Hypercalciuria and urolithiasis in a case of Costello syndrome

 Costello syndrome is characterized by postnatal growth deficiency, mental retardation, curly hair, coarse characteristic face, and loose skin of hands and feet. Patients with this syndrome have a high incidence of cardiac involvement, including arrhythmia, atrial septal defect, and hypertrophic cardiomyopathy. We report a 16-year-old adolescent female with Costello syndrome who presents with hypercalciuria and urolithiasis. Received: 15 October 1997 / Revised: 31 March 1998 / Accepted: 31 March 1998     

Clinical presentation and natural course of idiopathic hypercalciuria in children

Idiopathic hypercalciuria (IHC) has been reported mainly in children with hematuria in the 1980s and early 1990s, when renal sonography was just becoming routine. The presence of microcalculi, i.e., of hyperechogenic spots <3 mm in diameter in renal calyces, was not taken into account in those studies. We attempted to outline clinical presentation and natural course of IHC not only in children with hematuria, but also in those with dysuria and/or recurrent abdominal/flank pain and a family history of nephrolithiasis, taking into account the finding of microcalculi. We analyzed retrospectively the data at diagnosis from 74 consecutive children aged 2.4–18 years (mean 8.6) with IHC (calciuria 4.1–15.1 mg kg^–1 24 h^–1, mean 6.1) and the outcome of 30 of them who were followed ≥1 years (mean 3.2) with no specific therapy. At diagnosis, 38 patients (51%) had no hematuria, 42 (57%) had microcalculi and four (5%) had calculi. Of the patients with normal urinalysis, 71% had microcalculi or stones. The subjects with microcalculi and those with stones were significantly older than those without microcalculi and stones (P=0.004 and 0.007). A normal urinalysis at our evaluation and a history of abdominal/flank pain were significantly more frequent in patients with microcalculi than in those without (P=0.02 and 0.0001, respectively). During the follow-up, four of 30 patients formed stones 1–3 years after first diagnosis of IHC. More than half of children with IHC have microcalculi. The risk of formation of microcalculi or stones increases with age. The lack of hematuria does not exclude the presence of microcalculi or calculi. Hypercalciuria has to be suspected in children with dysuria and/or recurrent abdominal/ flank pain and a family history of nephrolithiasis, even when they have no hematuria. Received: 13 December 1999 / Revised: 26 April 2000 / Accepted: 19 May 2000     

The metabolic etiology of urolithiasis in Turkish children

Pediatric urolithiasis is an endemic disease, especially in certain developing regions of the world, such as the Far East, and to a certain extent the Middle East and Turkey. The aim of the study is to determine the metabolic etiology and the prevalence of formation of urinary calculi in Turkish pediatric patients with urolithiasis. Seventy-two pediatric patients diagnosed as having urolithiasis were studied from 1999–2005 in Dr. Behcet Uz Child Disease and Surgery Education and Research Hospital Nephrology Department, Izmir, according to their presenting signs and clinical and laboratory findings. The other necessary tests were also applied to detect the etiology of the calculi formation. Of the 72 patients, 50 (69.4%) were male and 22 (30.6%) were female, with ages ranging from 2 to 168 months (mean age 72 ± 35.7 months), and the male-to-female ratio of patients was 2.3. Twenty-four (33%) of them were diagnosed as having metabolic urolithiasis, 21 (30%) anatomic, 19 (26%) infectious and 8 (11%) idiopathic. The age at which urolithiasis was first diagnosed was found to be low in the metabolic and anatomic etiology groups (P = 0.028). Thirteen patients (18%) with urolithiasis were known to have a family history of stone disease, and in all of them metabolic etiology was considered to be the reason (P < 0.001). In all of the groups, the localization of the stone was found to be the upper urinary system most of the time, and in 17 (24%) with bilateral multiple stones, the etiology was found to be metabolic (P < 0.001). All of the patients were followed up for 3–72 months (mean 29.2 ± 13.7 months), and four of them (5.5%) had recurrences. In order to prevent renal damage and recurrences in pediatric patients with urolithiasis in Turkey in whom the etiology is mostly metabolic, the illnesses must be investigated very cautiously, and their early diagnosis and treatment modalities must be considered.     

Anesthetic management of a pediatric patient on a ketogenic diet

There are several specific considerations regarding seizure control during the perioperative period in patients who have been placed on a ketogenic diet (KD). A KD is high in fat and low in protein and carbohydrates and has a long history of use for the treatment of intractable seizures in children. Maintaining therapeutic ketosis and modifying the acid–base balance are particularly important for preventing seizures in patients on a KD. We report changes in the biochemical parameters of a patient with double cortex syndrome who was on a KD and who had been scheduled for the treatment of dental caries under sevoflurane anesthesia and acetate Ringer administration. Inhalation induction with a high concentration of sevoflurane should be reconsidered in view of recent reports describing the epileptogenic potential of sevoflurane.     

