Higher sclerostin is associated with pulmonary hypertension in pre-dialysis end-stage kidney disease patients: a cross-sectional prospective observational cohort study.

BACKGROUND: Pulmonary hypertension (PH) is a complication of chronic kidney disease (CKD) that contributes to mortality. Sclerostin, a SOST gene product that reduces osteoblastic bone formation by inhibiting Wnt/ß-catenin signaling, is involved in arterial stiffness and CKD-bone mineral disease, but scanty evidence to PH. This study explored the relationship between sclerostin and PH in CKD 5, pre-dialysis end-stage kidney disease (ESKD) patients. METHODS: This cross-sectional prospective observational cohort study included 44 pre-dialysis ESKD patients between May 2011 and May 2015. Circulating sclerostin levels were measured using an enzyme-linked immunosorbent assay. PH was defined as an estimated pulmonary artery systolic pressure > 35 mmHg on echocardiography. RESULTS: Patients with higher sclerostin levels ≥ 218.18pmol/L had echocardiographic structural cardiac abnormalities, especially PH (P < 0.01). On multivariate logistic analysis, sclerostin over 218.19pmol/L was significantly associated with PH (odds ratio [OR], 41.14; 95% confidence interval [CI], 4.53-373.89, P < 0.01), but multivariate Cox regression analysis showed the systemic vascular calcification score over 1 point (Hazard ratio [HR] 11.49 95% CI 2.48-53.14, P = 0.002) and PH ([HR] 5.47, 95% CI 1.30-23.06, P = 0.02) were risk factors for all-cause mortality in pre-dialysis ESKD patients. CONCLUSIONS: Serum sclerostin and PH have a positive correlation in predialysis ESKD patients. The higher systemic vascular calcification score and PH have an association to increase all-cause mortality in pre-dialysis ESKD 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.

Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial.

BACKGROUND: Sparsentan, a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist, significantly reduced proteinuria versus irbesartan, an angiotensin II receptor blocker, at 36 weeks (primary endpoint) in patients with immunoglobulin A nephropathy in the phase 3 PROTECT trial's previously reported interim analysis. Here, we report kidney function and outcomes over 110 weeks from the double-blind final analysis. METHODS: PROTECT, a double-blind, randomised, active-controlled, phase 3 study, was done across 134 clinical practice sites in 18 countries throughout the Americas, Asia, and Europe. Patients aged 18 years or older with biopsy-proven primary IgA nephropathy and proteinuria of at least 1·0 g per day despite maximised renin-angiotensin system inhibition for at least 12 weeks were randomly assigned (1:1) to receive sparsentan (target dose 400 mg oral sparsentan once daily) or irbesartan (target dose 300 mg oral irbesartan once daily) based on a permuted-block randomisation method. The primary endpoint was proteinuria change between treatment groups at 36 weeks. Secondary endpoints included rate of change (slope) of the estimated glomerular filtration rate (eGFR), changes in proteinuria, a composite of kidney failure (confirmed 40% eGFR reduction, end-stage kidney disease, or all-cause mortality), and safety and tolerability up to 110 weeks from randomisation. Secondary efficacy outcomes were assessed in the full analysis set and safety was assessed in the safety set, both of which were defined as all patients who were randomly assigned and received at least one dose of randomly assigned study drug. This trial is registered with ClinicalTrials.gov, NCT03762850. FINDINGS: Between Dec 20, 2018, and May 26, 2021, 203 patients were randomly assigned to the sparsentan group and 203 to the irbesartan group. One patient from each group did not receive the study drug and was excluded from the efficacy and safety analyses (282 [70%] of 404 included patients were male and 272 [67%] were White) . Patients in the sparsentan group had a slower rate of eGFR decline than those in the irbesartan group. eGFR chronic 2-year slope (weeks 6-110) was -2·7 mL/min per 1·73 m2 per year versus -3·8 mL/min per 1·73 m2 per year (difference 1·1 mL/min per 1·73 m2 per year, 95% CI 0·1 to 2·1; p=0·037); total 2-year slope (day 1-week 110) was -2·9 mL/min per 1·73 m2 per year versus -3·9 mL/min per 1·73 m2 per year (difference 1·0 mL/min per 1·73 m2 per year, 95% CI -0·03 to 1·94; p=0·058). The significant reduction in proteinuria at 36 weeks with sparsentan was maintained throughout the study period; at 110 weeks, proteinuria, as determined by the change from baseline in urine protein-to-creatinine ratio, was 40% lower in the sparsentan group than in the irbesartan group (-42·8%, 95% CI -49·8 to -35·0, with sparsentan versus -4·4%, -15·8 to 8·7, with irbesartan; geometric least-squares mean ratio 0·60, 95% CI 0·50 to 0·72). The composite kidney failure endpoint was reached by 18 (9%) of 202 patients in the sparsentan group versus 26 (13%) of 202 patients in the irbesartan group (relative risk 0·7, 95% CI 0·4 to 1·2). Treatment-emergent adverse events were well balanced between sparsentan and irbesartan, with no new safety signals. INTERPRETATION: Over 110 weeks, treatment with sparsentan versus maximally titrated irbesartan in patients with IgA nephropathy resulted in significant reductions in proteinuria and preservation of kidney function. FUNDING: Travere Therapeutics.

