Circulatory endostatin level and risk of cardiovascular events in patients with end-stage renal disease on hemodialysis.

BACKGROUND: Endostatin is released during extracellular matrix remodeling and is involved in the development of vascular pathology and cardiovascular (CV) disease. However, the role of circulating endostatin as a biomarker of vascular calcification and CV events in patients undergoing hemodialysis (HD) remains unclear. METHODS: A total of 372 patients undergoing HD were prospectively recruited. Plasma endostatin levels were measured at baseline, and their associations with circulating mineral bone disease (MBD) biomarkers and abdominal aortic vascular calcification scores were analyzed. The primary endpoint was defined as a composite of CV and cardiac events. RESULTS: Plasma levels of patients in endostatin tertile 3 were significantly associated with low-density lipoprotein cholesterol levels and predialysis systolic blood pressure in multivariate analysis. However, endostatin levels did not correlate with circulating MBD biomarkers or vascular calcification scores. Patients in endostatin tertile 3 had a significantly higher cumulative event rate for the composite of CV events (p = 0.006). Endostatin tertile 3 was also associated with an increased cumulative rate of cardiac events (p = 0.04). In multivariate Cox regression analyses, endostatin tertile 3 was associated with a 4.37-fold risk for composite CV events and a 3.88-fold risk for cardiac events after adjusting for multiple variables. CONCLUSION: Higher circulating endostatin levels were independently associated with atherosclerotic risk factors but did not correlate with MBD markers or vascular calcification. Higher circulating endostatin levels were associated with a greater risk of composite CV events in patients undergoing HD, and endostatin is a biomarker that helps to determine the high risk of CV events.

Association between albuminuria and retinal microvascular parameters measured with swept-source optical coherence tomography angiography in patients with diabetic retinopathy.

PURPOSE: To evaluate the relationship between urine albumin excretion (UAE) and retinal microvascular parameters assessed using swept-source optical coherence tomography angiography (SS-OCTA) in patients with diabetic retinopathy (DR). METHODS: This retrospective cross-sectional study included 180 patients with diabetes and 50 age-matched controls. Patients with diabetes were grouped according to the five-stage DR severity, combined with the presence of albuminuria. All subjects underwent 12×12mm2 field SS-OCTA. The foveal avascular zone metrics, vessel density, and capillary nonperfusion area (NPA) were quantified using a semi-automatic software algorithm on three different rectangular fields (3×3 mm2, 6×6 mm2, and 10×10 mm2). The correlations between albuminuria and the four OCTA parameters were analyzed. RESULTS: A total of 105 subjects had normal UAE, and 75 subjects had albuminuria. Of the 102 subjects whose DR severity was higher than mild non-proliferative DR (NPDR), capillary NPA on the 3×3 mm2, 6×6 mm2, and 10×10 mm2 fields was significantly larger in the albuminuria group. None of the OCTA parameters were significantly different between the two groups in subjects with mild NPDR or without DR. Multiple logistic regression analysis showed that an increase in NPA in the 6×6 mm2 and 10×10 mm2 fields was a significant risk factor for the presence of albuminuria (odds ratio = 1.92 and 1.35). CONCLUSION: An increase in capillary NPA was independently associated with albuminuria in patients with clinically significant DR levels. SS-OCTA imaging can be a useful marker for the early detection of diabetic nephropathy.

Target blood pressure in Korean hemodialysis patients for optimal survival.

