Browsing by Author "Bogdanović, Radovan (7004665744)"

Dent disease is an X-linked recessive disorder affecting the proximal tubule and is characterized by low-molecular-weight proteinuria (LMWP), hypercalciuria, nephrocalcinosis/nephrolithiasis with a variable number of features of Fanconi syndrome. It is most often associated with mutations in CLCN5, which encodes the endosomal electrogenic chloride/proton exchanger ClC-5. Renal acidification abnormalities are only rarely seen in Dent disease, whereas the hypokalemic metabolic alkalosis associated with hyperreninemic hyperaldosteronism (Bartter-like syndrome) has been reported in only one patient so far. We report on a 5-year-old boy with Dent disease caused by mutation in CLCN5 gene, c.1073G>A, who presented with hypokalemic metabolic alkalosis and hyperreninemic hyperaldosteronism persisting over the entire follow-up. No mutations were found in NKCC2, ROMK, NCCT, or ClC-Kb genes. In addition, the patient exhibited growth failure associated with partial growth hormone (GH) deficiency. Coexistence of Bartter-like syndrome features with LMWP should prompt a clinician to search for Dent disease. The Bartter syndrome phenotype seen in Dent disease patients may represent a distinct form of Bartter syndrome, the exact mechanism of which has yet to be fully elucidated. Growth delay that persists in spite of appropriate therapy should raise suspicion of other causes, such as GH deficiency. © 2010 IPNA.

Ciliopathies are genetically heterogeneous disorders characterized by variable expressivity and overlaps between different disease entities. This is exemplified by the short rib-polydactyly syndromes, Jeune, Sensenbrenner, and Mainzer-Saldino chondrodysplasia syndromes. These three syndromes are frequently caused by mutations in intraflagellar transport (IFT) genes affecting the primary cilia, which play a crucial role in skeletal and chondral development. Here, we identified mutations in IFT140, an IFT complex A gene, in five Jeune asphyxiating thoracic dystrophy (JATD) and two Mainzer-Saldino syndrome (MSS) families, by screening a cohort of 66 JATD/MSS patients using whole exome sequencing and targeted resequencing of a customized ciliopathy gene panel. We also found an enrichment of rare IFT140 alleles in JATD compared with nonciliopathy diseases, implying putative modifier effects for certain alleles. IFT140 patients presented with mild chest narrowing, but all had end-stage renal failure under 13 years of age and retinal dystrophy when examined for ocular dysfunction. This is consistent with the severe cystic phenotype of Ift140 conditional knockout mice, and the higher level of Ift140 expression in kidney and retina compared with the skeleton at E15.5 in the mouse. IFT140 is therefore a major cause of cono-renal syndromes (JATD and MSS). The present study strengthens the rationale for IFT140 screening in skeletal ciliopathy spectrum patients that have kidney disease and/or retinal dystrophy. © 2013 Wiley Periodicals, Inc.

Ciliopathies are genetically heterogeneous disorders characterized by variable expressivity and overlaps between different disease entities. This is exemplified by the short rib-polydactyly syndromes, Jeune, Sensenbrenner, and Mainzer-Saldino chondrodysplasia syndromes. These three syndromes are frequently caused by mutations in intraflagellar transport (IFT) genes affecting the primary cilia, which play a crucial role in skeletal and chondral development. Here, we identified mutations in IFT140, an IFT complex A gene, in five Jeune asphyxiating thoracic dystrophy (JATD) and two Mainzer-Saldino syndrome (MSS) families, by screening a cohort of 66 JATD/MSS patients using whole exome sequencing and targeted resequencing of a customized ciliopathy gene panel. We also found an enrichment of rare IFT140 alleles in JATD compared with nonciliopathy diseases, implying putative modifier effects for certain alleles. IFT140 patients presented with mild chest narrowing, but all had end-stage renal failure under 13 years of age and retinal dystrophy when examined for ocular dysfunction. This is consistent with the severe cystic phenotype of Ift140 conditional knockout mice, and the higher level of Ift140 expression in kidney and retina compared with the skeleton at E15.5 in the mouse. IFT140 is therefore a major cause of cono-renal syndromes (JATD and MSS). The present study strengthens the rationale for IFT140 screening in skeletal ciliopathy spectrum patients that have kidney disease and/or retinal dystrophy. © 2013 Wiley Periodicals, Inc.

