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Innate lymphoid cells (ILCs) are a recently discovered lymphocyte population with high cytokine productive capacity. Type-2 ILCs (ILC2s) are the most studied, and they exert a rapid type-2 immune response to eliminate helminth infections. Massive and sustainable ILC2 activation induces allergic tissue inflammation, so it is important to maintain correct ILC2 activity for immune homeostasis. The ILC2-activating cytokine IL-33 is released from epithelial cells upon tissue damage, and it is upregulated in various kidney disease mouse models and in kidney disease patients. Various kidney diseases eventually lead to renal fibrosis, which is a common pathway leading to end-stage renal disease and is a chronic kidney disease symptom. The progression of renal fibrosis is affected by the innate immune system, including renal-resident ILC2s; however, the roles of ILC2s in renal fibrosis are not well understood. In this review, we summarize renal ILC2 function and characterization in various kidney diseases and highlight the known and potential contributions of ILC2s to kidney fibrosis.

To determine whether acute kidney injury results in later long-term decline in kidney function we measured changes in kidney function over a 3-year period in adults undergoing coronary angiography who had serum creatinine measurements as part of their clinical care. Acute kidney injury was categorized by the magnitude of increase in serum creatinine (mild (50–99% or ≥0.3mg/dl) and moderate or severe (≥100%)) within 7 days of coronary angiography. Compared to patients without acute kidney injury, the adjusted odds of a sustained decline in kidney function at 3 months following angiography increased more than 4-fold for patients with mild to more than 17-fold for those with moderate or severe acute kidney injury. Among those with an estimated glomerular filtration rate after angiography less than 90ml/min per 1.73m2, the subsequent adjusted mean rate of decline in estimated glomerular filtration rate during long-term follow-up (all normalized to 1.73m2 per year) was 0.2ml/min in patients without acute kidney injury, 0.8ml/min following mild injury, and 2.8ml/min following moderate to severe acute kidney injury. Thus, acute kidney injury following coronary angiography is associated with a sustained loss and a larger rate of future decline in kidney function.

The role of exogenous microRNAs (miRNAs) in renal fibrosis is poorly understood. Here, the effect of exogenous miRNAs on renal fibrosis was investigated using a renal fibrosis mouse model generated by unilateral ureteral obstruction (UUO). miRNA microarray analysis and quantitative reverse-transcription polymerase chain reaction showed that miR−122−5p was the most downregulated (0.28-fold) miRNA in the kidneys of UUO mice. The injection of an miR−122−5p mimic promoted renal fibrosis and upregulated COL1A2 and FN1, whereas an miR−122−5p inhibitor suppressed renal fibrosis and downregulated COL1A2 and FN1. The expression levels of fibrosis-related mRNAs, which were predicted targets of miR−122−5p, were evaluated. The expression level of TGFBR2, a pro-fibrotic mRNA, was upregulated by the miR−122−5p mimic, and the expression level of FOXO3, an anti−fibrotic mRNA, was upregulated by the miR−122−5p inhibitor. The protein expressions of TGFBR2 and FOXO3 were confirmed by immunohistochemistry. Additionally, the expression levels of LC3, downstream anti-fibrotic mRNAs of FOXO3, were upregulated by the miR−122−5p inhibitor. These results suggest that miR−122−5p has critical roles in renal fibrosis.

Two types of alternatively activated macrophages, M2a induced by IL-4/IL-13 and M2c by IL-10/TGF-β, exhibit anti-inflammatory functions in vitro and protect against renal injury in vivo. Since their relative therapeutic efficacy is unclear, we compared the effects of these two macrophage subsets in murine adriamycin nephrosis. Both subsets significantly reduced renal inflammation and renal injury; however, M2c macrophages more effectively reduced glomerulosclerosis, tubular atrophy, interstitial expansion, and proteinuria than M2a macrophages. The M2c macrophages were also more effective than M2a in reduction of macrophage and CD4+ T-cell infiltration in kidney. Moreover, nephrotic mice treated with M2c had a greater reduction in renal fibrosis than those treated with M2a. M2c but not M2a macrophages induced regulatory T cells (Tregs) from CD4+CD25- T cells in vitro, and increased Treg numbers in local draining lymph nodes of nephrotic mice. To determine whether the greater protection with M2c was due to their capability to induce Tregs, the Tregs were depleted by PC61 antibody in nephrotic mice treated with M2a or M2c. Treg depletion diminished the superior effects of M2c compared to M2a in protection against renal injury, inflammatory infiltrates, and renal fibrosis. Thus, M2c are more potent than M2a macrophages in protecting against renal injury due to their ability to induce Tregs.

Treatment of chronic kidney disease (CKD) can slow its progression to end-stage renal disease (ESRD). However, the therapies remain limited. Blood pressure control using angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) has the greatest weight of evidence. Glycemic control in diabetes seems likely to retard progression. Several metabolic disturbances of CKD may prove to be useful therapeutic targets but have been insufficiently tested. These include acidosis, hyperphosphatemia, and vitamin D deficiency. Drugs aimed at other potentially damaging systems and processes, including endothelin, fibrosis, oxidation, and advanced glycation end products, are at various stages of development. In addition to the paucity of proven effective therapies, the incomplete application of existing treatments, the education of patients about their disease, and the transition to ESRD care remain major practical barriers to better outcomes.