Background: Hypertension is a major cardiovascular risk factor in hemodialysis patients. This study identified the optimal blood pressure (BP) target for Korean hemodialysis patients using the Korean Renal Dialysis System (KORDS) dataset from the Korean Society of Nephrology and a pooled analysis for previous studies. Methods: Hemodialysis patients were classified according to their systolic (SBP) and diastolic BP (DBP) at intervals of 20 and 10 mmHg, respectively. As a primary and secondary outcome, all-cause mortality and cardiovascular mortality were evaluated. Subsequently, pooled analysis with previous literatures was performed. Results: Among 70,607 patients, 13,708 (19.4%) died in 2,426 days (interquartile range, 1,256-4,075 days). Mean SBP and DBP were 143.0 ± 19.6 and 78.5 ± 12.0 mmHg. In multivariable Cox regression, the patients with SBP of <120 and ≥180 mmHg showed 1.10- and 1.12-times increased risk of all-cause mortality compared to SBP of 120-140 mmHg. Meanwhile, DBP showed no significant association. In subgroup analysis, patients aged <70 years and without diabetes had a U-shaped SBP-mortality association. Cardiovascular mortality was increased in SBP of ≥160 mmHg compared to 120-140 mmHg, but it was not in <120 mmHg. Pooled analysis with previous studies mostly showed elevated risk in SBP of <120 mmHg, but the risks in 140-160 and 160-180 mmHg were not consistent. Conclusion: Extremely lowering BP (<120 mmHg) or uncontrolled hypertension (≥160 mmHg) should be avoided to optimize survival in Korean hemodialysis patients. Detailed analysis for patients with SBP of 120-160 mmHg should be studied further under uniform BP measurement, along with consideration of risk of intradialytic hypotension. Tailored recommendations regarding patient risk factors also should be considered.

Clinical significance of the living kidney donor profile index for predicting long-term posttransplant outcomes: results from the Korean Organ Transplantation Registry.

Background: The usefulness of the living kidney donor profile index (LKDPI) has not been widely demonstrated; therefore, it requires verification before clinical application. We analyzed the LKDPI using data from the Korean Organ Transplantation Registry (KOTRY) to confirm whether the LKDPI can be used to predict the survival of allografts in living donor kidney transplantation (LDKT) patients in Korea. Methods: The study population was obtained from the KOTRY database. A total of 2,598 kidney recipients registered in the KOTRY database were enrolled between May 2014 and December 2020. Donor and recipient information was observed, and the LKDPI was measured. Results: Median LKDPI score was 15.5 with a follow-up duration of 33.7 ± 16.1 months. According to LKDPI scores (group 1, <0; group 2, 0-20; group 3, 20-40; and group 4, >40), LKDPI group 4 had significantly higher death-censored graft loss than LKDPI group 1 (hazard ratio [HR], 1.89; 95% confidence interval [CI], 1.06- 3.40; p = 0.03). When divided based on the cutoff value (LKDPI, 36.6), the high LKDPI group had higher graft loss than the low LKDPI group (HR, 2.14; 95% CI, 1.37-3.34; p < 0.001). When follow-up was repeated after transplantation, it was confirmed that the higher the LKDPI value was, the lower the average estimated glomerular filtration rate (p < 0.001). Conclusion: This study confirmed that LKDPI can serve as an independent predictor for assessing the risk of allograft failure and transplant outcomes in Korean LDKT patients.

How obesity and metabolic syndrome affect cardiovascular events, progression to kidney failure and all-cause mortality in chronic kidney disease.

BACKGROUND: Obesity and metabolic syndrome (MetS) are prevalent among chronic kidney disease (CKD) patients. However, it is unclear whether obesity without MetS is associated with a higher risk of adverse clinical outcomes in CKD patients. METHODS: We searched the National Health Insurance Service database of Korea for patients who underwent national health screenings in 2009-2011 and identified 59 725 CKD patients. Obesity was defined as a body mass index ≥25 kg/m2. MetS was defined as the presence of ≥3 metabolic risks. RESULTS: The cumulative event rate of cardiovascular events, progression to end-stage kidney disease (ESKD), and all-cause mortality was the lowest among obese patients without MetS (all P < 0.001). In multivariable analysis, obese (versus non-obese) patients without MetS were not at increased risks of cardiovascular events (adjusted hazard ratio [HR] 1.02; 95% confidence interval 0.94-1.11) or progression to ESKD (0.92; 0.77-1.09). Their risk of all-cause mortality was significantly decreased (0.82; 0.75-0.90). These findings were consistently observed in overweight, obese, and morbidly obese patients without MetS. Moreover, despite a linear increase in HR for each additional metabolic abnormality in both obese and non-obese patients, the slope of HR increase for cardiovascular events was significantly slower in obese patients (P for interaction = 0.038). CONCLUSIONS: Obesity without MetS did not increase the risk of cardiovascular complications or progression to ESKD. The healthy effect of obesity on all-cause mortality risk and its weakening effect on the association between metabolic hazards and cardiovascular risk should be considered in CKD patients.

