Aminoaciduria lead nephropathy

Renal Effects. The characteristics of early or acute lead-induced nephropathy in humans include nuclear inclusion bodies, mitochondrial changes, and cytomegaly of the proximal tubular epithelial cells dysfunction of the proximal tubules (Fanconi s syndrome) manifested as aminoaciduria, glucosuria, and phosphaturia with hypophosphatemia and increased sodium and decreased uric acid excretion. These effects appear to be reversible. Characteristics of chronic lead nephropathy include progressive interstitial fibrosis, dilation of tubules and atrophy or hyperplasia of the tubular epithelial cells, and few or no nuclear inclusion bodies, reduction in glomerular filtration rate, and azotemia. These effects are irreversible. The acute form is reported in lead-intoxicated children, whose primary exposure is via the oral route, and sometimes in lead workers. The chronic form is reported mainly in lead workers, whose primary exposure is via inhalation. Animal studies provide evidence of nephropathy similar to that which occurs in humans, particularly the acute form (see Section 2.2.3.2). 

Clinically, lead nephropathy is seen as either reversible tubular dysfunction or as an irreversible interstitial nephropathy. Tubular toxicity occurs most commonly in children following acute exposure and is characterized by glucosuria, phosphaturia, aminoaciduria, and occasionally proteinuria. One unique morphological feature of lead exposure is the formation of nuclear inclusion bodies within renal tubular cells. These bodies are complexes between lead... 

Early kidney disease is difficult to detect. The urinalysis is normal in early lead nephropathy and the blood urea nitrogen and serum creatinine increase only when two-thirds of kidney function is lost. Measurement of creatinine clearance can often detect earlier disease as can other methods of measurement of glomerular filtration rate. An abnormal Ca-EDTA mobilization test has been used to differentiate between lead-induced and other nephropathies, but this procedure is not widely accepted. A form of Fanconi syndrome with aminoaciduria, glycosuria, and hyperphosphaturia indicating severe injury to the proximal renal tubules is occasionally seen in children. 

Lead-induced nephropathy was first reported more than a century ago. However, the condition remains to be clearly defined. A study from Queensland, Australia, described 34 patients with a chronic nephropathy who had suffered from lead palsy in childhood following exposure to lead paints (Nye, 1933). Interstitial fibrosis, tubular atrophy and dilation have been observed in workers with heavy long-term exposure to lead. Renal tubular dysfunction characterized by glycosuria and aminoaciduria has been observed in lead-exposed children (Chisholm and Leahy, 1962). Lead exposure should be considered in the differential diagnosis of glycosuria occurring in childhood. 

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