Efficacy of sucrose and povidone-iodine mixtures in peritoneal dialysis catheter exit-site care.

BACKGROUND: Exit-site infection (ESI) is a common recurring complication in patients undergoing peritoneal dialysis (PD). Sucrose and povidone-iodine (SPI) mixtures, antimicrobial ointments that promote wound healing, have been used for the treatment of ulcers and burns, but their efficacy in exit-site care is still unclear. METHODS: This single-center retrospective observational study included patients who underwent PD between May 2010 and June 2022 and presented with episodes of ESI. Patients were divided into SPI and non-SPI groups and followed up from initial ESI onset until PD cessation, death, transfer to another facility, or June 2023. RESULTS: Among the 82 patients (mean age 62, [54-72] years), 23 were treated with SPI. The median follow-up duration was 39 months (range, 14-64), with an overall ESI incidence of 0.70 episodes per patient-year. Additionally, 43.1% of second and 25.6% of third ESI were caused by the same pathogen as the first. The log-rank test demonstrated significantly better second and third ESI-free survival in the SPI group than that in the non-SPI group (p < 0.01 and p < 0.01, respectively). In a Cox regression analysis, adjusting for potential confounders, SPI use was a significant predictor of decreased second and third ESI episodes (hazard ratio [HR], 0.22; 95% confidence interval [CI], 0.10-0.52 and HR, 0.22; 95%CI, 0.07-0.73, respectively). CONCLUSIONS: Our results showed that the use of SPI may be a promising option for preventing the incidence of ESI in patients with PD. TRIAL REGISTRATION: This study was approved by the Keio University School of Medicine Ethics Committee (approval number 20231078) on August 28, 2023. Retrospectively registered.

Combining hemodialysis with peritoneal dialysis improves cognitive function: a three-case report.

Chronic kidney disease (CKD) is associated with multiple complications, with recent scholarly attention underscoring cognitive impairment as a salient manifestation. Considering societal aging, preserving cognitive function has emerged as an urgent medical concern. Prolonged dialysis, encompassing hemodialysis (HD) and peritoneal dialysis (PD), has been associated with a decline in cognitive function. Here, we present the cases of three patients undergoing PD who exhibited a noticeable improvement in cognitive function upon the initiation of HD. One patient had exhibited mild cognitive decline, whereas the remaining two presented more severe impairment. Apart from a mild tendency for fluid retention, none of the three patients exhibited abnormalities in physical or imaging examinations. Evaluation using the Japanese version of the Montreal Cognitive Assessment (MoCA-J) yielded decreased scores across multiple domains, notably in executive and attention functions. However, after HD initiation, all patients demonstrated a marked enhancement in multiple MoCA-J parameters, accompanied by a significant improvement in subjective symptoms. Moreover, improvements in anemia and hypoalbuminemia were observed in all three patients, whereas consistent trends in other parameters were absent. These clinical observations suggest that the integration of HD into the therapeutic regimen of patients undergoing PD may enhance cognitive function, highlighting the contributory roles of hemoglobin and albumin in CKD-associated cognitive impairment.

Renal sinus fat is associated with intrarenal hemodynamic abnormalities independent of visceral fat in patients with chronic kidney disease.

