ADPKD Treatment Report

www.ADPKDTreatmentReport.com

Research

Salt, water, and vasopressin in polycystic kidney disease

https://www.kidney-international.org/article/S0085-2538(20)30635-9/fulltext

https://doi.org/10.1016/j.kint.2020.06.001

https://pubmed.ncbi.nlm.nih.gov/32998813/

TITLE:
Salt, water, and vasopressin in polycystic kidney disease

DATE:
Thu, 01 Oct 2020 06:00:00 -0400

AUTHORS:
Vicente E Torres

SOURCE:
Kidney international

DESCRIPTION:
Excessive salt intake and vasopressin may promote cyst growth in autosomal dominant polycystic kidney disease and glomerular filtration rate (GFR) decline in chronic kidney disease. Kramers et al. confirmed the effects of salt in a large autosomal dominant polycystic kidney disease cohort. Copeptin mediated 72% and 25% of the salt effects on GFR decline and kidney growth. Kidney growth did not significantly contribute to the copeptin-mediated salt effect on GFR. Differences in kidney growth and…

CONTENT:
Kidney Int. 2020 Oct;98(4):831-834. doi: 10.1016/j.kint.2020.06.001.

ABSTRACT

Excessive salt intake and vasopressin may promote cyst growth in autosomal dominant polycystic kidney disease and glomerular filtration rate (GFR) decline in chronic kidney disease. Kramers et al. confirmed the effects of salt in a large autosomal dominant polycystic kidney disease cohort. Copeptin mediated 72% and 25% of the salt effects on GFR decline and kidney growth. Kidney growth did not significantly contribute to the copeptin-mediated salt effect on GFR. Differences in kidney growth and GFR decline trajectories and factors other than cyst growth contributing to GFR decline may explain the divergent effects.

PMID:32998813 | DOI:10.1016/j.kint.2020.06.001

PUBMED ID:
pubmed:32998813

OTHER ID:
pmid:32998813,doi:10.1016/j.kint.2020.06.001

PUBLICATION DATE:
Thu, 01 Oct 2020 06:00:00 -0400
2020-10-01

RETRIEVAL DATE :
10/01/20 12:09PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/32998813/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1jmC0p0kwOiHcoERYElvPhktie_Gw8TL2aOwN185ZhQUSROsDP&fc=20200821211545&ff=20201001120951&v=2.12.1

LINK – DOI:
https://doi.org/10.1016/j.kint.2020.06.001

LINK – FULL TEXT:

NOTES:

Genetics May Predict Effectiveness of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease

https://www.karger.com/Article/FullText/509817

https://pubmed.ncbi.nlm.nih.gov/32784291/

Genetics May Predict Effectiveness of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease

Am J Nephrol
2020 Aug 12;1-7. doi: 10.1159/000509817. Online ahead of print.

PMID: 32784291 DOI: 10.1159/000509817

Abstract
Background: Tolvaptan is the only therapeutic drug for autosomal dominant polycystic kidney disease (ADPKD). The influence of mutations in polycystic kidney disease 1 and 2 genes (PKD1 and PKD2) on the treatment effects of tolvaptan is not well documented in the literature.

Methods: We retrospectively evaluated the relationship between genotype and the efficacy of tolvaptan in 18 patients with ADPKD who had been treated at Toranomon Hospital and undergone genetic testing between April 2016 and February 2020.

Results: The annual change in estimated glomerular filtration rate (ΔeGFR/y) from before to after tolvaptan was from a median of -5.5 to -2.5 mL/min/1.73 m2 in the PKD1 truncating group, -3.3 to -2.4 mL/min/1.73 m2 in the PKD1 non-truncating group, -3.1 to -1.6 mL/min/1.73 m2 in the PKD2 group, and -1.9 to -2.6 mL/min/1.73 m2 in the group with no PKD1/2 mutation. The median degrees of improvement of ΔeGFR/y were 2.5 (45%), 0.4 (10%), 0.6 (28%), and -0.7 (-37%) mL/min/1.73 m2, respectively. Compared with the group of patients with any PKD1/2 mutation, the group with no PKD1/2 mutation showed significantly less improvement in ΔeGFR/y with tolvaptan (0.6 vs. -0.7 mL/min/1.73 m2, respectively; p = 0.01) and significantly less improvement in the annual rate of increase in total kidney volume (TKV) with tolvaptan (-6.7 vs. -1.1%, respectively; p = 0.02).

