Circulating osteoprotegerin levels and cardiovascular outcomes in patients with pre-dialysis chronic kidney disease: results from the KNOW-CKD study.

While the relationship between circulating osteoprotegerin (OPG) and cardiovascular events is well-established in the general population, its association with cardiovascular risks in chronic kidney disease (CKD) patients remains less robust. This study hypothesized that elevated circulating OPG levels might be associated with an increased risk of major adverse cardiac events (MACE) in CKD patients, a total of 2,109 patients with CKD stages 1 through pre-dialysis 5 from the KNOW-CKD cohort were categorized into quartiles based on serum OPG levels. The primary outcome of the study was 3-point MACE, defined as a composite of nonfatal myocardial infarction, nonfatal stroke, or cardiac death. The median follow-up duration was 7.9 years. The cumulative incidence of 3-point MACE significantly varied across serum OPG levels in Kaplan-Meier curve analysis (P < 0.001, log-rank test), with the highest incidence observed in the 4th quartile. Cox regression analysis indicated that, relative to the 1st quartile, the risk of 3-point MACE was significantly higher in the 3rd (adjusted hazard ratio 2.901, 95% confidence interval 1.009 to 8.341) and the 4th quartiles (adjusted hazard ratio 4.347, 95% confidence interval 1.410 to 13.395). In conclusion, elevated circulating OPG levels are associated with adverse cardiovascular outcomes in pre-dialysis CKD patients.

The Impact of Obesity on Kidney Disease: Observational Cohort Study Analyzing 14,492 Kidney Biopsy Cases.

BACKGROUND: The obesity epidemic is associated with the emergence of new kidney diseases including obesity-related glomerulopathy (ORG) and metabolic syndrome-associated disorders. However, the effects of obesity on prevalence and outcome of biopsy-proven kidney disease are not well known. METHODS: We analyzed 14,492 kidney biopsies in 18 hospitals from 1979 to 2018 in Korea. Obesity was defined as a body mass index value of ≥ 30 kg/m². RESULTS: The most common disease was IgA nephropathy (IgAN) in both obese and non-obese participants (33.7% vs. 38.9%). Obesity was associated with a higher risk of focal segmental glomerulosclerosis (FSGS) and hypertensive nephropathy (HT-N) (odds ratio [OR], 1.72, 95% confidence interval [CI], 1.37-2.17; OR, 1.96, 95% CI, 1.21-3.19) and a lower risk of IgAN (OR, 0.74, 95% CI, 0.62-0.88). During the median follow up of 93.1 ± 88.7 months, obesity increased the risk of end-stage kidney disease (ESKD) in patients with IgAN (relative risk [RR], 1.49, 95% CI, 1.01-2.20) and lupus nephritis (LN) (RR, 3.43, 95% CI, 1.36-8.67). Of 947 obese individuals, ORG was detected in 298 (31.5%), and 230 participants had other kidney diseases, most commonly, IgAN (40.9%) followed by diabetic nephropathy (15.2%). Participants with ORG, when combined with other renal diseases, showed higher risks for developing ESKD compared to those with ORG alone (RR, 2.48, 95% CI, 1.09-5.64). CONCLUSION: Obesity is associated with an increased risk of FSGS and HT-N, and also increase the ESKD risk in IgAN and LN patients. ORG in obese participants may have favorable renal outcomes if it occurs alone without any other renal disease.

Insulin resistance is associated with incident chronic kidney disease in population with normal renal function.

Background: Insulin resistance is prevalent in chronic kidney disease and may accelerate the progression of chronic kidney disease. This study aimed to investigate whether insulin resistance is associated with the development of incident chronic kidney disease in a population with normal renal function. Methods: A total of 3,331 participants from a community-based cohort with normal renal function were prospectively analyzed. We determined the relationship of insulin resistance indices with the incident chronic kidney disease using the Cox proportional hazard model and Kaplan-Meier survival analysis. Results: During a mean follow-up of 11.03 ± 4.22 years, incident chronic kidney disease occurred in 414 participants (12.4%). The high homeostasis model assessment-insulin resistance level group had an increased risk of incident chronic kidney disease (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.13-1.74; p = 0.002) compared to the normal group after adjustment for age, sex, history of hypertension, body mass index, total cholesterol, alcohol drinking status, smoking status, and baseline estimated glomerular filtration rate. The risk of incident chronic kidney disease also increased with the lower quantitative insulin sensitivity check index level (HR, 0.62; 95% CI, 0.41-0.92; p = 0.02) and higher leptin-adiponectin ratio level (HR, 1.23; 95% CI, 1.06-1.42; p = 0.006). Conclusion: Higher insulin resistance indices are associated with the incidence of chronic kidney disease. Our data suggest that increased insulin resistance may be involved in the development of incident chronic kidney disease in a population with normal renal function.

