Kidney disease has not been considered a frequent complication in Down syndrome (DS) patients; a variety of urological abnormalities and glomerulopathies have been reported in this population, and some DS patients develop chronic renal failure (CRF). The aim of this study was to improve the understanding of renal disease in patients with DS, focusing on the incidence and range of kidney and urological abnormalities in a population of DS patients. A cross-sectional study was carried out in DS patients referred from a pediatric genetics unit of a tertiary care center. Medical records were reviewed. A 24-h urine specimen and a blood sample were obtained. Fractional excretion of sodium and potassium, tubular reabsorption of phosphate, urinary excretion of calcium, magnesium, uric acid, creatinine clearance and proteinuria were determined. Ultrasound was performed to evaluate the kidneys and the urinary tract. Laboratory data were reviewed for any possible renal disorder. Sixty-nine patients, aged 12 months to 24 years, were recruited. Pathological findings included three cases of voiding disturbances and a case of hypertension in a 7-year old girl. Eight patients (11.6%) had hyperuricemia without gout. Eighteen patients (24.2%) had hyperuricosuria. Urinalysis revealed three cases of mild proteinuria and two patients with microscopic hematuria. Minor radiological abnormalities were found in five patients (7.3%). Three patients (4.5%) had CRF. Renal disease in patients with DS is not as rare as previously thought, although the majority of findings are of minor relevance. According to the variety of pathologies, and in order to detect early irreversible renal injury, it seems quite reasonable to perform regular monitoring of renal function in these patients.

Cyclosporine is an alternative therpy in nephrotic children having proteinuria unresponsive to conventional treatment. The effects of sustained administration of cyclosporine in this group of patients are scarcely known. We studied 10 male children, aged from 2 years 10 months to 11 years 3 months, treated with cyclosporine over a period longer than 12 months ((X) over bar +/- SEM: 26 +/- 3 months) because of nephrotic syndrome either steroid-resistant or dependent on high doses of esteroids (4 minimal change nephropathies and 6 IgM glomerulonephritis). Ciclosporine was started at a dose of 4-5 mg/kg/day and dosages adjusted to maintain blood levels between 70 and 120 ng/ml. All children had received treatment with prednisone and cyclophosphamide. Cyclosporine therapy significantly (p < 0,001) increased the percentage of proteinuria-free time from 20.1 +/- 1.0 to 73.7 +/- 0.9%. The beneficial action on proteinuria was not associated with important undesirable clinical analytical side effects. Inverse correlation between albuminemia and hypercholesterolemia remained unchanged. Children grew better under cyclosporine treatment as shown by an increase (p < 0.01) in height Z score irom -0.29 +/- 0.34 to +0.06 +/- 0.35. This improvement was probably related to the lower cumulative prednisone dose received by the children while they were on cyclosporin (504 +/- 80 vs 199 +/- 30 mg/patient/month). Thus, sustained treatment with cyclosporin resulted in a better control of proteinuria and acceleration of growth without important toxocity, either clinical or on laboratory tests.

The present study was designed in an attempt to better define the pattern of growth in five-sixths-nephrectomized rats. Male Sprague-Dawley rats underwent two-stage (days 0 and 7) five-sixths nephrectomy (NX, n = 16) or sham surgery (SHAM, n = 9). At the time of sacrifice (day 21), renal failure (CRF) of NX rats was confirmed by elevated (p < or = 0.0001) serum concentrations (X +/- SEM) of urea nitrogen (SUN) (56 +/- 5 vs. 20 +/- 1 mg/dl) and creatinine (0.7 +/- 0.04 vs. 0.4 +/- 0.02 mg/dl) and reduced SUN (0.13 +/- 0.02 vs. 0.44 +/- 0.05 ml/min/100 g) and creatinine clearances (0.23 +/- 0.02 vs. 0.58 +/- 0.05 ml/min/100 g). As shown by lower cumulative gains of weight (41 +/- 6 vs. 74 +/- 4 g) and length (5.0 +/- 0.4 vs. 6.8 +/- 0.3 cm), NX rats grew subnormally. Detailed analysis of growth data revealed: (1) In spite of being identically matched in weight and length on day 0, at day 7, NX rats already weighed less than SHAM animals (147.1 +/- 2.3 vs. 153.4 +/- 1.9 g, p = 0.03). (2) From day 7 on, daily gain of weight was lower in the NX group only on days 8 (-6.08 +/- 0.52 vs. -1.60 +/- 0.69 g/100 g body weight) and 9 (-0.41 +/- 1.73 vs. 5.18 +/- 0.63 g/100 g body weight). (3) Following the early post-second-nephrectomy period, two subgroups of NX rats were clearly differentiated according to whether or not their daily growth rate was lower than that of SHAM animals. Maintained subnormal growth rate was observed in rats with severe CRF (SUN 73 +/- 5 mg/dl, range 54-90) but not in rats having milder uremia (42 +/- 3 mg/dl, range 31-51). Thus, growth in five-sixths-nephrectomized rats should be reported based on daily weight increments (g/100 g body weight). Subnormal growth can be attributed to CRF provided SUN is at least 3 times as high as normal while growth impairment of rats with less marked reduction of renal function is likely related to transient acute renal failure and postsurgical catabolic state.

