Impact of Serum Creatinine- and Cystatin C-Based Sarcopenia Index on Renal Outcomes in Non-Dialysis-Dependent Chronic Kidney Disease Patients: Results From the KNOW-CKD Study.

OBJECTIVE: To evaluate the impact of the serum creatinine- and cystatin C-based new sarcopenia index (SI) on renal outcomes in non-dialysis-dependent patients with chronic kidney disease (CKD). METHODS: In this observational Korean Cohort Study for Outcome in Patients With CKD (KNOW-CKD), 1957 patients with CKD stage 1 to stage 4 were analyzed from 2011 to 2019. Men and women were separately assigned to quartile groups according to their SI. The primary outcome was a composite renal outcome consisting of 50% reduction in estimated glomerular filtration rate or end-stage kidney disease. With use of Fine and Gray subdistribution hazard models, the association between the SI and the primary outcome was analyzed. RESULTS: During a median follow-up of 6.0 (4.2 to 7.7) years, the primary composite renal outcome occurred in 528 (28.6%) patients within a median of 3.0 (1.8 to 5.0) years. In unadjusted and adjusted models, lower SI groups had a poor primary outcome compared with the highest group (quartile 4). The hazard ratios for quartiles 1, 2, and 3 compared with quartile 4 in the fully adjusted model were 4.47 (95% CI, 3.05 to 6.56; P<.001), 3.08 (95% CI, 2.13 to 4.48; P<.001), and 2.09 (95% CI, 1.45 to 3.01; P<.001), respectively. Restricted cubic spline regression analyses found a relatively inverse linear relationship between the SI and the composite renal outcome. CONCLUSION: The new SI is an independent predictor of renal outcomes. A low SI is associated with poor renal outcome.

Placental growth factor deficiency initiates obesity- and aging-associated metabolic syndrome.

Obesity often leads to inadequate angiogenesis in expanding adipose tissue, resulting in inflammation and insulin resistance. We explored the role of placental growth factor (PlGF) in metabolic syndrome (MS) using mice models of type 2 diabetes, high-fat diet, or aging. Reduced serum PlGF levels were associated with decreased insulin sensitivity and development of MS features. PlGF was localized within endothelial cells and pericytes of adipose tissue. In vitro, low PlGF levels in hypoxic conditions worsened oxidative stress, apoptosis, and reduced autophagy. This was associated with a reduction in expression of vascular endothelial growth factor (VEGF)-A/VEGF-R1/-R2, which was influenced by a decrease and increase in PlGF/pAMPK/PI3K-pAkt/PLCγ1-iCa++/eNOS and PTEN/GSK3ß axes, respectively. PlGF-knockout mice exhibited MS traits through alterations in the same signaling pathways, and these changes were mitigated by recombinant PlGF and metformin. These enhanced angiogenesis and lipid metabolism, underscoring PlGF's role in age-related MS and its potential as a therapeutic target.

Hospitalization among adults with chronic kidney disease: results from the KoreaN cohort study for Outcomes in patients With Chronic Kidney Disease (KNOW-CKD) study.

Background: Chronic kidney disease (CKD) patients are hospitalized for various conditions. Hospitalization increases the readmission rate and mortality rate, seriously deteriorating patients' quality of life. Consequently, it is crucial to analyze the reasons for hospitalization in CKD patients from a broader perspective according to CKD grade. Methods: This is a prospective cohort study of CKD patients entitled the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD). A total of 2,238 patients were examined, and the reasons for hospitalization were classified into 16 disease categories. The incidence rate ratio (IRR) according to CKD stage was compared using negative bimodal regression analysis. Results: The all-cause hospitalization incidence was 184.96 per 1,000 person-years. The most common reason for hospitalization was circulatory system disease, followed by infection and digestive system disease. Among hospitalizations for acute kidney injury, endocrine-nutrition-metabolic-related illness, blood-related disease, and diseases of the nervous system and sensory organs, IRR increased as CKD grade advanced. The incidence of ophthalmologic surgery during hospitalization increased according to the CKD stage. The IRR of KNOW-CKD patients was 6.19 (95% confidence interval, 5.92-6.48; p < 0.001) compared with the general population. Conclusion: This in-depth analysis of hospitalizations among CKD patients confirmed that CKD patients were hospitalized for various reasons, such as metabolic, ophthalmic, and hematologic diseases. Early detection and intervention regarding causative diseases of CKD are important to reduce the hospitalization burden and improve patients' quality of life.

