Relationship Between High-Density Lipoprotein Cholesterol and Mortality in Elderly Hemodialysis Patients: Data From the Korean Society of Geriatric Nephrology Retrospective Cohort.

OBJECTIVES: The association between high-density lipoprotein (HDL) cholesterol levels and mortality in elderly patients undergoing hemodialysis is not well established. Thus, this study investigated HDL levels and mortality in elderly Korean patients undergoing hemodialysis. METHODS: We recruited 1860 incident hemodialysis patients aged greater than 70 years from a retrospective cohort of the Korean Society of Geriatric Nephrology. The primary outcome measure was all-cause mortality. RESULTS: The mean age of the cohort was 77.8 years, and 1049 (56.4%) were men. When we grouped the patients into HDL cholesterol tertiles, the T1 group (HDL level <30 mg/dL in men and <33 mg/dL in women) had a higher proportion of patients with end-stage kidney disease due to diabetic nephropathy. During the median follow-up period of 3.1 years, 1109 (59.7%) deaths occurred. In a multivariable Cox regression model, the T1 group had a significantly higher risk of mortality (hazard ratio [HR], 1.28; 95% confidence interval, 1.10-1.50; P = .002) compared to the T3 group. A nonlinear analysis using a restrictive spline curve showed that low HDL cholesterol levels were associated with increased HR when HDL cholesterol levels were <40 mg/dL; however, there was no association between HDL cholesterol and mortality when HDL cholesterol levels were >40 mg/dL. Triglyceride/HDL ratio was not significantly associated with the risk of mortality (HR per 1 log increase, 1.08; 95% confidence interval, 0.99-1.18; P = .069). CONCLUSIONS: Low HDL cholesterol levels are associated with an increased risk of mortality in elderly patients undergoing hemodialysis. However, there was no significant relationship between HDL cholesterol levels and mortality when levels were below 40 mg/dL. Therefore, low HDL cholesterol levels may be a useful risk factor for predicting mortality in elderly patients undergoing hemodialysis.

Effect of low-density lipoprotein level and mortality in older incident statin-naïve hemodialysis patients.

BACKGROUND: This study aimed to analyze low-density lipoprotein cholesterol (LDL-C) levels and their relationship with mortality in order to identify the appropriate lipid profile for older Korean hemodialysis patients. METHODS: We enrolled a total of 2,732 incident hemodialysis patients aged > 70 years from a retrospective cohort of the Korean Society of Geriatric Nephrology from 2010 Jan to 2017 Dec, which included 17 academic hospitals in South Korea. Of these patients, 1,709 were statin-naïve, and 1,014 were analyzed after excluding those with missing LDL-C level data. We used multivariate Cox regression analysis to select risk factors from 20 clinical variables among the LDL-C groups. RESULTS: The mean age of the entire patient population was 78 years, with no significant differences in age between quartiles Q1 to Q4. However, the proportion of males decreased as the quartiles progressed towards Q4 (p < 0.001). The multivariate Cox regression analysis, which included all participants, showed that low LDL-C levels were associated with all-cause mortality. In the final model, compared to Q1, the hazard ratios (95% confidence interval) were 0.77 (0.620-0.972; p = 0.027), 0.85 (0.676-1.069; p = 0.166), and 0.65 (0.519-0.824; p < 0.001) for Q2, Q3, and Q4, respectively, after adjusting for covariates, such as conventional and age-specific risk factors. The final model demonstrated that all-cause mortality increased as LDL-C levels decreased, as confirmed by a restrictive cubic spline plot. CONCLUSIONS: In older hemodialysis patients who had not previously received dyslipidemia treatment, elevated LDL-C levels were not associated with increased all-cause mortality. Intriguingly, lower LDL-C levels appear to be associated with an unfavorable effect on all-cause mortality among high-risk hemodialysis patients.

Circulating miRNAs in extracellular vesicles related to treatment response in patients with idiopathic membranous nephropathy.

