bims-bicyki 2022-02-06 papers

bims-bicyki

Biomed News

on Bicaudal-C1 and interactors in cystic kidney disease

Issue of 2022–02–06
thirteen papers selected by
Céline Gagnieux, École Polytechnique Fédérale de Lausanne

Should we screen for intracranial aneurysms in children with autosomal dominant polycystic kidney disease?
Successful management of multiple obstructing renal calculi in a 30-year-old patient with autosomal dominant polycystic kidney disease using Frequency-Doubled Double-Pulse neodymium: Yttrium - Aluminium garnet laser lithotripsy.
Multiregion sequencing of sarcomatoid renal cell carcinoma arising from autosomal dominant polycystic kidney disease.
Diagnosis and Risk Factors for Intracranial Aneurysms in Autosomal Polycystic Kidney Disease: A cross-sectional study from the Genkyst Cohort.
[Genetic screening is essential in polycystic kidney disease: It is never too late!]
OFD1: One gene, several disorders.
Angiopoietin-2-induced lymphatic endothelial cell migration drives lymphangiogenesis via the β1 integrin-RhoA-formin axis.
Circular RNA circCSPP1 promotes the occurrence and development of colon cancer by sponging miR-431 and regulating ROCK1 and ZEB1.
Legumain Is an Endogenous Modulator of Integrin αvβ3; Triggering Vascular Degeneration, Dissection, and Rupture.
A Comprehensive Immune Cell Atlas of Cystic Kidney Disease Reveals the Involvement of Adaptive Immune Cells in Injury-Mediated Cyst Progression in Mice.
α-/γ-Taxilin are required for centriolar subdistal appendage assembly and microtubule organization.
TubulinTracker, a Novel In Vitro Reporter Assay to Study Intracellular Microtubule Dynamics, Cell Cycle Progression, and Aneugenicity.
Tolvaptan Reduces Extracellular Fluid per Amount of Body Fluid Reduction Less Markedly than Conventional Diuretics.

Pediatr Nephrol. 2022 Feb 02.

Should we screen for intracranial aneurysms in children with autosomal dominant polycystic kidney disease?

Emma Y X Walker, Matko Marlais.

  This is an overview of the challenges associated with screening for asymptomatic intracranial aneurysms (ICA) in children with autosomal dominant polycystic kidney disease (ADPKD). ADPKD is the most common inherited kidney disease affecting 1 in 1,000 people. ICAs are an extra-kidney manifestation of ADPKD, and while the exact pathophysiology of how they develop is unknown, we know that they more commonly occur in the adult rather than paediatric population. ICAs can be found in up to 9-11.5% of adults with ADPKD, but ICA rupture remains a rare event in adults with an incidence of 0.04 per 100 patient years. ICA size is an important factor in determining the risk of aneurysm rupture and therefore affects the decision on intervention in asymptomatic adults. For some, unruptured aneurysms cause no clinical significance, but those that rupture can be associated with devastating morbidity and mortality. Therefore, if detected, the treatment for unruptured ICAs is usually endovascular coiling, alongside recognising the importance of preventative interventions such as hypertension management. There are, however, no current guidelines for either adult or paediatric patients with ADPKD supporting regular screening for asymptomatic ICAs, although there is a suggestion for individualised practice, for example, with those with a positive family history. The UK clinical guidelines for ADPKD in children make research recommendations due to a lack of published literature, which in itself indicates that ICA rupture is an extremely rare phenomenon in children.

Keywords:  ADPKD; Autosomal dominant polycystic kidney disease; Intracranial aneurysms; Paediatrics; Screening

DOI:  https://doi.org/10.1007/s00467-022-05432-5
Niger Postgrad Med J. 2022 Jan-Mar;29(1):29(1): 70-73

Successful management of multiple obstructing renal calculi in a 30-year-old patient with autosomal dominant polycystic kidney disease using Frequency-Doubled Double-Pulse neodymium: Yttrium - Aluminium garnet laser lithotripsy.

Jacob Olugbenga Awobusuyi, Olufunmilade Akinfolarin Omisanjo, Oluwaseun Oluwole Akinola, Emmanuel Iretola Awobusuyi.

  Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent genetic disorder that results in end-stage renal disease. Although ADPKD patients experience long disease trajectories, factors such as hypertension, proteinuria and renal calculi have been observed to lead to rapid renal function impairment in patients with ADPKD. Furthermore, due to the distorted anatomy that makes access to stone difficult, the management of nephrolithiasis in ADPKD patients is one of the several special situations in which urinary lithiasis presents management challenges. We report the case of a 30-year-old male with ADPKD and renal function impairment as a result of multiple obstructive calculi who was treated in Dialyser Medical Centre, Oshodi, Lagos, with Frequency-Doubled Double-Pulse Neodymium: Yttrium - Aluminium Garnet laser (FREDDY laser) lithotripsy, highlighting the possible advantage of FREDDY laser over other types of laser procedures given the minimal tissue-damaging potential of the laser type.

Keywords:  Autosomal dominant polycystic kidney disease; Frequency-Doubled Double-Pulse Neodymium: Yttrium − Aluminium Garnet laser; case report; lithotripsy; nephrolithiasis

DOI:  https://doi.org/10.4103/npmj.npmj_631_21
Mol Genet Genomic Med. 2022 Feb 05. e1853

Multiregion sequencing of sarcomatoid renal cell carcinoma arising from autosomal dominant polycystic kidney disease.

Elizabeth Lee, Peiyong Guan, Abner Herbert Lim, Jui Wan Loh, Grace Fangmin Tan, Tracy Loh, Dave Yong Xiang Ng, Jing Yi Lee, Shane Goh, Wei Liu, Cedric Chuan-Young Ng, Bin Tean Teh, Jason Yongsheng Chan.

   BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is an inherited cystic kidney disease associated with a spectrum of various renal and extrarenal manifestations, including increased risk of kidney cancers. Here, we present the initial molecular description of sarcomatoid renal cell carcinoma (sRCC) arising in the setting of ADPKD.
METHODS: Multiregion whole-exome sequencing and whole transcriptomic sequencing were used to examine intratumoral molecular heterogeneity among histologically-distinct spindle (sarcomatoid), epithelioid, or biphasic compartments within the tumor and compared with the non-malignant ADPKD component.
RESULTS: Spindle and biphasic components harbored several overlapping driver gene mutations, but do not share any with the epithelioid component. Mutations in ATM, CTNNB1, and NF2 were present only in the biphasic and spindle components, while mutations in BID, FLT3, ARID1B, and SMARCA2 were present only in the epithelioid component. We observed dichotomous evolutionary pathways in the development of epithelioid and spindle compartments, involving early mutations in TP53 and ATM/CTNNB1/NF2 respectively. Wnt, PI3K-mTOR, and MAPK signaling pathways, known key mechanisms involved in ADPKD development, featured prominently in the sarcomatoid component.
CONCLUSION: This highlights that common pro-oncogenic signals are present between ADPKD and sRCC providing insights into their shared pathobiology.

Keywords:  genetics; hereditary; phylogeny; tumor evolution

DOI:  https://doi.org/10.1002/mgg3.1853
Nephrol Dial Transplant. 2022 Feb 02. pii: gfac027. [Epub ahead of print]

Diagnosis and Risk Factors for Intracranial Aneurysms in Autosomal Polycystic Kidney Disease: A cross-sectional study from the Genkyst Cohort.

GENKYST Study Group

   BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is associated with an increased risk for developing intracranial aneurysms (IAs). We aimed to evaluate the frequency of diagnosis of IAs in the cross-sectional, population-based, Genkyst cohort, to describe ADPKD-associated IAs and to analyze the risk factors associated with the occurrence of IAs in ADPKD patients.
METHODS: Cross-sectional study performed in 26 nephrology centers from the Western part of France. All patients underwent genetic testing for PKD1/PKD2 and other cystogenes.
RESULTS: Among the 2449 Genkyst participants, 114 (4.65%) had a previous diagnosis of ruptured or unruptured IAs at inclusion, and ∼47% of them had a positive familial history for IAs. Most aneurysms were small and saccular and located in the anterior circulation; 26.3% of the patients had multiple IAs. The cumulative probabilities of a previous diagnosis of IAs were 3.9, 6.2 and 8.1% at 50, 60 and 70 y, respectively. While this risk appeared to be similar in male and female individuals <50 y, after that age, the risk continued to increase more markedly in female patients, reaching 10.8% vs 5.4% at 70 y. The diagnosis rate of IAs was more than twofold higher in PKD1 compared to PKD2 with no influence of PKD1 mutation type or location. In multivariate analysis, female sex, hypertension <35 y, smoking and PKD1 genotype were associated with an increased risk for diagnosis of IAs.
CONCLUSIONS: This study presents epidemiological data reflecting real-life clinical practice. The increased risk for IAs in postmenopausal women suggests a possible protective role of estrogen.

