Medium cut-off dialyzer improves reduction ratios of large middle molecules associated with vascular calcification.

Background: We aimed to investigate the change in the large middle molecule (>15 kDa) removal rate, which is associated with vascular calcification, when using a medium cut-off (MCO) dialyzer compared to a high-flux (HF) dialyzer. Methods: Twenty patients with clinically stable maintenance hemodialysis were investigated over a 15-week study period. Dialyzer efficacies were evaluated during the last midweek hemodialysis treatment for each consecutive dialyzer membrane use: 1st HF, MCO, and 2nd HF dialyzer; 5 weeks each period. Changes in α1-microglobulin (33 kDa) during a dialysis session were analyzed to assess the efficacy of the MCO dialyzer as a reference. The levels and reduction ratios of fibroblast growth factor 23 (FGF23, 32 kDa), osteoprotegerin (OPG, 60 kDa), and sclerostin (22 kDa) were analyzed. Large middle molecules were measured using an enzyme-linked immunosorbent assay. Results: Serum hemoglobin, phosphorus, and corrected calcium levels were not significantly different for each dialyzer period. Total protein and albumin values during the MCO dialyzer period did not decrease compared with the HF dialyzer period. The reduction ratio of α1-microglobulin was significantly higher in the MCO dialyzer than in the HF dialyzer (p < 0.001). The reduction ratios of FGF23 (p < 0.001), OPG (p < 0.001), and sclerostin (p < 0.001) were significantly higher in the MCO dialyzer than those in the HF dialyzer. Conclusion: The reduction rate of large middle molecules related to vascular calcification, such as FGF23, OPG, and sclerostin, was significantly higher when using the MCO dialyzer than the HF dialyzer.

Incomplete distal renal tubular acidosis uncovered during pregnancy: A case report.

BACKGROUND: Renal tubular acidosis (RTA) is a renal cause of non-anion-gap metabolic acidosis characterized by low urinary ammonia excretion. This condition has a low prevalence, and various congenital and acquired etiologies. To date, only a few cases of idiopathic RTA uncovered during pregnancy have been reported. CASE SUMMARY: A previously healthy 32-year-old Korean woman at 30 wk of gestation was admitted to Pusan National University Hospital with preterm labor. At admission, the patient presented with hypokalemia, non-anion-gap metabolic acidosis, and nephrocalcinosis. Distal RTA was diagnosed based on laboratory blood and urine findings and imaging examinations. Various tests, including next-generation gene sequencing panels for nephropathy, were performed to determine the etiology of the disease, which indicated that it was idiopathic. The patient received sodium bicarbonate and potassium chloride supplementation. After 3 wk, she delivered a baby who was subsequently diagnosed with corpus callosum agenesis and colpocephaly. During regular follow-ups for 6 mo postpartum, her hypokalemia and metabolic acidosis were gradually resolved, and medications eventually discontinued. CONCLUSION: Herein we describe a case of idiopathic distal RTA discovered during pregnancy. Hypokalemia and metabolic acidosis resolved spontaneously after delivery.

Serum and urine metabolomic biomarkers for predicting prognosis in patients with immunoglobulin A nephropathy.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most prevalent form of glomerulonephritis worldwide. Prediction of disease progression in IgAN can help to provide individualized treatment based on accurate risk stratification. METHODS: We performed proton nuclear magnetic resonance-based metabolomics analyses of serum and urine samples from healthy controls, non-progressor (NP), and progressor (P) groups to identify metabolic profiles of IgAN disease progression. Metabolites that were significantly different between the NP and P groups were selected for pathway analysis. Subsequently, we analyzed multivariate area under the receiver operating characteristic (ROC) curves to evaluate the predictive power of metabolites associated with IgAN progression. RESULTS: We observed several distinct metabolic fingerprints of the P group involving the following metabolic pathways: glycolipid metabolism; valine, leucine, and isoleucine biosynthesis; aminoacyl-transfer RNA biosynthesis; glycine, serine, and threonine metabolism; and glyoxylate and dicarboxylate metabolism. In multivariate ROC analyses, the combinations of serum glycerol, threonine, and proteinuria (area under the curve [AUC], 0.923; 95% confidence interval [CI], 0.667-1.000) and of urinary leucine, valine, and proteinuria (AUC, 0.912; 95% CI, 0.667-1.000) showed the highest discriminatory ability to predict IgAN disease progression. CONCLUSION: This study identified serum and urine metabolites profiles that can aid in the identification of progressive IgAN and proposed perturbed metabolic pathways associated with the identified metabolites.