Daily nitrogen intake was estimated in 19 children, aged (mean +/- SD) 9.9 +/- 5.0 (range: 1-19) years with chronic renal insufficiency (creatinine clearance 47.1 +/- 19.3 ml/min/1.73 m2, range: 11-75) by 31 three-day prospective dietary records (NIDR) and simultaneous 24-hour urine urea excretion (NIUE). Daily nitrogen intake was 11.05 +/- 3.9 g by NIDR and 8.52 +/- 3.3 g by NIUE, and a significant correlation (r = 0.61; p = 0.0003) existed between both methods of measurement. However, the difference in nitrogen intake estimated from dietary records and from 24-hour urine collection (NIDR-NIUE) was 2.5 +/- 3.3 g, greater than the mean estimated nitrogen intake calculated from both methods, (NIDR + NIUE)/2, 95% limits of agreement being +9.1 to -4.1. Thus, NIDR and NIUE values show a good correlation in children with chronic renal insufficiency, although both methods may provide quite a different estimation in a given child.

BACKGROUND:The role of the kidney in the development of essential hypertension is subject of debate.METHODS:We compared the renin, kallikrein and prostaglandin renal systems in two groups of normotensive boys, aged 7-16 years, with different degrees of risk for future hypertension: 27 had parents with essential hypertension and 12 had normotensive parents. Supine, standing and post-exercise plasma renin activity as well as levels of urinary kallikrein and prostaglandin E2 before and after exercise were measured.RESULTS:The ratio of post-exercise plasma renin activity (ng/ml/h) to 24 h urinary sodium excretion (mEq/kg/day) was lower in children with hypertensive parents (mean +/- SEM 1.86 +/- 0.24 compared with 3.62 +/- 0.94, P = 0.02). The boys with hypertensive parents had a lower ratio of urinary kallikrein to creatinine before (0.70 +/- 0.13 compared with 1.54 +/- 0.36, P = 0.01) and after exercise (0.80 +/- 0.13 compared with 1.35 +/- 0.23, P = 0.03). The ratio of urinary prostaglandin E2 to creatinine levels did not differ between the groups before or after exercise.CONCLUSION:The plasma renin activity response to exercise and urinary kallikrein excretion were decreased in boys at increased risk of future essential hypertension. These early abnormalities in the renin and kallikrein renal systems may be associated with the development of essential hypertension.

Nutritional status was evaluated in 15 children (11 males) with moderate chronic renal failure (CRF). Two 3-day prospective dietary records, anthropometric measures and biochemical determinations were performed 3 months apart. Energy, protein, carbohydrate, fat, polyunsaturated, monounsaturated and saturated fatty acid intakes, expressed as percentages of international recommendations, were 87±14, 223±42, 73±12, 110±27, 55±31, 129±51 and 111±26%, respectively. The relative distribution of calories was 15±2% from proteins, 48±5% from carbohydrates and 37±5% from lipids. Anthropometric indices, expressed as standard deviation score, were: weight −0.50±0.8, height −0.94±1.3, growth velocity −0.61±1.8, triceps skinfold thickness −0.30±0.6, subscapular skinfold thickness −0.19±0.8, mid-arm muscle circumference 0.38±0.3 and body mass index −0.22±1.0. Serum concentrations of albumin, total protein, transferrin, IgG, IgA, IgM, C3 and C4 and blood lymphocyte counts were within normal limits. The mean serum insulin-like growth factor-I concentration, expressed as standard deviation score, as 0.74±1.5. No anthropometric or biochemical signs of malnutrition were found in children with moderate CRF. However, their dietary intake of calories and carbohydrates was low and the protein and saturated fatty acid intake excessively high.

