Clinical characteristics and prognosis of patients with COVID-19 on mechanical ventilation undergoing continuous renal replacement therapy.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has significantly strained global healthcare, particularly in the management of patients requiring mechanical ventilation (MV) and continuous renal replacement therapy (CRRT). This study investigated the characteristics and prognoses of these patients. METHODS: This multicenter retrospective cohort study gathered data from patients with COVID-19 across 26 medical centers. Logistic analysis was used to identify the factors associated with CRRT implementation. RESULTS: Of the 640 patients with COVID-19 who required MV, 123 (19.2%) underwent CRRT. Compared to the non-CRRT group, the CRRT group was older and exhibited higher sequential organ failure assessment scores. The incidence of hypertension, diabetes, cardiovascular disease, chronic neurological disease, and chronic kidney disease was also higher in the CRRT group. Moreover, the CRRT group had higher intensive care unit (ICU) (75.6% vs. 26.9%, p < 0.001) and in-hospital (79.7% vs. 29.6%, p < 0.001) mortality rates. CRRT implementation was identified as an independent risk factor for both ICU mortality (hazard ratio [HR]:1.833, 95% confidence interval [CI]:1.342-2.505, p < 0.001) and in-hospital mortality (HR: 2.228, 95% CI: 1.648-3.014, p < 0.001). Refractory respiratory failure (n = 99, 19.1%) was the most common cause of death in the non-CRRT death group, and shock with multi-organ failure (n = 50, 40.7%) was the most common cause of death in the CRRT death group. Shock with multi-organ failure and cardiac death were significantly more common in the CRRT death group, compared to non-CRRT death group. CONCLUSION: This study indicates that CRRT is associated with higher ICU and in-hospital mortality rates in patients with COVID-19 who require MV. Notably, the primary cause of death in the CRRT group was shock with multi-organ failure, emphasizing the severe clinical course for these patients, while refractory respiratory failure was most common in non-CRRT patients.

The Factors Influencing Chronic Kidney Disease Incidence: Database from the Korean National Health Insurance Sharing Service (NHISS).

Background: The global prevalence of chronic kidney disease (CKD) is increasing, with diabetes accounting for the highest proportion. We analyzed the influence of clinical factors on the incidence of CKD according to the renal function, primary focusing on patients with diabetes. Methods: We used the Sample Cohorts Database provided by the National Health Insurance Sharing Service (NHISS) in Korea. Participants aged ≥ 40 years who underwent a health checkup in 2009 were categorized into six groups based on their eGFR values (<60 mL/min, 60-89 mL/min, ≥90 mL/min) and the presence of diabetes. And all patients with CKD at 2009 screening were excluded. The participants were tracked from 2010 to 31 December 2019. The CKD incidence rate according to the eGFR values and the effect of the accompanying factors on CKD incidence were confirmed. Results: 148,089 people without CKD were analyzed. The CKD incidence rate was highest in those with eGFR < 60 mL/min with diabetes and lowest in those with eGFR ≥ 90 mL/min without diabetes. The CKD incidence rates were similar between the eGFR < 60 mL/min group without diabetes and the eGFR 60-89 mL/min group with diabetes. Compared to under 44 years of age, the hazard ratio of CKD incidence was 8 times higher in over 75 years of age. Men had a 1.7-fold higher risk of developing CKD than women. Current smoker, hypertension, dyslipidemia, myocardial infarction history, and atrial fibrillation and flutter increased the risk of CKD incidence. Age, diabetes, and baseline eGFR are important factors in the occurrence of CKD. As age increases, the risk of developing CKD in men increases compared to women. Conclusions: These results will be helpful in predicting risk groups for CKD and establishing strategies to lowering CKD incidence.

Relationship between Permanent Catheter Patency and Nutrient Score in Patients Aged >75 Years Requiring Renal Replacement Therapy.

Background: Malnutrition is common in patients undergoing hemodialysis and is a powerful predictor of morbidity and mortality. This study aimed to investigate the effect of nutritional status on permanent catheter patency in elderly patients aged >75 years of age undergoing dialysis using tunneled dialysis catheters; Methods: Records of 383 patients whose nutritional factors and body cell mass (BCM) were measured simultaneously at the start of dialysis between 14 January 2020 and 30 September 2023, at Chungnam National University Hospital, were retrospectively reviewed. The relationships between permanent catheter patency at 180 days and BCM parameters and clinical parameters were studied using Kaplan-Meier survival curves and multivariate Cox proportional hazards analysis. Results: Age and sexual differences were significant (p ≤ 0.05), and most of the BCM parameters and BCM were not significant (p ≤ 0.05), except for intracellular water. Permanent catheter patency was superior at low controlling nutritional status (CONUT) scores (p < 0.05). After adjustment for covariates, the CONUT score remained an independent factor associated with permanent catheter-patency survival; Conclusions: CONUT scores measured before the start of dialysis are expected to play an important role in predicting the prognosis of permanent catheter-patency survival in patients aged >75 years.

