Renal Toxicology

Nendyah Roestijawati
Kidney as a target organ

Receive 25% CO potentially exposed to large

dose toxic materials
Osmotic gradients in the medulla concetrate
toxic agent to levels far excess
Capable acidifying the urine solutes may occur
in ionic forms
Acute renal dysfunction by
heavy metals
Exposure to divalent metals : chromium,
cadmium, mercury, vanadium
Workers welding cadmium-plated metals
xxposure cadmium through inhalation
Renal failure : acute tubular necrosis
Severe exposure : bilateral cortical necrosis
Acute renal dysfunction by organic
solvents (Halogenated hydrocarbons)
Carbon tetrachloride
Used : industrial solvent, basis for manufacture fluorinated
hydrocarbons, household cleaning agent, component of fire
extingusher
Lipophilic fat, liver, bone marrow, blood, brain, kidney
Chemical interaction : ethyl alcohol or other
Acute exposure : acute central nervous depression (confusion,
somnolence), nausea, vomiting, mucous membrane irritant effects
(burning eyes), abdominal pain, constipation, diarrhea, fever
PE : acute abdomen, 7-10 days : decline urine output anuria, pre
renal azotemia (low urinary sodium)
Urinalysis : red blood cells, protein
DD : acute glomerulonephritis
Tx : dialysis
Acute renal dysfunction by organic
solvents (Halogenated hydrocarbons)
Ethylene dichloride
Used : solvent for oils, fats, waxes, turpentine, rubber, insecticide, fumigant,
household cleaning, fire extingushers
Less potent as renal toxicant than CCl4 but causes far greater central nervous
system toxicity
Ingestion/inhalation : acute tubular necrosis similar mercury poisoning
Chloroform : More nephrotoxic than CCl4, enhanced by alcohol exposure
Trichloroethylene
Used : anesthetic agent
Inhalation acute renal failure
Comparable as CCl4 adn chloroform
Acute renal dysfunction by organic
solvents (Halogenated hydrocarbons)
Tetrachloroethane
Used : solvent for cellulose acetate, most toxic
Vinylidene chloride
Used : manufacture of plastics, is not used as a solvent
Similar toxicology with CCl4
Ethylene chlorohydrin
Used : solvent and chemical intermediate
Far more toxic
Penetrates the skin and absorbed through rubber gloves
Acute renal dysfunction by organic
solvents (Nonhalogenated hydrocarbons)
Dioxane
Less toxic than halogenated hydrocarbons
Symptoms : anorexia, nausea, vomiting, jaundice (uncommon)
PE : acute abdominal emergency, decrease urine output
Urinalysis ; blood, albumin
Toluene
Painters, sniffing glue
Acute renal failure and distal renal tubular acidosis
Acute renal dysfunction by organic
solvents (Nonhalogenated hydrocarbons)
Alkyl derivates of ethylene glycol
Absorbed through the skin, lungs, GI tract
Irritants of skin and mucous membrane, central nervous depresant
Symptoms : headache, drowsines, weakness, slurred speech, staggering gait,
blurred vision
Phenol
Local burns, absorbed through lungs and transdermally
Systemic symptoms : headache, vertigo, salivation, nausea, vomiting,
diarrhea
Severe intoxication : urinary albumin, red cells casts
Hypotermia, convulsions, oliguria, proteinuria, dark urine (green or brown,
carboluria) phenol is metabolized to hydroquinone oxidized to color
substance
Acute renal dysfunction by organic
solvents (Nonhalogenated hydrocarbons)
Pentachlorophenol
Used : preservative for timber, insecticide, herbicide, defoliant
Absorbed through skin
Acute renal failure, hypermetabloic state, hyperpirexia, vascular collapse
Dinitriphenois & dinitro-o-cresols
Used : pesticide, herbicide
Uncouple oxidative phosphorylation fatal hyperpirexia
Acute renal failure unknwon as direct effect or metabolic consequences
myoglobinuria
Acute renal dysfunction by unidentified
pesticides
Reduction glomerular filtration and tubular reaabsorption
conjunction with depression of serum cholinesterase
Organic mercurials as fungicide lead nephrotic syndomre,
increase glutamyl transpeptidase urine
Acute renal dysfunction by arsine
Heavy gas, the most nephrotoxic form of arsenic
Produced bay acids action on arsenical during coal or metal processing
operation
Used : semiconductor industry
Hemotoxic and hemolytic agent : malaise, abdominal cramps, nausea,
vomiting
Renal failure from acute tubular necrosis secondary to hemoglobinuria
Tx : mannitol, HD, transfusion
Residual interstitial nephritis
Chronic renal failure by lead
Early phase : increase mitotic activity in proximal tubular epithelium,
formation intranuclear inclusion bodies, glomerular filtration unimparired,
tubular damage, aminoaciduria, phosphaturia, glycosuria Fanconis
syndrome, decreased renal clearance of uric acid, mitochondrial destruction,
urinary lead
Second phase : decreased ability to form inclusion bodies, decreased renal
lead excretion, absent of Fanconi syndrome, decreased hyperuricemia and
renal uric acid, renal function, serum urea nitrogen and creatinine normal
Final phase : hypertension, hyperuricemia, gout, hyperkaliemia, proteinuria,
end stage renal failure, zinc protoporphyrin, blood lead
Blood lead level 60-100 g/dL, zinc protoporphyrin excess of 100 g/dL risk
renal dysfunction
Tx : EDTA
Chronic renal failure by cadmium

40-80% stored at liver and kidney, 1/3 kidney

Proteinuria, increase serum creatinine and 2
microglobulin
Cd absorbed accumulates renal proximal tubule
inhibits activity vitamin D1 hydroxylase osteomalacia
hypercalciuria renal stone
Target : cadmium renal cortex 180-220 g/g 10 g/g
creatinine urine
Chronic renal failure by mercury

Immunologic, genetic
Primarily membranous glomerulonephritis : proteinuria
Urinary transferrin, albumin, galactosidase
Tx : BAL
Chronic renal failure by berrylium

Used : electronic tubes, ceramic, bulbs

Principal route : inhalation
Systemic granulomatous disease lung, bone, bone marrow,
liver, lymph nodes, etc
Kidney : granulomas and interstitial fibrosis
Hypercalciuria, urinary tract stone, hyperuricemia
Goodpastures disease

Exposure to hydrocarbon
Progressive glomerulonephritis and pulmonary alveolar
hemorrhage
Cresent formation, endocapillary and exocapillary
proliferation, linear deposits of immunoglobulin in the
glomerulus