Nephrolithiasis in a neonate with transient renal wasting of calcium and magnesium

Following an uneventful full-term pregnancy, a 3-day-old girl presented with a focal seizure. Serological evaluation revealed hypomagnesemia and hypocalcemia. Renal ultrasonography performed because of hematuria showed bilateral nephrolithiasis. Renal wasting of calcium and magnesium was detected and urine citrate excretion was low. The hypocalcemia was refractory to calcium therapy, but responded briskly to magnesium supplementation. After 8 weeks of treatment with magnesium and calcium supplementation plus potassium citrate, the hypomagnesemia and hypocalcemia normalized spontaneously, as did the urinary calcium, magnesium, and citrate excretion. We speculate that our patient had a transient tubular defect in the thick ascending loop of Henle. Received: 22 May 2001 / Revised: 3 December 2001 / Accepted: 3 December 2001     

Urinary inhibitors of crystallization in hypercalciuric children with hematuria and nephrolithiasis

Urinary inhibitors are suggested to play a significant role in reducing crystallization in calcium (Ca) stone former and idiopathic hypercalciuria (IH). Urinary inhibitors such as magnesium (Mg), citrate, and glycosaminoglycans (GAGs) were evaluated, as well as urinary Ca and creatinine (Cr), in IH children with nephrolithiasis (LIT) or with hematuria plus IH (HEM) and were compared with a control group. The mean 24-h urinary excretion of Mg was similar in all groups. However, the urine Ca/Mg ratio was significantly increased (P <0.005) in LIT and HEM groups. A higher mean value for GAGs and citrate was found in the HEM group, but a very low level of GAGs (less than 60% of the normal value) and citrate (less than 30% of the normal value) was found in the LIT group. These data suggest that, despite a high urinary Ca excretion (3.6±0.1 mg/kg per day) in the HEM group, elevated urinary GAGs (32.0±1.0 mg/g Cr) and a normal urinary citrate (428.7±62.3 mg/24 h) excretion may prevent Ca crystallization and thus renal stones. In contrast, in the LIT group low urinary GAG (10.3±0.9 mg/g Cr) and citrate (235.2±52.3 mg/24 h) excretion may precipitate stone formation in the presence of a high urinary Ca excretion. Thus, it is reasonable to suggest that patients with hematuria and IH may not develop overt renal stone due to the presence of normal levels of renal stone inhibitors. Received October 30, 1995; accepted December 15, 1995     

Risk factors for nephrolithiasis in children

OBJECTIVE: The aim of this study is to evaluate the clinical outcome in children with urinary calculi, to detect risk factors for nephrolithiasis in childhood. MATERIAL AND METHODS: This retrospective study comprised 62 pediatric nephrolithiasis patients who have come for routine follow-up visits between the dates of January 2002-August 2006 (48% girls and 52% boys). RESULTS: The mean age of the patients was 8.8 +/- 4.5 years (1-16 years). Hypercalciuria was found in 25 (40%) patients. The mean urinary calcium excretion for hypercalciuric patients was 5.7 +/- 1.2 mg/kg (4.8 mg/kg per day). In our hypercalciuric patients 15 (60%) children had abdominal or flank pain, seven (28%) patients macroscopic hematuria and three (12%) dysuria. Hypocitraturia is the second important risk factor for nephrolithiasis. Urinary calcium excretion showed a positive correlation with the stone size (r = 0.482, P = 0.043). A positive correlation was found between recurrent urinary tract infection (UTI) and hypercalciuria (r = 0.528, P = 0.017). Urinary citrate excretion showed a negative correlation with recurrent UTI (r = -0.503, P = 0.024). Hyperuricaciduria, hyperoxaluria were found to have no effect on the stone size and UTI of the patients. Stones were disintegrated with ESWL in two patients, endoscopic interventions were used in one patient and two underwent an open surgical procedure. CONCLUSION: All children with nephrolithiasis should have a metabolic screen. Children with a positive family history and consanguinity should be followed carefully with respect to metabolic abnormalities.     

