Catheter-based renal sympathetic denervation induces acute renal inflammation through activation of caspase-1 and NLRP3 inflammasome.

OBJECTIVE: Catheter-based renal sympathetic denervation (RDN) is implemented as a strategy to treat resistant hypertension. Serum creatinine and estimated glomerular filtration rate have some limitations to predict the early stage of acute kidney injury (AKI). We investigated the changes of early inflammatory biomarkers in AKI following the RDN procedure. METHODS: Twenty-five female swine were divided into three groups: normal control (Normal, n=5), sham-operated (Sham, n=5), and RDN groups (RDN, n=15). The RDN group was further subdivided into three subgroups according to the time of sacrifice: immediately (RDN-0, n=5), 1 week (RDN-1, n=5), and 2 weeks (RDN-2, n=5) after RDN. Renal cortical tissue was harvested, and clinical parameters and inflammatory biomarkers were checked. RESULTS: There were no significant changes in the clinical parameters between the normal control and sham-operated groups using contrast media. Inflammatory interleukin (IL)-1ß, IL-18, IL-6, tumor necrosis factor-α, and anti-inflammatory IL-10 increased immediately and then decreased at week 2 after RDN in the renal cortical tissue. Leaderless protein, IL-1α level, increased at week 1 and then decreased at week 2 after RDN. Caspase-1 increased immediately after RDN until week 2. Apoptosis-associated speck-like protein containing a caspase recruitment domain and NLRP3 expressions increased immediately and then decreased at week 2 after RDN. CONCLUSION: The RDN could induce acute renal inflammation through the activation of caspase-1 and NLRP3 inflammasome.

Incidence and risk factors for tenofovir-associated nephrotoxicity among human immunodeficiency virus-infected patients in Korea.

BACKGROUND/AIMS: Little is known about tenofovir disoproxil fumarate (TDF)-induced nephrotoxicity in human immunodeficiency virus (HIV)-infected patients in Korea. The objective of this study was to evaluate the incidence and risk factors of TDF-associated nephrotoxicity among HIV-infected patients in Korea. METHODS: A single-center retrospective cohort study was conducted on HIVinfected patients in Korea. We included patients who had started TDF or abacavir (ABC)-based antiretroviral therapy (ART) between October 2006 and December 2014. Estimated glomerular filtration rate (eGFR) was estimated using the Chronic Kidney Disease-Epidemiology Collaboration equation. Renal dysfunction was defined as > 25% decrease of baseline eGFR. A propensity matched case-control study was conducted to compare renal dysfunction rates between the two groups. The risk factors of nephrotoxicity were analyzed by Cox regression analysis. RESULTS: A total of 210 HIV-infected patients were included in the study, of which, 108 were TDF-based ART group and 102 were ABC-based ART group. Renal dysfunction occurred in 16 patients (14.8%) in the TDF group and 11 (10.8%) in the ABC group. Incidence of renal dysfunction of TDF and ABC group was 9.66 per 100 person-years (PYs) and 5.14 per 100 PYs, respectively (p = 0.176). In propensityscore-matched analysis, renal dysfunction rates were TDF 13.3% versus ABC 13.3% (p > 0.999). In multivariable analysis, Centers for Disease Control and Prevention clinical category C was a significant risk factor for renal dysfunction. CONCLUSION: Approximately, 13% of HIV-infected patients treated with TDF had renal dysfunction. Advanced stage of HIV infection was a significant risk factor for renal dysfunction.

Long-term outcomes in acute kidney injury patients who underwent continuous renal replacement therapy: a single-center experience.

INTRODUCTION: Acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) is the most severe form of AKI associated with poor short- and long-term patient outcomes. The aim of this study was to evaluate the variables associated with long-term patient survival in our clinic. METHODS: This was a single-center retrospective study with AKI survivors who received CRRT from March 2011 to February 2015. During the study period, all consecutive AKI survivors who underwent CRRT were included. Patients on maintenance dialysis prior to CRRT were excluded. Data were collected by reviewing the patients' medical charts. Long-term follow-up data were gathered through February 2018. RESULTS: A total of 430 patients were included, and 62.8% of the patients were male. The mean age of the patients was 63.4 ± 14.6 years. The mean serum creatinine level at the time of CRRT initiation was 3.5 ± 2.5 mg/dL. At the time of discharge, the mean eGFR and serum creatinine levels were 58.4 ± 46.7 and 1.7 ± 1.6 mg/dL, respectively. After 3 years, 44.9% of the patients had survived. When we investigated the factors associated with long-term patient mortality, a longer stay in the ICU [OR 1.034 (1.016-1.053), p < 0.001], a history of cancer [OR 3.830 (1.037-3.308), p = 0.037], a prolonged prothrombin time [OR 1.852 (1.037-3.308), p = 0.037] and a lower eGFR at the time of discharge [OR 0.988 (0.982-0.995), p = 0.001] were independently associated with long-term patient mortality. CONCLUSION: Our study demonstrates that long-term mortality after CRRT is associated with longer ICU stays and lower eGFRs at the time of hospital discharge. Our data imply the importance of renal recovery for long-term survival of AKI patients treated with CRRT.