The association between transferrin saturation and all-cause mortality in chronic kidney disease: findings from Korean Cohort Study for Outcome in Patients with Chronic Kidney Disease.

Background: Transferrin saturation (TSAT) has been used as an indicator of iron deficiency. However, there is no consensus regarding its optimal range for patient with chronic kidney disease (CKD). We aimed to analyze the effect of TSAT on the prognosis of patients with non-dialysis CKD (NDCKD). Methods: From 2011 to 2016, 2157 NDCKD patients with baseline TSAT measurements were followed for 10 years. Patients were divided into three groups based on baseline TSAT values: <25%, ≥25% and <45%, and ≥45%. All-cause mortality and 4-point major adverse cardiovascular events (MACE) were analyzed using multivariable Cox regression analysis. Other iron biomarkers and mortality were also analyzed. Results: During a mean follow-up of 7.1 ± 2.9 years, 182 of a total of 2,157 patients (8.4%) died. Compared with the TSAT ≥25% and <45% group, the TSAT <25% group showed significantly increased all-cause mortality (hazard ratio [HR], 1.44; 95% confidence interval (CI), 1.02-2.03; p = 0.04). The occurrence of 4-point MACE was significantly increased in univariable analysis in the TSAT <25% group (HR, 1.48; 95% CI, 1.02-2.15; p = 0.04), but it was not significant in the multivariable analysis (HR, 1.38; 95% CI, 0.89-2.15; p = 0.15). Tertile comparisons of the iron-to-log-ferritin ratio showed increased mortality in the first tertile group. Conclusion: TSAT <25% is an independent risk factor for all-cause mortality in patients with NDCKD and care should be taken to prevent TSAT values of <25%. Other indicators, such as serum iron and iron-to-log-ferritin ratio, may also be used to assess iron deficiency.

Diagnostic Efficacy and Safety of Low-Contrast-Dose Dual-Energy CT in Patients With Renal Impairment Undergoing Transcatheter Aortic Valve Replacement.

OBJECTIVE: This study aimed to evaluate the diagnostic efficacy and safety of low-contrast-dose, dual-source dual-energy CT before transcatheter aortic valve replacement (TAVR) in patients with compromised renal function. MATERIALS AND METHODS: A total of 54 consecutive patients (female:male, 26:38; 81.9 ± 7.3 years) with reduced renal function underwent pre-TAVR dual-energy CT with a 30-mL contrast agent between June 2022 and March 2023. Monochromatic (40- and 50-keV) and conventional (120-kVp) images were reconstructed and analyzed. The subjective quality score, vascular attenuation, contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR) were compared among the imaging techniques using the Friedman test and post-hoc analysis. Interobserver reliability for aortic annular measurement was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. The procedural outcomes and incidence of post-contrast acute kidney injury (AKI) were assessed. RESULTS: Monochromatic images achieved diagnostic quality in all patients. The 50-keV images achieved superior vascular attenuation and CNR (P < 0.001 in all) while maintaining a similar SNR compared to conventional CT. For aortic annular measurement, the 50-keV images showed higher interobserver reliability compared to conventional CT: ICC, 0.98 vs. 0.90 for area and 0.97 vs. 0.95 for perimeter; 95% limits of agreement width, 0.63 cm² vs. 0.92 cm² for area and 5.78 mm vs. 8.50 mm for perimeter. The size of the implanted device matched CT-measured values in all patients, achieving a procedural success rate of 92.6%. No patient experienced a serum creatinine increase of ≥ 1.5 times baseline in the 48-72 hours following CT. However, one patient had a procedural delay due to gradual renal function deterioration. CONCLUSION: Low-contrast-dose imaging with 50-keV reconstruction enables precise pre-TAVR evaluation with improved image quality and minimal risk of post-contrast AKI. This approach may be an effective and safe option for pre-TAVR evaluation in patients with compromised renal function.

