Table 1 5R Summary by Causal Drug
Drug/Phenotype | Risk | Recognition | Response | Renal support | Rehabilitation | ||
|---|---|---|---|---|---|---|---|
Patient specific | Disease specific | Process of care | |||||
AKI | Age | Diabetes Volume depletion Sepsis Liver dysfunction CKD Hypokalemia Hypomagnesemia | Duration of therapy Type of aminoglycoside Frequency of dosing Elevated trough concentrations > 2mcg/mL [8, 77] Timing of administration Concurrent nephrotoxins (i.e. vancomycin) [77] Contrast administration | 12.2% for gentamicin in neonates [78] | Prevention: Once daily dosing [75] Consider using tobramycin instead of gentamicin since it has lower rates of nephrotoxicity [80, 81] Avoid midnight to 7 am administration [76] | No difference in need for renal support in no gentamicin vs. gentamicin treated infection endocarditis, 8 vs. 6% respectively [82] | 4.6% mortality in a cohort of 201 critically ill patients [8] 51% recovery within 21 days of AMG associated AKI [77] Cohort of critically ill patients, mortality in AKI vs. non-AKI group was 44.5 vs. 29.1%, respectively. [74] |
Acyclovir Nephrolithiasis/AKI | Older children [83] | Volume depletion CKD | Rapid intravenous administration Dose dependent Longer duration of therapy [83] Length of hospital stay [83] Concomitant nephrotoxins [86] | 12-48% crystal nephropathy with rapid intravenous bolus administration 0.27% AKI from oral acyclovir [87] 3.1-10.3% children developed AKI from intravenous acyclovir | Prevention: Hydration Slow intravenous administration Dose adjustment for CKD Treatment: Discontinuation Rehydration Hemodialysis | ||
Calcineurin Inhibitors [88] AKI/glomerular | Genetic variations in CYP3A4, MDR1, ACE, TGF-β, and CCR5 [89–93] | 42% in non-renal allografts [88] | Reduce dose Calcineurin minimization Calcineurin replacement with mTor inhibitors | ||||
AKI/tubular | Age African Americans | CKD | Concurrent nephrotoxins | 58% in pediatrics [52] 43.5% in adults [94] | Minimize concurrent nephrotoxin exposure | 49% with reduction in GFR, 71% with glucosuria, 67% with proteinuria over long term [95] | |
Colistin [96] AKI | Age Obesity | 48% in overweight or obese patients [96] | Minimize concurrent nephrotoxin exposure Consider alternative agents | 80% developed failure by RIFLE category [96] No statistically significant difference in hospital or 30 day mortality [96] | |||
AKI/tubular | Age | CKD Nephrectomy Tumor infiltration in kidney | Cumulative dose Method of administration Concurrent nephrotoxins (cisplatin, carboplatin) | 50% in pediatric cancer patients [97] | Minimize concurrent nephrotoxin exposure | No dialysis requirement [98] | No resolution of injury [98] |
Lithium Tubular/Glomerular | CKD | Duration of therapy | 11.6-15% develop AKI [99, 100] 26.1% develop concentrating defect [99] | Discontinuation of drug | 78% of patients with Scr ≥2.5 mg/dL at baseline required dialysis [101] | 42.1% develop ESRD [101] | |
Protease Inhibitors Atazanavir Indinavir Nephrolithiasis/ AKI | Asymptomatic crystalluria in 20-67% [102, 103] Nephrolithiasis in 3% [103] | Prevention: Patients should drink a minimum of 1.5 L/day of water to prevent stone formation Periodic monitoring of renal function and screening for pyuria during the first 6 months of therapy and biannually Treatment Hold if patient develops nephrolithiasis until rehydrated [104] Discontinue the drug if patient experiences pyuria, AKI, hypertension or rhabdomyolysis [104] | No dialysis requirements | 21% increased risk of CKD [105] 12% increased risk of CKD [105] | |||
Proton Pump Inhibitors AKI | Age > 60 years [12] | Current users higher risk compared to past users Concurrent nephrotoxins (antibiotics or diuretics) [10] | Discontinue drug Consider course of steroids [107] | No dialysis requirement reported | Spontaneous recovery after drug withdrawal [108] | ||
Sulfamethoxazole/trimethoprim | None | DM HTN CKD [109] | Concurrent nephrotoxins Contrast dye | Discontinue drug | 1% required dialysis | Complete recovery within 30 days | |
Tenofovir Tubular | 12-22% with proximal tubular injury [5, 6] 0.5% experience a renal event [111] 0.3% experience renal failure [111] 0.3-2% fanconi syndrome [112] | Prevention: Biannual screening for proteinuria and glycosuria with urinalysis, Scr, serum phosphate in patients with eGFR of < 90 ml/min/1.73 m2 [104] | <2% require dialysis [113] | 16% increased risk of CKD [105] May have partial or complete recovery within months to a year | |||
AKI | Age Obesity | Sepsis Hypotension CKD Active cancers | Trough concentrations > 15 ng/mL Doses greater than 4 g/day Duration of therapy Concurrent nephrotoxins (ACEI, acyclovir, aminoglycosides, amphotericin, colistin, piperacillin/tazobactam, vasopressor use) | Employ therapeutic drug monitoring and pharmacist consultation [41] Maintain trough concentrations to < 15 ng/mL [38] Maintain doses < 4 g/day Consider switching to alternative antibiotics such as telavancin or linezolid [39, 40] Avoid combination with piperacillin/tazobactam [119] Minimize concurrent nephrotoxin exposure | Resolution 21–72.5% [114, 119, 126] Mortality 45% [126] | ||
VEGF Inhibitors Glomerular | Dose related [127] | 21-63% incidence of hypertension [127] Case reports of nephropathy. | Reduce dose ACE inhibitors and nitrates to treat proteinuria and hypertension Discontinue drug | 33% resolution of injury after discontinuation of therapy [7] | |||