Serum interferon-γ and urinary monocyte chemoattractant peptide-1 are important factors in the pathogenesis of immunoglobulin A nephropathy.

BACKGROUND: Imbalance of T helper (Th) 1/2 cells has been shown to contribute to the development of immunoglobulin A nephropathy (IgAN). To address the inconsistent results on the role of Th1/Th2 polarization, we evaluated the levels of Th1/Th2 cytokines in various samples from patients with IgAN. METHODS: Thirty-one patients with biopsy-proven IgAN (age, 34.48 ± 12.10 years) and 25 healthy controls (age, 44.84 ± 13.72 years) were enrolled. We evaluated the relationship between the levels of Th1/Th2 cytokines and the response to glucocorticoid treatment. RESULTS: The levels of serum interferon-gamma (IFNγ) and urinary monocyte chemoattractant peptide (MCP)-1 were higher in the IgAN group than in the control group. The levels of MCP-1 in urine and secreted by peripheral blood mononuclear cells (PBMCs) were significantly different among three groups categorized based on daily proteinuria. The level of urinary MCP-1 was significantly correlated with proteinuria. The levels of urinary MCP-1, serum interleukin (IL)-4, IFNγ, and IL-2 secreted by PBMCs and intrarenal IL-1 messenger RNA (mRNA) were significantly correlated with the ratio of proteinuria at 6 months to baseline proteinuria in patients undergoing glucocorticoid treatment. MCP-1 mRNA and protein levels were significantly upregulated in mesangial cells stimulated with IFNγ among representative Th1/Th2 cytokines. CONCLUSION: IFNγ was shown to be a key cytokine in the pathogenic processes underlying IgAN, and its upregulation induced an increase in urinary MCP-1 production. These findings suggest that Th1 cytokines may play an important role in the development of IgAN.

Clinical relevance of cell-free mitochondrial DNA during the early postoperative period in kidney transplant recipients.

Recent studies indicate that urinary mitochondrial DNA (mtDNA) is predictive of ischemic AKI and is related to delayed graft function (DGF) in renal transplantation. Nevertheless, the clinical implications and prognostic value of urinary mtDNA in kidney transplantation remain undetermined. Here, we aimed to evaluate the associations between cell-free mtDNA and clinical parameters, including pathological findings in allograft biopsy and post-transplant renal function. A total of 85 renal transplant recipients were enrolled, and blood and urine samples were collected at a median of 17 days after transplantation. Cell-free nuclear and mtDNA levels were measured by quantitative polymerase chain reaction for LPL and ND1 genes. Urinary cell-free mtDNA levels were significantly higher in patients with DGF (P < 0.001) and cases of deceased donor transplantation (P < 0.001). The subjects with acute rejection showed higher urinary mtDNA levels than those without abnormalities (P = 0.043). In addition, allograft functions at 9- and 12-month post-transplantation were significantly different between tertile groups of mtDNA independent of the presence of DGF or acute rejection, showing significantly better graft outcome in the lowest tertile group. Urinary cell-free mtDNA levels during the early post-transplant period are significantly associated with DGF, acute rejection in graft biopsy, and short-term post-transplant renal function.

Sex-related differences in the intratubular renin-angiotensin system in two-kidney, one-clip hypertensive rats.

The intratubular renin-angiotensin system (RAS) is thought to play an essential role in hypertensive renal disease, but information regarding sex-related differences in this system is limited. The present study investigated sex differences in the intratubular RAS in two-kidney, one-clip (2K1C) rats. A 2.5-mm clip was placed on the left renal artery of Sprague-Dawley rats, and rats were euthanized 3 or 5 wk after the operation. Systolic blood pressure increased in 2K1C rats in both sexes but was significantly higher in male rats than in female rats, and an antihypertensive effect was not observed in 2K1C ovariectomized (OVX) female rats. Compared with male 2K1C rats, intratubular angiotensin-converting enzyme (ACE) and ANG II were repressed, and intratubular ACE2, angiotensin (1-7), and Mas receptor were increased in both kidneys in female 2K1C rats 5 wk after surgery. Comparison with male and female rats and intratubular mRNA levels of ACE and ANG II type 1 receptor were augmented in OVX female rats, regardless of the clipping surgery 3 wk postoperation. ANG II type 2 receptor was upregulated in female rats with or without OVX; thus, the ANG II type 1-to-type 2 receptor ratio was higher in male rats than in female rats. In conclusion, female rats were protected from hypertensive renal and cardiac injury after renal artery clipping. An increase in the intratubular nonclassic RAS [ACE2/angiotensin (1-7)/Mas receptor] and a decrease in the ANG II type 1-to-type 2 receptor ratio could limit the adverse effects of the classic RAS during renovascular hypertension in female rats, and estrogen is suggested to play a primary role in the regulation of intratubular RAS components.

