Membrane Carriers and Transporters in Kidney Physiology and Disease

The growing information suggests that chronic kidney disease may affect expression and function of membrane carriers and transporters in the kidney. The dysfunction of carriers and transporters entails deficient elimination of uremic solutes as well as xenobiotics (drugs and toxins) with subsequent clinical consequences. The renal carriers and transporters are also targets of drugs used in clinical practice, and intentional drug–drug interactions in the kidney are produced to increase therapeutic efficacy. The understanding of membrane carriers and transporters function in chronic kidney disease is important not only to better characterize drug pharmacokinetics, drug actions in the kidney, or drug–drug interactions but also to define the organ pathophysiology.

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Extrahepatic Drug Transporters in Liver Failure: Focus on Kidney and Gastrointestinal Tract

International Journal of Molecular Sciences ◽

10.3390/ijms21165737 ◽

2020 ◽

Vol 21 (16) ◽

pp. 5737 ◽

Cited By ~ 1

Author(s):

Marek Droździk ◽

Stefan Oswald ◽

Agnieszka Droździk

Keyword(s):

Gastrointestinal Tract ◽

Liver Failure ◽

Liver Dysfunction ◽

Drug Transporters ◽

Endogenous Compounds ◽

Clinical Consequences ◽

Drug Actions ◽

And Function ◽

Drug Pharmacokinetics

Emerging information suggests that liver pathological states may affect the expression and function of membrane transporters in the gastrointestinal tract and the kidney. Altered status of the transporters could affect drug as well as endogenous compounds handling with subsequent clinical consequences. It seems that changes in intestinal and kidney transporter functions provide the compensatory activity of eliminating endogenous compounds (e.g., bile acids) generated and accumulated due to liver dysfunction. A literature search was conducted on the Ovid and PubMed databases to select relevant in vitro, animal and human studies that have reported expression, protein abundance and function of the gastrointestinal and kidney operating ABC (ATP-binding cassette) transporters and SLC (solute carriers) carriers. The accumulated data suggest that liver failure-associated transporter alterations in the gastrointestinal tract and kidney may affect drug pharmacokinetics. The altered status of drug transporters in those organs in liver dysfunction conditions may provide compensatory activity in handling endogenous compounds, affecting local drug actions as well as drug pharmacokinetics.

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Endocrine Aspects of Kidney Disease

10.2310/nephro.12015 ◽

2020 ◽

Author(s):

Marcin Adamczak ◽

Piotr Kuczera ◽

Andrzej Wiecek

Keyword(s):

Chronic Kidney Disease ◽

Growth Hormone ◽

Kidney Disease ◽

Kidney Diseases ◽

Thyroid Stimulating Hormone ◽

Normal Serum ◽

Serum Prolactin ◽

Clinical Consequences ◽

Synthesis And Degradation ◽

Insulin Like Growth Factors

Kidneys play the major role in the synthesis and degradation of several hormones. Different coexisting conditions such as inflammation, malnutrition and metabolic acidosis and applied treatment may also cause endocrine abnormalities in chronic kidney disease (CKD) patients. A tendency towards decreased thyroxin and triiodothyronine with normal serum concentrations of reversed triiodothyronine (as opposed to other chronic non-thyroid, non-kidney diseases) and thyroid stimulating hormone are observed. As far as the somatotopic axis is concerned, in CKD normal serum concentration of growth hormone and its effector – the insulin-like growth factor are observed. Nevertheless, due to the phenomenon of GH/IGF-1 “resistance” CKD patients usually present a phenotype resembling GH deficiency. Serum prolactin concentrations are often elevated in CKD women and men. This leads to the dysregulation of the pituitary-gonadal axis causing hypogonadism and it’s clinical consequences regardless of patient’s gender. The alterations in hormones of gonadal origin caused by uremia, together with hyperprolactinemia lead to the development of sexual dysfunction and infertility in men and women. The alterations of thyroid, pituitary gland and gonads associated with CKD are discussed in this chapter. This review contains 4 tables, and 64 references. Keywords: chronic kidney disease, hypothyroidism, hyperthyroidism, growth hormone, recombinant human GH, insulin-like growth factors, hemodialysis

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1526 ECONOMIC AND CLINICAL CONSEQUENCES OF NEW ONSET POST-OPERATIVE CHRONIC KIDNEY DISEASE FOLLOWING RADICAL AND PARTIAL NEPHRECTOMY IN THE MANAGEMENT OF SMALL RENAL MASSES