Association between Serum GDF-15 and Cognitive Dysfunction in Hemodialysis Patients.

Cognitive dysfunction is more frequent in end-stage renal disease (ESRD) patients undergoing hemodialysis compared with the healthy population, emphasizing the need for early detection. Interest in serum markers that reflect cognitive function has recently increased. Elevated serum growth differentiation factor 15 (GDF-15) levels are known to be associated with an increased risk of decreased renal function and cognitive dysfunction. This study investigated the relationship between GDF-15 and cognitive dysfunction in hemodialysis patients using a retrospective analysis of 92 individuals aged ≥ 18 years. Cognitive function was assessed using the Korean version of the Mini-Mental Status Examination (K-MMSE), categorizing patients into normal (≥24 points) and cognitive dysfunction (<24 points). As a result, serum GDF-15 concentrations were at significantly higher levels in the cognitive dysfunction group (7500.42 pg/mL, p = 0.001). Logistic regression indicated an increased risk of K-MMSE scores < 24 points when serum GDF-15 exceeded 5408.33 pg/mL. After indoxyl sulfate exposure in HT22 cells, HT22 cells survival was decreased and GDF-15 expression in HT22 cells was increased. Similarly, exposure to indoxyl sulfate in mouse brain tissue resulted in an increased expression of GDF-15. This study highlights the potential of serum GDF-15 as a marker for cognitive dysfunction in hemodialysis patients, offering a valuable screening tool. Serum GDF-15 is related to cognitive dysfunction in hemodialysis patients and may be helpful in screening for cognitive dysfunction in hemodialysis patients.

Omega-3 Fatty Acids Attenuate Renal Fibrosis via AMPK-Mediated Autophagy Flux Activation.

The unilateral ureteral obstruction (UUO) injury model is well-known to mimic human chronic kidney disease, promoting the rapid onset and development of kidney injury. ω3-poly unsaturated fatty acids (PUFAs) have been observed to protect against tissue injury in many disease models. In this study, we assessed the efficacy of ω3-PUFAs in attenuating UUO injury and investigated their mechanism of action. The immortalized human proximal tubular cells human kidney-2 (HK2) were incubated for 72 h with docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) in various concentrations, in the presence or absence of transforming growth factor (TGF)-ß. DHA/EPA reduced the epithelial-mesenchymal transition in the TGF-ß-treated HK2 cells by enhancing autophagy flux and adenosine monophosphate-activated protein kinase (AMPK) phosphorylation. C57BL/6 mice were divided into four groups and treated as follows: sham (no treatment, n = 5), sham + ω3-PUFAs (n = 5), UUO (n = 10), and UUO + ω3-PUFAs (n = 10). Their kidneys and blood were harvested on the seventh day following UUO injury. The kidneys of the ω3-PUFAs-treated UUO mice showed less oxidative stress, inflammation, and fibrosis compared to those of the untreated UUO mice. Greater autophagic flux, higher amounts of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II, Beclin-1, and Atg7, lower amounts of p62, and higher levels of cathepsin D and ATP6E were observed in the kidneys of the omega-3-treated UUO mice compared to those of the control UUO mice. In conclusion, ω3-PUFAs enhanced autophagic activation, leading to a renoprotective response against chronic kidney injury.

ω-3 Polyunsaturated Fatty Acids Improve the Blood-Brain-Barrier Integrity in Contrast-Induced Blood-Brain-Barrier Injury in Uremic Mice.

In patients with chronic kidney disease, the need for examinations using contrast media (CM) increases because of underlying diseases. Although contrast agents can affect brain cells, the blood-brain barrier (BBB) protects against brain-cell damage in vivo. However, uremia can disrupt the BBB, increasing the possibility of contrast-agent-induced brain-cell damage in patients with chronic kidney disease (CKD). ω-3 polyunsaturated fatty acids (PUFAs) have shown protective effects on various neurological disorders, including uremic brain injury. This study examined whether ω-3 PUFAs attenuate damage to the BBB caused by uremia and contrast agents in a uremic mouse model and evaluated its associated mechanisms. C57BL/6 mice (eight weeks old, male) and fat-1 mice (b6 background/eight weeks old, male) were divided into groups according to uremic induction, CM, and ω-3 PUFA administration. Uremia was induced via 24 h ischemia-reperfusion (IR) renal injury. One day after CM treatment, the brain tissue, kidney tissue, and blood were collected. The expression levels of glial fibrillary acidic protein (GFAP), claudin 5, CD31, laminin α4, and laminin α5 increased in ω-3 PUFA + CM-treated uremic mice and the brain of fat-1 + CM-treated uremic mice compared with those in the brains of CM-treated uremic mice. The pro-apoptotic protein expression decreased, whereas the anti-apoptotic proteins increased in ω-3 PUFA + CM-treated uremic mice and fat-1 + CM-treated uremic mice compared with CM-treated uremic mice. In addition, the brain-expression levels of p-JNK, p-P53, and p-P38 decreased in the ω-3 PUFA + CM-treated uremic mice and fat-1 + CM-treated uremic mice compared with those in wild-type uremic mice. Our results confirm that uremic toxin and CM damage the BBB and cause brain-cell death. ω-3 PUFAs play a role in BBB protection caused by CM in uremic mice.

