Study on the immunopathological effect of titanium particles in peri-implantitis granulation tissue: A case-control study.

OBJECTIVES: To identify titanium particles (TPs) in biopsy specimens harvested from peri-implantitis lesions and secondarily to study the histopathological characteristics in peri-implantitis compared to periodontitis, in order to evaluate whether the presence of TPs could alter respective inflammatory patterns. MATERIAL AND METHODS: Biopsies containing granulation tissue were harvested during routine surgical treatment in 39 peri-implantitis cases and 35 periodontitis controls. Serial sections were obtained using titanium-free microtome blades. The first and last sections of the peri-implantitis specimens were used for identification of TPs by scanning electron microscopy coupled with dispersive X-ray spectrometry. Intermediate sections and periodontitis specimens were processed for descriptive histological study using haematoxylin-eosin staining and for immunohistochemical analysis using CD68, IL-6, Nf-kB and VEGF markers. RESULTS: TPs were identified in all peri-implantitis specimens as free metal bodies interspersed within granulation tissue. However, presence of macrophages or multinucleated giant cells engulfing the TPs were not identified in any specimen. Peri-implantitis granulations were characterized by a chronic inflammatory infiltrate rich in neutrophils. About half of peri-implantitis patients exhibited a subacute infiltrate characterized with lymphocytes interweaved with neutrophils and eosinophils. When compared to periodontitis, peri-implantitis tissues showed higher proportions of macrophages and a more intense neovascularization, based on significantly higher expression of CD68 and VEGF respectively. CONCLUSION: TPs were identified in all peri-implantitis specimens, but without evidencing any foreign body reaction suggestive for direct pathological effects of TPs. The peri-implantitis granulation tissue was characterized by intense neovascularization and presence of a chronic inflammatory infiltrate dominated by plasma cells, neutrophils and macrophages.

The effect of antioxidant status on overall survival in renal cell carcinoma.

INTRODUCTION: The oxidative stress contributes to all three phases of carcinogenesis and represents a concomitant condition in renal cell carcinoma (RCC). RCC is the most common type of neoplasm of the kidney, and despite numerous studies the set of predictive and prognostic markers of survival are still unknown. The aim of our study was to examine the relation between antioxidant (AO) status and overall survival (OS) in RCC patients. MATERIAL AND METHODS: Our study included 95 patients with RCC, who underwent radical nephrectomy. We analysed the prognostic role of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase, glutathione reductase, glutathione, and malondialdehyde) and other clinicopathological factors (size, grade, stage, and histological subtype) on the OS of RCC patients. RESULTS: The 5-year OS was 54.6%. The survival analysis related to AO parameters showed no significant difference in survival of RCC patients. The concentration of malondialdehyde, an indicator of lipid peroxidation, also had no significant effect on the survival rate of RCC patients. Univariate and multivariate analysis confirmed the significance of clinicopathological parameters (size, p < 0.001; Fuhrman grade, p = 0.001, and stage, p < 0.001) for patients' survival. CONCLUSIONS: In our cohort of patients, different antioxidant parameters were not found to be predictors for OS of patients with RCC, who underwent radical nephrectomy.

Non-Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus-11-Year Experience from a Single Center.

