Table 1.
Different classes of antibiotics and their various mechanisms of nephrotoxicity, along with the clinical presentation and proposed biomarkers
| Antibiotic class | Examples | Clinical presentation of toxicity | Mechanisms of toxicity | Biomarkers: pre-clinical | Biomarkers: clinical |
|---|---|---|---|---|---|
| Aminoglycosides | Neomycin Gentamicin Tobramycin |
-ATN (10%–20%) -Fanconi Syndrome |
-Accumulates in proximal tubule cells, causing mitochondrial dysfunction and cell apoptosis. -Causes mesangial cell contraction, decreasing glomerular filtration and surface area |
Serum: cystatin C Urine: --KIM-1 --clusterin --NAG --NGAL --OPN --IL-18 --miRNAs |
Serum: cystatin C Urine: --KIM-1 --NAG --NGAL --OPN --IL-18 --miRNAs |
| Glycopeptides | Vancomycin | -ATN -Non-crystalline cast nephropathy |
-Accumulates in proximal tubule cells, leading to cell injury and apoptosis via ROS induced damage -Causes tubular obstruction through formation of non-crystal vancomycin and uromodulin casts |
Urine: --KIM-1 --NGAL |
Serum: cystatin C Urine: --TIMP2/IGFBP7 --NGAL |
| Beta lactams | Penicillin Cephalosporins Piperacillin/Tazobactam |
-AIN | -Causes interstitial inflammation from delayed T cell mediated (type IV) hypersensitivity reaction. | Urine (in AIN) --MCP1 --NGAL --NAG --MMPs --KIM-1 --C5b-9 --INFα --IL-5, 6, 8, 9 ,12, 17 |
|
| Folate synthesis iInhibitors | TMP/SMX | -Pseudo-AKI -AIN -Crystalline nephropathy -Hyperkalemia |
-Trimethoprim competes with creatinine at the OAT-2 transporter -Interstitial inflammation from delayed T cell mediated (type IV) hypersensitivity reaction -Intratubular obstruction from precipitation of sulfamethoxazole -Inhibits sodium influx via ENaC, reducing the gradient for potassium excretion |
Urine (in AIN) --MCP1 --NGAL --NAG --MMPs --KIM-1 --C5b-9 --INFα --IL-5, 6, 8, 9 ,12, 17 |
|
| Sulfonamides | Sulfadiazine | -Crystalline nephropathy -Stone formation -AIN |
-Crystalline precipitation, causing tubular obstruction and interstitial inflammation | Urine (in AIN) --MCP1 --NGAL --NAG --MMPs --KIM-1 --C5b-9 --INFα --IL- 5, 6, 8, 9 ,12, 17 |
|
| Fluoroquinolones | Ciprofloxacin Levofloxacin Moxifloxacin |
-Crystalline nephropathy -AIN -ATN -Granulomatous interstitial nephritis (rare) |
-Crystalline precipitation, causing tubular obstruction and interstitial inflammation | Urine (in AIN) --MCP1 --NGAL --NAG --MMPs --KIM-1 --C5b-9 --INFα --IL-5, 6, 8, 9 ,12, 17 |
|
| Tetracyclines | Doxycycline Minocycline |
-Fanconi syndrome -AIN -Granulomatous interstitial nephritis (rare) |
-Accumulates in proximal tubular cells, inhibiting ribosomal protein production and causing cell damage -Interstitial inflammation from delayed T cell mediated (type IV) hypersensitivity reaction |
Urine (in AIN) --MCP1 --NGAL --NAG --MMPs --KIM-1 --C5b-9 --INFα --IL-5, 6, 8, 9 ,12, 17 |
|
| Polymixin | Colistin | -ATN (20%–60%) | - Accumulates in proximal tubular cells, causing cell membrane and mitochondrial damage, leading to cell apoptosis | Serum: cystatin C Urine: --KIM 1 --NGAL |
Serum: cystatin C Urine: clusterin |
AIN, acute interstitial nephritis; ATN, acute tubular necrosis; C5b-9, (terminal complement complex); ENaC, epithelial sodium channel; IFNα, interferon-alpha; IL, interleukin; KIM-1, kidney injury molecule-1; MCP-1, monocyte chemoattractant protein-1; MMP, matrix metalloproteinase; NAG, N-acetyl-beta-D-glucosaminidase; NGAL, neutrophil gelatinase associated lipocalin; OAT-2, organic anion transporter-2; OPN, osteopontin; TMP/SMX, trimethoprim-sulfamethoxazole.