Predictors of Renal Dysfunction in Adults with Childhood Vesicoureteral Reflux after Long-Term Follow-Up.

BACKGROUND: Triad of childhood vesicoureteral reflux (VUR), urinary infection (UTI) and renal scarring might initiate potentially serious consequences that lead to renal dysfunction manifested at the second or third decade of life. AIM: To identify the risk factors predictive for renal dysfunction in adults with primary VUR after long-term follow-up. METHODS: We evaluated the records of 101 children (94.1% female, 5.9% male) at a median age of 5.2 ± 2.3 years (1-12 years), suffering from UTI and VUR. The patients were interviewed after mean 21 years from the first episodes of VUR (8 to 32 years). Renal function was determined from the estimated glomerular filtration rate (eGFR). RESULTS: Renal scarring was detected in 68.3% out of 82 patients and bilateral one in 7.3% patients. Linear regression analysis revealed that presence of proteinuria (B = -33.7, p=0.0001), the greater number of years from VUR diagnosis (B = -1.6, p = 0.002) and renal scarring (B = -14.8, p = 0.005) appeared as independent predictors of reduced global eGFRcreat. The same variables plus microalbuminuria (B = -1.0, p = 0.012) appeared as independent predictors of reduced global eGFRcreat-cys. Bilateral scarring (OR=25.5, p = 0.003) appeared as independent predictor of greater risk for CKD assessed using eGFRcreat while greater number of years from VUR diagnosis (OR = 1.7, p = 0.092), microalbuminuria (OR = 1.3, p = 0.047) and again bilateral scarring (OR = 31.3, p = 0.040) appeared as predictors of risk for CKD assessed using eGFRcreat-cys. CONCLUSION: Identification of those with an increased risk of progression to CKD should be the goal in all patients with childhood VUR. Their systematic follow-up should be till adulthood and older age.

Voiding Urosonography with Second-Generation Ultrasound Contrast Agent for Diagnosis of Vesicoureteric Reflux: First Local Pilot Study.

BACKGROUND: Vesicoureteric reflux (VUR) is an important association of paediatric urinary tract infection (UTI) found in 30-50% of all children presenting with first UTI. Contrast-enhanced voiding ultrasonography (ceVUS) has become an important radiation-free method for VUR detection in children. Its sensitivity in detecting VUR has greatly improved due to the development of the contrast-specific ultrasound techniques and the introduction of the second-generation ultrasound contrast agent, superseding the diagnostic accuracy of standard radiological procedures. AIM: This article aimed to summarise the current literature and discuss the first local pilot study performed in our institution on detection of vesicoureteric reflux by contrast-enhanced voiding ultrasonography with second- generation agent (SonoVue, Bracco, Italy). MATERIAL AND METHODS: Retrospective review of the first 31 ceVUS (24 girls, 7 boys) was presented. Age range was 2 months to 18 years (mean = 6.4 ± 4.9). RESULTS: All examinations were well tolerated without any adverse incident. VUR was shown in 20 (64.5%) children in 32/62 (51.6) nephroureteral units (NUUs). In 18 NUUs, VUR was grade II/V, in 11 Grade III/V and in 3 grade IV/V, respectively. Urethra was shown in 19/31 children and in all boys, without pathological finding. In two girls spinning top urethra has been detected. Subsequent urodynamic studies revealed functional bladder problem in both. CONCLUSIONS: Contrast-enhanced voiding urosonography using intravesical second generation ultrasound contrast agent could be recommend as a valid alternative diagnostic modality for detecting vesicoureteral reflux and evaluation of the distal urinary tract in children, based on its radiation-free, highly efficacious, reliable, and safe characteristics.

Vesicoureteral Reflux Detected with (99m)Tc-DTPA Renal Scintigraphy during Evaluation of Renal Function.