Ratio of Extracellular to Intracellular Water Is Associated with Permanent Catheter Patency Survival in Patients Receiving Maintenance Hemodialysis.

Patients undergoing dialysis through a permanent catheter often experience infection or malfunction. However, few studies have clarified the predictors of permanent catheter patency survival in patients undergoing hemodialysis. We assessed the relationship between the parameters of body composition monitoring (BCM), determined before the initiation of dialysis, and the patency survival of the permanent catheters inserted in 179 patients who commenced hemodialysis between 14 January 2020 and 31 August 2021. The relationships between permanent catheter patency at 6 weeks and BCM parameters, laboratory tests, age, sex, comorbidities, and medications at baseline were studied using Kaplan-Meier survival curves. Permanent catheter patency was observed to be superior at high extracellular-to-intracellular (ECW/ICW) ratio (p < 0.005). After adjustment for covariates, the ECW/ICW ratio remained an independent factor associated with permanent catheter patency survival. When patients with non-patent catheters were subdivided into infection and malfunction groups, and the associations of BCM parameters were evaluated in those groups, the ECW/ICW ratio was not significantly associated with permanent catheter patency survival in the infection group (p = 0.327); instead, a significant association was found for the lean tissue index (p < 0.001). In the malfunction group, the ECW/ICW ratio remained significantly associated with permanent catheter patency survival (p < 0.001).

Leucine-enriched amino acid supplementation and exercise to prevent sarcopenia in patients on hemodialysis: a single-arm pilot study.

Background: Sarcopenia, which is strongly associated with mortality and quality of life, occurs in up to 40% of hemodialysis patients. Here, we investigated the preventive effects of leucine-enriched amino acid supplementation and resistance exercise in non-sarcopenic hemodialysis patients, and characterized the biochemical and immunophenotypic profiles of those who benefited from the intervention. Methods: Twenty-two patients on maintenance hemodialysis at our hospital were enrolled in this single center, prospective, single-arm pilot trial. For the first 12 weeks, the subjects were administered a total of 6 g of leucine per day. Three grams were supplied via capsules, and the remaining three grams were provided via beverages containing macro- and micro- nutrients, such as 10 µg of vitamin D and 290 mg of calcium. The supplements were not provided for the next 12 weeks. Muscle mass, grip strength, and physical performance were measured using the bioimpedance analyzer (BIA), handgrip strength (HGS), and short physical performance battery (SPPB) protocols, respectively, at baseline, 12 weeks, and 24 weeks. In addition, serum biochemistry, immunophenotype of peripheral blood mononuclear cells, and nutritional status was assessed at the three time points. Those who showed 5% or more improvement in parameters were defined as responders, otherwise, as non-responders (ClinicalTrials.gov identification number: NCT04927208). Results: Twenty-one out of twenty-two patients (95.4%) showed improvement in at least one or more parameters among muscle mass, grip strength, and physical performance. After 12 weeks of intervention, skeletal muscle index was increased in 14 patients (63.6%), and grip strength was improved in 7 patients (31.8%). Baseline grip strength lower than 35.0 kg was the strongest predictor of improvement in grip strength (AUC 0.933 from ROC curve). Grip strength showed a significant increase in females than males (7.6 ± 8.2 vs. -1.6 ± 7.2%, p = 0.03), in age over 60 than under 60 (5.3 ± 6.2 vs. -1.4 ± 9.1%, p = 0.04), and in higher (≥95%) than lower (<95%) exercise compliance (6.8 ± 7.7 vs. -3.2 ± 6.4%, p = 0.004). In SPPB study, gait speed and sit-to-stand time was improved in 13 patients (59.1%) and 14 patients (63.6%), respectively. Baseline hemoglobin lower than 10.5 g/dl and hematocrit lower than 30.8% were predictor of improvement in the sit-to-stand time (AUC 0.862 and 0.848, respectively). Serum biochemistry results showed that, compared to non-responders, responders in muscle mass had lower baseline monocyte fraction (8.4 ± 1.9 vs. 6.9 ± 1.1%, p = 0.03), and responders in grip strength had lower baseline total protein (6.7 ± 0.4 vs. 6.4 ± 0.3 g/dL, p = 0.04). Immunophenotypic analysis found that the intervention tended to increase the naïve/memory CD8+ T cell ratio (from 1.2 ± 0.8 to 1.4 ± 1.1, p = 0.07). Conclusion: Leucine-enriched amino acid supplementation and resistance exercise induced significant improvement in muscle mass, strength, and physical function in subpopulation of the non-sarcopenic hemodialysis patients. Those who benefited from the intervention were old-age females with lower baseline grip strength or lower hemoglobin or hematocrit, and who have good exercise compliance. Therefore, we propose that the intervention will help to prevent sarcopenia in selected patients on maintenance hemodialysis.