Predicting outcomes of continuous renal replacement therapy using body composition monitoring: a deep-learning approach.

Fluid balance is a critical prognostic factor for patients with severe acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT). This study evaluated whether repeated fluid balance monitoring could improve prognosis in this clinical population. This was a multicenter retrospective study that included 784 patients (mean age, 67.8 years; males, 66.4%) with severe AKI requiring CRRT during 2017-2019 who were treated in eight tertiary hospitals in Korea. Sequential changes in total body water were compared between patients who died (event group) and those who survived (control group) using mixed-effects linear regression analyses. The performance of various machine learning methods, including recurrent neural networks, was compared to that of existing prognostic clinical scores. After adjusting for confounding factors, a marginal benefit of fluid balance was identified for the control group compared to that for the event group (p = 0.074). The deep-learning model using a recurrent neural network with an autoencoder and including fluid balance monitoring provided the best differentiation between the groups (area under the curve, 0.793) compared to 0.604 and 0.606 for SOFA and APACHE II scores, respectively. Our prognostic, deep-learning model underlines the importance of fluid balance monitoring for prognosis assessment among patients receiving CRRT.

Akt1 is involved in renal fibrosis and tubular apoptosis in a murine model of acute kidney injury-to-chronic kidney disease transition.

Maladaptive repair after acute kidney injury (AKI) can predispose patients to chronic kidney disease (CKD). However, the molecular mechanism underlying the AKI-to-CKD transition remains unclear. The Akt signaling pathway has been reported to be involved in the pathological processes of both AKI and CKD. In this study, we investigated the role of Akt1 in a murine model of the AKI-to-CKD transition. Wild-type (WT) and Akt1-/- mice were subjected to unilateral ischemia-reperfusion injury (UIRI), with their kidneys harvested after two days and two, four, and six weeks after UIRI. The dynamic changes in tubulointerstitial fibrosis, markers of tubular epithelial-mesenchymal transition (EMT), and tubular apoptosis were investigated. Akt1 of the three Akt isoforms was activated during the AKI-to-CKD transition. After UIRI, tubulointerstitial fibrosis and tubular EMT were significantly increased in WT mice, but were attenuated in Akt1-/- mice. The expression of the transforming growth factor (TGF)-ß1/Smad was increased in both WT and Akt1-/- mice, but was not different between the two groups. The levels of phosphorylated glycogen synthase kinase (GSK)-3ß, Snail, and ß-catenin in the Akt1-/- mice were lower than those in the WT mice. The number of apoptotic tubular cells and the expression of cleaved caspase-3/Bax were both lower in Akt1-/- mice than in WT mice. Genetic deletion of Akt1 was associated with attenuation of tubulointerstitial fibrosis, tubular EMT, and tubular apoptosis during the AKI-to-CKD transition. These findings were associated with TGF-ß1/Akt1/GSK-3ß/(Snail and ß-catenin) signaling independent of TGF-ß1/Smad signaling. Thus, Akt1 signaling could serve as a potential therapeutic target for inhibiting the AKI-to-CKD transition.

Effect of fluid overload on survival in patients with sepsis-induced acute kidney injury receiving continuous renal replacement therapy.