OBJECTIVE: Obesity is a risk factor of chronic kidney disease (CKD), contributing to the rising incidence of cardiometabolic diseases. Renal sinus fat (RSF) is an ectopic fat depot located at the renal cavity that could impair renal function and hemodynamic through compression of renal structures. The major purpose of this study was to explore the relationship between RSF accumulation and renal dysfunction in CKD patients. METHODS: We evaluated the associations between computed tomography measured RSF volume and key clinical and histologic parameters involved in renal function and hemodynamics in 132 well-characterized CKD patients who underwent renal biopsy (median age: 62 years; 63.6% men). RESULTS: RSF volume normalized by renal volume (RSF%) positively correlated with obesity-related traits such body mass index and visceral fat volume (VFV) (all P < 0.001) whereas it negatively correlated with estimated glomerular filtration rate (eGFR) (ρ = -0.42, P < 0.001) and 24-h urinary creatinine clearance (CCr) (ρ = -0.34, P < 0.001). Notably, we found robust positive correlations between RSF% and renal resistive index (RRI) measured by the Doppler ultrasound (ρ = 0.40, P < 0.001), and the histological severity of global glomerular sclerosis (ρ = 0.48, P < 0.001) and interstitial fibrosis and tubular atrophy (IFTA) (ρ = 0.35, P < 0.001). In the multivariate linear regression models, after accounting for potential confounders including VFV, RSF% remained significantly associated with CCr (ß = -0.26, P < 0.001), RRI (ß = 0.17, P = 0.022), global glomerular sclerosis (ß = 0.21, P = 0.002), and IFTA (ß = 0.17, P = 0.012). CONCLUSION: RSF accumulation is associated with renal dysfunction and hemodynamic abnormalities independent of visceral adiposity. Our results suggest that RSF may have a potential unique role in the pathogenesis of CKD.

Secular trends and age-specific distribution of blood pressure in Japanese adolescents aged 12-18 years in 2000-2019.

Adolescent blood pressure is a predictor of future risk for hypertension and cardiovascular diseases, and therefore its status needs to be accurately determined. However, limited evidence is available regarding the secular trends and distribution of adolescent blood pressure. In the present study, we assessed the secular trends and age-specific distributions of blood pressure in Japanese adolescents aged 12-18 years by using data drawn from 20 years of annual health checkups conducted between 2000 and 2019. Participants underwent health checkups every year for three years at the same school and the data were divided into four 5-year cycles: 2000-2004, 2005-2009, 2010-2014, and 2015-2019. From a total of 124,460 records (33,496 individuals) retrieved, 3000 records (3000 individuals) from each year-cycle were randomly selected to avoid duplicating data from the same individuals. In the study period, in males systolic blood pressure showed a decreasing trend over time, whereas in females diastolic blood pressure showed an increasing trend. Subgroup analyses by school category (junior/senior high school) and by obesity category showed similar blood pressure trends as in the overall analysis. Age-specific blood pressure values in Japanese adolescents increased with age in males but not in females. Thus, different patterns of change in blood pressure values over the past 20 years were observed between males and females. Age-specific blood pressure distributions are also presented. Together, these findings will be useful for understanding blood pressure trends among adolescents.

Association Between Renal Sinus Fat and Cardiometabolic and Renin-Angiotensin System Parameters in Primary Aldosteronism.

Context: Renal sinus fat (RSF) accumulation is associated with cardiometabolic diseases, such as obesity, diabetes, hypertension, and chronic kidney disease. However, clinical implications of RSF in primary aldosteronism (PA) remain unclear. Objective: We aimed to investigate relationships between RSF volume and key cardiometabolic and renin-angiotensin system (RAS) parameters in PA patients and clarify the differences in these relationships between unilateral and bilateral subtypes. Methods: We analyzed data obtained from well-characterized PA patients that involved 45 unilateral (median age: 52 years; 42.2% men) and 92 bilateral patients (51 years; 42.4% men). Results: RSF volume normalized by renal volume (RSF%) was greater in the unilateral group than in the bilateral group (P < .05). RSF% was greater in men than in women (P < .05). RSF% positively correlated with parameters related to cardiometabolic risk, including age, body mass index, visceral fat volume, creatinine, triglycerides/high-density lipoprotein cholesterol ratio, uric acid, fasting glucose, and C-reactive protein regardless of PA subtypes (all P < .05). Intriguingly, RSF% positively correlated with plasma aldosterone concentration (PAC), aldosterone-to-renin ratio, and intact parathyroid hormone (iPTH) (all P < .05) in bilateral patients but did not correlate with RAS parameters and even showed an opposite trend in unilateral patients. In subgroup analyses by sex, these distinctions became more evident in women. After adjustment for potential confounders, RSF% remained positively correlated with PAC and iPTH in bilateral patients. Conclusion: Our results indicate that RSF accumulation is involved in cardiometabolic dysfunction associated with PA. However, there were distinct correlations between RSF volume and RAS parameters according to sex and PA subtypes.