Combination therapy of low-dose cyclosporine and steroid in adults with IgA nephropathy
.

BACKGROUND: A few clinical trials in IgA nephropathy (IgAN) have shown that cyclosporine A (CyA) had therapeutic efficacy in reducing proteinuria. MATERIALS AND METHODS: This is a retrospective study, and all cases were selected based on kidney biopsy-proven IgAN. We reviewed the data of IgAN patients in the glomerulonephritis registry at Kyung Hee University Medical center and collected data on 86 patients with urinary protein/Cr ratio (PCR; g/g) > 0.5 and estimated GFR (eGFR) of > 50 mL/min/1.73m2 who were treated with combination therapy of low-dose CyA plus low-dose steroid (C+P; n = 37) and high-dose steroid single therapy (P; n = 49). RESULTS: In the C+P group, the mean duration of therapy was 14.5 ± 13.1 months, and the mean duration of follow-up 66.2 ± 36.3 months. In the C+P group, the urine PCR levels significantly declined after treatment (< 0.05). After 6 months of treatment, 12 (32%) patients were in complete remission and 7 (19%) in partial remission in the C+P group, compared with 21 (42%) and 11 (22%) in the P group, respectively. Urine PCR levels were also significantly reduced in 12 patients in the C+P group who had initial urine PCR between 0.5 and 1.0. The degree of hematuria was significantly reduced after treatment in the C+P group. These effects of C+P therapy on proteinuria and hematuria were very comparable to high-dose P therapy. After 2 years, a decline in renal function, > 25% decrease in eGFR from baseline levels, developed in 3 (8.1%) in the C+P group, compared with 4 (8.2%) in the P group. The rate of decline in renal function during follow-up was -0.14 ± 0.40 mL/min/1.73m2/month in the C+P group compared with -0.12 ± 0.22 mL/min/1.73m2/month in the P group. There were no changes of mean eGFR during the first 24 months, but the eGFR significantly decreased at last follow-up in both groups. When patients in the C+P group were divided into progressive (n = 9) and nonprogressive (n = 28) groups, a significant reduction in the amount of proteinuria after treatment was observed in the nonprogressive group, in contrast to the progressive group. In the C+P group, there were no severe adverse effects, especially no acute renal impairment, requiring discontinuation of CyA in this study. The incidence of infection was much lower in the C+P group than that in the P group. The limitation is that CyA acts to nonspecifically reduce proteinuria, so it requires long-term follow-up off CyA therapy for more than 2 years to determine. CONCLUSION: Our retrospective uncontrolled study provides only weak evidence that combination therapy of low-dose C+P could be an alternative to high-dose P therapy and be safe in adult IgAN patients with relatively normal renal function and proteinuria of > 0.5 g/g. Development of safe and effective therapy is still a major challenge requiring well-controlled prospective studies with this or other combination therapies.

Conversion from acetate dialysate to citrate dialysate in a central delivery system for maintenance hemodialysis patients.

BACKGROUND: The objective of this study was to compare the impact of citrate dialysate (CD) and standard acetate dialysate (AD) in hemodialysis by central delivery system (CDS) on heparin demand, and clinical parameters. METHODS: We retrospectively evaluated 75 patients on maintenance hemodialysis with CDS. Patients underwent hemodialysis with AD over a six-month period (AD period), followed by another six-month period using CD (CD period). Various parameters including mean heparin dosage, high sensitivity C-reactive protein (hsCRP), calcium-phosphate product (CaxP), intact parathyroid hormone (iPTH), and urea reduction ratio (URR) were collated at the end of each period. RESULTS: Patients were 60.5 ± 14.7 years old, of whom 62.7% were male. Patients required less heparin when receiving CD (AD period: 1,129 ± 1,033 IU/session vs. CD period: 787 ± 755 IU/session, P < 0.001). After the CD period (ΔCD), pre-dialysis total CO2 increased to 1.21 ± 2.80 mmol/L, compared to -2.44 ± 2.96 mmol/L (P < 0.001) after the AD period (ΔAD). After the CD period, concentrations of iPTH (ΔAD: 73.04 ± 216.34 pg/mL vs. ΔCD: -106.66 ± 251.79 pg/mL, P < 0.001) and CaxP (ΔAD: 4.32 ± 16.63 mg2/dL2 vs. ΔCD: -4.67 ± 15.27 mg2/dL2, P = 0.015) decreased. While hsCRP levels decreased after the CD period (ΔAD: 0.07 ± 4.09 mg/L vs. ΔCD: -0.75 ± 4.56 mg/L, P = 0.705), the change was statistically insignificant. URR remained above clinical guideline of 65% after both periods (ΔAD: 72.33 ± 6.92% vs. ΔCD period: 69.20 ± 4.49%, P = 0.046). CONCLUSION: Our study confirmed that the use of CD in CDS required lower heparin doses compared to the use of AD. The use of CD also provided a more stable acid-base status.