The association between fluid overload and survival has not been well elucidated in critically ill patients with sepsis-induced acute kidney injury (SIAKI) receiving continuous renal replacement therapy (CRRT). We investigated the optimal cutoff value of fluid overload for predicting mortality and whether minimizing fluid overload through CRRT is associated with a survival benefit in these patients. We examined 543 patients with SIAKI who received CRRT in our intensive care unit. The degree of cumulative fluid overload in relation to body weight was expressed as the percentage fluid overload (%FO). %FO was further subdivided into %FO from AKI diagnosis to CRRT initiation (%FOpreCRRT) and total fluid overload (%FOtotal). The best cutoff value of fluid overload for predicting the 28-day mortality was %FOpreCRRT > 4.6% and %FOtotal > 9.6%. Multivariable analysis demonstrated that patients with %FOpreCRRT > 4.6% and %FOtotal > 9.6% were 1.9 times and 3.37 times more likely to die than those with %FOpreCRRT ≤ 4.6% and %FOtotal ≤ 9.6%. The 28-day mortality was the highest in patients with %FOpreCRRT > 4.6% and %FOtotal > 9.6% (84.7%), followed by those with %FOpreCRRT ≤ 4.6% and %FOtotal > 9.6% (65.0%), %FOpreCRRT > 4.6% and %FOtotal ≤ 9.6% (43.6%), and %FOpreCRRT ≤ 4.6% and %FOtotal ≤ 9.6% (22%). This study demonstrated that fluid overload was independently associated with the 28-day mortality in critically ill patients with SIAKI. Future prospective studies are needed to determine whether minimizing fluid overload using CRRT improves the survival of these patients.

Rapid decline in kidney function is associated with rapid deterioration of health-related quality of life in chronic kidney disease.

This study aimed to evaluate changes in health-related quality of life (HRQOL) in patients with chronic kidney disease (CKD) according to decline in kidney function. HRQOL was assessed using the Short Form-36 questionnaire composed of a physical component summary (PCS) and mental component summary (MCS). Rapid decline in kidney function was defined as a decline in the estimated glomerular filtration rate (eGFR) of > 3 mL/min/1.73 m2/year. Rapid deterioration of HRQOL was defined a change in the HRQOL value greater than the median. Among 970 patients, 360 (37.1%) were in the rapid kidney function decline group. In 720 patients who were 1:1 propensity score-matched, the baseline eGFR was not significantly different between the non-rapid and rapid kidney function decline groups. Compared with the baseline PCS score, the 5-year PCS score decreased in the non-rapid and rapid kidney function decline groups. The 5-year MCS score significantly decreased in the rapid kidney function decline group alone. Rapid decline in kidney function was significantly associated with rapid deterioration of the PCS (odds ratio [OR]: 1.48; 95% confidence interval [CI]: 1.07-2.05; P = 0.018) and MCS (OR: 1.89; 95% CI 1.36-2.62; P < 0.001) scores. Rapid decline in kidney function was associated with rapid deterioration of HRQOL in patients with CKD.

Hospital mortality and prognostic factors in critically ill patients with acute kidney injury and cancer undergoing continuous renal replacement therapy.

BACKGROUND: Whether continuous renal replacement therapy (CRRT) should be applied to critically ill patients with both acute kidney injury (AKI) and cancer remains controversial because of poor expected outcomes. The present study determined prognostic factors for all-cause in-hospital mortality in patients with AKI and cancer undergoing CRRT. METHODS: We included 471 patients with AKI and cancer who underwent CRRT at the intensive care unit of a Korean tertiary hospital from 2013 to 2020, and classified them by malignancy type. The primary outcomes were 28-day all-cause mortality rate and prognostic factors for in-hospital mortality. The secondary outcome was renal replacement therapy (RRT) dependency at hospital discharge. RESULTS: The 28-day mortality rates were 58.8% and 82% in the solid and hematologic malignancy groups, respectively. Body mass index (BMI), presence of oliguria, Sequential Organ Failure Assessment (SOFA) score, and albumin level were common predictors of 28-day mortality in the solid and hematologic malignancy groups. A high heart rate and the presence of severe acidosis were prognostic factors only in the solid malignancy group. Among the survivors, the proportion with RRT dependency was 25.0% and 33.3% in the solid and hematologic malignancy groups, respectively. CONCLUSION: The 28-day mortality rate of cancer patients with AKI undergoing CRRT was high in both the solid and hematologic malignancy groups. BMI, presence of oliguria, SOFA score, and albumin level were common predictors of 28-day mortality in the solid and hematologic malignancy groups, but a high heart rate and severe acidosis were prognostic factors only in the solid malignancy group.

Maintenance of the critical care system during the pandemic in non-COVID-19 patients requiring continuous renal replacement therapy: a single center experience.

