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Background/Aims: The metabolic syndrome (MetS), as assessed using dichotomous criteria, is associated with increased risk of future chronic kidney disease (CKD), though this relationship is unclear among African Americans, who have lower risk for MetS but higher risk for CKD. Methods: We performed logistic regression using a sex- and race-specific MetS-severity z-score to assess risk of incident CKD among 2,627 African-American participants of the Jackson Heart Study, assessed at baseline and 8 years later. Based on quartile of baseline MetS severity, we further assessed prevalence of being in the lowest quartile of baseline GFR, the lowest quartile of relative GFR at follow-up, microalbuminuria and incident CKD. Results: Higher MetS-severity was associated with higher prevalence of GFR in the lowest quartile at baseline among males and females. Among African-American females but not males, higher baseline MetS-severity was associated with a higher prevalence of baseline elevations in microabuminuria (p<0.01), steep decline in GFR (p<0.001) and a higher incidence of CKD (p<0.0001). Women in increasing quartiles of baseline MetS-severity exhibited a linear trend toward higher odds of future CKD (p<0.05), with those in the 4th quartile of MetS-severity (compared to the 1st) having an odds ratio of 2.47 (95% confidence interval 1.13, 5.37); no such relationship was seen among men (p value for trend 0.49). Conclusion: MetS-severity exhibited sex-based interactions regarding risk for future GFR deterioration and CKD, with increasing risk in women but not men. These data may have implications for triggering CKD screening among African-American women with higher degrees of MetS-severity. [ABSTRACT FROM AUTHOR]

As advances in Critical Care Medicine continue, critically ill patients are surviving despite the severity of their illness. The incidence of acute kidney injury (AKI) has increased, and its impact on clinical outcomes as well as medical expenditures has been established. The role, indications and technological advancements of renal replacement therapy (RRT) have evolved, allowing more effective therapies with less complications. With these changes, Critical Care Nephrology has become an established specialty, and ongoing collaborations between critical care physicians and nephrologist have improved education of multi-disciplinary team members and patient care in the ICU. Multidisciplinary programs to support these changes have been stablished in some hospitals to maximize the delivery of care, while other programs have continue to struggle in their ability to acquire the necessary resources to maximize outcomes, educate their staff, and develop quality initiatives to evaluate and drive improvements. Clearly, the role of the nephrologist in the ICU has evolved, and varies widely among institutions. This special article will provide insights that will hopefully optimize the role of the nephrologist as the leader of the acute care nephrology program, as clinician for critically ill patients, and as teacher for all members of the health care team. [ABSTRACT FROM AUTHOR]

Aims: The study aimed to determine whether the available literature supports a positive or negative influence of dialysis on regulatory T-cells (Tregs). Methods: We performed a systematic search and a meta-analysis. Mean differences in Tregs number of chronic kidney disease stages G5 on dialysis patients (CKD G5D) and healthy controls (HCs) were compared. Random effects model was applied. The software used was general package for meta-analysis (version 4.3-0, depends R (≥ 2.9.1)). Results: Five studies were included in the meta-analysis. The mean difference in percentage of Tregs on CD4+ T-cells between CKD G5D and HCs was not statistically different. Moreover, CKD GFR stages G5 not on dialysis (CKD G5) versus HC (p = 0.002; mean difference in Treg percentage was -2.47% in CKD G5 vs. HC) and CKD G5 versus CKD G5D (not significant). Conclusion: This metaanalysis demonstrates an association between the uremic state and lower Tregs, and supports the hypothesis that hemodialysis alter Tregs. Our findings highlight the need for new clinical studies. [ABSTRACT FROM AUTHOR]