Primary Glomerulonephritis with Unique C4d Deposition and Concurrent Non-infectious Intermediate Uveitis: a Case Report and Literature Review.

C4 glomerulopathy is a recently introduced entity that presents with bright C4d staining and minimal or absent immunoglobulin and C3 staining. We report a case of a 62-year-old man with C4 glomerulonephritis (GN) and uveitis. He presented to the nephrology department with proteinuria and hematuria. The patient also had intermediate uveitis along with proteinuria and hematuria. A kidney biopsy that was performed in light of continuing proteinuria and hematuria showed a focal proliferative, focal sclerotic glomerulopathy pattern on light microscopy, absent staining for immunoglobulin or C3 by immunofluorescence microscopy, with bright staining for C4d on immunohistochemistry, and electron-dense deposits on electron microscopy. Consequently, C4 GN was suggested as the pathologic diagnosis. Although laser microdissection and mass spectrometry for glomerular deposit and pathologic evaluation of the retinal tissue were not performed, this is the first report of C4 GN in Korea and the first case of coexisting C4 GN and uveitis in the English literature.

Change in kidney function after unilateral adrenalectomy in patients with primary aldosteronism: identification of risk factors for decreased kidney function.

PURPOSE: Glomerular filtration rate (GFR) has been reported to decrease after unilateral adrenalectomy in patients with primary aldosteronism (PA). The aim of this study was to identify clinical predictors for decreased GFR after adrenalectomy in patients with PA. METHODS: The records of 187 patients (98 patients with PA and 89 with non-PA adrenal disease) who were followed up for at least 6 months after unilateral adrenalectomy were retrospectively analyzed. Estimated GFR (eGFR) was investigated at 1, 3, and 6 months postoperatively. Preoperative risk factors for eGFR% decline at 1 month ([preoperative eGFR-eGFR at 1 month]/preoperative eGFR × 100) and postoperative CKD development were investigated. RESULTS: The eGFR decreased significantly at 1 month and remained stable in the PA group. However, there were no significant changes in eGFR in the non-PA group over the 6-month period. In the PA group, a high preoperative eGFR and high aldosterone to renin ratio (ARR) were independently associated with eGFR% decline at 1 month. In patients with PA but without preoperative CKD (n = 68), a low preoperative eGFR and high ARR were independent risk factors for developing postoperative CKD. The best preoperative cut-off values of eGFR and ARR for predicting the development of postoperative CKD were ≤ 102 ml/min/1.73 m2 and ≥ 448 ng/dl:ng/ml/h, respectively. CONCLUSIONS: Renal function deteriorated significantly after unilateral adrenalectomy in patients with PA. Clinicians must pay attention to postoperative renal function in PA patients at elevated risk of developing decreased kidney function.

Light Chain Deposition Disease Associated With Multiple Myeloma Developing in Late Pregnancy.

Preeclampsia is the most common cause of proteinuria with hypertension during pregnancy. Primary kidney disease and kidney disease secondary to systemic disorders may rarely occur during pregnancy, resulting in proteinuria. A 34-year-old woman was admitted to our hospital with abdominal distention and lower extremity edema. The pregnancy was terminated at the 24th week of gestation due to preterm labor. Even after the delivery, proteinuria and renal deterioration continued to progress. The M-peak was not found on serum and urine protein electrophoresis. The serum free light chains assay showed absolute elevation of lambda chains at 1013.9 mg/L with a decreased kappa to lambda ratio of 0.05. Kidney biopsy revealed light chain deposition disease with lambda light chain deposits on immunofluorescence. Bone marrow examination was compatible with multiple myeloma. To our knowledge, this is the first reported case of light chain deposition disease associated with multiple myeloma during pregnancy.