Atypical post-infectious glomerulonephritis with c-ANCA positivity followed by endocarditis.

Post-infectious glomerulonephritis (PIGN), an uncommon variety of glomerulonephritis (GN), is characterized by emergence of nephritic syndrome within a few weeks following an infectious event. PIGN typically presents as a mild condition and tends to resolve by the time of diagnosis for GN. Aggregatibacter actinomycetemcomitans belongs to the HACEK group of bacteria, which constitutes less than 3% of bacteria responsible for community-acquired infective endocarditis. We present a case of 29-year-old man suspected of lymphoma with B-symptoms along with severe splenomegaly and nephromegaly. Shortly after, he developed an episode of nephritic syndrome accompanied by acute kidney injury (AKI) and high titers of cytoplasmic ANCA (c-ANCA)-positivity. Kidney biopsy revealed PIGN with tubulointerstitial nephritis. Despite treatment with antibiotics and corticosteroid, he visited the emergency room due to worsening dyspnea and multi-organ failure. An echocardiogram showed a bicuspid aortic valve with vegetation unseen on previous echocardiogram. He underwent aortic valve replacement immediately without adverse events. Four months after valve replacement, his renal function and cardiac performance have remained stable. We report a case of PIGN with AKI and high titers of c-ANCA appearing later as an infective endocarditis due to Aggregatibacter actinomycetemcomitans. With careful clinical observation and appropriate and timely management, satisfactory outcomes for patient health are possible.

Proteinuria, measured or estimated albuminuria for risk prediction in patients with chronic kidney disease?

BACKGROUND: Although albuminuria is the gold standard for defining chronic kidney disease (CKD), total proteinuria has also been widely used in real-world clinical practice. Moreover, the superiority of the prognostic performance of albuminuria over proteinuria in patients with CKD remains inconclusive. Therefore, we aimed to compare the predictive performances of albuminuria and proteinuria in these patients. METHODS: From the Korean Cohort Study for Outcome in Patients with CKD we included 2099 patients diagnosed with CKD grades 1-5 who did not require kidney replacement therapy. We measured the spot urine albumin:creatinine ratio (mACR) and protein:creatinine ratio (PCR) and estimated the ACR (eACR) using the PCR. Kidney failure risk equation (KFRE) scores were calculated using the mACR, PCR and eACR. The primary outcome was the 5-year risk of kidney failure with replacement therapy (KFRT). RESULTS: The eACR significantly underestimated mACR in patients with low albuminuria levels. The time-dependent area under the receiver operating characteristics curve showed excellent predictive performance for all KFRE scores from the mACR, PCR and eACR. However, eACR was inferior to mACR based on the continuous net reclassification index (cNRI) and integrated discrimination improvement index (IDI) in all CKD cause groups, except for the group with an unclassified aetiology. Moreover, the cNRI and IDI statistics indicated that both eACR and PCR were inferior to mACR in patients with low albuminuria (<30 mg/g). Conversely, the predictive performance of PCR was superior in severe albuminuria and nephrotic-range proteinuria, in which the IDI and cNRI of the PCR were greater than those of the mACR. CONCLUSIONS: The mACR, eACR and PCR showed excellent performance in predicting KFRT in patients with CKD. However, eACR was inferior to mACR in patients with low albuminuria, indicating that measuring rather than estimating albuminuria is preferred for these patients.

