Gordana Milosevski-Lomic

Renal functional reserve in children with apparently normal congenital solitary functioning kidney

OBJECTIVE The aim of the study was to investigate renal functional reserve (RFR) and to assess its relationship with serum cystatin C and blood pressure in children with apparently normal congenital solitary functioning kidney (SFK). MATERIAL AND METHODS RFR was obtained from the difference of endogenous creatinine clearance (CrCs) before and after a meat-free oral protein load (OPL) in the patients who were pre-treated with cimetidine. Serum cystatin C and urinary protein excretion were determined before and after OPL. RESULTS Among 22 patients (13 boys), aged 9.5 ± 4.3 years, 72.7% had increased serum cystatin C, and 54.5% had decreased RFR. Following OPL, CrCs and urine creatinine increased, while serum creatinine and cystatin C remained unchanged. The multiple regression analysis demonstrated that cystatin C could predict more than 90% of RFR variability. CONCLUSION Half of the patients with apparently normal SFK had decreased RFR. Serum cystatin C is one of the best predictors of RFR.

Henoch-Schönlein purpura outcome in children: A ten-year clinical study

INTRODUCTION Henoch-Schönlein purpura (HSP) is the most common vasculitis of childhood. It is characterized by symptoms including nonthrombocytopenic purpura, abdominal pain, haematuria/proteinuria, and arthralgia/arthritis. The pleiomorphism of clinical signs in HSP could be confused with other conditions or other vasculitis forms. OBJECTIVE Evaluation of HSP clinical presentation, the onset and severity of renal manifestation in affected children and their outcome. METHODS A retrospective study of 49 patients diagnosed with HSP was conducted from September 1999 to September 2009. Children with severe renal manifestations (nephrotic range proteinuria, with or without nephrotic or nephritic syndrome) have undergone kidney biopsy. RESULTS Twenty-five patients developed renal manifestations after onset of the disease. In our study childs older age was a risk factor for association with HSP nephritis. Six of the patients required kidney biopsy. They were successfully treated with various immunosuppressive protocols, as well as three of nine patients with nephrotic range proteinuria. Two patients developed most severe form of HSP nephritis, nephrotic-nephritic syndrome with histology grade IIIb/IVb. During the study period (average followup 6 years), all patients had a normal global renal function with mild proteinuria in only two cases. The prognosis of renal involvement was better than reports from other patient series. CONCLUSION Long-term morbidity of HSP is predominantly attributed to renal involvement. During the study period, no patient had renal insufficiency or end stage renal disease after various combinations of immunosuppressive treatment. It is recommended that patients with HSP nephritis are followed for longer periods of time with a regular measurement of renal function and proteinuria.

Associations of Apgar score and size at birth with lipoprotein subclasses in juvenile obesity

Background/aim: Juvenile obesity is associated with several metabolic abnormalities, one of them being atherogenic dyslipidemia. Suboptimal fetal growth is associated with obesity risk in childhood, but also with increased rate of metabolic diseases in later life. This study investigated associations of neonatal data (Apgar score, birth weight and birth length) with low-density lipoprotein and high-density lipoprotein (LDL and HDL) subclasses in a group of obese children, as well as a possible impact of breastfeeding duration on obesity-associated lipoprotein subclasses distributions.Materials and methods: We included 42 obese children, aged 14.2 ± 2.1 years. LDL and HDL subfractions were separated by gradient gel electrophoresis and biochemical parameters were assessed by routine methods.Results: Compared with obese children with Apgar ≥ 9, the group with Apgar < 9 had significantly higher percentages of small, dense LDL particles (P < 0.05), due to reduced LDL I (P < 0.01) and increased LDL III subclasses (P < 0.05). Birth weight was positively associated with the proportions of LDL I particles (P < 0.001), whereas birth height positively correlated with the amount of HDL 2b subclasses (P < 0.05). The group of never or less than 3 months breastfed children had significantly smaller LDL size (P < 0.01) and lower proportion of HDL 2a particles (P < 0.05) than their ≥3 months breastfed peers.Conclusion: The results showed significant associations of neonatal characteristics with LDL and HDL particle distributions in obese children. In addition, our results point toward positive aspects of longer breastfeeding duration on lipoprotein particle distributions in obese children.