Plasma neutrophil gelatinase-associated lipocalin is associated with iron status in anemic patients with pre-dialysis chronic kidney disease.

BACKGROUND: Iron deficiency anemia is common in patients with chronic kidney disease (CKD). Neutrophil gelatinase-associated lipocalin (NGAL), a biomarker of acute kidney injury, is known to be associated with iron metabolism. We investigated whether plasma NGAL level is associated with iron status in pre-dialysis CKD patients with anemia. METHODS: This study included 419 patients who had anemia. The subjects were into categorized into a pre-dialysis group (estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m2, n = 288) and a non-CKD group (eGFR >60 ml/min/1.73 m2, n = 131). The associations between plasma NGAL and iron status (serum ferritin and transferrin saturation [TSAT]), eGFR, albumin, uric acid, total cholesterol, calcium, phosphate, and C-reactive protein (CRP) were assessed. RESULTS: In non-CKD group, plasma NGAL was not associated with any baseline variables including iron indices (TSAT and serum ferritin). In pre-dialysis group, univariate analysis showed plasma NGAL correlated with eGFR, CRP, TSAT, and serum ferritin. In multivariate analysis, plasma NGAL was independently associated with TSAT. However, serum ferritin lost its association with plasma NGAL. In ROC analysis for identifying iron deficiency, the plasma NGAL (best cut-off value ≤394 ng/ml) was superior to the serum ferritin (suggested cut-off value ≤500 ng/ml) in both sensitivity and specificity. CONCLUSIONS: Plasma NGAL is associated with iron status in anemic patients with pre-dialysis CKD. Further studies are needed to demonstrate the role of plasma NGAL in assessing the iron deficiency and in guiding the iron therapy for pre-dialysis CKD patients.

The role of the specialized team in the operation of continuous renal replacement therapy: a single-center experience.

BACKGROUND: The requirement of continuous renal replacement therapy (CRRT) is increasing with the growing incidence of acute kidney injury (AKI). The decision to initiate CRRT is not difficult if an adequate medical history is obtained. However, the handling and maintenance of CRRT constitute a labor-intensive intervention that requires specialized skills. For these reasons, our center organized a specialized CRRT team in March 2013. The aim of this study is to report on the role of a specialized CRRT team and to evaluate the team's outcome. METHODS: This retrospective single-center study evaluated AKI patients who underwent CRRT in the intensive care unit (ICU) from March 2011 to February 2015. Patients were divided into two groups based on whether they received specialized CRRT team intervention. We collected information on demographic characteristics, laboratory parameters, SOFA score, CRRT initiation time, actual delivered dose and CRRT down-time. In-hospital mortality was defined by medical chart review. Binary logistic regression analysis was used to define factors associated with in-hospital mortality. RESULTS: A total of 1104 patients were included in this study. The mean patient age was 63.85 ± 14.39 years old, and 62.8% of the patients were male. After the specialized CRRT team intervention, there was a significant reduction in CRRT initiation time (5.30 ± 13.86 vs. 3.60 ± 11.59 days, p = 0.027) and CRRT down-time (1.78 ± 2.23 vs. 1.38 ± 2.08 h/day, p = 0.002). The rate of in-hospital mortality decreased after the specialized CRRT team intervention (57.5 vs. 49.2%, p = 0.007). When the multivariable analysis was adjusted, delayed CRRT initiation (HR 1.054(1.036-1.072), p < 0.001) was a significant factor in predicting in-hospital mortality, along with an increased SOFA score, lower serum albumin and prolonged prothrombin time. CONCLUSIONS: Our study shows that specialized CRRT team intervention reduced CRRT initiation time, down-time and in-hospital mortality. This study could serve as a logical basis for implementing specialized CRRT teams hospital-wide.

Trends in Malignancies among Korean Patients Infected with Human Immunodeficiency Virus in the Highly Active Antiretroviral Therapy Era.

