Chemokine ligand 2 (CCL2) binds to its receptor C–C chemokine receptor 2 (CCR2), initiating tissue inflammation, and recent studies have suggested a beneficial effect of a blockade of this pathway in ...diabetic nephropathy. To investigate the mechanism of protection, we studied the effect of RS504393, a CCR2 antagonist, on insulin resistance and diabetic nephropathy in db/db mice. Administering this antagonist improved insulin resistance as confirmed by various biomarkers, including homeostasis model assessment index levels, plasma insulin levels, and lipid abnormalities. Mice treated with the antagonist had a significant decrease in epididymal fat mass as well as phenotypic changes of adipocytes into small differentiated forms with decreased CCL2 expression and lipid hydroperoxide levels. In addition, treatment with the CCR2 antagonist markedly decreased urinary albumin excretion, mesangial expansion, and suppressed profibrotic and proinflammatory cytokine synthesis. Furthermore, the CCR2 antagonist improved lipid metabolism, lipid hydroperoxide, cholesterol, and triglyceride contents of the kidney, and decreased urinary 8-isoprostane levels. Hence, our findings suggest that CCR2 antagonists can improve insulin resistance by modulation of the adipose tissue and restore renal function through both metabolic and anti-fibrotic effects in type 2 diabetic mice.
There is no established modality to repair kidney damage resulting from ischemia-reperfusion injury (IRI). Early responses to IRI involve lymphocytes, but the role of B cells in tissue repair after ...IRI is unknown. Here, we examined B cell trafficking into postischemic mouse kidneys and compared the repair response between control (wild-type) and muMT (B cell-deficient) mice with and without adoptive transfer of B cells. B cells infiltrated postischemic kidneys and subsequently activated and differentiated to plasma cells during the repair phase. Plasma cells expressing CD126 increased and B-1 B cells trafficked into postischemic kidneys with distinct kinetics. An increase in B lymphocyte chemoattractant in the kidney preceded B cell trafficking. Postischemic kidneys of muMT mice expressed higher IL-10 and vascular endothelial growth factor and exhibited more tubular proliferation and less tubular atrophy. Adoptive transfer of B cells into muMT mice reduced tubular proliferation and increased tubular atrophy. Treatment with anti-CD126 antibody increased tubular proliferation and reduced tubular atrophy in the late repair phase. These results demonstrate that B cells may limit the repair process after kidney IRI. Targeting B cells could have therapeutic potential to improve repair after IRI.
Background
The renoprotective effect of water intake remains unclear. We aimed to investigate the relationship between water intake and renal impairment in the Korean general population, focusing on ...individual differences in body fluid distribution and risk of chronic dehydration.
Methods
We conducted a cross-sectional analysis of the 2008–2017 Korea National Health and Nutrition Examination Survey (KNHANES). Adult participants who had body weight and serum creatinine data and had answered 24-h recall nutritional survey were included. Four water intake groups were defined by daily total water intake per body weight: lowest (< 20 mL/kg/day), low-moderate (20–29.9 mL/kg/day), high-moderate (30–49.9 mL/kg/day), and highest (≥ 50 mL/kg/day). We assessed the risk of renal impairment (estimated glomerular filtration rate ≤ 60 mL/min/1.73 m
2
) according to water intake.
Results
In total of 50,113 participants, 3.9% had renal impairment. The risk of renal impairment gradually decreased as water intake increased. After adjustment of sodium intake, the trend of renoprotective effect was remained in low-moderate and high-moderate water intake group compared to low intake group, whereas no significant impact was observed with the highest water intake due to concurrent intake of high sodium. In subgroup analysis, the renoprotective effect of water intake was significant in the participants with elderly, male and daily sodium intake over 2 g/day.
Conclusions
High daily water intake is renoprotective. Our data may provide an important basis for determining the amount of water intake needed to prevent renal impairment, considering variations in body weight, body composition and risk of chronic dehydration.