Keywords:  PKD1; PKD2; autosomal dominant polycystic kidney disease (ADPKD); genetics; intracranial aneurysms; risk factors; subarachnoid hemorrhage

DOI:  https://doi.org/10.1093/ndt/gfac027
Nephrol Ther. 2022 Jan 28. pii: S1769-7255(21)00538-1. [Epub ahead of print]

[Genetic screening is essential in polycystic kidney disease: It is never too late!]

Clémence Petit, Diego Cantarovich, Virginie Langs, Bertrand Isidor, Lucile Figueres.

  In France, numerous patients suffered from chronic kidney disease on polycystic kidney disorder. If PKD1 and PKD2 inactivating mutations are the most prevalent, several other genetic polycystic kidney diseases are responsible for similar kidney features and may be associated with severe extrarenal phenotypes. Genetic analysis in front of a polycystic disorder is not systematic, but is essential to assess the genetic diagnosis, discuss the intensity of treatment (vaptan) and precise the prognostic and the transmission of the phenotype. We detailed the case of a patient with end stage renal disease due to a polycystic kidney disease. Genetic analysis at 70 year of age revealed an oral-facial-digital syndrome type 1. The diagnosis had an important impact in the familial history and to attach the extrarenal phenotype to the syndrome. Our case illustrates that, in front of a polycystic kidney disease (even in aged patients with end stage renal disease) genetic screening is essential, for the propositus and their family and to take care of the extrarenal manifestations.

Keywords:  Genetic; Génétique; Oral-facial-digital syndrome; Polycystic kidney disease; Polykystose hépato-rénale; Syndrome oro-facio-digital

DOI:  https://doi.org/10.1016/j.nephro.2021.09.002
Am J Med Genet C Semin Med Genet. 2022 Feb 02.

OFD1: One gene, several disorders.

Nunziana Pezzella, Guglielmo Bove, Roberta Tammaro, Brunella Franco.

  The OFD1 protein is necessary for the formation of primary cilia and left-right asymmetry establishment but additional functions have also been ascribed to this multitask protein. When mutated, this protein results in a variety of phenotypes ranging from multiorgan involvement, such as OFD type I (OFDI) and Joubert syndromes (JBS10), and Primary ciliary dyskinesia (PCD), to the engagement of single tissues such as in the case of retinitis pigmentosa (RP23). The inheritance pattern of these condition differs from X-linked dominant male-lethal (OFDI) to X-linked recessive (JBS10, PCD, and RP23). Distinctive biological peculiarities of the protein, which can contribute to explain the extreme clinical variability and the genetic mechanisms underlying the different disorders are discussed. The extensive spectrum of clinical manifestations observed in OFD1-mutated patients represents a paradigmatic example of the complexity of genetic diseases. The elucidation of the mechanisms underlying this complexity will expand our comprehension of inherited disorders and will improve the clinical management of patients.

Keywords:  OFD1; X inactivation; X-linked Joubert; cilia; primary ciliary dyskinesia; variable expressivity

DOI:  https://doi.org/10.1002/ajmg.c.31962
Angiogenesis. 2022 Feb 01.

Angiopoietin-2-induced lymphatic endothelial cell migration drives lymphangiogenesis via the β1 integrin-RhoA-formin axis.

Racheal Grace Akwii, Md Sanaullah Sajib, Fatema Tuz Zahra, Paul Tullar, Masoud Zabet-Moghaddam, Yi Zheng, J Silvio Gutkind, Colleen L Doci, Constantinos M Mikelis.

  Lymphangiogenesis is an essential physiological process but also a determining factor in vascular-related pathological conditions. Angiopoietin-2 (Ang2) plays an important role in lymphatic vascular development and function and its upregulation has been reported in several vascular-related diseases, including cancer. Given the established role of the small GTPase RhoA on cytoskeleton-dependent endothelial functions, we investigated the relationship between RhoA and Ang2-induced cellular activities. This study shows that Ang2-driven human dermal lymphatic endothelial cell migration depends on RhoA. We demonstrate that Ang2-induced migration is independent of the Tie receptors, but dependent on β1 integrin-mediated RhoA activation with knockdown, pharmacological approaches, and protein sequencing experiments. Although the key proteins downstream of RhoA, Rho kinase (ROCK) and myosin light chain, were activated, blockade of ROCK did not abrogate the Ang2-driven migratory effect. However, formins, an alternative target of RhoA, were identified as key players, and especially FHOD1. The Ang2-RhoA relationship was explored in vivo, where lymphatic endothelial RhoA deficiency blocked Ang2-induced lymphangiogenesis, highlighting RhoA as an important target for anti-lymphangiogenic treatments.