Risk factors for post-contrast acute kidney injury in patients sequentially administered iodine- and gadolinium-based contrast media on the same visit to the emergency department: a retrospective study.

BACKGROUND: This study compares the incidence of post-contrast acute kidney injury (PC-AKI) in patients who received a single administration of iodine-based contrast medium (ICM) with that in patients who received a sequential administration of ICM and gadolinium- based contrast agents (GBCA) in a single visit to an emergency department (ED) to determine the risk factors for PC-AKI. METHODS: Patients who received one or more contrast media in the ED from 2016 to 2021 were included in this retrospective study. They were divided into the ICM alone and ICM + GBCA groups, and the incidence of PC-AKI was compared between the groups. The risk factors were assessed using a multivariable analysis after propensity score matching (PSM). RESULTS: Overall, 6,318 patients were analyzed, of whom 139 were in the ICM + GBCA group. The incidence of PC-AKI was significantly higher in the ICM + GBCA group than in the ICM alone group (10.9% vs. 27.3%, p < 0.001). In the multivariable analysis, sequential administration was a risk factor for PC-AKI, and single administration was not (adjusted odds ratio [95% confidence interval] in the 1:1, 2:1, and 3:1 PSM cohorts: 2.38 [1.25-4.55], 2.13 [1.26-3.60], and 2.28 [1.39-3.72], respectively). In subgroup analyses of the ICM + GBCA group, osmolality (1.05 [1.01-1.10]) and estimated glomerular filtration rate (eGFR, 0.93 [0.88-0.98]) were associated with PC-AKI. CONCLUSION: Compared with a single administration of ICM alone, sequential administration of ICM and GBCA during a single ED visit might be a risk factor for PC-AKI. Osmolality and eGFR might be associated with PC-AKI after sequential administration.

Ultrasound Renal Score to Predict the Renal Disease Prognosis in Patients with Diabetic Kidney Disease: An Investigative Study.

Renal disease associated with type 2 diabetes mellitus (T2DM) has become the leading cause of chronic kidney disease (CKD). Renal ultrasonography is an imaging examination required in the work-up of renal disease. This study aimed to identify the differences in renal ultrasonographic findings between patients with and without DM, and to evaluate the relationship between renal ultrasound findings and renal prognosis in patients with DM. A total of 252 patients who underwent renal ultrasonography at Chungnam National University Hospital were included. Kidney disease progression was defined as a ≥10% decline in the annual estimated glomerular filtration rate (eGFR), which, in this paper, is referred to as ΔeGFR/year, or the initiation of renal replacement therapy after follow-up. The renal scoring system was evaluated by summing up the following items: the value of renal parenchymal echogenicity (0: normal; 1: mildly increased; and 2: increased) and the shape of the cortical margin (0: normal and 1: irregular; right kidney length/height (RH-0 or 1), mean cortical thickness/renal length/height (CKH-0 or 1), and cortical thickness/parenchymal thickness (CK/PK-0 or 1) based on the median: 0-above median, and 1-below median). Patients with DM had thicker renal PKH than those without, despite having lower eGFRs (0.91 ± 0.15, 0.86 ± 0.14, p = 0.006). In the progression group, the renal scores were significantly higher than those from the non-progression group. In the multivariate logistic regression analysis, the higher renal scores, presence of DM, and younger age were independently predicted for renal disease progression after adjusting for confounding variables, such as the presence of hypertension, serum hemoglobin and albumin levels, and UPCR. In conclusion, patients with high renal scores were significantly associated with renal disease progression. Our results suggest that renal ultrasonography at the time of diagnosis provides useful prognostic information in patients with kidney disease.

Diagnostic and Prognostic Roles of C-Reactive Protein, Procalcitonin, and Presepsin in Acute Kidney Injury Patients Initiating Continuous Renal Replacement Therapy.

