Acute toxic kidney injury

Figures & data

Figure 1. Drug-induced nephrotoxicity – cellular mechanisms [12–23].

Figure 2. Pathophysiology of plants-induced nephrotoxicity [37,38,53–58].

Figure 3. The mechanisms of selected environmental and (agri)chemical nephrotoxicity [69–82].

Figure 4. Mechanisms of illicit drug nephrotoxicity [92–104].

Table 1. The clinical presentation and treatment options of selected nephrotoxic substances.

Type of toxin/poisonous substance	Clinical/laboratory presentation	Specific antidote and treatment options
Ethylene glycol [106–109]	Alteration of consciousness, hypotonia, hyporeflexia, seizures, ataxia, coma, heart failure, ARDS, oliguria, flank pain, AKI–ATN, tachycardia, severe MAC, urinary oxalate presents	10% Ethanol IV – 7.5 mL/kg LD and 1–2 mL/kg/h in nondrinkers and 2–4 mL/kg/h in drinkers to achieve a blood ethanol concentration of 100 mg/dL (22 mmol/L) Fomepizole IV – 15 mg/kg LD and 10 mg/kg every 12 h and after 48 h 15 mg/kg every 12 h Acute IHD in severe MAC, AKI and EG levels > 50 mg/dL
Isopropanol [106,110]	Nausea, vomiting, abdominal pain, gastritis, hematemesis, headache, dizziness, confusion, stupor, coma, AKI, RM, normal acid-base balance, hypotension, shock, hyperosmolarity, ketonemia, ketonuria	Acute IHD in neurological symptoms and isopropranol levels > 200 mg/dL Supportive therapy
Organophosphates [111–113]	Overstimulation of muscarinic ACR in PS: miosis, hypotension, bradycardia, bronchial secretion, vomiting, salivation, urination, diarrhea, lacrimation Overstimulation of nicotinic ACR in SyS and neuromuscular junction: tachycardia, fasciculations, crumps, hypertension, sweating Overstimulation ACR in CNS: confusion, agitation, coma, RF	Atropine 1–3 mg IV bolus-double dose after 5 min if no effects Pralidoxime chloride 2 g IV over 20–30 min – infusion 0.5–1 g/h Supportive therapy – infusion of crystalloids, support of respiratory function Benzodiazepines IV in agitation HP, HDF, PF – in cases
Morphine, heroin, opiates [114,115]	Miosis, depressed mental status, decreased respiratory rate and bowel sounds, hypotension	Naloxone hydrochloride 0.2–1 mg initially can be repeated in 2–3 min intervals. in coma – 2 mg IV initially
Synthetic cannabinoids [116]	Hyperemesis, excessive loss of fluids, psychosis, agitation, convulsions, anxiety, RF, RM, AKI, dysrhythmias, cardiac arrest or cerebral ischemia	IV infusion of crystalloids, Antiemetics, Benzodiazepines and neuroleptics in psychosis or agitation Neurological and cardiological interventions in ischemic symptoms
Cocaine [96–98,117]	Agitation, psychosis, seizures, status epilepticus, hemorrhagic and ischemic stroke, hyperthermia, MI, DIC, RM, MODS, ACS, tachycardia, aortic dissection, hypertension, pneumomediastinum, pneumothorax, alveolar hemorrhage, bronchoconstriction, bowel ischemia and perforation, AKI – thrombosis of renal vessels, renal infarction, acute TIN, GN, thrombotic microangiopathy	Benzodiazepines IV in seizures, Calcium channel blockers, Labetalol, Nitroglycerin in hypertension or ACS Cardiological, surgical, angiological and neurological specific interventions in ischemic symptoms IV infusions of crystalloids 200 mL/h initially in RM and hyperthermia to achieve adequate urine output Cooling techniques (or Dantrolen) in hyperthermia
Amphetamines [102,118,119]	Hyperthermia, psychosis, paranoid form of schizophrenia, hepatotoxicity, DIC, hypertension, tachycardia, cardiomyopathy (Tako-tsubo), ACS, chest pain, arrhythmia, RM, AKI – ATN	Benzodiazepines e.g. Diazepam 5 mg IV bolus and repeat after 5–10 min if necessary Midazolam 2.5 mg IV bolus and repeat after 5–10 min if necessary Supportive care. Betablockers – labetalol, carvedilol, metoprolol, propranolol in hyperadrenergic syndrome