Korean guidelines for the management of gout.

Gout is the most common form of arthritis, with the prevalence increasing worldwide. The present treatment guidelines provide recommendations for the appropriate treatment of acute gout, management during the inter-critical period, and prevention of chronic complications. The guidelines were developed based on evidence-based medicine and draft recommendations finalized after expert consensus. These guidelines are designed to provide clinicians with clinical evidence to enable efficient treatment of gout.

A questionnaire survey on the diagnosis and treatment of Fabry nephropathy in clinical practice.

BACKGROUND: Fabry nephropathy is characterized by a deficiency of lysosomal alpha-galactosidase A, which results in proteinuria and kidney disease. The ineffectiveness of enzyme replacement therapy (ERT) for severe kidney failure highlights the need for early detection and meaningful markers. However, because the diagnosis and treatment of Fabry disease can vary according to the expertise of physicians, we evaluated the opinions of Korean specialists. METHODS: A questionnaire regarding the management of Fabry nephropathy was emailed to healthcare providers with the experience or ability to treat individuals with Fabry nephropathy. RESULTS: Of the 70 experts who responded to the survey, 43 were nephrologists, and 64.3% of the respondents reported having treated patients with Fabry disease. Pediatricians are treating primarily patients with classic types of the disease, while nephrologists and cardiologists are treating more patients with variant types. Only 40.7% of non-nephrologists agreed that a kidney biopsy was required at the time of diagnosis, compared with 81.4% of nephrologists. Thirty-eight of 70 respondents (54.3%) reported measuring globotriaosylsphingosine (lyso-Gb3) as a biomarker. The most common period to measure lyso-Gb3 was at the time of diagnosis, followed by after ERT, before ERT, and at screening. For the stage at which ERT should begin, microalbuminuria and proteinuria were chosen by 51.8% and 28.6% of respondents, respectively. CONCLUSION: Nephrologists are more likely to treat variant Fabry disease rather than classic cases, and they agree that ERT should be initiated early in Fabry nephropathy, using lyso-Gb3 as a biomarker.

Korean guidelines for the management of gout.

Gout is the most common form of arthritis, with the prevalence increasing worldwide. The present treatment guidelines provide recommendations for the appropriate treatment of acute gout, management during the inter-critical period, and prevention of chronic complications. The guidelines were developed based on evidence-based medicine and draft recommendations finalized after expert consensus. These guidelines are designed to provide clinicians with clinical evidence to enable efficient treatment of gout.

Corrigendum: Development and validation of urinary exosomal microRNA biomarkers for the diagnosis of acute rejection in kidney transplant recipients.

[This corrects the article DOI: 10.3389/fimmu.2023.1190576.].

Development and validation of urinary exosomal microRNA biomarkers for the diagnosis of acute rejection in kidney transplant recipients.

