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Table 1 5R Summary by Causal Drug

From: The 6R’s of drug induced nephrotoxicity

Drug/Phenotype Risk Recognition Response Renal support Rehabilitation
Patient specific Disease specific Process of care
Aminoglycosides [8, 7476]
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]
11.5-60% for aminoglycosides in adults [8, 74, 77, 79]
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]
Obesity [55, 84, 85]
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 [8993]    42% in non-renal allografts [88] Reduce dose
Calcineurin minimization
Calcineurin replacement with mTor inhibitors
  
Cisplatin [52, 94]
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]
Ifosfamide [97, 98]
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]
8-32 per 100,000 person-years [11, 12, 106] 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
11-22% experience AKI [109, 110] 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
Vancomycin [29, 37, 114124]
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)
5-43% [29, 36, 114116, 118, 119, 125, 126] 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
Dialysis 0–7.1% [119, 126] 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]