INTRODUCTION: In patients with diabetes mellitus (DM), non-diabetic renal disease (NDRD) can also occurs, as well as diabetic nephropathy. NDRD is most accurately diagnosed using kidney biopsy. AIM: The aim of the study was to investigate the incidence and type of NDRD diagnosed by kidney biopsy in patients with type 2 DM and the correlation of clinical and laboratory findings with histopathological diagnosis. MATERIAL AND METHODS: From April 2007 to October 2018, 290 kidney biopsies were performed at the Department of Nephrology, Internal Medicine Clinic in Banja Luka, out of which 18 patients (males 9, mean age 59.8 years) were with type 2 DM. The US-guided (ultrasound device: Toshiba Famio 5) kidney biopsy was performed using an automatic biopsy instrument FAST-GUN® with needle 16G. Kidney tissue samples were analyzed by light microscopy and immunofluorescence. RESULTS: In 18 patients with type 2 DM, the average duration of the disease was 5.9 years, 5 patients had a retinopathy, and 16 patients had hypertension. Biopsy indications were: nephrotic syndrome in 11 patients, asymptomatic urinary abnormalities in 3 patients, and rapid chronic renal failure progression. Unsatisfactory quality sample for pathohistological analysis was obtained in one patient, and out of the other 17, 6 (35.3%) had NDRD, 3 (17.6%) had NDRD superimposed with the diabetic nephropathy, and 8 (47.1%) had diabetic nephropathy. Of the patients who had NDRD, 3 had membranous glomerulonephritis, 1 had focal segmental glomerulosclerosis, and two had hypertensive nephroangiosclerosis. Out of patients with coexisting NDRD and diabetic nephropathy, 2 had hypertensive nephroangiosclerosis and one diabetic nephropathy and lupus nephritis. CONCLUSION: NDRD was diagnosed using kidney biopsy in 9/17 patients with type 2 DM, which confirms the significance of the kidney biopsy in patients with DM with properly indications. Accurate diagnosis provides disease specific treatment and thus significantly improves the long-term prognosis of the patient.

Immunohistochemical expression of proliferative markers in renal cell carcinoma.

PURPOSE: The purpose of this study was to investigate into the expression of cyclin A and telomerase in renal cell carcinoma (RCC) and to analyze the relationship between expression and the clinicopathological characteristics of the tumor and their impact on survival. METHODS: The overall material included 74 samples of RCC and 4 of normal renal tissue. Primary cyclin A antibody from Santa Cruz Biotechnology and TERT MA5-16034 antibody from Thermo Fisher Scientific Inc were used. Staining was performed by streptavidin-biotin technique using DAKO LSAB+ kit. Statistical analyses were performed using of SPSS 23 Statistics software from IBM. RESULTS: No differences in cyclin A and telomerase expression among gender and age groups were found, nor did the tumor dimensions have any significant impact on expression. Also, tumor grades and stages did not differ. However, histological types differed in favor of the papillary type. A significant positive correlation between both markers, as well as between the expression and tumor stage and grade was noticed. Only the tumor stage had negative impact on survival. CONCLUSIONS: Although not affecting survival, the expression of cyclin A and telomerase increased with tumor stage and grade, suggesting that cyclin A and telomerase could be potential proliferative immunohistochemical markers of RCC.

Concomitance of Polymorphisms in Glutathione Transferase Omega Genes Is Associated with Risk of Clear Cell Renal Cell Carcinoma.

Glutathione S-transferases (GSTs), a superfamily of multifunctional enzymes, play an important role in the onset and progression of renal cell carcinoma (RCC). However, novel GST omega class (GSTO), consisting of GSTO1-1 and GSTO2-2 isoenzymes, has not been studied in RCC yet. Two coding single nucleotide polymorphisms (SNPs) supposedly affect their functions: GSTO1*C419A (rs4925) causing alanine to aspartate substitution (*A140D) and GSTO2*A424G (rs156697) causing asparagine to aspartate substitution (*N142D), and have been associated with several neurodegenerative diseases and cancers. Functional relevance of yet another GSTO2 polymorphism, identified at the 5' untranslated (5'UTR) gene region (GSTO2*A183G, rs2297235), has not been clearly discerned so far. Therefore, we aimed to assess the effect of specific GSTO1 and GSTO2 gene variants, independently and in interaction with established risk factors (smoking, obesity and hypertension) on the risk for the most aggressive RCC subtype, the clear cell RCC (ccRCC). Genotyping was performed in 239 ccRCC patients and 350 matched controls, while plasma levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, were determined by ELISA. As a result, combined effect of all three variant genotypes exhibited almost 3-fold risk of RCC development. Additionally, this association was confirmed at the haplotype level [variant GSTO1*A/GSTO2*G (rs156697)/GSTO2*G (rs2297235) haplotype], suggesting a potential role of those variants in propensity to RCC. Regarding the gene-environment interactions, variant GSTO2*G (rs156697) homozygous smokers are at higher ccRCC risk. Association in terms of oxidative DNA damage was found for GSTO2 polymorphism in 5'UTR and 8-OHdG. In conclusion, the concomitance of GSTO polymorphisms may influence ccRCC risk.