BACKGROUND: Radionuclide techniques, as direct radionuclide cystography and (99m)Tc-DMSA scintigraphy, have been used in evaluation of vesicoureteral reflux (VUR) and reflux nephropathy (RN) in children. Dynamic (99m)Tc-DTPA scintigraphy is reserved for evaluation of differential renal function and obstruction in children, where hydronephrosis is detected by ultrasonography (US) pre- or postnatally. CASE REPORT: Six year old boy was prenatally diagnosed with bilateral hydronephrosis. Postnatal, severe bilateral VUR was detected by voiding urethrocytography. US and (99m)Tc-DTPA scintigraphy performed in the first month of life showed small left kidney that participated with 2% in the global renal function. Bilateral cutaneous ureterostomy has been performed in order to obtain good renal drainage and promote optimal renal growth. Twelve months later, classic antireflux procedure was done. Control (99m)Tc-DTPA scintigraphy, 5 ys after antireflux surgery, revealed persisting radioactivity during the diuretic phase, in the left kidney that indicated antireflux procedure failure with VUR reappearance. CONCLUSION: (99m)Tc-DTPA scintigraphy is the first method of choice for long-term monitoring of individual kidney function in children with VUR and other congenital urinary tract anomalies. Additionally, it can be used as indirect radionuclide cystography when rising of radioactivity in the kidney region, during the diuretic phase can indicate presence of VUR.

The carrier rate and spectrum of MEFV gene mutations in central and southeastern European populations.

OBJECTIVES: Familial Mediterranean fever (FMF) is an autosomal-recessive disorder caused by mutations in MEFV gene. Eastern Mediterranean populations have the highest number of carriers, whereas western Mediterranean populations are less frequently affected. The aim of this study was to determine the carrier rate and spectrum of MEFV gene mutations in apparently healthy populations and in suspected FMF patients from central and southeastern European (CSEE) countries. METHODS: We screened 507 apparently healthy persons from 5 CSEE countries. Exons 2 and 10 of the MEFV gene were PCR amplified and subsequently sequenced with ABI prism310 genetic analyser. Six most common mutations in the MEFV gene were tested: V726A, K695R, M694V, M694I, M680I in exon 10, and E148Q in exon 2. In suspected FMF patients we screened all MEFV exons in selected cases. RESULTS: The overall carrier frequency of all MEFV mutations was higher than expected (9.3%). In the whole cohort we did not find any apparently healthy persons with two mutations. Heterozygous mutations were found in apparently healthy subjects from different CSEE countries as follows: Macedonia 16%, Serbia 11%, Bosnia and Herzegovina 8%, Slovenia 6% and Hungary 5%. The most common mutation in healthy controls was K695R, appearing in 40% of mutated alleles. The most common mutation in suspected FMF patients was M694V, followed by K695R. CONCLUSIONS: We found a higher than expected carrier rate of MEFV gene mutations in populations from CSEE countries. It is interesting to note that 40% of detected carriers carry the K695R mutation.

Mineral metabolism in European children living with a renal transplant: a European society for paediatric nephrology/european renal association-European dialysis and transplant association registry study.

BACKGROUND AND OBJECTIVES: Data on mineral metabolism in pediatric renal transplant recipients largely arise from small single-center studies. In adult patients, abnormal mineral levels are related to a higher risk of graft failure. This study used data from the European Society for Paediatric Nephrology/European Renal Association-European Dialysis and Transplant Association Registry to study the prevalence and potential determinants of mineral abnormalities, as well as the predictive value of a disturbed mineral level on graft survival in a large cohort of European pediatric renal transplant recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study included 1237 children (0-17 years) from 10 European countries, who had serum calcium, phosphorus, and parathyroid hormone measurements from 2000 onward. Abnormalities of mineral metabolism were defined according to European guidelines on prevention and treatment of renal osteodystrophy in children on chronic renal failure. RESULTS: Abnormal serum phosphorus levels were observed in 25% (14% hypophosphatemia and 11% hyperphosphatemia), altered serum calcium in 30% (19% hypocalcemia, 11% hypercalcemia), and hyperparathyroidism in 41% of the patients. A longer time since transplantation was associated with a lower risk of having mineral levels above target range. Serum phosphorus levels were inversely associated with eGFR, and levels above the recommended targets were associated with a higher risk of graft failure independently of eGFR. CONCLUSIONS: Abnormalities in mineral metabolism are common after pediatric renal transplantation in Europe and are associated with graft dysfunction.