Baseline High Blood Pressure is Associated with Clinico-Pathologic Findings and Later Renal Progression in Chronic Glomerulonephritis.

BACKGROUND: Several factors had been suggested to contribute to the development of hypertension in chronic glomerulonephritis (GN). This study was conducted to find the association of baseline blood pressure (BP) with pathophysiologic findings and later renal progression in chronic GN. METHODS: Clinico-pathological findings including serum creatinine (Cr), proteinuria, pathological findings, and urinary Na excretion were analyzed in a total of 233 patients with IgA nephropathy from The Kyung-Hee Cohort of GN. Glomerular surface area (GSA) was measured by imaging analysis and urine angiotensinogen (AGT) concentrations by human ELISA kits. RESULTS: Systolic BP was ≥130mmHg in 124 patients (53%). Systolic BP was negatively correlated with follow-up eGFR (r=-0.32, p<0.0001) and positively serum uric acid concentrations, while it had no significant relationships with initial serum Cr and eGFR. As compared with patients with systolic BP<130 mmHg, those with ≥130 mmHg were older and showed higher serum Cr, proteinuria, 24 hr urinary Na excretion, mean GSA, and T-I fibrosis, lower follow-up eGFR, and steeper decline in slope of eGFR. The results in patients with normal serum Cr concentrations were comparable to those in whole group. Systolic BP was positively correlated with age, baseline and follow-up proteinuria, serum uric acid concentrations and IgM deposit and negatively with follow-up eGFR. In subgroup analysis, systolic BP was also positively correlated with mean GSA and urinary AGT concentrations. CONCLUSION: This study showed that baseline systolic BP is related to urinary Na excretion, glomerulomegaly, T-I fibrosis and later renal progression in patients with IgA nephropathy.

Observations of the Effects of Angiotensin II Receptor Blocker on Angiotensin II-Induced Morphological and Mechanical Changes in Renal Tubular Epithelial Cells Using Atomic Force Microscopy.

OBJECTIVE: Angiotensin II (Ang II) plays a profibrotic role in the kidneys. Although many pathways of Ang II have been discovered, the morphological and mechanical aspects have not been well investigated. We observed the changes in tubular epithelial cells (TECs) after Ang II treatment with or without Ang II receptor blockers (ARBs) using atomic force microscopy (AFM). METHODS: TECs were stimulated with Ang II with or without telmisartan, PD123319, and blebbistatin. AFM was performed to measure the cellular stiffness, cell volume, and cell surface roughness. Epithelial to mesenchymal transition markers were determined via immunocytochemistry. RESULTS: After Ang II stimulation, cells transformed to a flattened and elongated mesenchymal morphology. Cell surface roughness and volume significantly increased in Ang II treated TECs. Ang II also induced an increase in phospho-myosin light chain and F-actin and a decrease in E-cadherin. Ang II coincubation with either telmisartan or blebbistatin attenuated these Ang II-induced changes. CONCLUSION: We report, for the first time, the use of AFM in directly observing the changes in TECs after Ang II treatment with or without ARBs. Simultaneously, we successfully measured the selective effect of PD123319 or blebbistatin. AFM could be a noninvasive evaluating strategy for cellular processes in TECs.

Urinary exosomal viral microRNA as a marker of BK virus nephropathy in kidney transplant recipients.