Conclusion: Patients with ADPKD and no PKD1/2 mutation showed less improvement in ΔeGFR/y and the annual rate of increase in TKV with tolvaptan. Detecting PKD1/2 mutations may be useful for predicting the effectiveness of tolvaptan.

Keywords: Autosomal dominant polycystic kidney disease; Genotype; Polycystic kidney disease 1; Polycystic kidney disease 2; Tolvaptan.

A novel ADPKD model using kidney organoids derived from disease-specific human iPSCs

https://www.sciencedirect.com/science/article/abs/pii/S0006291X20313590?via%3Dihub

https://doi.org/10.1016/j.bbrc.2020.06.141

https://pubmed.ncbi.nlm.nih.gov/32819584/

TITLE:
A novel ADPKD model using kidney organoids derived from disease-specific human iPSCs

DATE:
Fri, 21 Aug 2020 06:00:00 -0400

AUTHORS:
Tatsuya Shimizu,Shin-Ichi Mae,Toshikazu Araoka,Keisuke Okita,Akitsu Hotta,Kunihiro Yamagata,Kenji Osafune

SOURCE:
Biochemical and biophysical research communications

DESCRIPTION:
Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary disorder which manifests progressive renal cyst formation and leads to end-stage kidney disease. Around 85% of cases are caused by PKD1 heterozygous mutations, exhibiting relatively poorer renal outcomes than those with mutations in other causative gene PKD2. Although many disease models have been proposed for ADPKD, the pre-symptomatic pathology of the human disease remains unknown. To unveil the mechanisms of early…

CONTENT:
Biochem Biophys Res Commun. 2020 Sep 3;529(4):1186-1194. doi: 10.1016/j.bbrc.2020.06.141. Epub 2020 Aug 4.

ABSTRACT

Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary disorder which manifests progressive renal cyst formation and leads to end-stage kidney disease. Around 85% of cases are caused by PKD1 heterozygous mutations, exhibiting relatively poorer renal outcomes than those with mutations in other causative gene PKD2. Although many disease models have been proposed for ADPKD, the pre-symptomatic pathology of the human disease remains unknown. To unveil the mechanisms of early cytogenesis, robust and genetically relevant human models are needed. Here, we report a novel ADPKD model using kidney organoids derived from disease-specific human induced pluripotent stem cells (hiPSCs). Importantly, we found that kidney organoids differentiated from gene-edited heterozygous PKD1-mutant as well as ADPKD patient-derived hiPSCs can reproduce renal cysts. Further, we demonstrated the possibility of ADPKD kidney organoids serving as drug screening platforms. This newly developed model will contribute to identifying novel therapeutic targets, extending the field of ADPKD research.

PMID:32819584 | DOI:10.1016/j.bbrc.2020.06.141

PUBMED ID:
pubmed:32819584

OTHER ID:
pmid:32819584,doi:10.1016/j.bbrc.2020.06.141

PUBLICATION DATE:
Fri, 21 Aug 2020 06:00:00 -0400
2020-08-22

RETRIEVAL DATE :
08/21/20 09:26PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/32819584/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1jmC0p0kwOiHcoERYElvPhktie_Gw8TL2aOwN185ZhQUSROsDP&fc=20200821211545&ff=20200821211655&v=2.11.5

LINK – DOI:
https://doi.org/10.1016/j.bbrc.2020.06.141

LINK – FULL TEXT:
https://www.sciencedirect.com/science/article/abs/pii/S0006291X20313590?via%3Dihub

NOTES:

