Uric acid metabolism in children

The renal excretion of uric acid in children differs quantitatively, and perhaps qualitatively, from that in adult humans. The younger the child, the greater the renal clearance of uric acid and the greater the excretion of uric acid expressed as mg per kg body weight. During infancy, the reduced ability to maximally concentrate the urine may protect against precipitation of uric acid crystals within the kidney. Conversely, the extremely high urinary uric concentrations places the very small infant at jeopardy during sudden increases in the filtered load of uric acid. Understanding the pharmacologic and physiologic modulators of renal uric acid clearance will allow the pediatrician to minimize the risk of uric acid nephropathy, and to understand the implications of uric acid in the serum or urine in children with fluid and electrolyte disorders. Certainly evaluation of serum and urinary uric acid concentrations is essential in any child with acute renal failure.     

Uric acid excretion in children with urolithiasis

Urinary uric acid excretion was assessed in 38 children to determine whether hyperuricuria was a risk factor in children with urolithiasis. Uric acid excretion (measured per deciliter glomerular filtration rate), and fractional excretion of uric acid were similar in 27 children with hypercalciuria and calcium oxalate urinary stones, in six children with idiopathic calcium oxalate urolithiasis, and in five with uric acid urolithiasis, of whom four were white boys and one was an Asian girl. One boy with a urate stone had cystinosis. Serum uric acid concentrations exceeded 6.0 mg/dl (360 mumol/L) in two children with hypercalciuria and in two patients with idiopathic calcium oxalate urolithiasis. None of the children with calcium urolithiasis had excessive urinary excretion of uric acid. In children with hypercalciuria, uric acid excretion did not change significantly when dietary sodium was increased from 1.0 to 5.0 gm/1.73 m2. We conclude that excessive urinary uric acid excretion is seldom an additional risk factor in children with calcium urolithiasis and that dietary sodium chloride does not have a strong influence on urinary excretion of uric acid in children with hypercalciuria.     

Purine excretion during tumor lysis in children with acute lymphocytic leukemia receiving allopurinol: relationship to acute renal failure

We measured serial urine levels of hypoxanthine, xanthine, and uric acid in 19 children with acute lymphocytic leukemia (ALL) receiving allopurinol therapy during tumor lysis; four of these children developed acute renal failure. The urinary excretion of uric acid rose moderately from 447 +/- 251 micrograms/dl glomerular filtrate before chemotherapy to 778 +/- 463 micrograms/dl glomerular filtrate during tumor lysis (P less than 0.05) whereas the urinary excretion of hypoxanthine (17.9 +/- 15 to 292 +/- 213 micrograms/dl glomerular filtrate) and xanthine (74 +/- 62 to 1091 +/- 1085 micrograms/dl glomerular filtrate) rose dramatically (P less than 0.001). The urinary excretion of uric acid, hypoxanthine, and xanthine per deciliter of filtrate was significantly higher (P less than 0.001) in those who developed acute renal failure than in those who did not, but the highest urine concentration of these purine metabolites did not differ in the two groups. In all 19 children, the highest urine concentration of uric acid and hypoxanthine during tumor lysis did not exceed the solubility limit of each in an alkaline urine specimen. In contrast, the peak urine concentration of xanthine exceeded its solubility limit in an alkaline urine specimen in 16 of 19 children. The urine sediment during the period of tumor lysis was examined by diffuse reflectance infrared spectroscopy; precipitated xanthine was found in sediment from eight of the 19 children, was significantly (P less than 0.001) associated with a urine xanthine level greater than 350 mg/dL, and occurred with equal frequency in those who did or did not develop acute renal failure. We conclude that urinary excretion of hypoxanthine and xanthine increases dramatically whereas uric acid excretion rises moderately in children undergoing tumor lysis while receiving allopurinol, that acute renal failure occurs in children with a higher purine load per deciliter of glomerular filtrate, but that factors other than tubular precipitation of purine metabolites are likely to be involved in the pathogenesis of renal failure during tumor lysis.     

