Mortality was low in children with Shiga toxin-producing Escherichia coli hemolytic uremic syndrome, being central nervous system involvement the main cause of death. The best mortality predictors found were central nervous system involvement, hemoglobin, and sodium concentration. Hyponatremia may be a new Shiga toxin-producing Escherichia coli hemolytic uremic syndrome mortality predictor.

Renal disease is the most important long-term complication of hemolytic-uremic syndrome (HUS). A comparative study of renal function was carried out in two groups of patients. Group 1 included 19 children followed for a median of 11 years, 1960-1980, with a low-sodium diet, antihypertensive drugs, and a restricted protein intake in the end stage of renal disease. Group 2 included 26 children treated for a median of 9 years, 1988-2002, on a low-sodium diet, early restriction of protein intake according to recommendations, and angiotensin converting enzyme inhibitors (ACEi). Long-term renal function was assessed by the inverse of the plasma creatinine concentration (1/[Cr]) over time. Linear regression lines were fitted to individual values of 1/[Cr] for each child. Regression coefficients of children in group 1 were all negative, ranging from -0.031 to -0.00043; 7 were significantly different from zero, indicating a linear fall in renal function over time. In contrast, children from group 2 had 11 negative slopes (only 1 significant) and 15 positive slopes, ranging from 0.17893 to -0.3899. Fisher's exact test showed that group 1 had significantly more children with negative slopes than group 2. This comparatively better long-term outcome of renal function in children under contemporary treatment was probably associated with early restriction of protein and use of ACEi.

Our results suggest that adding losartan to persisting proteinuric D + HUS children already on enalapril is safe and reduces proteinuria more effectively. Whereas this effect is associated with long-term kidney protection, it should be determined by prospective controlled studies.

Proteinuria is the main indicator of renal disease progression in many chronic conditions. There is currently little information available on the efficacy, safety, and individual tolerance of patients with post-diarrheal hemolytic uremic syndrome (D+ HUS) nephropathy to therapies involving diet, enalapril, or losartan. A multicenter, double-blind, randomized controlled trail was conducted to evaluate the effect of a normosodic-normoproteic diet (Phase I) and the effect of normosodic-normoproteic diet plus enalapril (0.18-0.27 mg/kg/day) or losartan (0.89-1.34 mg/kg/day) (Phase II) on children with D+ HUS, normal renal function, and persistent, mild (5.1-49.9 mg/kg/day) proteinuria. Dietary intervention reduced the mean protein intake from 3.4 to 2.2 mg/kg/day. Of 137 children, proteinuria normalized in 91 (66.4 %) within 23-45 days; the remaining 46 patients were randomized to diet plus placebo (group 1, n = 16), plus losartan (group 2, n = 16), or enalapril (group 3, n = 14). In groups 1, 2, and 3, proteinuria was reduced by 30.0, 82.0, and 66.3%, respectively, and normalized in six (37.5%), three (81.3%), and 11 (78.6%) patients, respectively (χ(2)= 8.9, p = 0.015). These results suggest that: (1) a normosodic-normoproteic diet can normalize proteinuria in the majority of children with D+ HUS with mild sequelae, (2) the addition of enalapril or losartan to such dietary restrictions of protein further reduces proteinuria, and (3) these therapeutic interventions are safe and well tolerated. Whether these short-term effects can be extended to the long-term remains to be demonstrated.

Sirs, Renal tubule disorders have been reported in Menkes' disease (MNK) [1][2][3][4][5]. Among others, hypercalciuria has been observed [3,5]. We report the details of a child with MNK and nephrocalcinosis due to hypercalciuria.A 35-day-old boy was referred to our hospital with a diagnosis of MNK. He was the third child of an unrelated couple, and a previous son had died at 11 months of age from the same disease. The diagnosis of MNK was made on the basis of the following findings: hypotonia, seizures, sparse hypopigmented hair, low serum levels of copper (Cu) (30 μg/dl, normal range 70-140 μg/dl) and caeruloplasmin (7 mg/dl, normal range 15-54 mg/dl). Light microscopy of his hair showed pili torti. Subcutaneous Cu histidine therapy (350 μg/day) was initiated. With this treatment, Cu and caeruloplasmin levels were maintained within the normal ranges.When he was 7 months of age renal ultrasonography revealed multiple bladder diverticula and marked bilateral medullary hyperechogenicity suggestive of nephrocalcinosis. He had no history of calcium or vitamin D supplementation or other drugs linked to hypercalciuria. Malabsorption was ruled out.Because of the nephrocalcinosis, his renal function was investigated. On initial evaluation his blood laboratory parameters were as follows: urea 32 mg/dl, creatinine 0.46 mg/dl, sodium (Na) 140 mEq/l, potassium (K) 4.2 mEq/l, chloride (Cl) 105 mEq/l, pH 7.34, bicarbonate 22 mEq/l, calcium (Ca) 9.3 mg/dl, phosphate (P) 4.5 mg/dl, alkaline phosphatase 440 IU/l, intact parathyroid hormone (iPTH) 26 pg/ml, magnesium (Mg) 1.95 mg/dl, uric acid 1.6 mg/dl. Urinary parameters were: urine flow 4.1 ml/kg body weight per hour, specific gravity 1.015 g/l, calciuria 8.2 mg/kg per day (normal < 4 mg/kg per day), magnesiuria 1.9 mg/kg per day (normal < 2.5 mg/kg per day), uricosuria 15.5 mg/kg per day (normal < 18 mg/kg per day), tubular reabsorption of phosphate (TRP) 94.4% (normal 80-95%), proteinuria 12 mg/kg per day (normal <5 mg/kg per day), microalbumin 8 μg/min (normal <20 μg/min), β-2 microglobulin 1,575 μg/l (normal <137 μg/l), uroproteinogram tubular pattern, citraturia 267 mg/day (normal 140-900 mg/day), oxaluria 22.2 mg/day (normal 13-38 mg/day), and results for glucose and aminoaciduria were negative. Blood pressure was always within the normal ranges.Restriction of sodium intake up to 1 g/day, hydrochlorothiazide 2 mg/kg per day and potassium citrate 2 mEq K/kg per day were indicated to reduce the hypercalciuria. During 4 years of follow-up, his urinary β2-microglobulin levels rose to 8,040 μg/l and microalbumin to 188 μg/min; hypercalciuria persisted, despite treatment, and creatinine clearance decreased from 81 ml/min per 1.73 m 2 body surface area to 58.7 ml/min per 1.73 m 2 body surface area.An excessive amount of Cu accumulates in the proximal convoluted tubular cells of patients with MNK, and increased Cu was found in the form of Cu-metallothionein (Cu-MT) [2,3]. Metallothioneins are low molecular weight heavy metal-binding proteins, and Cu-MT overproduction is thought t...