Baseline characteristics of the Korean genetic cohort of inherited cystic kidney disease.

BACKGROUND: Identifying genetic mutations in individuals with inherited cystic kidney disease is necessary for precise treatment. We aimed to elucidate the genetic characteristics of cystic kidney disease in the Korean population. METHODS: We conducted a 3-year prospective, multicenter cohort study at eight hospitals from May 2019 to May 2022. Patients with more than three renal cysts were enrolled and classified into two categories, typical autosomal dominant polycystic kidney disease (ADPKD) and atypical PKD. We identified the clinical characteristics and performed a genetic analysis using a targeted gene panel. RESULTS: A total of 725 adult patients were included in the study, of which 560 (77.2%) were diagnosed with typical ADPKD and 165 (22.8%) had atypical PKD. Among the typical ADPKD cases, the Mayo imaging classification was as follows: 1A (55, 9.9%), 1B (149, 26.6%), 1C (198, 35.8%), 1D (90, 16.3%), and 1E (61, 11.0%). The atypical PKD cases were classified as bilateral cystic with bilateral atrophic (31, 37.3%), lopsided (27, 32.5%), unilateral (nine, 10.8%), segmental (eight, 9.6%), bilateral cystic with unilateral atrophic (seven, 8.4%), and asymmetric (one, 1.2%). Pathogenic variants were found in 64.3% of the patients using the ciliopathy-related targeted gene panel. The typical ADPKD group demonstrated a higher discovery rate (62.3%) than the atypical PKD group (41.8%). CONCLUSION: We present a nationwide genetic cohort's baseline clinical and genetic characteristics for Korean cystic kidney disease.

Factors Associated With the Development and Severity of Polycystic Liver in Patients With Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: Factors related to the development and severity of polycystic liver disease (PLD) have not been well established. We aimed to evaluate the genetic and epidemiologic risk factors of PLD in patients with autosomal dominant polycystic kidney disease (ADPKD). METHODS: Adult patients with inherited cystic kidney disease were enrolled from May 2019 to May 2021. Demographic, clinical, and laboratory data were collected at the initial study visit. The severity of PLD was graded based on the height-adjusted total liver volume: < 1,000 mL/m (Gr1), 1,000-1,800 mL/m (Gr2), and > 1,800 mL/m (Gr3). Targeted exome sequencing was done by a gene panel including 89 ciliopathy-related genes. We searched out the relative factors to the presence and the severity of PLD using logistic regression analysis. RESULTS: Of 602 patients with typical ADPKD, 461 (76.6%) patients had PLD. The patients with PLD showed female predominance and a higher frequency of other ADPKD-related complications. The genetic variants with truncating mutation of PKD1 (PKD1-protein-truncating [PT]) or PKD2 commonly affected the development and severity of PLD. An older age, female sex, and higher kidney volume with Mayo classification 1C-1E was significantly associated with the development of PLD, but not with the severity of PLD. On the other hand, higher body mass index, lower hemoglobin, and higher alkaline phosphatase (ALP) were the significant risk factors of severe PLD (≥ Gr2). CONCLUSION: Hepatic involvement in ADPKD could be related to kidney manifestations and genetic variants including PKD1-PT or PKD2. Monitoring hemoglobin and ALP and evaluating the genetic variants might help predict severe PLD. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0005580.

Prognostic role of the neutrophil-to-lymphocyte ratio in patients with chronic kidney disease.

