Pediatric primary urolithiasis: Symptoms, medical management and prevention strategies

In the past few decades pediatric urolithiasis has become more frequent. The reason for this increase is not completely clear but has been attributed to changes in climate, nutritional habits and possibly other environ-mental factors. Although less frequent than adult stone disease, urolithiasis in the pediatric age group is also related to significant morbidity, particularly since stones tend to recur, and, thus, should not be underestimated. Most children with idiopathic stone disease have an underlying metabolic abnormality substantiating the importance of metabolic evaluation already following initial diagnosis of urolithiasis. Identification of the metabolic abnormality allows for more specifc prescription of non pharmacological and pharmacological interventions aimed at preventing recurrent stone formation. A better understanding of the causes of kidney stone disease will provide better strategies for stone prevention in children.

Bone disease in pediatric idiopathic hypercalciuria

Idiopathic hypercalciuria （IH） is the leading metabolic risk factor for urolithiasis and affects all age groups without gender or race predominance. IH has a high morbidity with or without lithiasis and reduced bone mineral density （BMD）, as described previously in pe-diatric patients as well as in adults. The pathogenesis of IH is complex and not completely understood, given that urinary excretion of calcium is the end result of an interplay between three organs （gut, bone and kidney）, which is further orchestrated by hormones, such as 1,25 dihydroxyvitamin D, parathyroid hormone, calcitonin and fosfatonins （i.e., fbroblast growth-factor-23）. Usu-ally, a primary defect in one organ induces compensa-tory mechanisms in the remaining two organs, such as increased absorption of calcium in the gut secondary toa primary renal loss. Thus, IH is a systemic abnormality of calcium homeostasis with changes in cellular trans-port of this ion in intestines, kidneys and bones. Re-duced BMD has been demonstrated in pediatric patients diagnosed with IH. However, the precise mechanisms of bone loss or failure of adequate bone mass gain are still unknown. The largest accumulation of bone mass occurs during childhood and adolescence, peaking atthe end of the second decade of life. This accumulation should occur without interference to achieve the peak of optimal bone mass. Any interference may be a risk factor for the reduction of bone mass with increased risk of fractures in adulthood. This review will address the pathogenesis of IH and its consequence in bone mass.

Should pediatric idiopathic hypercalciuria be treated with hypocalciuric agents?

BACKGROUND Hypercalciuria is the most common metabolic risk factor for calcium urolithiasis and is associated with bone loss in adult patients.Reduced bone mineral density(BMD)was already described in idiopathic hypercalciuria(IH)children,but the precise mechanisms of bone loss or inadequate bone mass gain remain unknown.Life-long hypercalciuria might be considered a risk to change bone structure and determine low bone mass throughout life.The peak of bone mass should occur without interferences.A beneficial effect of citrate formulations and thiazides on bone mass in adult and pediatric patients with IH have been shown.AIM To evaluate whether pharmacological therapy has a beneficial effect on bone mass in children and adolescents with IH.METHODS This retrospective cohort study evaluated 40 hypercalciuric children nonresponsive to lifestyle and diet changes.After a 2-mo run-in period of citrate formulation(Kcitrate)usage,the first bone densitometry(DXA)was ordered.In patients with sustained hypercalciuria,a thiazide diuretic was prescribed.The second DXA was performed after 12 mo.Bone densitometry was performed by DXA at lumbar spine(L2-L4).A 24-h urine(calcium,citrate,creatinine)and blood samples(urea,creatinine,uric acid,calcium,phosphorus,magnesium,chloride,hemoglobin)were obtained.Clinical data included age,gender,weight,height and body mass index.RESULTS Forty IH children;median age 10.5 year and median time follow-up 6.0 year were evaluated.Nine patients were treated with Kcitrate(G1)and 31 with Kcitrate+thiazide(G2).There were no differences in age,gender,body mass index z-score and biochemical parameters between G1 and G2.There were no increases in total cholesterol,kalemia and magnesemia.Calciuria decreased in both groups after treatment.Lumbar spine BMD z-score increased after thiazide treatment in G2.There was no improvement in G1.CONCLUSION Results point to a beneficial effect of thiazide on lumbar spine BMD z-score in children with IH.Further studies are necessary to confirm the results of the present study.