Phosphodiesterase inhibitor ameliorates senescent changes of renal interstitial pericytes in aging kidney.

Pericytes are mesenchymal cells that surround endothelial cells, playing a crucial role in angiogenesis and vessel maturation. Additionally, they are associated with interstitial fibrosis as a major contributor to renal myofibroblasts. In this study, we aim to investigate whether the phosphodiesterase inhibitor, pentoxifylline (PTX), can ameliorate aging-related functional and histological deterioration in the kidney. We subjected aging C57BL/6 mice, dividing into young, aging, and PTX-treated aging groups. Renal function, albuminuria, and histological changes were assessed. Interstitial pericytes were assessed by immunohistochemistry analysis. We examined changes in pericytes in elderly patients using human kidney tissue obtained from healthy kidney donors for kidney transplantation. In vitro experiments with human pericytes and endothelial cells were performed. Aging mice exhibited declined renal function, increased albuminuria, and aging-related histological changes including mesangial expansion and tubulointerstitial fibrosis. Notably, number of pericytes declined in aging kidneys, and myofibroblasts increased. PTX treatment ameliorated albuminuria, histological alterations, and microvascular rarefaction, as well as modulated angiopoietin expression. In vitro experiments showed PTX reduced cellular senescence and inflammation. Human kidney analysis confirmed similar pericyte changes in aging kidneys. The phosphodiesterase inhibitor, PTX preserved microvascular density and improved renal interstitial fibrosis and inflammation in aging mice kidneys. These protective effects were suggested to be associated with the amelioration of pericytes reduction and the transition to myofibroblasts. Additionally, the upregulation of angiopoietin-1 expression may exert potential impacts. To the best of our knowledge, this is the first report on the changes in renal interstitial pericytes in aging human kidneys.

Oxidative Stress Induced by Lipotoxicity and Renal Hypoxia in Diabetic Kidney Disease and Possible Therapeutic Interventions: Targeting the Lipid Metabolism and Hypoxia.

Oxidative stress, a hallmark pathophysiological feature in diabetic kidney disease (DKD), arises from the intricate interplay between pro-oxidants and anti-oxidants. While hyperglycemia has been well established as a key contributor, lipotoxicity emerges as a significant instigator of oxidative stress. Lipotoxicity encompasses the accumulation of lipid intermediates, culminating in cellular dysfunction and cell death. However, the mechanisms underlying lipotoxic kidney injury in DKD still require further investigation. The key role of cell metabolism in the maintenance of cell viability and integrity in the kidney is of paramount importance to maintain proper renal function. Recently, dysfunction in energy metabolism, resulting from an imbalance in oxygen levels in the diabetic condition, may be the primary pathophysiologic pathway driving DKD. Therefore, we aim to shed light on the pivotal role of oxidative stress related to lipotoxicity and renal hypoxia in the initiation and progression of DKD. Multifaceted mechanisms underlying lipotoxicity, including oxidative stress with mitochondrial dysfunction, endoplasmic reticulum stress activated by the unfolded protein response pathway, pro-inflammation, and impaired autophagy, are delineated here. Also, we explore potential therapeutic interventions for DKD, targeting lipotoxicity- and hypoxia-induced oxidative stress. These interventions focus on ameliorating the molecular pathways of lipid accumulation within the kidney and enhancing renal metabolism in the face of lipid overload or ameliorating subsequent oxidative stress. This review highlights the significance of lipotoxicity, renal hypoxia-induced oxidative stress, and its potential for therapeutic intervention in DKD.

Practice of dialysis access interventional nephrology procedures in the Asia-Pacific region: Getting lay of the land.