BACKGROUND: Extracellular vesicle (EV)-microRNAs (miRNAs) are potential biomarkers for various renal diseases. This study attempted to identify the circulating EV-miRNA signature not only for discriminating idiopathic membranous nephropathy (IMN) from idiopathic nephrotic syndrome (INS), but also to predict the treatment response of patients with IMN. METHODS: We prospectively enrolled 60 participants, including those with IMN (n = 19) and INS (n = 21) and healthy volunteers (HVs; n = 20) in this study. Using RNA sequencing, we assessed the serum EV-miRNA profiles of all participants. To identify the EV-miRNAs predictive of treatment response in IMN, we also analyzed EV-miRNAs among patients with IMN with and without clinical remission. RESULTS: The expression levels of 3 miRNAs differed between IMN patients, INS patients and HVs. In addition, compared to HVs, RNA sequencing revealed differential expression of 77 and 44 EV-miRNAs in patients with IMN without and with remission, respectively. We also identified statistically significant (|fold change ≥ 2, p < 0.05) differences in the expression levels of 23 miRNAs in IMN without remission. Biological pathway analysis of miRNAs in IMN without remission indicated that they are likely involved in various pathways, including renal fibrosis. CONCLUSION: Our study identified EV-miRNAs associated with IMN as well as those associations with therapeutic response. Therefore, these circulating EV-miRNAs may be used as potential markers for the diagnosis and prediction of treatment response in patients with IMN.

Association between physical activity and risk of renal function decline and mortality in community-dwelling older adults: a nationwide population-based cohort study.

BACKGROUND: Physical activity (PA) is an important risk factor associated with health outcomes. However, the relationship between PA and kidney function decline in older adults remains unclear. We examined the influence of PA on kidney function decline and mortality in community-dwelling older adults. METHODS: Adults aged ≥ 65 years with an estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2 who had available health checkup data from 2009 to 2010 were included. The cohort was followed annually through December 2015 for anthropometric, sociodemographic, and medical information including outcomes and biennially for laboratory information from the health checkup. We divided these patients into three groups according to self-reported PA (Inactive group: no leisure-time PA, Active group: vigorous activity for at least 80 min/week or a sum of moderate-intensity activity and walking for at least 300 min/week, Low-active group: level of PA between the definitions of the other two groups). Associations between the intensity of PA and death, cardiovascular death, and ≥ 50% eGFR decline were investigated. RESULTS: Among 102,353 subjects, 32,984 (32.23%), 54,267 (53.02%), and 15,102 (14.75%) were classified into the inactive, low-active, and active groups, respectively. The active group was younger, contained a higher proportion of men, and had higher frequencies of hypertension, diabetes mellitus, drinking, and smoking than the other groups. The active group had significantly lower incidence rates of mortality, cardiovascular mortality, and kidney function decline than the other groups (all p < 0.001). The active group also showed lower all-cause (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.70-0.82) and cardiovascular mortality (HR, 0.64; 95% CI, 0.53-0.78) and protection against ≥ 50% eGFR decline (HR, 0.81; 95% CI, 0.68-0.97) compared with the inactive group in the fully adjusted Cox proportional hazards regression model. CONCLUSIONS: High PA was an independent modifiable lifestyle factor for reducing mortality and protecting against declines in kidney function in older adults.

Extracellular vesicles: a novel window into kidney function and disease.

PURPOSE OF REVIEW: There has been an increasing interest in extracellular vesicles as potential diagnostic, prognostic or therapeutic biomarkers for various kidney diseases, as extracellular vesicles mediate cell-cell or intercellular communication. This review explores the current state of knowledge regarding extracellular vesicles as a tool for examining kidney physiology and disease. RECENT FINDINGS: Urinary extracellular vesicles may be useful as biomarkers to detect abnormal function in renal endothelial and tubular cells as well as podocytes. Recent studies suggest that urinary extracellular vesicles may facilitate early diagnosis and/or monitoring in acute kidney injury, glomerular disease, autosomal dominanat polycyst kidney disease and urinary tract malignancies. Circulating extracellular vesicles may serve as biomarkers to assess cardiovascular disease. SUMMARY: Urinary and circulating extracellular vesicles have gained significant interest as potential biomarkers of renal diseases. Analysis of extracellular vesicles may serve as a logical diagnostic approach for nephrologists as well as provide information about disease pathophysiology.