Introduction: Acute rejection (AR) continues to be a significant obstacle for short- and long-term graft survival in kidney transplant recipients. Herein, we aimed to examine urinary exosomal microRNAs with the objective of identifying novel biomarkers of AR. Materials and methods: Candidate microRNAs were selected using NanoString-based urinary exosomal microRNA profiling, meta-analysis of web-based, public microRNA database, and literature review. The expression levels of these selected microRNAs were measured in the urinary exosomes of 108 recipients of the discovery cohort using quantitative real-time polymerase chain reaction (qPCR). Based on the differential microRNA expressions, AR signatures were generated, and their diagnostic powers were determined by assessing the urinary exosomes of 260 recipients in an independent validation cohort. Results: We identified 29 urinary exosomal microRNAs as candidate biomarkers of AR, of which 7 microRNAs were differentially expressed in recipients with AR, as confirmed by qPCR analysis. A three-microRNA AR signature, composed of hsa-miR-21-5p, hsa-miR-31-5p, and hsa-miR-4532, could discriminate recipients with AR from those maintaining stable graft function (area under the curve [AUC] = 0.85). This signature exhibited a fair discriminative power in the identification of AR in the validation cohort (AUC = 0.77). Conclusion: We have successfully demonstrated that urinary exosomal microRNA signatures may form potential biomarkers for the diagnosis of AR in kidney transplantation recipients.

Clinical implications of circulating follistatin-like protein-1 in hemodialysis patients.

Follistatin-like protein-1 (FSTL-1) is secreted glycoprotein, which regulates cardiovascular, immune and skeletal system. However, the clinical significance of circulating FSTL-1 levels remains unclear in hemodialysis patients. A total 376 hemodialysis patients were enrolled from June 2016 to March 2020. Plasma FSTL-1 level, inflammatory biomarkers, physical performance, and echocardiographic findings at baseline were examined. Plasma FSTL-1 levels were positively correlated with TNF-α and MCP-1. Handgrip strength showed weak positive correlation in male patients only, and gait speed showed no correlation with FSTL-1 levels. In multivariate linear regression analysis, FSTL-1 level was negatively associated with left ventricular ejection fraction (ß = - 0.36; p = 0.011). The cumulative event rate of the composite of CV event and death, and cumulative event rate of CV events was significantly greater in FSTL-1 tertile 3. In multivariate Cox-regression analysis, FSTL-1 tertile 3 was associated with a 1.80-fold risk for the composite of CV events and death(95% confidence interval (CI) 1.06-3.08), and a 2.28-fold risk for CV events (95% CI 1.15-4.51) after adjustment for multiple variables. In conclusion, high circulating FSTL-1 levels independently predict the composite of CV events and death, and FSTL-1 level was independently associated with left ventricular systolic dysfunction.

Novel Genetic Variants Associated with Chronic Kidney Disease Progression.

SIGNIFICANCE STATEMENT: eGFR slope has been used as a surrogate outcome for progression of CKD. However, genetic markers associated with eGFR slope among patients with CKD were unknown. We aimed to identify genetic susceptibility loci associated with eGFR slope. A two-phase genome-wide association study identified single nucleotide polymorphisms (SNPs) in TPPP and FAT1-LINC02374 , and 22 of them were used to derive polygenic risk scores that mark the decline of eGFR by disrupting binding of nearby transcription factors. This work is the first to identify the impact of TPPP and FAT1-LINC02374 on CKD progression, providing predictive markers for the decline of eGFR in patients with CKD. BACKGROUND: The incidence of CKD is associated with genetic factors. However, genetic markers associated with the progression of CKD have not been fully elucidated. METHODS: We conducted a genome-wide association study among 1738 patients with CKD, mainly from the KoreaN cohort study for Outcomes in patients With CKD. The outcome was eGFR slope. We performed a replication study for discovered single nucleotide polymorphisms (SNPs) with P <10 -6 in 2498 patients with CKD from the Chronic Renal Insufficiency Cohort study. Several expression quantitative trait loci (eQTL) studies, pathway enrichment analyses, exploration of epigenetic architecture, and predicting disruption of transcription factor (TF) binding sites explored potential biological implications of the loci. We developed and evaluated the effect of polygenic risk scores (PRS) on incident CKD outcomes. RESULTS: SNPs in two novel loci, TPPP and FAT1-LINC02374 , were replicated (rs59402340 in TPPP , Pdiscovery =7.11×10 -7 , PCRIC =8.13×10 -4 , Pmeta =7.23×10 -8 ; rs28629773 in FAT1-LINC02374 , Pdiscovery =6.08×10 -7 , PCRIC =4.33×10 -2 , Pmeta =1.87×10 -7 ). The eQTL studies revealed that the replicated SNPs regulated the expression level of nearby genes associated with kidney function. Furthermore, these SNPs were near gene enhancer regions and predicted to disrupt the binding of TFs. PRS based on the independently significant top 22 SNPs were significantly associated with CKD outcomes. CONCLUSIONS: This study demonstrates that SNP markers in the TPPP and FAT1-LINC02374 loci could be predictive markers for the decline of eGFR in patients with CKD.