Altered gut microbiome plays an important role in AKI to CKD transition in aged mice.

Introduction: This study investigated the role of renal-intestinal crosstalk in the transition from acute kidney injury (AKI) to chronic kidney disease (CKD) in elderly individuals. Methods: Using young and aged mice, we induced bilateral ischemia-reperfusion injury (IRI) and compared intestinal and kidney inflammation over 28 days. To determine the role of the microbiome in gut-kidney crosstalk, we analyzed the microbiome of fecal samples of the young vs. aged mice and examined the effects of probiotic supplementation. Results: In the post-IRI recovery phase, prolonged intestinal and renal inflammation along with dysbiosis were evident in aged vs. younger mice that was associated with severe renal dysfunction and fibrosis progression in aged mice. Probiotic supplementation with Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI alleviated intestinal inflammation but not intestinal leakage, characterized by decreased inflammatory cytokine levels and decreased infiltration of macrophages, neutrophils, and Th17 cells. This was associated with improved M1-dominant renal inflammation and ultimately improved renal function and fibrosis, suggesting that renal-intestinal crosstalk in aged mice contributes to the transition from AKI to CKD. Discussion: Our study findings suggest that exacerbation of chronic inflammation through the gut-kidney axis might be an important mechanism in the transition from AKI to CKD in the elderly.

Smoking amplifies the risk of albuminuria in individuals with high sodium intake: the Korea National Health and Nutrition Examination Survey (KNHANES) 2008-2011 and 2014-2018.

Background: Smoking and sodium intake (SI) have been evaluated as risk factors for kidney disease; however, the data are inconsistent. We assessed the association between SI and cotinine-verified smoking status and the risk of albuminuria. Methods: An observational study using the Korea National Health and Nutrition Examination Survey (2008-2011 and 2014-2018) was performed. We included 37,410 adults with an estimated glomerular filtration rate of ≥60 mL/min/1.73 m2 . The smoking status was assumed based on the urine cotinine/creatinine ratio (Ucot/Ucrea). SI was estimated from spot urine sodium using the Kawasaki formula. Results: Ucot/Ucrea levels were significantly higher in current smokers (920.22 ± 9.00 ng/mg) than in ex-smokers and nonsmokers (48.31 ± 2.47 and 23.84 ± 1.30 ng/mg) (p < 0.001). Ucot/Ucrea levels were significantly higher in second-hand smokers than in participants without a history of smoking (p < 0.001). Ucot/ Ucrea levels were positively associated with SI (p for trend < 0.001). Smoking status was not associated with albuminuria. SI had a linear relationship with albuminuria (p < 0.001). In groups with the highest Ucot/Ucrea levels, the highest SI quartile indicated a significantly higher risk of albuminuria than that in the lowest quartile (risk ratio, 2.22; 95% confidence interval, 1.26-3.92; p = 0.006). The risk of albuminuria was not significant in groups with the lowest and middle tertile adjusted for multiple risk factors. Conclusion: Smokers consume higher dietary sodium and dietary SI was positively related to the risk of albuminuria. Smoking is not associated with albuminuria as a single factor. The risk of albuminuria is the higher in participants with smoking and high SI.