HTERT promoter methylation and single nucleotide polymorphism (-245 T>C) affect renal cell carcinoma behavior in Serbian population.

PURPOSE: Renal cell carcinoma (RCC) is the most common renal cancer in adults and includes several subtypes that may be distinguished by their histology, genetic background, clinical course and responses to treatment. Human telomerase reverse transcriptase (hTERT), a crucial enzyme for telomere maintenance, has been linked to RCC development. The purpose of this study was to search for genetic and epigenetic alterations in hTERT (promoter mutations and methylation and gene amplification), and to establish a possible association between molecular and clinico-pathological characteristics of RCC. METHODS: DNA was extracted from 31 formalin-fixed, paraffin-embedded tumor samples and 23 blood samples from 54 patients with RCC. Polymerase chain reaction (PCR) products were sequenced and analyzed using the Sequencher software. HTERT amplification was determined by quantitative PCR, while the promoter methylation status was assessed by methylation specific PCR. Statistical analysis was performed using SPSS. RESULTS: No mutations could be detected in the hTERT promoter but only a single nucleotide polymorphism (SNP) (-245 T>C). In 54 analyzed RCC cases, the variant allele C was present in homozygous or heterozygous form in 48% of the patients. The C allele was significantly more frequent in low grade tumors (p=0.046). Gene amplification was detected in 19.4% of the 31 RCCs and hTERT methylation in 54.8% of the 31 samples. An association was established between methylation and histological type of RCC (p=0.047). CONCLUSIONS: HTERT seems to be implicated in RCC pathogenesis since the promoter polymorphism exerts a modulation effect on tumor behavior. In addition, hTERT promoter methylation status is related to RCC histology.

Genome-wide association study identifies multiple risk loci for renal cell carcinoma.

Previous genome-wide association studies (GWAS) have identified six risk loci for renal cell carcinoma (RCC). We conducted a meta-analysis of two new scans of 5,198 cases and 7,331 controls together with four existing scans, totalling 10,784 cases and 20,406 controls of European ancestry. Twenty-four loci were tested in an additional 3,182 cases and 6,301 controls. We confirm the six known RCC risk loci and identify seven new loci at 1p32.3 (rs4381241, P=3.1 × 10-10), 3p22.1 (rs67311347, P=2.5 × 10-8), 3q26.2 (rs10936602, P=8.8 × 10-9), 8p21.3 (rs2241261, P=5.8 × 10-9), 10q24.33-q25.1 (rs11813268, P=3.9 × 10-8), 11q22.3 (rs74911261, P=2.1 × 10-10) and 14q24.2 (rs4903064, P=2.2 × 10-24). Expression quantitative trait analyses suggest plausible candidate genes at these regions that may contribute to RCC susceptibility.

Polymorphisms of survivin -31 G/C gene are associated with risk of urothelial carcinoma in Serbian population.

PURPOSE: Survivin is thought to play an important role in carcinogenesis and is found to be associated with poor clinical outcome in various malignancies. Gene -31 G/C polymorphism has been identified as a risk factor for the development of several types of tumors. The purpose of this study was to investigate the association between survivin gene promoter -31C/G polymorphism and urothelial carcinoma (UC) risk in Serbian population and to compare the different expressions of survivin in UC of different disease stages, histological grades and tumor location in the upper or lower urinary tract. METHODS: DNA from 94 patients with primary UC and from 82 healthy subjects was subjected to PCR restriction fragment length polymorphism analysis (PCR-RFLP) to identify individual genotypes. UC samples were subjected to immunohistochemical analysis to assess survivin expression in these lesions. RESULTS: It was observed that the frequency of G/G genotype was greater in patients with UC (58.7%) than in controls (32%). Compared with study subjects carrying the C/G or C/C genotypes, significantly increased UC risk was found for individuals carrying the G/G genotype. Those carrying the G/G genotype had a significantly increased UC risk compared with those with C/G or C/C genotypes. Patients with UC carrying the G/G genotype had a greater prevalence of muscle-invading (stage T2-T4), high-grade (G2) tumor and immunohistochemicaly overexpressed survivin compared with those carrying the C/G or C/C genotypes. CONCLUSIONS: G/G genotype of the -31C/G polymorphism might be a risk factor for UC development.