For reducing the high mortality rate of severe acute kidney injury (AKI) patients initiating continuous renal replacement therapy (CRRT), diagnosing sepsis and predicting prognosis are essential. However, with reduced renal function, biomarkers for diagnosing sepsis and predicting prognosis are unclear. This study aimed to assess whether C-reactive protein (CRP), procalcitonin, and presepsin could be used to diagnose sepsis and predict mortality in patients with impaired renal function initiating CRRT. This was a single-center, retrospective study involving 127 patients who initiated CRRT. Patients were divided into sepsis and non-sepsis groups according to the SEPSIS-3 criteria. Of the 127 patients, 90 were in the sepsis group and 37 were in the non-sepsis group. Cox regression analysis was performed to determine the association between the biomarkers (CRP, procalcitonin, and presepsin) and survival. CRP and procalcitonin were superior to presepsin for diagnosing sepsis. Presepsin was closely related to the estimated glomerular filtration rate (eGFR) (r = -0.251, p = 0.004). These biomarkers were also evaluated as prognostic markers. Procalcitonin levels ≥3 ng/mL and CRP levels ≥31 mg/L were associated with higher all-cause mortality using Kaplan-Meier curve analysis. (log-rank test p = 0.017 and p = 0.014, respectively). In addition, procalcitonin levels ≥3 ng/mL and CRP levels ≥31 mg/L were associated with higher mortality in univariate Cox proportional hazards model analysis. In conclusion, a higher lactic acid, sequential organ failure assessment score, eGFR, and a lower albumin level have prognostic value to predict mortality in patients with sepsis initiating CRRT. Moreover, among these biomarkers, procalcitonin and CRP are significant factors for predicting the survival of AKI patients with sepsis-initiating CRRT.

Artery-to-Fistula Diameter Ratio as a Predictor of Early Re-Occlusion of Immature Right Radio-Cephalic Arteriovenous Fistula after Primary PTA.

Percutaneous transluminal angioplasty (PTA) is widely performed for arteriovenous fistula (AVF) that fails to mature after initial formation. We observed that some immature AVFs re-occlude earlier than others. We sought to investigate the predictors for early post-intervention failure of immature fistulas after primary PTA. We retrospectively reviewed the records and angiographic images of patients who had immature fistulas and thereby received PTA between 2013 and 2019 at our center. We investigated the short-term post-intervention outcomes of the patients within 90 days post-PTA. Patients who had re-occlusion within the period were defined as the early failure group and the rest as the patent group. We investigated factors associated with early failure. There were 80 eligible patients with 22 brachio-cephalic (BC) and 58 radio-cephalic (RC) AVFs. The median age of the patients was 64 years [range, 38-87]. There were 51 (63%) males and 29 (36%) females. Among the 58 RC AVFs, 10 (17%) patients had early failure. Logistic regression analysis showed that a larger artery to fistula (A/F) diameter ratio was the sole independent predictor of early failure after primary PTA (odd ratio 2.29 [1.023-5.147], p value = 0.044). Although further studies on a larger scale are required to confirm the clinical significance, a larger A/F diameter ratio was a potential predictor of early re-occlusion in immature fistulas after primary PTA.

Urine-Derived Stem Cell-Secreted Klotho Plays a Crucial Role in the HK-2 Fibrosis Model by Inhibiting the TGF-ß Signaling Pathway.

Renal fibrosis is an irreversible and progressive process that causes severe dysfunction in chronic kidney disease (CKD). The progression of CKD stages is highly associated with a gradual reduction in serum Klotho levels. We focused on Klotho protein as a key therapeutic factor against CKD. Urine-derived stem cells (UDSCs) have been identified as a novel stem cell source for kidney regeneration and CKD treatment because of their kidney tissue-specific origin. However, the relationship between UDSCs and Klotho in the kidneys is not yet known. In this study, we discovered that UDSCs were stem cells that expressed Klotho protein more strongly than other mesenchymal stem cells (MSCs). UDSCs also suppressed fibrosis by inhibiting transforming growth factor (TGF)-ß in HK-2 human renal proximal tubule cells in an in vitro model. Klotho siRNA silencing reduced the TGF-inhibiting ability of UDSCs. Here, we suggest an alternative cell source that can overcome the limitations of MSCs through the synergetic effect of the origin specificity of UDSCs and the anti-fibrotic effect of Klotho.

Serum Growth Differentiation Factor-15/Albumin Ratio as a 2-Year Survival Marker of End-Stage Renal Disease Patients Initiating Maintenance Hemodialysis.