OBJECTIVE: Bkv-miR-B1-5p, one of the microRNAs encoded by BK virus, was recently reported to be elevated in the blood among the patients with BK virus nephropathy (BKVN). Urinary exosome was suggested to be a possible source of biomarker for kidney diseases, but it was unknown whether it could contain viral microRNA as well as human microRNAs. The aim of this study was to evaluate whether urinary exosomal BK viral microRNA were expressed during replication and could be used to diagnose BKVN in kidney transplant recipients. MATERIALS AND METHODS: In a cross-sectional multicenter study, we collected and analyzed 458 graft biopsies from 385 kidney transplant recipients. Urine samples were collected at the time of graft biopsy, and microRNAs in urinary exosome were measured once. For 13 patients with BKVN and 67 age, sex-matched kidney transplant recipients, we measured BK viral microRNA B1-5p, 3p and human microRNA-16 in urinary exosomal fraction and compared the diagnostic value with BK viral load in plasma and urine. RESULTS: Pathology proven BKVN was diagnosed in 13 patients (2.8%). High levels of bkv-miR-B1-5p and bkv-miR-B1-3p were shown in all patients with BKVN. Meanwhile, plasma BK viral load assay (cut-off value of ≥ 4.0 log10 copies/mL) showed false negative in 3 cases and urinary BK viral load assay (cut-off value of ≥ 7.0 log10 copies/mL) showed false negative in 1 case among these 13 patients. The receiver operator characteristics curve analysis for bkv-miR-B1-5p and bkv-miR-B1-5p/miR-16 showed excellent discriminative power for the diagnosis of BKVN, with area under the curve values of 0.989 and 0.985, respectively. CONCLUSIONS: This study suggests that urinary exosomal bkv-miR-B1-5p and bkv-miR-B1-5p/miR-16 could be surrogate markers for the diagnosis of BKVN.

Renal Tubular Acidosis in Patients with Primary Sjögren's Syndrome.

Primary Sjögren's syndrome (pSS) is characterized by lymphocytic infiltration of the exocrine glands resulting in decreased saliva and tear production. It uncommonly involves the kidneys in various forms, including tubulointerstitial nephritis, renal tubular acidosis, Fanconi syndrome, and rarely glomerulonephritis. Its clinical symptoms include muscle weakness, periodic paralysis, and bone pain due to metabolic acidosis and electrolyte imbalance. Herein, we describe the cases of two women with pSS whose presenting symptoms involve the kidneys. They had hypokalemia and normal anion gap metabolic acidosis due to distal renal tubular acidosis and positive anti-SS-A and anti-SS-B autoantibodies. Since one of them experienced femoral fracture due to osteomalacia secondary to renal tubular acidosis, an earlier diagnosis of pSS is important in preventing serious complications.

Clinicopathological features of diabetic and nondiabetic renal diseases in type 2 diabetic patients with nephrotic-range proteinuria.

Heavy proteinuria with or without features of nephrotic syndrome is associated with many primary and systemic diseases. For diabetic patients, distinguishing nondiabetic renal disease (NDRD) from diabetic nephropathy (DN) is important in choosing treatment modalities and determining renal prognosis. However, clinical relevance of heavy proteinuria is inconsistent with clinical DN assessments. This study investigated the clinicopathological features and renal outcomes of DN and NDRD in type 2 diabetic patients with nephrotic-range proteinuria.We enrolled 220 cases of type 2 diabetic patients who underwent renal biopsy. They were grouped according to the presence of nephritic-range proteinuria and pathological features. Baseline characteristics, laboratory findings, types of pathological diagnosis, and renal outcomes were analyzed in patients with heavy proteinuria.Upon kidney biopsy, 129 patients (58.6%) showed nephritic-range proteinuria. Patients with heavy proteinuria (an average urine protein-to-creatinine ratio of 10,008 ±â€Š7307 mg/gCr) showed lower serum albumin levels and higher total cholesterol levels, but did not show any difference in age, duration of diabetes, renal function, or the presence of retinopathy compared with those with mild-to-moderate proteinuria (an average urine protein-to-creatinine ratio of 1581 ±â€Š979 mg/gCr). Renal biopsy revealed that the prevalence of NDRD was 37.2% in patients with heavy proteinuria, which was significantly lower than that in patients with mild-to-moderate proteinuria (63.7%). The most common pathological types of NDRD were membranous nephropathy (41.7%), IgA nephropathy (14.6%), and minimal change disease (10.4%). NDRD patients showed lower prevalence of diabetic retinopathy and better kidney function irrespective of proteinuria. Immunosuppressive treatment was administered more frequently in patients with heavy proteinuria (56.3%) compared with patients with mild-to-moderate proteinuria (20%) because of the pathological differences according to the amount of proteinuria. Renal outcomes were significantly worse in patients with DN than in patients with NDRD.DN patients with heavy proteinuria exhibited different prevalence of NDRD and worse prognosis. Renal biopsy in type 2 diabetic patients should be more extensively considered to accurately diagnose NDRD, guide further management, and predict renal outcomes, especially in patients with nephrotic-range proteinuria.