Risk factors for hyperlipidemia in long-term pediatric renal transplant recipients

Hyperlipidemia (HL) is a common problem in adult renal transplant (TP) recipients, contributing to an increased risk of cardiovascular disease and chronic TP nephropathy. There are multiple causes of HL post renal TP in adult patients, including pre TP HL, immunosuppressive agents, renal dysfunction, hypoalbuminemia secondary to nephrotic syndrome, obesity, and conditions that lead to end-stage renal disease (ESRD). We evaluated the incidence and risk factors of HL in 62 pediatric renal TP recipients (15.4±4.2 years, range-3.0–22.3 years) with long-term (6.7±3.1 years) functioning [glomerular filtration rate (GFR) 66.7±23.2 ml/min per 1.73 m²] allografts. The mean serum cholesterol (C) level was 205.5±43.6 mg/dl. Thirty-two patients (51.6%) exhibited elevated serum C levels. The mean serum triglyceride (TG) level was 157.3±88.4 mg/dl. Serum TG levels were elevated in 32 patients (51.6%). In patients with elevated serum levels of either C or TG, the mean low-density lipoprotein level (LDL) was 138.6±44.1 mg/dl (normal <130 mg/dl) and the high-density lipoprotein (HDL) level 54.6±15.9 mg/dl (normal>34 mg/dl). Of those patients studied, 45.5% had high LDL levels, whereas 9.1% exhibited low HDL levels. The two risk factors for elevated serum C levels in our patient population were pre-TP HL and increased years since TP. The only risk factor for elevated serum TG levels was reduced GFR. A family history of HL had a significant deleterious impact upon serum levels of C (P=0.01), but did not affect serum TG levels (P=0.7). Years on dialysis prior to TP, history of prior TP, gender, body mass index, and disease leading to ESRD had no influence upon the development of post-TP HL. We conclude that post-renal TP HL is a significant problem in pediatric renal TP recipients. Received: 13 January 1999 / Revised: 19 May 1999 / Accepted: 21 May 1999     

A practical primary care approach to hematuria in children

Although hematuria is a common finding in the unselected population of children, the approach to evaluation is quite variable. Changes in the practice of primary care medicine in the United States mandate an approach to common office problems that is practical and realistic. This review addresses three areas: the current approach to evaluation of hematuria in children, a classification of children with hematuria into four distinct and easily identified clinical categories, and the development of an algorithm for application in the primary care setting. Each category is discussed relative to the more-common etiologies of hematuria, with recommendations for appropriate evaluation as well as suggestions of an appropriate referral to the nephrologist. An algorithm is proposed that provides a practical, systematic approach to the problem without the requirement for a specific diagnosis in every patient. The proposed classification and approach to the evaluation of children with hematuria should help simplify and clarify a potentially complex process. Received: 30 September 1998 / Revised: 5 February 1999 / Accepted: 8 February 1999     

Urinary calcium excretion in healthy children and adolescents

Urinary calcium (Ca) excretion was determined in 1,578 24-h urine samples from 507 healthy children and adolescents (252 boys, 255 girls; 2.8–18.4 years) participating in the DONALD Study and is presented for 32 different age and sex groups. Calciuria values related to body weight (mg/kg per day) were relatively constant except for a transient decrease during puberty in all centiles, with a later onset in boys than girls. Distribution of calciuria (mg/kg per day) was best normalized by log transformation, with an almost constant standard deviation of the log-transformed values. Ca excretion was ≥4 mg/kg per day in 8.6% and ≥6 mg/kg per day in 1.5% of the urine samples. Based on Ca excretion rates of 1,080 pairs of 24-h urine samples from 364 children and adolescents, sensitivity, specificity, and the predictive value for hypercalciuria (≥4 mg/kg per day) in the next urine sample were calculated at three test levels classifying calciuria of the initial urine sample. In summary, this study presents normal values of urinary Ca excretion related to age and sex in a population of healthy German children and adolescents consuming a typical western-style diet. A high level of calciuria in a random urine sample is important in the diagnosis of hypercalciuria. Received: 25 February 1997 / Revised: 28 April 1999 / Accepted: 3 May 1999     

Long-term follow-up in distal renal tubular acidosis with sensorineural deafness

A 20-year-old man presented with failure to thrive and bilateral genu valgum. On the basis of growth failure, skeletal deformity, hyperchloremic metabolic acidosis with alkaline urine and hypokalemia, nephrocalcinosis, and hearing loss, a diagnosis of distal renal tubular acidosis (DRTA) with sensorineural deafness was made. The genu valgum was treated by corrective osteotomy. Skeletal deformity was corrected and impaired growth improved after sustained therapy of metabolic acidosis with alkali supplementation. During an 8-year follow-up period the patient’s glomerular filtration rate remained stable, the nephrocalcinosis did not progress, and his height increased 10 cm. Although nephrolithiasis led to atrophy of the right kidney, at last follow-up, when the patient was 44 years old, his creatinine clearance was 50 ml/min per 1.73 m² body surface. Received: 17 December 1999 / Revised: 26 April 2000 / Accepted: 2 May 2000     

