Nephrotoxicity in children

Goldman RD, Koren G. Amphotericin B nephrotoxicity in children. J Pediatr Hematol Oncol. 2004 26 421-426. 

Skinner R, Pearson AD, English MW, Price L, Wyllie RA, Coulthard MG, Craft AW. Risk factors for ifosfamide nephrotoxicity in children. Lancet 1996 348(9027) 578-80. 

Brock PR, Koliouska DE, BarattTM, Yeomans E, Pritchard J. Partial reversibility of cisplatin nephrotoxicity in children. J Pediatric 1991,118 531-4. 

Skinner R, Sharkey IM, Pearson ADJ, et al. Ifosfamide, Mesnaand nephrotoxicity in children. J Clin Oncol 11 173-190,1993. 

Kranz B, Vester U, Buscher R, Wingen AM, Hoyer PF. Cyclosporine-A-induced nephrotoxicity in children with minimal-change nephrotic syndrome long-term treatment up to 10 years. Pediatr Nephrol 2008 23 581-586. 

Vincent F, Laskow DA, Neylan JF, Mendez R, Matas AJ. One-year follow-up of an open-label trial of FK506 for primary kidney transplantation. A report of the U.S. Multicenter FK506 Kidney Transplant Group. Transplantation 1996 61 1576-1581. McLaughlin GE, Abitbol CL. Reversal of oliguric tacrolimus nephrotoxicity in children. Nephrol Dial Transplant 2005 20 1471-1415. 

Loebstein R, Koren G (1998) Ifosfamide -induced nephrotoxicity in children critical review of predictive risk factors. Pediatr 10LE8-E12... 

Skinner R (2003) Chronic ifosfamide nephrotoxicity in children. Med Pediatr Oncol 41 190-197... 

Hanly L, Chen N, Rieder M, Koren G (2009) Ifosfamide nephrotoxicity in children a mechanistic base for pharmacological prevention. Expert Opin Drug Saf 8 155-168... 

Hanly LN, Chen N, Aleksa K et al (2011) N-acetylcysteine as a Novel Prophylactic Treatment for Ifosfamide-induced Nephrotoxicity in Children Translational Pharmacokinetics. J Clin Pharmacol 52(l) 55-64... 

Kengne-Wafo S, Massella L, Diomedi-Camassei F, Gianviti A, Vivarelli M, Greco M, Stringini GR, Emma F. Risk factors for cyclosporin A nephrotoxicity in children with steroid-dependant nephrotic syndrome. Clin J Am Soc Nephrol 2009 4(9) 1409-16. 

G. Koren, N. Chen and K. Aleksa, Drug-induced nephrotoxicity in children pharmacologically based prevention of long-term impairment, Paediatr. Drugs., 2007, 9, 139-142. 

Thimerosal is a preservative used in vaccines that has been purported to cause autism in children. The assumption is that thimerosal, also known as ethyl mercury, causes similar effects as methyl mercury, which has neurotoxic and nephrotoxic... 

Administration of 3 -amino-3 -deoxy-A,ALdimethyladenosine (the amino-nucleoside of puromycin) to rats produces a nephrotic syndrome that is clinically indistinguishable from the nephrotic syndrome of unknown origin frequently observed in children [365]. Rats, monkeys, and humans are susceptible to this nephrotoxicity and susceptibility has been related to specie ability to demethylate the aminonucleoside [213]. 7V -Methyladenosine prevents development of this syndrome [365a]. 

Uses Severe, systemic fungal Infxns oral cutaneous candidiasis Action Binds ergosterol in the fungal membrane to alter permeability Dose Adults Peds. Test dose 1 mg IV adults or 0.1 mg/kg to 1 mg IV in children then 0.25-1.5 mg/kg/24 h IV over 2-6 h (range 25-50 mg/d or qod). Total dose varies w/ indication PO 1 mL qid Caution [B, ] Disp Inj SE -1- K /Mg from renal wasting anaphylaxis reported, HA, fever, chills, n hrotox, -1- BP, anemia, rigors Notes -1- In renal impair pre-Tx w/ APAP antihistamines (Benadryl) X SE Interactions T Nephrotoxic effects W/ antineoplastics, cyclosporine, furosemide, vancomycin, aminoglycosides, T hypokalemia W/ corticost oids, skeletal muscle relaxants EMS May cause electrolyte imbalances, monitor ECG OD May effect CV and resp Fxn symptomatic and supportive... 