An association between kidney stone composition and urinary metabolic disturbances in children

ObjectiveTo determine kidney stone composition in children and to correlate stone fractions with urinary pH and metabolic urinary risk factors.Patients and methodsWe studied 135 pediatric patients with upper urinary tract lithiasis in whom excreted or extracted stones were available for analyses. Composition of stones was analyzed. A 24-hour urine assessment included volume, pH and daily excretions of calcium, oxalate, uric acid, cystine, creatinine, phosphate, magnesium and citrate.ResultsCalcium oxalate was the major component of 73% stones, followed by struvite (13%) and calcium phosphate (9%). Uric acid was present in almost half of stones, but in rudimentary amounts. The calcium oxalate content in calculi showed a strong relationship with calciuria, and moderate association with oxaluria, magnesuria and acidification of urine. The percent content of struvite presented reverse and lower correlations with regard to the above parameters. Calcium phosphate stone proportion had low associations with urinary risk factors.ConclusionsCalciuria, oxaluria, magnesuria and low urine pH exerted the biggest influence on calcium oxalate content in pediatric renal stones. Relationships of urinary risk factors with calculi calcium phosphate content were of unclear significance. Urinary citrate excretion did not significantly correlate with kidney stone composition in children.     

Acute kidney injury after acute gastroenteritis in an infant with hereditary hypouricemia

Hereditary hypouricemia is a rare disorder characterized by extremely low serum uric acid levels caused by excessive urinary excretion due to an inherited tubular defect in urate handling. Exercise-induced acute kidney injury (AKI) is the main complication of this disorder, though AKI may also be induced by other factors. A 7-month-old boy with hereditary hypouricemia developed AKI associated with severe dehydration caused by rotavirus gastroenteritis. He also showed severe hypernatremia and metabolic acidosis and received continuous renal replacement therapy for 3 days. He showed no signs of hydronephrosis or urolithiasis. However, hypouricemia was noted when his renal function recovered (serum uric acid <0.6 mg/dl). Analysis of the urate transporter 1 gene revealed a homozygous nonsense mutation in exon 4 (c.774G > A, p.W258X). Both parents were heterozygous for the mutation and his younger brother was later determined to have severe hypouricemia (0.6 mg/dl). Conclusion: Uric acid is an essential factor for scavenging oxidative stressors. In this patient, severe dehydration may have directly caused pre-renal AKI, but susceptibility to oxidative stressors under severe dehydration, as well as exercise, may also contribute to AKI. Careful attention should be paid to dehydration, especially in young children, to avoid the development of AKI in patients with hereditary hypouricemia.     

Recurrent exercise-induced acute renal failure in renal hypouricemia

We describe a male patient with four episodes of acute renal failure after strenuous exercise occurring between the age of 14 and 25 years. He was found to have low serum uric acid (0.4mgdl⁻¹ after recovery) and high fractional excretion of uric acid. A benzbromarone, pyrazinamide test suggested that renal hypouricemia was due to defective proximal tubular reabsorption of uric acid at a pre-secretory site. A renal biopsy revealed acute tubular necrosis, a renal computer tomography scan showed patchy contrast enhancement and a treadmill exercise test induced an immediate fall in creatinine clearance. These findings suggest that the cause of acute renal failure was renal vasoconstriction rather than obstruction by uric acid crystals.     

Transient renal acidification defect during acute infantile diarrhea: the role of urinary sodium

We studied urinary acidification daily during the hospital course of 16 infants with acute gastroenteritis and metabolic acidosis. Urine pH value on admission was higher than 5.5 in 14 (87%) patients. We hypothesized that inappropriate urinary acidification was due to sodium deficiency and inadequate sodium delivery to the distal nephron. Forty-one urinary samples were collected during metabolic acidosis. The mean pH of 24 urine samples with sodium concentration less than 10 mmol/L was significantly higher than the pH of 17 samples with sodium concentration greater than 10 mmol/L (6.04 +/- 0.06 vs 5.19 +/- 0.1; p less than 0.001). The urine ratios of titratable acid to creatinine and of total acidity to creatinine were significantly higher in urine samples containing more sodium (p less than 0.02), whereas the ammonium/creatinine ratio was not. After administration of furosemide or correction of the sodium deficit, appropriate acidification was observed. We conclude that impaired urinary acidification is frequently found during metabolic acidosis in infants with acute gastroenteritis and results from a sodium deficit rather than from transient distal renal tubular acidosis.     