GSTM1 genotype is an independent prognostic factor in clear cell renal cell carcinoma.

PURPOSE: Owing to dual functionality of cytosolic glutathione S-transferases (GSTs), they might affect both the development and the progression of renal cell carcinoma (RCC). However, the data on the prognostic value of GST polymorphism in patients with RCC are scarce. Hence, we evaluated the effect of GST gene variants on both the risk of RCC development and the postoperative prognosis in patients with clear cell RCC (ccRCC). METHODS: GST genotypes were determined in 305 patients with RCC and 326 matched controls, whereas the overall survival was evaluated in patients with ccRCC only. The presence of GSTM1:ASK1 protein-protein interaction in ccRCC tissue samples was analyzed by methods of immunoprecipitation and immunoblot. RESULTS: We noted an increased risk of RCC development in carriers of GSTM1-null and GSTP1-variant genotype (P<0.05). On the contrary, survival analysis indicated shorter overall survival for patients with ccRCC with GSTM1-active genotype (P = 0.026). Furthermore, patients with ccRCC with GSTM1-active genotype had significantly higher hazard ratio (P<0.05), in analyzed regression models, compared with the carriers of GSTM1-null genotype. Finally, the presence of GSTM1:ASK1 protein-protein interaction was found in all RCC tissue samples studied. CONCLUSIONS: Carriers of GSTM1-null and GSTP1-variant genotypes are in increased risk of RCC development. On the contrary, GSTM1-null genotype is associated with favorable postoperative prognosis in ccRCC. The possible molecular mechanism underlying the role of GSTM1 protein in RCC progression might be the presence of GSTM1:ASK1 protein-protein interaction. Hence, determination of GSTM1-genotype might serve as a valuable indicator in both RCC risk assessment and postoperative prognosis.

Clinicopathological characteristics and survival in Serbian patients with renal cell carcinoma: a retrospective analysis.

PURPOSE: Indications of kidney cancer outcome in lowerincome countries are based on an incidence/mortality ratio due to lack of survival information. This study was conducted to provide outcome data in Serbian patients with renal cell carcinoma (RCC) and to identify prognostic factors that could affect their overall survival (OS). METHODS: This retrospective study included 185 patients who underwent nephrectomy. We assessed certain clinicopathological data including age, gender, tumor size, grade, stage and histological subtypes for their possible impact on OS. RESULTS: The 5-year OS was 63.2%. Significant association was found between OS and age (log-rank 12.455, p=0.006), tumor size (log-rank 26.425, p=0.000), grade (log-rank 13.249, p=0.000) and stage (log-rank 43.235, p=0.000). Univariate analysis indicated size (p=0.000), grade (p=0.001) and stage (p=0.000) as prognostic factors for OS. In multivariate analysis, grade (p=0.014) and stage (p=0.000) remained significant predictors of OS. CONCLUSION: Tumor grade and stage were identified as independent prognostic factors of OS survival in Serbian patients with RCC.

Combined GSTM1-Null, GSTT1-Active, GSTA1 Low-Activity and GSTP1-Variant Genotype Is Associated with Increased Risk of Clear Cell Renal Cell Carcinoma.

