Pathogenesis of Renal Cysts in Dominantly Inherited Polycystic Kidney Disease

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.

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Percutaneous drainage by multiple and bilateral puncture of infected renal cysts in autosomal dominant polycystic kidney disease

Nephrology Dialysis Transplantation ◽

10.1093/ndt/13.6.1606 ◽

1998 ◽

Vol 13 (6) ◽

pp. 1606-1608 ◽

Cited By ~ 4

Author(s):

J Palou

Keyword(s):

Kidney Disease ◽

Polycystic Kidney Disease ◽

Percutaneous Drainage ◽

Autosomal Dominant ◽

Renal Cysts ◽

Polycystic Kidney ◽

Autosomal Dominant Polycystic Kidney

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Osmoregulation in Polycystic Kidney Disease: Relationship with Cystogenesis and Hypertension

Annals of Nutrition and Metabolism ◽

10.1159/000488125 ◽

2018 ◽

Vol 72 (Suppl. 2) ◽

pp. 33-38 ◽

Cited By ~ 1

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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Autosomal dominant polycystic kidney disease

10.1093/med/9780199592548.003.0307_update_001 ◽

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.

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The child with renal cysts

10.1093/med/9780199592548.003.0305 ◽

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.

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Non-compaction of ventricular myocardium with polycystic kidney disease with cardiogenic cerebral embolism

BMJ Case Reports ◽

10.1136/bcr-2019-232458 ◽

2020 ◽

Vol 13 (1) ◽

pp. e232458

Author(s):

Monu Rani ◽

Rajesh Rajput ◽

Sanat Mishra ◽

Rakesh Garg

Keyword(s):

Kidney Disease ◽

Polycystic Kidney Disease ◽

Treatment Guidelines ◽

Renal Cysts ◽

Ventricular Myocardium ◽

Sudden Onset ◽

Left Ventricular ◽

Cerebral Embolism ◽

Polycystic Kidney ◽

Characteristic Appearance

Non-compaction of ventricular myocardium is a rare cardiomyopathy involving an early arrest of normal compaction of myocardium during fetal ontogenesis. Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary nephropathy characterised by multiple renal cysts replacing the renal parenchyma and extrarenal manifestations. Here, we report a case of 65-year-old man, chronic smoker, presented with sudden onset right brachial monoparesis, exertional dyspnoea, orthopnoea, bipedal swelling and diagnosed as a case of ADPKD with left ventricular non-compaction cardiomyopathy with acute left ventricular failure and cardiogenic cerebral embolism (no evidence of atrial fibrillation); based on characteristic appearance on two-dimensional echocardiography and cardiac magnetic resonance. The patient was managed with guideline-directed pharmacotherapy for heart failure and anticoagulation as a secondary stroke prevention measure. Through this case report, we try to discuss the association between two rare entities and individualisation of treatment options available as a case-based approach, as no standard treatment guidelines are available.

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Inversin Forms a Complex with Catenins and N-Cadherin in Polarized Epithelial Cells

Molecular Biology of the Cell ◽

10.1091/mbc.e02-04-0195 ◽

2002 ◽

Vol 13 (9) ◽

pp. 3096-3106 ◽

Cited By ~ 74

Author(s):

Jens Nürnberger ◽

Robert L. Bacallao ◽

Carrie L. Phillips

Keyword(s):

Cell Adhesion ◽

Kidney Disease ◽

Polycystic Kidney Disease ◽

Polyclonal Antibodies ◽

Cell Monolayer ◽

Renal Cysts ◽

Cell Junctions ◽

Metanephric Mesenchyme ◽

Polycystic Kidney ◽

Cell Cell

Nephrogenesis starts with the reciprocal induction of two embryonically distinct analages, metanephric mesenchyme and ureteric bud. This complex process requires the refined and coordinated expression of numerous developmental genes, such as inv. Mice that are homozygous for a mutation in the inv gene (inv/inv) develop renal cysts resembling autosomal-recessive polycystic kidney disease. The gene locus containing inv has been proposed to serve as a common modifier for some human and rodent polycystic kidney disease phenotypes. We generated polyclonal antibodies to inversin to study its subcellular distribution, potential binding partners, and functional aspects in cultured murine proximal tubule cells. A 125-kDa inversin protein isoform was found at cell-cell junctions. Two inversin isoforms, 140- and 90-kDa, were identified in the nuclear and perinuclear compartments. Plasma membrane allocation of inversin is dependent upon cell-cell contacts and was redistributed when cell adhesion was disrupted after incubation of the cell monolayer with low-calcium/EGTA medium. We further show that the membrane-associated 125-kDa inversin forms a complex with N-cadherin and the catenins. The 90-kDa nuclear inversin complexes with β-catenin. These findings indicate that the inv gene product functions in several cellular compartments, including the nucleus and cell-cell adhesion sites.

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