Impact of donor hypertension on graft survival and function in living and deceased donor kidney transplantation: a nationwide prospective cohort study.

OBJECTIVES: Hypertensive living donors are potential candidates to expand the kidney donor pool. However, the impact of donor hypertension on graft survival and function remains to be clarified. METHODS: We analyzed 3907 kidney transplant recipients registered in a nationwide prospective cohort from 2014 to 2018. Patients were divided by donor types and the presence of donor hypertension. The primary and secondary outcome was the occurrence of death-censored graft failure and renal allograft function, respectively. RESULTS: The prevalence of hypertension was 9.4% (258/2740) and 19.9% (232/1167) in living and deceased donors, respectively. During a median follow-up of 21.8 months, death-censored graft survival rate was significantly worse in recipients of hypertensive living donors than in those of normotensive living donors ( P  = 0.008). In multivariable analysis, recipients of hypertensive living donors had a significantly increased risk of graft loss (adjusted hazard ratio 2.91; P  = 0.009). The risk of allograft loss was not different between recipients of hypertensive living and normotensive deceased donors. Propensity score-matched analyses had consistent worse graft survival rate in recipients of hypertensive living donors compared to those of normotensive living donors ( P  = 0.027), while it was not different between recipients of hypertensive living and normotensive deceased donors. Hypertension in living donors had a significant negative impact on one-year graft function (adjusted unstandardized ß -3.64; P  = 0.011). CONCLUSIONS: Hypertensive living donor recipients have significantly higher risks of renal allograft loss than normotensive living donor recipients, and showed similar outcomes compared to recipients of normotensive deceased donors.

Glycated hemoglobin levels and risk of all-cause and cause-specific mortality in hemodialysis patients with diabetes.

AIM: Adequate glycemic control is fundamental for improving clinical outcomes in hemodialysis patients with diabetes. However, the target for glycated hemoglobin (HbA1c) level and whether cause-specific mortality differs based on HbA1c levels remain unclear. METHODS: A total of 24,243 HD patients with diabetes were enrolled from a multicenter, nationwide registry. We examined the association between HbA1c levels and the risk of all-cause and cause-specific mortality. RESULTS: Compared to patients with HbA1c 6.5%-7.5%, patients with HbA1c 8.5-9.5% and ≥9.5% were associated with a 1.26-fold (95% CI, 1.12-1.42) and 1.56-fold (95% CI, 1.37-1.77) risk for all-cause mortality. The risk of all-cause mortality did not increase in patients with HbA1c < 5.5%. In cause-specific mortality, the risk of cardiovascular deaths significantly increased from small increase of HbA1c levels. However, the risk of other causes of death increased only in patients with HbA1c > 9.5%. The slope of HR increase with increasing HbA1c levels was significantly faster for cardiovascular causes than for other causes. CONCLUSIONS: There was a linear relationship between HbA1c levels and risk of all-cause mortality in hemodialysis patients, and the risk of cardiovascular death increased earlier and more rapidly, with increasing HbA1c levels, compared with other causes of death.

Hydrophilic Versus Lipophilic Statin Treatments in Patients With Renal Impairment After Acute Myocardial Infarction.