Management of anemia in children receiving chronic peritoneal dialysis.

Little information exists regarding the efficacy, modifiers, and outcomes of anemia management in children with CKD or ESRD. We assessed practices, effectors, and outcomes of anemia management in 1394 pediatric patients undergoing peritoneal dialysis (PD) who were prospectively followed in 30 countries. We noted that 25% of patients had hemoglobin levels below target (<10 g/dl or <9.5 g/dl in children older or younger than 2 years, respectively), with significant regional variation; levels were highest in North America and Europe and lowest in Asia and Turkey. Low hemoglobin levels were associated with low urine output, low serum albumin, high parathyroid hormone, high ferritin, and the use of bioincompatible PD fluid. Erythropoiesis-stimulating agents (ESAs) were prescribed to 92% of patients, and neither the type of ESA nor the dosing interval appeared to affect efficacy. The weekly ESA dose inversely correlated with age when scaled to weight but did not correlate with age when normalized to body surface area. ESA sensitivity was positively associated with residual diuresis and serum albumin and inversely associated with serum parathyroid hormone and ferritin. The prevalence of hypertension and left ventricular hypertrophy increased with the degree of anemia. Patient survival was positively associated with achieved hemoglobin and serum albumin and was inversely associated with ESA dose. In conclusion, control of anemia in children receiving long-term PD varies by region. ESA requirements are independent of age when dose is scaled to body surface area, and ESA resistance is associated with inflammation, fluid retention, and hyperparathyroidism. Anemia and high ESA dose requirements independently predict mortality.

Nutritional status, protein intake and progression of renal failure in children.

Nutritional status and progression of renal failure in 35 children (22 males and 13 females; mean age: 8.85+/-4.13 years) with moderate renal failure were followed for 2 years. All children were on an "ad libidum" diet. Protein intake was determined by a minimum of two dietary diaries kept by the parents and the appearance of urea nitrogen. The children were divided into two groups according to their protein intake: Group 1 - sub-optimal intake (46% of the children, all with significantly lower protein intake); Group 2 - adequate protein intake. The mean protein intake (expressed as a percentage of the WHO recommendations) based on the diets of the patients was 94.79% in Group 1 children and 175.45% in Group 2 children (p<0.05). All patients had a calorie intake of at least 80% of the WHO recommendations. Nutritional status was determined by anthropometric measurements expressed as a standard deviation score. There was no significant anthropometric or biochemical evidence of malnutrition in children with moderate chronic renal failure (CRF). The glomerular filtration rate (GFR) in patients with a sub-optimal intake of protein was -5.41+/-2.87 ml/2 year versus-9.53+/-8.61 ml/2 year in the normal protein intake group. There was no correlation between protein intake, nutritional status and progression of renal failure in children with moderate CRF within the 2-year study period.

Renal infarction in a child with systemic lupus erythematosus.

Although patients with systemic lupus erythematosus (SLE), especially those with antiphospholipid antibodies, have a high incidence of arterial and venous thrombotic manifestations, renal infarction has been rarely reported in these patients and is probably underestimated. A 9-year-old boy with renal infarction, diagnosed by computed tomography and scintigraphy, is described. Initially he complained of severe flank pain; he had no urinary abnormalities and his blood pressure was normal. No evidence of systemic disease was found. He responded well to antibiotic treatment without the need for immunosuppressive therapy. In subsequent years he presented a spectrum of clinical symptoms, including fever, malaise, arterial hypertension headache, and mononeuritis multiplex, accompanied by an increased erythrocyte sedimentation rate and transitory proteinuria. This suggested vasculitis involving peripheral vessels as well as the central nervous system. Treatment with oral prednisone and azathioprine led to remission. Four years after the renal infarction, the child presented with recurrence of systemic disease. The diagnosis of SLE was established, with positive antiphospholipid antibodies. The sudden appearance of severe unexplained flank pain should alert the clinician to a possible underlying renal vessel thrombosis. Renal venous thrombosis is probably much more common; however, renal arterial thrombosis and infarction in association with SLE with positive antiphospholipid antibodies should be added to the differential diagnosis.