Background
The association between proteinuria and malignancy has been frequently reported, but the issue is matter of controversy. Thus, in order to shed light on the association, we evaluated ...proteinuria as a risk factor for malignancy using the dataset from the Korean National Health Insurance System (NHIS).
Methods
The subjects had undergone a medical examination in 2009 (index year) among the entire Korean adult population. From a pool of 10,505,818 participants, we excluded subjects who were younger than 19 years (15,327), had a previous diagnosis of cancer (152,095), had missing data for at least one variable (544,508), and were diagnosed with cancer within 1 year from the index year (79,501). Proteinuria was examined by a single dipstick urinalysis.
Results
A total of 9,714,387 subjects were included in this study and tracked until December 31, 2017. The participants were divided into three groups; no (95.2%), trace (2.3%), and overt (2.5%) proteinuria. Over the duration of this study, we observed that overt proteinuria was associated with an increased risk of cancer development (all cancers) (adjusted HR 1.154, 95% CI 1.134–1.173) and the long-term risk of cancer incidence increased proportionally according to the changes in proteinuria over a four-year period.
Limitations
Our study population consisted of Korean adults. Therefore, the results of this study may not be generalized to other ethnicities.
Conclusions
We found a significant relationship between proteinuria and the risk of overall and site-specific cancer development. Further studies are needed to find an explanation of these findings.
Background. Ischaemia/reperfusion is a major cause of acute kidney injury and can result in poor long-term graft function. Although most of the patients with acute kidney injury recover their renal ...function, significant portion of patients suffer from progressive deterioration of renal function. A persistent inflammatory response might be associated with long-term changes following acute ischaemia/reperfusion. Macrophages are known to infiltrate into tubulointersitium in animal models of chronic kidney disease. However, the role of macrophages in long-term changes after ischaemia/reperfusion remains unknown. We aimed to investigate the role of macrophages on the development of tubulointerstitial fibrosis and functional impairment following acute ischaemia/reperfusion injury by depleting macrophages with liposome clodronate. Methods. Male Sprague–Dawley rats underwent right nephrectomy and clamping of left renal vascular pedicle or sham operation. Liposome clodronate or phosphate buffered saline was administered for 8 weeks. Biochemical and histological renal damage and gene expression of various cytokines were assessed at 4 and 8 weeks after ischaemia/reperfusion. Results. Ischaemic/reperfusion injury resulted in persistent inflammation and tubulointerstital fibrosis with decreased creatinine clearance and increased urinary albumin excretion at 4 and 8 weeks. Macrophage depletion attenuated those changes. This beneficial effect was accompanied with a decrease in gene expression of inflammatory and profibrotic cytokines. Conclusions. These results suggest that macrophages play an important role in mediating persistent inflammation and fibrosis after ischaemia/reperfusion leading to a development of chronic kidney disease. Strategies targeting macrophage infiltration or activation can be useful in the prevention of development of chronic kidney disease following ischaemic injury.
Background. Peroxisome proliferator-activated receptors (PPARs) are nuclear transcription factors that play a role in insulin sensitivity, lipid metabolism and inflammation. However, the effects of ...PPARγ agonist on renal inflammation have not been fully examined in type 2 diabetic nephropathy. Methods. In the present study, we investigated the effect and molecular mechanism of the PPARγ agonist, pioglitazone, on the progression of diabetic nephropathy in type 2 diabetic rats. Inflammatory markers including NF-κB, MCP-1 and pro-fibrotic cytokines were determined by RT-PCR, western blot, immunohistochemical staining and EMSA. In addition, to evaluate the direct anti-inflammatory effect of PPARγ agonist, we performed an in vitro study using mesangial cells. Results. Treatment of OLETF rats with pioglitazone improved insulin sensitivity and kidney/body weight, but had a little effect on blood pressure. Pioglitazone treatment markedly reduced urinary albumin and MCP-1 excretion, and ameliorated glomerulosclerosis. In cDNA microarray analysis using renal cortical tissues, several inflammatory and profibrotic genes were significantly down-regulated by pioglitazone including NF-κB, CCL2, TGFβ1, PAI-1 and VEGF. In renal tissues, pioglitazone treatment significantly reduced macrophage infiltration and NF-κB activation in association with a decrease in type IV collagen, PAI-1, and TGFβ1 expression. In cultured mesangial cells, pioglitazone-activated endogenous PPARγ transcriptional activity and abolished high glucose-induced collagen production. In addition, pioglitazone treatment also markedly suppressed high glucose-induced MCP-1 synthesis and NF-κB activation. Conclusions. These data suggest that pioglitazone not only improves insulin resistance, glycaemic control and lipid profile, but also ameliorates renal injury through an anti-inflammatory mechanism in type 2 diabetic rats.
