Drug Induced Nephropathy Stephanie Mahooty, DNP

Acute Kidney Injury (AKI) Defined as: Abrupt (within 48 hours) reduction in kidney function due to a rise in the serum creatinine by ≥0.3 mg/dL or Documented oliguria of <0.5 mL/kg/h for more than 6 hours. Classified as prerenal, postrenal and intrinsic renal injury Intrinsic renal injury can be glomerular, microvascular, interstitial or tubular. Acute tubular necrosis is a condition in which the small filtering tubes in the kidney are injuried. It can be caused by sepsis, surgery, direct injury to the kidney, severe burns, severe muscle injury, and medications. Acute glomerulonephritis is a condition where the tiny blood vessels in the kidney become inflamed and damaged. Also can be caused by abnormal immune system response. Acute interstitial nephritis is inflammation of the kidneys, usually caused by a medication.

Epidemiology Drugs cause approximately 20% community and hospital acquired episodes of AKI. The incidence of drug-induced nephrotoxicity is as high as 66% among older adults. One of the leading cause of AKI It can be costly, require multiple interventions, and hospitalization.

Risk Factors Age, sex Pre-existing CKD Hypoalbuminemia-hepatic failure with ascites, nephrotic, heart failure Sepsis Diabetes mellitus Dehydration and intravascular volume depletion Exposure to multiple nephrotoxins

Pathologic Mechanisms Intraglomerular hemodynamics- ACEi/ARBs/NSAIDs/Calcineurin inhibitors (cyclosporin, tacrolimus) Tubular cell toxicity- aminoglycosides, amphotericin B, cisplatin, beta lactams, quinolones, rifampin, sulfonamides, vancomycin, acyclovir, and contrast agents. Inflammation-Numerous drugs have been know to cause 1.) these drugs can cause nephrotoxicity by altering intraglomerular hemodynamics 2.) induce renal tubular cell injury by impairing mitochondrial function, and interfering with tubular transport, and increasing oxidative stress and free radicals. 3.) Drugs can cause inflammatory changes in the glomerulus, renal tubular cells, and the surrounding interstitum, leading to fibrosis and renal scarring. Acute interstitial nephritis, glomerulonephritis, and (chronic interstitial nephritis)

Pathologic Mechanisms Crystal nephropathy-ampicillin, ciprofloxacin, sulfonamides, acyclovir, ganciclovir, methotrexate, and triamterene. Can result from chemo due to uric acid deposition Rhabdomyolysis-statins Thrombotic microangiopathy-antiplatelets, ticlopidine, cyclosporine, mitomycin-C, quinine 1.) these drugs may produce crystals that are insoluble in human urine. These crystals precipitate usually within the distal tubular lumen, obstructing urine flow and trigger an interstitial reaction. 2.) Induces kidney injury secondary to direct toxicity, tubular obstruction, and alterations in GFR. Cocaine, methadone, heroine, meth have been reported to cause rhabdomyolysis. 3.) organ damage is caused by platelet thrombi in the microcirculation. Mechanisms of renal injury secondary to drug induce thrombotic microangiopathy include immune mediated reaction or direct endothelial toxicity.

Drugs With Nephrotoxicity Potential Non-steroidal anti-inflammatory drugs-most common causes of drug-induced renal injury Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers Antimicrobial agents-aminoglycosides, sulfmethoxazole-trimethoprim, sulfa based antibiotics,Vancomycin,Ciprofloxacin. Antivirals- acyclovir, foscarnet, antiretroviral drugs Anti fungal-amphotericin B

Drugs With Nephrotoxicity Potential Chemotherapeutic agents-cisplatin, ifosfamide, MTX, bisphosphonates Radiocontrast agents- Immunosuppressive agents-tacrolimus and cyclosporine Miscellaneous-Lithium, acetaminophen, proton- pump inhibitors, statins, osmotic agents-e.g, mannitol, 1.) 2.) 3.) 4.) is associated with chronic interstitial nephritis leading to fibrosis and renal scarring.

Vancomycin (VCM) Vancomycin is a glycopeptide antibiotic Used first line to treat MRSA VCM nephrotoxicity is generally due to acute tubular necrosis or acute interstitial nephritis. Risk factors for the development of nephrotoxicity with VCM involves trough levels >15 mg/L, long duration of therapy, and concomitant administration of other nephrotoxins (e.g., aminoglycosides)

Case Study 69 year old Native American Male had prolong hospitalization secondary to vancomycin toxicity and subsequent acute kidney injury. He put his foot in hot water to take a bath, due to his neuropathy he did not realize how hot it was and developed a blisters along lateral part of his foot and over toes 3 and 4. He then developed an ulcer. Was treated with silver silvadene, apparently got worse. Hospitalized: 4/15-5/3 PMH: Acute on chronic kidney disease stage 3, insulin-dependent DM, severe PVD, degloving injury secondary to thermal burn in 4/2016 of his left foot, peripheral neuropathy, chronic pain, major recurrent depression, nonhealing left foot ulcer-distal fifth metatarsal, osteomyelitis left foot, hyperlipidemia, hypertension, hypothyroidism, chronic pancreatitis, BPH

Case Study Medications prior to hospitalization: Levothyroxine, pantoprazole, fluoxetine, glimepiride, pregabalin, calcium, cyanocobalamin, cholecalciferol, ranitidine, Tamsulosin, fentanyl patch, morphine sulfate SR, detemir insulin, doxepin HCL, metformin HCL, silver sulfadiazine cream Inhouse Medications: Zosyn: 4/15-17 Rocephin 4/18-25 Vancomycin 4/17-18 Back on Zosyn 4/28-5/02

Case Study LABS: 4/05 creatinine 0.87 eGFR >60 4/14 creatinine 1.12 4/26 creatinine 4.7 eGFR 12 sodium 140, potassium 4.0 bicarbonate 21, WBC 15.8 from 12.6, hgb 11 hgb A1c 9.7 4/30 creatinine 3.8 eGFR 15 Wound cultures grew out group b strep and methicillin-susceptible staphylococcus aureus 5/3 creatinine 3.6 eGFR 16 Year later: creatinine 1.13 mg/dL, eGFR > 60 mL/min, hgb A1c 11.1%, UPCR 1.0 IMAGING: 4/27 MRI done, significant osteomyelitis of third and second toes. 2/4/ renal u/s showed cyst in right kidney, otherwise unremarkable. Most drug induce AKI is reversible Returns to baseline when recognized early and offending medication is discontinued