Keywords:  Ang2; Angiopoietin-2; Cell migration; Formins; HDLEC; Integrins; Lymphangiogenesis; Lymphatic endothelial cells; RhoA; Small GTPase

DOI:  https://doi.org/10.1007/s10456-022-09831-y
J Transl Med. 2022 Jan 31. 20(1): 58

Circular RNA circCSPP1 promotes the occurrence and development of colon cancer by sponging miR-431 and regulating ROCK1 and ZEB1.

Jin Wang, Lei Zhou, Bingxin Chen, Zhuwen Yu, Jianglei Zhang, Zhe Zhang, Chenrui Hu, Yanjin Bai, Xiaokang Ruan, Shengjia Wang, Jun Ouyang, Airong Wu, Xin Zhao.

   BACKGROUND: Colon cancer is a common malignant tumor of the digestive tract, and its incidence is ranked third among gastrointestinal tumors. The present study aims to investigate the role of a novel circular RNA (circCSPP1) in colon cancer and its underlying molecular mechanisms.
METHODS: Bioinformatics analysis and reverse transcription-quantitative PCR were used to detect the expression levels of circCSPP1 in colon cancer tissues and cell lines. The effects of circCSPP1 on the behavior of colon cancer cells were investigated using CCK-8, transwell and clonogenic assays. Bioinformatics analysis along with luciferase, fluorescence in situ hybridization and RNA pull-down assays were used to reveal the interaction between circCSPP1, microRNA (miR)-431, Rho associated coiled-coil containing protein kinase 1 (ROCK1) and zinc finger E-box binding homeobox 1 (ZEB1).
RESULTS: It was found that circCSPP1 expression was significantly upregulated in colon cancer tissues and cell lines. Overexpression of circCSPP1 significantly promoted the proliferation, migration and invasion of colon cancer cells, whereas silencing of circCSPP1 exerted opposite effects. Mechanistically, circCSPP1 was found to bind with miR-431. In addition, ROCK1 and ZEB1 were identified as the target genes of miR-431. Rescue experiments further confirmed the interaction between circCSPP1, miR-431, ROCK1 and ZEB1. Moreover, circCSPP1 promoted the expression level of ROCK1, cyclin D1, cyclin-dependent kinase 4, ZEB1 and Snail, and lowered the E-cadherin expression level.
CONCLUSION: Taken together, the findings of the present study indicated that circCSPP1 may function as a competing endogenous RNA in the progression of colon cancer by regulating the miR-431/ROCK1 and miR-431/ZEB1 signaling axes.

Keywords:  Cell cycle; Colon cancer; Epithelial-to-mesenchymal transition; Rho associated coiled-coil containing protein kinase 1; Zinc finger E-box binding homeobox 1; circCSPP1; miR-431

DOI:  https://doi.org/10.1186/s12967-022-03240-x
Circulation. 2022 Jan 31.

Legumain Is an Endogenous Modulator of Integrin αvβ3; Triggering Vascular Degeneration, Dissection, and Rupture.

Lihong Pan, Peiyuan Bai, Xinyu Weng, Jin Liu, Yingjie Chen, Siqin Chen, Xiurui Ma, Kai Hu, Aijun Sun, Junbo Ge.