Mechanisms of Piperacillin/Tazobactam Nephrotoxicity: Piperacillin/Tazobactam-Induced Direct Tubular Damage in Mice.

Piperacillin/tazobactam (PT) is one of the most commonly prescribed antibiotics for critically ill patients in intensive care. PT has been reported to cause direct nephrotoxicity; however, the underlying mechanisms remain unknown. We investigated the mechanisms underlying PT nephrotoxicity using a mouse model. The kidneys and sera were collected 24 h after PT injection. Serum blood urea nitrogen (BUN), creatinine, neutrophil gelatinase-associated lipocalin (NGAL), and renal pathologies, including inflammation, oxidative stress, mitochondrial damage, and apoptosis, were examined. Serum BUN, creatinine, and NGAL levels significantly increased in PT-treated mice. We observed increased IGFBP7, KIM-1, and NGAL expression in kidney tubules. Markers of oxidative stress, including 8-OHdG and superoxide dismutase, also showed a significant increase, accompanied by mitochondrial damage and apoptosis. The decrease in the acyl-coA oxidase 2 and Bcl2/Bax ratio also supports that PT induces mitochondrial injury. An in vitro study using HK-2 cells also demonstrated mitochondrial membrane potential loss, indicating that PT induces mitochondrial damage. PT appears to exert direct nephrotoxicity, which is associated with oxidative stress and mitochondrial damage in the kidney tubular cells. Given that PT alone or in combination with vancomycin is the most commonly prescribed antibiotic in patients at high risk of acute kidney injury, caution should be exercised.

Role of the Circadian Clock and Effect of Time-Restricted Feeding in Adenine-Induced Chronic Kidney Disease.

Most physiological functions exhibit circadian rhythmicity that is partly regulated by the molecular circadian clock. Herein, we investigated the relationship between the circadian clock and chronic kidney disease (CKD). The role of the clock gene in adenine-induced CKD and the mechanisms of interaction were investigated in mice in which Bmal1, the master regulator of the clock gene, was knocked out, and Bmal1 knockout (KO) tubule cells. We also determined whether the renoprotective effect of time-restricted feeding (TRF), a dietary strategy to enhance circadian rhythm, is clock gene-dependent. The mice with CKD showed altered expression of the core clock genes with a loss of diurnal variations in renal functions and key tubular transporter gene expression. Bmal1 KO mice developed more severe fibrosis, and transcriptome profiling followed by gene ontology analysis suggested that genes associated with the cell cycle, inflammation, and fatty acid oxidation pathways were significantly affected in the mutant mice. Tubule-specific deletion of BMAL1 in HK-2 cells by CRISPR/Cas9 led to upregulation of p21 and tumor necrosis α and exacerbated epithelial-mesenchymal transition-related gene expression upon transforming growth factor ß stimulation. Finally, TRF in the mice with CKD partially restored the disrupted oscillation of the kidney clock genes, accompanied by improved cell cycle arrest and inflammation, leading to decreased fibrosis. However, the renoprotective effect of TRF was abolished in Bmal1 KO mice, suggesting that TRF is partially dependent on the clock gene. Our data demonstrate that the molecular clock system plays an important role in CKD via cell cycle regulation and inflammation. Understanding the role of the circadian clock in kidney diseases can be a new research field for developing novel therapeutic targets.

Korean Society of Nephrology 2022 Recommendations on Controversial Issues in Diagnosis and Management of Hyponatremia.

The Korean Society for Electrolyte and Blood Pressure Research, in collaboration with the Korean Society of Nephrology, has published a clinical practice guideline (CPG) document for hyponatremia treatment. The document is based on an extensive evidence-based review of the diagnosis, evaluation, and treatment of hyponatremia with the multidisciplinary participation of representative experts in hyponatremia with methodologist support for guideline development. This CPG consists of 12 recommendations (two for diagnosis, eight for treatment, and two for special situations) based on eight detailed topics and nine key questions. Each recommendation begins with statements graded by the strength of the recommendations and the quality of the evidence. Each statement is followed by rationale supporting the recommendations. The committee issued conditional recommendations in favor of rapid intermittent bolus administration of hypertonic saline in severe hyponatremia, the use of vasopressin receptor antagonists in heart failure with hypervolemic hyponatremia, and syndrome of inappropriate antidiuresis with moderate to severe hyponatremia, the individualization of desmopressin use, and strong recommendation on the administration of isotonic fluids as maintenance fluid therapy in hospitalized pediatric patients. We hope that this CPG will provide useful recommendations in practice, with the aim of providing clinical support for shared decision-making to improve patient outcomes.