Aim: Aim of the study was to determine if carotid intima media thickness in children with idiopathic nephrotic syndrome is greater than in healthy subjects, and to assess whether carotid intima media thickness in children with nephrotic syndrome is associated with clinical (including disease duration, cumulative dose of steroids, number of relapses) and biochemical parameters. Methods: A cross-sectional study included 40 patients with nephrotic syndrome (mean age 11.7 ± 4.7 years). Steroid dependent nephrotic syndrome was established in 32 patients (80%), while 8 (20%) had steroid resistant nephrotic syndrome. Control group consisted of 20 age and gender matched healthy children. Blood pressure based on 24-h ambulatory blood pressure monitoring (ABPM), carotid intima media thickness, fasting glucose, insulin, HbA1c, lipid concentrations were measured in all children. Results: A significant difference was detected in carotid intima media thickness values (P = 0.036). Children with nephrotic syndrome had significantly greater carotid intima media thickness compared with healthy children (0.42 ± 0.06 and 0.38 ± 0.03 mm). Carotid intima-media thickness was positively associated with duration of nephrotic syndrome (r = 0.45; P = 0.004), body mass index (r = 0.48; P = 0.002), daytime systolic blood pressure (r = 0.46; P = 0.003) and night-time systolic blood pressure (r = 0.52; P = 0.001). Multiple linear regression showed that duration of nephrotic syndrome was the only independent predictor of carotid intima media thickness in children with nephrotic syndrome (R2 = 0.244; β=0.327; P = 0.037). Conclusion: The findings of the present study suggest subclinical vascular damage in patients with nephrotic syndrome. Duration of nephrotic syndrome was the only independent predictor of carotid intima media thickness. © 2020 Société francophone de néphrologie, dialyse et transplantation

Conclusions: The most important finding of our study is that nestin can be used as a potential new early morphological predictor of kidney dysfunction in childhood onset of FSGS, since nestin has been obviously decreased in both sclerotic and normal glomeruli seen by light microscopy.; Methods: Among 649 renal biopsy samples, obtained from two children’s hospitals, FSGS was diagnosed in 60 children. Thirty-eight patients, who met the criteria for this study, were followed up for 9.0 ± 5.2 years. Using Kaplan–Meier and Cox’s regression analysis, potential clinical and morphological predictors were applied in two models of prediction: after disease onset and after the biopsy.; Results: The present study revealed the following significant predictors of kidney dysfunction: patients’ ages at disease onset, as well as age at biopsy, resistance to corticosteroid treatment, serum creatinine level, urine protein/creatinine ratio, vascular involvement, tubular atrophy, interstitial fibrosis, and decreased glomerular nestin expression.; Background: A high prevalence of chronic kidney disease among children with focal segmental glomerulosclerosis (FSGS) leads to a permanent quest for good predictors of kidney dysfunction. Thus, we carried out a retrospective cohort study in order to examine known clinical and morphological predictors of adverse outcome, as well as to investigate glomerular nestin expression as a potential new early predictor of kidney dysfunction in children with FSGS. Relationships between nestin expression and clinical and morphological findings were also investigated. © 2014, IPNA.

Background: Growth retardation is one of the most visible comorbid conditions of chronic kidney disease (CKD) in children. To our knowledge, published data on longitudinal follow-up of growth in pediatric patients with CKD is lacking from the region of South-East Europe. Herein we report the results from the Serbian Pediatric Registry of Chronic Kidney Disease.; Methods: The data reported in the present prospective analysis were collected between 2000 and 2012. A total of 324 children with CKD were enrolled in the registry.; Results: Prevalence of growth failure at registry entry was 29.3 %. Mean height standard deviation scores (HtSDS) in children with stunting and those with normal stature were −3.00 [95 % confidence interval (CI) −3.21 to −2.79] and −0.08 (95 % CI −0.22 to 0.05) (p < 0.001), respectively. Children with hereditary nephropathy had worse growth at registration (−1.51; 95 % CI −1.97 to −1.04, p = 0.008). Those with CKD stages 4 and 5 before registration had more chance to have short stature at registration than those with CKD stages 2 and 3 [odds ratio (OR) = 0.458, CI 0.268–0.782, p = 0.004]. Dialysis was an independent negative predictor for maintaining optimal stature during the follow-up period (OR = 0.324, CI = 0.199–0.529, p < 0.001), while transplantation was an independent positive predictor for improvement of small stature during follow-up (OR = 3.706, CI = 1.785–7.696, p < 0.001).; Conclusion: Growth failure remains a significant problem in children with CKD, being worst in patients with hereditary renal disease. Growth is not improved by standard dialysis, but transplantation has a positive impact on growth in children. © 2014, Italian Society of Nephrology.