AIM: This cross-sectional survey aimed to determine the prevalence of Interventional Nephrology (IN) practice amongst nephrologists in the Asia-Pacific Region (APR), specifically related to dialysis access (DA). METHODS: The Association of VA and intervenTionAl Renal physicians (AVATAR) Foundation from India conducted a multinational online survey amongst nephrologists from the Asia-Pacific to determine the practice of IN in the planning, creation, and management of dialysis access. The treatment modalities, manpower and equipment availability, monthly cost of treatment, specifics of dialysis access interventions, and challenges in the training and practice of IN by nephrologists were included in the survey. RESULTS: Twenty-one countries from the APR participated in the survey. Nephrologists from 18 (85.7%) countries reported performing at least one of the basic dialysis access-related IN procedures, primarily the placement of non-tunnelled central catheters (n-TCC; 71.5%). Only 10 countries (47.6%) reported having an average of <4% of nephrologists performing any of the advanced IN access procedures, the most common being the placement of a peritoneal dialysis (PD) catheter (20%). Lack of formal training (57.14%), time (42.8%), incentive (38%), institutional support (38%), medico-legal protection (28.6%), and prohibitive cost (23.8%) were the main challenges to practice IN. The primary obstacles to implementing the IN training were a lack of funding and skilled personnel. CONCLUSION: The practice of dialysis access-related IN in APR is inadequate, mostly due to a lack of training, backup support, and economic constraints, whereas training in access-related IN is constrained by a lack of a skilled workforce and finances.

The 2021 KDIGO blood pressure target and the progression of chronic kidney disease: Findings from KNOW-CKD.

BACKGROUND: The 2021 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline for the management of blood pressure (BP) in chronic kidney disease (CKD) recommends a target systolic BP of <120 mmHg as this target can provide cardiovascular benefits. However, it remains unclear whether implementing the new BP target could improve kidney outcomes. METHODS: The association between the 2021 KDIGO BP target and CKD progression was examined and compared with the 2012 KDIGO BP target among 1724 participants included in the KoreaN Cohort Study for Outcomes in Patients With CKD. The main exposure was the BP status categorized according to the 2012 or 2021 KDIGO guideline: (1) controlled within the 2021 target, (2) controlled within the 2012 target only, and (3) above both targets. The primary outcome was a composite kidney outcome of ≥50% decline in the estimated glomerular filtration rate from baseline or the initiation of kidney replacement therapy during the follow-up period. RESULTS: Composite kidney outcomes occurred in 650 (37.7%) participants during the 8078 person-years of follow-up (median, 4.9 years). The incidence rates of this outcome were 55, 66.5, and 116.4 per 1000 person-years in BP controlled within the 2021 and 2012 KDIGO targets, and BP above both targets, respectively. In the multivariable cause-specific hazard model, hazard ratios for the composite outcome were 0.76 (95% confidence interval (CI), 0.60-0.95) for BP controlled within the 2021 target and 1.36 (95% CI, 1.13-1.64) for BP above both targets, compared with BP controlled within 2012 target only. CONCLUSION: The newly lowered BP target by the 2021 KDIGO guideline was associated with improved kidney outcome compared with BP target by the 2012 KDIGO guideline.

Predictive performance of the new race-free Chronic Kidney Disease Epidemiology Collaboration equations for kidney outcome in Korean patients with chronic kidney disease.

