Association between systemic inflammation biomarkers and mortality in patients with sepsis-associated acute kidney injury receiving intensive care and continuous kidney replacement therapy: results from the RENERGY (REsearches for NEphRology and epidemioloGY) study

Identifying risk factors and improving prognostication for mortality among patients with sepsis-associated acute kidney injury (AKI) undergoing continuous kidney replacement therapy (CKRT) is important in improving the adverse prognosis of this patient population. This study aimed to compare the prognostic value of existing systemic inflammation biomarkers and determine the optimal systemic inflammation biomarker in patients with sepsis-associated AKI receiving CKRT. Methods: This multi-center, retrospective, observational cohort study included 1,500 patients with sepsis-associated AKI treated with intensive care and CKRT. The main predictor was a panel of 13 different systemic inflammation biomarkers. The primary outcome was 28-day mortality after CKRT initiation. Secondary outcomes included 90-day mortality after CKRT initiation, CKRT duration, kidney replacement therapy dependence at discharge, and lengths of intensive care unit (ICU) and hospital stays. Results: When added to the widely accepted Acute Physiology and Chronic Health Evaluation II score, platelet-to-albumin ratio (PAR) and neutrophil-platelet score (NPS) had the highest improvements in prognostication of 28-day mortality, where the corresponding increases in C-statistic were 0.01 (95% confidence interval [CI], 0.00–0.02) and 0.02 (95% CI, 0.01–0.03). Similar findings were observed for 90-day mortality. The 28- and 90-day mortality rates were significantly lower for the higher PAR and NPS quartiles. These associations remained significant even after adjustment for potential confounding variables in multivariable Cox proportional hazards models. Conclusion: Of the available systemic inflammation biomarkers, the addition of PAR or NPS to conventional ICU prediction models improved the prognostication of patients with sepsis-associated AKI receiving intensive care and CKRT.

Phosphate level predicts mortality in acute kidney injury patients undergoing continuous kidney replacement therapy and has a U-shaped association with mortality in patients with high disease severity: a multicenter retrospective study

This study investigated the association between serum phosphate level and mortality in acute kidney injury (AKI) patients undergoing continuous kidney replacement therapy (CKRT) and evaluated whether this association differed according to disease severity. Methods: Data from eight tertiary hospitals in Korea were retrospectively analyzed. The patients were classified into four groups (low, normal, high, and very high) based on their serum phosphate level at baseline. The association between serum phosphate level and mortality was then analyzed, with further subgroup analysis being conducted according to disease severity. Results: Among the 3,290 patients identified, 166, 955, 1,307, and 862 were in the low, normal, high, and very high phosphate groups, respectively. The 90-day mortality rate was 63.9% and was highest in the very high group (76.3%). Both the high and very high groups showed a significantly higher 90-day mortality rate than did the normal phosphate group (high: hazard ratio [HR], 1.35, 95% confidence interval [CI], 1.21–1.51, p < 0.001; very high: HR, 2.01, 95% CI, 1.78–2.27, p < 0.001). The low group also exhibited a higher 90-day mortality rate than did the normal group among those with high disease severity (HR, 1.47; 95% CI, 1.09–1.99; p = 0.01) but not among those with low disease severity. Conclusion: High serum phosphate level predicted increased mortality in AKI patients undergoing CKRT, and low phosphate level was associated with increased mortality in patients with high disease severity. Therefore, serum phosphate levels should be carefully considered in critically ill patients with AKI.

First snapshot on behavioral characteristics and related factors of patients with chronic kidney disease in SouthKorea during the COVID-19 pandemic (June to October 2020)