Urinary microRNA in kidney disease: utility and roles.

MicroRNAs (miRNAs) are small, noncoding single-stranded RNA oligonucleotides that modulate physiological and pathological processes by modulating target gene expression. Many miRNAs display tissue-specific expression patterns, the dysregulation of which has been associated with various disease states, including kidney disease. Mounting evidence implicates miRNAs in various biological processes, such as cell proliferation and differentiation and cancer. Because miRNAs are relatively stable in tissue and biological fluids, particularly when carried by extracellular vesicles, changes in their levels may reflect the development of human disease. Urinary miRNAs originate from primary kidney and urinary tract cells, cells infiltrating the renal tissue and shed in the urine, or the systemic circulation. Although their validity as biomarkers for kidney disease has not been fully established, studies have been applying analysis of miRNAs in the urine in an attempt to detect and monitor acute and chronic renal diseases. Because appreciation of the significance of miRNAs in the renal field is on the rise, an understanding of miRNA pathways that regulate renal physiology and pathophysiology is becoming critically important. This review aims to summarize new data obtained in this field of research. It is hoped that new developments in the use of miRNAs as biomarkers and/or therapy will help manage and contain kidney disease in affected subjects.

Early podocyte injury and elevated levels of urinary podocyte-derived extracellular vesicles in swine with metabolic syndrome: role of podocyte mitochondria.

Metabolic syndrome (MetS) is associated with nutrient surplus and kidney hyperfiltration, accelerating chronic renal failure. The potential involvement of podocyte damage in early MetS remains unclear. Mitochondrial dysfunction is an important determinant of renal damage, but whether it contributes to MetS-related podocyte injury remains unknown. Domestic pigs were studied after 16 wk of diet-induced MetS, MetS treated with the mitochondria-targeted peptide elamipretide (ELAM; 0.1 mg·kg-1·day-1 sc) for the last month of diet, and lean controls (n = 6 pigs/group). Glomerular filtration rate (GFR) and renal blood flow (RBF) were measured using multidetector computed tomography, and podocyte and mitochondrial injury were measured by light and electron microscopy. Urinary levels of podocyte-derived extracellular vesicles (pEVs; nephrin positive/podocalyxin positive) were characterized by flow cytometry. Body weight, blood pressure, RBF, and GFR were elevated in MetS. Glomerular size and glomerular injury score were also elevated in MetS and decreased after ELAM treatment. Evidence of podocyte injury, impaired podocyte mitochondria, and foot process width were all increased in MetS but restored with ELAM. The urinary concentration of pEVs was elevated in MetS pigs and directly correlated with renal dysfunction, glomerular injury, and fibrosis and inversely correlated with glomerular nephrin expression. Additionally, pEV numbers were elevated in the urine of obese compared with lean human patients. Early MetS induces podocyte injury and mitochondrial damage, which can be blunted by mitoprotection. Urinary pEVs reflecting podocyte injury might represent early markers of MetS-related kidney disease and a novel therapeutic target.

Clinical characteristics of sepsis-induced acute kidney injury in patients undergoing continuous renal replacement therapy.

