Neonatal polycystic kidney disease: a novel variant

2021 ◽  
Vol 14 (7) ◽  
pp. e242991
Author(s):  
Catherine Finnegan ◽  
Claire Murphy ◽  
Fionnuala Breathnach
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Renal Cysts ◽  
Fetal Life ◽  
Polycystic Kidney ◽  
Cystic Kidneys ◽  
Hypomorphic Allele ◽  
Novel Variant ◽  
Uncertain Significance ◽  
Renal Enlargement

Polycystic kidney disease (PKD) is a condition typified by multiple renal cysts and renal enlargement. Classification is usually determined by mode of inheritance—autosomal dominant PKD (ADPKD) or autosomal recessive PKD (ARPKD). ARPKD frequently presents in fetal life, but here we report a rare case of a family with two siblings diagnosed with ADPKD manifesting in utero with novel genetic findings. During the first pregnancy, enlarged cystic kidneys were noted at the gestational age (GA) of 18 weeks, which became progressively larger and anyhdramnios ensued by GA of 25 weeks. The couple opted to terminate the pregnancy. The second pregnancy similarly presented with bilateral enlarged cystic kidneys, but amniotic fluid remained normal throughout and she delivered at GA of 36 weeks. Genetic testing revealed the fetus to be heterozygous in AD PKD1, which is known to cause ADPKD and heterozygous for a hypomorphic allele for ADPKD of uncertain significance. The fetus was also found to be heterozygous in the AR PKHD1 gene with a variant not previously described in the literature. Where fetal features consistent with ARPKD are identified in the setting of familial ADPKD, this fetal manifestation of ADPKD, resulting from combined variants in the PKD1 gene, should be considered.

Apoptosis in polycystic kidney disease: involvement of caspases

2000 ◽  
Vol 278 (3) ◽  
pp. R763-R769 ◽  
Author(s):  
Shujath M. Ali ◽  
Victoria Y. Wong ◽  
Kristine Kikly ◽  
Todd A. Fredrickson ◽  
Paul M. Keller ◽  
...  
Keyword(s):  
Cell Death ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Apoptotic Cell ◽  
Renal Cysts ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Homozygous Mutation ◽  
Polycystic Kidney ◽  
Apoptosis Pathway ◽  
Cystic Kidneys

Polycystic kidney disease (PKD) is characterized by the development of large renal cysts and progressive loss of renal function. Although the cause of the development of renal cysts is unknown, recent evidence suggests that excessive apoptosis occurs in PKD. With the use of terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, we have confirmed the presence of apoptotic bodies in cystic kidneys of congenital polycystic kidney (cpk) disease mice carrying a homozygous mutation at 3 wk of age. Apoptosis was localized primarily to the interstitium with little evidence of cell death in cyst epithelium or noncystic tubules. In addition, we observed that the expression of various caspases, bax and bcl-2, was upregulated in cystic kidneys. With the use of various substrates in enzyme activity assays, we have demonstrated a greater than sevenfold increase in caspase 4 activity and a sixfold increase in caspase 3 activity. These data suggest that there is a caspase-dependent apoptosis pathway associated with PKD and support the hypothesis that apoptotic cell death contributes to cyst formation in PKD.

The child with renal cysts

2015 ◽  
Author(s):  
Carsten Bergmann ◽  
Nadina Ortiz-Brüchle ◽  
Valeska Frank ◽  
Klaus Zerres
Keyword(s):  
Family History ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Renal Cysts ◽  
Polycystic Kidney ◽  
Polycystic Kidneys ◽  
Cystic Kidneys ◽  
Common Diagnosis ◽  
The Family ◽  
Autosomal Dominant Polycystic Kidney

Renal cysts of different aetiology are a common diagnosis in paediatric nephrology. The classification is usually based on the clinical picture, morphology, and family history. In syndromic forms, additional features have to be evaluated. Most common are cystic dysplastic kidneys with a broad phenotypic spectrum ranging from asymptomatic clinical courses in unilateral cases to severe, lethal manifestations in patients with considerable bilateral involvement. Simple cysts are rare. Polycystic kidneys are usually subdivided according to the mode of inheritance into autosomal recessive and autosomal dominant polycystic kidney disease. The most useful investigation in order to distinguish between these two types is the family history with parental ultrasound and demonstration of polycystic kidneys in one parent in the majority of cases with dominant polycystic kidney disease. Finally, cystic kidneys are associated with a variety of hereditary, usually recessive syndromes affecting cilia.