BACKGROUND: During the COVID-19 pandemic, maintenance of essential healthcare systems became very challenging. We describe the triage system of our institute, and assess the quality of care provided to critically ill non-COVID-19 patients requiring continuous renal replacement therapy (CRRT) during the pandemic. METHODS: We introduced an emergency triage pathway early in the pandemic. We retrospectively reviewed the medical records of patients who received CRRT in our hospital from January 2016 to March 2021. We excluded end-stage kidney disease patients on maintenance dialysis. Patients were stratified as medical and surgical patients. The time from hospital arrival to intensive care unit (ICU) admission, the time from hospital arrival to intervention/operation, and the in-hospital mortality rate were compared before (January 2016 to December 2019) and during (January 2021 to March 2021) the pandemic. RESULTS: The mean number of critically ill patients who received CRRT annually in the surgical department significantly decreased during the pandemic in (2016-2019: 76.5 ± 3.1; 2020: 56; p < 0.010). Age, sex, and the severity of disease at admission did not change, whereas the proportions of medical patients with diabetes (before: 44.4%; after: 56.5; p < 0.005) and cancer (before: 19.4%; after: 32.3%; p < 0.001) increased during the pandemic. The time from hospital arrival to ICU admission and the time from hospital arrival to intervention/operation did not change. During the pandemic, 59.6% of surgical patients received interventions/operations within 6 hours of hospital arrival. In Cox's proportional hazard modeling, the hazard ratio associated with the pandemic was 1.002 (0.778-1.292) for medical patients and 1.178 (0.783-1.772) for surgical patients. CONCLUSION: Our triage system maintained the care required by critically ill non-COVID-19 patients undergoing CRRT at our institution.

Worsening or improving hypoalbuminemia during continuous renal replacement therapy is predictive of patient outcome: a single-center retrospective study.

BACKGROUND: Hypoalbuminemia at the initiation of continuous renal replacement therapy (CRRT) is a risk factor for poor patient outcomes. However, it is unknown whether the patterns of changes in serum albumin levels during CRRT can be used to predict patient outcomes. METHODS: This retrospective study analyzed data that had been consecutively collected from January 2016 to December 2020 at the Third Affiliated Hospital. We included patients with acute kidney injury who received CRRT for ≥ 72 h. We divided the patients into four groups based on their serum albumin levels (albumin ≥ 3.0 g/dL or < 3.0 g/dL) at the initiation and termination of CRRT. RESULTS: The 793 patients in this study were categorized into the following albumin groups: persistently low, 299 patients (37.7%); increasing, 85 patients (10.4%); decreasing, 195 patients (24.6%); and persistently high, 214 patients (27.1%). In-hospital mortality rates were highest in the persistently low and decreasing groups, followed by the increasing and persistently high groups. The hazard ratio for in-hospital mortality was 0.481 (0.340-0.680) in the increasing group compared to the persistently low group; it was 1.911 (1.394-2.620) in the decreasing group compared to the persistently high group. The length of ICU stay was 3.55 days longer in the persistently low group than in the persistently high group. CONCLUSIONS: Serum albumin levels changed during CRRT, and monitoring of patterns of change in serum albumin levels is useful for predicting in-hospital mortality and the length of ICU stay.

1,25-dihydroxyvitamin D deficiency is independently associated with cardiac valve calcification in patients with chronic kidney disease.

Cardiac valve calcification is highly prevalent in patients with chronic kidney disease (CKD). Low vitamin D levels are associated with vascular calcification in CKD. However, the association between vitamin D levels and cardiac valve calcification is unknown. A total of 513 patients with pre-dialysis CKD were included in this cross-sectional study. Aortic valve calcification (AVC) and mitral valve calcification (MVC) were assessed using two-dimensional echocardiography. The associations between AVC and MVC and baseline variables were investigated using logistic regression analyses. In multivariable analysis, serum 1,25(OH)2D level was independently associated with AVC (odds ratio [OR], 0.87; P < 0.001) and MVC (OR, 0.92; P < 0.001). Additionally, age, diabetes, coronary heart disease, calcium × phosphate product, and intact parathyroid hormone levels were independently associated with AVC and MVC. Systolic blood pressure was independently associated with AVC. A receiver-operating characteristic (ROC) curve analysis showed that the best cutoff values of serum 1,25(OH)2D levels for predicting AVC and MVC were ≤ 12.5 and ≤ 11.9 pg/dl, respectively. Serum 1,25(OH)2D deficiency is independently associated with AVC and MVC in patients with CKD, suggesting that serum 1,25(OH)2D level may be a potential biomarker of AVC and MVC in these patients.