Objectives: Recognition of cognitive impairment in chronic kidney disease (CKD) and its impact on functioning in adults is growing. The vast majority of studies to date have been conducted in older populations where CKD is more pronounced; however, the degree to which age-related cognitive changes could be influencing these findings remains unaddressed. This current study thus aimed to review cognitive impairment findings by stage in non-elderly CKD samples. Methods: PubMed and Medline via Scopus were searched for cross-sectional or cohort studies and randomized controlled trials that assessed cognitive function in individuals with CKD in any research setting. CKD studies including patients at any illness stage were included providing participants were below 65 years old, were not on peritoneal dialysis and had not undergone a kidney transplant. Results: Fifteen studies, with a total of 9304 participants, were included. Cognitive function broadly deteriorated from stage 1 to stage 5. Early stage CKD was associated with a drop in speed of processing, attention, response speed, and short-term memory abilities. Moderate stage CKD was associated with deficits in executive functioning, verbal fluency, logical memory, orientation and concentration. People with end stage kidney disease manifested significant deficits in all previous cognitive domains, along with cognitive control, delayed and immediate memory, visuospatial impairment, and overall cognitive impairment. Conclusions: Cognitive impairment is evident across the stages of CKD, independent of age-related changes, for both lower-order and higher-order cognitive abilities. These impairments also increase between the stages, suggesting a cumulative effect. Future directions for research are discussed. (JINS, 2019, 25, 101–114)

An emergent hypothesis is that a resistance to the anabolic drive by insulin may contribute to loss of strength and muscle mass in patients with chronic kidney disease (CKD). We tested whether insulin resistance extends to protein metabolism using the forearm perfusion method with arterial insulin infusion in 7 patients with CKD and metabolic acidosis (bicarbonate 19mmol/l) and 7 control individuals. Forearm glucose balance and protein turnover (2H-phenylalanine kinetics) were measured basally and in response to insulin infused at different rates for 2h to increase local forearm plasma insulin concentration by approximately 20 and 50μU/ml. In response to insulin, forearm glucose uptake was significantly increased to a lesser extent (-40%) in patients with CKD than controls. In addition, whereas in the controls net muscle protein balance and protein degradation were decreased by both insulin infusion rates, in patients with CKD net protein balance and protein degradation were sensitive to the high (0.035mU/kg per min) but not the low (0.01mU/kg per min) insulin infusion. Besides blunting muscle glucose uptake, CKD and acidosis interfere with the normal suppression of protein degradation in response to a moderate rise in plasma insulin. Thus, alteration of protein metabolism by insulin may lead to changes in body tissue composition which may become clinically evident in conditions characterized by low insulinemia.

Background Chronic kidney disease (CKD) is a significant global health concern, with increasing focus on predicting renal prognosis. While renal prognosis is often studied in advanced CKD, variability in renal function and its implications for long-term outcomes in early-stage CKD remain insufficiently examined. This study aimed to investigate renal prognosis in early-stage CKD within the general population, focusing on patterns of renal function variability and factors associated with high variability. Methods This retrospective nationwide cohort study included participants from various geographical regions across Japan. A total of 1,765 adults with early-stage CKD (eGFR 45–59 mL/min/1.73 m 2 ), based on two initial screening results, were analyzed. The primary outcome was the pattern of eGFR variability identified by cluster analysis using three parameters: mean residual (difference between linear prediction and observed value), maximum residual, and range. In addition, we used a logistic regression model in order to assess associations between clinical factors and the high-risk cluster. Results We identified three distinct clusters based on eGFR variability using cluster analysis. Among these clusters, one exhibited significantly high variability with a high residual (median of mean residuals of 10.9 mL/min/1.73 m 2 and median of maximum residuals of 22.6 mL/min/1.73 m 2 ) and a wide range (median of range of 25.1 mL/min/1.73 m 2 ) (referred to as the \"high variability cluster\"). This cluster, comprising 4.6% of patients with early-stage CKD, demonstrated a more pronounced decline in eGFR over time. Factors such as younger age, proteinuria, antihypertensive drug use, and hyperglycemia were associated with the high variability cluster. Conclusions This study highlights the presence of distinct eGFR variability patterns in early-stage CKD and identifies a subgroup at high risk for rapid renal decline. Monitoring eGFR variability provides critical insights into long-term prognosis and may inform targeted interventions. Considering these findings, early detection and management of patients with early CKD may improve disease progression and reduce the risk of adverse outcomes. Trial registration This study is an observational study using a database and does not involve a health care intervention on human participants. Therefore, trial registration is not applicable.

Background Intestinal dysbiosis has been documented in humans with chronic kidney disease (CKD) and is thought to contribute to production of the uremic toxins indoxyl sulfate (IS) and p‐cresol sulfate (pCS). Characteristics of the fecal microbiome in cats with CKD and correlation to serum concentrations of uremic toxins are unknown. Objectives To characterize the fecal microbiome and measure serum IS and pCS concentrations of cats with CKD in comparison to healthy older cats. Animals Thirty client‐owned cats with CKD (International Renal Interest Society stages 2‐4) and 11 older (≥8 years) healthy control cats. Methods Prospective, cross‐sectional study. Fecal samples were analyzed by sequencing of 16S rRNA genes and Escherichia coli quantitative PCR (qPCR). Serum concentrations of IS and pCS measured using liquid chromatography tandem mass spectrometry. Results Cats with CKD had significantly decreased fecal bacterial diversity and richness. Escherichia coli qPCR showed no significant difference in bacteria count between control and CKD cats. Cats with stage 2 (P = .01) and stages 3 and 4 (P = .0006) CKD had significantly higher serum IS concentrations compared to control cats. No significant difference found between stage 2 and stages 3 and 4 CKD. The pCS concentrations were not significantly different between CKD cats and control cats. Conclusions and Clinical Importance Decreased fecal microbiome diversity and richness is associated with CKD in cats. Indoxyl sulfate concentration is significantly increased with CKD, and cats with stage 2 CKD may suffer from a similar uremic toxin burden as do cats with later stage disease.