It is important to identify risk factors related to mortality in end-stage renal disease (ESRD) patients starting renal replacement therapy. Recently, several studies proposed that growth-differentiation factor-15 (GDF-15) is a possible biomarker for the prognosis of patients on maintenance hemodialysis. Here, we investigated the predictive value of serum GDF-15/Albumin ratio on two-year mortality in ESRD patients initiating maintenance hemodialysis. The study was a single center, retrospective study on ESRD patients starting maintenance hemodialysis with a follow-up of two years. All patients completed laboratory test and bioimpedance spectroscopy prior to the initiation of the first dialysis. The patients were stratified into quartiles according to the quartiles of serum GDF-15/Albumin ratio. Among the 159 patients, the mean age was 61.78 ± 12.52 years and median survival was 20.03 ± 7.73 months. The highest GDF-15/Albumin quartile was significantly more associated with the increased risk of all-cause mortality than other quartiles (unadjusted hazard ratio (HR): 8.468, 95% CI 2.981-24.054, p < 0.001). Older age and a higher overhydration state were associated with GDF-15/Albumin ratio. The ROC analysis confirmed that the ability of the GDF-15/Albumin ratio to predict mortality was superior to GDF-15 or albumin alone. In conclusion, the GDF-15/Albumin ratio measured at the initial maintenance hemodialysis is an independent prognostic marker of two-year mortality in ESRD patients.

Effect of cilostazol on arteriovenous fistula in hemodialysis patients / Efecto del cilostazol en una fístula arteriovenosa en pacientes en hemodiálisis

Background: The maturation and patency of permanent vascular access are critical in patients requiring hemodialysis. Although numerus trials have been attempted to achieve permanently patent vascular access, little have been noticeable. Cilostazol, a phosphodiesterase-3 inhibitor, has been shown to be effective in peripheral arterial disease including vascular injury-induced intimal hyperplasia. We therefore aimed to determine the effect of cilostazol on the patency and maturation of permanent vascular access. Methods: This single-center, retrospective study included 194 patients who underwent arteriovenous fistula surgery to compare vascular complications between the cilostazol (n=107) and control (n=87) groups. Results: The rate of vascular complications was lower in the cilostazol group than in the control group (36.4% vs. 51.7%; p=0.033), including maturation failure (2.8% vs. 11.5%; p=0.016). The rate of reoperation due to vascular injury after hemodialysis initiation following fistula maturation was also significantly lower in the cilostazol group than in the control group (7.5% vs. 28.7%; p<0.001). However, there were no significant differences in the requirement for percutaneous transluminal angioplasty (PTA), rate of PTA, and the interval from arteriovenous fistula surgery to PTA between the cilostazol and control groups. Conclusion: Cilostazol might be beneficial for the maturation of permanent vascular access in patients requiring hemodialysis. (AU)

Antecedentes: La maduración y la permeabilidad del acceso vascular permanente son fundamentales en los pacientes que requieren hemodiálisis. Aunque se han realizado numerosos ensayos para conseguir un acceso vascular permanentemente permeable, pocos han conseguido resultados destacables. El cilostazol, un inhibidor de la fosfodiesterasa 3, ha demostrado ser eficaz en la enfermedad arterial periférica, incluida la hiperplasia intimal inducida por lesiones vasculares. Por lo tanto, nuestro objetivo era determinar el efecto del cilostazol en la permeabilidad y la maduración del acceso vascular permanente. Métodos: Este estudio unicéntrico y retrospectivo incluyó 194 pacientes sometidos a una cirugía de fístula arteriovenosa para comparar las complicaciones vasculares entre los grupos de cilostazol (n=107) y de control (n=87). Resultados: La tasa de complicaciones vasculares fue menor en el grupo de cilostazol que en el grupo de control (36,4% frente a 51,7%; p=0,033), incluido el fracaso de la maduración (2,8% frente a 11,5%; p=0,016). La tasa de reintervención por lesión vascular tras el inicio de la hemodiálisis después de la maduración de la fístula también fue significativamente menor en el grupo de cilostazol que en el grupo de control (7,5% frente a 28,7%; p<0,001). Sin embargo, no hubo diferencias significativas en la necesidad de angioplastia transluminal percutánea (ATP), la tasa de ATP y el intervalo desde la cirugía de la fístula arteriovenosa hasta la ATP entre los grupos de cilostazol y de control. Conclusión: El cilostazol podría ser beneficioso para la maduración del acceso vascular permanente en pacientes que necesitan hemodiálisis. (AU)

Progression to chronic kidney disease according to albumin uria in diabetic nephropathy patients with preserved renal function / Progresión a enfermedad renal crónica según albuminuria en pacientes con nefropatía diabética con función renal preservada