Renal functional reserve in children with a solitary functioning kidney and chronic kidney disease

O bjective – To examine renal functional reserve (RFR) and blood pressure (BP) in children with a solitary functioning kidney (SFK) and stage 1-3 chronic kidney disease (CKD). M ethod – RFR was measured in 48 children with SFK and in 10 healthy children, as the difference between unstimulated and stimulated clearance of endogenous creatinine by a meat-free oral protein load (OPL). Cimetidine was given 48 h prior to the measurement when the study subjects were on a diet free of meat, fish and poultry. Serum cystatin C and urinary protein (UPRT)/urinary creatinine (UCr) were examined before and 2 hours after OPL. BP was determined by office and by 24-h ambulatory BP monitoring (ABPM). R esults – The majority of the patients (79.6%) had congenital SFK, while the remaining had acquired SFK due to unilateral nephrectomy. Sixteen patients had CKD1, 19 patients had CKD2 and 13 had CKD3. The patients and controls did not differ in terms of age, gender, body size, office and 24-h blood pressure readings and basal GFR. Kidney size was greater and serum cystatin C was higher in patients than in controls. Increased proteinuria and arterial hypertension were found in 24.3% and 18.9% of the patients, respectively. Nocturnal hypertension was more common than that during the daytime. After OPL, GFR significantly increased, more in controls than in patients. Among the patients, the RFR was the highest in the CKD3 group. Conclusion – OPL induced an increase in GFR above its basal value. This response was higher in healthy children than in those with SFK. The positive relationship between RFR and CKD stage and the highest RFR in CKD3 patients suggests well preserved renal functional reserve in patients with moderate renal failure. ABPM is necessary for BP evaluation in children with SFK.

Hypercalciuria caused by CYP24A1 mutation: Fourteen years of the patient’s follow-up

Introduction Recently, inactivation mutations of CYP24A1, the gene encoding vitamin D 24-hydroxylase, were identified in hypercalciuric nephrolithiasis and nephrocalcinosis. Here, we describe а long-term follow-up of a patient with hypercalciuric nephrolithiasis caused by CYP24A1 mutations. Case outline A male Montenegro patient first presented with microhematuria at the age of five years. Hypercalciuria had been documented and for some time he had been treated by hydrochlorothiazide. After 12 years, the patient presented with macrohematuria and left-sided nephrolithiasis. He was found to have intermittent borderline hypercalcemia, suppressed parathyroid hormone, hypercalciuria, and increased plasma 25-hydroxy vitamin D [25(OH)D3]. The patient denied any vitamin D supplementation and all other causes of hypercalcemia were ruled out. Positive family history for nephrolithiasis (both parents and grandmother) and similar biochemical abnormalities detected in father and son pointed to an inherited disorder. A homozygous mutation in CYP24A1 (E143del) was found in the patient and his father, while mother is heterozygous. During the follow-up of two years, the patient underwent four extracorporeal shockwave lithotripsies, he was advised to increase water intake, and to avoid sunlight exposure. At the end of follow-up he was asymptomatic, and his renal ultrasound was normal, as well as his renal function, but hypercalciuria and low parathyroid hormone levels persisted. Conclusion Hypervitaminosis D should be considered in children with idiopathic hypercalciuria, nephrolithiasis and nephrocalcinosis of unknown etiology. Recognition of CYP24A1 mutations in these patients may help to decrease the serious consequences by avoiding vitamin D supplements and excessive sun exposure.

