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Renal Toxicology Explained: Occupational Hazards, Diagnosis, and Management

Dive into renal toxicology with insights on occupational hazards, diagnosis methods, and effective management strategies for kidney diseases caused by environmental exposures. Understand renal functions, toxicants, clinical presentations, and diagnostic tests.

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Renal Toxicology Explained: Occupational Hazards, Diagnosis, and Management

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  1. Renal toxicology By : Dr ASLANI OCCUPATIONAL MEDICINE SPECIALIST

  2. PHYSIOLOGY

  3. Function • Regulation of electrolytes • Maintenance of acid-base balance • Regulation of BP • Remove wastes from the blood • Reabsorption of H2O,G,AA • Produce hormones

  4. Introduction • True incidence of CKD due to occupational & environmental exposure is unknown. • Kidney is especially vulnerable to these exposures & toxins can be concentrated in kidney. • These exposure are preventable causes of CKD.

  5. Kidney Diseases • Duration • Acute(Weeks) • Chronic(Years) • Location • Glomerular • Non-glomerular(tubular , interstitial) • The most common site of injury for toxicants is the proximal tubule. Aghaee2a@gmail.com

  6. Diagnosis • History • Physical examination • Clinical presentation of the renal disease Monitoring of exposed workers: • lack of sensitive and specific tests • Serial measurement Cr & BUN

  7. Clinical history • Exposure histories: • Frequency • Intensity • Personal protection

  8. Clinical history & physical examination • Factors that enhancing nephrotoxicity: • Age • Genetic • HTN • Diabetes • Gout • Pre-exiting chronic renal disease

  9. Hematuria: • Urinary tract cancer • Papillary necrosis • GN • Proteinuria: • HMW Proteinuria (albuminuria) • LMW proteinuria (β2-microglobulin & RBP)

  10. Diagnostic Test (U.S. Department of Health ) • correlate with site of possible damage & detect early renal tubular damage . • glomerular injury (urine albumin) • proximal tubule damage (RBP, glucosaminidase, alanine amino peptidase) • distal tubule injury (osmolality)

  11. Limitations • unstable at certain urine pHs • return to normal levels despite renal damage • large inter-individual variations • predictive value of these newer tests has not been validated.

  12. Clinical presentation • Acute renal failure: ATN • Chronic renal failure: Chronic interstitial nephritis

  13. Acute renal dysfunction • Usually after high-dose exposure • renal lesion : ATN • extra renal manifestations usually dominate • clinical presentation, course of ARF are very similar in all exposures.

  14. ATN • Hours to days after exp: urine output< 500 ml/d. • The urine analysis: renal tubular cells, muddy brown granular casts, Pr, RBC,WBC or casts of either cell type: Neg • BUN ,Cr and electrolyte abnormalities • After 1-2 weeks: diuresis

  15. ATN • Treatment • Hemodialysis and/or hemoperfiision have almost no role in accelerating the clearance of occupational and environmental toxins. • These techniques are effective: • certain alcohols, salicylate, lithium, theophylline

  16. ARF caused by heavy metals • Divalent metals, Cr, Cd, Hg & vanadium • Exposure: welding cadmium-plated metals • Exposure to Cd fumes → cough & progressive pulmonary distress to ARDS • RF in form of ATN • Bilateral cortical necrosis in severe exposure

  17. ARF caused by organic solvents • Route of absorption: lungs (most common), skin • Lipophilic & distribute in: fat, liver, BM, blood, brain & kidney

  18. Organic solvents A) halogenated Hydrocarbons carbon tetrachloride (CCL4): - Acute exposure: - CNS GI -after 7-10d :↓urine output, prerenalazotemia

  19. Organic solvents Other aliphatic halogenated hydrocarbons: 1-ethylene dichloride (C2H4Cl2): --less potent than CCl4 as a renal toxicant but greater CNS toxicity 2-Chloroform (CCl3H): --more nephrotoxic than CCl4 3-Trichloroethylene (C2HCl3): -- cleaning agent 4-Tetrachloroethane (C2H2Cl4): --most toxic of halogenated hydrocarbons 5- Ethylene chlorohydrin --penetrates the skin readily and is absorbed through rubber gloves

  20. B) Nonhalogenated hydrocarbons : 1-Dioxane: less toxic than halogenated hydrocarbons 2 -Toluene: -- reversible ATN due to toluene inhalation (glue-sniffing) 3- Ethylene Glycol: --Mono ethyl ether, mono methyl , butyl ether --irritants of skin and mucous membranes, CNS depressants. 4-phenol (carbolic acid): --Local burns, dark urine

  21. ARF caused by Arsine • semiconductor industry • Primarily hemotoxic • Firs sign immediately or after a delay up to 24h: • malaise, abd cramps, nausea, vomiting • RF due to ATN secondary to hemoglobinuria • Hydration, manitol • Exchange transfusion to prevent further hemolysis