Dialysis unit blood pressure two hours after hemodialysis is useful for predicting home blood pressure and ambulatory blood pressure in maintenance hemodialysis patients.

This study aimed to determine which BP measurement obtained in the HD unit correlated best with home BP and ambulatory BP monitoring (ABPM). We retrospectively analyzed data from 40 patients that received maintenance HD who had available home BP and ABPM data. Dialysis unit BPs were the averages of pre-, 2hr- (2 h after starting HD), and post-HD BP during a 9-month study. Home BP was defined as the average of morning and evening home BPs. Dialysis unit BP and home BP were compared over the 9-month study period. ABPM was performed once for 24 h in the absence of dialysis during the final 2 weeks of the study period and was compared to the 2-week dialysis unit BP and home BP. There was a significant difference between dialysis unit systolic blood pressure (SBP) and home SBP over the 9-month period. No significant difference was observed between the 2hr-HD SBP and home SBP. When analyzing 2 weeks of dialysis unit BP and home BP, including ABPM, SBPs were significantly different (dialysis unit BP > home BP > ABPM; P = 0.009). Consistent with the 9-month study period, no significant difference was observed between 2hr-HD SBP and home SBP (P = 0.809). The difference between 2hr-HD SBP and ambulatory SBP was not significant (P = 0.113). In conclusion, the 2hr-HD SBP might be useful for predicting home BP and ABPM in HD patients.

Clinical features and outcomes of elderly patients with antineutrophil cytoplasmic antibody-positive vasculitis: a single-center retrospective study.

BACKGROUND: We aimed to investigate the clinical characteristics and outcomes of patients aged ≥65 years with antineutrophil cytoplasmic autoantibody (ANCA)-positive ANCA-associated vasculitis (AAV) in Korea. METHODS: Seventy patients diagnosed with ANCA-positive AAV from 2006 to 2019 at a single center were analyzed and categorized into younger (aged <65 years) or elderly (aged ≥65 years) groups. Initial induction treatments were investigated according to age group. All-cause mortality and kidney outcomes were evaluated. RESULTS: After categorization by age, 34 (48.6%) and 36 patients (51.4%) were in the younger and elderly groups, respectively. In the elderly group, more patients were treated with oral cyclophosphamide (CYC) (30.6%) than with intravenous CYC (19.4%). During a median follow-up of 14.6 months (range, 3.0-53.1 months), 13 patients died (elderly group: 11 patients, 84.6%). In the elderly group, older age (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.09-1.90; p = 0.01), lower hemoglobin (HR, 0.21; 95% CI, 0.08-0.60; p = 0.003), and higher serum creatinine level (HR 14.17; 95% CI, 1.29-155.84; p = 0.03) were significant risk factors for allcause mortality after adjustment. Oral CYC + steroid treatment was associated with decreased all-cause mortality compared to untreated induction immunosuppressants (HR, 0.01; 95% CI, 0.001-0.47; p = 0.02). Kidney failure or kidney recovery outcomes were not significantly different between the younger and elderly groups. CONCLUSION: Patients aged ≥65 years had higher mortality rates than younger patients, and mortality was associated with older age, lower hemoglobin, higher serum creatinine level, and nontreatment compared to oral CYC + steroids.

Immunoglobulin A nephropathy in a patient with neurofibromatosis type 1: A case report and literature review.