OBJECTIVE: The aim of this study was to investigate the clinical characteristics of sepsis-induced acute kidney injury (AKI) in patients undergoing continuous renal replacement therapy (CRRT). METHODS: From 2011 to 2015, we enrolled 340 patients who were treated with CRRT for sepsis at the Presbyterian Medical Center. In all patients, CRRT was performed using the PRISMA platform. We divided these patients into two groups (survivors and non-survivors) according to the 28-day all-cause mortality. We compared clinical characteristics and analyzed the predictors of mortality. RESULTS: The 28-day all-cause mortality was 62%. Survivors were younger than non-survivors and had higher platelet counts (178 ± 101 × 103/mL vs. 134 ± 84 × 103/mL, p < .01) and serum creatinine levels (4.2 ± 2.8 vs. 3.3 ± 2.7, p < .01). However, survivors had lower red blood cell distribution width (RDW) scores (14.9 ± 2.1 vs. 16.1 ± 3.3, p < .01) and APACHE II scores (24.5 ± 5.8 vs. 26.9 ± 5.7, p < .01) than non-survivors. Furthermore, survivors were more likely than non-survivors to have a urine output of >0.05 mL/kg/h (66% vs. 86%, p = .001) in the first day. In a multivariate logistic regression analysis, age, platelet count, RDW score, APACHE II score, serum creatinine level, and a urine output of <0.05 mL/kg/h the first day were prognostic factors for the 28-day all-cause mortality. CONCLUSION: Age, platelet count, APACHE II score, RDW score, serum creatinine level, and urine output the first day are useful predictors for the 28-day all-cause mortality in sepsis patients requiring CRRT.

Clinical severity of drug-induced hyponatremia: thiazides vs. psychotropics.

BACKGROUND: The aim of this study was to investigate the clinical characteristics of patients with hyponatremia who received thiazide diuretics, psychotropic drugs, or both. METHODS: From 2007 to 2013, 266 patients were diagnosed with hyponatremia (P-Na < 135 mol/L) associated with thiazide diuretics (T), psychotropic drugs (P), or both (C). We compared clinical characteristics among the thiazide (T) group (n = 93), the psychotropic drug (P) group (n = 83), and the combination (C) group (n = 90). RESULTS: There were no differences in clinical characteristics except for correction time among the three groups. We evaluated the clinical severity among the three groups through initial serum sodium levels (mild: > 125 mmol/L, moderate: 120 - 125 mmol/L, severe: < 120 mmol/L), patient symptoms (mild: general weakness, moderate: nausea or vomiting, severe: syncope or seizure). There were no significant differences in the incidence of severe hyponatremia on the basis of initial serum sodium levels (73.1% vs. 67.5% vs. 71.1%, p = 0.710) and symptoms (20.4% vs. 30.1% vs. 17.8%, p = 0.192) among groups. However, correction time was significantly longer in group C than in groups T or P (41.98 ± 26.89 vs. 34.91 ± 23.96 vs. 51.10 ± 43.86 mg/dL, p = 0.026). CONCLUSION: Although patients in group C did not have clinical features that were any more severe than those of the other two groups in terms of initial serum sodium levels and symptoms, correction time was significantly longer for group C than for groups T or P. Therefore, it is of utmost importance to closely monitor patients who receive a thiazide and psychotropic drug simultaneously.

Prognostic Factors in Cholinesterase Inhibitor Poisoning.

BACKGROUND: Organophosphates and carbamates are insecticides that are associated with high human mortality. The purpose of this study is to investigate the prognostic factors affecting survival in patients with cholinesterase inhibitor (CI) poisoning. MATERIAL AND METHODS: This study included 92 patients with CI poisoning in the period from January 2005 to August 2013. We divided these patients into 2 groups (survivors vs. non-survivors), compared their clinical characteristics, and analyzed the predictors of survival. RESULTS: The mean age of the included patients was 56 years (range, 16-88). The patients included 57 (62%) men and 35 (38%) women. When we compared clinical characteristics between the survivor group (n=81, 88%) and non-survivor group (n=11, 12%), there were no differences in renal function, pancreatic enzymes, or serum cholinesterase level, except for serum bicarbonate level and APACHE II score. The serum bicarbonate level was lower in non-survivors than in survivors (12.45±2.84 vs. 18.36±4.73, P<0.01). The serum APACHE II score was higher in non-survivors than in survivors (24.36±5.22 vs. 12.07±6.67, P<0.01). The development of pneumonia during hospitalization was higher in non-survivors than in survivors (n=9, 82% vs. n=31, 38%, P<0.01). In multiple logistic regression analysis, serum bicarbonate concentration, APACHE II score, and pneumonia during hospitalization were the important prognostic factors in patients with CI poisoning. CONCLUSIONS: Serum bicarbonate and APACHE II score are useful prognostic factors in patients with CI poisoning. Furthermore, pneumonia during hospitalization was also important in predicting prognosis in patients with CI poisoning. Therefore, prevention and active treatment of pneumonia is important in the management of patients with CI poisoning.