BACKGROUND: The new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations without a race coefficient have gained recognition across the United States. We aimed to test whether these new equations performed well in Korean patients with chronic kidney disease (CKD). METHODS: This study included 2,149 patients with CKD G1-G5 without kidney replacement therapy from the Korean Cohort Study for Outcome in Patients with CKD (KNOW-CKD). The estimated glomerular filtration rate (eGFR) was calculated using the new CKD-EPI equations with serum creatinine and cystatin C. The primary outcome was 5-year risk of kidney failure with replacement therapy (KFRT). RESULTS: When we adopted the new creatinine equation [eGFRcr (NEW)], 81 patients (23.1%) with CKD G3a based on the current creatinine equation (eGFRcr) were reclassified as CKD G2. Accordingly, the number of patients with eGFR of <60 mL/min/1.73 m2 decreased from 1,393 (64.8%) to 1,312 (61.1%). The time-dependent area under the receiver operating characteristic curve for 5-year KFRT risk was comparable between the eGFRcr (NEW) (0.941; 95% confidence interval [CI], 0.922-0.960) and eGFRcr (0.941; 95% CI, 0.922-0.961). The eGFRcr (NEW) showed slightly better discrimination and reclassification than the eGFRcr. However, the new creatinine and cystatin C equation [eGFRcr-cys (NEW)] performed similarly to the current creatinine and cystatin C equation. Furthermore, eGFRcr-cys (NEW) did not show better performance for KFRT risk than eGFRcr (NEW). CONCLUSION: Both the current and the new CKD-EPI equations showed excellent predictive performance for 5-year KFRT risk in Korean patients with CKD. These new equations need to be further tested for other clinical outcomes in Koreans.

Comparison of cardiovascular event predictability between the 2009 and 2021 Chronic Kidney Disease Epidemiology Collaboration equations in a Korean chronic kidney disease cohort: the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease.

BACKGROUND: The 2009 Chronic Kidney Disease Epidemiology Collaboration creatinine-based estimated glomerular filtration rate (eGFRcr) equation contains a race component that is not based on biology and may cause a bias in results. Therefore, the 2021 eGFRcr and creatinine-cystatin C-based eGFR (eGFRcr-cysC) equations were developed with no consideration of race. This study compared the cardiovascular event (CVE) and all-cause mortality and CVE combined predictability among the three eGFR equations in Korean chronic kidney disease (CKD) patients. METHODS: This study included 2,207 patients from the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease. Receiver operating characteristic (ROC) and net reclassification improvement (NRI) index were used to compare the predictability of the study outcomes according to the 2009 eGFRcr, 2021 eGFRcr, and 2021 eGFRcr-cysC equations. RESULTS: The overall prevalence of CVE and all-cause mortality were 9% and 7%, respectively. There was no difference in area under the curve of ROC for CVE and mortality and CVE combined among all three equations. Compared to the 2009 eGFRcr, both the 2021 eGFRcr (NRI, 0.013; 95% confidence interval [CI], - 0.002 to 0.028) and the eGFRcr-cysC (NRI, -0.001; 95% CI, -0.031 to 0.029) equations did not show improved CVE predictability. Similar findings were observed for mortality and CVE combined predictability with both the 2021 eGFRcr (NRI, -0.019; 95% CI, -0.039-0.000) and the eGFRcr-cysC (NRI, -0.002; 95% CI, -0.023 to 0.018). CONCLUSION: The 2009 eGFRcr equation was not inferior to either the 2021 eGFRcr or eGFRcr-cysC equation in predicting CVE and the composite of mortality and CVE in Korean CKD patients.

Response and Dynamics of Renal Function in Transplantation-Eligible Multiple Myeloma Patients Treated with a Novel Agent: The CAREMM-2201 Study.