Hyperuricaemia in cyanotic congenital heart disease

This study examines the exacerbating factors of hyeruricaemia in patients with cyanotic congenital heart disease (CCHD). We studied 59 CCHD patients aged 1 month-30 years. The following variables were assessed: serum uric acid levels, red blood cell count, haemoglobin, hematocrit, partial oxygen pressure and arterial oxygen saturation. Uric acid excretion and renal function were also measured in ten patients with serum levels of uric acid greater than 8 mg/dl (hyperuricaemia group). Serum uric acid level correlated significantly with age and severity of polycythaemia. However, it did not correlate with partial oxygen pressure or arterial oxygen saturation. Uric acid excretion was measured in hyperuricaemia group. Urinary uric acid excretion (24 h) was within normal limits in infants but markedly lower in patients over 15 years of age. The aetiology of hyperuricaemia and decreased uric acid fractional excretion and clearance in infants appears to be secondary to diminished excretion of uric acid in concert with uric acid overproduction. Hyperuricaemia in adolescents and adults with CCHD, however, results mainly from age-related impairment of uric acid excretion.     

Higher urinary excretion of inorganic phosphate during early induction chemotherapy predicts a good prognosis in childhood acute leukemia

The rapidity of response to induction therapy is emerging as an important prognostic factor in children with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Urine inorganic phosphate (IP) and uric acid (UA) may increase in patients with acute leukemia who undergo their induction chemotherapy, owing to the breakdown of tumor cells. The crystallization of UA or calcium phosphate in renal tubules can result in acute tumor lysis syndrome (ATLS). Some reports indicate that patients who experience ATLS have a better prognosis than those who do not. We investigated the relationship between urinary IP and UA excretion and treatment outcome in children with acute leukemia. Participants included 93 patients with ALL and 31 patients with AML. Urine samples were collected and measured for the first 3 days of induction chemotherapy. Among patients with ALL, urinary IP excretion was significantly higher in patients without relapse than in those with relapse and correlated with long-term outcome. Among patients with AML, urinary IP excretion was significantly higher in patients without induction failure (IF) than those with IF. We propose that higher urinary IP excretion could be a useful prognostic marker for determining favorable outcomes in patients with acute leukemia.     

Urinary citrate excretion in idiopathic nephrolithiasis

OBJECTIVE: To determine urinary citrate excretion in children with nephrolithiasis and normal controls. DESIGN: Prospective. SETTING: Tertiary care center in New Delhi. METHODS: This study was done on 50 children, below the age of 12 years, with idiopathic urinary calculi and 150 age and weight matched controls. The children were divided into 3 groups: Group 1 (1-4 years), Group 2 (5-8 years) and Group 3 (9-12 years). Urinary citrate was estimated in a 24-hour urine sample using colorimetric method. The stones removed from these children were also analysed. RESULTS: There was a preponderance of urinary stones in males; the highest incidence being in Group 1. Excretion of citrate in 24-hour urine sample was significantly lower in patients compared to controls, for males in all age groups and for females in Group 3. However, there was no statistically significant difference in the urinary citrate value between males and females in a given age group for either controls or patients. The urinary citrate excretion increased with age in patients and controls, but the levels in patients were lower. Depending upon the constituents, four types of stones were identified, calcium phosphate, calcium oxalate, uric acid and magnesium ammonium phosphate. Nine stones had at least more than one major constituent. Hypocitraturia was detected in 43 percent cases. The incidence was 76 percent for calcium phosphate, 87 percent for calcium oxalate, 40 percent for uric acid stones and 50 percent for magnesium ammonium phosphate. CONCLUSION: This study shows that low urinary citrate is associated with urinary stones in children, especially in endemic areas, in the absence of obvious etiological factors. Urinary citrate excretion should be determined in all children with nephrolithiasis.     

Increased urinary excretion of renal N-acetyl-beta-glucosaminidase in hypercalciuria

Urinary excretion of N-acetyl-beta-glucosaminidase (NAG), a lysosomal enzyme, was examined in 33 children with hypercalciuria. Urinary NAG excretion in 13 healthy children was 5.84 +/- 9.35 nmole/hr/mg of creatinine (NAG/Cr) (mean +/- SD) compared with 35.61 +/- 42.04 nmole/hr/mg of creatinine in 23 children with renal hypercalciuria, and 28.99 +/- 13.69 nmole/hr/mg of creatinine in ten children with absorptive hypercalciuria. In children with renal hypercalciuria, NAG/Cr excretion was not statistically different between children with either urolithiasis or hematuria without calculi. In six children with renal hypercalciuria, no significant change in NAG/Cr excretion occurred after a mean duration of 25 weeks of hydrochlorothiazide therapy although urinary calcium to creatinine ratios (UCa/Cr) decreased from 0.24 +/- 0.11 to 0.16 +/- 0.11. We conclude that increased urinary calcium excretion produces renal tubular injury and that the renal injury may not be reversed by short-term alterations in urinary calcium excretion.     

