Anti-Factor H Antibody-Associated Atypical Hemolytic Uremic Syndrome: A Case Report.

Introduction: Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy, caused by dysregulation of the complement alternative pathway. Deletion of the complement factor H-related genes, CFHR1 and CFHR3, together with the presence of CFH autoantibodies are reported in aHUS patients, representing 10% of cases of patients with aHUS. Case presentation: We report here on a case of 4-year-old girl with anti-CFH antibody-associated aHUS. The measurement of complement factors and anti-factor H antibodies, was the main guideline for making an accurate diagnosis and providing the appropriate therapy, with the patient responding positively to plasma exchanges (PEs) and cyclophosphamide pulses. We then, one year after disease onset, continued with glucocorticoids and mycophenolate mofetil (MMF), as maintenance therapy. There were no complications during the therapy other than neutropenia. Now, one year after the cessation of the immune suppression therapy, she is in remission with normal kidney function, no signs of hemolysis, normal C3 levels, and normal range proteinuria. The anti-factor H autoantibody titer decreased but still remained positive, the factor H antigen values remained low all throughout. Close follow-up is applied with frequent urine testing and complete blood count with an intention for early detection of relapse of the disease. Conclusion: The purpose of this case report is to emphasize the value of complement factor measurements and also to separate anti-CFH antibody-associated aHUS as an entity, because immunosuppressive therapy provides an excellent response..

NEUTROPHIL GELATINASE-ASSOCIATED LIPOCALIN AS AN EARLY BIOMARKER OF ACUTE KIDNEY INJURY IN NEWBORNS.

The aim of the study was to determine the incidence, risk factors and efficiency of the neutrophil gelatinase-associated lipocalin (NGAL) biomarker in early diagnosis of acute kidney injury (AKI) in newborns. The study was designed as a prospective, clinical, epidemiological investigation conducted in the period of three years, which included 50 newborns with AKI hospitalized in the Neonatal Intensive Care Unit, University Children's Hospital in Skopje. The estimated prevalence of AKI was 6.4%, while the prevalence according to RIFLE classification was 8.7%. Perinatal asphyxia was a common predisposing factor associated to kidney injury. The mortality rate was 32% and was significantly higher in the group of newborns with congenital heart diseases. There was a significant difference between NGAL values and creatinine values on the day of admission. There was a significant difference in NGAL values between newborns with AKI and lethal outcome and newborns without lethal outcome (p<0.001). In conclusion, AKI is a life-threatening condition. It is an independent contributor to mortality. Urinary NGAL is an early predictive biomarker of AKI in critically ill newborns.

Association between timing of dialysis initiation and clinical outcomes in the paediatric population: an ESPN/ERA-EDTA registry study.

BACKGROUND: There is no consensus regarding the timing of dialysis therapy initiation for end-stage kidney disease (ESKD) in children. As studies investigating the association between timing of dialysis initiation and clinical outcomes are lacking, we aimed to study this relationship in a cohort of European children who started maintenance dialysis treatment. METHODS: We used data on 2963 children from 21 different countries included in the European Society of Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association Registry who started renal replacement therapy before 18 years of age between 2000 and 2014. We compared two groups according to the estimated glomerular filtration rate (eGFR) at start: eGFR ≥8 mL/min/1.73 m2 (early starters) and eGFR <8 mL/min/1.73 m2 (late starters). The primary outcomes were patient survival and access to transplantation. Secondary outcomes were growth and cardiovascular risk factors. Sensitivity analyses were performed to account for selection- and lead time-bias. RESULTS: The median eGFR at the start of dialysis was 6.1 for late versus 10.5 mL/min/1.73 m2 for early starters. Early starters were older [median: 11.0, interquartile range (IQR): 5.7-14.5 versus 9.4, IQR: 2.6-14.1 years]. There were no differences observed between the two groups in mortality and access to transplantation at 1, 2 and 5 years of follow-up. One-year evolution of height standard deviation scores was similar among the groups, whereas hypertension was more prevalent among late initiators. Sensitivity analyses resulted in similar findings. CONCLUSIONS: We found no evidence for a clinically relevant benefit of early start of dialysis in children with ESKD. Presence of cardiovascular risk factors, such as high blood pressure, should be taken into account when deciding to initiate or postpone dialysis in children with ESKD, as this affects the survival.

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.

Chronic kidney disease - pediatric risk factors.

The knowledge about the progression of chronic kidney disease is an important issue for every pediatric nephrologist and pediatrician in order to implement appropriate measures to prevent wasting of renal function and the final consequence - end stage renal disease with the need for the dialysis and transplantation. Therefore it is important to know, treat or ameliorate the standard risk factors such as hypertension, proteinuria, anemia, hyperparathyroidism etc. In this review devoted to the World Kidney Day 2016 we will pay attention to the low birth parameters, obesity, hyperuricemia and smoking which emerged as particularly important risk factors for children and adolescent with chronic kidney disease.

Nephrotic syndrome occurring during tiopronin treatment for cystinuria.

Cystinuria is an autosomal recessive disorder characterized with abnormal tubular reabsorption of cystine and dibasic amino acids leading to cystine urolithiasis. The classical form is caused by mutations in the SLC3A1 gene (OMIM 220100). The cornerstone of the treatment is high hydration and alkalization of the urine to achieve urine pH between 7.0 and 7.5, at which point, cystine solubility in the urine is optimal. These measures very often fail, and thus addition of sulfhydryl agents like penicillamine and tiopronin (mercaptopropionyl glycine) is recommended. Herein, we report a 3-year-old boy with cystinuria resulting in recurrent nephrolithiasis requiring surgery and extracorporeal shock wave lithotripsy. Nine months after introduction of tiopronin, the boy manifested generalized edema, oliguria, and biochemical indices of nephrotic syndrome. Tiopronin was withdrawn, and the boy was given only supportive treatment. Within 10 days, he entered into clinical and biochemical remission. Pediatricians should be aware of this adverse effect of tiopronin, and therefore, testing of the urine with strips or sulfosalicylic acid at least once weekly at home may be very helpful for early detection of proteinuria.

Determinants of eGFR at start of renal replacement therapy in paediatric patients.

BACKGROUND: Few studies have investigated the determinants of glomerular filtration rate (GFR) in paediatric patients starting on dialysis or with a transplant. METHODS: Data were collected as part of the European Society of Paediatric Nephrology/European Renal Association-European Dialysis and Transplant Association registry from 14 European countries and referred to incident paediatric patients starting on renal replacement therapy (RRT) between 2002 and 2007 under the age of 18 years. Estimated glomerular filtration rate (eGFR) was calculated using the Schwartz formula. Data were adjusted for age, gender, treatment modality at start, primary cause of renal failure (PRD) and regions in Europe (eGFR(adj)). RESULTS: Median eGFR in the 938 patients starting RRT was 10.4 mL/min/1.73 m(2) (5th and 95th percentile: 4.0-26.9). Twenty-six patients (2.8%), mainly infants with Finnish-type nephropathy, started with eGFR levels >50 mL/min/1.73 m(2). Younger age, female gender, starting on dialysis and having a short time between the first visit to a paediatric nephrologist (PN) and start of RRT were associated with lower eGFR at start of RRT. Gender differences were only present during adolescent age and disappeared when using the same K value for both genders. The various PRDs showed large differences in the rate of decline in eGFR between the first visit to a PN and start of RRT; however, this did not result in differences in eGFR(adj) at start of RRT. CONCLUSIONS: The main determinants of eGFR at start of RRT were age, gender, treatment modality at start, and the time between the first visit to a PN and start of RRT. Research is needed to determine the consequences of these differences.

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.