Newly diagnosed multiple myeloma (NDMM) frequently results in renal impairment (RI), and its natural course has not been fully elucidated in the era of novel agents. We aimed to identify the dynamics of renal function after autologous stem cell transplantation (ASCT) following induction treatment using a novel agent in transplantation-eligible NDMM patients with RI (estimated glomerular filtration rate [eGFR] ≤50 mL/min/1.73 m2) at diagnosis. The factors associated with achieving a renal response based on the term renal benefit regardless of baseline eGFR were investigated as well. In a multicenter registry database including 1795 patients with plasma cell disorder, 140 transplantation-eligible NDMM patients who developed RI at the time of initiation of treatment for NDMM were identified. They received protocol-based treatment (PBT) consisting of induction treatment using proteasome inhibitors and/or immunomodulatory drugs followed by ASCT. MM and renal responses were evaluated using the International Myeloma Working Group response criteria. To evaluate the standardized improvement of renal function irrespective of baseline eGFR, renal benefit was defined as a sustained (for at least 3 months) increase in eGFR >15 mL/min/1.73 m2. The mean patient age was 54.7 ± 7.4 years. With a mean baseline eGFR of 24.8 ± 13.9, the renal complete response (renalCR) and renal benefit rates were 49.3% and 67.9%, respectively. In a multivariable analysis, the 3 factors significantly associated with reduced likelihood of achieving both renalCR and renal benefit were age ≥55 years, light chain type NDMM, and failure to improve eGFR by 5 mL/min/1.73 m2 with supportive care when measured 3 days prior to induction therapy and at the initiation of chemotherapy. Hypertension and advanced eGFR also were associated with poor renalCR achievement. The mean eGFR improved until the time of ASCT and then decreased gradually over time. The mean eGFR improved significantly until 4 months post-PBT compared with each eGFR at previous time points, but this significant improvement disappeared by 5 months post-PBT. In a subgroup of patients who developed RI after undergoing ASCT (n = 55), the eGFR increased temporarily at 1 month post-ASCT; however, this improvement reverted to baseline at 2 months post-ASCT. Among another subgroup of 27 patients who were dialysis-dependent at the time of initial treatment, 18 (66.7%) were no longer dialysis-dependent after a median of 60 days. The best renal response was acquired early during the PBT period, and ASCT did not have a robust impact on the renal outcome. Patients who failed to achieve a renal benefit should be provided with the best supportive care for chronic kidney disease, and this simplified criterion for evaluating the renal response needs to be validated in larger studies before it can be recommended. © 2022 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Serum creatinine to cystatin C ratio and clinical outcomes in adults with non-dialysis chronic kidney disease.

Background: Studies have suggested that the serum creatinine/cystatin C (Cr/CysC) ratio is a surrogate marker for muscle wasting is associated with adverse outcomes in several disease conditions. To clarify the utility of the Cr/CysC ratio as a prognostic marker in chronic kidney disease (CKD) we evaluated the association between the Cr/CysC ratio clinical outcomes in patients with non-dialysis CKD. Methods: This prospective observational cohort study included 1,966 participants of the KoreaN cohort study Outcomes in patients With CKD (KNOW-CKD). We evaluated associated factors with the serum Cr/CysC ratio and association between the serum Cr/CysC ratio and composite outcomes of all-cause death and cardiovascular events (CVEs). Results: The mean age was 54 ± 12 (SD) years and 61% were men. The mean serum Cr/CysC ratio was 10.97 ± 1.94 in men and 9.10 ± 1.77 in women. The Cr/CysC ratio correlated positively with urinary creatinine excretion, a marker of muscle mass. In the fully adjusted Cox proportional hazard model, the Cr/CysC ratio was associated with the occurrence of adverse outcomes through a median follow-up of 5.9 years [hazard ratio (HR) = 0.92, 95% confidence interval (CI) = 0.85-0.99 for the composite outcomes, HR = 0.87, 95% CI, 0.78 - 0.97 for all-cause death, and HR = 0.93; 95% CI, 0.84-1.04 for CVEs]. In subgroup analyses, there were interactions of the Cr/CysC ratio with age and sex for risk of the clinical outcomes, but not eGFR group. Conclusion: A higher Cr/CysC ratio is associated with a lower risk of the composite outcomes, especially all-cause mortality, even after adjusting for eGFR. These suggest that the Cr/CysC ratio is a useful prognostic marker in CKD.

Adiponectin receptor agonist ameliorates cardiac lipotoxicity via enhancing ceramide metabolism in type 2 diabetic mice.