Since the introduction of highly active antiretroviral therapy, the life span of people with human immunodeficiency virus (HIV) or AIDS (PWHA) has been extended significantly. Therefore, the importance of non-AIDS-defining cancers (NADCs), as well as AIDS-defining cancers (ADCs) has increased. There is little information concerning the epidemiology of malignancies in PWHA in Korea. A descriptive epidemiologic study was conducted at a tertiary care hospital in Korea. PWHA who visited Pusan National University Hospital from January 2000 to October 2014 were included. Demographics and clinical data were obtained from the medical records and analyzed. A total of 950 PWHA were observed for 4,439.71 person-years. Forty-eight episodes (5.05%) of cancers were diagnosed in 47 patients. Mean age of the enrolled patients was 40.66 ± 12.15 years and 88% were male. Among the 48 cancer episodes, 20 (42%) were ADCs and 28 were NADCs. The most common ADCs was non-Hodgkin's lymphoma (53.6%), followed by Kaposi's sarcoma (17.9%). The most common NADCs were lung cancer (25%) and hepatocellular carcinoma (25%). The overall incidence of total cancers, ADCs, and NADCs was 10.8 (95% confidence interval [CI], 8.0-14.3), 4.5 (95% CI, 2.8-7.0), and 6.3 (95% CI, 4.2-9.1)/1,000 person-years, respectively. NADCs accounted for 12/15 (80%) of cancers among PWHA with good adherence to care. The 5-year survival rate of PWHA and NADC was 26.3%. NADCs have become the main type of malignancy among Korean PWHA with good adherence to care. Effective strategies to improve screening of NADCs among PWHA are required in Korea.

Variability in glycated albumin levels predicts the progression of diabetic nephropathy.

AIM: The present study was performed to assess variability in glycated albumin (GA) using a coefficient of variation (CV) to predict the progression of diabetic nephropathy in type 2 diabetic patients, independently of HbA1c and other conventional risk factors. METHODS: The present study consecutively enrolled 369 patients with type 2 diabetes mellitus from outpatient clinic. During the follow-up period, GA and HbA1c levels were measured repeatedly (≥5 times), and the CV of GA (GA-CV) was calculated for each patient. The patients were divided into two subgroups: Group 1, a MEAN-HbA1c value <7.2% (55mmol/mol); Group 2, a MEAN-HbA1c value ≥7.2% (55mmol/mol). The primary outcome was the renal composite outcome (RCO), which was based on the progression rates of chronic kidney disease and albuminuria and renal death. RESULTS: The median follow-up period was 33months. The RCO was developed in 109 patients (29.5%). In Group 1, the third highest and highest quartile groups for GA-CV had higher cumulative incidences of the RCO than those of the lowest quartile group (Q4 vs. Q1: HR=5.43, P=0.007, Q3 vs. Q1: HR=5.16, P=0.009). After adjusting for HbA1c levels and other risk factors, the GA-CV remained significantly associated with the development of the RCO. However, Group 2 did not exhibit any significant differences in terms of the cumulative incidence of the RCO among the four GA-CV quartile groups. CONCLUSIONS: The present findings suggest that variability in GA may be a better predictor of the progression of diabetic nephropathy in type 2 diabetic patients regardless of HbA1c.

Fluid overload and survival in critically ill patients with acute kidney injury receiving continuous renal replacement therapy.

BACKGROUND: Fluid overload is known to be associated with increased mortality in patients with acute kidney injury (AKI) who are critically ill. In this study, we intended to uncover whether the adverse effect of fluid overload on survival could be applied to all of the patients with AKI who received continuous renal replacement therapy (CRRT). METHODS: We analyzed 341 patients with AKI who received CRRT in our intensive care units. The presence of fluid overload was defined as a minimum 10% increase in body weight from the baseline. Demographics, comorbid diseases, clinical data, severity of illness [the sequential organ failure assessment (SOFA) score, number of vasopressors, diagnosis of sepsis, use of ventilator] upon ICU admission, fluid overload status, and time elapsed from AKI diagnosis until CRRT initiation were reviewed from the medical charts. RESULTS: Patients with total fluid overload from 3 days before CRRT initiation to ICU discharge had a significantly lower survival rate after ICU admission, as compared to patients with no fluid overload (P < 0.001). Among patients with sepsis (P < 0.001) or with high SOFA scores (P < 0.001), there was a significant difference in survival of the patients with and without fluid overload. In patients without sepsis or with low SOFA score, there was no significant difference in survival of patients irrespective of fluid overload. CONCLUSION: Our study demonstrates that the adverse effect of fluid overload on survival is more evident in patients with sepsis or with more severe illness, and that it might not apply to patients without sepsis or with less severe illness.

Enhanced expression of two discrete isoforms of matrix metalloproteinase-2 in experimental and human diabetic nephropathy.