The recent novel coronavirus disease 2019 (COVID-19) pandemic has led to unprecedented changes in behavior. We evaluated the current status of precautionary behavior and physical activity in chronic kidney disease (CKD) patients during the COVID-19 pandemic. Methods: A population of CKD patients (n = 306) registered in the Study on Kidney Disease and Environmental Chemicals (SKETCH, Clinical Trial No. NCT04679168) cohort recruited from June 2020 to October 2020 was included in the study. We conducted a questionnaire survey related to risk perception of COVID-19, precautionary behavior, and physical activity. Results: There were 187 patients (61.1%) with estimated glomerular filtration rate of <45 mL/min/1.73 m2 . This population showed a higher degree of risk perception for COVID-19 than the general population. Age was the most significant determinant of risk perception among CKD patients. During the pandemic, social distancing and hygiene-related behavior were significantly increased (p < 0.001). The frequency of exercise was decreased only in those who took regular exercise, without diabetes, or with a lower Charlson comorbidity index (CCI) (p < 0.001), with no change among the other groups. Socioeconomic status and comorbidities significantly affected behavioral characteristics regardless of the category. Education and income were significantly associated with precautionary behaviors such as staying at home and hand sanitizer use. Patients with higher CCI status significantly increased frequency of exercise (adjusted odds ratio, 2.10; 95% confidence interval, 1.01–4.38). Conclusion: CKD patients showed higher risk perception with active precautionary behavioral changes than the general population. Healthcare providers should be aware of the characteristics to comprise precautionary behavior without reducing physical activity.

Recalibration and validation of the Charlson Comorbidity Index in acute kidney injury patients underwent continuous renal replacement therapy

Comorbid conditions impact the survival of patients with severe acute kidney injury (AKI) who require continuous renal replacement therapy (CRRT). The weights assigned to comorbidities in predicting survival vary based on type of index, disease, and advances in management of comorbidities. We developed a modified Charlson Comorbidity Index (CCI) for use in patients with AKI requiring CRRT (mCCI-CRRT) and improved the accuracy of risk stratification for mortality. Methods: A total of 828 patients who received CRRT between 2008 and 2013, from three university hospital cohorts was included to develop the comorbidity score. The weights of the comorbidities were recalibrated using a Cox proportional hazards model adjusted for demographic and clinical information. The modified index was validated in a university hospital cohort (n = 919) using the data of patients treated from 2009 to 2015. Results: Weights for dementia, peptic ulcer disease, any tumor, and metastatic solid tumor were used to recalibrate the mCCI-CRRT. Use of these calibrated weights achieved a 35.4% (95% confidence interval [CI], 22.1%–48.1%) higher performance than unadjusted CCI in reclassification based on continuous net reclassification improvement in logistic regression adjusted for age and sex. After additionally adjusting for hemoglobin and albumin, consistent results were found in risk reclassification, which improved by 35.9% (95% CI, 23.3%–48.5%). Conclusion: The mCCI-CRRT stratifies risk of mortality in AKI patients who require CRRT more accurately than does the original CCI, suggesting that it could serve as a preferred index for use in clinical practice.

Effects of residential greenness on clinical outcomes of patients with chronic kidney disease: a large-scale observation study

Background@#As industrialization and urbanization are accelerating, the distribution of green areas is decreasing, particularly in developing countries. Since the 2000s, the effects of surrounding greenness on self-perceived health, including physical and mental health, longevity, and obesity have been reported. However, the effects of surrounding green space on chronic kidney disease are not well understood. Therefore, we investigated the impact of residential greenness on the mortality of chronic kidney disease patients and progression from chronic kidney disease to end-stage renal disease (ESRD). @*Methods@#Using a large-scale observational study, we recruited chronic kidney disease patients (n = 64,565; mean age, 54.0 years; 49.0% of male) who visited three Korean medical centers between January 2001 and December 2016. We investigated the hazard ratios of clinical outcomes per 0.1-point increment of exposure to greenness using various models. @*Results@#During the mean follow-up of 6.8 ± 4.6 years, 5,512 chronic kidney disease patients developed ESRD (8.5%) and 8,543 died (13.2%). In addition, a 0.1-point increase in greenness reduced all-cause mortality risk in chronic kidney disease and ESRD patients and progression of chronic kidney disease to ESRD in a fully adjusted model. The association between mortality in ESRD patients and the normalized difference vegetation index was negatively correlated in people aged >65 years, who had normal weight, were nonsmokers, and lived in a nonmetropolitan area. @*Conclusion@#Chronic kidney disease patients who live in areas with higher levels of greenness are at reduced risk of all-cause mortality and progression to ESRD.