ABSTRACT Background : Albuminuria predicts progression of diabetic nephropathy (DN) but lacks specificity and sensitivity for the diagnosis of chronic kidney disease (CKD) and progressive decline in estimated glomerular filtration rate (eGFR). We evaluated the decline in renal function in patients with DN and analyzed the prognosis of renal function according to the level of albuminuria and the incidence of cardiovascular disease (CVD), cerebrovascular diseases, and peripheral artery disease (PAD) according to the level of albuminuria. Methods: This retrospective study included 331 patients with eGFR >60 mL/min/1.73 m2 and urinary albumin/creatinine (Cr) ratio (ACR) >30 mg/g Cr who were treated at the Chungnam National University Hospital between January 2012 and December 2018. Patients were divided into mildly increased albuminuria, moderately increased albuminuria, and severely increased albuminuria groups according to their urine ACRs of 30-300, 300 900, and >900 mg/g Cr, respectively. Renal outcomes and incidence of CVD, cerebrovascular disease, and PAD were compared among the three groups. Results: More severe albuminuria was associated with higher rates of progression to CKD (p< 0.001) and >50% reduction in eGFR from baseline (p< 0.001). There was a statistically significant difference in the rate of PCI with angina or myocardial infarction (p=0.030). However, cerebrovascular disease and PAD did not significantly differ among the three groups. Conclusión: Among patients with DN who maintained a relatively preserved renal function with an eGFR >60 mL/min/1.73 m2, the rates of renal deterioration and progression to CKD were significantly more frequent in those with more severe albuminuria.

RESUMEN Antecedentes: La albuminuria predice la progresión de la nefropatía diabética (ND) pero carece de especificidad y sensibilidad para el diagnóstico de la enfermedad renal crónica (ERC) y la disminución progresiva en la tasa de filtración glomerular estimada (eGFR). Evaluamos la disminución de la función renal en pacientes con ND y analizamos el pronóstico de la función renal de acuerdo con el nivel de albuminuria y la incidencia de enfermedad cardiovascular (ECV), enfermedades cerebrovasculares y enfermedad de las arterias periféricas (EAP) de acuerdo con el nivel de albuminuria. Material y métodos: Este estudio retrospectivo incluyó a 331 pacientes con eGFR >60 ml/min/1,73 m2 y de albúmina urinaria/creatinina (CR) (ACR) >30 mg/g CR que fueron tratados en el Hospital Universitario Nacional de Chungnam entre enero de 2012 y diciembre de 2018. Los pacientes se dividieron en tres grupos: albuminuria ligeramente aumentada, aumento moderado de albuminuria y aumento severo de albuminuria de acuerdo con sus ACRs de orina de 30-300, 300-900 y >900 mg/g Cr, respectivamente. Los resultados renales e incidencia de ECV, enfermedad cerebrovascular y EAP se compararon entre los tres grupos. Resultados: La albuminuria más severa se asoció con tasas más altas de progresión a ERC (P <0,001) y una reducción >50% en eGFR desde la línea de base (P <0,001). Hubo una diferencia estadísticamente significativa en la tasa de PCI con la angina o el infarto de miocardio (P =0,030). Sin embargo, la enfermedad cerebrovascular y la EAP no difirieron significativamente entre los tres grupos. Conclusión: entre los pacientes con ND que mantuvieron una función renal relativamente conservada con un eGFR >60 ml/ min/1,73 m2, las tasas de deterioro renal y la progresión a la ERC fueron significativamente más frecuentes en aquellos con albuminuria más severa.

Collecting Duct-Specific CR6-Interacting Factor-1-Deletion Aggravates Renal Inflammation and Fibrosis Induced by Unilateral Ureteral Obstruction.

Although inflammation and fibrosis, which are key mechanisms of chronic kidney disease, are associated with mitochondrial damage, little is known about the effects of mitochondrial damage on the collecting duct in renal inflammation and fibrosis. To generate collecting duct-specific mitochondrial injury mouse models, CR6-interacting factor-1 (CRIF1) flox/flox mice were bred with Hoxb7-Cre mice. We evaluated the phenotype of these mice. To evaluate the effects on unilateral ureteral obstruction (UUO)-induced renal injury, we divided the mice into the following four groups: a CRIF1flox/flox (wild-type (WT)) group, a CRIF1flox/flox-Hob7 Cre (CRIF1-KO) group, a WT-UUO group, and a CRIF1-KO UUO group. We evaluated the blood and urine chemistries, inflammatory and fibrosis markers, light microscopy, and electron microscopy of the kidneys. The inhibition of Crif1 mRNA in mIMCD cells reduced oxygen consumption and membrane potential. No significant differences in blood and urine chemistries were observed between WT and CRIF1-KO mice. In UUO mice, monocyte chemoattractant protein-1 and osteopontin expression, number of F4/80 positive cells, transforming growth factor-ß and α-smooth muscle actin staining, and Masson's trichrome staining were significantly higher in the kidneys of CRIF1-KO mice compared with the kidneys of WT mice. In sham mice, urinary 8-hydroxydeoxyguanosine (8-OHDG) was higher in CRIF1-KO mice than in WT mice. Moreover, CRIF1-KO sham mice had increased 8-OHDG-positive cell recruitment compared with WT-sham mice. CRIF1-KO-UUO kidneys had increased recruitment of 8-OHDG-positive cells compared with WT-UUO kidneys. In conclusion, collecting duct-specific mitochondrial injury increased oxidative stress. Oxidative stress associated with mitochondrial damage may aggravate UUO-induced renal injury.

