scholarly journals Tubular Obstruction Leads to Progressive Proximal Tubular Injury and Atubular Glomeruli in Polycystic Kidney Disease

2014 ◽  
Vol 184 (7) ◽  
pp. 1957-1966 ◽  
Author(s):  
Carolina I. Galarreta ◽  
Jared J. Grantham ◽  
Michael S. Forbes ◽  
Robin L. Maser ◽  
Darren P. Wallace ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Tubular Injury ◽  
Polycystic Kidney ◽  
Atubular Glomeruli ◽  
Proximal Tubular

scholarly journals Dietary phosphate restriction attenuates polycystic kidney disease in mice

2020 ◽  
Vol 318 (1) ◽  
pp. F35-F42 ◽  
Author(s):  
Faith Omede ◽  
Shiqin Zhang ◽  
Cassandra Johnson ◽  
Emily Daniel ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Type I ◽  
Tubular Injury ◽  
Polycystic Kidney ◽  
Restricted Diet ◽  
Kidney Fibrosis ◽  
Dietary Phosphate

Studies in rodents with reduced nephron mass have suggested a strong positive correlation between dietary phosphate consumption and CKD progression. Prior work by our group demonstrated that dietary phosphate restriction can prevent tubular injury and microcyst formation in rodents with glomerulonephritis. Tubular injury and cystic dilation of tubules are key contributors to kidney function decline in polycystic kidney disease (PKD). Here, we determined whether dietary phosphate restriction slows renal cyst growth and fibrosis in a mouse model of PKD. Pcy/pcy mice received a normal phosphate (0.54%) or a phosphate-restricted (0.02%) diet ( n = 10/group) from 7 to 20 wk of age. All of the other major dietary constituents, including protein source and content, were comparable between the two diets. At 20 wk, body weight, kidney weight-to-body weight ratio (KW/BW), cystic area, cyst number, and kidney fibrosis were quantified. Pcy/pcy mice fed a phosphate-restricted diet had lower serum phosphate, fibroblast growth factor 23, and parathyroid hormone levels, along with elevated serum calcium levels and increased kidney Klotho gene expression compared with mice that consumed the control diet. Dietary phosphate restriction resulted in a 25% lower KW/BW ratio and reduced the cyst number, cystic index, and gene expression for the tubular injury markers neutrophil gelatinase-associated lipocalin and interleukin-18. Mice fed the phosphate-restricted diet exhibited lower kidney expression for pathways involved in collagen deposition and myofibroblast activation (collagen type I-α1, phosphorylated SMAD3, and α-smooth muscle actin); however, histological differences in kidney fibrosis were not appreciated. Dietary phosphate restriction slows cystogenesis and inhibits the activation of key pathways in the generation of kidney fibrosis in PKD mice.

scholarly journals Proximal Tubular Cysts in Fetal Human Autosomal Recessive Polycystic Kidney Disease

2000 ◽  
Vol 11 (4) ◽  
pp. 760-763 ◽  
Author(s):  
KOICHI NAKANISHI ◽  
WILLIAM E. SWEENEY ◽  
KLAUS ZERRES ◽  
LISA M. GUAY-WOODFORD ◽  
ELLIS D. AVNER
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Gestational Age ◽  
Autosomal Recessive ◽  
Cyst Formation ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Polycystic Kidney ◽  
Proximal Tubular ◽  
Collecting Tubules

Abstract. Standard texts describe human autosomal recessive polycystic kidney disease (ARPKD) as a cystic kidney disease in which lesions are localized to collecting tubules. Murine models of ARPKD consistently demonstrate an early phase of proximal tubular (PT) cystic involvement, which disappears shortly after birth. This is followed by a phase of collecting tubular (CT) cyst formation and progressive enlargement leading to compromise of renal function and death. Because the description of cystic lesions in human ARPKD has been largely based on postnatal specimens, PT cyst formation was hypothesized to be a characteristic feature of fetal human, as well as murine, ARPKD. This study examines nephron segment-specific cyst localization histochemically by lectin binding in 11 human ARPKD specimens obtained at different fetal and postnatal ages. PT cysts were found in human fetal specimens from gestational age 14 wk to 26 wk. The percentage of cysts involving PT segments ranged from 2 to 41%. The cystic index of PT cysts ranged from 2 to 5. In all specimens in which PT cysts were found, both the percentage of CT cysts and their cystic index were equal to or greater than the percentage of PT cysts and the associated PT cystic index. PT cysts were absent in all kidney specimens older than 34 wk gestational age. It is concluded that human ARPKD, like murine ARPKD, has a transient phase of PT cyst formation during early fetal development.

