The Rationale of Complement Blockade of the MCPggaac Haplotype following Atypical Hemolytic Uremic Syndrome of Three Southeastern European Countries with a Literature Review.

We present eight cases of the homozygous MCPggaac haplotype, which is considered to increase the likelihood and severity of atypical hemolytic uremic syndrome (aHUS), especially in combination with additional risk aHUS mutations. Complement blockade (CBT) was applied at a median age of 92 months (IQR 36-252 months). The median number of relapses before CBT initiation (Eculizumab) was two. Relapses occurred within an average of 22.16 months (median 17.5, minimum 8 months, and maximum 48 months) from the first subsequent onset of the disease (6/8 patients). All cases were treated with PI/PEX, and rarely with renal replacement therapy (RRT). When complement blockade was applied, children had no further disease relapses. Children with MCPggaac haplotype with/without additional gene mutations can achieve remission through renal replacement therapy without an immediate need for complement blockade. If relapse of aHUS occurs soon after disease onset or relapses are repeated frequently, a permanent complement blockade is required. However, the duration of such a blockade remains uncertain. If complement inhibition is not applied within 4-5 relapses, proteinuria and chronic renal failure will eventually occur.

Plasmapheresis in Pediatric Intensive Care Unit.

INTRODUCTION: Plasmapheresis also known as a therapeutic plasma exchange (TPE) is extracorporeal procedure by which individual components of plasma that are harmful or blood cells can be removed from organism by using a blood separation technology. AIM: To present the results of the implementation of plasmapheresis in children in the Department of Pediatric Intensive Care of Pediatric Clinic, Clinical center of Sarajevo University, Bosnia and Herzegovina. PATIENTS AND METHODS: Research (period from December 2011 to June 2016) analyzed 66 plasmapheresis (11 patients-6 plasmapheresis per patient). RESULTS: Out of 11 patients, 7 (63.6%) were girls and 4 (36.4%) were boys. The average age of patients was 11.6 ± 3.9 years (the youngest patient had 4 years and 7 months, while the oldest had 16 years and 10 months). Plasmapheresis were significantly more often done in the winter and summer. Underlying disease was in 54.5% of cases of neurological origin. The treatment was in form of receiving IVIG in 7 patients, or the application of mechanical ventilation in 6 patients. The most common complication was hypotension, which occurred in 45.5% of patients, followed by bleeding in 36.3%, hypercoagulability in 27.2% of patients and hematoma in 27.2% of patients. Lethal outcome occurred in 3 (27.2%) patients. CONCLUSION: Plasmapheresis represents an invasive method due to need for placement of centralized venous catheter that provides adequate blood flow during the procedure. Although complications can be serious, they are rare and are mainly related to the presence of central venous catheter, hemostasis disorders due to use of anticoagulant therapy, and hypotension of the cardiovascular system. It should be noted that for success of plasmapheresis in children multidisciplinary approach is necessary (children's nephrologist, neuropediatrician, intensive care doctor) as well as well-trained team of doctors and nurses with the acquired knowledge and skills.

Evaluation of Inflammatory Parameters Following Extracorporeal Shock Wave Lithotripsy (ESWL) and Ureteroscopy for the Treatment of Proximal Ureteral Stones.

Introduction Inflammation can arise as a consequence of both extracorporeal shock wave lithotripsy (ESWL) and ureteroscopy (URS) treatments. Alterations in inflammatory parameters may serve as indicators of kidney injuries and the ensuing inflammation. This study aims to investigate the effects of ESWL and URS procedures on inflammatory parameters for proximal ureteral stone treatment. Materials and methods A prospective interventional study comprised 120 patients with confirmed stones measuring less than 10 mm in the upper half of the proximal ureter. These patients were randomly assigned to either the ESWL or URS treatment groups. Laboratory analyses encompassed interleukin-6 (IL-6), leukocyte count, fibrinogen levels, and erythrocyte sedimentation rate (ESR), which were assessed prior to the intervention, on the first postoperative day, and six months later. IL-6 levels in the serum were determined using a chemiluminescence immunoassay (CLIA). Results There was no significant difference in IL-6 levels between pre-intervention and the first post-intervention day in patients treated with ESWL (1.8 (1.4-2.59) pg/mL vs. 2.33 (1.22-3.19) pg/mL). However, for patients treated with URS, the pre-intervention IL-6 value was 2.9 (1.9-3.34) pg/mL, and it increased significantly to 7.1 (3.85-28.07) pg/mL on the first post-intervention day (p<0.001). On the first post-intervention day, levels of IL-6, CRP, leukocyte count, and ESR were significantly higher in patients treated with URS compared to ESWL (p<0.001; p<0.001; p=0.03; p=0.03, respectively). Conclusion Our research findings suggest that monitoring IL-6 levels can offer valuable insights into the degree of inflammation and tissue damage during and following observed procedures, particularly among patients undergoing URS, even within the initial days post-procedure.

