Aminoglycoside-Induced Reversible Tubular Dysfunction

Alexandridis, George; Liberopoulos, Evangelos N.; Elisaf, Moses

doi:10.1159/000067797

Cited by 43 publications

(28 citation statements)

References 19 publications

(35 reference statements)

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“…Gentamicin can interfere with specific transport mechanisms in the primal tubular system or can induce RFS. Usually, aminoglycoside-induced RFS is seen in patients with impaired renal function, but some reports of patients with normal kidney function exist [143]. Gentamicin enters the cell through the megalin-cubulin system [41].…”

Section: Aminoglycosides and Tetracyclinesmentioning

confidence: 99%

Drug-induced acid-base disorders

et al. 2014

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The incidence of acid-base disorders (ABDs) is high, especially in hospitalized patients. ABDs are often indicators for severe systemic disorders. In everyday clinical practice, analysis of ABDs must be performed in a standardized manner. Highly sensitive diagnostic tools to distinguish the various ABDs include the anion gap and the serum osmolar gap. Drug-induced ABDs can be classified into five different categories in terms of their pathophysiology: (1) metabolic acidosis caused by acid overload, which may occur through accumulation of acids by endogenous (e.g., lactic acidosis by biguanides, propofol-related syndrome) or exogenous (e.g., glycol-dependant drugs, such as diazepam or salicylates) mechanisms or by decreased renal acid excretion (e.g., distal renal tubular acidosis by amphotericin B, nonsteroidal antiinflammatory drugs, vitamin D); (2) base loss: proximal renal tubular acidosis by drugs (e.g., ifosfamide, aminoglycosides, carbonic anhydrase inhibitors, antiretrovirals, oxaliplatin or cisplatin) in the context of Fanconi syndrome; (3) alkalosis resulting from acid and/or chloride loss by renal (e.g., diuretics, penicillins, aminoglycosides) or extrarenal (e.g., laxative drugs) mechanisms; (4) exogenous bicarbonate loads: milk-alkali syndrome, overshoot alkalosis after bicarbonate therapy or citrate administration; and (5) respiratory acidosis or alkalosis resulting from drug-induced depression of the respiratory center or neuromuscular impairment (e.g

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Section: Aminoglycosides and Tetracyclinesmentioning

confidence: 99%

Drug-induced acid-base disorders

et al. 2014

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“…It is also associated with a decrease in urinary concentration along with increased excretion of sodium [1] . We have shown that a gentamicin (GM)-induced urinary concentration defect may in part be accounted for by a reduced abundance of aquaporin water channels in the kidney [2] .…”

Section: Introductionmentioning

confidence: 99%

Gentamicin Decreases Guanylyl Cyclase Activity in Rat Glomerulus

Bae¹,

Park³

et al. 2007

Kidney Blood Press Res

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Background: Effects of gentamicin (GM) on the local natriuretic peptide (NP) and nitric oxide (NO) systems in the kidney were investigated. Methods: Male Sprague-Dawley rats (180–200 g) were intramuscularly injected with GM (100 mg/kg/day) for 5 days. The expression of NO synthase (NOS) isoforms was determined by Western blot analysis, and that of NPs by real-time polymerase chain reaction. The activity of guanylyl cyclase was also determined by the amount of guanosine 3′,5′-cyclic monophosphate (cGMP) generated in responses to atrial natriuretic peptide (ANP) or sodium nitroprusside (SNP). Results: GM treatment resulted in renal failure in association with increases in urinary flow and the fractional excretion of sodium. Accordingly, the expression of inducible NOS was increased in the cortex, while that of endothelial NOS remained unchanged. The urinary excretion of NO metabolites was increased. The expression of ANP, brain natriuretic peptide and C-type natriuretic peptide mRNA was increased in the kidney. The cGMP production provoked by either ANP or SNP was decreased in the glomerulus, but not in the papilla. Conclusion: GM-induced nephropathy may be causally related with decreased guanylyl cyclase activities in the glomerulus.

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“…Hypomagnesemia is often found in the patients with renal failure [Kelepouris and Agus, 1998;Alexandridis et al, 2003]. Magnesium deficiency enhances drug-induced nephrotoxicity [Lajer et al, kinases (CDKs) at different phases of the cell cycle [Draetta, 1990;Sherr, 1994;Jung et al, 2010].…”

mentioning

confidence: 99%

Magnesium deficiency suppresses cell cycle progression mediated by increase in transcriptional activity of p21Cip1 and p27Kip1 in renal epithelial NRK-52E cells

et al. 2011

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Lack of magnesium suppresses cell growth, but the molecular mechanism is not examined in detail. We examined the effect of extracellular magnesium deficiency on cell cycle progression and the expression of cell cycle regulators in renal epithelial NRK-52E cells. In synchronized cells caused by serum-starved method, over 80% cells were distributed in G1 phase. Cell proliferation and percentage of the cells in S phase in the presence of MgCl(2) were higher than those in the absence of MgCl(2) , suggesting that magnesium is involved in the cell cycle progression from G1 to S phase. After serum addition, the expression levels of p21(Cip1) and p27(Kip1) in the absence of MgCl(2) were higher than those in the presence of MgCl(2) . The exogenous expression of p21(Cip1) or p27(Kip1) increased the percentage in G1 phase, whereas it decreased that in S phase. The mRNA levels and promoter activities of p21(Cip1) and p27(Kip1) in the absence of MgCl(2) were higher than those in the presence of MgCl(2) . The phosphorylated p53 (p-p53) level was decreased by MgCl(2) addition. Pifithrin-α, a p53 inhibitor, decreased the p-p53, p21(Cip1) and p27(Kip1) levels, and the percentage in G1 phase in the absence of MgCl(2) . Rotenone, a mitochondrial respiratory inhibitor, decreased ATP content and increased the p-p53 level in the presence of MgCl(2) . Together, lack of magnesium may increase p21(Cip1) and p27(Kip1) levels mediated by the decrease in ATP content and the activation of p53, resulting in the suppression of cell cycle progression from G1 to S phase in NRK-52E cells.

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Aminoglycoside-Induced Reversible Tubular Dysfunction

Cited by 43 publications

References 19 publications

Drug-induced acid-base disorders

Drug-induced acid-base disorders

Gentamicin Decreases Guanylyl Cyclase Activity in Rat Glomerulus

Magnesium deficiency suppresses cell cycle progression mediated by increase in transcriptional activity of p21Cip1 and p27Kip1 in renal epithelial NRK-52E cells

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