Effects of statin therapy on clinical outcomes after acute myocardial infarction in patients with advanced renal dysfunction: A propensity score-matched analysis.

OBJECTIVE: Lipid lowering therapy is widely used for the prevention of cardiovascular complications after acute myocardial infarction (AMI). However, some studies show that this benefit is uncertain in patients with renal dysfunction, and the role of statins is based on the severity of renal dysfunction. In this study, we investigated the impact of statin therapy on major adverse cardiac events (MACEs) and all-cause mortality in patients with advanced renal dysfunction undergoing percutaneous coronary intervention (PCI) after AMI. METHODS: This study was based on the Korea Acute Myocardial Infarction Registry database. We included 861 patients with advanced renal dysfunction from among 33,205 patients who underwent PCI after AMI between November 2005 and July 2012. Patients were divided into two groups: a statin group (n = 537) and a no-statin group (n = 324). We investigated the 12-month MACEs (cardiac death, myocardial infarction, repeated PCI or coronary artery bypass grafting) and all-cause mortality of each group. Subsequently, a propensity score-matched analysis was performed. RESULTS: In the total population studied, no significant differences were observed between the two groups with respect to the rate of recurrent MI, repeated PCI, coronary artery bypass grafting (CABG), or all-cause mortality. However, the cardiac death rate was significantly lower in the statin group (p = 0.009). Propensity score-matched analysis yielded 274 pairs demonstrating, results similar to those obtained from the total population. However, there was no significant difference in the cardiac death rate in the propensity score-matched population (p = 0.103). Cox-regression analysis revealed only left ventricular ejection fraction to be an independent predictor of 12-month MACEs (Hazard ratio [HR] of 0.979, 95% confidence interval [CI], 0962-0.996, p = 0.018). CONCLUSIONS: Statin therapy was not significantly associated with a reduction in the 12-month MACEs or all-cause mortality in patients with advanced renal dysfunction undergoing PCI after AMI.

Both absolute and relative quantification of urinary mRNA are useful for non-invasive diagnosis of acute kidney allograft rejection.

Urinary mRNA analysis with three-gene set (18S rRNA, CD3ε, and IP-10) has been suggested as a non-invasive biomarker of acute rejection (AR) in kidney transplant recipients using quantitative real-time PCR (qPCR). Application of droplet digital PCR (ddPCR), which has been suggested to provide higher sensitivity, accuracy, and absolute quantification without standard curves, could be a useful method for the quantifying low concentration of urinary mRNA. We investigated the urinary expression of these three genes in Korean patients with kidney transplantation and also evaluated the usefulness of ddPCR. 90 urine samples were collected at time of allograft biopsy in kidney recipients (n = 67) and from patients with stable renal function more than 10 years (n = 23). Absolute quantification with both PCR system showed significant higher mRNA levels of CD3ε and IP-10 in AR patients compared with stable transplants (STA), but there was no difference in 18S rRNA expression across the patient groups. To evaluate discrimination between AR and STA, ROC curve analyses of CTOT-4 formula yielded area under the curve values of 0.72 (95% CI 0.60-0.83) and 0.77 (95% CI 0.66-0.88) for qPCR and ddPCR, respectively. However, 18S normalization of absolute quantification and relative quantification with 18S showed better discrimination of AR from STA than those of the absolute method. Our data indicate that ddPCR system without standard curve would be useful to determine the absolute quantification of urinary mRNA from kidney transplant recipients. However, comparative method also could be useful and convenient in both qPCR and ddPCR analysis.

Potential urine proteomics biomarkers for primary nephrotic syndrome.

