DIFFERENTIAL DIAGNOSIS OF HEREDITARY KIDNEY DISEASES IN CHILDREN USING NON-INVASIVE MARKERS OF DAMAGE

Aim. To develop the diagnostic method to determine the likelihood of a specific hereditary kidney disease. Material and methods. KIM-1, TGF-β1, RBP, β2-MG, creatinine, daily proteinuria (Pt) and GFR were determined in 23 patients with hereditary nephritis and 19 patients with tubulopathies. The average age at the time of the study was 13.5 (9-17) years. The ratio of boys/girls (%) was 24:18 (57.1:42.9). Results. The distribution of factors in the groups was considered. Statistically significant differences were found in terms of serum TGF-β1 and daily Pt. According to the results of mono-factor analysis, the factors that confirmed the prognostic significance were selected: urinary β2-MG (OR = 0.892 (0.696-1.175)), serum TGF-β1 (OR = 1.01 (1.002-1.018)) and daily Pt (OR = 25 (1.774-350)). For these factors the threshold values were calculated: urinary β2-MG = 0, serum TGF-β1>280, daily Pt>0.8. The nomogram and classification scheme were built on the basis of the mathematical model for the practical application. Conclusion. As a result of the study, 3 factors were established and 2 from these 3 markers were non-invasive (urinary β2-MG and daily proteinuria). The use of these markers makes possible to diagnose hereditary nephritis in children with high accuracy.

Hereditary Nephritis and Thin Glomerular Basement Membrane Lesion

Hereditary nephritis (HN) and thin glomerular basement membrane (GBM) lesion share a common clinical presentation of persistent hematuria, thin GBM by kidney biopsy electron microscopic examination, and a mutation in type IV collagen. However, the clinical course and treatment for these entities are different with varying patterns of heredity. Ultrastructural examination of a renal biopsy specimen is essential for the morphologic diagnosis of HN and thin GBM lesion, whereas light microscopy may only give limited diagnostic clues. Additional workup including immunostaining for subtypes of type IV collagen may provide further information on underlying genetic mutations. The diagnosis of HN may lead to treatment with renin-angiotensin system blockade in patients at risk of early-onset renal failure to delay progression to end-stage renal disease. Additionally, patients with isolated microscopic hematuria and thin GBM lesion are at increased risk for chronic kidney disease when associated with other comorbidities; those patients should receive regular clinical assessment to prevent renal function decline.

POLYMORPHISM OF STAT4, PTPN22, VEGF, TGF-B, PDCD1 AND PD-L1 GENES IN CHILDREN WITH HEREDITARY NEPHRITIS AND POLYCYSTIC KIDNEY DISEASE

The study of the molecular and genetic nature of inherited kidney diseases is relevant in modern nephrology. It allows us to establish the etiology, develop new methods of treatment and prevention. The aim of the research was to study the genetic polymorphism of STAT4, PTPN22, VEGF, TGF-B, PDCD1 and PD-L1 in children with hereditary kidney diseases. The study included patients with hereditary nephritis (n = 40), polycystic kidney disease (n = 26) and chil dren without kidney diseases (n = 416). We use a standard method of phenol-chloroform extraction to isolate genomic DNA. Polymorphic variants of genes were determined using such methods of polymerase chain reaction (PCR) as estriction fragment length polymorphism PCR and real-time PCR. Genotyping of polymorphic of loci rs7574865 and rs 3821236 of the STAT4 gene in the group of patients with polycystic kidney disease compared with the control was observed significant differences in genotype frequencies in boys. The development of polycystic kidney disease is associated with the presence of genotypes GT + TT and minor allele T of the polymorphic locus rs7574865 of the STAT4 gene and genotypes GA + AA and allele A of the polymorphic locus rs3821236 of the STAT4 gene which is especially pronounced in groups of male patients. Analysis of the frequency distribution of genotypes/alleles in the boys confirmed a significant association of the CC genotype and the minor allele C of polymorphic locus rs2297136 of the PD-L1 gene with the risk of development of hereditary nephritis. The frequencies of genotypes/alleles of the polymorphic loci of PTPN22 rs2476601, TGF-B rs1800469, PDCD1 rs11568821 and VEGF rs699947, rs2010963 in children with hereditary nephritis and polycystic kidney disease didn't significantly differ from the similar indicators in the control group.