Beyond kidney stones:Why pediatricians should worry about hypercalciuria

The incidence of urolithiasis(UL)is increasing,and it has become more common in children and adolescents over the past few decades.Hypercalciuria is the leading metabolic risk factor of pediatric UL,and it has high morbidity,with or without lithiasis as hematuria and impairment of bone mass.The reduction in bone mineral density has already been described in pediatric idiopathic hypercalciuria(IH),and the precise mechanisms of bone loss or failure to achieve adequate bone mass gain remain unknown.A current understanding is that hypercalciuria throughout life can be considered a risk of change in bone structure and low bone mass throughout life.However,it is still not entirely known whether hypercalciuria throughout life can compromise the quality of the mass.The peak bone mass is achieved by late adolescence,peaking at the end of the second decade of life.This accumulation should occur without interference in order to achieve the peak of optimal bone mass.The bone mass acquired during childhood and adolescence is a major determinant of adult bone health,and its accumulation should occur without interference.This raises the critical question of whether adult osteoporosis and the risk of fractures are initiated during childhood.Pediatricians should be aware of this pediatric problem and investigate their patients.They should have the knowledge and ability to diagnose and initially manage patients with IH,with or without UL.

Rituximab for troublesome cases of childhood nephrotic syndrome

Nephrotic syndrome(NS) is the most common glomerular disease of childhood. Steroid-dependent and steroid-resistant nephrotic syndrome present challenges in their pharmaceutical management; patients may need several immunosuppressive medication for optimum control, each of which medication has its own safety profile. Rituximab(RTX) is a monoclonal antibody that targets B cells and has been used successfully for management of lymphoma and rheumatoid arthritis. Recent clinical studies showed that rituximab may be an efficacious and safe alternative for the treatment of complicated nephrotic syndrome. In this review article, we aim to review the efficacy and safety of RTX therapy in nephrotic syndrome. We reviewed the literature pertaining to this topic by searching for relevant studies on Pub Med and Medline using specific keywords. The initial search yielded 452 articles. These articles were then examined to ensure their relevance to the topic of research. We focused on multicenter randomized controlled trials with relatively large numbers of patients. A total of 29 articles were finally identified and will be summarized in this review. The majority of clinical studies of RTX in complicated pediatric NS showed that rituximab is effective in approximately 80% of patients with steroid-dependent NS, as it decreases the number of relapses and steroid dosage. However, RTX is less effective at achieving remission in steroid-resistant NS. RTX use was generally safe, and most side effects were transient and infusion-related. More randomized, double-blinded clinical studies are needed to assess the role of RTX in children with nephrotic syndrome.

Parathyroid ultrasonography and bone metabolic profile of patients on dialysis with hyperparathyroidism

AIM To evaluate the parathyroid ultrasonography and define parameters that can predict poor response to treatment in patients with secondary hyperparathyroidism due to renal failure.METHODS This cohort study evaluated 85 patients with chronic kidney disease stage V with parathyroid hormone levels above 800 pg/mL. All patients underwent ultrasonography of the parathyroids and the following parameters were analyzed: Demographic characteristics(etiology of chronic kidney disease, gender, age, dialysis vintage, vascular access, use of vitamin D), laboratory(calcium, phosphorus, parathyroid hormone, alkaline phosphatase, bone alkaline phosphatase), and the occurrence of bone changes, cardiovascular events and death. The χ~2 test were used to compare proportions or the Fisher exact test for small sample frequencies. Student t-test was used to detect differences between the two groups regarding continuous variables.RESULTS Fifty-three patients(66.4%) had parathyroid nodules with higher levels of parathyroid hormone, calcium and phosphorus. Sixteen patients underwent parathyroidectomy and had higher levels of phosphorus and calcium × phosphorus product(P = 0.03 and P = 0.006, respectively). They also had lower mortality(32% vs 68%, P = 0.01) and lower incidence of cardiovascular or cerebrovascular events(27% vs 73%, P = 0.02). Calcium × phosphorus product above 55 mg^2/dL^2 [RR 1.48(1.06, 2.08), P = 0.03], presence of vascular calcification [1.33(1.01, 1.76), P = 0.015] and previous occurrence of vascular events [RR 2.25(1.27, 3.98), P < 0.001] were risk factors for mortality in this population. There was no association between the occurrence of nodules and mortality.CONCLUSION The identification of nodules at ultrasonography strengthens the indication for parathyroidectomy in patients with secondary hyperparathyroidism due to renal failure.