BACKGROUND: We recently reported on the enhanced expression of two isoforms of matrix metalloproteinase-2 (MMP-2) in human renal transplantation delayed graft function. These consist of the conventional secreted, full length MMP-2 isoform (FL-MMP-2) and a novel intracellular N-Terminal Truncated isoform (NTT-MMP-2) generated by oxidative stress-mediated activation of an alternate promoter in the MMP-2 first intron. Here we evaluated the effect of hyperglycemia and diabetes mellitus on the in vitro and in vivo expression of the two MMP-2 isoforms. METHODS: We quantified the abundance of the FL-MMP-2 and NTT-MMP-2 transcripts by qPCR in HK2 cells cultured in high glucose or 4-hydroxy-2-hexenal (HHE) and tested the effects of the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC). The streptozotocin (STZ) murine model of Type I diabetes mellitus and renal biopsies of human diabetic nephropathy were used in this study. RESULTS: Both isoforms of MMP-2 in HK2 cells were upregulated by culture in high glucose or with HHE. PDTC treatment did not suppress high glucose-mediated FL-MMP-2 expression but potently inhibited NTT-MMP-2 expression. With STZ-treated mice, renal cortical expression of both isoforms was increased (FL-MMP-2, 1.8-fold; NTT-MMP-2, greater than 7-fold). Isoform-specific immunohistochemical staining revealed low, but detectable levels of the FL-MMP-2 isoform in controls, while NTT-MMP-2 was not detected. While there was a modest increase in tubular epithelial cell staining for FL-MMP-2 in STZ-treated mice, NTT-MMP-2 was intensely expressed in a basolateral pattern. FL-MMP-2 and NTT-MMP-2 isoform expression as quantified by qPCR were both significantly elevated in renal biopsies of human diabetic nephropathy (12-fold and 3-fold, respectively). CONCLUSIONS: The expression of both isoforms of MMP-2 was enhanced in an experimental model of diabetic nephropathy and in human diabetic nephropathy. Selective MMP-2 isoform inhibition could offer a novel approach for the treatment of diabetic renal disease.

Three cases of spontaneous lumbar artery rupture in hemodialysis patients.

We encountered three cases of retroperitoneal hematoma caused by spontaneous lumbar artery rupture, a rare vascular complication. At the time of retroperitoneal hematoma, two patients were on anticoagulant/antiplatelet therapy. One patient was not taking any anticoagulant/antiplatelet agents but was receiving hemodialysis treatment with heparin. Lumbar artery rupture was successfully controlled by transcatheter arterial embolization in all patients, but one patient developed multiple organ failure and died. We suggest that spontaneous lumbar artery rupture may occur in patients being treated with maintenance hemodialysis or anticoagulant/antiplatelet therapy. Therefore, clinicians should suspect lumbar artery rupture in patients with unstable vital signs and rapid onset of anemia because early diagnosis and appropriate intervention are necessary to decrease the risks of morbidity and mortality.

Unmasked chronic renal function deterioration after unilateral adrenalectomy in patients with primary aldosteronism.

We report 2 cases of chronic estimated glomerular filtration rate (eGFR) decline after unilateral adrenalectomy due to primary aldosteronism. The patients were diagnosed with unilateral adrenal cortical adenoma releasing aldosterone. Two patients were examined for hypertension and hypokalemia. Unilateral laparoscopic adrenalectomy was performed in both cases, and pathology confirmed adrenal cortical adenoma. After adrenalectomy, hypertension and hypokalemia improved to within normal range. However, the eGFR decreased postoperatively, and abdominal computed tomography scan showed decreased kidney size compared to previous images. Kidney biopsy was performed to delineate the exact cause of renal function deterioration and revealed hypertensive changes with chronic interstitial changes, indicating that glomerular hyperfiltration with aldosterone excess masked renal function damage. Physicians have to consider the probability of postadrenalectomy eGFR decline related to chronic hypertensive change.

Short- and Long-Term Mortality Rates of Elderly Acute Kidney Injury Patients Who Underwent Continuous Renal Replacement Therapy.