The aim of this study was to evaluate specific glutathione S-transferase (GST) gene variants as determinants of risk in patients with clear cell renal cell carcinoma (cRCC), independently or simultaneously with established RCC risk factors, as well as to discern whether phenotype changes reflect genotype-associated risk. GSTA1, GSTM1, GSTP1 and GSTT1 genotypes were determined in 199 cRCC patients and 274 matched controls. Benzo(a)pyrene diolepoxide (BPDE)-DNA adducts were determined in DNA samples obtained from cRCC patients by ELISA method. Significant association between GST genotype and risk of cRCC development was found for the GSTM1-null and GSTP1-variant genotype (p = 0.02 and p<0.001, respectively). Furthermore, 22% of all recruited cRCC patients were carriers of combined GSTM1-null, GSTT1-active, GSTA1-low activity and GSTP1-variant genotype, exhibiting 9.32-fold elevated cRCC risk compared to the reference genotype combination (p = 0.04). Significant association between GST genotype and cRCC risk in smokers was found only for the GSTP1 genotype, while GSTM1-null/GSTP1-variant/GSTA1 low-activity genotype combination was present in 94% of smokers with cRCC, increasing the risk of cRCC up to 7.57 (p = 0.02). Furthermore, cRCC smokers with GSTM1-null genotype had significantly higher concentration of BPDE-DNA adducts in comparison with GSTM1-active cRCC smokers (p = 0.05). GSTM1, GSTT1, GSTA1 and GSTP1 polymorphisms might be associated with the risk of cRCC, with special emphasis on GSTM1-null and GSTP1-variant genotypes. Combined GSTM1-null, GSTT1-active, GSTA1 low activity and GSTP1-variant genotypes might be considered as "risk-carrying genotype combination" in cRCC.

The MMP-2 and MMP-9 promoter polymorphisms and susceptibility to salivary gland cancer.

PURPOSE: Matrix metalloproteinases (MMPs) are a family of endopeptidases that may play an important role in the development of salivary gland cancer (SGC). MMP-2 and MMP-9, members of the gelatinase protein family, are capable of degrading type IV collagen of basement membranes, and their overexpression is often associated with tumor aggressiveness and poor prognosis. The aim of this study was to establish the role of single nucleotide polymorphisms (SNPs) in MMP-2 and MMP-9 genes as putative susceptibility factors for the development of SGC. METHODS: The MMP-2 -1306 C>T, MMP-2 -1575 G>A and MMP-9 -1562 C>T polymorphisms were analyzed in 93 SGC cases and 100 controls using PCR-RFLP. RESULTS: The T allele for the MMP-2-1306 C>T polymorphism exhibited its effect in heterozygous carriers, increasing the risk for SGC (odds ratio/OR 1.98, 95% CI 1.07-3.65, p=0.03). According to the dominant model, CT+TT genotypes had a 2-fold increased risk of developing SGCs (p=0.02).When the dominant model was applied for the MMP2 -1575 G>A, individuals with GA+AA genotypes exhibited a 1.77-fold increase in cancer risk, but with borderline significance (p=0.049). Heterozygous carriers of the variant T allele for the MMP-9 -1562 C>T polymorphism had roughly a 2-fold increase in susceptibility for SGC compared to wild type homozygotes (CC) (p=0.02). CONCLUSION: Our findings suggest MMP-2-1306 C>T and MMP-9-1562 C>T polymorphisms genotypes seem to influence the development of SGCs, whereas MMP-2 -1575 G>A seems to be of a minor importance.

Acute Renal Failure in Different Malignant Tumors.

Acute renal failure (ARF) represents a severe complication of malignancies, that causes significant morbidity and mortality. ARF is a common part of multiple organ dysfunction in critically ill patients with cancer with reported mortality rates from 72% to 85% in patients who need renal replacement therapy. The pathways leading to ARF in cancer patients are common to the development of ARF in other conditions. However, certain factors leading to the development of ARF may be associated to the tumor or to the tumor therapy. The purpose of this review is to give specific aspects of renal disease in critically ill cancer patients (CICPs), to overview the causes of ARF in CICPs and to describe recent progress in the management of these complications, including treatment toxicity and bone marrow transplantation (BMT). The prevention of ARF is obligatory and therefore the possible treatments of ARF in CICPs are also discussed.

Cytomegalovirus induces Interleukin-6 mediated inflammatory response in salivary gland cancer.