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.

scholarly journals Autosomal recessive polycystic kidney disease: case report of a newborn with rare PKHD1 mutation, rapid renal enlargement and early fatal outcome

2020 ◽  
Vol 46 (1) ◽  
Author(s):  
Gregorio Serra ◽  
Giovanni Corsello ◽  
Vincenzo Antona ◽  
Maria Michela D’Alessandro ◽  
Nicola Cassata ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Recessive ◽  
Fatal Outcome ◽  
Pulmonary Insufficiency ◽  
Homozygous Mutation ◽  
Polycystic Kidney ◽  
Disease Case ◽  
Renal Enlargement

Abstract Introduction Autosomal recessive polycystic kidney disease (ARPKD; MIM#263200) is one of the most frequent pediatric renal cystic diseases, with an incidence of 1:20,000. It is caused by mutations of the PKHD1 gene, on chromosome 6p12. The clinical spectrum is highly variable, ranging from late-onset milder forms to severe perinatal manifestations. The management of newborns with severe pulmonary insufficiency is challenging, and causes of early death are sepsis or respiratory failure. In cases of massive renal enlargement, early bilateral nephrectomy and peritoneal dialysis may reduce infant mortality. However, there is no conclusive data on the role of surgery, and decision-making is driven by patient’s clinical condition and expertise of the center. Patient presentation We hereby describe a preterm female newborn with perinatal, rapid and bilateral, abnormal growth of both kidneys, respiratory failure and initial signs of liver disease. She was subsequently confirmed to be affected by a rare and severe homozygous mutation of the PKHD1 gene, inherited from both her consanguineous parents. Our patient died 78 days after birth, due to a fungal sepsis which worsened her respiratory insufficiency. Conclusions This patient report shows some of the clinical and ethical issues of neonatal ARPKD, and the need of multidisciplinary approach and good communication with the family. Target next generation sequencing (NGS) techniques may guide and support clinicians, as well as guarantee to these patients the most appropriate clinical management, avoiding unnecessary and/or disproportionate treatments.

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.

scholarly journals Osmoregulation in Polycystic Kidney Disease: Relationship with Cystogenesis and Hypertension

2018 ◽  
Vol 72 (Suppl. 2) ◽  
pp. 33-38 ◽  
Author(s):  
Conor F. Underwood ◽  
Jacqueline K. Phillips ◽  
Cara M. Hildreth
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Experimental Studies ◽  
Extracellular Fluid ◽  
Renal Cysts ◽  
Fluid Loss ◽  
Polycystic Kidney ◽  
Stimulatory Action ◽  
Cross Sectional ◽  
Vasopressin Release

Polycystic kidney disease (PKD) is a group of monogenetic conditions characterised by the progressive accumulation of multiple renal cysts and hypertension. One of the earliest features of PKD is a reduction in urinary concentrating capacity that impairs extracellular fluid conservation. Urinary concentrating impairment predisposes PKD patients to periods of hypohydration when fluid loss is not adequately compensated by fluid intake. The hypohydrated state provides a blood hyperosmotic stimulus for vasopressin release to minimise further water loss. However, over-activation of renal V2 receptors contributes to cyst expansion. Although suppressing vasopressin release with high water intake has been shown to impair disease progression in rodent models, whether this approach is efficacious in patients remains uncertain. The neural osmoregulatory pathway that controls vasopressin secretion also exerts a stimulatory action on vasomotor sympathetic activity and blood pressure during dehydration. Recurrent dehydration leads to a worsening of hypertension in rodents and cross-sectional data suggests that reduced urinary concentrating ability may contribute to hypertension development in the clinical PKD population. Experimental studies are required to evaluate this hypothesis and to determine the underlying mechanism.

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