Diversity of kidney care referral pathways in national child health systems of 48 European countries.

Background: Primary, secondary and tertiary healthcare services in Europe create complex networks covering pediatric subspecialties, sociology, economics and politics. Two surveys of the European Society for Paediatric Nephrology (ESPN) in 1998 and 2017 revealed substantial disparities of kidney care among European countries. The purpose of the third ESPN survey is to further identify national differences in the conceptualization and organization of European pediatric kidney health care pathways during and outside normal working hours. Methods: In 2020, a questionnaire was sent to one leading pediatric nephrologist from 48 of 53 European countries as defined by the World Health Organization. In order to exemplify care pathways in pediatric primary care nephrology, urinary tract infection (UTI) was chosen. Steroid sensitive nephrotic syndrome (SSNS) was chosen for pediatric rare disease nephrology and acute kidney injury (AKI) was analyzed for pediatric emergency nephrology. Results: The care pathways for European children and young people with urinary tract infections were variable and differed during standard working hours and also during night-time and weekends. During daytime, UTI care pathways included six different types of care givers. There was a shift from primary care services outside standard working hours to general outpatient polyclinic and hospital services. Children with SNSS were followed up by pediatric nephrologists in hospitals in 69% of countries. Patients presenting with community acquired AKI were admitted during regular working hours to secondary or tertiary care hospitals. During nights and weekends, an immediate shift to University Children's Hospitals was observed where treatment was started by intensive care pediatricians and pediatric nephrologists. Conclusion: Gaps and fragmentation of pediatric health services may lead to the risk of delayed or inadequate referral of European children with kidney disease to pediatric nephrologists. The diversity of patient pathways outside of normal working hours was identified as one of the major weaknesses in the service chain.

Outcomes of acute kidney injury in critically ill children who need renal replacement therapy.

Aim To determine an outcome of acute kidney injury (AKI) in critically ill children (CIC) who needed renal replacement therapy (RRT) and were admitted to the Paediatric and Neonatal Intensive Care Unit (PICU and NICU) at the Paediatric Clinic, University Clinical Centre Sarajevo (UCCS). Methods The research included 81 children with AKI. The Kidney Disease: Improving Global Outcomes (KDIGO) criteria to define AKI was used. Other laboratory findings and imaging tests were made depending on children's primary disease that led to the AKI. Results Among 81 children with AKI, 38 were girls and 43 boys. A total of 39 (48.1%) patients died; the death was due to the nature of the primary disease and multiple organ failure syndromes. Out of the total of 81 patients the highest mortality rate was found in children in the first year of life, 22 (56.4%), while 17 (43.6%) patients died after the first year of life. Conclusion Without an accurate diagnosis at the right time, due to the lack of adequate biomarkers for AKI screening, the heterogeneity of AKI, comorbidities often lead to unfavourable outcomes of the disease, among CIC, especially in infants with low birth weight and extreme immaturity. Some causes of AKI are preventable and can be reduced by a better organization of primary and secondary health care.

The Causes of Acute Kidney Injury in Critically Ill Children Who Needs Renal Replacement Therapy.

Background: Acute kidney injury (AKI) is the result of various causes and is associated with significant morbidity and mortality as well as long-term renal sequelae in pediatric patients. Objectives: The aim of the study is to determine the causes of AKI in pediatric patients who needed renal replacement therapy (RRT) and were admitted to the Pediatric and Neonatal Intensive Care Unit (PICU and NICU) at the Pediatric Clinic, University Clinical Center Sarajevo (UCCS). Methods: Our research included 81 children with AKI who needed RRT. We used the Kidney Disease: Improving Global Outcomes (KDIGO) criteria to define AKI. Severe acute kidney injury was defined as stage 2 or 3 of AKI when plasma creatinine level ≥2 times the baseline level or urine output <0.5 ml per kilogram of body weight per hour for ≥12 hours. Other laboratory findings and imaging tests were made depending on their primary disease that led to the AKI and its complications. Results: Our research analyzed 81 children with AKI who needed RRT 38 girls and 43 boys ages from birth to 18 years. Mean age of presentation was 6.28 years. Male female ratio in this study was 1.1:1. Non-olyguric AKI was diagnosed in 12 (14.8%) of children with AKI, while the rest 69 (85.2%) had the olyguric type. Patients with AKI were analyzed after a rough division on prerenal in 57 (70.4%) children, intrarenal in 23 (28.4%) and post-renal in 1 (1.2%) patient. Conclusion: As the AKI plays a key role in the mortality and morbidity in pediatric patients, especially in infants, it is important to recognise and treatment on time different etiologies of this serious condition. Some causes of AKI in our country can be prevented by better organization of primary and secondary health care, which would also reduce mortality and morbidity from AKI.