Evaluating the Image Quality of Neck Structures Scanned on Chest CT with Low-Concentration-Iodine Contrast Media.

BACKGROUND: The purpose of this study was to investigate and compare the image quality of low-concentration-iodine (240 mgI/mL) contrast media (CM) and high-concentration-iodine (320 mgI/mL) CM according to the radiation dose. METHODS: A total of 366 CT examinations were examined. Based on an assessment of quantitative and qualitative parameters by two radiologists, the quality was compared between Group A (low-concentration-iodine CM) and Group B (high-concentration-iodine CM) images of thyroid gland, sternocleidomastoid muscle (SCM), internal jugular vein (IJV), and common carotid artery (CCA). Another subgroup analysis compared Group a, (using ≤90 kVp in Group A), and Group b, (using ≥100 kVp in Group B) for finding the difference in image quality when the tube voltage is lowered. RESULTS: Image quality did not differ between Groups A and B or between Groups a and b. The signal-to-noise ratio and contrast-to-noise ratio were significantly higher for Group B than Group A for the thyroid gland, IJV, and CCA. No statistical differences were found in the comparison of all structures between Groups a and b. CONCLUSION: There was no significant difference in image quality based on CM concentration with variable radiation doses. Therefore, if an appropriate CT protocol is applied, clinically feasible neck CT images can be obtained even using low-concentration-iodine CM.

[Korean Clinical Practice Guidelines for Adverse Reactions to Intravenous Iodinate and MRI-Gadolinium Contrast Agents: Revised Clinical Consensus and Recommendations (3rd Edition, 2022)]. / 주사용 요오드화 ì¡°ì˜ì œ 및 MRI용 가돌리늄 ì¡°ì˜ì œ ìœ í•´ë°˜ì‘ì— 대한 한국 임상진료지침: ê°œì •ëœ ìž„ìƒì  합의 및 ê¶Œê³ ì•ˆ(2022ë „ ì œ3판).

The Korean Society of Radiology and Medical Guidelines Committee amended the existing 2016 guidelines to publish the "Korean Clinical Practice Guidelines for Adverse Reactions to Iodide Contrast for Injection and Gadolinium Contrast for MRI: The Revised Clinical Consensus and Recommendations (2022 Third Edition)." Expert members recommended and approved by the Korean Society of Radiology, the Korean Academy of Asthma, Allergy and Clinical Immunology, and the Korean Nephrology Society participated together. According to the expert consensus or systematic literature review, the description of the autoinjector and connection line for the infection control while using contrast medium, the acute adverse reaction, and renal toxicity to iodized contrast medium were modified and added. We would like to introduce the revised contents.

Korean Society of Nephrology 2022 recommendations on controversial issues in diagnosis and management of hyponatremia.

The Korean Society for Electrolyte and Blood Pressure Research, in collaboration with the Korean Society of Nephrology, has published a clinical practice guideline (CPG) document for hyponatremia treatment. The document is based on an extensive evidence-based review of the diagnosis, evaluation, and treatment of hyponatremia with the multidisciplinary participation of representative experts in hyponatremia with methodologist support for guideline development. This CPG consists of 12 recommendations (two for diagnosis, eight for treatment, and two for special situations) based on eight detailed topics and nine key questions. Each recommendation begins with statements graded by the strength of the recommendations and the quality of the evidence. Each statement is followed by rationale supporting the recommendations. The committee issued conditional recommendations in favor of rapid intermittent bolus administration of hypertonic saline in severe hyponatremia, the use of vasopressin receptor antagonists in heart failure with hypervolemic hyponatremia, and syndrome of inappropriate antidiuresis with moderate to severe hyponatremia, the individualization of desmopressin use, and strong recommendation on the administration of isotonic fluids as maintenance fluid therapy in hospitalized pediatric patients. We hope that this CPG will provide useful recommendations in practice, with the aim of providing clinical support for shared decision-making to improve patient outcomes.