BACKGROUND: Nephrotic syndrome (NS) is a nonspecific kidney disorder, commonly caused by minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and membranous nephropathy (MN). Here we analyzed urinary protein profiles, aiming to discover disease-specific biomarkers of these three common diseases in NS. METHODS: Sixteen urine samples were collected from patients with biopsy-proven NS and healthy controls. After removal of high-abundance proteins, the urinary protein profile was analyzed by LC-MS/MS to generate a discovery set. For validation, ELISA was used to analyze the selected proteins in 61 urine samples. RESULTS: The discovery set included 228 urine proteins, of which 22 proteins were differently expressed in MCD, MN, and FSGS. Among these, C9, CD14, and SERPINA1 were validated by ELISA. All three proteins were elevated in MCD, MN, and FSGS groups compared with in IgA nephropathy and healthy controls. When a regression model was applied, receiver operating characteristic analysis clearly discriminated MCD from the other causative diseases in NS. CONCLUSIONS: We developed a disease-specific protein panel that discriminated between three main causes of NS. Through this pilot study, we suggest that urine proteomics could be a non-invasive and clinically available tool to discriminate MCD from MN and FSGS.

Syndrome of inappropriate antidiuretic hormone secretion associated with seronegative neuromyelitis optica spectrum disorder.

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a potential cause of hyponatremia of the central nervous system (CNS). Although SIADH has been reported to be associated with many other central nervous disorders, its association with neuromyelitis optica (NMO) or NMO spectrum disorders are rare. NMO is a demyelinating disorder characterized by optic neuritis and transverse myelitis. Aquaporin-4 (AQP4), which is the target antigen for a NMO autoantibody, is the predominant CNS water channel. However, some NMO patients show seronegative AQP4 antibody results. The spectrum of NMO has been changed, and new findings about the disease have been reported. Here, we report a case of seronegative NMO spectrum disorder associated with SIADH.

Ameliorating Effect of Gemigliptin on Renal Injury in Murine Adriamycin-Induced Nephropathy.

Background. Previous studies have shown the antiapoptotic and anti-inflammatory potential of DPP-IV inhibitor in experimental models of renal injury. We tested whether DPP-IV inhibitor (gemigliptin) ameliorates renal injury by suppressing apoptosis, inflammation, and oxidative stress in mice with adriamycin nephropathy. Methods. Mice were treated with normal saline (control), gemigliptin (GM), adriamycin (ADR), or adriamycin combined with gemigliptin (ADR+GM). Apoptosis, inflammation, and oxidative stress were analyzed via western blotting, real-time PCR, light microscopy, and immunofluorescence. Results. In the ADR+GM group, urine albumin creatinine ratio decreased significantly compared with that in the ADR group on day 15. Glomerulosclerosis index and tubulointerstitial injury index in mice with adriamycin-induced nephropathy decreased after gemigliptin treatment. ADR group showed higher levels of apoptosis, inflammation, and oxidative stress-related molecules compared with the control group. The upregulation of these molecules was significantly reduced by gemigliptin. In the ADR group, the staining intensities of WT-1 and nephrin reduced, but these changes were ameliorated in the ADR+GM group. Conclusion. We demonstrated that gemigliptin ameliorates nephropathy by suppressing apoptosis, inflammation, and oxidative stress in mice administered adriamycin. Our data demonstrate that gemigliptin has renoprotective effects on adriamycin-induced nephropathy.

The pharmacodynamics of low and standard doses of ticagrelor in patients with end stage renal disease on hemodialysis.

BACKGROUND: Patients with end-stage renal disease (ESRD) on maintenance hemodialysis (HD) respond poorly to clopidogrel. We assessed the utility of low-dose ticagrelor in ESRD patients on maintenance HD. METHODS: In this single-center, prospective, randomized pharmacodynamic study, 52 ESRD patients on HD were prescribed clopidogrel (300mg loading dose [LD], then 75mg daily), standard-dose ticagrelor (180mg LD, then 90mg twice daily), or low-dose ticagrelor (90mg LD, then 90mg daily) for 14days. Platelet function was evaluated before and after therapy via light transmittance aggregometry and the VerifyNow™ P2Y12 assay. RESULTS: The adenosine diphosphate (ADP)-induced maximal extent of platelet aggregation differed significantly between the low-dose ticagrelor and clopidogrel groups (ANCOVA, p=0.04 after stimulation with 5µmol/L ADP; p<0.01 after stimulation with 20µmol/L ADP). Inhibition of platelet aggregation increased significantly in the order of clopidogrel, low-dose ticagrelor, and standard-dose ticagrelor, as revealed by adjusted intergroup comparison analysis (ANCOVA, p=0.04 after stimulation with 5µmol/L ADP; p=0.005 after stimulation with 20µmol/L ADP). The rates of onset of the antiplatelet effect curves from 0 to 5h after administration of the LDs were greater in the standard- and low-dose ticagrelor groups than in the clopidogrel group. Significant sequential reductions in P2Y12 reaction units were noted, in the following order: clopidogrel, low-dose ticagrelor, and standard-dose ticagrelor (ANCOVA, p<0.001). No bleeding occurred in the low-dose ticagrelor group. CONCLUSIONS: Low-dose ticagrelor afforded greater platelet inhibition than did clopidogrel in ESRD patients on HD.