Background Hydrophilic and lipophilic statins have similar efficacies in treating coronary artery disease. However, specific factors relevant to renal impairment and different arterial pathogeneses could modify the clinical effects of statin lipophilicity, and create differences in protective effects between statin types in patients with renal impairment. Methods and Results A total of 2062 patients with acute myocardial infarction with an estimated glomerular filtration rate <60 mL/min per 1.73 m2 were enrolled from the Korea Acute Myocardial Infarction Registry between November 2011 and December 2015. The primary end point was a composite of 2-year major adverse cardiac and cerebrovascular events (MACEs) after acute myocardial infarction occurrence. MACEs were defined as all-cause death, recurrent myocardial infarction, revascularization, and stroke. Propensity-score matching and Cox proportional hazards regression were performed. A total of 529 patients treated with hydrophilic statins were matched to 529 patients treated with lipophilic statins. There was no difference in the statin equivalent dose between the 2 statin groups. The cumulative event rate of MACEs, all-cause mortality, and recurrent myocardial infarction were significantly lower in patients treated with hydrophilic statins in the propensity-score matched population (all P<0.05). In the multivariable Cox regression analysis, patients treated with hydrophilic statins had a lower risk for composite MACEs (hazard ratio [HR], 0.70 [95% CI, 0.55-0.90]), all-cause mortality (HR, 0.67 [95% CI, 0.49-0.93]), and recurrent myocardial infarction (HR, 0.40 [95% CI, 0.21-0.73]), but not for revascularization and ischemic stroke. Conclusions Hydrophilic statin treatment was associated with lower risk of MACEs and all-cause mortality than lipophilic statin in a propensity-score matched observational cohort of patients with renal impairment following acute myocardial infarction.

Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Response After Heterologous Immunizations With ChAdOx1/BNT162b2 in End-Stage Renal Disease Patients on Hemodialysis.

The Korean government decided to schedule heterologous vaccinations on dialysis patients for early achievement of immunization against Coronavirus disease 2019(COVID-19). However, the effects of heterologous immunizations in hemodialysis (HD) patients are unclear. One hundred (HD) patients from Gangdong Kyung Hee University Hospital and Kyung Hee Medical Center and 100 hospital workers from Gangdong Kyung Hee University Hospital were enrolled in this study. The HD patients received the mixing schedule of ChAdOx1/BNT162b2 vaccinations at 10-week intervals, while hospital workers received two doses of ChAdOx1 vaccines at 12-week intervals. Serum IgG to a receptor-binding domain (RBD) of the S1 subunit of the spike protein of SARS-CoV-2 was measured 1 month after the first dose, 2 months and 4 months after the second dose. The median [interquartile range] anti-RBD IgG was 82.1[34.5, 176.6] AU/ml in HD patients and 197.1[124.0, 346.0] AU/ml in hospital workers (P < 0.001) after the first dose. The percentage of positive responses (IgG > 50 AU/ml) was 65.0% and 96.0% among the both group, respectively (P < 0.001). The anti-RBD IgG levels increased significantly by 2528.8 [1327.6, 5795.1] AU/ml with a 100.0% positive response rate in HD patients 2 months after the second dose, which was higher than those in hospital workers 981.4[581.5, 1891.4] AU/ml (P < 0.001). Moreover, anti-RBD IgG remains constantly high, and positive response remains 100% in HD patients 4 months after the second dose. This study suggests that heterologous vaccinations with ChAdOx1/BNT162b2 can be an alternative solution on HD patients for early and strong induction of humoral response.

Galactose-Deficient IgA1 as a Candidate Urinary Marker of IgA Nephropathy.

