The Importance of Tubular Function in Chronic Kidney Disease

Glomerular filtration rate (GFR) and proteinuria-albuminuria are the renal functional parameters currently used to evaluate chronic kidney disease (CKD) severity. However, tubular secretion is another important renal functional parameter to be taken into account since proximal tubule (PT) secretion,...

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Autores:
Risso, Maria A
Sallustio, Sofía
Sueiro, Valentin
Bertoni, Victoria
Gonzalez Torres, Henry
Musso, Carlos G
Tipo de recurso:
Fecha de publicación:
2019
Institución:
Universidad Simón Bolívar
Repositorio:
Repositorio Digital USB
Idioma:
eng
OAI Identifier:
oai:bonga.unisimon.edu.co:20.500.12442/4461
Acceso en línea:
https://hdl.handle.net/20.500.12442/4461
Palabra clave:
Tubular function
Chronic kidney disease
Drugs
Rights
License
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
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dc.title.eng.fl_str_mv The Importance of Tubular Function in Chronic Kidney Disease
title The Importance of Tubular Function in Chronic Kidney Disease
spellingShingle The Importance of Tubular Function in Chronic Kidney Disease
Tubular function
Chronic kidney disease
Drugs
title_short The Importance of Tubular Function in Chronic Kidney Disease
title_full The Importance of Tubular Function in Chronic Kidney Disease
title_fullStr The Importance of Tubular Function in Chronic Kidney Disease
title_full_unstemmed The Importance of Tubular Function in Chronic Kidney Disease
title_sort The Importance of Tubular Function in Chronic Kidney Disease
dc.creator.fl_str_mv Risso, Maria A
Sallustio, Sofía
Sueiro, Valentin
Bertoni, Victoria
Gonzalez Torres, Henry
Musso, Carlos G
dc.contributor.author.none.fl_str_mv Risso, Maria A
Sallustio, Sofía
Sueiro, Valentin
Bertoni, Victoria
Gonzalez Torres, Henry
Musso, Carlos G
dc.subject.eng.fl_str_mv Tubular function
Chronic kidney disease
Drugs
topic Tubular function
Chronic kidney disease
Drugs
description Glomerular filtration rate (GFR) and proteinuria-albuminuria are the renal functional parameters currently used to evaluate chronic kidney disease (CKD) severity. However, tubular secretion is another important renal functional parameter to be taken into account since proximal tubule (PT) secretion, in particular, is a crucial renal mechanism for endogenous organic cations, anions and drug elimination. The residual diuresis is a relevant survival predictor in patients on dialysis, since their urine is produced by the glomerular and tubular functions. It has been hypothesized that drugs which up-regulate some renal tubular transporters could contribute to uremic toxin excretion, and nephroprevention. However, if tubular transporters' down-regulation observed in CKD patients and experimental models is a PT adaptation to avoid intracellular accumulation and damage from uremic toxins, consequently the increase of toxin removal by inducing tubular transporters' up-regulation could be deleterious to the kidney. Therefore, a deeper understanding of this phenomenon is currently needed. In conclusion, tubular function has an important role for endogenous organic cations, anions and drug excretion in CKD patients, and a deeper understanding of its multiple mechanisms could provide new therapeutic alternatives in this population.
publishDate 2019
dc.date.accessioned.none.fl_str_mv 2019-12-13T16:32:03Z
dc.date.available.none.fl_str_mv 2019-12-13T16:32:03Z
dc.date.issued.none.fl_str_mv 2019
dc.type.eng.fl_str_mv article
dc.type.coar.fl_str_mv http://purl.org/coar/resource_type/c_6501
dc.identifier.issn.none.fl_str_mv 11787058
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/20.500.12442/4461
identifier_str_mv 11787058
url https://hdl.handle.net/20.500.12442/4461
dc.language.iso.eng.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv Attribution-NonCommercial-NoDerivatives 4.0 Internacional
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http://creativecommons.org/licenses/by-nc-nd/4.0/
http://purl.org/coar/access_right/c_abf2
dc.publisher.eng.fl_str_mv Dove Press
dc.source.eng.fl_str_mv International Journal of Nephrology and Renovascular Disease
dc.source.none.fl_str_mv Vol. 12 (2019)