Elevated levels of serum myostatin have been proposed as a biomarker for sarcopenia. Recent studies have shown that elevated level of serum myostatin was associated with physical fitness and ...performance. This study aimed to examine the significance of myostatin in the association between muscle mass and physical performance in the elderly.
This cross-sectional study is based on the Korean Frailty and Aging Cohort study involving 1053 people aged 70 years or over. Anthropometric, physical performance, and laboratory data were collected.
The mean age of the participants was 75.8 years, and 50.7% of them were female. Serum myostatin levels in men (3.7 ± 1.2 vs. 3.2 ± 1.1 ng/mL,
< 0.001) were higher compared with that in women. Serum myostatin level was associated with appendicular skeletal muscle mass (ASM) index and eGFR by cystatin C. Serum myostatin/ASM ratio was associated with handgrip strength in women.
Higher serum myostatin levels were related with higher muscle mass and better physical performances in the elderly. Serum myostatin/ASM ratio may be a predictor for physical performance rather than myostatin.
Introduction: Acute pyelonephritis (APN) is a common infection during pregnancy that increases the risk of unfavorable maternal and fetal outcomes. However, it has not been clearly elucidated which ...demographic and clinical characteristics are associated with the incidence of APN during pregnancy. Objective: This population-based cohort study aimed to determine the risk factors for APN during pregnancy. Methods: Using the database of the Health Insurance Review and Assessment Service of South Korea, we enrolled Korean women who delivered infants between 2010 and 2014 in Korea and had complete health examination records within 1 year of pregnancy. We performed multivariate logistic regression analysis to evaluate the risk factors for APN during pregnancy. Results: Of 370,248 women, 2,526 (0.7% of the total participants) were treated for APN while in hospitalization during pregnancy. Younger age, history of previous APN within 1 year of pregnancy, and abnormal results of health examination before pregnancy, such as high fasting glucose level (>100 mg/dL) and proteinuria, were associated with an increased risk of APN during pregnancy. Conclusion: Certain maternal demographic and clinical characteristics were associated with the incidence of APN during pregnancy, and these should be monitored closely during antenatal care.
Kidney ischemia-reperfusion injury (IRI) is, in part, mediated by immune and inflammatory factors. Since microbial stimuli are known to alter immune and inflammatory responses, we hypothesized that ...differences in perinatal microbial status would modify renal injury following IRI. We performed bilateral renal IRI on 6-wk-old germ-free and control mice and studied the effects on kidney lymphocyte trafficking, cytokines, function, and structure. Compared with control mice, normal kidneys of germ-free mice exhibited more NKT cells and lower IL-4 levels. Postischemia, more CD8 T cells trafficked into postischemic kidneys of germ-free mice compared with control mice. Renal structural injury and functional decline following IRI were more severe in germ-free mice compared with control mice. When germ-free mice were conventionalized with the addition of bacteria to their diet, the extent of renal injury after IRI became equivalent to age-matched control mice, with similar numbers and phenotypes of T cells and NKT cells, as well as cytokine expression in both normal kidneys and postischemic kidneys of conventionalized germ-free mice and age-matched control mice. Thus microbial stimuli influence the phenotype of renal lymphocytes and the expression of cytokines of normal kidneys and also modulate the outcome of IRI.
PDF
