In its early stages, symptoms of chronic kidney disease (CKD) are usually not apparent. Significant reduction of the kidney function is the first obvious sign of disease. If diagnosed early (stages 1 to 3), the progression of CKD can be altered and complications reduced. In stages 4 and 5 extensive kidney damage is observed, which usually results in end-stage renal failure. Currently, the diagnosis of CKD is made usually on the levels of blood urea and serum creatinine (sCr), however, sCr has been shown to be lacking high predictive value. Due to the development of genomics, epigenetics, transcriptomics, proteomics, and metabolomics, the introduction of novel techniques will allow for the identification of novel biomarkers in renal diseases. This review presents some new possible biomarkers in the diagnosis of CKD and in the prediction of outcome, including asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), uromodulin, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), miRNA, ncRNA, and lincRNA biomarkers and proteomic and metabolomic biomarkers. Complicated pathomechanisms of CKD development and progression require not a single marker but their combination in order to mirror all types of alterations occurring in the course of this disease. It seems that in the not so distant future, conventional markers may be exchanged for new ones, however, confirmation of their efficacy, sensitivity and specificity as well as the reduction of analysis costs are required.

Objectives• To elucidate genetic polymorphisms of the matrix metalloproteinases (MMPs) MMP1 (rs1799750), MMP2 (rs243865), MMP9 (rs3918242), MMP12 (rs2276109) and tissue inhibitors of MMPs (TIMPs) TIMP1 (rs2070584) and TIMP3 (rs9619311) genes that may be involved in susceptibility to bladder cancer (BC). Patients and Methods• We enrolled 241 patients with BC and 199 controls.• Genomic DNA samples were extracted from peripheral blood and polymorphisms were analysed by high-resolution melting analysis and by real-time polymerase chain reaction using TaqMan fluorescent probes. T with MMP9 -1562C/T (rs3918242) allele T was found to increase BC risk (OR 2.00, 95% CI 1.10-3.62; P = 0.022). Results • Of the six evaluated polymorphisms of Conclusions• Our results suggest that genetic variations in five polymorphisms of MMPs and TIMPs are not associated with a high risk of BC.• Only MMP1 polymorphism may be related to the risk of BC, notably in 'ever smokers' . • Our study suggests that the effects of polymorphisms of MMPs and TIMPs on BC risk deserve further investigation.

IntroductionBreakdown of the extracellular matrix by matrix metalloproteinases (MMPs), as we know, is one of mechanisms involved and required in tumor invasion. MMP7 is a negative prognostic factor of various malignances, while MMP8 exhibits an inhibitory effect on tumorigenesis and metastasis. We evaluated the potential association of functional polymorphisms in the promoter of the MMP7 (rs11568818) and MMP8 (rs11225395) genes and bladder cancer (BCa) risk.Materials and methodsThe study included 241 BCa cases and 199 healthy population controls that were collected at the First Department of Urology, Medical University (Łódź, Poland) and at the Nofer Institute of Occupational Medicine (Łódź, Poland). Genomic DNA samples were isolated from venous blood and genetic polymorphisms were analyzed by real–time polymerase chain reaction using TaqMan fluorescent probes. Associations between genotype and allele status were estimated by logistic regression models adjusted for classic risk factors (e.g. age, gender and cigarette smoking).ResultsMMP7 and MMP8 genotypes were distributed similarly in BCa patients and in controls and at least one variant allele was not associated with BCa cancer risk (OR, 0.91; 95% CI, 0.60–1.39; p = 0.662 for MMP7 and OR, 0.96; 95% CI, 0.63–1.46; p = 0.836 for MMP8). We observed higher prevalence of MMP7 GG genotypes among BCa patients than in controls (OR, 1.54; 95% CI, 0.93–2.55; p = 0.093). Additionally, genetic polymorphisms in the MMP7 and MMP8 were not associated with the tumor grade or stage.ConclusionsOur results suggest that genetic variations in two genes encoding members of the MMP7 and MMP8 are not associated with a risk of BCa in the Caucasian population.

Background: Low concentrations of selenium (Se) in humans have been associated with risk of cancer. Selenoprotein mRNAs can potentially be regulated by Se status. Methods: Se status, GPx1 Pro198Leu and Sep15 1125G/A genetic polymorphism and human (h)GPx1, hGPx3, hSep15 and hSeP1 transcript levels in peripheral leukocytes of 33 males with bladder cancer and 47 healthy male controls were analysed. Results: All the subjects expressed detectable selenoprotein mRNA concentrations in leukocytes. Significantly lower expression of hGPx1, hGPx3, hSep15 and hSeP1 in leukocytes of bladder cancer patients compared to controls was observed. hGPx1, hGPx3 and hSep15 expression was significantly lower in non-smokers in the control group compared with smokers in the control group. A positive relationship between expression of all studied genes was also observed in non-smoking controls. Expression of hGPx3 and hSep15 gradually increased with tumour grade in patients with cancer. We did not find any association between selenoprotein mRNA levels, Se status and selenoprotein genetic polymorphism. Conclusions: This study showed significant downregulation of hGPx1, hGPx3, hSep15 and hSeP1 mRNA levels in leukocytes of patients with bladder cancer compared to controls. Selenoprotein transcript levels in circulating leukocytes of patients with bladder cancer and controls revealed no potential impact of Se status on selenoprotein expression.

PurposeNRF2 transcription factor is involved in modulation of various antioxidant and metabolic genes and, therefore, may modulate anti-carcinogenic potential. Association between polymorphisms of NRF2 and five NRF2-regulated genes and urinary bladder cancer (BC) risk was analyzed.MethodsThe study group included 244 BC patients, while the control group comprised 365 individuals with no evidence of malignancy. Genotyping of GSTM1 (deletion), GSTT1 (deletion), GSTA1 −69C/T (rs3957357), GSTP1 Ile105Val (rs1695), SOD2 Ala16Val (rs4880) and NRF2 −617C/A (rs6721961) in blood genomic DNA was performed by means of real-time PCR assays. The associations between gene polymorphism and BC risk were computed by logistic regression.ResultsThe frequency of GSTA1, GSTP1, SOD2 and NRF2 genotypes did not differ in both groups. A significantly higher BC risk was associated with GSTM1 null genotype after adjusting to age, sex and smoking habit (OR 1.85, 95 % CI 1.30–2.62; P = 0.001). GSTT1 null (OR 0.50, 95 % CI 0.31–0.81; P = 0.005) and GSTP1 Val105Val (OR 0.52, 95 % CI 0.27–0.98; P = 0.04) genotypes were associated with reduced BC risk separately or in combination (OR 0.24, 95 % CI 0.11–0.51; P < 0.0001) (P heterogeneity = 0.01). Combined GSTT1 null and SOD2 with at least one 16Val allele among never smokers encompass reduced BC risk (OR 0.14, 95 % CI 0.03–0.63; P = 0.01) (P heterogeneity = 0.04).ConclusionsThis study supports hypothesis that GSTM1 null genotype may be a moderate BC risk factor. The gene–gene and gene–environment interactions associated with combined GSTP1/GSTT1 and combined GSTT1/SOD2 genetic polymorphisms along with cigarette smoking habit may play a significant role in BC risk modulation.