Pediatric blood pressure category predicts longitudinal blood pressure change in adolescence and early adulthood.

BACKGROUND: Patterns of blood pressure (BP) change from early adolescence to young adulthood have not been well-described. The objective of this study was to examine the predictive value of pediatric BP classification on BP change and identify subpopulations with large BP increases during adolescence and early adulthood. METHODS: Baseline data were obtained from medical checkups of Japanese adolescents aged 12-13 years in 2009 or 2010 and subsequent BP values were followed for a 9-year period. Mixed-effects models were used to estimate the effects of baseline factors on subsequent BP changes. RESULTS: Hypertensive and elevated BP group consistently had higher BP values than normal BP group throughout the observation period. Multivariate mixed-effects model analyses revealed group-by-time interactions between systolic BP change and BP category in males and uric acid category in females, and between diastolic BP change and white blood cell count in males and obesity and high-density lipoprotein cholesterol in females; however, these factors had limited effects on the rate of BP increase, indicating that they are not suitable as clinical predictors of BP increase. CONCLUSIONS: Pediatric BP category predicted BP values, but there was no factor that identified subpopulations with large BP increases in adolescence and early adulthood. IMPACT: Blood pressure category in the American Academy of Pediatrics clinical practice guideline at age 12-13 years predicted subsequent blood pressure values during adolescence and early adulthood. No baseline factor that identified a subpopulation with large increase in blood pressure during adolescence and early adulthood in clinical practice was found. Our study contributes to the existing literature by demonstrating the usefulness of the American Academy of Pediatrics clinical practice guideline for blood pressure classification in a Japanese population.

DNA-damaged podocyte-CD8 T cell crosstalk exacerbates kidney injury by altering DNA methylation.

Recent epigenome-wide studies suggest an association between blood DNA methylation and kidney function. However, the pathological importance remains unclear. Here, we show that the homing endonuclease I-PpoI-induced DNA double-strand breaks in kidney glomerular podocytes cause proteinuria, glomerulosclerosis, and tubulointerstitial fibrosis with DNA methylation changes in blood cells as well as in podocytes. Single-cell RNA-sequencing analysis reveals an increase in cytotoxic CD8+ T cells with the activating/costimulatory receptor NKG2D in the kidneys, which exhibit a memory precursor effector cell phenotype, and the CD44high memory CD8+ T cells are also increased in the peripheral circulation. NKG2D blockade attenuates the renal phenotype caused by podocyte DNA damage. Blood methylome shows increased DNA methylation in binding sites for STAT1, a transcription factor contributing to CD8+ T cell homeostasis. Collectively, podocyte DNA damage alters the blood methylome, leading to changes in CD8+ T cells, which contribute to sustained renal injury in chronic kidney disease.

Compared effectiveness of sodium zirconium cyclosilicate and calcium polystyrene sulfonate on hyperkalemia in patients with chronic kidney disease.

Hyperkalemia is a well-recognized electrolyte abnormality in patients with chronic kidney disease (CKD). Potassium binders are often used to prevent and treat hyperkalemia. However, few studies have evaluated the difference in serum potassium (K+) level-lowering effect during the post-acute phase between the novel potassium binder, sodium zirconium cyclosilicate (ZSC), and conventional agents. This retrospective study included patients who received potassium binders (either ZSC or calcium polystyrene sulfonate [CPS]) in our hospital between May 2020 and July 2022. The patients were divided into the ZSC and CPS groups. After propensity score matching, we compared changes from baseline to the first follow-up point, at least 4 weeks after initiating potassium binders, in electrolytes including K+ level between the two groups. Of the 132 patients, ZSC and CPS were administered in 48 and 84 patients, respectively. After matching, 38 patients were allocated to each group. The ZSC group showed greater reduction in K+ levels than did the CPS group (P < 0.05). Moreover, a significant increase in serum sodium minus chloride levels, a surrogate marker for metabolic acidosis, was observed in the ZSC group (P < 0.05). Our results demonstrated that ZSC could potentially improve hyperkalemia and metabolic acidosis in patients with CKD.