institution Universidad Simón Bolívar
dc.source.uri.none.fl_str_mv https://doi.org/10.2147/IJNRD.S216673
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spelling Risso, Maria Ab0fc27f0-b150-450d-ab32-afbadfc0cfd3Sallustio, Sofía99e935c4-0e4c-498b-9497-92d62841f8acSueiro, Valentinb053f27d-d838-4b77-9de3-0e06bed1452fBertoni, Victoria2f841343-ad37-428b-8df0-f7118563626bGonzalez Torres, Henryc4a88cdf-b874-40af-badc-44d95f4856dfMusso, Carlos G5baae5f2-418f-4210-b146-93cefb2cea4c2019-12-13T16:32:03Z2019-12-13T16:32:03Z201911787058https://hdl.handle.net/20.500.12442/4461Glomerular filtration rate (GFR) and proteinuria-albuminuria are the renal functional parameters currently used to evaluate chronic kidney disease (CKD) severity. However, tubular secretion is another important renal functional parameter to be taken into account since proximal tubule (PT) secretion, in particular, is a crucial renal mechanism for endogenous organic cations, anions and drug elimination. The residual diuresis is a relevant survival predictor in patients on dialysis, since their urine is produced by the glomerular and tubular functions. It has been hypothesized that drugs which up-regulate some renal tubular transporters could contribute to uremic toxin excretion, and nephroprevention. However, if tubular transporters' down-regulation observed in CKD patients and experimental models is a PT adaptation to avoid intracellular accumulation and damage from uremic toxins, consequently the increase of toxin removal by inducing tubular transporters' up-regulation could be deleterious to the kidney. Therefore, a deeper understanding of this phenomenon is currently needed. In conclusion, tubular function has an important role for endogenous organic cations, anions and drug excretion in CKD patients, and a deeper understanding of its multiple mechanisms could provide new therapeutic alternatives in this population.engDove PressAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/http://purl.org/coar/access_right/c_abf2International Journal of Nephrology and Renovascular DiseaseVol. 12 (2019)https://doi.org/10.2147/IJNRD.S216673Tubular functionChronic kidney diseaseDrugsThe Importance of Tubular Function in Chronic Kidney Diseasearticlehttp://purl.org/coar/resource_type/c_6501Suchy-Dicey AM, Laha T, Hoofnagle A, et al. Tubular secretion in CKD. J Am Soc Nephrol. 2016;27(7):2148–2155. doi:10.1681/ASN. 2014121193Musso CG, Gavrilovici C, Covic A. Tubular secretion in chronic kidney disease staging: a new proposal. Int Urol Nephrol. 2017;49 (11):2087–2089. doi:10.1007/s11255-017-1673-0Masereeuw R, Mutsaers HA, Toyohara T, et al. The kidney and uremic toxin removal: glomerulus or tubule? Semin Nephrol. 2014;34 (2):191–208. doi:10.1016/j.semnephrol.2014.02.010Jansen J, De Napoli IE, Fedecostante M, et al. Human proximal tubule epithelial cells cultured on hollow fibers: living membranes that actively transport organic cations. Sci Rep. 2015;5:16702. doi:10. 1038/srep16702Nigam SK, Bush KT, Martovetsky G, et al. The organic anion transporter (OAT) family: a systems biology perspective. Physiol Rev. 2015;95(1):83–123. doi:10.1152/physrev.00025.2013Vallon V, Eraly SA, Rao SR, et al. A role for the organic anion transporter OAT3 in renal creatinine secretion in mice. Am J Physiol Renal Physiol. 2012;302(10):F1293–9. doi:10.1152/ajprenal.00013. 2012Suzuki T, Toyohara T, Akiyama Y, et al. Transcriptional regulation of organic anion transporting polypeptide SLCO4C1 as a new therapeutic modality to prevent chronic kidney disease. J Pharm Sci. 2011;100(9):3696–3707. doi:10.1002/jps.22641Shen H, Liu T, Morse BL, et al. Characterization of organic anion transporter 2 (SLC22A7): a highly efficient transporter for creatinine and species-dependent renal tubular expression. Drug Metab Dispos. 2015;43(7):984–993. doi:10.1124/dmd.114.062364Xu L, Shi Y, Zhuang S, Liu N. Recent advances on uric acid transporters. Oncotarget. 2017;8(59):100852–100862. doi:10.18632/ oncotarget.20135Dousdampanis P, Trigka K, Musso CG, Fourtounas C. Hyperuricemia and chronic kidney disease: an enigma yet to be solved. Ren Fail. 2014;36(9):1351–1359. doi:10.3109/0886022X.2014.947516Musso CG, Alvarez Gregori J, Jauregui JR, Macías Núñez JF. Creatinine, urea, uric acid, water and electrolytes renal handling in the healthy oldest old. World J Nephrol. 