Background: The development of thoracic aortic dissection (TAD) is closely related to the extracellular matrix (ECM) degradation and the vascular smooth muscle cell (VSMC) transformation from contractile to synthetic type. Legumain (Lgmn) degrades ECM components directly or by activating downstream signals. However, the role of Lgmn in the VSMC differentiation and the occurrence of TAD remains elusive. Methods: Microarray datasets concerning vascular dissection or aneurysm were downloaded from the Gene Expression Omnibus (GEO) database to screen differentially expressed genes (DEGs). Four-week-old male Lgmn knockout mice (Lgmn-/-), macrophage-specific Lgmn knockout mice (LgmnF/F; LysMCre) and RR-11a treated C57BL/6 mice were given β-aminopropionitrile monofumarate (BAPN, 1g/kg/day) in drinking water for four weeks for TAD modeling. RNA-Seq analysis was performed to recapitulate transcriptome profile changes. Cell interaction was examined in macrophage and VSMC coculture system. The reciprocity of macrophage derived Lgmn with integrin αvβ3 in VSMCs was tested by co-immunoprecipitation assay and colocalization analyses. Results: Microarray datasets from the GEO database indicated up-regulated Lgmn in aorta from TAD patients and Ang II induced aortic abdominal aneurysm (AAA) mice. Elevated Lgmn was evidenced in the aortas and serums from TAD patients and BAPN-induced TAD mice in this study. BAPN induced TAD progression was significantly ameliorated in Lgmn deficient or inhibited mice. Macrophage specific deletion of Lgmn alleviated BAPN induced ECM degradation. Unbiased profiler PCR-array and GO analysis displayed that Lgmn regulated VSMC phenotype transformation. Macrophage specific deletion of Lgmn ameliorated VSMC phenotypic switch in BAPN treated mice. Macrophage derived Lgmn inhibited VSMC differentiation in vitro as assessed by macrophages and VSMCs coculture system. Mechanically, macrophage derived Lgmn bound to integrin αvβ3 in VSMCs and blocked integrin αvβ3, therefore attenuating Rho GTPase activation, down-regulating VSMCs differentiation markers and eventually exacerbating TAD development. Rho-kinase (ROCK) inhibitor Y-27632 reversed the protective role of Lgmn depletion in vascular dissection. Conclusions: These findings indicate that Lgmn signaling may be a novel target for the prevention and treatment of TAD.

DOI: https://doi.org/10.1161/CIRCULATIONAHA.121.056640
J Am Soc Nephrol. 2022 Feb 02. pii: ASN.2021030278. [Epub ahead of print]

A Comprehensive Immune Cell Atlas of Cystic Kidney Disease Reveals the Involvement of Adaptive Immune Cells in Injury-Mediated Cyst Progression in Mice.

Cheng Song, Zhang Li, Ummey Khalecha Bintha Ahmed, Sarah Bland, Alex Yashchenko, Shanrun Liu, Ernald Aloria, Jeremie Lever, Nancy Gonzalez, Marisa Bickel, Cory Giles, Constantin Georgescu, Jonathan Wren, Mark Lang, Etty Benveniste, Laurie Harrington, Leo Tsiokas, James George, Kenneth Jones, David Crossman, Anupam Agarwal, Michal Mrug, Bradley Yoder, Katharina Hopp, Kurt Zimmerman.

Background: Inducible disruption of cilia-related genes in adult mice results in slowly progressive cystic disease, which can be greatly accelerated by renal injury. Methods: To identify in an unbiased manner modifier cells that may be influencing the differential rate of cyst growth in injured versus non-injured cilia mutant kidneys at a time of similar cyst severity, we generated a single-cell atlas of cystic kidney disease. We conducted RNA-seq on 79,355 cells from control mice and adult-induced conditional Ift88 mice (hereafter referred to as cilia mutant mice) that were harvested ~7 months post-induction or 8 weeks post 30-minute unilateral ischemia reperfusion injury. Results: Analyses of single-cell RNA seq data of CD45+ immune cells revealed that adaptive immune cells differed more in cluster composition, cell proportion, and gene expression than cells of myeloid origin when comparing cystic models to one another and to non-cystic controls. Surprisingly, genetic deletion of adaptive immune cells significantly reduced injury-accelerated cystic disease but had no effect on cyst growth in non-injured cilia mutant mice, independent of the rate of cyst growth or underlying genetic mutation. Using NicheNet, we identified a list of candidate cell types and ligands that were enriched in injured cilia mutant mice compared to aged cilia mutant mice and non-cystic controls that may be responsible for the observed dependence on adaptive immune cells during injury-accelerated cystic disease. Conclusions: Collectively, these data highlight the diversity of immune cell involvement in cystic kidney disease.

DOI: https://doi.org/10.1681/ASN.2021030278
Elife. 2022 Feb 04. pii: e73252. [Epub ahead of print]11

α-/γ-Taxilin are required for centriolar subdistal appendage assembly and microtubule organization.

Dandan Ma, Fulin Wang, Rongyi Wang, Yingchun Hu, Zhiquan Chen, Ning Huang, Yonglu Tian, Yuqing Xia, Junlin Teng, Jianguo Chen.