BACKGROUND/AIMS: The neutrophil-to-lymphocyte ratio (NLR) has a prognostic value in cardiovascular disease, infection, inflammatory disease, and several malignancies. Therefore, the NLR has a possible predictive value in patients with chronic kidney disease (CKD), but this predictive value has not been validated. Here, we aimed to investigate the possibility of NLR as a predictor of CKD progression. METHODS: This retrospective observational study included 141 patients with non-dialysis CKD. The participants were divided into terciles (T1, T2, and T3) according to NLR. The primary outcome was defined as a composite kidney event, which included a decline in the estimated glomerular filtration rate (eGFR) of at least 50% or initiation of renal replacement therapy during the follow-up period. RESULTS: The mean follow-up duration was 5.45 ± 2.11 years. The mean NLRs were 1.35 ± 0.05 in T1 (n = 47), 2.16 ± 0.04 in T2 (n = 47), and 4.29 ± 0.73 in T3 (n = 47). The group with the highest NLR (T3) had higher baseline CKD and serum creatinine and lower eGFR levels than the group with the lowest NLR (T1). The cumulative incidence rate of composite kidney events was significantly higher in T3 compared with T1 (p < 0.001, log-rank test). Cox regression analysis revealed that high NLR was associated with the risk of composite kidney events (adjusted hazard ratio, 3.33; 95% confidence interval, 1.43-7.76). CONCLUSION: A higher NLR reflects the more advanced stage of CKD and suggests a role for NLR as a biomarker for predicting CKD progression.

Underweight status and development of end-stage kidney disease: A nationwide population-based study.

BACKGROUND: Underweight status increases the risk of cardiovascular disease and mortality in the general population. However, whether underweight status is associated with an increased risk of developing end-stage kidney disease is unknown. METHODS: A total of 9 845 420 participants aged ≥20 years who underwent health checkups were identified from the Korean National Health Insurance Service database and analysed. Individuals with underweight (body mass index [BMI] < 18.5 kg/m2 ) and obesity (BMI ≥ 25 kg/m2 ) were categorized according to the World Health Organization recommendations for Asian populations. RESULTS: During a mean follow-up period of 9.2 ± 1.1 years, 26 406 participants were diagnosed with end-stage kidney disease. After fully adjusting for other potential predictors, the moderate to severe underweight group (<17 kg/m2 ) had a significantly higher risk of end-stage kidney disease than that of the reference (normal) weight group (adjusted hazard ratio, 1.563; 95% confidence interval, 1.337-1.828), and competing risk analysis to address the competing risk of death also showed the similar results (adjusted hazard ratio, 1.228; 95% confidence interval, 1.042-1.448). Compared with that of the reference BMI group (24-25 kg/m2 ), the adjusted hazard ratios for end-stage kidney disease increased as the BMI decreased by 1 kg/m2 . In the sensitivity analysis, sustained underweight status or progression to underweight status over two repeated health checkups, when compared with normal weight status, had a higher hazard ratio for end-stage kidney disease. CONCLUSIONS: Underweight status is associated with an increased risk of end-stage kidney disease, and this association gradually strengthens as BMI decreases.

Model-Based Needle Identification Using Image Analysis and Needle Library Matching for Ultrasound-Guided Kidney Biopsy: A Feasibility Study.

OBJECTIVE: The aim of the work described here was to determine the feasibility of using a novel biopsy needle detection technique that achieves high sensitivity and specificity in a trade-off of resolution, detectability and depth of imaging. METHODS: The proposed needle detection method consists of a model-based image analysis, temporal needle projection and needle library matching: (i) Image analysis was formulated under the signal decomposition framework; (ii) temporal projection converted the time-resolved needle dynamics into a single image of the desired needle; and (iii) the enhanced needle structure was spatially refined by matching a long, straight linear object in the needle library. The efficacy was examined with respect to different needle visibility. RESULTS: Our method effectively eliminated confounding effects of the background tissue artifacts more robustly than conventional methods, thus improving needle visibility even with the low contrast between the needle and tissue. The improvement in needle structure further resulted in an improvement in estimation performance for the trajectory angle and tip position. CONCLUSION: Our three-step needle detection method can reliably detect needle position without the need for external devices, increasing the needle conspicuity and reducing motion sensitivity.

Nutritional Status is Associated With Preserved Kidney Function in Patients With Autosomal Dominant Polycystic Kidney Disease.