Is there a gender difference in antidiuretic response to desmopressin in children?

Women with nocturia are more sensitive to desmopressin, a synthetic arginine vasopressin (AVP) analogue, with significant antidiuretic responses to desmopressin orally disintegrating tablet (ODT) 25 μg, compared with men who require 58 μg to achieve similar responses. In children the current desmopressin dose recommendation to treat primary nocturnal enuresis (PNE) is the same for boys and girls. This post hoc analysis of data from a randomised, doubleblind single-dose study of 84 children with PNE aged 6 - 12 years explored gender differences in sensitivity to desmopressin in children. Following water loading to suppress endogenous AVP, placebo or desmopres-sin 30, 60, 120, 240, 360 or 480 μg was administered when urinary production reached >0.13 mL/min/kg. The endpoints of urinary osmolality and duration of urinary-concentrating action (DOA) (above three thresholds: 125, 200 and 400 mOsm/kg) were analysed to compare efficacy in boys and girls, in each treatment group. The DOA and urinary osmolality were similar in both genders in the desmopressin 120 - 480 μg groups. Boys receiving desmopressin ODT 30 - 60 μg tended to increased urinary osmolality and experienced 1 - 2 hours longer DOA than girls. The same pattern of higher values in boys compared with girls was seen for all measures of urinary osmolality. Conclusion: In a limited sample of pre-pubertal children the antidiuretic response to desmopressin was largely similar between genders, in contrast to findings in adults.

Prevalence of risk factors for cardiovascular and kidney disease in Brazilian healthy preschool children

AIM To investigate the prevalence of nutritional parameters of risk for cardiovascular disease(CVD) and kidney diseases in healthy preschool children.METHODS This is an observational cross-sectional study with 60 healthy children, of both genders, aged two to six years old and 56 mothers, in Belo Horizonte, Minas Gerais, Brazil. Preschool children and their families with regular activities at public schools were invited to paticipate in the study. The following characteristics were assessed: Socio-demographic condictions, clinical health, anthropometric, biochemical, lifestyle and data on food consumption. The 56 healthy children were divided into two groups, overweight(C1) and non-overweight(C2), as well as their mothers, respectively, in overweight(M1) and non-overweight(M2). Nutritional status was defined according to results obtained through the Anthro? Software for nutritional analysis. RESULTS Thirty-five children were male, with mean age of 4.44 ± 1.0 years old. Eighty-nine percent of them were eutrophic, 86.7% were sedentary and they had five meals a day. Body mass index(BMI) for age and total cholesterol(TC) was higher on C1(P = 0.0001) and high density lipoprotein cholesterol(HDL-c) was higher on C2. Mothers were 32.5 ± 7.1 years old, mostly married and employed. Eighty-six percent of them were sedentary and 62.5% were overweight with BMI = 26.38 ± 5.07 kg/m2. Eighteen percent of the overweight mothers had isolated total hypercholesterolemia(TC levels elevated) and 12.5% had low HDL-c levels. The present study showed an association between overweight and obesity during the preschool years and the correspondent mothers' nutritional status of overweight and obesity(OR = 4.96; 95%CI: 0.558-44.17). There was a positive correlation between the food risk associated with CVD by children and mothers when their consumption was 4 times/wk(P = 0.049; r = 0.516) or daily(P = 0.000008; r = 0.892).CONCLUSION Analyzed children showed high rates of physical inactivity, high serum cholesterol levels and high consumption of food associated with risk for CVD and renal disease. Changes in habits should be encouraged early in kindergarten.