Calyceal microlithiasis in children: report on 196 cases

Recognition of children at greatest risk for urolithiasis may allow early detection or prevention of stone formation. We report clinical data from 196 children aged 0.9–15.9 years in whom renal ultrasound examination revealed hyperechogenic spots in renal calyces less than 3 mm in diameter. We called this finding “calyceal microlithiasis” (CM). There was a history of urolithiasis in 70.4% of patients in at least one first- or second-degree relative. Presenting symptoms were recurrent abdominal pain, dysuria, and hematuria, occurring alone or in combination. Hematuria was the presenting symptom in 41% of patients and was the only urinary finding in more than one-third. Hypercalciuria was present in about one-third and hyperuricuria in one-fifth of the patients. Of 29 patients who were followed for at least 2 years, 9 developed calculi 4–7 mm in diameter. CM possibly represents the first step in calculus formation. The finding of CM might explain a number of symptoms and signs that are often mild and non-specific, thus reducing invasive diagnostic procedures. Received November 26, 1996; received in revised form August 7, 1997; accepted November 5, 1997     

Perioperative management of a paediatric patient on the ketogenic diet

The ketogenic diet has become commonplace for the treatment of paediatric patients with refractory epilepsy. I describe the perioperative management of a patient on the ketogenic diet. The basis, complications and anaesthetic implications of the diet are discussed.     

Prognostic factors in Saudi children with posterior urethral valves

Posterior urethral valves (PUV) account for a sizeable proportion of children with chronic renal failure. Several criteria have been identified as predictive of future renal function in children with PUV. We compared the presenting features and initial treatment in two groups of Saudi children treated for PUV, with the aim of identifying any factors that might account for the differences observed in their renal function. One group (group A, 19 patients) had a serum creatinine of 80 μmol/l or less at follow-up and the other (group B, 13 patients) had higher levels. There was no significant difference in age or weight at presentation, incidence and severity of reflux, urinary tract infection, or type of primary treatment (valve ablation versus vesicostomy) between the two groups. However, after 5–7 days of catheter drainage, the mean serum creatinine level was 88±62 μmol/l for patients in group A compared with 172±77 μmol/l for those in group B (P<0.0001). This difference was highly significant. Linear regression analysis of post-drainage creatinine and serum creatinine at last follow-up showed a correlation coefficient of 0.7171 (P<0.0001). Hence the serum creatinine level after catheter drainage correlated strongly with renal function during short-term follow-up of Saudi children with PUV. This might help in the selection of the optimal initial therapy and provide some basis for prognostication. Received: 20 October 1998 / Revised: 10 June 1999 / Accepted: 11 June 1999     

Hypercalciuria in ex-preterm children, aged 7-8 years

In a previous study, 8 of 28 ex-preterm infants, aged 4–5 years, had increased urinary calcium excretion. The aim of this study was to confirm this finding and to determine if raised urinary calcium excretion is associated with reduced bone mineralisation. Forty-six ex-preterm children, aged 7–9 years, and 40 age- and sex-matched controls were recruited. The calcium excretion measured from 3 separate 24-h urine collections was recorded and a dietary assessment made from a diary record. Data were retrieved from the neonatal case notes and included aminoglycoside usage. Dual energy X-ray absorptiometry was used to measure bone mineral content and bone mineral density (BMD) in all children. The mean maximum 24-h urinary calcium was significantly higher in the preterm group than the term group (P=0.01). Increased calcium excretion was associated with raised neonatal aminoglycoside levels (P=0.0013). Height standard deviation score and hip BMD were significantly lower in the 21 preterm children with a 24-h urinary calcium above 4 mg/kg per day than term controls (P=0.04 and P=0.004, respectively). Urinary calcium excretion had a negative relationship with hip BMD in the preterm group (P=0.004). This difference in BMD was not observed in the 25 preterm children with normocalciuria. In the 10 preterm girls with hypercalciuria, hip BMD was lower than in control females (P=0.01). This difference in hip BMD between the 11 preterm boys with hypercalciuria and term boys was not significant (P=0.05). In conclusion, preterm children are shorter and have a lower hip BMD than those with normocalciuria. Further prospective studies are required to assess this risk and its influence on subsequent impaired bone mineralisation. Received: 28 September 2000 / Revised: 2 April 2001 / Accepted: 2 April 2001     