The Journal of Urology ◽

10.1016/j.juro.2011.02.1519 ◽

2011 ◽

Vol 185 (4S) ◽

Cited By ~ 2

Author(s):

Steven L Chang ◽

Lauren E Cipriano ◽

Steven M Brunelli ◽

Benjamin I Chung

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Partial Nephrectomy ◽

Small Renal Masses ◽

Renal Masses ◽

Clinical Consequences ◽

New Onset

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Clinical consequences of arterial calcifications and soft-tissue calcifications in chronic kidney disease

The Spectrum of Mineral and Bone Disorders in Chronic Kidney Disease ◽

10.1093/med/9780199559176.003.018 ◽

2010 ◽

pp. 303-315

Author(s):

Gérard M. London ◽

Bruno Pannier ◽

Alain P. Guerin ◽

Sylvain J. Marchais

Keyword(s):

Chronic Kidney Disease ◽

Soft Tissue ◽

Kidney Disease ◽

Clinical Consequences

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Intestinal drug transporters in pathological states: an overview

Pharmacological Reports ◽

10.1007/s43440-020-00139-6 ◽

2020 ◽

Vol 72 (5) ◽

pp. 1173-1194 ◽

Cited By ~ 1

Author(s):

Marek Drozdzik ◽

Izabela Czekawy ◽

Stefan Oswald ◽

Agnieszka Drozdzik

Keyword(s):

Gastrointestinal Tract ◽

Kidney Failure ◽

Drug Transporters ◽

Drug Bioavailability ◽

Gastrointestinal Pathology ◽

Endogenous Compounds ◽

Clinical Consequences ◽

Drug Actions ◽

And Function

Abstract Emerging information suggests that gastrointestinal and systemic pathology states may affect expression and function of membrane transporters in the gastrointestinal tract. Altered status of the transporters could affect drug as well as endogenous compounds handling with subsequent clinical consequences. It seems that in some pathologies, e.g., liver or kidney failure, changes in the intestinal transporter function provide compensatory functions, eliminating substrates excreted by dysfunctional organs. A literature search was conducted on Ovid and Pubmed databases to select relevant in vitro, animal and human studies that have reported expression, protein abundance and function of intestinal drug transporters. The accumulated data suggest that gastrointestinal pathology (inflammatory bowel disease, celiac disease, cholestasis) as well as systemic pathologies (kidney failure, liver failure, hyperthyroidism, hyperparathyroidism, obesity, diabetes mellitus, systemic inflammation and Alzheimer disease) may affect drug transporter expression and function in the gastrointestinal tract. The altered status of drug transporters may provide compensatory activity in handling endogenous compounds, affect local drug actions in the gastrointestinal tract as well as impact drug bioavailability. Graphic abstract

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The role of inflammation in chronic kidney disease

10.1093/med/9780199592548.003.0110 ◽

2015 ◽

Author(s):

Juan Jesús Carrero ◽

Peter Stenvinkel

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Endocrine Disorders ◽

Low Grade ◽

Protein Energy Wasting ◽

Protein Levels ◽

Reactive Protein ◽

Protein Energy ◽

Persistent Inflammation ◽

Clinical Consequences

Low-grade persistent inflammation is a common feature of chronic kidney disease. This chapter provides an overview of the pathogenesis and clinical consequences of elevated pro-inflammatory cytokines in the uraemic milieu with an emphasis on dialysis stages. It reviews the multifactorial dialysis- and non-dialysis-related causes of inflammation and its purported role in the development of protein energy wasting, vascular calcification, endocrine disorders, and depression. The chapter also discusses the use and the need of monitoring C-reactive protein levels regularly in the clinical setting and comments on possible therapeutic approaches to reduce inflammation in these patients.

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The chronic kidney disease “epidemy”

Orvosi Hetilap ◽

10.1556/oh.2013.29524 ◽

2013 ◽

Vol 154 (2) ◽

pp. 43-51 ◽

Cited By ~ 1

Author(s):

Judit Nagy

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Adult Population ◽

Public Health Problem ◽

General Term ◽

Structure And Function ◽

Global Public Health ◽

New Classification ◽

And Function ◽

Global Public Health Problem

Chronic kidney disease is a general term for heterogenous disorders with >3 months duration affecting kidney structure and function. Nowadays, involving 10–16% of the adult population worldwide, chronic kidney disease is recognised as a major global public health problem. The number of cases is continuously increasing. In this review, epidemiology, definition, new classification and a conceptual model for development, progression and complications of chronic kidney disease as well as strategies to improve outcome are summarized. Orv. Hetil., 2013, 154, 43–51.

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