Several Dengue: About 2 Cases with Pulmonary Disease

The most widespread arbovirus in the world, dengue fever has been rampant since the 18th century. Since then, several epidemics have been documented in Asia, the Caribbean, South America and Africa. The authors report two cases of dengue fever in children aged six (6) and twelve (12) years respectively. The diagnosis of several dengue pulmonary was retained in these children, clinico-radiological and biological arguments. In addition to the hemorrhagic syndrome, the pulmonary symptomatology associated cough, dyspnea. Chest X-ray revealed bilateral and extensive alveolar interstitial radiological lesions. From a biological point of view, the positivity of dengue-specific IgM has confirmed arboviruses. From the diagnostic peculiarities of the cases observed, the authors suggest the search for factors associated with a primary dengue infection from several onsets to pulmonary manifestation in children. Indeed, this fringe of the population is no longer concerned with acute respiratory infections. In addition, the socio-cultural context of poverty, of pre-hospital therapeutic itinerary favoring traditional medicine, delays hospital care.

Bartter's syndrome:clinical findings,genetic causes and therapeutic approach

Backgound Bartter's syndrome(BS)is a rare group of salt losing tubulopathies due to the impairment of transport mecha-nisms at the thick ascending limb of the Henle's loop.Data sources Literature reviews and original research articles were collected from database,including PubMed and Scopus.Results According to the time of onset and symptoms,BS can be classified into antenatal and classic BS.Molecular studies have identified different subtypes of BS.BS types Ⅰ,Ⅱ and Ⅲ are caused by mutations on genes encoding the luminal Na^(+)-K^(+)-2Cl^(-) co-transporter,the luminal K+ channel ROMK,and the basolateral chloride channel ClC-Kb(CLCNKB),respectively.Loss-of-function mutations of Barttin CLCNK type accessory beta subunit cause BS type Ⅳa.Simultaneous mutations of CLCNKB and CLCNKA cause BS type Ⅳb.BS type Ⅴ consists in a novel transient form characterized by antenatal presentation due to mutations in the MAGE family member D2.Severe gain-of-function mutations of the extracellular calcium sensing receptor gene can result in an autosomal dominant condition of BS.Main clinical and biochemical alterations in BS include polyuria,dehydration,hypokalemia,hypochloremic metabolic alka-losis,hyperreninemia,high levels of prostaglandins,normal or low blood pressure,hypercalciuria and failure to thrive.Treatment focuses mainly at correcting dehydration and electrolyte disturbances and in measures to reduce polyuria,including the use of nonsteroidal anti-inflammatory medications to control excessive renal prostaglandin E2 production.Conclusions Early diagnosis and treatment of BS may prevent long-term consequences such as growth failure,nephrocal-cinosis and end-stage renal disease.

Distal renal tubular acidosis:genetic causes and management

Background Distal renal tubular acidosis(dRTA)is a kidney tubulopathy that causes a state of normal anion gap metabolic acidosis due to impairment of urine acidification.This review aims to summarize the etiology,pathophysiology,clinical findings,diagnosis and therapeutic approach of dRTA,with emphasis on genetic causes of dRTA.Data sources Literature reviews and original research articles from databases,including PubMed and Google Scholar.Manual searching was performed to identify additional studies about dRTA.Results dRTA is characterized as the dysfunction of the distal urinary acidification,leading to metabolic acidosis.In pediatric patients,the most frequent etiology of dRTA is the genetic alteration of genes responsible for the codification of distal tubule channels,whereas,in adult patients,dRTA is more commonly secondary to autoimmune diseases,use of medications and uropathies.Patients with dRTA exhibit failure to thrive and important laboratory alterations,which are used to define the diagnosis.The oral alkali and potassium supplementation can correct the biochemical defects,improve clinical manifestations and avoid nephrolithiasis and nephrocalcinosis.Conclusions dRTA is a multifactorial disease leading to several clinical manifestations.Clinical and laboratory alterations can be corrected by alkali replacement therapy.