In patients with IgA nephropathy (IgAN), circulatory IgA1 and IgA1 in the mesangial deposits contain galactose-deficient IgA1 (Gd-IgA1). Some of the Gd-IgA1 from the glomerular deposits is excreted in the urine and thus urinary Gd-IgA1 may represent a disease-specific marker. We recruited 338 Japanese biopsy-proven IgAN patients and 120 patients with other renal diseases (disease controls). Urine samples collected at the time of renal biopsy were used to measure Gd-IgA1 levels using a specific monoclonal antibody (KM55 mAb). Urinary Gd-IgA1 levels were significantly higher in patients with IgAN than in disease controls. Moreover, urinary Gd-IgA1 was significantly correlated with the severity of the histopathological parameters in IgAN patients. Next, we validated the use of urinary Gd-IgA1 levels in the other Asian cohorts. In the Korean cohort, urinary Gd-IgA1 levels were also higher in patients with IgAN than in disease controls. Even in Japanese patients with IgAN and trace proteinuria (less than 0.3 g/gCr), urinary Gd-IgA1 was detected. Thus, urinary Gd-IgA1 may be an early disease-specific biomarker useful for determining the disease activity of IgAN.

Acute Kidney Injury: Biomarker-Guided Diagnosis and Management.

Acute kidney injury (AKI) is a common clinical syndrome that is characterized by abnormal renal function and structure. The Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference in 2019 reviewed the stages of AKI and the definitions of AKI-related terminologies, and discussed the advances in the last decade. Along with serum creatinine level and urine output, more accurate novel biomarkers for predicting AKI are being applied for the early detection of renal dysfunction. A literature search was conducted in PubMed, Scopus, Medline, and ClinicalTrials.gov using the terms AKI and biomarker, combined with diagnosis, management, or prognosis. Because of the large volume of data (160 articles) published between 2005 and 2022, representative literature was chosen. A number of studies have demonstrated that new biomarkers are more sensitive in detecting AKI in certain populations than serum creatinine and urine output according to the recommendations from the Acute Disease Quality Initiative Consensus Conference. To be specific, there is a persistently unresolved need for earlier detection of patients with AKI before AKI progresses to a need for renal replacement therapy. Biomarker-guided management may help to identify a high-risk group of patients in progression to severe AKI, and decide the initiation time to renal replacement therapy and optimal follow-up period. However, limitations such as biased data to certain studied populations and absence of cutoff values need to be solved for worldwide clinical use of biomarkers in the future. Here, we provide a comprehensive review of biomarker-based AKI diagnosis and management and highlight recent developments.

Efficacy of Nitric Oxide-Releasing Nanofibers in Reducing Renal Ischemia-Reperfusion Injury in a Rat Model.

BACKGROUND This study aimed to analyze the preventive effect of nitric oxide (NO)-releasing nanofibers against ischemia-reperfusion injury (IRI) and to determine the mechanism of action as a novel NO delivery system in a rat model. MATERIAL AND METHODS Eight-week-old male Sprague-Dawley rats, weighing 250 to 280 g, were divided into 3 groups: sham, untreated (n=5); control, renal ischemia injury for 55 min (n=4); and NO24, renal ischemia injury for 55 min with kidney wrapping of NO-releasing nanofiber for 24 h (n=6). mRNA expression was measured by real-time polymerase chain reaction (PCR), whereas protein expression was assessed by immunohistochemistry and western blot analysis. RESULTS Serum creatinine levels in the sham, control, and NO24 groups were 0.48±0.08, 4.66±0.33, and 2.60±1.00 mg/dL, respectively (P=0.002). Anti-apoptotic Bcl-2 protein expression differed significantly between the control and the NO24 groups (Bcl-2/ß-actin; control, 0.50±0.12; NO24, 1.56±0.56; P=0.024). mRNA expression level of the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) was significantly higher in the control group (23.24±11.32, P=0.016) than in the sham group (1.00±1.21), and mRNA expression of TNF-alpha in the NO24 group (1.28±1.16, P=0.010) was significantly lower than in the control group. Histological analysis revealed decreased atrophy and necrosis in the NO24 group compared to those in the control group. CONCLUSIONS This study demonstrated that kidney wrapping of NO-releasing nanofibers had a protective effect against kidney IRI through anti-apoptotic and anti-inflammatory mechanisms.