OBJECTIVE: Malnutrition is a common complication in autosomal dominant polycystic kidney disease (ADPKD). We examined whether nutritional status is associated with the preservation of kidney function, using a cohort of typical ADPKD. METHODS: We enrolled ambulatory ADPKD patients in 9 tertiary medical centers in Korea from May 2019 to December 2021. We excluded patients who were aged less than 18 years, who had known end-stage kidney disease at the time of enrollment, who had a diagnosis of atypical ADPKD, and who were Tolvaptan users. The primary outcome was an estimated glomerular filtration rate (eGFR) decline >3 mL/min/1.73 m2, based on nutritional status assessed by subjective global assessment (SGA). We also evaluated an eGFR decline >1 mL/min/1.73 m2, an increase in urine protein-creatinine ratio (UPCR) > 0, and an increase in UPCR >0.3 as secondary outcomes, based on SGA after the 1-year follow-up. A logistic regression (LR) model was used to calculate the odds ratio (OR) for the primary outcome. Because there were differences in several baseline variables, such as Mayo classification, serum hemoglobin, serum creatinine, and UPCR between SGA groups, we matched propensity scores. RESULTS: In total, 805 patients were prospectively enrolled. Among them, 236 patients who had 1-year follow-up data and typical imaging findings were analyzed to evaluate the effect of nutritional status on kidney function. SGA was used to assess the nutritional status. The mean age was 45.0 ± 13.3 years, and 49.6% of the patients were female. The mean eGFR was 81.9 mL/min/1.73 m2. Among the 236 patients, 91 (38.6%) experienced a 1-year eGFR decline >3 mL/min/1.73 m2. When a multivariable LR was applied, SGA 3-6 was identified as a significant factor related to a 1-year eGFR decline >3 mL/min/1.73 m2 (adjusted OR = 1.22 [1.04-1.43]; P = .017). Despite matching propensity scores, the 1-year eGFR decline >3 mL/min/1.73 m2 was still higher in the SGA 3-6 group regardless of proteinuria. CONCLUSION: Good nutritional status is associated with better-preserved kidney function in non-obese typical ADPKD patients who do not take Tolvaptan.

Farnesoid X receptor protects against cisplatin-induced acute kidney injury by regulating the transcription of ferroptosis-related genes.

The side effects of cisplatin, a widely used chemotherapeutic agent, include nephrotoxicity. Previous studies have reported that cisplatin induces ferroptosis and lipid peroxide accumulation. Ferroptosis, a type of regulated cell death, is characterized by iron-dependent lipid peroxidation. Although previous studies have examined the regulation of ferroptosis in acute kidney injury (AKI), the regulatory mechanism of ferroptosis has not been elucidated. Here, the ability of activated farnesoid X receptor (FXR) to attenuate cisplatin-induced AKI through the regulation of ferroptosis was examined. FXR deficiency exhibited more ferroptosis responses, such as increase in lipid peroxidation, iron content and heme oxygenase 1 protein, and a decrease in glutathione/glutathione disulfide ratio and glutathione peroxidase 4 levels in HK2 cells and mice. Increased blood urea nitrogen, serum creatinine, and ferroptotic responses in the cisplatin-induced AKI mouse model were mitigated upon treatment with the FXR agonist GW4064 but were exacerbated in FXR knockout mice. RNA sequencing analysis revealed that ferroptosis-associated genes were novel targets of FXR. FXR agonist upregulated the expression of lipid and glutathione metabolism-related genes and downregulated cell death-related genes. Additionally, chromatin immunoprecipitation assays, using mice renal tissues, revealed that agonist-activated FXR could bind to its known target genes (Slc51a, Slc51b, Osgin1, and Mafg) and ferroptosis-related genes (Aifm2, Ggt6, and Gsta4). Furthermore, activated FXR-dependent MAFG, a transcriptional repressor, could bind to Hmox1, Nqo1, and Tf in the renal tissues of FXR agonist-treated mice. These findings indicate that activated FXR regulates the transcription of ferroptosis-related genes and protects against cisplatin-induced AKI.

ß-Elemene Attenuates Renal Fibrosis in the Unilateral Ureteral Obstruction Model by Inhibition of STAT3 and Smad3 Signaling via Suppressing MyD88 Expression.