Cellular immune disturbances, and T lymphocyte function in particular, have been previously implicated in idiopathic nephrotic syndrome (INS) of childhood. There are different patterns of cytokine expression in various forms of glomerulonephritis, which suggests that local production of these peptides plays an important role in the pathogenesis and progression of glomerulonephritis. To investigate T-cell and monocyte/macrophage cytokine production in INS, interleukin-12 (IL-12) and interferon-γ (IFN-γ) production by peripheral blood mononuclear cells (PBMC) of 11 children with steroid-sensitive nephrotic syndrome (SSNS), 9 with focal segmental glomerulosclerosis (FSGS), and 17 healthy controls was determined. Children with SSNS were studied in relapse, during corticosteroid treatment, and in stable remission, off corticosteroid treatment. IL-12 was not detected in serum, urine, and in supernatants of unstimulated PBMC. IL-12 production by concanavalin A (Con A)-stimulated PBMC of children with SSNS and FSGS was not different from controls. IFN-γ production by Con A-stimulated PBMC was decreased in children with relapsing SSNS, both in relapse and and during corticosteroid treatment. However, in stable remission it was similar to controls. Markedly decreased IFN-γ production (P < 0.001) was observed by pokeweed mitogen-stimulated PBMC of relapsing SSNS patients and moderately decreased production by PBMC of FSGS patients. This study has established a decreased production of IFN-γ by PBMC of relapsing SSNS and FSGS patients, but does not allow differentiation between these two different conditions. IL-12 did not have a pathogenic role in either SSNS or FSGS.

Severe and reproducible low-renin hypertension responsive to salt restriction and amiloride-thiazide therapy in a 13-year-old otherwise asymptomatic boy suggested Liddle syndrome. This assumption was strengthened by a positive family history of hypertension poorly responsive to conventional treatment or sudden deaths under 40 years of age in four generations. DNA analysis of the beta and gamma subunits of the epithelial sodium channel revealed a heterozygous mutation c.C1852T (p.Pro618Ser) in the SCNN1B gene in the patient and in both his hypertensive mother and uncle. A PubMed search revealed 21 different disease-causing mutations reported to date, all but two clustering in the cytoplasmic C-terminal regions of either beta (16 mutations) or gamma (5) subunit, leading to a three- to eightfold increase in the amiloride-sensitive sodium current. Inter- and intrafamilial variability in both hypertension and hypokalemia were disclosed, which may not be obligatory among the subjects carrying a Liddle mutation. Conclusion: Liddle syndrome should be considered as a cause of hypertension in children or adolescents particularly with suppressed renin activity. Early diagnosis and appropriately tailored treatment avoid complications of long-term unrecognized or inappropriately managed hypertension. © Springer-Verlag 2011.

Background: Pulmonary renal syndrome (PRS), denoting the presence of diffuse alveolar hemorrhage and glomerulonephritis as manifestations of systemic autoimmune disease, is very rare in childhood. The coexistence of circulating anti-neutrophil cytoplasmic antibody (ANCA) and anti-glomerular basement membrane (GBM) disease in children affected by this syndrome is exceptional, with unfavorable outcome in five out of seven patients reported to date. We describe a child with PRS associated with both circulating anti-myeloperoxidase (anti-MPO) ANCA and anti-GBM disease on renal biopsy who was successfully treated with immunosuppressive therapy. Case presentation. A 10-year old girl presented with fever, fatigue, malaise, and pallor followed by hemoptysis and severe anemia. Diffuse alveolar hemorrhage was revealed on fiberoptic bronchoscopy. Renal findings consisted of microscopic hematuria, moderate proteinuria, and anti-GBM disease on renal biopsy. ANCA with anti-MPO specificity were present whereas anti-GBM antibodies were on borderline for positivity. Methyl-prednisolone pulses followed by prednisone led to cessation of hemoptysis, marked improvement of lung fuction, and normal finding on chest x-ray within 10 days. An immunosuppressive regimen was then given consisting of prednisone daily for 4 weeks with subsequent taper on alternate day, i.v. cyclophosphamide pulses monthly for 6 doses, followed by mycophenolate mofetil that resulted in normal lung function tests, hemoglobin concentration, and anti-MPO level within four subsequent weeks. During 10-months of follow-up she remained well, her blood pressure and renal function tests were normal, and proteinuria and hematuria gradually resolved. Conclusion: We report a child with an exceptionally rare coexistence of circulating ANCA and anti-GBM disease manifesting as PRS in whom renal disease was not the prominent part of clinical presentation, contrary to other reported pediatric patients. A review of literature on disease with double positive antibodies is also presented. Evaluation of a patient with PRS should include testing for presence of different antibodies. An early diagnosis and rapid institution of aggressive immunosuppressive therapy can induce remission and preserve renal function. Renal prognosis depends on the extent of kidney injury at diagnosis and appropriate treatment. © 2013 Bogdanović et al.; licensee BioMed Central Ltd.