A systematic review and meta-analysis of the clinical impact of stopping renin-angiotensin system inhibitor in patients with chronic kidney disease.

Although renin-angiotensin system (RAS) inhibitors reduce the risk of cardiovascular diseases and end-stage kidney disease (ESKD) in chronic kidney disease (CKD) patients, they are often discontinued in clinical practice due to drug-related adverse events. However, limited evidence is available about the clinical impact of RAS inhibitor discontinuation in CKD patients. A comprehensive search of publications investigating the effect of discontinuing RAS inhibitors on clinical outcomes in CKD patients in PubMed, the Cochrane Library, and Web of Science was conducted (inception to November 7, 2022), and potentially relevant studies were searched by hand (through November 30, 2022). Two reviewers independently extracted data according to the PRISMA and MOOSE guidelines and assessed the quality of each study with risk-of-bias tools, RoB2 and ROBINS-I. The pooled hazard ratio (HR) for each outcome was integrated with a random-effect model. A total of 1 randomized clinical trial and 6 observational studies involving 248,963 patients were included in the systematic review. The meta-analysis of observational studies showed that discontinuation of RAS inhibitors was associated with a higher risk of all-cause mortality (HR, 1.41 [95% CI, 1.23-1.62]; I2 = 97%), ESKD (1.32 [95% CI, 1.10-1.57]; I2 = 94%) and MACE (1.20 [95% CI 1.15-1.25]; I2 = 38%), but not with hyperkalemia (0.79 [95% CI 0.55-1.15]; I2 = 90%). Overall risk of bias was moderate-to-serious, and quality of evidence (GRADE system) was low-to-very low. The present study suggests that CKD patients would benefit from continuing RAS inhibitors.

Plasminogen activator inhibitor 1 is not a major causative factor for exacerbation in a mouse model of SARS-CoV-2 infection.

Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a global pandemic. Although several vaccines targeting SARS-CoV-2 spike proteins protect against COVID-19 infection, mutations affecting virus transmissibility and immune evasion potential have reduced their efficacy, leading to the need for a more efficient strategy. Available clinical evidence regarding COVID-19 suggests that endothelial dysfunction with thrombosis is a central pathogenesis of progression to systemic disease, in which overexpression of plasminogen activator inhibitor-1 (PAI-1) may be important. Here we developed a novel peptide vaccine against PAI-1 and evaluated its effect on lipopolysaccharide (LPS)-induced sepsis and SARS-CoV-2 infection in mice. Administration of LPS and mouse-adapted SARS-CoV-2 increased serum PAI-1 levels, although the latter showed smaller levels. In an LPS-induced sepsis model, mice immunized with PAI-1 vaccine showed reduced organ damage and microvascular thrombosis and improved survival compared with vehicle-treated mice. In plasma clot lysis assays, vaccination-induced serum IgG antibodies were fibrinolytic. However, in a SARS-CoV-2 infection model, survival and symptom severity (i.e., body weight reduction) did not differ between vaccine- and vehicle-treated groups. These results indicate that although PAI-1 may promote the severity of sepsis by increasing thrombus formation, it might not be a major contributor to COVID-19 exacerbation.

Efficacy of pre-emptive kidney transplantation for adults with end-stage kidney disease: a systematic review and meta-analysis.