Renal fibrosis is a chronic pathological process that seriously endangers human health. However, the current therapeutic options for this disease are extremely limited. Previous studies have shown that signaling factors such as JAK2/STAT3, Smad3, and Myd88 play a regulatory role in renal fibrosis, and ß-elemene is a plant-derived sesquiterpenoid organic compound that has been shown to have anti-inflammatory, anti-cancer, and immunomodulatory effects. In the present study, the anti-fibrotic effect of ß-elemene was demonstrated by in vivo and in vitro experiments. It was shown that ß-elemene inhibited the synthesis of extracellular matrix-related proteins in unilateral ureteral obstruction mice, and TGF-ß stimulated rat interstitial fibroblast cells, including α-smooth muscle actin, vimentin, and connective tissue growth factor, etc. Further experiments showed that ß-elemene reduced the expression levels of the above-mentioned fibrosis-related proteins by blocking the phosphorylation of JAK2/STAT3, Smad3, and the expression or up-regulation of MyD88. Notably, knockdown of MyD88 attenuated the phosphorylation levels of STAT3 and Smad3 in TGF-ß stimulated NRK49F cell, which may be a novel molecular mechanism by which ß-elemene affects renal interstitial fibrosis. In conclusion, this study elucidated the anti-interstitial fibrosis effect of ß-elemene, which provides a new direction for future research and development of drugs related to chronic kidney disease.

Maslinic Acid Attenuates Ischemia/Reperfusion-Induced Acute Kidney Injury by Suppressing Inflammation and Apoptosis Through Inhibiting NF-κB and MAPK Signaling Pathway.

Inflammation and apoptosis are the major contributors to the mechanisms of acute kidney injury (AKI) due to renal ischemia-reperfusion injury (IRI). Maslinic acid (MA), a pentacyclic triterpene acid mostly found in dietary plants, the current study was to demonstrate the renoprotective effect of MA on IRI-induced AKI, and to investigate the role of inflammation and apoptosis-related signaling pathways as a molecular mechanism. C57BL/6J mice were subjected to IRI for 72 h, and MA was daily administered by intraperitoneal injection during this period. In parallel, rat renal proximal tubule cells (NRK52E) were prophylactically treated with MA and then exposed to hydrogen peroxide (H2O2). MA treatment significantly inhibited the mRNA expression of interleukin (IL-1ß), tumor necrosis factor-α (TGF-α), monocyte chemoattractant protein-1 (MCP-1), and intercellular adhesion molecule-1(ICAM-1). Also, MA reduced the expression of Bax/Bcl2 ratio and cleaved caspase-3. In NRK52 cells, MA inhibited the IκBα degradation, blocked NF-κB/p65 phosphorylation, and nuclear translocation. The phosphorylation of ERK, JNK, and p38 was attenuated by MA in IRI-induced kidney injury and H2O2-stimulated NRK52 cells. The expression levels of IL-1ß, MCP-1, and ICAM-1 were upregulated in H2O2-stimulated NRK52E cells, which was attenuated by NF-κB inhibitor. H2O2 treatment increased the Bax/Bcl2 ratio and cleaved caspase-3 in NRK52E cells, which was counteracted by MAPK inhibitors. Together, our data demonstrate that MA suppresses IR-induced AKI injury through NF-κB and MAPK signaling pathways and that MA is a promising agent in the treatment of kidney diseases.

Complete Atrioventricular Block After Kidney Transplantation in a Patient With Fabry Disease Receiving Enzyme Replacement Therapy: A Case Report.