Effects of residential greenness on clinical outcomes of patients with chronic kidney disease: a large-scale observation study

Background@#As industrialization and urbanization are accelerating, the distribution of green areas is decreasing, particularly in developing countries. Since the 2000s, the effects of surrounding greenness on self-perceived health, including physical and mental health, longevity, and obesity have been reported. However, the effects of surrounding green space on chronic kidney disease are not well understood. Therefore, we investigated the impact of residential greenness on the mortality of chronic kidney disease patients and progression from chronic kidney disease to end-stage renal disease (ESRD). @*Methods@#Using a large-scale observational study, we recruited chronic kidney disease patients (n = 64,565; mean age, 54.0 years; 49.0% of male) who visited three Korean medical centers between January 2001 and December 2016. We investigated the hazard ratios of clinical outcomes per 0.1-point increment of exposure to greenness using various models. @*Results@#During the mean follow-up of 6.8 ± 4.6 years, 5,512 chronic kidney disease patients developed ESRD (8.5%) and 8,543 died (13.2%). In addition, a 0.1-point increase in greenness reduced all-cause mortality risk in chronic kidney disease and ESRD patients and progression of chronic kidney disease to ESRD in a fully adjusted model. The association between mortality in ESRD patients and the normalized difference vegetation index was negatively correlated in people aged >65 years, who had normal weight, were nonsmokers, and lived in a nonmetropolitan area. @*Conclusion@#Chronic kidney disease patients who live in areas with higher levels of greenness are at reduced risk of all-cause mortality and progression to ESRD.

Cumulative fluid balance and mortality in elderly patients with acute kidney injury requiring continuous renal-replacement therapy: a multicenter prospective cohort study

Background@#The effect of fluid balance on outcomes in elderly patients with acute kidney injury (AKI) requiring continuous renal-replacement therapy (CRRT) is not explained well. We investigated outcomes according to cumulative fluid balance (CFB) in elderly patients with AKI undergoing CRRT. @*Methods@#A total of 607 patients aged 65 years or older who started CRRT due to AKI were enrolled and stratified into two groups (fluid overload [FO] vs. no fluid overload [NFO]) based on the median CFB value for 72 hours before CRRT initiation. Propensity score-matching analysis was performed. @*Results@#The median age of included patients was 73.0 years and 60.0% of the population was male. The median 72-hour CFB value was 2,839.0 mL. The overall cumulative survival and 28-day survival rates were lower in the FO group than in the NFO group (P < 0.001 for both) and remained so after propensity score-matching. Furthermore, patients in the FO group demonstrated a higher overall mortality risk after adjustment for age, sex, systolic blood pressure, Charlson comorbidity index, Acute Physiology and Chronic Health Evaluation II score, serum albumin, creatinine, diuretic use, and mechanical ventilation status (hazard ratio, 1.38; 95% confidence interval, 1.13 to 1.89; P < 0.001). Among survivors, both the duration of CRRT and the total duration of hospitalization from CRRT initiation showed no difference between the FO and NFO groups. @*Conclusion@#A higher CFB value is associated with an increased risk of mortality in elderly patients with AKI requiring CRRT.

Cumulative fluid balance and mortality in elderly patients with acute kidney injury requiring continuous renal-replacement therapy: a multicenter prospective cohort study

Background@#The effect of fluid balance on outcomes in elderly patients with acute kidney injury (AKI) requiring continuous renal-replacement therapy (CRRT) is not explained well. We investigated outcomes according to cumulative fluid balance (CFB) in elderly patients with AKI undergoing CRRT. @*Methods@#A total of 607 patients aged 65 years or older who started CRRT due to AKI were enrolled and stratified into two groups (fluid overload [FO] vs. no fluid overload [NFO]) based on the median CFB value for 72 hours before CRRT initiation. Propensity score-matching analysis was performed. @*Results@#The median age of included patients was 73.0 years and 60.0% of the population was male. The median 72-hour CFB value was 2,839.0 mL. The overall cumulative survival and 28-day survival rates were lower in the FO group than in the NFO group (P < 0.001 for both) and remained so after propensity score-matching. Furthermore, patients in the FO group demonstrated a higher overall mortality risk after adjustment for age, sex, systolic blood pressure, Charlson comorbidity index, Acute Physiology and Chronic Health Evaluation II score, serum albumin, creatinine, diuretic use, and mechanical ventilation status (hazard ratio, 1.38; 95% confidence interval, 1.13 to 1.89; P < 0.001). Among survivors, both the duration of CRRT and the total duration of hospitalization from CRRT initiation showed no difference between the FO and NFO groups. @*Conclusion@#A higher CFB value is associated with an increased risk of mortality in elderly patients with AKI requiring CRRT.

