Impaired Renal Tubular Function in Chronic Alcoholics

Labib, M; Abdel‐Kader, Mahmoud H.; Ranganath, L.; Martin, Sherry Joseph; Marks, Victoria

doi:10.1177/014107688908200307

Cited by 14 publications

(13 citation statements)

References 11 publications

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“…A significant number of individuals—perhaps a third of heavy alcohol users—progress to alcoholic hepatitis [1, 2, 40] that associates with significant mortality [2]. Kidney filtration is affected by this chronic ethanol use [11–13], but alcoholic disease is uniformly viewed as hepatic disease. Despite this, the mortality of patients hospitalized with alcoholic hepatitis correlates to the rapid development of kidney dysfunction, not the underlying hepatitis [14].…”

Section: Discussionmentioning

confidence: 99%

“…blood urea nitrogen, BUN). Kidney expresses 5 to 10% of total body CYP2E1 [7–10] and while chronic alcoholism associates with chronic kidney disease [11–13], it is the development of AKI that associates with the mortality of alcoholic hepatitis [14]. This chronic ethanol use is modeled in rats by feeding relevant amounts of ethanol for 28 days [15].…”

Section: Introductionmentioning

confidence: 99%

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Chronic ethanol ingestion induces oxidative kidney injury through taurine-inhibitable inflammation

Latchoumycandane

Nagy

McIntyre

2014

Free Radical Biology and Medicine

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Chronic ethanol ingestion mildly damages liver through oxidative stress and lipid oxidation, which is ameliorated by dietary supplementation with the anti-inflammatory β-amino acid taurine. Kidney, like liver, expresses cytochrome P450 2E1 that catabolizes ethanol with free radical formation, and so also may be damaged by ethanol catabolism. Sudden loss of kidney function, and not liver disease itself, foreshadows mortality in patients with alcoholic hepatitis [J. Altamirano, Clin Gastroenterol Hepatol. 2012, 10:65]. We found ethanol ingestion in the Lieber-deCarli rat model increased kidney lipid oxidation, 4-hydroxynonenal protein adduction, and oxidatively truncated phospholipids that attract and activate leukocytes. Chronic ethanol ingestion increased myeloperoxidase-expressing cells in kidney and induced an inflammatory cell infiltrate. Apoptotic Terminal deoxynucleotidyl transferase Nick End Labeling (TUNEL)-positive cells and active caspase-3 increased in kidney after ethanol ingestion, with reduced filtration with increased circulating Blood Urea Nitrogen and creatinine. These events were accompanied by release of albumin, myeloperoxidase, and the Acute Kidney Injury biomarkers Kidney Injury Molecule-1 (KIM-1), Neutrophil Gelatinase-associated Lipocalin (NGAL), and Cystatin c to urine. Taurine sequesters HOCl from myeloperoxidase of activated leukocytes, and taurine supplementation reduced renal lipid oxidation, reduced leukocyte infiltration, and reduced the increase in myeloperoxidase-positive cells during ethanol feeding. Taurine supplementation also normalized circulating BUN and creatinine levels, and suppressed enhanced myeloperoxidase, albumin, KIM-1 and cystatin c in urine. Thus, chronic ethanol ingestion oxidatively damages kidney lipids and proteins, damages renal function, and induces Acute Kidney Injury through an inflammatory cell infiltrate. The anti-inflammatory nutraceutical taurine effectively interrupts this ethanol-induced inflammatory cycle in kidney.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chronic ethanol ingestion induces oxidative kidney injury through taurine-inhibitable inflammation

Latchoumycandane

Nagy

McIntyre

2014

Free Radical Biology and Medicine

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“…Kidney dysfunction is common in alcoholic cirrhosis, and associates with nearly all of the mortality of hospitalized patients with severe alcoholic hepatitis [3]. Chronic alcoholism additionally associates with chronic kidney disease [4–6]. The common perception is that kidney damage must be secondary to liver injury since this is the major site of ethanol catabolim, but this is unproven.…”

Section: Introductionmentioning

confidence: 99%

Myeloperoxidase formation of PAF receptor ligands induces PAF receptor-dependent kidney injury during ethanol consumption