Fabry disease (FD) is a rare X-linked lysosomal storage disorder that results from the deficient activity of the lysosomal enzyme α-galactosidase A (α-Gal A) enzyme. Kidney transplantation is an option for treating end-stage renal disease in patients with FD. However, only a few cases of kidney transplantation have been reported involving patients with FD and end-stage renal disease and cardiomyopathy after enzyme replacement therapy. A 53-year-old man who underwent peritoneal dialysis was referred to our department because his brother was diagnosed with FD. The diagnosis of FD was also confirmed in our patient on account of the reduced leukocyte α-Gal A enzyme activity and mutation in the α-galactosidase A gene (p.Arg301Gln). Though our patient had end-stage renal disease, he received enzyme replacement therapy with 1 mg/kg agalsidase-ß every 2 weeks (Fabrazyme; Genzyme Co, Mass, USA) owing to markedly diffuse cardiac hypertrophy. Six years later, he underwent successful deceased-donor kidney transplantation. The post-transplantation course was uneventful, 4 months after transplantation. However, though he showed T-cell-mediated rejection on kidney biopsy, lamellar lysosomal inclusions were not present in vascular endothelial cells. After several months, a permanent pacemaker was inserted owing to a complete atrioventricular block; the patient died of sepsis and candidemia 1 year later. Deceased-donor kidney transplantation was successfully performed in an FD patient with sustained enzyme replacement therapy. However, owing to high cardiac morbidity and infection risks even after enzyme replacement therapy, close monitoring of these risks is essential for increasing patient survival after kidney transplantation.

Retroperitoneal emphysema caused by a renal abscess: a case report.

We report a case of retroperitoneal emphysema caused by a renal abscess. A 45-year-old man with underlying type 2 diabetes mellitus visited the emergency department with right flank pain and a fever. On physical examination, right costovertebral tenderness in the ipsilateral flank was noted. Leukocytosis and high inflammatory marker levels were observed. Urinalysis showed pyuria and glucosuria. Urine culture was positive for Streptococcus agalactiae. A computed tomography scan of the abdomen showed a focal, low-attenuation lesion in the right kidney with a 3 cm, exophytic, high-attenuation lesion in the right kidney upper pole and gas-containing fluid collection within the retroperitoneal space. The diagnosis was retroperitoneal emphysema caused by a renal abscess. As the vital signs were stable and the patient refused puncture, we decided on a course of antibiotics alone with follow-up without percutaneous drainage or surgery. The patient improved without any complications. This is a rare case of a renal abscess penetrating the renal fascia and progressing to a posterior paranephric emphysema. The patient was treated with antibiotics alone and cured successfully. Early diagnosis and proper treatment are needed, and percutaneous drainage or urgent surgery would be beneficial for such cases depending on the patient's condition.

Risk of Kidney Failure in Patients With Cancer: A South Korean Population-Based Cohort Study.

RATIONALE & OBJECTIVE: Reduced kidney function is associated with an increased risk of cancer; however, it is unclear if cancer increases the risk of kidney failure with replacement therapy (KFRT). We assessed the risk of KFRT among patients with various types of cancer collectively and with specific types of cancer. STUDY DESIGN: Retrospective population-based cohort study. SETTING & PARTICIPANTS: A total of 2,473,095 participants with (n = 824,365) or without (n = 1,648,730) cancer registered in the Korean National Health Insurance Service database. PREDICTORS: Cancer and cancer subtypes defined using International Classification of Diseases, 10th Revision, Clinical Modification, codes. OUTCOMES: Primary outcome was KFRT defined as the initiation of hemodialysis or peritoneal dialysis or kidney transplantation. ANALYTICAL APPROACH: For each patient with cancer, 2 controls matched for age, sex, estimated glomerular filtration rate, diabetes, and hypertension were included. To address the competing risk of death, a competing risk survival analysis was conducted using the Fine and Gray method. RESULTS: Occurrence of KFRT was higher in patients with cancer than in controls without cancer (incidence rates of 1.07 vs 0.51 cases per 1,000 person-years). Competing risk analysis showed that cancer was significantly associated with an increased risk of KFRT after adjusting for other potential predictors (adjusted hazard ratio, 2.29 [95% CI, 2.20-2.39]). Multiple myeloma, leukemia, lymphoma, and kidney, ovarian, and liver cancer were most significantly associated with an increased KFRT risk, with multiple myeloma conferring the highest risk across age and sex groups. All subgroups of patients with cancer (based on age, sex, smoking, alcohol, exercise, obesity, and comorbid conditions) exhibited a higher risk of KFRT. LIMITATIONS: Causal association between cancer and kidney outcomes could not be confirmed. CONCLUSIONS: Patients with cancer, particularly those with multiple myeloma, exhibited an increased risk of KFRT after accounting for the competing risk of death.

Association between the progression of immunoglobulin A nephropathy and a controlled status of hypertension in the first year after diagnosis.