Omega-3 Polyunsaturated Fatty Acid Attenuates Uremia-Induced Brain Damage in Mice.

Although the cause of neurological disease in patients with chronic kidney disease (CKD) has not been completely identified yet, recent papers have identified accumulated uremic toxin as its main cause. Additionally, omega-3 polyunsaturated fatty acid (ω-3 PUFA) plays an important role in maintaining normal nerve function, but its protective effects against uremic toxin is unclear. The objective of this study was to identify brain damage caused by uremic toxicity and determine the protective effects of ω-3 PUFA against uremic toxin. We divided mice into the following groups: wild-type (wt) sham (n = 8), ω-3 PUFA sham (n = 8), Fat-1 sham (n = 8), ischemia-reperfusion (IR) (n = 20), and ω-3 PUFA+IR (n = 20) Fat-1+IR (n = 20). Brain tissue, kidney tissue, and blood were collected three days after the operation of mice (sham and IR operation). This study showed that Ki67 and neuronal nuclei (NeuN) decreased in the brain of uremic mice as compared to wt mice brain, but increased in the ω-3 PUFA-treated uremic mice and the brain of uremic Fat-1 mice as compared to the brain of uremic mice. The pro-apoptotic protein expressions were increased, whereas anti-apoptotic protein expression decreased in the brain of uremic mice as compared to wt mice brain. However, apoptotic protein expression decreased in the ω-3 PUFA-treated uremic mice and the brain of uremic Fat-1 mice as compared to the brain of uremic mice. Furthermore, the brain of ω-3 PUFA-treated uremic mice and uremic Fat-1 mice showed increased expression of p-PI3K, p-PDK1, and p-Akt as compared to the brain of uremic mice. We confirm that uremic toxin damages the brain and causes cell death. In these injuries, ω-3 PUFA plays an important role in neuroprotection through PI(3)K-Akt signaling.

Body Fat Plays an Important Role in of Bioimpedance Spectroscopy-Based Dry Weight Measurement Error for Patients with Hemodialysis.

Accurate dry weight (DW) estimation is important for hemodialysis patients. Although bioimpedance spectroscopy (BIS) is commonly used to measure DW, the BIS-based DW frequently differs from the clinical DW. We analyzed the characteristics of patients whose BIS-based DWs were over- and underestimated. In this retrospective cohort study, we evaluated 1555 patients undergoing maintenance hemodialysis in Chungnam National University Hospital. The gap (DWCP-BIS) was calculated by comparing the BIS and clinical DWs. We analyzed the clinical characteristics of patients with positive (n = 835) and negative (n = 720) gaps. Compared with other patients, the DWCP-BIS-positive group had higher extracellular water (ECW) level and extracellular/intracellular water index (E/I) and had lower weight, body mass index (BMI), lean tissue index (LTI), fat tissue index (FTI), fat mass (FAT), and adipose tissue mass (ATM). The DWCP-BIS-negative group exhibited elevated BMI, FTI, FAT, and ATM; however, it had lower height, ECW, and E/I. Linear regression analysis revealed that FAT significantly predicted DWCP accuracy. The clinical DW of patients with a low fat mass tended to be underestimated, while the clinical DW of patients with comparatively large fat reserves tended to be overestimated. These characteristics will aid in the reduction of BIS-based DW errors.

Confirming Genetic Abnormalities of Hypokalemic Periodic Paralysis Using Next-Generation Sequencing: A Case Report and Literature Review.

Hypokalemic periodic paralysis (hypoPP) is a disorder characterized by episodic, short-lived, and hypo-reflexive skeletal muscle weakness. HypoPP is a rare disease caused by genetic mutations related to expression of sodium or calcium ion channels. Most mutations are associated with autosomal dominant inheritance, but some are found in patients with no relevant family history. A 28-year-old man who visited the emergency room for paralytic attack was assessed in this study. He exhibited motor weakness in four limbs. There was no previous medical history or family history. The initial electrocardiogram showed a flat T wave and QT prolongation. His blood test was delayed, and sudden hypotension and bradycardia were observed. The blood test showed severe hypokalemia. After correcting hypokalemia, his muscle paralysis recovered without any neurological deficits. The patient's thyroid function and long exercise test results were normal. However, because of the history of high carbohydrate diet and exercise, hypoPP was suspected. Hence, next-generation sequencing (NGS) was performed, and a mutation of Arg669His was noted in the SCN4A gene. Although hypoPP is a rare disease, it can be suspected in patients with hypokalemic paralysis, and iden tification of this condition is important for preventing further attacks and improving patient outcomes. Diagnosing hypoPP through targeted NGS is a cost-effective and useful method.