What is the association between heavy metals and chronic tubulointerstitial nephritis?
Prolonged environmental or occupational exposure to cadmium may lead to chronic tubulointerstitial nephritis and eventual progression to kidney failure. Proximal tubular dysfunction, presenting as Fanconi syndrome, characterized by glycosuria, aminoaciduria, and tubular proteinuria, is common.
Increased urinary cadmium excretion is characteristic. Currently, the treatment for cadmium nephrotoxicity is primarily supportive.
Similar to cadmium, the proximal tubule cells tend to be the site of accumulation for lead, thereby leading to a Fanconi-type picture. Chronic tubulointerstitial nephritis secondary to lead exposure for several years is characterized histopathologically by progressive tubular atrophy and widespread fibrosis.
Lead nephropathy also reduces urinary excretion of uric acid, thereby leading to hyperuricemia and gout. This syndrome, called “saturnine gout,” gained prominence with increased ingestion of moonshine.
The diagnosis of lead nephropathy is established by increased urinary excretion of chelated lead (i.e., after the administration of ethylenediamine tetraacetic acid [EDTA]). Cumulative body stores of lead are estimated by doing an EDTA mobilization test or by performing an x-ray fluorescence, which determines bone lead content. In the EDTA mobilization test, 2 g of EDTA are administered either by the intravenous or intramuscular route, and then patients collect a 24-hour urine for lead. Urinary lead greater than 0.6 g/day is considered abnormal. One major limitation of the EDTA mobilization test is that it cannot mobilize lead deposits in bone.
Lead decreases the enzymatic activity of erythrocyte delta-aminolevulinic acid dehydratase (ALAD). Thus, peripheral blood ALAD is a good biomarker for lead toxicity. Since uremia can also decrease ALAD activity, reduced levels of ALAD compared with levels of ALAD “restored” by the addition of dithiothreitol may be even more efficient in detecting increased body lead burden in patients with chronic kidney failure.
It is important to note that serum levels of lead, although elevated during acute exposure, are not very helpful in the chronically exposed. The explanation for this is that, during acute exposure, lead is concentrated in the RBCs, which later die and the lead then moves to the bones and other tissues. A kidney biopsy shows nonspecific findings seen in chronic tubulointerstitial nephritis.
The treatment of lead nephropathy is EDTA chelation therapy or oral succimer, which has been shown to slow the progression of CKD.