RATIONALE: Neurofibromatosis type 1 (NF-1) is an autosomal-dominant neurocutaneous disorder that affects the skin, bones, and nervous system. The most common manifestation of kidney involvement is renal artery stenosis; glomerulonephritis is extremely rare. In this case report, we present a patient with NF-1 and immunoglobulin A nephropathy (IgAN). PATIENT CONCERNS: A 51-year-old Korean man previously diagnosed with NF-1 presented with persistent proteinuria and hematuria identified during a routine medical check-up. He had no history of hypertension or diabetes, and denied a history of alcohol use or smoking. DIAGNOSIS: The contrast-enhanced computed tomography scan revealed normal-sized kidneys and no evidence of renal artery stenosis. On the day of the kidney biopsy, laboratory tests showed a serum creatinine level of 1.1 mg/dL, urine protein/creatinine ratio of 1.3 g/g, and urine red blood cell count of >10 to 15/HPF. The kidney biopsy sample revealed IgAN grade III, according to Lee glomerular grading system. INTERVENTION: The patient was advised to take 4 mg of perindopril. OUTCOME: Three months after the treatment, the urine protein/creatinine ratio decreased to 0.6 g/g, with no change in the serum creatinine level (1.03 mg/dL). LESSONS: A genetic link between NF-1 and IgAN or other glomerular diseases is not established. However, activation of the mTOR pathway may explain this association.

Pembrolizumab-induced focal segmental glomerulosclerosis: A case report.

RATIONALE: Focal segmental glomerulosclerosis (FSGS) is the most common primary glomerular disorder that leads to end-stage kidney disease. Pembrolizumab, an immune checkpoint inhibitor, is an anti-programmed death 1 (PD-1) immunoglobulin G4 antibody approved for the treatment of advanced melanoma and can cause various renal immune-related adverse events (AEs), including acute kidney injury. Several cases of anti PD-1 therapy-induced glomerulonephritis have been reported so far, but FSGS has seldom been reported. PATIENT CONCERNS: 46-year old woman presented to our hospital with generalized edema. DIAGNOSES: Laboratory examination revealed features of nephrotic syndrome, and kidney biopsy confirmed FSGS. After other etiological factors of secondary FSGS were ruled out, she was diagnosed with FSGS caused by pembrolizumab. INTERVENTIONS: She did not resume treatment with pembrolizumab and was treated with irbesartan and furosemide according to the American Society of Clinical Oncology Practice guidelines. OUTCOMES: After 2 months, the features of nephrotic syndrome resolved. LESSONS: This case provides valuable insight into the etiology of FSGS that can occur as a renal immune-related AE of PD-1 inhibitor therapy. Therefore, patients should undergo evaluation for renal function and urinalysis at baseline and after treatment. If patients treated with PD-1 inhibitors present with renal injury and/or unexplained proteinuria >1 g/day, we would recommend a kidney biopsy to determine the underlying cause and establish an appropriate therapeutic plan.

Effects of blood urea nitrogen independent of the estimated glomerular filtration rate on the development of anemia in non-dialysis chronic kidney disease: The results of the KNOW-CKD study.

BACKGROUND: Anemia is a common complication of chronic kidney disease (CKD). Blood urea nitrogen (BUN) in CKD represents nitrogenous uremic toxin accumulation which could be involved in anemia of CKD. We investigated the effects of BUN independent of estimated glomerular filtration rate (eGFR) on anemia in non-dialysis CKD (NDCKD). METHODS: This prospective study included 2,196 subjects enrolled in the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD) cohort with BUN and hemoglobin level data. Initially, we investigated the association between BUN and hemoglobin level. To examine the impact of baseline BUN on the incident anemia, a longitudinal study was performed on 1,169 patients without anemia at study enrollment. BUN residuals were obtained from the fitted curve between BUN and eGFR. Anemia was defined as a hemoglobin level of <13.0 g/dL for men and <12.0 g/dL for women. RESULTS: BUN residuals were not related to eGFR but to daily protein intake (DPI), while BUN was related to both eGFR and DPI. BUN was inversely associated with hemoglobin level (ß -0.03; 95% confidence interval [CI] -0.04, -0.03; P <0.001) in the multivariable linear regression analysis adjusted for multiple confounders including eGFR, and BUN residual used instead of BUN was also inversely associated with hemoglobin level (ß -0.03; 95% CI -0.04, -0.02; P <0.001). Among the 1,169 subjects without anemia at baseline, 414 (35.4%) subjects newly developed anemia during the follow-up period of 37.5 ± 22.1 months. In the multivariable Cox regression analysis with adjustment, both high BUN level (Hazard ratio [HR] 1.02; 95% CI 1.01, 1.04; P = 0.002) and BUN residual used instead of BUN (HR 1.02; 95% CI 1.00, 1.04; P = 0.031) increased the risk of anemia development. Moreover, BUN, rather than eGFR, increased the risk of anemia development in patients with CKD stage 3 in the multivariable Cox regression. CONCLUSION: Higher BUN levels derived from inappropriately high protein intake relative to renal function were associated with low hemoglobin levels and the increased risk of anemia independent of eGFR in NDCKD patients.

