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End-stage renal disease patients on dialysis (CKD-G5D) have a high mortality rate due to cardiovascular diseases (CVD). In these patients, inflammation, oxidative stress, and uremia increase the production of glycation products (AGEs) which in turn accelerate CVD onset and progression. Recently, attention has been given to the soluble receptor for AGEs (sRAGE) as a marker of inflammation, oxidative stress, atherosclerosis, and heart failure in CKD-G5D. However, its association with patient outcomes is still under debate. Our aim is to explore whether sRAGE may be a predictor of mortality in CKD-G5D. We studied 123 CKD-G5D for 24 months. Of these patients, 56 were on hemodialysis (HD) and 67 on peritoneal dialysis (PD). Demographic, anthropometric, biochemical, and clinical data were recorded. sRAGE was quantified by enzyme-linked immunosorbent assay. sRAGE was a predictor of mortality at 2 -year follow-up. Each increase of 100 pg/mL in sRAGE levels was associated with an approximately 7% increased risk of mortality. Furthermore, in the entire study group, as well as in PD and HD patient subgroups, sRAGE was positively correlated with brain natriuretic peptide (BNP) levels. Mortality rates as well as sRAGE levels in patients who died did not differ between PD and HD patients. In conclusion, the positive association observed with BNP levels suggests a role for sRAGE as a prognostic factor for mortality in CKD-G5D patients displaying an active process of cardiac remodeling.

Advanced glycation end products (AGEs) may induce cardiac remodeling in kidney disease by promoting fibroblast growth factor 23 (FGF-23) expression. Since AGEs are increased in diabetes mellitus (DM), our first aim was to evaluate the existence of any potential association between AGEs, FGF-23, inflammation, and increased cardiovascular risk in DM patients on dialysis (CKD-G5D). Secondarily, we explored the potential role of the soluble receptor for AGEs (sRAGE) as a marker of heart failure. Levels of glycated albumin (GA), sRAGE, c-terminal FGF-23 (cFGF-23), brain natriuretic peptide (BNP), and inflammatory mediators were compared between DM and non-DM CKD-G5D patients. The levels of sRAGE, cFGF-23, BNP, and proinflammatory markers were over the ranges of normality in both DM and non-DM groups. Only GA and sRAGE levels were increased in DM compared to non-DM patients. Plasma levels of sRAGE and CRP were the only independent predictors of BNP concentration. In conclusion, in DM CKD-G5D patients, sRAGE appeared to be a marker of cardiac remodeling. Indeed, its increase could be a potential protective mechanism against the increased risk of cardiovascular complications related to AGEs and inflammation. The causal relationship between sRAGE and cardiovascular risk in these patients needs to be further confirmed by mechanistic studies.

Cardiorenal syndrome (CRS) type 3 is a subclassification of the CRS whereby an episode of acute kidney injury (AKI) leads to the development of acute cardiac injury or dysfunction. In general, there is limited understanding of the pathophysiologic mechanisms involved in CRS type 3. An episode of AKI may have effects that depend on the severity and duration of AKI and that both directly and indirectly predispose to an acute cardiac event. Experimental data suggest that cardiac dysfunction may be related to immune system activation, inflammatory mediators release, oxidative stress, and cellular apoptosis which are well documented in the setting of AKI. Moreover, significant derangements, such as fluid and electrolyte imbalance, metabolic acidosis, and uremia, which are typical features of acute kidney injury, may impair cardiac function. In this review, we will focus on multiple factors possibly involved in the pathogenesis issues regarding CRS type 3.

Cardiorenal Syndrome Type 1 (Type 1) is a specific condition which is characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). Even though its pathophysiology is complex and not still completely understood, oxidative stress seems to play a pivotal role. In this study, we examined the putative role of oxidative stress in the pathogenesis of CRS Type 1. Twenty-three patients with acute heart failure (AHF) were included in the study. Subsequently, 11 patients who developed AKI due to AHF were classified as CRS Type 1. Quantitative determinations for IL-6, myeloperoxidase (MPO), nitric oxide (NO), copper/zinc superoxide dismutase (Cu/ZnSOD), and endogenous peroxidase activity (EPA) were performed. CRS Type 1 patients displayed significant augmentation in circulating ROS and RNS, as well as expression of IL-6. Quantitative analysis of all oxidative stress markers showed significantly lower oxidative stress levels in controls and AHF compared to CRS Type 1 patients (P < 0.05). This pilot study demonstrates the significantly heightened presence of dual oxidative stress pathway induction in CRS Type 1 compared to AHF patients. Our findings indicate that oxidative stress is a potential therapeutic target, as it promotes inflammation by ROS/RNS-linked pathogenesis.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is an inherited condition caused by PKD1 and PKD2 mutations. Complete analysis of both genes is typically required in each patient. In this study, we explored the utility of High-Resolution Melt (HRM) as a tool for mutation analysis of the PKD2 gene in ADPKD families., Methods: HRM is a mismatch-detection method based on the difference of fluorescence absorbance behavior during the melting of the DNA double strand to denatured single strands in a mutant sample as compared to a reference control. Our families were previously screened by linkage analysis. Subsequently, HRM was used to characterize PKD2-linked families. Amplicons that produced an overlapping profile sample versus wild-type control were not further evaluated, while those amplicons with profile deviated from the control were consequently sequenced., Results: We analyzed 16 PKD2-linked families by HRM analysis. We observed ten different variations: six single-nucleotide polymorphisms and four mutations. The mutations detected by HRM and confirmed by sequencing were as follows: 1158T>A, 2159delA, 2224C>T, and 2533C>T. In particular, the same haplotype block and nonsense mutation 2533C>T was found in 8 of 16 families, so we suggested the presence of a founder effect in our province., Conclusions: We have developed a strategy for rapid mutation analysis of the PKD2 gene in ADPKD families, which utilizes an HRM-based prescreening followed by direct sequencing of amplicons with abnormal profiles. This is a simple and good technique for PKD2 genotyping and may significantly reduce the time and cost for diagnosis in ADPKD., (© 2014 Wiley Periodicals, Inc.)