Evaluation of Congenital Hydronephrosis with Static and Dynamic Magnetic Resonance Urography in Comparation to Dynamic Renal Scintigraphy.

INTRODUCTION: Congenital hydronephrosis (CH) is a condition with dilated renal pelvis with or without dilation of renal calyces. AIM: To examine the role of magnetic resonance urography in the detection of congenital hydronephrosis in comparison to dynamic renal scintigraphy (DRS). PATIENTS AND METHODS: Resarch included 58 (n=58) patients with diagnosis of congenital unilateral or bilateral dilatation of kidney duct system. Each patient had a one-time or multiple hospitalization at the Nephrology Department of the Pediatric Clinic, with performed: ultrasound which confirmed CH, voiding cystourethrography / voiding urosonography was confirmed based on which the vesicoureteral reflux (VUR) was established / excluded, dynamic renal scintigraphy and magnetic urography (analysis was made by CHOP-fMRU software) on the basis of which the uterine anatomy and the relative renal function were evaluated. RESULTS: Male patients were represented in 40 cases (69%). The average age was 4.4 ± 4.3 years with the youngest patient at the age of 2 months, and the oldest was 17 years old. According to diagnostic entities, the most common diagnosis was ureteropelvic junction (UPJ) obstruction in over half of cases (30 or 51.7%), followed by subjects with ureterovesical junction (UVJ) obstruction (11 or 19%), VUR was recorded in 9 (15.5%) cases, and pyelon fissus in 7 (12.1%), and one case (1.7%) was recorded with bilateral megaureter. Comparison of the value of the renal function obtained with DRS and CHOP-fMRU methods shows that there were no statistically significant differences between two methods. In the case of right kidney, the mean DRS value was 53.4 ± 18.4% (range 13-100%), while CHOP-fMRU was 51.8 ± 22.4 (range 0-96.7%). In the case of left kidney, the average value according to the DRS method was 46.9 ± 18.9% (range 0-87%) and according to CHOP-fMRU 47.6 ± 21.5% (range 8.3-100%). The correlation coefficients of both right and left kidneys show a highly statistically significant correlation between these two methods. CONCLUSION: Magnetic resonance urography in the pediatric population in CH based on results should be an integral part of the management of these patients, especially in congenital obstructive uropathy, in complex and associated congenital anomalies, as it provides morphological and functional data on the state of the kidneys and urinary tract.

Vesicoureteral Reflux and Renal Scarring in Infants After the First Febrile Urinary Tract Infection.

INTRODUCTION: The objective of this research was to determine whether vesicoureteral reflux(VUR) was associated with evolution to renal scarring (RS) following a febrile urinary tract infection (UTI) in infants. MATERIALS AND METHODS: Our research included 100 infants, ages up to 1 year with a first febrile UTI. The diagnostic was based on results of: laboratory findings, ultrasonography (USG), voiding cystourethrography (VCUG) and initial and control renal scintigraphy (DMSA renal scan) withtechnetium99mTcsuccimer (dimercaptosuccinic acid), to assess the acute pyelonephritis (APN), VUR and RS. RESULTS: APN was proven with DMSA renal scan in 66 (66%) infants. Twenty-two infants (33.3%) had VUR in-group of patients with APN. On the control DMSA scan, performed 6 months after the first DMSA, the presence of RS was found in 18 (27.27%) infants. In infants with renal scars VUR were discovered in 9 of them (50%). CONCLUSIONS: The pathogenesis of RS after febrile UTI in young children is multifactorial. Children with VUR have an increased risk for APN and RS. However, VUR is not the only precondition for RS. Creating a renal scarring cannot be imagined without the inflammatory process of the upper urinary system. Therefore, early detection and treatment of febrile UTIs in children and identify children at risk for RS are of primary importance.