Prognostic value of chronicity grading on renal outcomes in patients with IgA nephropathy.

Many studies have shown that chronic changes are strong predictors of renal outcomes in various kidney diseases, including IgA nephropathy. The Mayo Clinic/Renal Pathology Society suggested a glomerulonephritis reporting system with a proposal for standardized grading of chronic changes. The purpose of this study was to predict renal outcomes in patients with IgA nephropathy using chronicity grading in comparison to the Oxford classification which did not include global sclerosis. A total of 4,151 patients with IgA nephropathy were enrolled from the Korean GlomeruloNephritis Study Group registry. Chronicity grading was categorized into minimal, mild, moderate, and severe according to the extent of chronic changes. The Oxford T and S scores were considered as chronic lesions. Three prediction models were constructed: the Oxford classification model (Oxford S plus T), chronicity grading model A (chronicity grading), and chronicity grading model B (chronicity grading plus Oxford S). Using these three prediction models, the primary renal outcome (end-stage renal disease) was evaluated using Cox regression analysis and prediction performance. During the median follow-up of 6.1 (2.7-9.9) years, 304 (7.3%) patients progressed to end-stage renal disease with a cumulative incidence rate of 1.02 events per 100 person-years. In a fully adjusted multivariable model, chronicity grading was independently associated with the primary renal outcome in both models A and B. Compared to the Oxford model, both models A and B showed improvements in model fit, but not in discrimination (ΔC 0.001; 95% CI, -0.010 to 0.013 and ΔC 0.002; 95% CI, -0.005 to 0.008, respectively). Model B demonstrated improvements in integrated discrimination improvement (0.01; 95% CI, 0-0.03) and continuous net reclassification improvement (0.49; 95% CI, 0.02-0.72). The severity of chronicity grading is closely related to adverse renal outcomes in patients with IgA nephropathy, and chronicity grading could provide additional information in clinical practice alongside the Oxford classification.

Accelerated 3D T2-weighted images using compressed sensing for pediatric brain imaging.

PURPOSE: The purpose of this study was to compare the image quality of the 3D T2-weighted images accelerated using conventional method (CAI-SPACE) with the images accelerated using compressed sensing (CS-SPACE) in pediatric brain imaging. METHODS: A total of 116 brain MRI (53 with CAI-SPACE and 63 with CS-SPACE) were obtained from children 16 years old or younger. Quantitative image quality was evaluated using the apparent signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). The sequences were qualitatively evaluated for overall image quality, general artifact, cerebrospinal fluid (CSF)-related artifact, and grey-white matter differentiation. The two sequences were compared for the total and two age groups (< 24 months vs. ≥ 24 months). RESULTS: Compressed sensing application in 3D T2-weighted imaging resulted in 8.5% reduction in scanning time. Quantitative image quality analysis showed higher apparent SNR (median [Interquartile range]; 29 [25] vs. 23 [14], P = 0.005) and CNR (0.231 [0.121] vs. 0.165 [0.120], P = 0.027) with CS-SPACE compared to CAI-SPACE. Qualitative image quality analysis showed better image quality with CS-SPACE for general (P = 0.024) and CSF-related artifact (P < 0.001). CSF-related artifacts reduction was prominent in the older age group (≥ 24 months). Overall image quality (P = 0.162) and grey-white matter differentiation (P = 0.397) were comparable between CAI-SPACE and CS-SPACE. CONCLUSION: Compressed sensing application in 3D T2-weighted images modestly reduced acquisition time and lowered CSF-related artifact compared to conventional images of the pediatric brain.

Korean Society of Nephrology 2022 Recommendations on controversial issues in diagnosis and management of hyponatremia.

