Emilija Golubović

Interleukin-12 and interferon-γ production in childhood idiopathic nephrotic syndrome

Abstract. 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.

Hemolytic uremic syndrome associated with novel influenza A H1N1 infection

Sirs, During 2009, a pandemic influenza A H1N1 virus emerged end spread all over the world [1]. Renal involvement in influenza A virus infection is rare, but one case of hemolytic uremic syndrome (HUS) during season influenza has been reported [2]. We present a patient with novel A H1N1 virus complicated with HUS. A previously healthy 11-year-old boy was transferred to our Children’s Clinic with a history of fever, coughing, fatigue, jaundice, and oliguria. He had no diarrhea. On admission his temperature was over 38.5°C, and his blood pressure was 130/80 mmHg. He had no edema. Laboratory investigations revealed a sign of hemolysis (with declining hemoglobin to 6.5 g/l, and reticulocytosis) with thrombocytopenia (38,000 mm) and renal failure (serum creatinine 280 μmol/l, blood urea nitrogen 22 mmol/l). Blood smear showed fragmented and damaged erythrocytes. Serum chemistry showed a high level of total bilirubin (48 μmol/ l) and a very high level of lactate dehydrogenase (LDH 4,800 μ/l, normal range 250–480 μ/l). Alanine and aspartate transferases were slightly elevated. Urine analyses revealed 3+ proteinuria, 3+ hemoglobinuria, and erythrocyte casts. Prothrombin time and activated partial thromboplastin time were normal, D-dimer was elevated, and direct and indirect Coombs tests were negative. C3 and C4 were normal. A chest X-ray showed viral, interstitial pneumonia. Two other family members also started coughing and developed fever and fatigue. Based on the above findings the patient was diagnosed with HUS. On the day of admission he was treated with ceftriaxone 100 mg/kg per day and infusion of low doses of dopamine and furosemide. On his second day in hospital we decided to start plasma therapy, which may be recommended in nondiarrheal/nonpneumococcal HUS. However, a few hours after the first doses of fresh-frozen plasma he showed aggravated hemolytic anemia (hemoglobin level decreased to 5 g/l, LDH severely increased). We stopped plasma infusion, and continued with fluid and diuretics. In the meantime we received his respiratory spacemen test, which was positive for novel influenza A H1N1 by real-time reverse transcriptase PCR. Oseltamivir (75 mg every 12 h) was started, and continued for 6 days. Symptoms subsided in the next few days. He gradually recovered, lost the fever, his urine output increased with improving renal function, and his blood count too. He was discharged after 15 days with serum creatinine 77 μmol/l, normal levels of LDH, and hemoglobin 10 g/l. Usually, influenza A H1N1 turns out to be a benign disease. The association of pneumococcal infection with the current and previous influenza pandemics is well known. Pneumococcal HUS is an uncommon condition, with reports of this complication in patients with invasive infections, but also in one patient during influenza A and pneumococcal coinfection [3, 4]. We did not confirm bacterial super infection in throat swab, sputum and blood culture in our patient. It is E. Golubovic (*) : P. Miljkovic Department of Pediatric Nephrology, Children’s Clinic, University of Nis, Zorana Djindjica 48, 18000 Nis, Serbia e-mail: ema.golubovic@gmail.com

Epidemiology of chronic kidney disease in children in Serbia

BACKGROUND The epidemiological information from well-defined populations regarding childhood chronic kidney disease (CKD), particularly those concerning non-terminal stages, are scanty. The epidemiology of CKD in children is often based on renal replacement therapy (RRT) data, which means that a considerable number of children in earlier stages of CKD are missed as they will reach end-stage renal disease (ESRD) in adulthood. Here, we report the basic epidemiological data on childhood CKD in Serbia, gathered over the 10-year period of activity of the Serbian Pediatric Registry of Chronic Kidney Disease. METHODS Since 2000-09, data on incidence, prevalence, aetiology, treatment modalities and outcome of children aged 0-18 years, with CKD Stages 2-4 and CKD Stage 5, were collected by reporting index cases from paediatric centres. RESULTS Three hundred and thirty-six children were registered (211 boys, 125 girls, male/female ratio 1.7). The median age at registration was 9.0 years [interquartile range (IQR) 3-13]. Median follow-up was 4.0 years (IQR, 1-9). The median glomerular filtration rate (GFR) at the time of the registration was 39.6 mL/min/1.73m(2) (IQR, 13.8-65.4). Median annual incidence of CKD 2-5 stages was 14.3 per million age-related population (p.m.a.r.p.), while those of CKD 2-4 or CKD 5 were 9.1 and 5.7 p.m.a.r.p., respectively. The median prevalence of CKD 2-5 was 96.1 p.m.a.r.p., 52.8 p.m.a.r.p. in CKD 2-4 and 62.2 p.m.a.r.p. in CKD 5. The main causes of CKD were congenital anomalies of kidney and urinary tract and hereditary nephropathies. Kidney survival was the worst in children with glomerular diseases and in those with advanced CKD. Haemodialysis was the most common first modality of RRT. Mortality rate was 4.5%, mainly due to cardiovascular and infectious complications. CONCLUSIONS Epidemiology of paediatric CKD in Serbia is similar to that reported from developed European countries. The knowledge of the epidemiology of earlier stages of CKD is essential for both institution of renoprotective therapy and planning of RRT, a fact of paramount importance in countries with limited resources.

Hypertensive encephalopathy as a late complication of autonomic dysreflexia in a 12-year-old boy with a previous spinal cord injury

The scope of paediatric autonomic disorders is not well recognised, and paediatricians seem to be generally unaware of the complexity and diversity of their clinical manifestations. We report a 12-year-old boy presenting with hypertensive encephalopathy caused by autonomic dysreflexia. Conclusion: This observation emphasises the importance of the recognition of this rare autonomic disorder, which can have potentially life-threatening neurological complications.