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Drug-Induced Nephrotoxicity Module

Module drug_induced_nephrotoxicity 1 disorder Pathograph 5
A conserved treatment-toxicity module representing the final common pathway by which nephrotoxic drugs injure the renal tubule and cause acute kidney injury. The culprit agent varies — cisplatin and other platinums, aminoglycosides, vancomycin, tenofovir, amphotericin B, iodinated contrast, NSAIDs — but because the kidney concentrates, transports, and excretes these compounds, the downstream sequence repeatedly converges on proximal tubular drug accumulation, oxidative and mitochondrial stress, tubular epithelial cell death (apoptosis and acute tubular necrosis), tubulointerstitial inflammation, and a fall in glomerular filtration rate. This is a "side effect as mechanism" module: it captures the adverse-drug-reaction pathophysiology shared across nephrotoxic drugs, so a drug-toxicity entry can declare conformance rather than re-deriving the chain. It models the dose-dependent acute-tubular-injury arm; crystal/cast obstruction and immune-mediated interstitial nephritis are distinct arms noted in the literature but not the focus here.
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Pathophysiology Nodes

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5 shared nodes are defined in this module.
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Cell Types

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proximal tubule epithelial cell CL:0002306
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Biological Processes

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xenobiotic transport GO:0042908 INCREASED response to oxidative stress GO:0006979 INCREASED cell death GO:0008219 INCREASED apoptotic process GO:0006915 INCREASED inflammatory response GO:0006954 INCREASED renal system process GO:0003014 DECREASED
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Notes

This is a mechanism module, not a specific disease. Disorder entries reference individual nodes via conforms_to (e.g., "drug_induced_nephrotoxicity#Proximal Tubular Epithelial Cell Death"). Conforming nodes should substitute the drug-specific uptake/transport route (e.g. OCT2/cisplatin, megalin-endocytosis/aminoglycosides) while preserving the conserved uptake → oxidative/mitochondrial stress → tubular cell death → inflammation → AKI chain. The key conformance / central-effector target is "drug_induced_nephrotoxicity#Proximal Tubular Epithelial Cell Death".
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Used By Disorder Entries

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Hospital-Acquired Acute Kidney Injury via Nephrotoxic Injury → Proximal Tubular Epithelial Cell Death
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Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence-backed metadata.
Pathograph: causal mechanism network for Drug-Induced Nephrotoxicity Module Interactive directed graph showing how this shared module's pathophysiology nodes connect.
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Pathophysiology

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Nephrotoxic Drug Exposure and Tubular Uptake
trigger
The conserved initiating lesion is renal handling of the drug: the proximal tubule is exposed to filtered and secreted compounds and takes them up via apical endocytosis or basolateral organic anion/cation transporters, leading to intracellular accumulation. This renal handling, combined with the drug's inherent toxicity, concentrates the insult in tubular epithelial cells.
proximal tubule epithelial cell CL:0002306
xenobiotic transport GO:0042908 INCREASED
Downstream
  • Tubular Oxidative Stress and Mitochondrial Injury Accumulated drug provokes oxidative and mitochondrial stress in tubular cells.
Tubular Oxidative Stress and Mitochondrial Injury
amplifier
Intracellular drug accumulation generates reactive oxygen species and damages mitochondria in the metabolically active proximal tubule, the major amplifying event linking drug uptake to tubular cell death.
proximal tubule epithelial cell CL:0002306
response to oxidative stress GO:0006979 INCREASED
mitochondrion GO:0005739
Downstream
  • Proximal Tubular Epithelial Cell Death Oxidative and mitochondrial injury precipitate tubular epithelial cell death.
Proximal Tubular Epithelial Cell Death
central effector
Oxidative and mitochondrial injury precipitate proximal tubular epithelial cell death by apoptosis and acute tubular necrosis (ATN). This is the central effector lesion and the key conformance target; conforming disorder nodes substitute the drug-specific upstream driver but converge here.
proximal tubule epithelial cell CL:0002306
cell death GO:0008219 INCREASED apoptotic process GO:0006915 INCREASED
Used by disorders
Hospital-Acquired Acute Kidney Injury as Nephrotoxic Injury
Downstream
  • Tubulointerstitial Inflammation Dying tubular cells release signals that recruit inflammatory cells.
  • Acute Kidney Injury Loss of functional tubular epithelium reduces kidney function.
Tubulointerstitial Inflammation
amplifier
Tubular cell death releases damage-associated signals that drive tubulointerstitial inflammation, which amplifies and extends the tubular injury.
proximal tubule epithelial cell CL:0002306
inflammatory response GO:0006954 INCREASED
Downstream
  • Acute Kidney Injury Sustained inflammatory injury extends nephron loss toward clinical AKI.
Acute Kidney Injury
consequence
Accumulated tubular cell loss and inflammation reduce the glomerular filtration rate, producing acute kidney injury — the defining clinical consequence and frequently a dose-limiting toxicity that necessitates dose reduction or drug withdrawal.
proximal tubule epithelial cell CL:0002306
renal system process GO:0003014 DECREASED