Heavy metals [120–123]	Mercury – hyperpigmentation, AKI-ATN, GN, nephrotic syndrome, loose teeth, bluish discoloration, nausea, vomiting, diarrhea, hematemesis, necrotic colitis, ataxia, tremor, dysartria Lead – altered mental status, seizures, coma, abdominal colic, peripheral motor neuropathy, hypochromic microcytic anemia, fatigue, emotional lability, AKI or chronic TIN, decreased fertility, hypertension Cadmium – femoral bone pain, skeletal deformities, AKI, chronic nephropathy, proteinuria (Itai-itai disease) reduced steroidogenesis, hypertension, hyperkeratosis, acanthosis Uranium – natural – high radioactivity – acute radiation syndrome Depleted uranium – AKI, chronic nephropathy, reduced bone growth, hepatotoxicity, emphysema, pulmonary fibrosis, lung cancer, affected cognitive function and locomotion, infectious and autoimmune diseases	Chelators: DTPA, DMSA, DMPS, d-penicillamine, dimercaprol, EDTA, EHBP, Siderophores such as catechoylamide and hydroxypyridones Calixarenes for skin decontamination Supportive care: gastric tube, GIT decontamination, activated charcoal administration 25 g every 4 h Additive therapy- Zn, Mg, Se, vitamins A, C, E, Natrium bicarbonate, hydrogen sulfide Plasma exchange in emergency situation (in cadmium poisoning) Prevention: Industrial activities: natural (Moringa oleifera) and chemical water decontamination
Paraquat (1,1-dimethyl-4,4-bipyridinium dichloride) [124–126]	Nausea, vomiting, gastric pain, mucosal lesions of oral cavity and pharynx, loss of consciousness, fever. Leukocytosis, anemia, acid-base disorders, acute hepatitis, AKI, RF, shock, hypotension	Supportive care, gastrointestinal decontamination, activated charcoal – 50 g in water into gastric tube Exposed skin wash with soap and water for up to 15 min HP – within 4 h of ingestion HD, HDF – in AKI Dexamethasone 8 mg IV every 8 h for 5 weeks Fluid resuscitation
Plants containing belladonna alkaloids (atropine effects) e.g. Datura, Atropa belladona [127,128]	Hallucinations (due to L-atropine, DL-hyoscyamine and hyoscine), loss of short term memory, agitation Anticholinergic syndrome: RF, cardiovascular collapse, dry skin, high fever, tachycardia, mydriasis, mucosal dryness, ileus, urinary retention – AKI, convulsion, coma	Physostigmine salicylate IV 0.5–2 mg slowly bolus, repeated according to clinical response after 20 min Supportive therapy, Gastrointestinal decontamination
Plants containing colchicine, e.g., Gloriosa superba, Colchicinum autumnale [128]	vomiting and severe diarrhea, dehydration, hemodynamic instability, hypotension, shock, AKI and eventually MODS	Anticolchicine antibodies (polyclonal Fab fragments) – no commercial production Supportive care fluid resuscitation IHD in AKI
Snake bites [62]	AKI, RM, DIC, shock, hypotension, local necrotic tissue, hemolysis	Specific antivenom serum Supportive therapy – fluid resuscitation

ACR: acetylcholine receptors; ACS: acute coronary syndrome; AKI: acute kidney injury; ARDS: acute respiratory distress syndrome; ATN: acute tubular necrosis; CNS: central nervous system; DIC: disseminated intravascular coagulation; DMSA: meso-2,3-dimercaptosuccinic acid; DMPS: 2,3-dimercapto-1-propanesulfonic acid; DTPA: diethylenetriamine pentaacetic acid; EDTA: ethylenediaminetetracetic acid; EG: ethylene glycol; EHBP: Ethane-1-hydroxy-1,1-bisphosphonate; GN: glomerulonephritis; HDF: hemodiafiltration; HP: hemoperfusion; IHD: intermittent hemodialysis; IV: intravenously; LD: loading dose; MAC: metabolic acidosis; MI: myocardial infarction; MODS: multiple organ dysfunction syndrome; PF: plasmapheresis; PS: parasympathetic system; RF: respiratory failure; RM: rhabdomyolysis; SyS: sympathetic system; TIN: tubulointerstitial nephritis.

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