Disaster preparedness for earthquakes in hemodialysis units in Gyeongju and Pohang, South Korea

In 2016 and 2017, there were earthquakes greater than 5.0 in magnitude on the Korean Peninsula, which has previously been considered an earthquake-free zone. Patients with chronic kidney disease are particularly vulnerable to earthquakes, as the term “renal disaster” suggests. In the event of a major earthquake, patients on hemodialysis face the risk of losing maintenance dialysis due to infrastructure disruption. In this review, we share the experience of an earthquake in Pohang that posed a serious risk to patients on hemodialysis. We review the disaster response system in Japan and propose a disaster preparedness plan with respect to hemodialysis. Korean nephrologists and staff in dialysis facilities should be trained in emergency response to mitigate risk from natural disasters. Dialysis staff should be familiar with the action plan for natural disaster events that disrupt hemodialysis, such as outages and water treatment system failures caused by earthquakes. Patients on hemodialysis also need to be educated about disaster preparedness. In the event of a disaster situation that results in dialysis failure, patients need to know what to do. At the local and national government level, long-term preparations should be made to handle renal disaster and patient safety logistics. Moreover, Korean nephrologists should also be prepared to manage cardiovascular disease and diabetes in disaster situations. Further evaluation and management of social and national disaster preparedness of hemodialysis units to earthquakes in Korea are needed.

Antimicrobial Effects of Ursolic Acid against Mutans Streptococci Isolated from Koreans

Ursolic acid is a triterpenoid compound present in many plants. This study examined the antimicrobial activity of ursolic acid against mutans streptococci (MS) isolated from the Korean population. The antimicrobial activity was evaluated by the minimum inhibitory concentration (MIC) and time kill curves of MS. The cytotoxicity of ursolic acid against KB cells was tested using an MTT assay. The MIC90 values of ursolic acid for Streptococcus mutans and Streptococcus sobrinus isolated from the Korean population were 2 microg/ml and 4 microg/ml, respectively. Ursolic acid had a bactericidal effect on S. mutans ATCC 25175T and S. sobrinus ATCC 33478T at > 2 x MIC (4 microg/ml) and 4 x MIC (8 microg/ml), respectively. Ursolic acid had no cytotoxic effect on KB cells at concentrations at which it exerted antimicrobial effects. The results suggest that ursolic acid can be used in the development of oral hygiene products for the prevention of dental caries.

Development of Quantitative Real-Time PCR Primers for the Detection of Aggregatibacter actinomycetemcomitans

The purpose of this study was to develop species-specific real-time quantitative PCR (RT-qPCR) primers for use in the detection of Aggregatibacter actinomycetemcomitans. These primers were designed based on the nucleotide sequences of the RNA polymerase beta-subunit gene (rpoB). We assessed the specificity of the primers against nine strains of A. actinomycetemcomitans, eight strains (three species) of the Haemophilus genus, and 40 strains of 40 other oral bacterial species. Primer sensitivity was determined by testing serial dilutions of the purified genomic DNAs of A. actinomycetemcomitans ATCC 33384T. Our data reveal that we had obtained species-specific amplicons for all of the tested A. actinomycetemcomitans strains, and that none of these amplicons occurred in any of the other species. Our PCR protocol proved able to detect as little as 2 fg of A. actinomycetemcomitans chromosomal DNA. Our findings suggest that these qRT-PCR primers are suitable for application in epidemiological studies.