BACKGROUND: Pre-emptive kidney transplantation (PEKT), i.e., transplantation performed before initiation of maintenance dialysis, is considered an ideal renal replacement therapy because there is no exposure to long-term dialysis therapy. Therefore, we summarized advantages/disadvantages of PEKT to assist in deciding whether kidney transplantation should be performed pre-emptively. METHODS: This study was registered with PROSPERO, CRD42021269163. Observational studies comparing clinical outcomes between PEKT and non-PEKT were included; those involving only pediatric recipients or simultaneous multi-organ transplantations were excluded. The PubMed/MEDLINE, Cochrane Library, and Ichushi-Web databases were searched on 1 August 2021. Studies were pooled using the generic inverse-variance method with random effects model, and risk of bias was assessed using ROBINS-I. RESULTS: Seventy-six studies were included in the systematic review (sample size, 23-121,853; enrollment year, 1968-2019). PEKT patients had lower all-cause mortality (adjusted HR: 0.78 [95% CI 0.66-0.92]), and lower death-censored graft failure (0.81 [0.67-0.98]). Unadjusted RRs for the following outcomes were comparable between the two patient groups: cardiovascular disease, 0.90 (0.58-1.40); biopsy-proven acute rejection, 0.75 (0.55-1.03); cytomegalovirus infection, 1.04 (0.85-1.29); and urinary tract infection, 0.89 (0.61-1.29). Mean differences in post-transplant QOL score were comparable in both groups. The certainty of evidence for mortality and graft failure was moderate and that for other outcomes was very low following the GRADE classification. CONCLUSIONS: The present meta-analysis shows the potential benefits of PEKT, especially regarding patient and graft survival, and therefore PEKT is recommended for adults with end-stage kidney disease.

Significance of podocyte DNA damage and glomerular DNA methylation in CKD patients with proteinuria.

The number of chronic kidney disease (CKD) patients is increasing worldwide, and it is necessary to diagnose CKD patients in earlier stages to improve their prognosis. Previously, in a study using human samples, we reported that DNA methylation and DNA damage in podocytes are potential markers for kidney function decline in IgA nephropathy; however, these candidate markers have not been adequately investigated in other glomerular diseases. Here, we report that the association of podocyte DNA damage and DNA methylation with eGFR decline and proteinuria differs depending on the type of glomerular disease. Patients diagnosed with minor glomerular abnormality (MGA, n = 33), membranous nephropathy (MN, n = 9) or diabetic nephropathy (DN, n = 10) following kidney biopsy at Keio University Hospital from 2015 to 2017 were included. In MGA patients, both podocyte DNA damage and glomerular DNA methylation were associated with the severity of proteinuria. In DN patients, podocyte DNA double-strand breaks (DSBs) and glomerular DNA methylation were associated with an eGFR decline. When patients with urinary protein levels of more than 1 g/gCr were examined, fewer podocyte DNA DSBs were detected in MN patients than in MGA patients, and the level of glomerular DNA methylation was lower in MN patients than in MGA or DN patients. These results indicate that investigating podocyte DNA DSBs and DNA methylation changes may be useful for understanding the pathogenesis of CKD with proteinuria in humans. This study suggested the association of podocyte DNA damage and subsequent DNA methylation with proteinuria in minor glomerular abnormalities (MGA) patients and those with eGFR declines in diabetic nephropathy (DN) patients, respectively.

Late Dialysis Modality Education Could Negatively Predict Peritoneal Dialysis Selection.

Patients with end-stage renal disease are less likely to choose peritoneal dialysis (PD) as renal replacement therapy (RRT). The reasons for this biased selection are still poorly understood. In this study, we evaluated the effect of the timing of RRT education on PD selection. This single-center retrospective observational study included patients who initiated maintenance dialysis at our hospital between April 2014 and July 2021. A logistic regression analysis was performed to investigate the association of RRT education timing with PD selection. Among the 355 participants (median age [IQR] 70 (59−79) years; 28.7% female), 53 patients (14.9%) and 302 patients (85.1%) selected PD and hemodialysis, respectively. Multivariate analysis demonstrated that high estimated glomerular filtration (eGFR) at RRT education positively predicted PD selection (p < 0.05), whereas old age (p < 0.01) and high Charlson comorbidity index (p < 0.05) were negative predictors of PD selection. Female sex (p = 0.44), welfare public assistance (p = 0.78), living alone (p = 0.25), high geriatric nutritional risk index (p = 0.10) and high eGFR at first visit to the nephrology department (p = 0.83) were not significantly associated with PD selection. Late RRT education could increase the biased selection of dialysis modality.