2012;1(5):123–126. doi:10.5527/wjn.v1.i5.123Musso CG, Juarez R, Vilas M, Navarro M, Rivera H, Jauregui R. Renal calcium, phosphorus, magnesium and uric acid handling: comparison between stage III chronic kidney disease patients and healthy oldest old. Int Urol Nephrol. 2012;44(5):1559–1562. doi:10.1007/ s11255-012-0230-0Eraly SA, Vallon V, Rieg T, et al. Multiple organic anion transporters contribute to net renal excretion of uric acid. Physiol Genomics. 2008;33(2):180–192. doi:10.1152/physiolgenomics.00207.2007Jing J, Ekici A, Sitter T, et al. Genetics of serum urate concentrations and gout in a highrisk population, patients with chronic kidney disease. Sci Rep. 2018;8:13184. doi:10.1038/s41598-018-31282-zMandal AK, Mount DB. The molecular physiology of uric acid homeostasis. Annu Rev Physiol. 2015;77:323–345. doi:10.1146/ annurev-physiol-021113-170343Emami Riedmaier A, Nies AT, Schaeffeler E, Schwab M. Organic anion transporters and their implications in pharmacotherapy. Pharmacol Rev. 2012;64(3):421–449. doi:10.1124/pr.111.004614Toyohara T, Suzuki T, Morimoto R, et al. SLCO4C1 transporter eliminates uremic toxins and attenuates hypertension and renal inflammation. J Am Soc Nephrol. 2009;20(12):2546–2555. doi:10.1681/ASN.2009070696Nigam SK, Wu W, Bush KT, Hoenig MP, Blantz RC, Bhatnagar V. Handling of drugs, metabolites,and uremic toxins by kidney proximal tubule drug transporters. Clin J Am Soc Nephrol. 2015;10 (11):2039–2049. doi:10.2215/CJN.02440314Bhatnagar V, Richard EL, Wu W, et al. Analysis of ABCG2 and other urate transporters in uric acid homeostasis in chronic kidney disease: potential role of remote sensing and signaling. Clin Kidney J. 2016;9 (3):444–453. doi:10.1093/ckj/sfw010Nigam SK. syndrome of chronic kidney disease: altered remote sensing and signalling. Nat Rev Nephrol. 2019;15(5):301–316. doi:10.1038/s41581-019-0111-1Wu W, Bush K, Nigam S. Key role for the Organic Anion Transporters, OAT1 and OAT3, in the in vivo handling of uremic toxins and solutes. Sci Rep. 2017;7:4939. doi:10.1038/s41598-017- 04949-2Wanchai K, Yasom S, Tunapong W, et al. Probiotic Lactobacillus paracasei HII01 protects rats against obese-insulin resistance induced kidney injury and impaired renal organic anion transporter 3 function. Clin Sci (Lond). 2018;132(14):1545–1563. doi:10.1042/CS20180148Ranganathan N, Ranganathan P, Friedman EA, et al. Pilot study of probiotic dietary supplementation for promoting healthy kidney function in patients with chronic kidney disease. Adv Ther. 2010;27 (9):634–647. doi:10.1007/s12325-010-0059-9Blanco VE, Hernandorena CV, Scibona P, Belloso W, Musso CG. Acute kidney injury pharmacokinetic changes and its impact on drug prescription. Healthcare (Basel). 2019;7(1):E10. doi:10.3390/ healthcare7010010Saito H. Pathophysiological regulation of renal SLC22A organic ion transporters in acute kidney injury: pharmacological and toxicological implications. Pharmacol Ther. 2010;125(1):79–91. doi:10.1016/j. pharmthera.2009.09.008Watanabe H, Sakaguchi Y, Sugimoto R, et al. Human organic anion transporters function as a high-capacity transporter for p-cresyl sulfate, a uremic toxin. Clin Exp Nephrol. 2014;18(5):814–820. doi:10. 1007/s10157-013-0902-9De Broe ME, Porter GA, Bennett WM, Deray G. Clinical Nephrotoxins. Renal Injury from Drugs and Chemicals. New York: Springer; 2008.Takada T, Yamamoto T, Matsuo H, et al. Identification of ABCG2 as an exporter of uremic toxin indoxyl sulfate in Mice and as a crucial factor influencing CKD progression. Sci Rep. 2018;8:11147. doi:10. 1038/s41598-018-29208-wWikoff WR, Nagle MA, Kouznetsova VL, Tsigelny IF, Nigam SK. Untargeted metabolomics identifies enterobiome metabolites and putative uremic toxins as substrates of organic anion transporter 1 (Oat1). J Proteome Res. 2011;10(6):2842–2851. doi:10.1021/pr20 0093wLowenstein J, Grantham JJ. The rebirth of interest in renal tubular function. Am J Physiol Renal Physiol. 2016;310(11):F1351–5. doi:10.1152/ajprenal.00055.2016Steubl D, Block M, Herbst V, et al. Plasma uromodulin correlates with kidney function and identifies early stages in chronic kidney disease patients. 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