Quest for the Cure: Testing the Old and New to Prevent Progression of Autosomal Dominant Polycystic Kidney Disease

https://www.kidneymedicinejournal.org/article/S2590-0595(19)30147-5/fulltext

https://doi.org/10.1016/j.xkme.2019.10.004

https://pubmed.ncbi.nlm.nih.gov/33015606/

TITLE:
Quest for the Cure: Testing the Old and New to Prevent Progression of Autosomal Dominant Polycystic Kidney Disease

DATE:
Mon, 05 Oct 2020 06:00:00 -0400

AUTHORS:
Godela Brosnahan

SOURCE:
Kidney medicine

DESCRIPTION:
No abstract

CONTENT:
Kidney Med. 2019 Oct 31;1(6):329-331. doi: 10.1016/j.xkme.2019.10.004. eCollection 2019 Nov-Dec.

NO ABSTRACT

PMID:33015606 | PMC:PMC7525136 | DOI:10.1016/j.xkme.2019.10.004

PUBMED ID:
pubmed:33015606

OTHER ID:
pmid:33015606,pmc:PMC7525136,doi:10.1016/j.xkme.2019.10.004

PUBLICATION DATE:
Mon, 05 Oct 2020 06:00:00 -0400
2020-10-05

RETRIEVAL DATE :
10/05/20 12:50PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33015606/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1jmC0p0kwOiHcoERYElvPhktie_Gw8TL2aOwN185ZhQUSROsDP&fc=20200821211545&ff=20201005125047&v=2.12.3

LINK – DOI:
https://doi.org/10.1016/j.xkme.2019.10.004

LINK – FULL TEXT:

NOTES:

Caffeine Accelerates Cystic Kidney Disease in a Pkd1-Deficient Mouse Model

https://www.cellphysiolbiochem.com/Articles/000072/

https://www.ncbi.nlm.nih.gov/pubmed/30977988?dopt=Abstract

Caffeine Accelerates Cystic Kidney Disease in a Pkd1-Deficient Mouse Model.

Cell Physiol Biochem. 2019;52(5):1061-1074

Authors: Meca R, Balbo BE, Ormanji MS, Fonseca JM, Iannuzzi LR, Santana Costa E, Onuchic LF, Heilberg IP

Abstract

BACKGROUND/AIMS: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst formation and growth, leading to end-stage renal disease. A higher kidney volume is predictive of a more accelerated decline in renal function. This study aimed to examine the effects of caffeine, a phosphodiesterase inhibitor, on the progression of cystic kidney disease in a mouse model orthologous to human disease (Pkd1cond/cond:Nestincre).

METHODS: Caffeine was administered to male cystic (CyCaf) and noncystic (NCCaf) mice (Pkd1cond/cond) from conception and at the postweaning period through 12 weeks of life (3 mg/d), while control animals consumed water (CyCtrl and NCCtrl). Renal ultrasonography was performed at 10 weeks of life to calculate total kidney volume and cystic index. At the end of the protocol, blood and urine samples were collected for biochemical analysis, and animals were euthanized. Kidneys were harvested to obtain renal tissue for determinations of adenosine 3´5´-cyclic monophosphate (cAMP) by an enzymatic immunoassay kit and phosphorylated extracellular signal-regulated kinase (p-ERK) by Western blotting. Renal fibrosis (picrosirius staining), renal cell proliferation (ki-67 immunohistochemistry) and apoptotic rates (TUNEL analysis) were also determined.

RESULTS: At 12 weeks, CyCaf mice exhibited higher serum urea nitrogen, renal cystic index, total kidney volume, kidney cell proliferation, apoptosis and fibrosis compared with CyCtrl mice. Serum cystatin C was significantly higher in CyCaf than in NCCaf and NCCtrl mice. CyCaf mice had higher total kidney weight than all other groups but not higher heart and liver weight. The levels of cAMP and p-ERK did not differ among the groups.

CONCLUSION: Caffeine consumption from conception through 12 weeks led to increased cystic index and total kidney volume and worsened renal function in Pkd1-deficient cystic mice, suggesting that high consumption of caffeine may contribute to a faster progression of renal disease in ADPKD.

PMID: 30977988 [PubMed – in process]

PubMed:30977988