Background: The reticulon 1 gene (RTN1) encodes reticulons, endoplasmic reticulum stress proteins recently implicated in kidney disease progression.Methods: RTN1 single nucleotide polymorphisms (SNPs) were tested for association with type 2 diabetes (T2D)-associated end-stage kidney disease (ESKD) in African Americans (AAs) and European Americans (EAs), and AAs with non-diabetic ESKD. RTN1 SNPs that were associated with T2D-ESKD in AA cases compared to non-nephropathy controls were identified from a discovery genome-wide association study (n=1,797), then tested for replication in 1,847 additional AA T2D-ESKD cases and controls.Results: Three intronic RTN1 variants were nominally associated with T2D-ESKD in both discovery and replication analyses: rs1952034, rs12431381 and rs12434215 (additive models); combined T2D-ESKD (discovery+replication) p values were 0.015-3.0×10(-4) (ORs 0.67-0.77; minor alleles protective). In addition, rs12434215 was weakly associated with T2D-ESKD in 557 EA T2D-ESKD cases contrasted with 753 EA non-nephropathy controls (p=0.019; OR 0.69, dominant model). Nominal association extended to non-diabetic causes of ESKD in 1,459 additional AA cases (rs12431381 and rs12434215 p values 0.014-0.015; OR 0.77). An all-cause ESKD association analysis contrasted the 3,594 AA ESKD cases with 1,489 AA non-nephropathy controls and detected association with rs12434215 (p=6.7×10(-4), OR 0.73) and rs12431381 (p=7.5×10(-4), OR 0.75) in dominant models. Of the 3 SNPs, only rs12434215 was weakly associated with T2D per se when contrasting T2D non-nephropathy cases with non-diabetic controls (additive model p=0.032 AAs; p=0.048 EAs).Conclusions: These results suggest evidence of genetic association between common variants in RTN1 and ESKD in AAs and EAs. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) contributes to progressive kidney disease. Although significant advances have been made in the understanding of mechanisms of AKI, less is known about the biological basis that links the initial injury to progressive interstitial fibrosis, tubular dysfunction, and capillary rarefaction. The round table discussion focused on mechanisms of renal recovery and fibrosis following AKI. The knowledge gained by understanding these pathways will serve to identify novel therapeutic targets in the future. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Along with the increase in aging of our population, the proportion of older patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) is on the rise as a result of the accumulation of comorbidities as well as biological processes associated with aging. Older patients with acute kidney injury (AKI) comprise an increasing proportion of patients with CKD/ESRD as well. In this review, we will discuss biological processes of aging that predispose patients to AKI and CKD. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is an increasing medical burden and is independently associated with mortality. AKI is a common comorbidity in the intensive care unit (ICU), with sepsis-associated AKI seen in almost a quarter of all ICU patients. Due to the high mortality seen in these patients, improved therapeutic options are needed. Data from experimental studies in animals support observations in humans that the host immune response to sepsis and trauma contributes to multiorgan failure and the high morbidity and mortality seen in critically ill patients. The spleen, a major component of the reticuloendothelial system, appears to be a key player in the 'cytokine storm' that develops after infection and trauma, and the resultant systemic inflammation is regulated by the autonomic nervous system. Over the past decade, evidence has suggested that controlling the splenic cytokine response improves tissue function and mortality in sepsis and other inflammatory-mediated diseases. One pathway that controls the response of the spleen to sepsis and trauma is the cholinergic anti-inflammatory pathway, and it may provide a key target for therapeutic intervention. Here, we review this concept and highlight the potential use of ultrasound to stimulate the cholinergic anti-inflammatory pathway and reduce systemic inflammation and disease severity. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aims: The role of kidney infiltrating T cells in the pathology of lupus nephritis is unclear. This study was undertaken to investigate whether CD4+ T cell responses to a surrogate mesangial antigen can initiate glomerulonephritis. Methods: Ovalbumin (OVA) was deposited in the glomerular mesangium of C57BL/6 (B6) mice using anti-α8-integrin immunoliposomes (α8ILs). This was followed by injection of activated OVA-reactive CD4+ transgenic OT2 T cells. Trafficking of antigen-specific OT2 T cells to kidneys and lymph nodes was studied by flow cytometry. Glomerular pathology and immune cell infiltration was characterized by immunostaining. Role of CCR2 deficiency on T cell-mediated glomerulonephritis was investigated using B6.ccr2-/- mice. Results: α8ILs delivered OVA