Toxicities are numerous and frequently include nephrotoxicity, hypertension, hyperglycemia, liver dysfunction, and hirsutism. A significant increase in the incidence of cholelithiasis has been observed in children treated with cyclosporine after heart transplantation. Cyclosporine causes very little bone marrow toxicity. While an increased incidence of lymphoma and other cancers (Kaposi s sarcoma, skin cancer) has been documented in transplant recipients receiving cyclosporine, other immunosuppressive agents may also predispose recipients to cancer. Some evidence suggests that tumors may arise after cyclosporine treatment because it induces TGF-3, which promotes tumor invasion and metastasis. 

Sevoflurane is a chemical analogue of isoflurane. It is less chemically stable than the other volatile anaesthetics in current use. About 3% is metabolised in the body and it is degraded by contact with carbon dioxide absorbents, such as soda lime. The reaction with soda lime causes the formation of a vinyl ether (Compound A), which may be nephrotoxic. Sevoflurane is less soluble than isoflurane and is very pleasant to breathe, which makes it an excellent choice for inhalational induction of anaesthesia, particularly in children. The respiratory and cardiovascular effects of sevoflurane are very similar to isoflurane. 

Goren MP, Viar MJ, Shenep JL, Wright RK, Baker DK, Kalwinsky DK. Monitoring serum aminoglycoside concentrations in children with amphotericin B nephrotoxicity. Pediatr Infect Dis J 1988 7(10) 698-703. 

The susceptibility factors associated with chronic ifosfamide nephrotoxicity up to 28 months after treatment have been studied in 23 children. The authors concluded that cumulative doses of 100 g/m or higher should be avoided in children with cancers (11). 

Isepamicin is similar to amikacin but has better activity against strains that produce type I 6 -acetyltransferase. It can cause nephrotoxicity, vestibular toxicity, and ototoxicity. However, it is one of the less toxic of the aminoglycosides (1). The antibacterial spectrum of isepamicin includes Enterobacteriaceae and staphylococci anaerobes, Neisseriae, and streptococci are resistant (1). Isepamicin was as effective and safe as amikacin in the treatment of acute pyelonephritis in children and might prove an advantageous alternative in areas with a high incidence of resistance to other aminoglycosides (2). 

In 35 children who had taken cisplatin for a maximum of 2 years, nephrotoxicity was not related to total dose but was less severe in children who received cisplatin in doses below 40 mg/m /day (200). During follow-up for 2 years there was partial but significant recovery of renal function. 

English MW, Skinner R, Pearson AD, Price L, Wyllie R, Craft AW. Dose-related nephrotoxicity of carboplatin in children. Br J Cancer 1999 81(2) 336 1. 

In children with febrile neutropenia and Gram-positive bacteremia associated with antineoplastic drug therapy, teicoplanin was significantly less nephrotoxic than vancomycin (14). 

Aztreonam, a monobactam, is a useful alternative for patients with aerobic gram-negative infections who are allergic to penicillins, but has no activity against anaerobes. Aztreonam appears to be the only p-lactam antibiotic that can be safely administered to penicillin-allergic patients [58]. Aztreonam has a spectrum of activity that is comparable to the aminoglycosides but it is less nephrotoxic in patients [59] and it appears to be well tolerated in infants and children [60]. 

Halothane and sevoflurane are commonly used for inhaled induction of anesthesia in children because they do not have a noxious smell. These drugs and isoflurane or desflurane are then used to maintain anesthesia, according to the preference of the anesthesiologist. Enflurane is rarely used today because it irritates the airway [115]. Therefore, of the inhaled agents currently used in pediatric patients, only sevoflurane has nephrotoxic potential. 

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