BACKGROUND: The world's population is aging faster and the incidence of acute kidney injury (AKI) needing continuous renal replacement therapy (CRRT) is increasing in elderly population. The outcome of AKI needing CRRT in elderly patients is known to be poor. However, the definitions of elderly used in the previous literatures were diverse and, there were few data that compared the long-term mortality rates of these patients with middle aged patients. This study was aimed to evaluate this issue. METHODS: This study was a single-center, retrospective cohort study of patients who underwent CRRT from January 2013 to December 2015. The patients were divided into the following four age cohorts: middle-aged (55-64), young-old (65-74), middle-old (75-84), and old-old (≥85). The short- and long-term mortality rates for each age cohort were compared. RESULTS: A total of 562 patients met the inclusion criteria. The short-term mortality rate was 57.3% in the entire cohort. Compared with the middle-aged cohort, the middle-old cohort (HR 1.48 (1.09-2.02), p = 0.012) and the old-old cohort (HR 2.33 (1.30-4.19), p = 0.005) showed an increased short-term mortality rate along with an increased SOFA score, acidemia and a prolonged prothrombin time. When we analyzed the long-term mortality rate of the 238 survived patients, the middle-old cohort (HR 3.76 (1.84-7.68), p<0.001), the old-old cohort (HR 4.40(1.20-16.10), p = 0.025), a lower BMI, the presence of liver cirrhosis, the presence of congestive heart failure and a history of sepsis were independent risk factors for the prediction of long-term mortality. CONCLUSION: Compared with the middle-aged cohort, the middle-old and the old-old cohort showed an increased short-term and long-term mortality rate. However, in the young-old cohort, neither the short-term nor the long-term mortality rate was increased.

Is Multi-Drug Resistant Tuberculosis More Prevalent in HIV-Infected Patients in Korea?

The epidemiological synergy between human immunodeficiency virus (HIV) and tuberculosis (TB) is a major threat to public health. However, the association between HIV and multi-drug resistant tuberculosis (MDR-TB) is not clear. To explore the association between HIV and MDR-TB infection, a case-control study was performed in Korea. A total of 1606 culture-proven TB patients (45 HIV vs. 1561 non-HIV) from January 2006 to October 2014 were included in this analysis. MDR-TB rates were 11.1% and 8.2% in the HIV and non-HIV groups, respectively (p=0.42), thus indicating that MDR-TB was not significantly associated with HIV infection in Korea.

Alpha1-Antitrypsin Attenuates Renal Fibrosis by Inhibiting TGF-ß1-Induced Epithelial Mesenchymal Transition.

Alpha1-antitrypsin (AAT) exerts its anti-inflammatory effect through regulating the activity of serine proteinases. This study evaluated the inhibitory effects of AAT against the transforming growth factor (TGF)-ß1 induced epithelial-to-mesenchymal transition (EMT) in unilateral ureter obstruction (UUO) mice and Madin-Darby canine kidney (MDCK) cells. C57BL/6 mice with induced UUO were injected intraperitoneally with AAT (80 mg/Kg) or vehicle for 7 days. MDCK cells were treated with TGF-ß1 (2 ng/mL) for 48 hours to induce EMT, and co-treated with AAT (10 mg/mL) to inhibit the EMT. Masson's trichrome and Sirius red staining was used to estimate the extent of renal fibrosis in UUO mice. The expression of alpha-smooth muscle actin (α-SMA), vimentin, fibronectin, collagen I, and E-cadherin in MDCK cells and kidney tissue were evaluated. Masson's and Sirius red staining revealed that the area of renal fibrosis was significantly smaller in AAT treated UUO group compared with that of UUO and vehicle treated UUO groups. AAT treatment attenuated upregulation of Smad2/3 phosphorylation in UUO mouse model. Co-treatment of MDCK cells with TGF-ß1 and AAT significantly attenuated the changes in the expression of α-SMA, vimentin, fibronectin, collagen I, and E-cadherin. AAT also decreased the phosphorylated Smad3 expression and the phosphorylated Smad3/Smad3 ratio in MDCK cells. AAT treatment inhibited EMT induced by TGF-ß1 in MDCK cells and attenuated renal fibrosis in the UUO mouse model. The results of this work suggest that AAT could inhibit the process of EMT through the suppression of TGF-ß/Smad3 signaling.

Decreased plasma α-Klotho predict progression of nephropathy with type 2 diabetic patients.