The renal effects of radiocontrast administration during cardioangiography in two different groups with congenital heart disease

Renal effects of the administration of contrast media during cardiac catheterisation were compared in two groups of patients with congenital heart diseases. Group A consisted of 21 patients with cardiac malformations, characterised primarily by left ventricular valvular defects. Group B consisted of 23 patients with lesions affecting the right ventricle which are rarely associated with left heart failure, such as: Tetralogy of Fallot and Pulmonic stenosis.Patients in Group A showed a significant increment in both plasma creatinine and uric acid levels in the 24 h following heart catheterisation. This observation was significantly more prominent in the older age group (above the age of 5 years). In Group B no changes in these parameters were encountered. Plasma renin activity and fractional sodium excretion increased and decreased respectively, by a similar degree in both groups in the 24h following contrast media administration. No difference in renal tubular handling of uric acid was observed between both groups, nor did any of the patients studied demonstrate any degree of proteinuria or abnormality in the urine sediment, prior to or following heart catheterisation.We suggest that chronic pre-existing left ventricular overload should be considered a risk factor among the other known risk factors which promote the incidence of acute renal failure after contrast media administration. We also suggest that the reduction in glomerular filtration rate as evidenced in Group A by the increase in plasma creatinine and uric acid levels could be attributed to indirectly renin-mediated changes in systemic haemodynamics, probably induced by the high osmotically active contrast media. Patients with chronic pre-existing left ventricular volume overload are probably more prone to develop transient cardiac decompensation due to the transient hyper-osmolar state caused by the contrast media and which results in renal function impairment. Older children who have longstanding left ventricular overload are more prone to develop this transient cardiac decompensation, resulting in renal function impairment, than younger ones with the same cardiac lesions.Abbreviations GFR glomerular filtration rate - FeNa fractional sodium excretion - FeUa fractional uric acid excretion     

Urinary calculi in children in Western Australia: 1972–86

Abstract Records of all children presenting with urinary calculi in the period 1972–86 were reviewed in order to detail clinical features, laboratory and radiographic findings and treatment. Of a total of 85 children, 59 were Aboriginal and 26 were Caucasian. The features of urolithiasis differed between these groups. In the Aboriginal patients, calculi consisted mainly of uric acid and urates. Important clinical characteristics of this group included a young age at presentation (median = 2.1 years) and frequent presentation with failure to thrive. Calculi were commonly located in the upper urinary tract and most required surgical removal. Documented sequelae included renal scarring and hypertension. Caucasian children presented at a later age (median = 10.5 years), frequently with abdominal pain, and most calculi were associated with an underlying urological or metabolic abnormality.     

Urinary calculi in children in Western Australia: 1972-86

Records of all children presenting with urinary calculi in the period 1972-86 were reviewed in order to detail clinical features, laboratory and radiographic findings and treatment. Of a total of 85 children, 59 were Aboriginal and 26 were Caucasian. The features of urolithiasis differed between these groups. In the Aboriginal patients, calculi consisted mainly of uric acid and urates. Important clinical characteristics of this group included a young age at presentation (median = 2.1 years) and frequent presentation with failure to thrive. Calculi were commonly located in the upper urinary tract and most required surgical removal. Documented sequelae included renal scarring and hypertension. Caucasian children presented at a later age (median = 10.5 years), frequently with abdominal pain, and most calculi were associated with an underlying urological or metabolic abnormality.     

Renal oxypurine deposition in Lesch-Nyhan syndrome: sonographic evaluation

Lesch-Nyhan syndrome is a rare X-linked recessive disorder of purine metabolism associated with a virtually complete deficiency of the enzyme hypoxanthine-guanine phosphoribosyl-transferase (HPRT). The disease is characterized by hyperuricemia, self-multilation, choreoathetosis, spasticity, and mental retardation. The abnormalities of purine metabolism are present at birth and may lead to uric acid crystalluria and stone formation early in life [1]. Radiographic findings described in Lesch-Nyhan syndrome include faintly radio-opaque stones on abdominal radiographs or, if renal disease is present, small kidneys with poor function on intravenous urogram. Radiolucent stones are usually composed of uric acid; however, several cases of xanthine and hypoxanthine-containing calculi in Lesch-Nyhan patients receiving allopurinl therapy have also been described [2, 3]. Oxypurine is the collective name for the compounds hypoxanthine, xanthine, and uric acid, and all may be radiolucent. We report a case of Lesch-Nyhan syndrome with presumed renal parenchymal oxypurine deposition demonstrated readily by ultrasonography but not detected on standard radiographs or intravenous urograms.     