specifically to the renal glomeruli. Adoptively transferred OT2 T cells preferentially accumulated in renal lymph nodes and in the renal cortex. Kidneys showed glomerular inflammation with recruitment of endogenous T cells, dendritic cells and macrophages. T cell-mediated inflammation induced mesangial cell activation and an increase in glomerular MCP1 and fibronectin. The formation of inflammatory foci was driven by Ly6C monocytes and was CCR2 dependent. Conclusions: The findings from this study show that T cells reactive with antigens in the mesangium are sufficient to initiate glomerular pathology. Antigen-specific CD4 T cells act by inducing glomerular MCP1 production which mediates recruitment of inflammatory monocytes resulting in glomerulonephritis. Thus, downmodulation of T cell responses within the kidneys of lupus patients will be a beneficial therapeutic approach. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Ischemia-reperfusion injury (IRI) is one of the major causes of acute kidney injury (AKI) and evidence supporting the involvement of both innate and adaptive immunity in renal IRI has accumulated in recent years. In addition to leukocytes, kidney endothelial cells promote inflammation after IRI by increasing adhesion molecule expression and vascular permeability. Kidney tubular epithelial cells increase complement binding and upregulate toll-like receptors, both of which lead to cytokine/chemokine production in IRI. Activation of kidney resident dendritic cells, interferon-γ-producing neutrophils, infiltrating macrophages, CD4+ T cells, B cells and invariant natural killer T cells are all implicated in the pathogenesis of AKI. The complex interplay between innate and adaptive immunity in renal IRI is still not completely understood, but major advances have been made. This review summarizes these recent advances to further our understanding of the immune mechanisms of acute kidney injury. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Renal interstitial inflammation is a consequence of unilateral ureteral obstruction (UUO). Following ischemia/reperfusion, adenosine reduces renal inflammation and injury, effects which are potentiated by type 4 phosphodiesterase inhibitors. We therefore studied the effects of A2A adenosine receptor agonist (ATL146e), and PDE4 inhibitor (rolipram) in mice subjected to UUO. Methods: Mice were subjected to UUO or sham operation, and received either vehicle or ATL146e + rolipram by osmotic minipump for 1 or 7 days. At 1, 3, 7, or 14 days after operation, renal macrophage infiltration, apoptosis, proliferation, tubular atrophy, and interstitial fibrosis were quantitated, and expressions of IL-6 and TGF-β mRNA were determined. Results: ATL146e + rolipram reduced macrophage infiltration by 40% after 3 days UUO (p < 0.05). Tubular apoptosis, tubular atrophy, and interstitial fibrosis were increased by 7 or 14 days UUO, but were unaffected by ATL146e + rolipram. However, cellular proliferation was increased by ATL146e + rolipram in the obstructed kidney. ATL146e + rolipram had no effect on the renal expression of IL-6 and TGF-β mRNA. Conclusions: A2A receptor activation and PDE4 inhibition transiently reduce renal macrophage infiltration, but do not ameliorate the renal response to UUO. We speculate that the persistent stimulus for inflammation triggered by UUO cannot be reversed by agents that suppress inflammatory cell activation alone. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The pathogenesis of human acute ischemic renal failure is complex. Studies in animals have revealed a number of factors that could contribute to the injury associated with acute ischemic renal failure. Despite these discoveries, we have yet to devise a therapeutic regimen that will ameliorate or prevent acute renal failure in humans. Nevertheless we have made great strides in understanding mechanisms that contribute to acute ischemic renal failure. An important component is the contribution of the inflammatory cascade brought about by tissue reperfusion following an ischemic period. This review summarizes recent studies that implicate the inflammatory cells in the development of renal injury associated with acute ischemic renal failure. Because of the complex overlapping pathways involved in the inflammatory cascade, blocking single molecules is unlikely to be successful in reducing renal injury. Rather broadly abrogating the inflammatory cascade is likely to yield the greatest success in the treatment and prevention of acute ischemic renal failure.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A foreword to "Nephron Physiology" is presented.