Accumulation of lipids and their metabolites induces lipotoxicity in diabetic cardiomyopathy. Lowering ceramide concentration could reduce the impact of metabolic damage to target organs. Adiponectin improves lipotoxicity through its receptors (AdiopRs), which have sequence homology with ceramidase enzymes. Therefore, cardioprotective role of AdipoR agonism by AdipoRon was investigated. Sixteen-week-old male db/m and db/db mice were fed a diet containing AdipoRon for four weeks. Phenotypic and metabolic profiles with associated cellular signaling pathways involved in lipid metabolism were investigated in the mice heart and human cardiomyocytes to establish treatment effect of AdipoRon. AdipoRon ameliorated insulin resistance, fibrosis, M1-dominant inflammation, and apoptosis in association with reduced accumulations of free fatty acid, triglycerides, and TLR4-related ceramide in the heart. This resulted in overall reduction in the level of oxidative stress which ameliorated cardiac hypertrophy and its function. AdipoRon increased the expression of AdipoR1 and AdipoR2 via pAMPK/FoxO1-induced Akt phosphorylation resulting from a decrease in PP2A level. It also increased acid ceramidase activity which reduced ceramide and increased sphingosine-1 phosphate levels in the heart of db/db mice and cultured human cardiomyocytes. Consistent upregulation of AdipoRs and their downstream regulatory pathways involving pAMPK/PPARα/PGC-1α levels led to lipid metabolism enhancement, thereby improving lipotoxicity-induced peroxisome biogenesis and oxidative stress. AdipoRon might control oxidative stress, inflammation, and apoptosis in the heart through increased AdipoR expression, acid ceramidase activity, and activation of AMPK-PPARα/PGC-1α and related downstream pathways, collectively improving cardiac lipid metabolism, hypertrophy, and functional parameters.

Clinical predictors of recurrent cephalic arch stenosis and impact of the access flow reduction on the patency rate.

OBJECTIVE: Despite the widespread use of conventional percutaneous transluminal angioplasty (PTA), recurrence of cephalic arch stenosis (CAS), and low patency rate after PTA remain challenging problem. We aimed to identify the clinical predictors of recurrence of CAS and evaluate the effect of the access flow reduction on the fistula patency rate in patients with recurrent CAS. METHODS: In 1118 angiographies of 220 patients with CAS, access circuit patency rates after PTA and potential clinical predictors of recurrence of CAS were assessed. The effect of the banding procedure was evaluated in terms of post-interventional primary patency rate, and the number of interventions per access-year. RESULTS: At 3, 6, and 12 months after the first PTA on CAS, the post-interventional access circuit primary patency rates were 68.8%, 40.5%, and 25.1%, respectively. High CV to CA ratio (the ratio of the maximal diameter of the distal cephalic vein to the diameter of the cephalic arch) (Hazard ratio (HR), 1.437; 95% confidence interval (CI), 1.036-1.992) and involvement of the proximal segment of cephalic arch (HR, 1.828; 95% CI, 1.194-2.801) were significant predictors of recurrent CAS. For those with recurrent CAS (>3 times/year) and an access flow rate >1.5 L/minute, endovascular banding procedure was performed. The banding procedure significantly reduced the number of interventions per access-year (t = 3.299, p = 0.005 and t = 2.989, p = 0.007, respectively). Post-interventional access circuit primary patency rate after banding was significantly higher than that before banding (p = 0.01). CONCLUSIONS: High CV to CA ratio and involvement of the proximal segment of the cephalic arch are independent clinical predictors of recurrent CAS. Endovascular banding might delay recurrence of CAS in patients with high CV to CA ratio and high access flow.

Blood Pressure Control in Patients with Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is the most common cause of end-stage kidney disease. Blood pressure (BP) control can reduce the risks of cardiovascular (CV) morbidity, mortality, and kidney disease progression. Recently, the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines have suggested the implementation of a more intensive BP control with a target systolic BP (SBP) of <120 mmHg based on the evidence that the CV benefits obtained is outweighed by the kidney injury risk associated with a lower BP target. However, an extremely low BP level may paradoxically aggravate renal function and CV outcomes. Herein, we aimed to review the existing literature regarding optimal BP control using medications for DKD.