Children with Steroid-Resistant Nephrotic Syndrome: A Single -Center Experience.

BACKGROUND: Nephrotic syndrome (NS) is one of the most frequent glomerular diseases among children. While most of the children with primary NS respond to steroid treatment, 10 to 20% of the patients are steroid-resistant, and the best therapy for such cases has never been defined. OBJECTIVE: The present study aimed to evaluate steroid-resistant nephrotic syndrome (SRNS) patients. MATERIALS AND METHODS: Our research included 50 children (56% female and 44% male) with NS. NS was defined as the presence of edema, massive proteinuria, hypoalbuminemia and hyperlipidemia. Patients with NS were treated according to international protocol. SRNS was diagnosed in patients with idiopathic NS based on lack of complete remission despite treatment with steroids. Renal biopsy was performed in 22 patients with SRNS at the Pediatric Clinic II of the University Clinical Center in Sarajevo (UCCS). Histopathologic analyzes of renal biopsy were performed at the Department of Pathology, University Clinical Center in Tuzla (UCCT). Patients with SRNS, after kidney biopsy were treated with nonsteroidal immunosuppressant's. RESULTS: Eight (36.4%) of the 22 patients who had undergone renal biopsies had minimal change disease (MCNS) and seven (31.8%) had focal segmental glomerulosclerosis (FSGS). The immunosuppressive drugs used in SRNS were Cyclosporine (CsA), Cyclophosphamide (CYC), Mycophenolat mofetil (MMF) and Rituximab (RTX). Three patients (13.6%) did not respond to any treatment and had developed end - stage renal disease (ESRD). CONCLUSION: With current treatments, some children will ultimately achieve a sustained remission with one of the second line or third line of the proposed drugs. Patients with refractory NS will go to progression towards ESRD. The rapid development of molecular genetics will give a new contribution to the pathogenesis and treatment of this disease.

Influence of Plasminogen Activator Inhibitor -1 Gene Polymorphism on Renal Scarring After First Febrile Urinary Tract Infection in Infants.

BACKGROUND: The pathogenesis of renal scarring (RS) after first febrile urinary tract infection (UTI) in children is multifactorial. In addition to well-known risk factors, a role for genetic predisposition has been suggested. AIMS: To determine whether deoxyribonucleic acid (DNA) polymorphisms at the plasminogen activator inhibitor -1 (PAI-1) gene were associated with evolution to RS following a febrile UTI in infants. MATERIALS AND METHODS: Our research included 100 infants, 84 girls and 16 boys, ages up to 1 year with a first febrile UTI, increased inflammatory parameters and positive urine culture treated at the Pediatric Clinic II of the University Clinical Center Sarajevo (UCCS). The diagnostic was based on the imaging studies: ultrasonography, voiding cystourethrography (VCUG) and initial and control static renal scintigraphy (DMSA renal scan), to assess the renal parenchymal damage (RPD). The polymorphisms of the PAI-1 were determined based on polymerase chain reaction technique. The distribution of PAI-1 genotypes and the allele frequencies were compared between different groups of patients with febrile UTI. RESULTS: Results presented that 66 infants had acute pyelonephritis (APN) and 22 had vesicoureteral reflux (VUR). On initial DMSA renal scan examination, we detected no RPD in any patient. After 6 months, the repeat DMSA renal scan revealed the presence of RPD in 18 (27%) out of 66 infants with APN. Distribution of PAI-1 genotypes was not different between various groups of patients with febrile UTI. CONCLUSIONS: The results of our study have not shown that individual genetic variation in PAI-1 is an independent variable that predispose same of children for RS after first febrile UTI. Maybe that yet unknown gene polymorphisms together with geographical and /or socio-economic differences can influence on the development of RS.

Relationship between ultrasound criteria and voiding ultrasonography (VUS) in the evaluation of vesicoureteral reflux (VUR).

AIM: To analyze the usefulness of five ultrasound parameters (ureteral dilatation, renal pelvis dilatation, renal parenchyma width reduction, calyceal dilatation, and urothelial reaction) in detecting vesicoureteral reflux (VUR). METHODS: The study included 101 patients with diagnosed and therapeutically treated urinary infection. The ultrasound examination and voiding urosonography (VUS) were carried out according to a standard protocol. In the group of patients with proven VUR the presence of the indirect ecomorphological signs of VUR was evaluated. RESULTS: The referral diagnosis urinary tract infection was present at the admission in 53 patients, while the remaining 48 patients were admitted with the diagnosis of infectio tractus urinarii recidivans. Pathological VUS was found in 53 patients. The ultrasound parameter with the highest sensitivity, specificity, and negative predictive value (77.4%, 79.2%, and 76.0%, respectively) in detection of VUR was urethral dilatation, while the parameter with the highest positive predictive value (62.5%) in detection of VUR was urothelial reaction. CONCLUSION: In case of ultrasound verification of ureteral dilatation or urothelial reaction, especially in if the urinary infection has proved, it is necessary to exclude the existence of VUR.