The optimal treatment, surgical or conservative, for multicystic dysplastic kidney (MDK) is still undetermined. We analyzed prospectively the evolution of 12 children with MDK who were managed conservatively. After a mean follow-up of 32 months, the only complication found was an episode of urinary tract infection in 3 patients. Complete involution of MDK was observed in 9 patients (75%), the mean period for sonographical disappearance being 16 months. Infants with MDK should be closely monitored and nephrectomy performed when MDK compresses neighbor organs or hypertension develops. There is no agreement on the best therapeutic approach in patients in whom MDK involution has not occurred after a prudential waiting time still not determined.

The syndrome of renal tubular acidosis (RTA) and nerve deafness is a distinct nosological entity that is inherited as an autosomal recessive trait. We studied a pair of dizygotic twin brothers both with nerve deafness but only one with RTA. Distal RTA was diagnosed in twin A because of inappropriately high urinary pH (6.9) and low net acid excretion (40.0 μEq/min per 1.73 m2) in the presence of hyperchloraemic metablic acidosis, and fractional bicarbonate excretion of 1.6% at a normal serum bicarbonate concentration. The urine minus bloodPCO2 differences (U-BPCO2) during a neutral sodium phosphate load and in alkaline urine induced by bicarbonate supplementation were: 11 and 0 mm Hg, respectively. Twin A developed nephrocalcinosis and, after a 9.5-year follow-up period, was 5.3 cm taller than his brother. Twin B remained asymptomatic. Periodic determinations of blood pH and serum bicarbonate were normal and urine pH decreased to 4.6 in the face of ammonium chloride-induced metabolic acidosis. The U-BPCO2 assessed in alkaline urine was 33.5 mm Hg. Audiograms demonstrated bilateral nerve deafness in both brothers. The presence of deafness without RTA has not been previously reported in this syndrome. This report also shows that a primary distal acidification defect is responsible for the RTA observed in this syndrome.

A careful, thorough history is probably the most important step in the workup of a child with a renal disorder. This includes careful monitoring as to the color, volume, and frequency of the urine output, as well as any pain on voiding or difficulty with initiating or stopping micturition. The presence of flank pain or loin pain radiating to the groin may indicate a renal disorder, as can a history of edema, either peripheral, especially periorbital edema, or pulmonary. Less obvious clues are the symptoms of uremia, which include persistent nausea and/or vomiting, anorexia, lassitude, changes in mental status, headache, and even seizures.

The influence of chronic renal failure (CRF) on growth hormone (GH) and insulin-like growth factor I (IGF-I) metabolisms is not well understood. Clinical studies on GH secretion in CRF have yielded conflicting results. In vitro, pituitary GH secretion has been shown to be unimpaired in moderate uremia. CRF reduces binding of GH to liver as a result of decreased number of GH receptors. CRF induces elevation of serum GH concentrations and does not modify the circulating values of IGF-I. However, the somatomedin bioactivity of uremic serum is depressed, and unsaturated low-molecular-weight IGF-I-binding proteins have been suggested to act as inhibitory factors of IGF-I action. Circulating GH and IGF-I do not necessarily reflect the state of GH and IGF-I in tissues, and further investigations on the effect of CRF on GH and IGF-I metabolisms at the growth plate level are clearly required.

Renal cell carcinoma is extremely infrequent in children. We report a case of renal cell carcinoma in a 13-year-old male. Presenting manifestations were loin pain, fever, and weight loss. A palpable abdominal mass was found. Imaging studies showed a solid mass into the right kidney. Nephrectomy was performed and pathological examination demonstrated characteristic findings of renal cell carcinoma. This report emphasizes that renal cell carcinoma should be included in the differential diagnosis of renal masses in children.