The Korean Society for Electrolyte and Blood Pressure Research, in collaboration with the Korean Society of Nephrology, has published a clinical practice guideline (CPG) document for hyponatremia treatment. The document is based on an extensive evidence-based review of the diagnosis, evaluation, and treatment of hyponatremia with the multidisciplinary participation of representative experts in hyponatremia with methodologist support for guideline development. This CPG consists of 12 recommendations (two for diagnosis, eight for treatment, and two for special situations) based on eight detailed topics and nine key questions. Each recommendation begins with statements graded by the strength of the recommendations and the quality of the evidence. Each statement is followed by rationale supporting the recommendations. The committee issued conditional recommendations in favor of rapid intermittent bolus administration of hypertonic saline in severe hyponatremia, the use of vasopressin receptor antagonists in heart failure with hypervolemic hyponatremia, and syndrome of inappropriate antidiuresis with moderate to severe hyponatremia, the individualization of desmopressin use, and strong recommendation on the administration of isotonic fluids as maintenance fluid therapy in hospitalized pediatric patients. We hope that this CPG will provide useful recommendations in practice, with the aim of providing clinical support for shared decision-making to improve patient outcomes.

Cognitive Sequelae and Hippocampal Dysfunction in Chronic Kidney Disease following 5/6 Nephrectomy.

Neurological disorders are prevalent in patients with chronic kidney disease (CKD). Vascular factors and uremic toxins are involved with cognitive impairment in CKD. In addition, vascular dementia-induced alterations in the structure and function of the hippocampus can lead to deficits in hippocampal synaptic plasticity and cognitive function. However, regardless of this clinical evidence, the pathophysiology of cognitive impairment in patients with CKD is not fully understood. We used male Sprague Dawley rats and performed 5/6 nephrectomy to observe the changes in behavior, field excitatory postsynaptic potential, and immunostaining of the hippocampus following CKD progression. We measured the hippocampus volume on magnetic resonance imaging scans in the controls (n = 34) and end-stage renal disease (ESRD) hemodialysis patients (n = 42). In four cognition-related behavior assays, including novel object recognition, Y-maze, Barnes maze, and classical contextual fear conditioning, we identified deficits in spatial working memory, learning and memory, and contextual memory, as well as the ability to distinguish familiar and new objects, in the rats with CKD. Immunohistochemical staining of Na+/H+ exchanger1 was increased in the hippocampus of the CKD rat models. We performed double immunofluorescent staining for aquaporin-4 and glial fibrillary acidic protein and then verified the high coexpression in the hippocampus of the CKD rat model. Furthermore, results from recoding of the field excitatory postsynaptic potential (fEPSP) in the hippocampus showed the reduced amplitude and slope of fEPSP in the CKD rats. ESRD patients with cognitive impairment showed a significant decrease in the hippocampus volume compared with ESRD patients without cognitive impairment or the controls. Our findings suggest that uremia resulting from decreased kidney function may cause the destruction of the blood-brain barrier and hippocampus-related cognitive impairment in CKD.

A Case Report of Thrombotic Thrombocytopenia After ChAdOx1 nCov-19 Vaccination and Heparin Use During Hemodialysis.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but life-threatening complication. VITT strongly mimics heparin-induced thrombocytopenia (HIT) and shares clinical features. Heparin is commonly used to prevent coagulation during hemodialysis. Therefore, nephrologists might encounter patients needing dialysis with a history of heparin exposure who developed thrombotic thrombocytopenia after vaccination. A 70-year-old male presented with acute kidney injury and altered mental status due to lithium intoxication. He needed consecutive hemodialysis using heparin. Deep vein thrombosis of left lower extremity and accompanying severe thrombocytopenia of 15,000/µL on 24 days after vaccination and at the same time, nine days after heparin use. Anti-platelet factor 4 antibody test was positive. Anticoagulation with apixaban and intravenous immunoglobulin (IVIG) infusion resolved swelling of his left calf and thrombocytopenia. There were no definitive diagnostic tools capable of differentiating between VITT and HIT in this patient. Although VITT and HIT share treatment with IVIG and non-heparin anticoagulation, distinguishing between VITT and HIT will make it possible to establish a follow-up vaccination plan in a person who has had a thrombocytopenic thrombotic event. Further research is needed to develop the tools to make a clear distinction between the clinical syndromes.

The effect of periodontitis on recipient outcomes after kidney transplantation.