合并使用咪唑立宾及贝那普利诱发高尿酸血症伴急性肾损伤1例报告并文献复习

目的 探讨咪唑立宾(MZR)诱发高尿酸血症及急性肾损伤(AKI)的临床特点及发病机制.方法 回顾分析1例合并使用MZR及贝那普利诱发高尿酸血症伴AKI的IgA肾病患儿的临床资料.结果 男性患儿,13岁,确诊IgA肾病5个月,基础肾功能无异常,合并使用MZR和贝那普利后出现一过性高尿酸血症和AKI,尿酸清除率明显降低至3...     

Renal effects of cyclosporin A in children treated for idiopathic nephrotic syndrome

Little data have been published on tubular renal function during cyclosporin A treatment in children without transplants. We studied 12 young subjects (mean age 10 years) with steroid-responsive idiopathic nephrotic syndrome and with signs of steroid toxicity. After achieving remission with prednisone 60 mg/m², 8 children started cyclosporin A therapy (6 mg/kg/day) (group A) and 4 children were given cyclophosphamide 2.5 mg/kg/day (group B). The latter were considered as controls together with 10 other children with idiopathic nephrotic syndrome in complete remission and off therapy (group C). We monitored creatinine clearance and tubular handling of β₂-microglobulin, sodium, phosphorus and uric acid for one year. Cyclosporin A induced a decrease in creatinine clearance with a decrease in fractional excretion of β₂-microglobulin; sodium excretion was similar in the two treated groups and a transient decrease in fractional excretion of uric acid was seen only in patients receiving cyclosporin A. Both groups showed an increased renal threshold phosphate concentration. Our results suggest that in children, cyclosporin A therapy induces a decrease in glomerular filtration rate associated with increased reabsorption activity of proximal tubular cells.     

Uric acid metabolism in therapy of glycogen storage disease type I.

Factors which may explain lower serum uric in a new therapy of patients with glycogen storage disease (GSD) type I have been studied. [1-14C]Glycine incorporation into urine uric acid was 0.68% of the injected dose during a 6-day period of frequent high carbohydrate feedings, 0.40% with the same diet and nocturnal nasogastric feeding by Vivonex, and 0.18% in a control patient with GSD type III. Fractional renal uric acid excretion in the patient with GSD type I increased from 11.3% to 26.3% after beginning nocturnal nasogastric feeding of Vivonex. Red cell phosphoribosylpyrophosphate leve,ls were not changed by the therapy. Addition of Vivonex nocturnal feedings to frequent high carbohydrate feedings (1) decreased the accelerated de novo purine synthesis to a level still higher than control and (2) increased fractional renal uric acid excretion.     

Acute renal failure after exercise in a child with renal hypouricemia

We describe a 15 year old boy with renal hypouricemia who developed acute renal failure after a school athletics meeting, accompanied by appendicitis. During acute renal failure, the highest level of uric acid was 5.0 mg/dL, creatinine 7.9 mg/dL and urea nitrogen 58.6 mg/dL. After recovery, the serum uric acid fell to 0.9 mg/dL and the fractional excretion of uric acid (FEu_A) exceeded the normal range. The probenecid and pyrazinamide tests showed that the patient had a total defect of uric acid reabsorption. This case suggested that strenuous exercise could be responsible for acute renal failure in patients with renal hypouricemia.     

Complete deficiency of adenine phosphoribosyltransferase: a third case presenting as renal stones in a young child.

We report a third case of 2, 8-dihydroxyadenine stones in a child with a complete lack of the adenine salvage enzyme--adenine phosphoribosyltransferase (APRT). The propositus, a 20-month-old girl of consanguineous Arab parents, presented with multiple urinary tract infections and supposed 'uric acid' stones in the right renal pelvis and left ureter. Both parents and one brother were heterzygotes for the defect, in keeping with an autosomal recessive mode of inheritance. In contrast with the other purine salvage enzyme disorder of childhood with true uric acid stones (the Lesch-Nyhan syndrome), uric acid excretion was normal in all family members. As in our previous case, treatment with allopurinol, without alkali, has eliminated the urinary excretion of 2, 8-dihydroxyadenine: the stones were removed surgically. 2, 8-Dihydroxyadenine should be considered in any child thought to have uric acid stones and tests made to distinguish the two compounds.