Vaccination against connective tissue growth factor attenuates the development of renal fibrosis.

There is a critical need for efficient treatment of chronic kidney disease (CKD). Renal fibrosis is a final common pathway to end-stage renal disease independent of the underlying etiology, and connective tissue growth factor (CTGF) is a well-recognized profibrotic factor in fibrosis of various organ systems. Here, we developed a novel peptide vaccine against CTGF to attenuate the development of renal fibrosis. Three inoculations with this CTGF vaccine at 2-week intervals elicited antibodies specifically binding to human full-length CTGF, and the antigen-specific serum IgG antibody titers were maintained for > 30 weeks. The efficacy of the CTGF vaccine on renal fibrosis was evaluated in adenine-induced CKD and unilateral ureteral obstruction (UUO) murine models. In adenine-induced CKD model, immunization with the CTGF vaccine attenuated renal interstitial fibrosis. Vaccinated mice showed low levels of serum creatinine and urea nitrogen and low urine albumin-creatinine ratio compared with vehicle-treated mice. In UUO model, the CTGF vaccination also suppressed the onset of renal fibrosis. In an in vitro study, CTGF vaccine-elicited IgG antibodies efficiently suppressed CTGF-induced- and transforming growth factor-ß-induced α-smooth muscle actin expression in kidney fibroblasts. These results demonstrate that the CTGF vaccine is a promising strategy to attenuate the development of renal fibrosis.

Effects of renin-angiotensin system inhibitors on the incidence of unplanned dialysis.

Unplanned dialysis initiation is associated with poor outcomes. It is controversial whether patients with advanced chronic kidney disease (CKD) should receive renin-angiotensin system (RAS) inhibitor therapy. The aim of this study was to evaluate the effect of RAS inhibitor therapy in patients with advanced CKD on the incidence of unplanned dialysis initiation. This single-center, retrospective study included patients who started maintenance dialysis at our hospital between April 2014 and March 2021. Patients who initiated dialysis within 6 months of nephrology referral or after kidney transplant were excluded. Among 334 patients (aged 70.0 [59.0-79.0] years; 28.4% women), 186 (55.7%) and 148 (44.3%) had planned and unplanned dialysis initiation, respectively. Multivariate logistic regression analysis revealed that the use of RAS inhibitors was significantly associated with a lower incidence of unplanned dialysis initiation (odds ratio [OR], 0.36; P < 0.01). Female sex (OR, 0.41; P < 0.05), use of potassium binders (OR, 0.28; P < 0.001), earlier referral to nephrology (OR, 0.39; P < 0.01), and earlier discussion of renal replacement therapy (OR, 0.33; P < 0.001) were also significantly associated with a lower incidence, whereas older age (OR, 1.28; P < 0.05), higher Charlson Comorbidity Index (OR, 1.24; P < 0.05), and faster decline in kidney function (OR, 1.29; P < 0.01) were associated with a higher risk of unplanned dialysis initiation. RAS inhibitor therapy in patients with advanced CKD is associated with a lower risk of unplanned dialysis initiation.

Serum thymus and activation-regulated chemokine level is associated with the severity of chronic kidney disease-associated pruritus in patients undergoing peritoneal dialysis.

