Table 3 Likely concomitant nephrotoxic medications in neonatal study subjects.

Acyclovir

• Short (term neonates: 3 h)

• Substrate and specific inhibitor of herpesvirus DNA polymerase

• Crystal nephropathy due to poor solubility in urine which may lead to tubular obstruction

• Renal: Primarily by GFR with a small contribution from tubular secretion

Amphotericin B deoxycholate, amphotericin B liposomal

• Short (infants/children: 18.1 h)

• Fungicidal via binding to ergosterol of the lipid bilayer of the fungi and disrupting membrane permeability, leading to loss of anions and glucose

• Acute tubular necrosis: increased tubule permeability, electrolyte wasting, and glomerular damage/filtration impairment secondary to drug binding to cholesterol in cell membranes

• < 5% excretion via renal and biliary routes; continues to be renally eliminated as it is released from tissues and is detectable in urine for 7+ weeks after last use

Aspirin

• Short (adult: 3 h)

• Irreversible inhibitor of COX-1 and 2 enzymes which leads to decreased formation of prostaglandin precursors and inhibited platelet aggregation

• Interstitial nephritis

• Hydrolyzed by esterases in GI tract, blood, and synovial fluid to salicylate which is then metabolized via hepatic conjugation; excreted in urine

Captopril, enalapril

• Short (infants with CHF captopril: 1.2–12.4 h; enalapril: 10.3 h)

• Competitive inhibitor of angiotensin-converting enzyme which leads to increased plasma renin activity and reduced aldosterone secretion

• Hemodynamic AKI: increased efferent blood flow

• Hepatic metabolism to metabolites (captopril) or active drug (enalapril → enalaprilat), then excreted in the urine as unchanged drug and metabolites

Ganciclovir, valganciclovir

Short (neonates ganciclovir: 2.4 h; infants valganciclovir: 3.5 h)

Competitively inhibits to binding of deoxyguanosine triphosphate to DNA polymerase which leads to inhibition of viral DNA synthesis

• Crystal nephropathy: drug precipitates in renal tubules

• Valganciclovir converted to ganciclovir by intestinal mucosal cells and hepatocytes; ganciclovir excreted in the urine as unchanged drug

Gentamicin, tobramycin

• Short (neonates gentamicin: 3–11.5 h; neonates tobramycin: 2–9 h)

• Inhibit bacterial protein synthesis by binding to the 30 S ribosomal subunit

• Acute tubular necrosis: accumulation within proximal tubule cells is directly cytotoxic

• Reduction of GFR via tubuloglomerular feedback mechanism

• Renal

Ibuprofen, Indomethacin, ketorolac

• Short (6 mo-2 yrs ibuprofen: 1.8 h; neonates indomethacin: 11–20 h; >6 months ketorolac: 4 h)

• Reversible inhibitor of COX-1 and 2 enzymes which leads to decreased formation of prostaglandin precursors

• Hemodynamic AKI: reduced afferent blood flow

• Hepatic metabolism; primarily excreted in urine, a small amount in the feces

Iodine-containing contrast (i.e. iohexol, ioversol)

• Short but may be prolonged

• Opacifies vessels and anatomic structures in the path of flow of the contrast media

• Acute tubular necrosis

• Renal: unchanged in the urine

Nafcillin

• Short (about 2 h for neonates/infants)

• Beta-lactam antibiotic which inhibits bacterial wall synthesis

• Acute interstitial nephritis: (allergy-mediated, not dose-dependent)

• Hepatic metabolism; primarily excreted in feces, about 30% via urine as unchanged drug

Piperacillin/ tazo-bactam

• Short (3.5 h)

• Piperacillin: beta-lactam antibiotic which inhibits bacterial wall synthesis

• Tazobactam: inhibits beta-lactamases

• Acute interstitial nephritis (allergy-mediated, not dose-dependent)

• Acute proximal tubular necrosis

• Renal: primarily as unchanged drug

Vancomycin

• Short (term neonates: 6.7 h)

• Glycopeptide antibiotic which inhibits cell wall synthesis of gram-positive bacteria

• Acute tubular necrosis (caused by oxidative stress on proximal tubular cells or, less commonly, proximal tubule obstruction from formation of casts)

• Renal: unchanged in the urine via GFR ( ≥ 90%)