A boy who developed haemolytic-uraemic syndrome (HUS) at 8 years 6 months of age had four further episodes of the disease during the next 3 years. No renal abnormalities were detected between the attacks nor in the 2.5 years after the last recurrence. Reduced levels of serum complement were found during four of the episodes and in two intervening periods. © 1988 IPNA.

Renal tubular acidosis (RTA) is common in adults with primary Sjogren syndrome (pSS) but to date this condition has only been identified in 12 pediatric cases of pSS. Here we present the case of a 13-year-old, otherwise asymptomatic girl in whom the search for the etiology of incidentally found nephrocalcinosis led to diagnosis of distal RTA and nephrogenic diabetes insipidus secondary to SS-associated tubulointerstitial nephritis. Immunosupressive treatment and alkali/electrolyte supplementation resulted in stable renal function over the 6-year follow-up. A review of the literature focuses on two aspects of pSS: (1) the difficulties in diagnosing pSS in childhood and (2) clinical-pathological features, treatment and outcome of renal tubulointerstitial disease in childhood pSS. SS should be considered in older children, particularly females with otherwise unexplained RTA. A careful search for other renal dysfunctions is necessary, and renal biopsy may be of value in assessing the extent of renal damage and the need for immunomodulatory therapy. © 2012 Japan College of Rheumatology.

The health care system in Serbia is based on a network of public health institutions funded by the National Health Insurance and from the state budget. Access to public health institutions is free. Preventive and curative services are provided at the local level in primary health care centers. Over the past 5-7 years, the number of pediatricians in primary health care centers decreased because of reduced number of applicants for pediatric training, which endangers the maintenance of the traditional model of pediatric care. Secondary medical care is offered in pediatric departments of local and regional general hospitals or outpatient clinics, and in specialized hospitals for children or adults. Tertiary medical care is provided by inpatient or outpatient subspecialty services in 5 major university children's clinics. The health reforms undertaken in the recent 10 years have aimed at strengthening preventive health care and reducing the overall costs for pediatric care. Current initiatives of the Ministry of Health and national pediatric associations are aimed at reestablishing and strengthening the capacity of the primary pediatric health care model by increasing the number of physicians and developing new processes of care. © 2016 Elsevier Inc.

Eight boys aged 2-12 weeks with urinary tract malformations (UTMs) exhibited features of transient type 1 pseudo-hypoaldosteronism (TPHA1) in the course of urinary tract infection (UTI). Hyponatremia (120.9±5.8 mmol/l), hyperkalemia (6.9±0.9 mmol/l), metabolic acidosis (plasma bicarbonate 11±1.4 mmol/l), and a rise in serum creatinine levels (145±101 μmol/l) were associated with high urinary sodium (Na) and low potassium (K) excretion. Tubular resistance to aldosterone was indicated by high plasma aldosterone concentrations (170.4±100.5 ng/dl), high levels of the plasma aldosterone to potassium ratio (25.2±15.6), and diminished urinary K/Na values (0.31±0.19). With appropriate therapy, serum electrolytes, creatinine, and acid-base balance normalized within 2 weeks. A Medline search revealed another 85 cases of TPHA1 reported to date. All of the 93 patients were less than 7 months of age and 90% were less than 3 months of age, 90.3% suffered from UTM, with associated UTI in 89% of them, 11% had UTM in the absence of UTI, and 9.7% showed isolated UTI. These findings indicate that early infancy is the main contributing factor for TPHA1 to occur and that UTI and UTM are additional factors, with at least one being required for its development. © IPNA 2009.