease in children and young adults

2015 ◽  
Author(s):  
Carsten Bergmann ◽  
Klaus Zerres
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Renal Cysts ◽  
Cyst Formation ◽  
Polycystic Kidney ◽  
Hypomorphic Allele ◽  
Extrarenal Manifestations ◽  
Children And Young Adults ◽  
Autosomal Dominant Polycystic Kidney

Many children with autosomal dominant polycystic kidney disease have renal cysts on ultrasound, some are even being diagnosed antenatally, although the statistics on this are not well understood. Most are asymptomatic but hypertension may be more common than generally appreciated, and a minority of patients develop early renal failure. The cause of early presentations is probably often inheritance of a hypomorphic allele on another gene implicated in cyst formation, or in cilia. Extrarenal manifestations of polycystic kidney disease are very rare in childhood.

Extrarenal Manifestations of Autosomal Dominant Polycystic Kidney Disease

Nephrology ◽  
1991 ◽  
pp. 1537-1543
Author(s):  
Dominique Chauveau ◽  
Yves Pirson ◽  
Dominique Droz ◽  
Joseph Rosenfeld ◽  
Jean-Pierre Grünfeld
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Polycystic Kidney ◽  
Extrarenal Manifestations ◽  
Autosomal Dominant Polycystic Kidney

scholarly journals Cell-Autonomous Hedgehog Signaling Is Not Required for Cyst Formation in Autosomal Dominant Polycystic Kidney Disease

2019 ◽  
Vol 30 (11) ◽  
pp. 2103-2111 ◽  
Author(s):  
Ming Ma ◽  
Emilie Legué ◽  
Xin Tian ◽  
Stefan Somlo ◽  
Karel F. Liem
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Mouse Models ◽  
Hedgehog Signaling ◽  
Autosomal Dominant ◽  
Cyst Formation ◽  
Hedgehog Pathway ◽  
Adult Onset ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney

BackgroundPKD1 or PKD2, the two main causal genes for autosomal dominant polycystic kidney disease (ADPKD), encode the multipass transmembrane proteins polycystin-1 (PC1) and polycystin-2 (PC2), respectively. Polycystins localize to the primary cilium, an organelle essential for cell signaling, including signal transduction of the Hedgehog pathway. Mutations in ciliary genes that build and maintain the cilium also cause renal cystic disease through unknown pathways. Although recent studies have found alterations in Hedgehog signaling in ADPKD-related models and tissues, the relationship between Hedgehog and polycystic kidney disease is not known.MethodsTo examine the potential role of cell-autonomous Hedgehog signaling in regulating kidney cyst formation in vivo in both early- and adult-onset mouse models of ADPKD, we used conditional inactivation of Pkd1 combined with conditional modulation of Hedgehog signaling components in renal epithelial cells, where mutations in Pkd1 initiate cyst formation. After increasing or decreasing levels of Hedgehog signaling in cells that underwent inactivation of Pkd1, we evaluated the effects of these genetic manipulations on quantitative parameters of polycystic kidney disease severity.ResultsWe found that in Pkd1 conditional mutant mouse kidneys, neither downregulation nor activation of the Hedgehog pathway in epithelial cells along the nephron significantly influenced the severity of the polycystic kidney phenotype in mouse models of developmental or adult-onset of ADPKD.ConclusionsThese data suggest that loss of Pkd1 function results in kidney cysts through pathways that are not affected by the activity of the Hedgehog pathway.

scholarly journals Somatostatin in renal physiology and autosomal dominant polycystic kidney disease

2019 ◽  
Vol 35 (8) ◽  
pp. 1306-1316 ◽  
Author(s):  
A Lianne Messchendorp ◽  
Niek F Casteleijn ◽  
Esther Meijer ◽  
Ron T Gansevoort
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Unmet Need ◽  
Cyst Formation ◽  
Renal Physiology ◽  
Intracellular Camp ◽  
Kidney Volume ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney

Abstract Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst formation, leading to growth in kidney volume and renal function decline. Although therapies have emerged, there is still an important unmet need for slowing the rate of disease progression in ADPKD. High intracellular levels of adenosine 3′,5′-cyclic monophosphate (cAMP) are involved in cell proliferation and fluid secretion, resulting in cyst formation. Somatostatin (SST), a hormone that is involved in many cell processes, has the ability to inhibit intracellular cAMP production. However, SST itself has limited therapeutic potential since it is rapidly eliminated in vivo. Therefore analogues have been synthesized, which have a longer half-life and may be promising agents in the treatment of ADPKD. This review provides an overview of the complex physiological effects of SST, in particular renal, and the potential therapeutic role of SST analogues in ADPKD.