Clinical outcomes and prognostic factors of mortality in liver cirrhosis patients on continuous renal replacement therapy in two tertiary hospitals in Korea.

BACKGROUND: Data on liver cirrhosis (LC) patients undergoing continuous renal replacement therapy (CRRT) are lacking despite of the dismal prognosis. We therefore evaluated clinical characteristics and predictive factors related to mortality in LC patients undergoing CRRT. METHODS: We performed a retrospective observational study at two tertiary hospitals in Korea. A total of 229 LC patients who underwent CRRT were analyzed. Patients were classified into survivor and non-survivor groups. We used multivariable Cox regression analyses to identify predictive factors of in-hospital mortality. RESULTS: During a median follow-up of 5 days (interquartile range, 1-19 days), in-hospital mortality rate was 66.4%. In multivariable analysis, the Acute Physiology and Chronic Health Evaluation II (APACHE II) score (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.01-1.06; p = 0.02), Model for End-Stage Liver Disease (MELD) score (HR, 1.08; 95% CI, 1.04-1.11; p <0.001), and delivered CRRT dose (HR, 0.95; 95% CI, 0.92-0.98; p = 0.002) were significant risk factors for in-hospital mortality. Patients with a CRRT delivered dose < 25 mL/kg/hr had a higher mortality rate than those with a delivered dose > 35 mL/kg/hr (HR, 3.13; 95% CI, 1.62-6.05; p = 0.001). Subgroup analysis revealed that a CRRT delivered dose < 25 mL/kg/hr was a significant risk factor for in-hospital mortality among LC patients with a MELD score ≥ 30. CONCLUSION: High APACHE II score, high MELD score, and low delivered CRRT dose were significant risk factors for in-hospital mortality. CRRT delivered dose impacted mortality significantly, especially in patients with a MELD score ≥ 30.

Effect of Phoxilium on prognostic predictors in patients undergoing continuous venovenous hemodiafiltration.

BACKGROUND: Phosphorus-containing dialysis solution is used to prevent hypophosphatemia in patients undergoing continuous venovenous hemodiafiltration (CVVHDF). This study evaluated the effect of phosphorus-containing dialysis solution on mortality in patients undergoing CVVHDF based on changes in phosphorus and red cell distribution width-coefficient of variation (RDW-CV) levels. METHODS: We included 272 patients with acute kidney injury (AKI) who underwent CVVHDF at the medical intensive care unit from 2017 to 2019 and classified them according to Phoxilium (Baxter Healthcare Ltd.), as a phosphorus-containing dialysis solution, use within 48 hours after CVVHDF initiation. Clinical data were collected at baseline and 48 hours after CVVHDF initiation. The primary outcome was all-cause mortality during the follow-up period. RESULTS: The non-Phoxilium (NP) group had higher phosphorus and lower RDW-CV levels than the Phoxilium (P) group (phosphorus, 7.3 ± 4.3 vs. 5.0 ± 2.8 mg/dL; RDW-CV, 14.6 ± 1.9 vs. 15.7 ± 2.6%; all p < 0.001). In the multivariable Cox proportional hazard regression of the NP group, an increase in phosphorus and RDW-CV at 48 hours of CVVHDF was associated with mortality (delta phosphorus: median, >0 mg/dL vs. <-2.0 mg/dL; hazard ratio [HR], 8.62; 95% confidence interval [CI], 2.10-35.32; p = 0.003/delta RDW-CV: median, >0% vs. <-0.2%; HR, 4.34; 95% CI, 1.49-13.18; p = 0.008). Meanwhile, in the P group, an increase in delta RDW-CV was associated with mortality (delta RDW-CV: >0% vs. >-0.2% and <0%; HR, 2.65; 95% CI, 1.12-6.24; p = 0.03), while an increase in delta phosphorus was not. CONCLUSION: In patients with AKI undergoing CVVHDF, the risk factors for all-cause mortality differed according to the initial phosphorus levels and use of Phoxilium.