PURPOSE: The purpose of this study was to examine whether cytomegalovirus (CMV) is present in different histological types of salivary gland cancer (SGC) by detecting CMV immediate-early (IE) and early gene products, and to determine the presence of its association with the overexpression of interleukin (IL)-6. METHODS: Immunohistochemical analysis of 92 cases of different histological types of SGC was performed to determine the presence of IL-6 and CMV antigen and its intensity in tumor tissue. Twenty samples of normal salivary gland tissue obtained during autopsy served as healthy controls. RESULTS: CMV antigens were not found in healthy acinar tissue of salivary glands, but were expressed in epithelium of salivary gland ducts. Negative expression of CMV antigens was also found in salivary gland tissue surrounding tumors. On the other hand, CMV was detected in 65/92 SGC cases (70.6%). Higher expression of IL-6 was found in SGC (70.7%) than in normal tissue (20%). There was a high association of CMV antigen presence with the presence of IL-6, and with the IL-6 expression intensity. CONCLUSIONS: Positive expression of CMV antigens in a high percentage of SGC cells suggests that it might play an important role in carcinogenesis by increasing IL-6 production and leading to inhibition of apoptosis and tumor development.

Tissue kidney injury molecule-1 expression in the prediction of renal function for several years after kidney biopsy.

OBJECTIVES: Retrospective study was designed to examine the importance of tissue kidney injury molecule-1 (KIM-1) expression in predicting kidney function in sixty patients (27 males) aged 34.15 ± 12.23 years with different kidney diseases over three years after kidney biopsy. MATERIALS AND METHODS: Tissue KIM-1 expression was determined immunohistochemically and KIM-1 staining was scored semiquantitatively, as well as tubulointerstitialis (TIN), inflammation, atrophy, and fibrosis. Kidney function (MDRD formula) and proteinuria/day were evaluated at the time of biopsy (GFR0) and 6, 12, 24, and 36 months later. RESULTS: Significantly positive correlations between tissue KIM-1 expression and age (r = 0.313), TIN inflammation (r = 0.456), fibrosis (r = 0.317), and proteinuria at 6 months (r = 0.394) as well as negative correlations with GFR0 (r = -0.572), GFR6 (r = -0.442), GFR24 (r = -0.398), and GFR36 (r = -0.412) were found. Meanwhile, TIN inflammation was the best predictor of all measured kidney functions during three years, while tissue KIM-1 expression (P = 0.016) was a predictor only at 6 months after biopsy. CONCLUSION: Tissue KIM-1 expression significantly predicts kidney function solely at 6 months after biopsy, when the effects of immune and nonimmune treatments are the strongest.

Age-related reduction of structural complexity in spleen hematopoietic tissue architecture in mice.

The effects of aging on structural complexity in hematopoietic tissue are unknown. In this work, in a mouse experimental model, we report the age-related reduction of spleen hematopoietic tissue (SHT) complexity. Spleen tissue was obtained from the total of 64 male Swiss albino mice divided into 8 age groups: newborns (0 days old), 10 days, 20 days, 30 days, 120 days, 210 days, 300 and 390 days old. SHT was stained using conventional hematoxylin/eosin, and DNA-binding toluidine blue dyes. Fractal dimension as an indicator of cellular complexity, and lacunarity as indicator of tissue heterogeneity were determined based on the binarized SHT micrographs. Results indicate that fractal dimension of mice spleen hematopoietic tissue decreases with age, while lacunarity increases. These changes/trends have been detected in SHT stained both with toluidine blue and conventional hematoxylin/eosin. Fractal dimension was negatively correlated with lacunarity. The detected reduction in complexity suggests that age-related structural changes are present in mouse SHT both in general tissue architecture and progenitor cell DNA.

Complexity reduction of chromatin architecture in macula densa cells during mouse postnatal development.