Serum Neutrophil Gelatinase-Associated Lipocalin and Urinary Kidney Injury Molecule-1 as Potential Biomarkers of Subclinical Nephrotoxicity After Gadolinium-Based and Iodinated-Based Contrast Media Exposure in Pediatric Patients with Normal Kidney Function

Background New renal biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) show promise in early diagnosis of contrast media induced acute kidney injury (CI-AKI). The purpose of our study was to compare the subclinical nephrotoxicity (a condition without changes in standard renal biomarkers) of gadolinium-based contrast media (Gd-DTPA, gadopentetate dimeglumine) and iodinated-based contrast media (iopromide) in pediatric patients with normal kidney function. Material/Methods The first group (n=58) of patients included in the study were undergoing angiography with iopromide, and the second group (n=65) were undergoing magnetic resonance (MR) angiography/urography with Gd-DTPA administration. The concentrations of NGAL and KIM-1 were measured four times in the urine (pre-contrast, then at four hours, 24 hours, and 48 hours after contrast administration), and serum NGAL was measured at 0 (baseline), 24 hours, and 48 hours after contrast exposure. Results After 24 hours, serum NGAL increase of ≥25% was noticed in 32.6% of the patients in the iopromide group and in 25.45% of the patients in the gadolinium group, with significantly higher average percent of this increase in first group (62.23% vs. 36.44%, p=0.002). In the Gd-DTPA group, we observed a statistically significant increase in urinary KIM-1 24 hours after the procedure. Normalized urinary KIM-1, 24 hours after contrast exposure, was a better predictive factor for CI-AKI than other biomarkers (AUC 0.757, cut off 214 pg/mg, sensitivity 83.3%, specificity 54.2%, p=0.035). Conclusions In children with normal renal function, exposure to iodinated-based and gadolinium-based media might lead to subclinical nephrotoxicity, which could be detected using serum NGAL and urinary KIM-1.

Hypertension, lipoprotein subclasses and lipid transfer proteins in obese children and adolescents

Abstract Background: Obesity-related childhood hypertension is associated with disturbances of serum lipids, but less is known about distribution of lipoprotein subclasses and activities of proteins involved in reverse cholesterol transport in hypertensive obese children. Our objective was to determine low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses distribution and activities of lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) in hypertensive and non-hypertensive obese children. Methods: A total of 40 hypertensive and 25 non-hypertensive obese children were enrolled. Lipoprotein subclasses were assessed by polyacrylamide gradient gel electrophoresis. LCAT and CETP activities were determined as a rate of formation and a rate of transfer of cholesteryl esters. Results: Despite of comparable values of serum lipid parameters, a shift toward smaller LDL and HDL subclasses was observed in hypertensive compared to normotensive obese children. Activities of LCAT were similar, but proatherogenic CETP activities were significantly higher in the hypertensive group (p = 0.036). LCAT/net CETP ratio inversely correlated with relative proportion of small, dense LDL particles (ρ = −0.423; p = 0.025) in the group with hypertension. Conclusions: The results of our study demonstrated a tendency toward altered distribution of lipoprotein subclasses in favor of more proatherogenic particles in childhood hypertension. Also, hypertensive obese children had increased proatherogenic CETP activity.

Associated extrarenal vascular diseases may complicate the treatment and outcome of renovascular hypertension

This studied reviewed renovascular hypertension (RVH) due to renal artery stenosis (RAS) in two Serbian paediatric centres from 2001 to 2013.

Pulmonary inflammatory myofibroblastic tumor associated with nephrotic syndrome

Inflammatory myofibroblastic tumor (IMT) of the lung is a benign, non-metastasizing tumor with the possibility of local infiltration, recurrence or persistent local growth. This kind of tumor arises due to an unregulated growth of inflammatory cells. To our knowledge, IMT associated with nephrotic syndrome has not yet been recognized. Therefore, we present the case of a 14-year-old girl with lung IMT associated with secondary nephrotic syndrome (NS), which was cured after tumor removal.