Renal Lesions in Wilson's Disease

Proteinuria and other renal functions in Wilson's disease

“…Some authors described hematuria [6] and a mild reduction in GFR and renal plasma flow which, similar to the tubular dysfunction, was usually reversible after treatment with D-penicillamine [4,6,22]. Early studies had failed to show significant pathoanatomical changes in kidney biopsies, but Wolff [23] described five autopsy cases with tubular necrosis and degeneration.…”

“…Structural alterations of mitochondria found in proximal tubular cells of patients with WD [26] indicate a disturbance of renal energy metabolism. The nephrotoxic action of copper was also demonstrated in mice and rats where it led to necrosis of proximal tubules and other renal lesions [23,24,27,28].…”

Copper-related diseases: From chemistry to molecular pathology

“…In Sardinia, an Italian island of the Mediterranean sea, WD reaches a higher frequency, with an approximate incidence of about 1:7000 live births [205]. Pathological changes in affected individuals are mainly due to accumulation of copper excess in the liver [13], in the brain [14], and in kidney [206]. Copper concentration in the liver of affected patients normally exceeds 250 mg/kg d.t.…”

“…A mutation in the WD gene may reduce the functionality of ATP7B, leading to a block in copper excretion into the bile and therefore to hepatic copper accumulation [11], chronic hepatitis [12], and cirrhosis [13]. As a consequence, copper serum levels may rise, leading to copper accumulation in the central nervous system [14], in the cornea [15], in the kidney [16,17], and in other organs [18,19]. The loss of functional ATP7B protein in the Golgi apparatus may cause failure in the incorporation of copper atoms in the apoceruloplasmin, resulting in the decreased ceruloplasmin blood levels found in the majority of WD patients.…”

Nephrotic syndrome in the course of treatment of Wilson's disease with DL-penicillamine.

“…The experimental intraperitoneal injection of copper solution into mice (Vogel, 1960) or rats (Wolff, 1960) showed that copper might cause toxic kidney damage. In these experiments, degeneration and sloughing of epithelium were demonstrated in the proximal convoluted tubules in which copper granules had accumulated.…”