Posterior reversible encephalopathy syndrome (PRES).

Posterior reversible encephalopathy syndrome (PRES) is described neurological condition identifiable by clinical and radiological presentation. It occurs due to elevated blood pressure which exceeds auto-regulatory capacity of brain vasculature. PRES is characterized by headache, confusion, seizures, and altered mental function. In this report we describe a case of eleven-year-old boy who was hospitalized, because of nausea, vomiting, intermittent fever, headache, confusion and distress. Because of suspicion of encephalitis CT and MRI examinations were performed immediately where was established diagnose of PRES syndrome.

[Asymptomatic isolated microhaematuria--a reason for concern?]. / Asimptomatska izolovana mikrohematurija--razlog za brigu?

Nephrologists and urologists are frequently faced with patients with asymptomatic isolated microhaematuria (AIMH). This entity is defined as the presence of more than 5 red cells/uL in the sediment of first morning urine, in the absence of symptoms by the urinary tract and in the absence of proteinuria. From 201 children who were referred on the clinical examinations on the Pediatric Clinic in Sarajevo under the diagnosis haematuria in period from 01/01/1997 until 31/08/2002, 87 had AIMH. Age of life was from 0 to 16 years (mean 8 years). Fourteen children (16.1%) had a hypercalciuria, 10 (11.5%) had a state after purpura Henoch-Schonlein nad scarlatine, while 6 (6.9%) had glomerulopathy. Five children (5.7%) had anomalies of urinary system, 5 (5.7%) had evidence of nephrolithiasis, while 4 (4.6%) had asymptomatic urinary tract infection. Cause out of urinary system was found in 29 children (33.3%) and for 14 children (16.1%) etiology remained unknown. Transient microhaematuria was noted in 43 children (49.4%), recurrent in 37 (42.5%) and persistent in 7 (8.1%). Renal biopsy was performed in 5 children (5.7%) because of indications of glomerular disease and all of them had glomerular lesions. Sixty nine children of these 87 were followed up from 2 to 11 years (mean period of 3 years) and none of them developed hypertension or renal impairment. Most patients who have AIMH do not have clinically significant glomerular pathology and they don't need renal biopsy, but only periodic follow up. Any degree of proteinuria accompanying haematuria should be fully investigated, as proteinuria is often a sign of serious renal disease.

[Urinary tract infections and vesicoureteral reflux as a cause of renal parenchymal damage]. / Infekcija urinarnog trakta i vezikoureteralni refluks kao uzrok renalnog parenhimnog ostecenja.

GOAL: Infection of the urinary tract is a risk for the damage of parenchyma and kidney function. Dimercaptosuccinil acid (DMSA) scan was used based on the relation between vesicoureteral reflux (VUR), infection of the urinary tract (UTI) and parenchymal kidney damage. METHODOLOGY: The number of observed children was 79, 58 (73.41%) girls and 21 (26.58%) boys: following the first UTIs, recidiv infect and with positive VUR contrast voiding cistourethrography (VCUG) and ultrasound tests were compelted following the treatment of infect within 6 weeks and DMSA within 4 months. The classification of VUR was done of I to V degrees. The damage to the renal parenchyma after DMSA was defined as inhomogen distribution, reduced bonding with radio-farmake as well as portion of the kidney in the overall renal function smaller than 45%. RESULTS: Among 45.56% (36/79) patients VUR was registered. Reflux over III/V was registered among 27.84 (22/79) among whom 24.05% (19/79) were younger than 5 years of age. DMSA scan showed reduced kidney function bellow 45%, in one direction 33.33% (12/36) and 25.00% (9/36) in both directions. The correlation between clinically proved acute pielonephrities and damage to the parenchyma was not proven. It was proven in 30.37% (24/79) reoccurring urinal infection. CONCLUSION: DMSA is a sensitive method that should not be routinely used on every child with urinary infection. It should be left to assess the renal damage in cases of high degree reflux and reoccurring urinary infection.