AIM: To determine whether complexity of chromatin structure in kidney macula densa cells (MDC) decreases during postnatal development in mice. METHODS: The levels of chromatin structural complexity were measured by determining fractal dimension of MDC nuclei. Kidney tissue was obtained from the total of 32 male Swiss albino mice divided into four age groups (n = 8): newborn (0 days), 10 days old, 20 days old and 30 days old. For a total of 640 MDC chromatin structures, fractal dimension, lacunarity, as well as parameters of Grey level co-occurrence matrix (GLCM) texture were determined. RESULTS: Chromatin fractal dimension in animals aged 10 days, 20 days and 30 days was significantly lower (P < 0.05, P < 0.01 and P < 0.001, respectively), compared with newborn mice. This complexity reduction of chromatin architecture is in accordance with previously published studies, which detected generalized and sustained loss of both tissue and cell complexity during aging. The loss of complexity was texture-independent, since there was no statistically significant difference (P > 0.05) in both chromatin angular second moment and inverse difference moment between the age groups. CONCLUSION: Our results indicate that age-related nuclear intrinsic factors which do not influence chromatin texture may have an important role in MDC postnatal development.

Renal involvement in primary Sjogren syndrome of childhood: case report and literature review.

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.

Survivin gene promoter -31 G/C polymorphism is associated with Wilms tumor susceptibility in Serbian children.

Survivin, an apoptotic inhibitor, is overexpressed in various types of cancer. Mechanisms of survivin upregulation are still poorly understood, but single nucleotide polymorphisms in the survivin gene promoter have been shown to modulate survivin expression and consequently the risk for some types of cancer. The aim of the present study was to investigate whether survivin promoter -31 G/C and -241 C/T polymorphisms could represent susceptibility factors for Wilms tumor (WT) development in Serbian population. Genotype and allele frequencies for the 2 polymorphisms in survivin promoter have been analyzed by polymerase chain reaction/restriction fragment length polymorphism in 59 WT patients and 82 controls. The frequencies of alleles and genotypes were significantly different between patients and controls for the -31 G/C polymorphism. Individuals with CC and CG genotypes had significantly decreased risk of WT compared with GG individuals (odds ratio 0.26, 95% confidence interval, 0.07-0.96; odds ratio 0.30, 95% confidence interval, 0.15-0.60). There was also a statistically significant difference in genotype frequencies between intermediate and high-risk prognostic groups (P=0.015). The -241 C/T polymorphism did not show association with WT susceptibility. Our findings suggest that the G allele at -31 survivin gene promoter position is associated with a significantly higher cancer risk in Serbian children, with a gene dosage effect.

Indications and results of renal biopsy in children: a 10-year review from a single center in Serbia.

BACKGROUND: This study was conducted to retrospectively investigate the indications for renal biopsy in native kidneys and to analyze pathological findings in the last 10 years in a single tertiary pediatric hospital in Serbia. METHODS: All patients who underwent renal biopsy at our hospital between 2001 and 2010 were included in the present study. Renal biopsy was performed under fluoroscopy with a biopsy gun. All renal biopsies were studied under light and immunofluorescent microscopy, while electron microscopy was rarely performed. RESULTS: The study group included 150 patients (56% female) who underwent 158 percutaneous native kidney biopsies. Median age was 11.5 years (range 0.2-20 years). The most frequent indications for renal biopsy were nephrotic syndrome (32.9%), asymptomatic hematuria (23.4%), urinary abnormalities in systemic diseases (15.8%) and proteinuria (11.4%). Primary glomerulonephritis (GN) was the most common finding (57.4%), followed by secondary GN (15.5%) and tubulointerstitial diseases (4.5%). According to histopathological diagnosis, the most common causes of primary GN were focal segmental glomerulosclerosis (20.9%), mesangioproliferative GN (14.6%), IgA nephropathy (8.9%) and minimal change disease (13%). Lupus nephritis (6%) and Henoch-Schönlein nephritis (4%) were the most common secondary glomerular diseases. CONCLUSIONS: The epidemiology of glomerular disease in our single-center report is similar to that in data from adjacent Croatia and Greece. Focal segmental glomerulosclerosis was the dominant histopathological finding, followed by mesangioproliferative GN and IgA nephropathy.