Urea resolves gross hematuria in a 15 year old with hemoglobin C trait

Hematuria is a rare complication seen in patients with hemoglobin C trait. We report a 15-year-old African-American female with hemoglobin C trait, who presented with persistent hematuria. None of the urological, serological or histological workups revealed any other pathology. Hematuria failed to respond to all conventional modalities used in the treatment of the same condition seen in sickling hemoglobinopathies. This case is the first known case of persistent hematuria in a pediatric patient with hemoglobin C trait, which resolved with intravenous urea administration. Received: 27 June 2000 / Revised: 18 October 2000 / Accepted: 19 October 2000     

Pediatric urolithiasis in southern Israel: the role of uricosuria

We describe three cases of severe obstructive uropathy in children under 2 years of age, due to radio-lucent renal stones. Metabolic work-up revealed only normouricemic hyperuricosuria (HU) as the single identifiable risk factor for urolithiasis (UL) in these infants. We reviewed records of 66 cases of pediatric UL seen in our service over an 8-year period. UL prevalence was greater for Bedouin than for Jewish children (1.02 vs. 0.13 cases/1,000 inhabitants at risk respectively, P<0.01). HU (>0.6 mg uric acid/dl GFR) was the only biochemical risk factor that differed between Bedouin and Jewish children (mean uric acid excretion index 0.8±0.39 vs. 0.55±0.26 mg/dl GFRrespectively, P<0.05). Bedouin children comprised 85% of patients in the HU group versus 59% in the non-hyperuricosuric group (P<0.05). The mean age of onset of UL was 38±44 months and 93±52 months in the HU and the non-HU group, respectively (P<0.05). The UA excretion index in the HU group was inversely correlated with age (r=0.41, P<0.01) and its slope and constant were different from an age-matched non-UL control population. In conclusion, pediatric UL in southern Israel is predominant in Bedouin toddlers. HU was the only identifiable biochemical risk factor that could explain this difference. Received: 3 November 1999 / Revised: 8 February 2000 / Accepted: 9 February 2000     

Bartter syndrome in a neonate: early treatment with indomethacin

The neonatal form of Bartter syndrome is characterized by intrauterine onset of polyuria leading to severe polyhydramnios. We report a patient with the early onset of the syndrome and a similar history in a previous sibling who died in early neonatal life. The patient is a female product of 33 weeks of gestation complicated by severe polyhydramnios. Her birth weight was 2,100 g. Polyuria led to severe dehydration on the 3rd day of life. Laboratory studies showed hypokalemia, hyponatremia, and elevated plasma levels of renin and aldosterone. Hypercalciuria was associated with echographic evidence of nephrocalcinosis. Indomethacin therapy resulted in a significant reduction in urine volume and correction of biochemical abnormalities. Growth and development are satisfactory after 4 years of indomethacin therapy, but nephrocalcinosis remains unchanged. Received: 22 December 1998 / Revised: 13 May 1999 / Accepted: 1 June 1999     

Impact of age on reference values for serum concentration of cystatin C in children

Recently, cystatin C (cyst C) was proposed for the assessment of glomerular filtration rate, being more accurate than creatinine determination. Reference intervals for cyst C do not vary with age and sex, like creatinine values. Elevated values of cyst C were reported for pre- and full-term infants. Nevertheless, the age cut-off for stable cyst C values i.e., age independence, remains under discussion. Therefore, we conducted a prospective study in 98 healthy children, 51 being under 18 months of age. Cyst C was determined by the nephelometric method. The infants under the age of 18 months had a higher mean serum cyst C value (0.94±0.24 mg/l) than the older children (0.65±0.19 mg/l). There was a negative correlation between age and cyst C in the infant group under the age of 18 months (r ²=0.631, P<0.01). Our results indicate that mean serum cyst C is higher in infants than older children; the age cut-off appears over the age of 1 year of life, presumably reflecting kidney maturation. Our study does not allow accurate assessment of the age cut-off at 18 months or 36 months. Received: 31 December 1999 / Revised: 10 October 2001 / Accepted: 11 October 2001     

Rickets in an infant with Williams syndrome

Calcium homeostasis is altered in patients with Williams syndrome. We report an infant in whom Williams syndrome was diagnosed at 4 weeks who presented with hypercalcemia, hypercalciuria, and medullary nephrocalcinosis. Fluorescence in situ hybridization demonstrated a deletion of the elastin gene on chromosome 7. This infant was treated with a low-calcium/vitamin D-deficient infant formula that resulted in the development of rickets. Replacement of the low-calcium/vitamin D-deficient formula with standard formula led to resolution of the rickets. Received: 6 April 1999 / Revised: 10 August 1999 / Accepted: 13 August 1999