Proteinuria and other renal functions in Wilson's disease

Sözeri, Emine; Feist, Dietrich G.; Ruder, H.; Schärer, K

doi:10.1007/s004670050282

Cited by 44 publications

(35 citation statements)

References 25 publications

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“…In some metabolic disorders renal tubular involvement was only a transient feature noted before adequate treatment was introduced, e.g., dietary restriction in hereditary fructose intolerance or galactosaemia. In other metabolic disorders renal alterations may have been secondary to treatment, as in Wilson disease complicated by proteinuria [27]. A third group of metabolic diseases, represented by cystinosis, was dominated by an inexorable development towards ESRD.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Outcome of Paediatric Patients with Hereditary Tubular Disorders

Haffner

Weinfurth²,

Manz³

et al. 1999

Nephron

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Background: An increasing number of children with hereditary tubular disorders (HTD) reach adult life due to diagnostic and therapeutic advances which results in growing need to manage these patients by adult centres. Data on the prevalence and the late clinical problems of these patients are limited. Methods: We observed 177 paediatric patients with isolated or complex HTD between 1969 and 1994. The median age at the time of diagnosis was 3 (range 0–18) years and the median observation period 10 (range 1–43) years. The long-term outcomes with respect to renal function, bone disease, and body growth were analyzed. Results: The prevalence of HTD was 3.2% of all patients observed in our renal unit and 14% of those patients with chronic renal failure and/ or end-stage renal disease. The three most frequent disorders observed were nephropathic cystinosis (n = 34), X-linked hypophosphataemic rickets (n = 26), and idiopathic hypercalciuria (n = 17). At the last observation, 12% of the patients with isolated HTD and 30% of those with complex HTD had developed preterminal chronic renal failure; end-stage renal disease was observed in 5 and 25%, respectively (p < 0.001). Progressive disease occurred mainly in patients having cystinosis, primary hyperoxaluria, the syndrome of hypomagnesaemia/hypercalciuria, primary Fanconi syndrome, Fanconi-Bickel syndrome, and methylmalonic aciduria. Nephrocalcinosis was found in 42%, urolithiasis in 14%, bone deformities and/or fractures in 28%, and other extrarenal alterations in 29% of all patients. The median body height at last observation was 2.0 SD below the normal mean (range from –10.4 to +2.6), and the adult height was subnormal in 48% of 67 grown-up patients. Growth retardation was more severe in complex than in isolated HTD. The mortality decreased from 17% in 1969–1981 to 12% in 1982–1994. Conclusion: Although HTD are rare nephropathies, their frequently progressive course associated with extrarenal complications requires the attention of nephrologists beyond the paediatric age.

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Section: Discussionmentioning

confidence: 99%

Long-Term Outcome of Paediatric Patients with Hereditary Tubular Disorders

Haffner

Weinfurth²,

Manz³

et al. 1999

Nephron

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“…Untreated patients typically have a higher impairment in tubular function verses impairment in glomerular function [19]. Pathogenesis of proximal tubular dysfunction is likely linked to the localized accumulation of copper in the proximal tubules [9].…”

Section: Discussionmentioning

confidence: 99%

Expression in Mouse Kidney of Membrane Copper Transporters Atp7a and Atp7b

Moore¹,

Cox²

2002

Nephron

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Copper is essential for activity of many enzymes, but is toxic in excess. Several copper proteins are required for copper homeostasis. ATP7A and ATP7B are genes encoding membrane copper transporters. ATP7A, defective in Menkes disease (MNK), is expressed in many tissues involved primarily in copper uptake from dietary sources. ATP7B, defective in Wilson disease (WND), is essential for copper excretion. Although MNK patients have a copper deficiency in most tissues, copper accumulates in proximal tubules in the kidney. WND patients also have copper accumulation in the proximal tubules. In some WND patients this copper accumulation may result in tubular dysfunction, resulting in the increased excretion of low molecular weight substances (e.g. amino acids and calcium). In mouse, we have demonstrated, by in situ hybridization, the expression pattern in the kidney of mouse orthologues, Atp7a and Atp7b, and have confirmed Atp7b expression by immunohistochemistry. Both Atp7a and Atp7b are expressed in glomeruli; however, Atp7b is also seen in the kidney medulla. This suggests that glomeruli are responsible for regulating copper levels in the filtrate. In WND patients, urinary copper levels are extremely high suggesting Atp7b in the loops of Henle may have a role in copper reabsorption.

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“…A free sulphydryl group acts as the copper-chelator (7). In 1956 penicillamine was introduced as the first oral drug for treating of WD by John Walshe (3,8). Chelating drugs are used in cases where rapid reduction of high toxic copper levels is essential (9).…”

Section: Case Reportmentioning

confidence: 99%

“…Anti-copper treatment in WD should be selected carefully because D-PA has serious toxicity (11). The drug may have a nephrotoxic action in WD, although this effect has mainly been described in other disorders such as rheumatoid arthritis (3). According to Grasedyck (12), the total incidence of side effects in D-PA treatment amounts to 30-60%, but newest data established possible adverse effects in 10-25% of the patients (7,11,13,14).…”

Section: Case Reportmentioning

confidence: 99%