Clinical characteristics of acute kidney injury in patients with scrub typhus--RIFLE criteria validation.

There are limited data available on the validity of the RIFLE classification for AKI in patients with scrub typhus. We investigated the incidence and clinical characteristics of scrub typhus associated AKI using the RIFLE criteria. From 2010 to 2012, 238 patients were diagnosed with scrub typhus. Of these, we included 223 patients who were followed up until renal recovery or for at least three months. We evaluated the incidence, clinical characteristics, and severity of AKI based on the RIFLE classification. Of the 223 patients, 47 (21%) had scrub typhus-associated AKI. The incidence of AKI was 21.1%; of which, 10.7%, 9.4% and 1% were classified as Risk, Injury and Failure, respectively. In comparison with patients in the non-AKI group, the patients in the AKI group were older (70 ± 9 vs 61 ± 14 year, P = 0.01) and had one or more comorbidities such as hypertension, diabetes, and chronic kidney disease (77% vs 22%, p = 0.01). In the AKI group, forty-four patients had AKI prior to admission, and three patients experienced AKI during their hospitalization. By multivariate logistic regression analysis, age and comorbidity were significant predictors of AKI. All patients recovered baseline renal function without renal replacement therapy following antibiotics therapy and supportive care. The incidence of AKI in patient with scrub typhus is 21%. Age and co-morbidity are significant predictors of AKI in scrub typhus. In cases of scrub typhus-associated AKI, anti-rickettsia agent and supportive care are very important.

Impact of obesity on renal function in elderly Korean adults: a national population-based cohort study.

Background: Obesity is a well-known risk factor for chronic kidney disease and its progression. However, the impact of obesity on the renal function of the elderly population is uncertain. We investigated the association between obesity and renal outcomes in the elderly. Methods: We analyzed 130,504 participants from the Korean National Health Insurance Service-Senior cohort. Obesity was classified according to body mass index (BMI), sex-specific waist circumference (WC), and the presence of metabolic syndrome. The primary outcome was renal function decline, defined as a decline in the estimated glomerular filtration rate (eGFR) of at least 50% from baseline or new-onset end-stage renal disease. Results: During a follow-up period of 559,531.1 person-years (median, 4.3 years), 2,486 participants (19.0%; incidence rate of 4.44 per 1,000 person-years) showed renal function decline. A multivariate Cox proportional hazards model revealed that BMI/WC was not associated with renal function decline. However, the group with metabolic syndrome had a significantly increased risk of renal function decline compared to the group without metabolic syndrome (adjusted hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.13-1.36). Compared with the non-metabolic syndrome group, the adjusted HRs (95% CI) for participants with one through five components were 0.96 (0.84-1.11), 1.10 (0.96-1.27), 1.24 (1.06-1.45), 1.37 (1.12-1.66), and 1.99 (1.42-2.79), respectively (p for trend < 0.001). Conclusion: In elderly Korean adults, metabolic syndrome and the number of its components were associated with a higher risk of renal function decline, but BMI or WC was not significant.

Association between dementia diagnosis at dialysis initiation and mortality in older patients with end-stage kidney disease in South Korea.