Metabolic Acidosis Is an Independent Risk Factor of Renal Progression in Korean Chronic Kidney Disease Patients: The KNOW-CKD Study Results.

Background: We aimed to evaluate serum bicarbonate as a risk factor for renal progression, cardiovascular events, and mortality in Korean CKD patients. Methods: We analyzed 1,808 participants from a Korean CKD cohort whose serum bicarbonate levels were measured at enrollment. Serum bicarbonate levels were categorized as low, lower normal, higher normal, and high (total carbon dioxide <22, 22-26, 26.1-29.9, and ≥30 mmol/L, respectively) groups. Metabolic acidosis was defined as a serum bicarbonate level <22 mmol/L. The primary outcome was renal events defined as doubling of serum creatinine, 50% reduction of eGFR from the baseline values, or development of end-stage kidney disease. The secondary outcome consisted of cardiovascular events and death. In addition, patients whose eGFR values were measured more than three times during the follow-up period were analyzed for eGFR decline. The rapid decline in eGFR was defined as lower than the median value of the eGFR slope. Results: The mean serum bicarbonate level was 25.7 ± 3.7 mmol/L and 240 (13.2%) patients had metabolic acidosis. During the follow-up period of 55.2 ± 24.1 months, 545 (30.9%) patients developed renal events and 187 (10.6%) patients developed a composite of cardiovascular events and death. After adjustment, the low serum bicarbonate group experienced 1.27 times more renal events than the lower normal bicarbonate group [hazard ratio (HR): 1.27; 95% CI: 1.01-1.60, P = 0.043]. There was no significant association between the bicarbonate groups and the composite outcome of cardiovascular events and death. The low bicarbonate group showed a significantly rapid decline in eGFR [odds ratio (OR): 2.12; 95% CI: 1.39-3.22, P < 0.001] compared to the lower normal bicarbonate group. Conclusions: Metabolic acidosis was significantly associated with increased renal events and a rapid decline in renal function in Korean predialysis CKD patients.

Comparative analysis of therapeutic effects between medium cut-off and high flux dialyzers using metabolomics and proteomics: exploratory, prospective study in hemodialysis.

In this single-center prospective study of 20 patients receiving maintenance hemodialysis (HD), we compared the therapeutic effects of medium cut-off (MCO) and high flux (HF) dialyzers using metabolomics and proteomics. A consecutive dialyzer membrane was used for 15-week study periods: 1st HF dialyzer, MCO dialyzer, 2nd HF dialyzer, for 5 weeks respectively. 1H-nuclear magnetic resonance was used to identify the metabolites and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was used to identify proteins. To compare the effects of the HF and MCO dialyzers, orthogonal projection to latent structure discriminant analysis (OPLS-DA) was performed. OPLS-DA showed that metabolite characteristics could be significantly classified by 1st HF and MCO dialyzers. The Pre-HD metabolites with variable importance in projection scores ≥ 1.0 in both 1st HF versus MCO and MCO versus 2nd HF were succinate, glutamate, and histidine. The pre-HD levels of succinate and histidine were significantly lower, while those of glutamate were significantly higher in MCO period than in the HF period. OPLS-DA of the proteome also substantially separated 1st HF and MCO periods. Plasma pre-HD levels of fibronectin 1 were significantly higher, and those of complement component 4B and retinol-binding protein 4 were significantly lower in MCO than in the 1st HF period. Interestingly, as per Ingenuity Pathway Analysis, an increase in epithelial cell proliferation and a decrease in endothelial cell apoptosis occurred during the MCO period. Overall, our results suggest that the use of MCO dialyzers results in characteristic metabolomics and proteomics profiles during HD compared with HF dialyzers, which might be related to oxidative stress, insulin resistance, complement-coagulation axis, inflammation, and nutrition.