  The centrosome composed of a pair of centrioles (mother and daughter) and pericentriolar material, and is mainly responsible for microtubule nucleation and anchorage in animal cells. The subdistal appendage (SDA) is a centriolar structure located at the mother centriole's subdistal region, and it functions in microtubule anchorage. However, the molecular composition and detailed structure of the SDA remain largely unknown. Here, we identified α-taxilin and γ-taxilin as new SDA components that form a complex via their coiled-coil domains and that serve as a new subgroup during SDA hierarchical assembly. The taxilins' SDA localization is dependent on ODF2, and α-taxilin recruits CEP170 to the SDA. Functional analyses suggest that α- and γ-taxilin are responsible for SDA structural integrity and centrosomal microtubule anchorage during interphase and for proper spindle orientation during metaphase. Our results shed light on the molecular components and functional understanding of the SDA hierarchical assembly and microtubule organization.

Keywords:  cell biology; centrosome; human; microtubule; super-high resolution

DOI:  https://doi.org/10.7554/eLife.73252
Toxicol Sci. 2022 Jan 30. pii: kfac008. [Epub ahead of print]

TubulinTracker, a Novel In Vitro Reporter Assay to Study Intracellular Microtubule Dynamics, Cell Cycle Progression, and Aneugenicity.

M E Geijer, N Moelijker, G Zhang, R Derr, T Osterlund, G Hendriks, I Brandsma.

  Aneuploidy is characterized by the presence of an abnormal number of chromosomes and is a common hallmark of cancer. However, exposure to aneugenic compounds does not necessarily lead to cancer. Aneugenic compounds are mainly identified using the in vitro micronucleus assay but this assay cannot standardly discriminate between aneugens and clastogens and cannot be used to identify the exact mode-of-action (MOA) of aneugens; tubulin stabilization, tubulin destabilization, or inhibition of mitotic kinases. To improve the classification of aneugenic substances and determine their MOA, we developed and validated the TubulinTracker assay that uses a GFP-tagged tubulin reporter cell line to study microtubule stability using flow cytometry. Combining the assay with a DNA stain also enables cell cycle analysis. Substances whose exposure resulted in an accumulation of cells in G2/M phase, combined with increased or decreased tubulin levels, were classified as tubulin poisons. All known tubulin poisons included were classified correctly. Moreover, we correctly classified compounds, including aneugens, that did not affect microtubule levels. However, the MOA of aneugens not affecting tubulin stability, such as Aurora kinase inhibitors, could not be identified. Here we show that the TubulinTracker assay can be used to classify microtubule stabilizing and destabilizing compounds in living cells. This insight into the MOA of aneugenic agents is important, for example to support a weight-of-evidence approach for risk assessment, and the classification as an aneugen as opposed to a clastogen or mutagen, has a big impact on the assessment.

Keywords:  Aneugenicity; Genotoxicity; Genotoxicity testing; Microtubules; Tubulin

DOI:  https://doi.org/10.1093/toxsci/kfac008
Intern Med. 2022 Feb 01.

Tolvaptan Reduces Extracellular Fluid per Amount of Body Fluid Reduction Less Markedly than Conventional Diuretics.

Hirotsugu Iwatani, Masafumi Yamato, Saki Bessho, Yuki Mori, Shoki Notsu, Yuta Asahina, Shintaro Koizumi, Yoshiki Kimura, Akihiro Shimomura.

  Objective Tolvaptan, a vasopressin V2 receptor antagonist, is a water diuretic, removing electrolyte-free water from the kidneys and affecting the water balance between the intracellular and extracellular fluid. We previously reported that tolvaptan efficiently reduced the intracellular fluid volume, suggesting its utility for treating cellular edema. Furthermore, tolvaptan is known for its low incidence of worsening the renal function, with conventional diuretics use associated with worsening of the renal function Methods In this retrospective observational study, five chronic kidney disease (CKD) patients with fluid retention were assessed by the bioelectrical impedance (BIA) method twice (before and after tolvaptan therapy). Tolvaptan was used with conventional diuretics. The post/pre ratio of extracellular water (ECW)/total body water (TBW) in the tolvaptan group was compared with that in 18 CKD patients undergoing body fluid reduction with conventional diuretics alone (conventional diuretics groups), taking the reduced amount of body fluid into consideration. Results Removing body fluid, either by tolvaptan or by conventional diuretics alone, decreased the ECW/TBW ratio. Of note, the reduction in extracellular fluid was milder in the tolvaptan group than in the conventional diuretics group. Conclusion Tolvaptan reduces the extracellular fluid per amount of body fluid reduction less markedly than conventional diuretics.

Keywords:   worsening of renal function; bioimpedance; conventional diuretics; extracellular fluid (ECF); intracellular fluid (ICF); tolvaptan

DOI:  https://doi.org/10.2169/internalmedicine.8533-21