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The expression of somatostatin receptor 2 decreases during cyst growth in mice with polycystic kidney disease.

ABSTRACT:

Impact statement

Somatostatin (SST) analogs have been shown to halt cyst growth and progression of autosomal dominant polycystic kidney disease by several clinical trials. However, two studies suggest that the effect of the SST analog octreotide on kidney growth during the first year of treatment is reduced in the subsequent follow-ups and the kidney enlargement resumes. This biphasic change in kidney growth during octreotide treatment may be partially explained by alterations in SSTR2 expression. Here, we found that SSTR2 is mainly expressed in distal tubules and collecting ducts in murine kidneys, and the expression of SSTR2 decreases during cyst growth in two PKD mouse models. Our data may thus provide possible explanations for the lack of efficacy in long-term treatment with SST analogs.

SUBMITTER: Lin C

PROVIDER: S-EPMC6434459 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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The expression of somatostatin receptor 2 decreases during cyst growth in mice with polycystic kidney disease.

Lin Cong C Lin Cong C Happé Hester H Veraar Kimberley K Scharpfenecker Marion M Peters Dorien Jm DJ

Experimental biology and medicine (Maywood, N.J.) 20180927 13

<h4>Impact statement</h4>Somatostatin (SST) analogs have been shown to halt cyst growth and progression of autosomal dominant polycystic kidney disease by several clinical trials. However, two studies suggest that the effect of the SST analog octreotide on kidney growth during the first year of treatment is reduced in the subsequent follow-ups and the kidney enlargement resumes. This biphasic change in kidney growth during octreotide treatment may be partially explained by alterations in SSTR2 e ...[more]

PMID: 30261745

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Project description:Background and objectivesTo evaluate the growth pattern of kidney cyst number and cyst volume in association with kidney size, demographics, and genotypes in autosomal dominant polycystic kidney disease.Design, setting, participants, & measurementsKidney cyst number and cyst volume were measured from serial magnetic resonance images, giving a maximum follow-up of 14.23 years, from 241 patients with autosomal dominant polycystic kidney disease (15-46 years old at baseline). The growth pattern was analyzed, in association with sex, age, height-adjusted total kidney volume, and genotype, using linear mixed models of repeated measurements and tests of interactions with age (as a time-dependent covariate) to assess rates of change over time. Models were also fit using Irazabal class. Genotypic groups were characterized as either (1) PKD1 truncating, PKD1 nontruncating, and PKD2 plus patients with no mutation detected; or (2) in combination with PKD1 mutation strength groups.ResultsImaging and genetic data were collected (at least one visit) for 236 participants. The mean height-adjusted total cyst number increased exponentially over time from a baseline value of 762 to 1715 at the last clinic visit, while the mean height-adjusted total cyst volume increased exponentially from 305 to 770 ml. Height-adjusted total kidney volume, height-adjusted total cyst number, and height-adjusted total cyst volume were all highly correlated over time. Female participants and participants with larger height-adjusted total kidney volume at baseline showed smaller rates of change in the log of height-adjusted total cyst number and cyst volume. PKD1 was associated with significant increases in both cyst number and volume at a given age, but genotype did not significantly affect the rate of growth.ConclusionsBoth height-adjusted total cyst number and height-adjusted total cyst volume increased exponentially and more than doubled over 14.23 years of follow-up. Compared with PKD2 plus no mutation detected, PKD1 was associated with a greater cyst number and volume at a given age, but no significant difference in the rate of growth.

Dataset Information

The expression of somatostatin receptor 2 decreases during cyst growth in mice with polycystic kidney disease.

Impact statement

Publications

The expression of somatostatin receptor 2 decreases during cyst growth in mice with polycystic kidney disease.

Similar Datasets

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