Background: The prevalence of dementia is 2- to 7-fold higher among patients with end-stage kidney disease (ESKD) than among the general population; however, its clinical implications in this population remain unclear. Therefore, this study aimed to determine whether comorbid dementia increases mortality among older patients with ESKD undergoing newly initiated hemodialysis. Methods: We analyzed data from the Korean Society of Geriatric Nephrology retrospective cohort, which included 2,736 older ESKD patients (≥70 years old) who started hemodialysis between 2010 and 2017. Kaplan-Meier survival and Cox regression analyses were used to examine all-cause mortality between the patients with and without dementia in this cohort. Results: Of the 2,406 included patients, 8.3% had dementia at the initiation of dialysis; these patients were older (79.6 ± 6.0 years) than patients without dementia (77.7 ± 5.5 years) and included more women (male:female, 89:111). Pre-ESKD diagnosis of dementia was associated with an increased risk of overall mortality (hazard ratio, 1.503; p < 0.001), and this association remained consistent after multivariate adjustment (hazard ratio, 1.268; p = 0.009). In subgroup analysis, prevalent dementia was associated with mortality following dialysis initiation in female patients, those aged <85 years, those with no history of cerebrovascular accidents or severe behavioral disorders, those not residing in nursing facilities, and those with no or short-term hospitalization. Conclusion: A pre-ESKD diagnosis of dementia is associated with mortality following dialysis initiation in older Korean population. In older patients with ESKD, cognitive assessment at dialysis initiation is necessary.

Importance of dialysis specialists in early mortality in elderly hemodialysis patients: a multicenter retrospective cohort study.

The early mortality rate in elderly patients undergoing hemodialysis is more than twice that in young patients, requiring more specialized healthcare. We investigated whether the number of professional dialysis specialists affected early mortality in elderly patients undergoing hemodialysis. This multicenter retrospective cohort study analyzed data from 1860 patients aged ≥ 70 years who started hemodialysis between January 2010 and December 2017. Study regions included Seoul, Gyeonggi-do, Gangwon-do, Daejeon/Chungcheong-do, Daegu/Gyeongsangbuk-do, and Busan/Ulsan/Gyeongsangnam-do. The number of patients undergoing hemodialysis per dialysis specialist was calculated using registered data from each hemodialysis center. Early mortality was defined as death within 6 months of hemodialysis initiation. Gangwon-do (28.3%) and Seoul (14.5%) showed the highest and lowest early mortality rate, respectively. Similarly, Gangwon-do (64.6) and Seoul (43.9) had the highest and lowest number of patients per dialysis specialist, respectively. Relatively consistent results were observed for the regional rankings of early mortality rate and number of patients per dialysis specialist. Multivariate Cox regression analysis-adjusted for previously known significant risk factors-revealed that the number of patients per dialysis specialist was an independent risk factor for early mortality (hazard ratio: 1.031, p < 0.001). This study underscores the growing need for dialysis specialists for elderly hemodialysis patients in Korea.

Type III membranoproliferative glomerulonephritis in a patient with primary Sjögren's syndrome.

Renal involvement in the form of glomerulonephritis in Sjögren's syndrome (SS) is less common and usually a latent sequel in the course of the disease. We report a patient with Type III membarnoproliferative glomerulonephritis (MPGN) with hypothyroidism, which precedes the onset of the clinical manifestation of SS. She received immunosuppressions consisting of i.v. cyclophosphamide and high-dose corticosteroid and subsequently oral corticosteroid resulting in complete remission of nephrotic syndrome. To our knowledge, this is the first report of successfully treated Type III MPGN associated with SS.

Clinical characteristics and treatment of patients with IgA nephropathy and hepatitis B surface antigen.

BACKGROUND: The aim of this study is to investigate the clinical characteristics and our experience of treating patients with IgA nephropathy (IgAN) and IgA nephropathy with hepatitis B surface antigen (HBs-IgAN). METHODS: From 1996 to 2011, biopsy-proven IgAN was diagnosed in 477 patients and 22 (4.6%) had hepatitis B surface antigen (HBsAg). Of these, we included 360 patients who had more than 6-month follow-up period, and compared clinical characteristics and renal function decline between the patients with IgAN and HBs-IgAN. RESULTS: Of 360 patients, 22 were classified as HBs-IgAN. There were no differences in the clinical characteristics and renal function decline between idiopathic IgAN and HBs-IgAN (-0.01 vs. -0.17 mL/min per 1.73 m(2)/month, p = 0.319). Of 22 patients with HBs-IgAN, nine had hepatitis B virus (HBV) replication marker (RM), of which six were treated with anti-viral agents. However, there were no differences in renal function decline and urinary protein excretion between patients who did or did not receive anti-viral therapy. Five patients with HBs-IgAN received corticosteroid therapy. Of these, three without HBV RM and one with HBV RM who received entecavir did not exhibit active viral replication, whereas the other patients with HBV RM experienced viral replication after lamivudine was discontinued. CONCLUSION: There were no differences in the clinical characteristics and prognosis between the patients with IgAN and HBs-IgAN. Further, there were no differences in renal function decline and urinary protein excretion between patients with and without anti-viral therapy. Anti-viral therapy may be considered for treating patients with HBs-IgAN receiving immunosuppressants according to HBV RM.

