Copper and Zinc Metabolism in Aminonucleoside-Induced Nephrotic Syndrome

Abstract

Copper (Cu) and zinc (Zn) were measured in urine, serum and tissues from rats with nephrotic syndrome (NS) induced with a single subcutaneous dose of puromycin aminonucleoside (PAN; 15 mg/l00 g BW). Control animals were pair-fed. Urine was collected daily, and the rats were sacrificed on day 10. PAN-nephrotic rats had proteinuria (days 3-10), high urinary Cu (days 1,2,4-10) and Zn (days 3-10) excretion. On day 10, nephrotic rats had: (a) albuminuria, hypoalbuminemia, hypoproteinemia, high urine and low serum levels of ceruloplasmin; (b) low Cu and Zn serum levels; (c) high clearance and fractional excretion of Cu and Zn, and (d) low kidney and liver Cu content and essentially normal tissue Zn levels. The alterations in Cu metabolism were more intense than those in Zn metabolism. Urine Cu and Zn showed a positive correlation with urine total protein on days 3-10 which suggests that high urinary excretion of Cu and Zn may be due to the excretion of its carrier proteins. In conclusion, these rats did not show a typical Zn deficiency but a clear decrease in Cu in the liver and kidney.

Trace Elements in Children Suffering from Idiopathic Nephrotic Syndrome

“…Additionally, we found that plasma zinc level was lower in the NS group in active and remission phase, which is in good agreement with the results published by Reimold [16] and Perrone et al [7], but not with those of Mishra et al [9], who observed no difference between NS and control groups in terms of plasma zinc level. Furthermore, in an experimental study, low serum v and high urinary zinc excretion were observed in nephrotic rats [17]. There are studies reporting an impaired oxidant-antioxidant balance in children with NS [8,9,18].…”

Nephrotic Syndrome and End-stage Kidney Disease Accompanied by Bicytopenia due to Copper Deficiency

“…It has been reported that urinary copper excretion is significantly correlated with urinary protein excretion in aminonucleoside-induced nephrotic rats (15) and patients with NS (16)(17)(18). However, except for one case of severe proteinuria (33 g/L) due to congenital NS (19), no cases of severe copper and Cp depletion causing severe anemia have been previously reported in the setting of human NS, as the rate of copper excretion via urinary nephrotic excretion [1.0 to 4.0 μmol (15,16)] is less than that of physiological absorption via the small intestine [0.5 to 1.5 mg (7.9 to 23.6 μmol) per day (4)].…”

“…However, except for one case of severe proteinuria (33 g/L) due to congenital NS (19), no cases of severe copper and Cp depletion causing severe anemia have been previously reported in the setting of human NS, as the rate of copper excretion via urinary nephrotic excretion [1.0 to 4.0 μmol (15,16)] is less than that of physiological absorption via the small intestine [0.5 to 1.5 mg (7.9 to 23.6 μmol) per day (4)]. It is likely that, in our patient, the copper deficiency-associated bicytopenia was caused primarily by the lack of copper in the long-term TPN therapy and not by the excretion of copper via urinary nephrotic excretion.…”

Nutritional and Non-nutritional Management of the Nephrotic Syndrome

“…While the urinary loss of this 151 kDa protein may cause a decrease in blood copper [6,8], it results in no clinically recognized manifestations [176]. The most important zinc-binding protein is albumin, with the greatest losses occurring in the nephrotic syndrome.…”