AIM: The potential role of soluble α-klotho in diabetic kidney disease has not yet been evaluated. The aim of this study was to evaluate the association of plasma and/or urine α-klotho with the progression of type 2 diabetic nephropathy. METHODS: The baseline values of plasma and urine α-klotho were measured in 147 patients with type 2 diabetes mellitus with an estimated glomerular filtration rate (eGFR) of ≥60mL/min/1.73m(2). In this prospective observational study, a total of 109 type 2 diabetic patients were followed up for 34months (8-50 months). RESULTS: Plasma α-klotho, but not urine α-klotho, was negatively correlated with the decline of eGFR (r=-0.304, P=0.001; r=0.042, P=0.068, respectively). After adjusting for several clinical parameters, baseline eGFR and urine ACR, plasma α-klotho was significantly associated with the decline of eGFR (r=-0.219, P=0.008). In the normoalbuminuria group (n=63), the plasma α-klotho remained significantly associated with a decline in eGFR (r=0.324, P=0.004) in the final model. CONCLUSIONS: It is suggested that plasma α-klotho may be an early biomarker for predicting renal impairment in type 2 diabetic patients. The disappearance of a compensatory increase of plasma α-klotho might be a predictive marker for the progression of type 2 diabetic nephropathy.

Incidence and risk factors of hepatitis C virus infection among human immunodeficiency virus (HIV) patients in a large HIV clinic in South Korea.

BACKGROUND/AIMS: Increasing incidences of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected men who have sex were reported in the United States and Europe. However, few studies regarding the epidemiology of HCV infection in HIV-infected patients in Asian countries have been reported. METHODS: To determine the prevalence and incidence of HCV infection in HIV-infected patients, a retrospective cohort study was conducted. All HIV-infected patients who visited a tertiary care hospital in Korea from 2000 to 2013 were identified. Patients with ≥ 1 HCV antibody (Ab) test were included and observed until December 2014. RESULTS: Among 996 HIV-infected patients, 790 patients (79%) had baseline HCV Ab tests and 41 (5.2%) were positive at baseline and four at follow-up. Experience of injecting drug use (IDU; adjusted odds ratio, 16.20; 95% confidence interval [CI], 1.56 to 167.89; p < 0.01) was significantly associated with prevalent HCV infection. Conversion to HCV Ab positivity was observed in four of 384 included patients, with an incidence rate of 2.22 (95% CI, 0.60 to 5.80)/1,000 person-years (PYs); 164.89 (95% CI, 34.00 to 481.88)/1,000 PYs in patients with IDU, and 1.40 (95% CI, 0.35 to 7.79)/1,000 PYs in men who have sex with men who denied IDU. There was no significant increase in incidence rate of HCV in HIV-infected patients from 2009 to 2014 (p = 0.119). Among 19 patients who were positive for HCV RNA, genotype 1b (73%) was the most common following 2a/2c (20%). CONCLUSIONS: IDU was an independent risk factor for prevalent HCV infection. Prevalence of HCV infection was low and incidence of HCV infection was not significantly increased in HIV-infected patients in South Korea.

Predictors of Poor Retention in Care of HIV-infected Patients Receiving Antiretroviral Therapy in Korea: Five-Year Hospital-based Retrospective Cohort Study.

Poor retention in care (RIC) is associated with higher antiretroviral therapy (ART) failure and worse survival. Identifying high risk patients for poor RIC is important for targeted intervention. A retrospective cohort study was conducted at a tertiary care hospital in Korea. HIV-infected patients initiating ART during 2002-2008 were included. 5 year-RIC was measured by hospital visit constancy (HVC) at 5 years after initiating ART. Among 247 enrolled patients, 179 (72.5%) remained in care, 20 (8.1%) were transferred to other hospitals, 9 (3.6%) died and 39 (15.8%) were lost to follow-up. We compared the demographic, psychosocial, and clinical characteristics between the groups with 100% HVC (n = 166, 67.2%) and ≤ 50% HVC (n = 33, 13.4%). In multivariable analysis, ART-starting age ≤ 30 years (odds ratio [OR] 4.08 vs. > 50; 95% confidence interval [CI] 1.10-15.15, P = 0.036), no non-HIV related comorbidity (OR 2.94 vs. comorbidity ≥ 1; 95% CI 1.02-8.49, P = 0.046), baseline CD4 cell count > 300 cells/µL (OR 3.58 vs. ≤ 200; 95% CI 1.33-9.65, P = 0.012) were significant predictable factors of poor RIC. HIV/AIDS care-givers should pay attention to young patients with higher baseline CD4 cell counts and no non-HIV related comorbidity.