BACKGROUND/AIMS: Hypertension is considered a risk factor in immunoglobulin A nephropathy (IgAN). However, after IgAN diagnosis, the relationship between early blood pressure control and renal prognosis remains unclear. This study aimed to analyze the association between the prognosis of IgAN patients and a controlled status of hypertension within the first year of IgAN diagnosis. METHODS: We retrospectively analyzed 2,945 patients diagnosed with IgAN by renal biopsy. The patients were divided into 'normal,' 'new-onset,' 'well-controlled,' and 'poorly-controlled' groups using blood pressure data from two consecutive measurements performed within a year. The Kaplan-Meier survival analysis and Cox proportional-hazards regression model were used to survey the independent association between recovery from hypertension and the risk of IgAN progression. The primary endpoint was IgAN progression defined as the initiation of dialysis or kidney transplantation. RESULTS: Before IgAN diagnosis, 1,239 patients (42.1%) had been diagnosed with hypertension. In the fully adjusted Cox proportional-hazards models, the risk of IgAN progression increased by approximately 1.7-fold for the prevalence of hypertension. In the subgroup analyses, the 'well-controlled' group showed a statistically significant risk of IgAN progression (hazard ratio [HR], 3.19; 95% confidence interval [CI], 1.103 to 9.245; p = 0.032). Moreover, the 'new-onset' and 'poorly-controlled' groups had an increased risk of IgAN progression compared to the 'normal' group (HR, 2.58; 95% CI, 1.016 to 6.545; p = 0.046 and HR, 3.85;95% CI, 1.541 to 9.603; p = 0.004, respectively). CONCLUSION: Although hypertension was well-controlled in the first year after IgAN diagnosis, it remained a risk factor for IgAN progression.

Vimentin Targeted Nano-gene Carrier for Treatment of Renal Diseases.

BACKGROUND: Chronic kidney disease (CKD) is a global health problem, and there is no permanent treatment for reversing kidney failure; thus, early diagnosis and effective treatment are required. Gene therapy has outstanding potential; however, the lack of safe gene delivery vectors, a reasonable transfection rate, and kidney targeting ability limit its application. Nanoparticles can offer innovative ways to diagnose and treat kidney diseases as they facilitate targetability and therapeutic efficacy. METHODS: Herein, we developed a proximal renal tubule-targeting gene delivery system based on alternative copolymer (PS) of sorbitol and polyethyleneimine (PEI), modified with vimentin-specific chitobionic acid (CA), producing PS-conjugated CA (PSC) for targeting toward vimentin-expressing cells in the kidneys. In vitro studies were used to determine cell viability, transfection efficiency, serum influence, and specific uptake in the human proximal renal tubular epithelial cell line (HK-2). Finally, the targeting efficiency of the prepared PSC gene carriers was checked in a murine model of Alport syndrome. RESULTS: Our results suggested that the prepared polyplex showed low cytotoxicity, enhanced transfection efficiency, specific uptake toward HK-2 cells, and excellent targeting efficiency toward the kidneys. CONCLUSION: Collectively, from these results it can be inferred that the PSC can be further evaluated as a potential gene carrier for the kidney-targeted delivery of therapeutic genes for treating diseases.

Hypertension as a risk factor for retinal vein occlusion in menopausal women: A nationwide Korean population-based study.

ABSTRACT: Retinal vein occlusion (RVO) is an important cause of blindness. Hypertension is a well-known risk factor for RVO. Although the prevalence of hypertension increases in women after menopause, the relationship between blood pressure and RVO in women before and after menopause has not been studied in detail.We retrospectively analyzed 2,619,206 patients from the Korean National Health Insurance System database. A Cox proportional hazard regression model was used to evaluate the independent association between blood pressure and the risk of RVO development and identify differences between premenopausal and postmenopausal women.The incidence of RVO was higher among postmenopausal women than in premenopausal women. In the model adjusted for socioeconomic and clinical variables, there was an association between blood pressure and RVO development in premenopausal and postmenopausal women; however, this was stronger than premenopausal women.Both systolic and diastolic blood pressure are associated with an increased risk of RVO, and their effects are more potent in premenopausal women than postmenopausal women. Thus, comprehensive management of hypertension in premenopausal women is essential to reduce the risk of RVO.