BACKGROUND: Recent several reports have demonstrated that periodontitis is prevalent and adversely affects the survival in patients with chronic kidney disease (CKD) or end-stage kidney disease. However, its impact on transplant outcomes remains uncertain. METHODS: This retrospective cohort study included 136 and 167 patients, respectively, who underwent living donor kidney transplantation (KT) at Seoul National University Hospital from July 2012 to August 2016 and Korea University Hospital from April 2008 to October 2018. We divided patients into three groups according to stages of periodontitis based on a new classification system. RESULTS: Patients with severe periodontitis were older, had a higher prevalence of diabetes, a higher body mass index and C-reactive protein level, a lower cardiac output, and were more likely to be smokers, indicating its association with chronic systemic inflammation. After KT, stage IV periodontitis was independently associated with a lower incidence of acute T cell-mediated rejection, suggesting the possible effect of periodontitis on immune function. However, 1-year and 3-year estimated glomerular filtration rates were not different. Among the KT recipients followed up more than 3 years, new-onset cardiovascular disease occurred in nine patients, and coronary artery disease occurred more frequently in patients with stage IV periodontitis. However, diabetes was the independent predictor of new-onset coronary artery disease in multivariate logistic regression analysis. CONCLUSION: Our findings showed that periodontitis might be an important player in determining posttransplant outcomes in recipients. Further interventional trials to test whether treating periodontitis could modify transplant outcome are needed.

The effect of probiotic supplementation on systemic inflammation in dialysis patients.

BACKGROUND: Emerging evidence suggests that intestinal dysbiosis contributes to systemic inflammation and cardiovascular diseases in dialysis patients. The purpose of this study was to evaluate the effects of probiotic supplementation on various inflammatory parameters in hemodialysis (HD) patients. METHODS: Twenty-two patients with maintenance HD were enrolled. These patients were treated twice a day with 2.0 ×1010 colony forming units of a combination of Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI for 3 months. The microbiome and fecal short-chain fatty acids (SCFAs) were analyzed. The percentages of CD14+ CD16+ proinflammatory monocytes and CD4+ CD25+ regulatory T-cells (Tregs) before and after probiotic supplementation were determined by flow cytometry. Serum levels of calprotectin and cytokine responses upon lipopolysaccharide (LPS) challenge were compared before and after probiotic supplementation. RESULTS: Fecal SCFAs increased significantly after probiotic supplementation. Serum levels of calprotectin and interleukin 6 upon LPS stimulation significantly decreased. The anti-inflammatory effects of probiotics were associated with a significant increase in the percentage of CD4+ CD25+ Tregs (3.5% vs. 8.6%, p < 0.05) and also with a decrease of CD14+ CD16+ proinflammatory monocytes (310/ mm2 vs. 194/mm2 , p < 0.05). CONCLUSION: Probiotic supplementation reduced systemic inflammatory responses in HD patients and this effect was associated with an increase in Tregs and a decrease in proinflammatory monocytes. Hence, targeting intestinal dysbiosis might be a novel strategy for decreasing inflammation and cardiovascular risks in HD patients.

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.

Impact of acute kidney injury on long-term adverse outcomes in obstructive uropathy.

Obstructive uropathy is known to be associated with acute kidney injury (AKI). This study aimed to investigate the etiologies, clinical characteristics, consequences and also assess the impact of AKI on long-term outcomes. This multicenter, retrospective study of 1683 patients with obstructive uropathy who underwent percutaneous nephrostomy (PCN) analyzed clinical characteristics, outcomes including progression to end-stage kidney disease (ESKD), overall mortality, and the impact of AKI on long-term outcomes. Obstructive uropathy in adults was most commonly caused by malignancy, urolithiasis, and other causes. AKI was present in 78% of the patients and was independently associated with preexisting chronic kidney disease (CKD). Short-term recovery was achieved in 56.78% after the relief of obstruction. ESKD progression rate was 4.4% in urolithiasis and 6.8% in other causes and older age, preexisting CKD, and stage 3 AKI were independent factors of progression. The mortality rate (34%) was highly attributed to malignant obstruction (52%) stage 3 AKI was also an independent predictor of mortality in non-malignant obstruction. AKI is a frequent complication of adult obstructive uropathy. AKI negatively affects long-term kidney outcomes and survival in non-malignant obstructions. A better understanding of the epidemiology and prognostic factors is needed for adult obstructive uropathy.