Pkd1-targeted mutation reveals a role for the Wolffian duct in autosomal dominant polycystic kidney disease

2019 ◽  
Vol 11 (1) ◽  
pp. 78-85 ◽  
Author(s):  
J. B. Tee ◽  
A. V. Dnyanmote ◽  
M. K. Lorenzo ◽  
O. R. Lee ◽  
S. Grisaru ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
High Throughput Sequencing ◽  
Autosomal Dominant ◽  
Cyst Formation ◽  
Wolffian Duct ◽  
Renal Tubules ◽  
Polycystic Kidney ◽  
Cystic Kidneys ◽  
Autosomal Dominant Polycystic Kidney

AbstractSeveral life-threatening diseases of the kidney have their origins in mutational events that occur during embryonic development. In this study, we investigate the role of the Wolffian duct (WD), the earliest embryonic epithelial progenitor of renal tubules, in the etiology of autosomal dominant polycystic kidney disease (ADPKD). ADPKD is associated with a germline mutation of one of the two Pkd1 alleles. For the disease to occur, a second event that disrupts the expression of the other inherited Pkd1 allele must occur. We postulated that this secondary event can occur in the pronephric WD. Using Cre-Lox recombination, mice with WD-specific deletion of one or both Pkd1 alleles were generated. Homozygous Pkd1-targeted deletion in WD-derived tissues resulted in mice with large cystic kidneys and serologic evidence of renal failure. In contrast, heterozygous deletion of Pkd1 in the WD led to kidneys that were phenotypically indistinguishable from control in the early postnatal period. High-throughput sequencing, however, revealed underlying gene and microRNA (miRNA) changes in these heterozygous mutant kidneys that suggest a strong predisposition toward developing ADPKD. Bioinformatic analysis of this data demonstrated an upregulation of several miRNAs that have been previously associated with PKD; pathway analysis further demonstrated that the differentially expressed genes in the heterozygous mutant kidneys were overrepresented in signaling pathways associated with maintenance and function of the renal tubular epithelium. These results suggest that the WD may be an early epithelial target for the genetic or molecular signals that can lead to cyst formation in ADPKD.

Autosomal dominant polycystic kidney disease

2018 ◽  
Author(s):  
Albert C. M. Ong ◽  
Timothy Ellam
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Functional Decline ◽  
Renal Cysts ◽  
Common Symptom ◽  
Polycystic Kidney ◽  
Cystic Change ◽  
Autosomal Dominant Polycystic Kidney ◽  
Cyst Growth

Autosomal dominant polycystic kidney disease (ADPKD) is responsible for up to 10% of prevalent patients with end-stage renal disease (ESRD). It is characterized by the enlargement of multiple bilateral renal cysts, present in almost all patients by their fifth decade. Loin pain is a common symptom that may be caused by cyst growth, intracyst haemorrhage, nephrolithiasis, or infection. Gross haematuria is also a common feature, but usually settles spontaneously. Excretory impairment develops after extensive cystic change has occurred and progresses to ESRD in half of all affected patients by the age of 60. However, the onset of cystic change and rate of renal functional decline are highly variable between individuals. ADPKD associated with the PKD1 gene has an earlier average age of cyst development and ESRD than PKD2, but the two cannot be distinguished on clinical grounds. Polycystins 1 and 2 are expressed in various organs and extrarenal disease may be the presenting feature. Intracranial aneurysms are five times more common in patients with ADPKD, but rupture is infrequent. Liver cysts are present in most patients and may be complicated by haemorrhage or infection, though liver failure is very rare. Massive hepatic cystic disease is confined to women, reflecting stimulatory effects of oestrogen on hepatic cyst growth. Cardiovascular disease is the leading cause of death in ADPKD and vascular dysfunction is present in many patients even before the development of excretory impairment. However, despite the multisystem manifestations of ADPKD, survival from ESRD is better for patients with ADPKD than for other non-diabetic causes of kidney failure.

A role for CFTR in human autosomal dominant polycystic kidney disease

1996 ◽  
Vol 270 (1) ◽  
pp. C389-C399 ◽  
Author(s):  
K. Hanaoka ◽  
O. Devuyst ◽  
E. M. Schwiebert ◽  
P. D. Wilson ◽  
W. B. Guggino
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Primary Cultures ◽  
Cyst Formation ◽  
Disulfonic Acid ◽  
Polycystic Kidney ◽  
Acid Sensitivity ◽  
Autosomal Dominant Polycystic Kidney

Human autosomal dominant polycystic kidney disease (ADPKD) is the most common lethal dominant hereditary disorder characterized by enormous renal enlargement and the development of multiple cysts originating from nephrons. We investigated the pathogenesis of cyst formation in ADPKD by using patch-clamp and immunocytochemical techniques. Adenosine 3',5'-cyclic monophosphate-activated Cl- currents are present in primary cultures of ADPKD cells and have characteristics such as a linear current-voltage relation, insensitivity to 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, sensitivity to glibenclamide and diphenylamine carboxylic acid, and an anion selectivity sequence of Br- > Cl- > I- > glutamate, all of which are identical to cystic fibrosis transmembrane conductance regulator (CFTR). With the use of CFTR antibodies raised against the regulatory and first nucleotide-binding domains, CFTR was detected in primary cultures of ADPKD cells. Similar results were obtained in vivo in cyst-lining epithelial cells in ADPKD kidneys, where staining was seen associated with the apical membrane regions. These data indicate that the CFTR Cl- channel exists in apical membranes of ADPKD cells and may play an important role in cyst formation or enlargement.

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