How Long Should We Monitor the Patient for Bleeding after Percutaneous Renal Biopsy? / 대한신장학회지

PURPOSE: Percutaneous renal biopsy (PRB) may become complicated by serious bleeding. Overnight observation after renal biopsy is a standard safety strategy. Although it was recently reported that outpatient observation is safe, appropriate observation time after the renal biopsy is still in debate. We evaluated prospectively the incidence, onset time and risk factors of hemorrhagic complications to determine the optimal duration of observation after PRB. METHODS: We enrolled 100 patients who underwent renal biopsy from October 2009 to April 2010 using the standard strategy. The biopsy was performed by two experienced nephrologists using 16-gauge spring-loaded biopsy gun under real-time ultrasound guidance. Serial color Doppler ultrasound was done immediately, 8 hours, 24 hours and 1 week after the PRB. RESULTS: The 32 patients experienced hemorrhagic complications (32.0%, 10 with gross hematuria, 26 with hematoma, and 4 with both), and 1 major complication occurred 3 days after PRB. Baseline serum creatinine of the patient with the major complication was 6.0 mg/dL. Serum creatinine and BMI were higher in complication group (p<0.05). Number of needle passes, blood pressure, and degree of edema and proteinuria were not related to the complication. In multivariate analysis, serum creatinine was the only significant risk factor of complication (p=0.007). Hemorrhagic complications developed in 9 patients (28.1%) between 8 and 24 hours after PRB, all of which were minor. CONCLUSION: The 8 hours' observation time after renal biopsy may be deemed appropriate for stable patients with normal creatinine.

A Case of Pulmonary Adenocarcinoma Developed on a Previous Lesion from Microscopic Polyangiitis / 대한신장학회지

This report examines a patient with pulmonary adenocarcinoma that developed on a previous lesion from microscopic polyangiitis. A 59-year-old woman had been diagnosed with microscopic polyangiitis in October of 1988 based on her clinical symptoms and serological tests, which were positive for anti-neutrophil cytoplasmic antibodies. Her glomerulonephritis had been well controlled with low-dose prednisolone. She presented in October of 2005 with vague chest discomfort and dyspnea on exertion. Physical examination was unremarkable. A non-contrast computed tomography (CT) scan of the chest showed patch ground-glass opacity at the right lower lobe of the lung. Because we did not believe the lesion to be a definite malignancy, we decided to follow up with chest images over a short interval. During the 18 months following the images, the lesion did not change. However, the opacity of the lesion increased slightly over the last two months, and a non-contrast CT scan of the chest was therefore performed. A CT scan showed persistent ground-glass opacity with a slightly solid portion. To diagnose the previous finding and possibly to provide treatment, a right lower lobectomy of the lung via video-assisted thoracoscopic surgery was performed. The pathologic review of the resected lung revealed an adenocarcinoma, stage pT1N0. After one year, fluorodeoxyglucose positron emission tomography was performed, and no evidence of a recurrent malignancy was found.

Proliferative Glomerulopathy with Unusual Subendothelial Deposits of Striated Structure in Multiple Myeloma / 대한신장학회지

A 50-year-old woman was admitted for the evaluation of proteinuria and renal biopsy. On the basis of the serum monoclonal protein, marrow plasma cell dyscrasia and end organ damage (nephrotic range proteinuria), multiple myeloma was diagnosed. A renal biopsy showed a membranoproliferative glomerulonephritis pattern of injury and unusual organized deposits of striated structure in the subendothelial space, which were identified as non-amyloid non-immunoglobulin-derived deposits. These deposits contained regularly stacked straight electron-dense bands, which have not been described in the setting of paraproteinemia and/or plasma cell dyscrasia.

Clinical Significance and Outcomes of Initial No Growth Peritonitis from Peritoneal Dialysis Patients: Role of Mycobacterial or Fungal Peritonitis / 대한신장학회지

