Occupational Renal Diseases

By: Dr. Majid Golabadi

Introduction The etiology of the renal failure in a significant

percentage of patients is never fully elucidated

Diagnosis of renal disease of occupational origin is rarely considered.

The true incidence of chronic kidney disease secondary to occupational and environmental exposures is unknown.

These exposures represent potentially preventable causes of chronic kidney disease.

The kidney is especially vulnerable to occupational and environmental exposures.

Occupational and environmental toxins can be highly concentrated in the kidney

Monitoring workers for the possible renal effects of occupational exposures is very difficult: lack of sensitive and specific tests of renal injury Serial measurement of the traditional tests such as

creatinine or blood urea nitrogen (BUN) is inadequate

The currently recommended tests: possible glomerular injury (urine albumin) proximal tubule damage (retinol binding protein, N-

acetyl-β-D-­glucosaminidase, alanine amino peptidase) distal tubule injury (osmolality)

ACUTE RENAL DYSFUNCTION A large number of occupational and environmental toxins can

cause acute renal failure, usually after high-dose exposure Most common: acute tubular necrosis (ATN) Hours to days after the exposure

Manifestations: decreased urine output (oliguric range of less than 500 mL/d). renal tubular cells, granular casts, and little or no protein. Without Red blood cells, white blood cells, or casts Increases in BUN and creatinine Recovery: after 1-2 weeks, with diuresis

Occupational causes of ARF 1. heavy metals:

Significant exposure to any of the divalent metals (chromium, cadmium, mercury, and vanadium)

Welders exposed to cadmium fumes Severe exposure: bilateral cortical necrosis

2. Organic solvents Halogenated hydrocarbons Nonhalogenated hydrocarbons

Halogenated hydrocarbons

Carbon tetrachloride (CCl4)Acute abdomen, 7-10 days, prerenal azotemia

Ethylene dichloride (C2H4CI2) Chloroform (CCI3H) TetrachloroethaneThe most toxic Vinylidene chloride

Nonhalogenated hydrocarbons

Dioxane acute abdomen Toluene Glu sniffing, metabolic acidosis Alkyl derivatives of ethylene glycol Phenol Local burns, Albuminuria, RBC, hypothermia

and convulsion, carboluria

Nonhalogenated hydrocarbons PentachlorophenolSkin, hypermetabolic state, hyperpyrexia Dinitriphenols Fatal hyperpyrexia

ARF caused by unidentified pesticides

Reduction in GFR Tubular reabsorption of phosphate organophosphate

Occupational causes of ARF Arsine (AsH3) is a heavy gas and is the

most nephrotoxic form of arsenic. Exposures: semiconductor industry a potent hemolytic agent Renal failure due to hemoglobinuria.

elemental yellow phosphorus: acute hepatic and acute renal necrosis Chronic exposure: proteinuria

Balkan-Endemic Nephropathy

Interstitial nephritis Aristolochic acid Papillary transitional cell cancer

Analgesic nephropathy Renal dysfunction as a consequence of NSAIDs

and cyclooxygenase inhibitors three dif­ferent forms:

hemodynamic renal failure (loss of prostaglandin-mediated afferent arteriolar vasodilation)

acute renal failure secondary to acute interstitial nephritis (accompanied by nephrotic range proteinuria)

Both forms: reversible after discontinuation of the offending drug

papillary necrosis (not reversible): occurs after many years of high doses of NSAIDs.

It is controversial whether chronic acetaminophen use causes papillary necrosis.

CHRONIC KIDNEY DISEASE

Most common causes:

Lead

Cadmium

Mercury

Silica

Organic solvents

Chronic renal dysfunction

Interstitial tubular nephritis

1-Heavy metals• (lead, cadmium)

2-Pesticides

Nephrotic syndrome

1-Organic solvents 2-Silicosis 3-Mercury

Lead Occupations:

battery-making, smelting, painting, glazing, mining

Accumulates in the body (mainly in bones)

The classic presentation: history of hypertension and gout 1+ to 2+ proteinuria without cells or cellular casts or

normal 24h urine collection: nonnephrotic range proteinuria renal ultrasonography: small, contracted kidneys. Renal biopsy: nonspecific tubular atrophy, interstitial

fibrosis, and minimal inflammatory infiltrates Inclusion body

Diagnosis: documenting significant lead exposure Serum lead levels are not useful unless

elevated, because low serum levels do not exclude chronic lead exposure.

Treatment: Continued EDTA injections thrice weekly, with the

goal of normalizing the urinary lead chelate. The oral lead chelator DMSA is currently being

studied

Cadmium Occupations: welding, battery-making, smelting,

mining, soldering, pigment-producing, plating

accumulates in the body having a biological half-life in humans in excess of 10 years (40% to 80% in the liver and kidneys)

Fanconi syndrome, Hypercalciuria with normocalcemia, hyperphosphaturia, and distal renal tubular acidosis all contribute to the osteomalacia, pseudofractures, and nephrolithiasis

PTH

Mercury Occupations: medical equipment, environmental

exposure

accumulates in the proximal tubule

acute tubular necrosis and nephrotic syndrome

Membranous nephropathy, minimal change disease,

Treatment: removal from exposure and chelation with British antilewisite (dimercaprol BAL).

Beryllium­

Granulomas, interstitial fibrosis Hypercalciuria, renal stone PTH hyperuricemia

Silica Silicosis is a form of pneumoconiosis

associated with pulmonary exposure to silica.

Heavy exposure: generalized systemic

disease

Glomerulonephritis with immune mechanism

Organic solvents Solvent exposure may occur in many

industries where there is use of paints, degreasers, and fuels, including the petrochemical and aerospace industries.

antiglomerular basement membrane anti­body-mediated glomerulonephritis