BACKGROUND: Thymus and activation-regulated chemokine (TARC), which induces a Th2-dominated inflammation, is a well-known biomarker that reflects the severity of atopic dermatitis. The present study aimed to evaluate TARC as a Th2-associated marker with chronic kidney disease-associated pruritus (CKD-aP) in patients with peritoneal dialysis (PD). METHODS: This single-centre cross-sectional study included patients who underwent PD in our hospital between August 2020 and July 2021. The severity and impaired quality of life (QOL) of CKD-aP were assessed using the visual analogue scale (VAS) and Japanese version of the 5-D itch scale (5D-J), respectively. RESULTS: A total of 48 patients with PD were included in the present study. Age and dialysis vintage were (mean ± SD) 64.8 ± 12.0 year and (median (IQR)) 38.5 (11.5-91.5) month, respectively. VAS and 5D-J scores were 3.3 ± 2.0 and 10.5 (9.0-12.0), respectively. Serum TARC level was 481.5 (278.9-603.4) pg/mL (upper limits of normal 450 pg/mL) and significantly correlated with VAS (r = 0.39, p = 0.006) and 5D-J score (r = 0.37, p = 0.009). Multivariate linear analysis revealed that higher serum TARC level was significantly associated with VAS (p < 0.001) and 5D-J score (p < 0.001). Furthermore, the serum brain natriuretic peptide level tended to be associated with VAS (p = 0.060) and 5D-J score (p = 0.029). CONCLUSION: Serum TARC level is an independent predictor of the severity and impaired QOL of CKD-aP in patients with PD, and TARC might be involved in the pathogenesis of CKD-aP.

Fibronectin Glomerulopathy Confused with Glomerular Endothelial Injury in a Patient with Takotsubo Cardiomyopathy.

A 46-year-old woman developed takotsubo cardiomyopathy and nephrotic syndrome. The first kidney biopsy suggested non-immune-complex-mediated membranoproliferative glomerulonephritis (MPGN), and she was diagnosed with glomerular endothelial injury associated with takotsubo cardiomyopathy. A second biopsy was performed two years later because of persistent proteinuria despite renin-angiotensin system inhibition. This biopsy indicated non-immune-complex-mediated MPGN, but a mesangial and subendothelial substance of a higher electron density than that in the first biopsy was detected, suggesting the possibility of glomerular disease with non-immune deposits rather than endothelial injury. Finally, she was diagnosed with fibronectin nephropathy. Although rare, fibronectin glomerulopathy should be considered in non-immune-complex-mediated MPGN.

Blood Pressure Tracking From Childhood to Adulthood.

Hypertension is the most common non-communicable disease among adults and is the most important modifiable risk factor for premature cardiovascular disease. The increasing worldwide burden of hypertension is a major global health issue. Early prevention with lifestyle modification or pharmaceutical treatment reduces the incidence of hypertension and the risk of subsequent cardiovascular disease. Therefore, identification of young persons at risk for hypertension has the obvious benefit of providing a chance for early intervention. Previous studies have demonstrated the positive association of elevated childhood blood pressure with hypertension in adulthood. Accumulated evidence also indicates the possibility that elevated pediatric blood pressure is associated with increased risk of future cardiovascular disease. In this article, we review the tracking of blood pressure from childhood to adulthood and emphasize the importance of pediatric blood pressure monitoring and control for predicting and preventing adult hypertension and cardiovascular disease.

DNA repair factor KAT5 prevents ischemic acute kidney injury through glomerular filtration regulation.

The "preconditioning effect" in AKI is a phenomenon in which an episode of ischemia-reperfusion results in tolerance to subsequent ischemia-reperfusion injury. However, its relationship between DNA damage repair has not been elucidated. Here, we show the role of KAT5 in the preconditioning effect. Preconditioning attenuated DNA damage in proximal tubular cells with elevated KAT5 expression. Ischemia-reperfusion (IR) injuries were exacerbated, and preconditioning effect vanished in proximal tubular-cell-specific KAT5 knockout mice. Investigation of tubuloglomerular feedback (TGF) by MALDI-IMS and urinary adenosine revealed that preconditioning caused attenuated TGF at least in part via KAT5. In addition, K-Cl cotransporter 3 (KCC3) expression decreased in damaged proximal tubular cells, which may be involved in accelerated TGF following IR. Furthermore, KAT5 induced KCC3 expression by maintaining chromatin accessibility and binding to the KCC3 promoter. These results suggest a novel mechanism of the preconditioning effect mediated by the promotion of DNA repair and attenuation of TGF through KAT5.