PURPOSE: Peritoneal dialysis associated peritonitis (PD peritonitis) is an important complication in maintaining. There have been only a few reports on the clinical outcome of initial no-growth peritonitis (INGP). METHODS: We reviewed 332 episodes of PD peritonitis between January 2002 and August 2009. INGP was defined as PD peritonitis with no growth of etiologic microorganism within 3 days of peritonitis. INGP was compared with initial positive growth peritonitis (IPGP) in view of clinical manifestations and outcomes. RESULTS: We divided PD peritonitis episodes into two groups: INGP (n=90) and IPGP (n=242). Peritonitis-related mortality was 5.6% in INGP, while 0.8% in IPGP (p=0.017). Further relapse was noted in INGP (10.0%) than in IPGP (vs. 4.1%; p=0.041). Salvage antibiotics were used more frequently in INGP (21.1%) than in IPGP (vs. 11.6%; p=0.027). Odds ratio of INGP to IPGP for peritonitis-related mortality was 7.14 (95% CI 1.36-37.51; p=0.017). Growth of mycobacteria or fungi increased the risk of peritonitis-related mortality with an odds ratio of 18.11 (95% CI 2.99-109.89; p=0.013). In multivariate analysis, growth of mycobacteria or fungi was the only independent risk factor for peritonitis-related mortality with an odds ratio of 10.63 (95% CI 1.27-88.75; p=0.029). CONCLUSION: INGP revealed poorer outcome than IPGP. Higher growth rate of mycobacteria or fungi in INGP than in IPGP accounted for the poor outcome. Thus one should make vigorous efforts to detect surreptitious organism when there is no growth by 3 days, especially for the possibility of either mycobacteria or fungi.

Clinicopathologic Characteristics of C1q nephropathy / 대한신장학회지

PURPOSE: C1q nephropathy (C1qN) is a rare glomerulonephritis characterized by mesangial deposits, predominantly C1q, without the evidence of systemic lupus erythematosus (SLE). It showed various clinical courses, however, the clinicopathologic features of C1qN have not been well defined as yet. METHODS: We retrospectively reviewed the clinicopathologic features of 11 patients (0.8%) diagnosed as C1qN among 1,403 patients aged > or = 18 years who had undergone renal biopsy due to primary glomerular disease from Jan. 2000 to Jan. 2009. Diagnostic criteria of C1qN were as follows; 1) the presence of dominant or co-dominant immunofluorescence staining for C1q in the mesangium, 2) corresponding mesangial dense deposit by electron microscopy, and 3) lack of clinical evidence of SLE. RESULTS: The male-to-female ratio was 6:5 and their mean age was 41.1+/-22.6 yrs (range, 19-69 yrs). Eight patients presented with urinary abnormalities and three with nephrotic syndrome. At the time of biopsy, three patients had hypertension. The mean value of 24-hour urine protein was 4.4+/-5.5 g/day (range, 0.5-18.5 g/day). On light microscopy, normal glomerular architecture (4/11) and segmental sclerosis (7/11) were observed. Complete or partial remission was achieved in six of the seven patients treated with immunosuppressive agents (steroid and/or immunosuppressants). Among these patients, two using steroid monotherapy had relapsed. The mean follow-up duration was 14+/-11 months (range, 2-31 months) and renal function deterioration was observed in three patients. CONCLUSION: C1qN showed various clinical manifestations and prognosis. Therefore, additional studies are needed to fully define the clinicopathologic features.

Effect of Leaf-Extract from Camellia sinensis and Seed-Extract from Casia tora on Viability of Mutans Streptococci isolated from the interface between orthodontic brackets and tooth surfaces / 대한치과교정학회지

Mutans streptococci is the major causative factor in dental caries. Especially, orthodontic patients with fixed appliance are a risk group for dental caries. Because fixed appliances attached on teeth may change the environment of dental plaque, the enamel decalcification or dental caries around the bracket and band is a major side effect of orthodontic treatment. The aim of this study was to search plant extracts that have antimicrobial effect on mutans streptococci. Seed-extract of Casia tora were prepared with ethanol and CHMC-2032, the leaf-extracts from Camellia sinensis extract, was obtained extract, 2 type strains and 20 clinical isolates of mutans streptococci isolated from the interface between orthodontic brackets and tooth surfaces in the orthodontic patients were used in this study. The minimal inhibitory concentration of CHMC-2032 was 5 mg/ml on the S. mutans KCTC 3065, S. sobrinus KCTC 3088, and 8 clinical isolates of S. sobrinus. However, there was no antibacterial effect of seed-extract of C. tora on mutans streptococci. These data suggest that green tea may be more effective than the tea prepared from C. tora in the prevention of enamel decalcification or dental caries around brackets.