Clinical characteristics of acute kidney injury in patients with glyphosate surfactant herbicide poisoning.

BACKGROUND: In this study, we investigated the clinical characteristics of acute kidney injury (AKI) in patients with glyphosate surfactant herbicide (GSH) poisoning. METHODS: This study was performed between 2008 and 2021 and included 184 patients categorized into the AKI (n = 82) and nonAKI (n = 102) groups. The incidence, clinical characteristics, and severity of AKI were compared between the groups based on the Risk of renal dysfunction, Injury to the kidney, Failure or Loss of kidney function, and End-stage kidney disease (RIFLE) classification. RESULTS: The incidence of AKI was 44.5%, of which 25.0%, 6.5%, and 13.0% of patients were classified into the Risk, Injury, and Failure categories, respectively. Patients in the AKI group were older (63.3 ± 16.2 years vs. 57.4 ± 17.5 years, p = 0.02) than those in the non-AKI group. The length of hospitalization was longer (10.7 ± 12.1 days vs. 6.5 ± 8.1 days, p = 0.004) and hypotensive episodes occurred more frequently in the AKI group (45.1% vs. 8.8%, p < 0.001). Electrocardiographic (ECG) abnormalities on admission were more frequently observed in the AKI group than in the non-AKI group (80.5% vs. 47.1%, p < 0.001). Patients in the AKI group had poorer renal function (estimated glomerular filtration rate at the time of admission, 62.2 ± 22.9 mL/min/1.73 m2 vs. 88.9 ± 26.1 mL/min/1.73 m2 , p < 0.001) on admission. The mortality rate was higher in the AKI group than in the non-AKI group (18.3% vs. 1.0%, p < 0.001). Multiple logistic regression analysis showed that hypotension and ECG abnormalities upon admission were significant predictors of AKI in patients with GSH poisoning. CONCLUSION: The presence of hypotension on admission may be a useful predictor of AKI in patients with GSH intoxication.

Clinical significance of the ratio between FOXP3 positive regulatory T cell and interleukin-17 secreting cell in renal allograft biopsies with acute T-cell-mediated rejection.

The aim of this study is to investigate the clinical significance of the ratio between interleukin-17 (IL-17) secreting cell and FOXP3-positive regulatory T cell (FOXP3(+) Treg) infiltration in renal allograft tissues with acute T-cell-mediated rejection (ATCMR). Fifty-six patients with biopsy-proven ATCMR were included. Infiltration of FOXP3(+) Treg and IL-17-secreting cells was evaluated with immunostaining for FOXP3 or IL-17 on the biopsy specimens, and the patients were divided into the FOXP3 high group (Log FOXP3/IL-17 > 0·45) or the IL-17 high group (Log FOXP3/IL-17 < 0·45). We compared the allograft function, severity of tissue injury, and clinical outcome between the two groups. In the IL-17 high group, allograft function was significantly decreased compared with the FOXP3 high group (P < 0·05). The severity of interstitial and tubular injury in the IL-17 high group was higher than the FOXP3 high group (P < 0·05). The proportions of steroid-resistant rejection, incomplete recovery and recurrent ATCMR were higher in the IL-17 high group than in the FOXP3 high group (all indicators, P < 0·05). The IL-17 high group showed lower 1-year (54% versus 90%, P < 0·05) and 5-year (38% versus 85%, P < 0·05) allograft survival rates compared with the FOXP3 high group. Multivariate analysis revealed that the FOXP3/IL-17 ratio was a significant predictor for allograft outcome. The FOXP3/IL-17 ratio is a useful indicator for representing the severity of tissue injury, allograft dysfunction and for predicting the clinical outcome of ATCMR.