The Predictive Role of Serum Triglyceride to High-Density Lipoprotein Cholesterol Ratio According to Renal Function in Patients with Acute Myocardial Infarction.

OBJECTIVE: A high serum triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio has been reported as an independent predictor for cardiovascular events in the general population. However, the prognostic value of this ratio in patients with renal dysfunction is unclear. We examined the association of the TG/HDL-C ratio with major adverse cardiovascular events (MACEs) according to renal function in patients with acute myocardial infarction (AMI). METHOD: This study was based on the Korea Acute Myocardial Infarction Registry database. Of 13,897 patients who were diagnosed with AMI, the study population included the 7,016 patients with available TG/HDL-C ratio data. Patients were stratified into three groups according to their estimated glomerular filtration rate (eGFR), and the TG/HDL-C ratio was categorized into tertiles. We investigated 12-month MACEs, which included cardiac death, myocardial infarction, and repeated percutaneous coronary intervention or coronary artery bypass grafting. RESULTS: During the 12-month follow up period, 593 patients experienced MACEs. There was a significant association between the TG/HDL-C ratio and MACEs (p<0.001) in the entire study cohort. Having a TG/HDL-C ratio value in the highest tertile of TG/HDL-C ratio was an independent factor associated with increased risk of MACEs (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.26-1.93; p<0.001). Then we performed subgroup analyses according to renal function. In patients with normal renal function (eGFR ≥ 90 ml/min/1.73m2) and mild renal dysfunction (eGFR ≥ 60 to < 90ml/min/1.73m2), a higher TG/HDL-C ratio was significantly associated with increased risk of MACEs (HR, 1.64; 95% CI, 1.04-2.60; p = 0.035; and HR, 1.56; 95% CI, 1.14-2.12; p = 0.005, respectively). However, in patients with moderate renal dysfunction (eGFR < 60 ml/min/1.73m2), TG/HDL-C ratio lost its predictive value on the risk of MACEs (HR, 1.23; 95% CI, 0.82-1.83; p = 0.317). CONCLUSIONS: In patients with AMI, TG/HDL-C ratio is a useful independent predictor of 12-month MACEs. However, this ratio does not have predictive power in patients with moderate renal dysfunction.

Elevated serum immunoglobulin E level as a marker for progression of immunoglobulin A nephropathy.

BACKGROUND: Immunoglobulin E (IgE) has traditionally been associated with anaphylaxis and atopic disease. Previous studies reported that serum IgE levels are elevated in nephrotic syndrome and suggested IgE levels as a prognostic indicator in glomerular diseases. The aim of this study was to explore the association between serum IgE levels and renal outcome in patients with immunoglobulin A nephropathy (IgAN). METHODS: We included 117 patients with biopsy-proven IgAN. Renal progression was defined if a patient meets one of these criteria: (1) a negative value of delta estimated glomerular filtration rate (mL/min/1.73 m(2)/mo) or (2) a rise in serum creatinine to an absolute level of ≥ 1.3 mg/dL (male) or 1.2 mg/dL (female). We defined delta changes in serum creatinine, estimated glomerular filtration rate, and proteinuria as a difference of values during the follow-up period. RESULTS: A total of 117 patients with IgAN were included. The serum IgE level was significantly high in the renal progressive group compared with the nonprogressive group. Sex and history of gross hematuria were significantly different between the high-IgE group and the low-IgE group. Regression analysis showed that a male sex, initial proteinuria, and change of proteinuria were significantly associated with serum IgE levels. CONCLUSION: The serum IgE level is potentially associated with disease progression and pathogenesis of IgAN.