Latchoumycandane

Nagy

McIntyre

2015

Free Radical Biology and Medicine

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Cytochrome P450 2E1 (CYP2E1) induction and oxidative metabolism of ethanol in hepatocytes inflames and damages liver. Chronic ethanol ingestion also induces kidney dysfunction, which associates with mortality of alcoholic hepatitis. Whether kidney is directly affected by ethanol or is secondary to liver damage is not established. We found CYP2E1 was induced in kidney tubules of mice chronically ingesting a modified Lieber-deCarli liquid ethanol diet. Phospholipids of kidney tubules were oxidized and fragmented in ethanol fed mice with accumulation of azelaoyl phosphatidylcholine (Az-PC), a non-biosynthetic product formed only by oxidative truncation of polyunsaturated phosphatidylcholine. Az-PC stimulates the inflammatory PAF receptor (PTAFR) abundantly expressed by neutrophils and kidney tubules, and inflammatory cells and myeloperoxidase-containing neutrophils accumulated in kidney of ethanol fed mice after significant hysteresis. Decreased kidney filtration and induction of the Acute Kidney Injury biomarker KIM-1 in tubules temporally correlated with leukocyte infiltration. Genetic ablation of PTAFR reduced accumulation of PTAFR ligands, and reduced leukocyte infiltration into kidney. Loss of this receptor in PTAFR−/− mice also suppressed oxidative damage and kidney dysfunction without affecting CYP2E1 induction. Neutrophilic inflammation was responsible for ethanol-induced kidney damage because loss of neutrophil myeloperoxidase in MPO−/− mice was similarly protective. We conclude ethanol catabolism in renal tubules results in a self-perpetuating cycle of CYP2E1 induction, local PTAFR ligand formation, neutrophil infiltration and activation that leads to myeloperoxidase-dependent oxidation and damage to kidney function. Hepatocytes do not express PTAFR, so this oxidative cycle is a local response to ethanol catabolism in kidney.

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“…Native American people are thought to be of oriental origin; therefore, Native Americans and Japanese might have a common predisposition to MesPGN, particularly IgA nephropathy. Impaired renal tubular function with increased α 1 -microglobulin excretion was also reported in chronic alcoholics [19, 20]. However, in this study, proteinuria was strongly associated with hematuria; therefore, organic glomerulopathy might have existed.…”

Section: Discussionmentioning

confidence: 51%

Induction of Transient Proteinuria, Hematuria, and Glucosuria by Ethanol Consumption in Japanese Alcoholics

Ito

Ueno

Izumi³

et al. 1999

Nephron

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Urinalysis was carried out in 231 inpatients with alcohol dependence syndrome (215 males and 16 females). Fifty-nine patients (25.5%) showed proteinuria, 97 (42.0%) showed glucosuria, and 62 patients (26.8%) showed hematuria on admission. A total of 135 out of 231 patients (58.4%) showed abnormal urinalysis. Proteinuria was related to high blood pressure, high serum glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, lactate dehydrogenase, uric acid, and triglyceride levels, and high urinary amylase concentration. Glucosuria was related to high serum glutamic-oxaloacetic transaminase concentration and a history of gastrectomy. Hematuria was related to high age and high urinary amylase levels. By chi-square test, there was a significant correlation between proteinuria and hematuria (p < 0.001) and between hematuria and glucosuria (p < 0.001), but no correlation was found between proteinuria and glucosuria. The incidence of diabetes mellitus was 10.8% (25 out of 231 patients), but transient hyperglycemia was observed in some patients without diabetes mellitus on admission. Elevated hemoglobin A1, hemoglobin A1c, and fructosamine concentrations were observed in patients with either impaired glucose tolerance or transient hyperglycemia, which suggested the presence of persistent hyperglycemia before admission. On discharge, only 12 out of 198 patients (6.1%) showed abnormal urinalysis. We report that heavy ethanol consumption induces transient abnormal urinalysis results in Japanese alcoholics.

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Impaired Renal Tubular Function in Chronic Alcoholics

Cited by 14 publications

References 11 publications

Chronic ethanol ingestion induces oxidative kidney injury through taurine-inhibitable inflammation

Chronic ethanol ingestion induces oxidative kidney injury through taurine-inhibitable inflammation

Myeloperoxidase formation of PAF receptor ligands induces PAF receptor-dependent kidney injury during ethanol consumption

Induction of Transient Proteinuria, Hematuria, and Glucosuria by Ethanol Consumption in Japanese Alcoholics

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