The Oxford classification as a predictor of prognosis in patients with IgA nephropathy.

BACKGROUND: In 2009, the Oxford classification was developed as a pathological classification system for immunoglobulin A nephropathy (IgAN) to predict the risk of disease progression. The aim of this retrospective study was to evaluate the clinical and pathologic relevance of the Oxford classification in Korean patients with a pathologic diagnosis of IgAN. PATIENTS AND METHODS: We reviewed the renal pathology archives from January 2000 to December 2006 at Seoul St Mary's Hospital in Korea and identified 273 patients, who were diagnosed as having IgAN. We enrolled 197 patients who were available for further clinicopathologic analysis. All cases of IgAN were categorized according to the WHO classification, the semiquantitative classification and the Oxford classification. These pathologic classifications were compared. The clinical and laboratory findings at the time of biopsy were compared with those at the end of the follow-up according to the Oxford classification. RESULTS: When three pathologic classifications were compared, M1, S1, E1, T1 or T2 were associated with a higher score in the activity index. S1, T1 or T2 were associated with a higher score in the chronicity index and a higher grade in the WHO classification. The clinical and laboratory findings were compared according to the Oxford classification. At the time of biopsy, the proteinuria in patients with M1 was more than that of M0 (P = 0.035). At the end of follow-up, the number of antihypertensive drugs taken among patients with M1 was greater than that of patients with M0 (P = 0.001). At the time of biopsy, the proteinuria of patients with S1 was greater than that of S0 patients (P = 0.009). At the end of follow-up, the number of patients who received immunosuppressants was increased as the grade of T increased (P = 0.000). At the end point of the follow-up, the estimated glomerular filtration rate (eGFR) decreased as the grade of T increased (P = 0.008). The time-average proteinuria after adjusting the initial proteinuria increased significantly with increasing degree of T (P = 0.000). Levels of tubular atrophy/interstitial fibrosis were predictive for survival from end-stage renal disease or of having a 50% reduction of eGFR. CONCLUSION: The pathologic variables of the Oxford classification correlated significantly with other classifications (the WHO classification and the semiquantitative classification). The Oxford classification is a simple method for predicting renal outcome and differentiating between active and chronic lesions. We suggest that the Oxford classification offers an advantage for determining treatment policy for patients with IgAN.

Clinical usefulness of BK virus plasma quantitative PCR to prevent BK virus associated nephropathy.

The present study investigated the clinical usefulness of plasma real-time polymerase chain reaction (PCR) (plasma-PCR) in the prevention of BK virus-associated nephropathy (BKVAN). First, we investigated the diagnostic value of plasma BK-PCR, urine BK-PCR, and urine cytology for the prediction of BKVAN retrospectively. Then we designed a prospective study of regular plasma-PCR monitoring and pre-emptive immunosuppression (IS) reduction based on the result. In the retrospective cohort, the prevalence of BKVAN was 3.7% (14/379) and the positive rate of decoy cells, urine-PCR (>1 × 10(10) copies/ml), and plasma-PCR (>1 × 10(4) copies/ml) was 18.6%, 11.1%, and 5.5%, respectively. Plasma-PCR was superior to urine-PCR or urine cytology in specificity and positive predictive value for detection of BKVAN. In prospective study, regular monitoring of plasma-PCR detected significant BKV viremia in 8.3% (12/145) and BKVAN in 1 patient (0.6%). After IS reduction, BKV viremia was eliminated in 91.6% (11/12) within 103 days (25-254). In patients with viremia, the frequency of acute rejection did not increase and allograft function did not differ significantly compared with those in patients without viremia during the first year post-transplant (P > 0.05, in both). Plasma-PCR is useful to predict an increased risk for BKVAN, and regular monitoring is effective to prevent the development of BKVAN.