  22. Chronic kidney diseases caused by lead • Exposure: ingestion of leaded paint, battery manufacturing, mining, combustion of leaded gasoline • Absorbed by GI (adults:10% , children:50%) & lungs • Concentrated in bone (90%) & kidneys Chronic lead exposure→ ( fanconi-type syndrome) • After 5-30y : progressive tubular atrophy & interstitial fibrosis

  23. Cont,… • Mechanisms of gout : 1-↓urine clearance of uric acid 2- crystallization at low urate concentration 3- lead-induced formation of guanine crystals • Mechanisms ofHTN: • acute lead intoxication 1-↑ intracellular Ca 2-inhibition Na+,K+ ATPase 3-direct vasoconstriction 4-alteration in RAA axis

  24. Cont,… • Classic presentation of lead nephropathy: • CKD+ HTN+ gout. • CKD+ low-grade proteinuria , ( without gout or HTN ) • U/A 24 hr: 1-2 g • Ultrasonography :small, contracted kidneys • Renal biopsy :tubular atrophy, interstitial fibrosis, and minimal inflammatory infiltrates. • Electron microscopy : • intranuclearinclusion bodies usually are present in the early stages of lead exposure but often are absent after chronic exposure or after lead chelation.

  25. Cont,… Diagnosis : • Measuring blood lead level • EDTA lead mobilization test • Tibial K x-ray fluorescence correlate with bone lead

  26. Chronic kidney diseases caused by cadmium • Exposure: • Cd-sulfide in ores of zinc, lead, and copper. • nickel-cadmium batteries, pigments, glass, metal alloys, and electrical equipment. • 40% - 80% of Cd is stored in: liver, kidneys (1/3) • Cd is a contaminant of tobacco smoke. • Only 25% of ingested Cd is absorbed.

  27. Cont,… • Cd blood rises then falls because it taken by the liver. • RBC & soft tissues: Cd-metallothionein. • This complex is filtered at the glomerulus, undergoes endocytosis in the prox.T, and is later degraded in the lysosomes. • The adverse effects of Cd on the Prox.T: • Unbound Cd, that interfere with zinc-dependent enzymes.

  28. Cont,… • Target organs : kidney & lung • fanconi syndrome • Hypercalciuria with normocalcemia, hyperphosphaturia→ osteomalacia, pseudofx, nephrolithiasis • Uretral colic from calculi in 40% • Itai-itai dx : painful bone dx with pseudofx in japan

  29. Cont,… Possible causes of osteomalacia: 1- a direct effect of cd on bone 2- ↓renal tubular reabsoroption of Ca & P 3- ↑PTH & ↓ hydroxylation of vit D

  30. Cont,… Renal cadmium toxicity • low-molecular-weight proteinuria • urinary calculi • multiple tubular abnormalities • Cd urine >10 µg/g Treatment : • except removal from the exposure • treatment of osteomalacia

  31. Chronic kidney diseases caused by mercury Exp: Inhalational of Metal fume & ingestion 1- ATN 2-Nephrotic syndrome mercury exposure: • Membranous nephropathy • minimal-change disease • anti-GBM

  32. Cont,… • Clinical presentation of ATN: extrarenal manifestations Dx: history of exposure • glomerular disease such as membranous nephropathy?? • blood and urine mercury concentrations do not correlate with renal disease. • Spontaneous resolution of the proteinuria following removal from the source of mercury exposure is consistent with mercury-mediated glomerular disease.

  33. Beryllium Exposure: • manufacture of electronic tubes • fluorescent light bulbs • metal foundries Absorption: • inhalation

  34. Cont,… manifestation of berylliosis : • systemic granulomatous disease: • lungs, bone, bone marrow, liver, lymph nodes, … • kidneys: • granulomas and interstitial fibrosis. • Hypercalciuria, Hyperuricemia ,urinary tract stones.(30%) • PTH depressed,

  35. Reproductive Toxicity

  36. Reproductive Toxicity • Reproductive function • Women Who Are Pregnant • Women of Child Bearing Age • Men

  37. Male: Spermatogoniumspermatocyte spermatid mature spermatozoa (3 months)

  38. Adverse Male Reproductive Effects • Hormonal disorder • Hormonal & semen disorder • Oligospermia • Azoospermia • Asthenospermia & teratospermia • Asthenospermia & oligospermia

  39. Female: Embryonic Fetal 8w 1-2w Minor malformation Functional defects Major malformation Prenatal death

  40. Difficulty in studying reproductive toxicity in women • nature of the female cycle • relative frequency spontaneous abortions • common occurrence of birth defects in general population

  41. Adverse Female Reproductive Effects • Infertility: • Mens dis: • LBW (< 2500 gr):

  42. Birth defects: • Preterm (<37wk): • SAB (fetal loss 20 wk ):

  43. Theend

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