Clinicopathologic and ultrastructural findings of hereditary nephritis; a 16-year single center survey in Iran

Introduction: Hereditary nephritis is an umbrella term for a group of congenital childhood diseases including but not limited to Alport syndrome, thin basement membrane disease, and Fabry disease. Objectives: The purpose of this study was a clinicopathologic investigation of Alport syndrome, thin basement membrane disease, and Fabry disease with a focus on the role of electron microscopy and toluidine blue staining in diagnosis. Patients and Methods: In this cross-sectional study, we investigated kidney biopsies with a final diagnosis of either Alport syndrome, thin basement membrane disease or Fabry disease from 2001 to 2016. Electron microscopy and light microscopy were done and the clinical and paraclinical data were extracted from the patients’ medical charts. Electron microscopy role was assessed in terms of necessary, helpful or non-necessary, while correlations between clinical and para-clinical data were determined using appropriate statistical tests. Results: Among the 2865 kidney biopsies, there were 22 patients of hereditary nephritis including 15 (0.52%) Alport syndrome, 5 (0.17%) thin basement membrane disease and 2 (0.07%) Fabry disease diagnosed by electron microscopy. Electron microscopy was essential for the diagnosis of 19 (86.4%) cases, helpful for 3(13.6%) and there was no case for which electron microscopy was non-necessary. The patients’ mean age was 16.1 ± 9.0 years. The most common finding in Alport syndrome was proteinuria (86.7%) followed by hematuria (60.0%). Conclusion: Considering the rate of misdiagnosis of hereditary nephritis using light microscopy and clinical findings alone, electron microscopy study and toluidine blue staining has an essential role in the precise diagnosis in these patients. With regard to the progressive nature of these diseases, prompt diagnosis using electron microscopy is pertinent for therapeutic decisions.

Non-visible haematuria in a military setting

Asymptomatic non-visible haematuria is a common finding at routine military medical examinations. This article briefly reviews the possible causes, which include malignancy, structural causes, exertion haematuria, hereditary nephritis, thin basement membrane disease (TBMD), immunoglobulin A nephropathy (IgAN), tuberculosis (TB) and schistosomiasis. This paper discusses how these conditions may affect potential military recruits as well as currently serving members of the Armed Forces, and offers a general approach to the management of a patient with non-visible haematuria.

MARKERS LEVEL OF ENDOTHELIAL DYSFUNCTION (ENDOTELIN-1 AND NITROGEN OXIDE) IN BLOOD SYROVISTS AND ALBUMINURIA IN CHILDREN WITH ERYTHROCYTURIA

The aim of our study was to investigate the levels of endothelin-1 and aside nitrogen in the serum of children with kidney diseases that clinically present with hematuria syndrome. Materials and methods: a total of 158 children aged 1 to 18 years with kidney disease, having a course with hematuria. Patients were divided into 3 groups: group 1 – glomerulonephritis; group 2 – hereditary nephritis; group 3 – dismetabolic nephropathy. It was studied the level of endothelin, nitric oxide in serum, the level of hematuria, AU in urine, blood biochemistry, glomerular filtration. Results: the highest level of ET-1 was detected in patients with glomerulonephritis - 0,82±0.055 fmol/ml, with the variation range from 0.10 to 3.2 fmol/ml, which twice exceeded the mean values in the control group, whereas the growth rate of hereditary nephritis and DN was more moderate (0,64±0,063 and 0,54±0,072 fmol/ml, respectively). The NO level increased significantly in patients with glomerulonephritis to 120,2±12,3 μmol/l. Conclusions. Determining the level of ET-1 and NO in the serum of children with kidney diseases, having a course with hematuria, gives the opportunity to get an idea about the presence of endothelium dysfunction. Indicators of endothelial dysfunction can be used as markers of severity and progression of the disease.