scholarly journals Atubular glomeruli in a rat model of polycystic kidney disease

2002 ◽  
Vol 62 (6) ◽  
pp. 1947-1957 ◽  
Author(s):  
George A. Tanner ◽  
Marcus A. Tielker ◽  
Bret A. Connors ◽  
Carrie L. Phillips ◽  
Judith A. Tanner ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Rat Model ◽  
Polycystic Kidney ◽  
Atubular Glomeruli

scholarly journals Lectin characterization of cystogenesis in the SBM transgenic model of polycystic kidney disease.

1992 ◽  
Vol 3 (4) ◽  
pp. 975-983
Author(s):  
V D'Agati ◽  
M Trudel
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Simian Virus 40 ◽  
Renal Cysts ◽  
Simian Virus ◽  
Coding Region ◽  
Polycystic Kidney ◽  
Electron Microscopic ◽  
Proximal Tubular ◽  
Collecting Tubules

The generation of a novel transgenic mouse model of polycystic kidney disease with a construct (SBM) that links the coding region of the c-myc proto-oncogene to the simian virus 40 enhancer and beta-globin promoter was previously reported (see reference 1). In order to determine the site of origin and histogenesis of renal cysts in this model, lectin/immunohistochemical and electron microscopic studies on mice of varying ages (from birth to adulthood) are described here. Cysts are detectable at birth and increase in number and diameter with age. Cysts predominantly involve the collecting tubules of young transgenic mice but progressively affect the proximal tubules with advancing age. A minority of cysts are of distal tubular origin in all age groups studied. Tubular hyperplasias are primarily reactive with proximal tubular markers and appear to precede the development of proximal tubular cysts in adult mice. This particular phenotypic evolution of polycystic kidney disease with advancing age suggests that the cystogenic potential of the transgene is modulated by yet unidentified tubular segment-specific responses.

An endocytosis defect as a possible cause of proteinuria in polycystic kidney disease

2001 ◽  
Vol 280 (2) ◽  
pp. F244-F253 ◽  
Author(s):  
Nicholas Obermüller ◽  
Bettina Kränzlin ◽  
Werner F. Blum ◽  
Norbert Gretz ◽  
Ralph Witzgall
Keyword(s):  
Growth Factor ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Polycystic Kidney ◽  
Endocytic Machinery ◽  
Proximal Tubular ◽  
Autosomal Dominant Polycystic Kidney ◽  
Renal Tubular ◽  
Cyst Lining

Because proteinuria has been demonstrated in patients with autosomal-dominant polycystic kidney disease (ADPKD), we have investigated whether proteinuria also occurs in the ( cy/ +) rat, a widely used model for ADPKD. Increased urinary excretion of proteins, in particular of albumin, can be found in 16-wk-old ( cy/ +) rats, with a gel electrophoresis pattern compatible with a tubular origin of proteinuria. Using FITC-labeled dextran as an in vivo tracer for renal tubular endosomal function, we could show that portions of cyst-lining epithelia from proximal tubules have lost the ability to endocytose, which is necessary for the reabsorption of low-molecular-weight proteins. By immunohistochemistry, the expression of other proteins implicated in endocytosis, such as the chloride channel ClC-5 and the albumin receptor megalin, correlated well with the presence and absence of FITC-dextran in cysts. As an example of growth factor systems possibly being affected by this endocytosis defect, we could detect increased urinary levels of insulin-like growth factor-I protein in ( cy/ +) animals. These data indicate that proteinuria and albuminuria in the aforementioned rat model for ADPKD are due to a loss of the endocytic machinery in epithelia of proximal tubular cysts. This may also affect the concentration of different growth factors and hormones in cyst fluids and thus modulate cyst development.

scholarly journals Proteomic analysis of AQP11-null kidney: Proximal tubular type polycystic kidney disease

2018 ◽  
Vol 13 ◽  
pp. 17-21 ◽  
Author(s):  
Tatsuya Saito ◽  
Yasuko Tanaka ◽  
Yoshiyuki Morishita ◽  
Kenichi Ishibashi
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Proteomic Analysis ◽  
Polycystic Kidney ◽  
Tubular Type ◽  
Proximal Tubular
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