Endostatin is released during extracellular matrix remodeling and is involved in the development of vascular pathology and cardiovascular (CV) disease. However, the role of circulating endostatin as a biomarker of vascular calcification and CV events in patients undergoing hemodialysis (HD) remains unclear. Methods: A total of 372 patients undergoing HD were prospectively recruited. Plasma endostatin levels were measured at baseline, and their associations with circulating mineral bone disease (MBD) biomarkers and abdominal aortic vascular calcification scores were analyzed. The primary endpoint was defined as a composite of CV and cardiac events. Results: Plasma levels of patients in endostatin tertile 3 were significantly associated with low-density lipoprotein cholesterol levels and predialysis systolic blood pressure in multivariate analysis. However, endostatin levels did not correlate with circulating MBD biomarkers or vascular calcification scores. Patients in endostatin tertile 3 had a significantly higher cumulative event rate for the composite of CV events (p = 0.006). Endostatin tertile 3 was also associated with an increased cumulative rate of cardiac events (p = 0.04). In multivariate Cox regression analyses, endostatin tertile 3 was associated with a 4.37-fold risk for composite CV events and a 3.88-fold risk for cardiac events after adjusting for multiple variables. Conclusion: Higher circulating endostatin levels were independently associated with atherosclerotic risk factors but did not correlate with MBD markers or vascular calcification. Higher circulating endostatin levels were associated with a greater risk of composite CV events in patients undergoing HD, and endostatin is a biomarker that helps to determine the high risk of CV events.

Operational tolerance (OT), defined as maintaining stable graft function without immunosuppression after transplant surgery, is an ideal goal for kidney transplant recipients (KTRs). Recent investigations have demonstrated the distinctive features of B cells, T cells, and dendritic cell-related gene signatures and the distributions of circulating lymphocytes in these patients; nonetheless, substantial heterogeneities exist across studies. This study was conducted to determine whether previously reported candidate gene biomarkers and the profiles of lymphocyte subsets of OT could be applied in Korean KTRs. Peripheral blood samples were collected from 153 patients, including 7 operationally tolerant patients. Quantitative real-time PCR and flow cytometry were performed to evaluate gene expression and lymphocyte subsets, respectively. Patients with OT showed significantly higher levels of B cell-related gene signatures (IGKV1D-13 and IGKV4-1), while T cell-related genes (TOAG-1) and dendritic cell-related genes (BNC2, KLF6, and CYP1B1) were not differentially expressed across groups. Lymphocyte subset analyses also revealed a higher proportion of immature B cells in this group. In contrast, the distributions of CD4⁺ T cells, CD8⁺ T cells, mature B cells, and memory B cells showed no differences across diagnostic groups. An OT signature, generated by the integration of IGKV1D-13, IGKV4-1, and immature B cells, effectively discriminated patients with OT from those in other diagnostic groups. Finally, the OT signature was observed among 5.6% of patients who had stable graft function for more than 10 years while on immunosuppression. In conclusion, we validated an association of B cells and their related signature with OT in Korean KTRs.
B-Lymphocytes ; Biomarkers ; Flow Cytometry ; Gene Expression ; Humans ; Immunosuppression ; Kidney Transplantation ; Kidney* ; Lymphocyte Subsets ; Lymphocytes ; Memory ; Precursor Cells, B-Lymphoid ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; T-Lymphocytes ; Transplant Recipients* ; Transplants

BACKGROUND: The aim of this multicenter study was to evaluate the safety and efficacy of tolvaptan (TLV) in Korean patients with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). METHODS: Of 51 enrolled patients with SIADH, 39 patients (16 female patients, aged 70.8 ± 11.3 years) were included in an intention to treat analysis. All patients received 15 mg/day as the initial dose, and the dose was then increased up to 60 mg/day (as needed) until day 4. RESULTS: Serum sodium increased significantly from baseline during the first 24 hours (126.8 ± 4.3 vs. 133.7 ± 3.8 mmol/L, P < 0.001), rose gradually between days 1 and 4 (133.7 ± 3.8 vs. 135.6 ± 3.6 mmol/L, P < 0.05), and then plateaued until day 11 (136.7 ± 4.5 mmol/L). The correlation between the change in serum sodium for the first 24 hours and initial serum sodium concentration was significant (r = −0.602, P < 0.001). In severe hyponatremia (< 125 mmol/L), the change was significantly higher (11.1 ± 4.8 mmol/L) than in moderate (6.4 ± 2.5 mmol/L, P < 0.05) or mild hyponatremia (4.3 ± 3.3 mmol/L, P < 0.01). In addition, logistic regression analysis showed that body weight (odds ratio [OR], 0.858; 95% confidence interval [CI], 0.775–0.976; P = 0.020) and body mass index (BMI) (OR, 0.692; 95% CI, 0.500–0.956; P = 0.026) were associated with rapid correction. No serious adverse events were reported, but in 13% of patients hyponatremia was overcorrected. CONCLUSION: TLV is effective in correcting hyponatremia and well-tolerated in Korean patients with SIADH. However, those with low body weight, low BMI or severe hyponatremia, could be vulnerable to overcorrection with the initial dose of 15 mg TLV.

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.
Acid-Base Equilibrium ; Acidosis ; Acidosis, Renal Tubular* ; Autoantibodies ; Diagnosis ; Exocrine Glands ; Fanconi Syndrome ; Female ; Femoral Fractures ; Glomerulonephritis ; Humans ; Hypokalemia ; Kidney ; Muscle Weakness ; Nephritis, Interstitial ; Osteomalacia ; Paralysis ; Saliva ; Tears

One of the major pathophysiological features of primary hypertension is an inappropriate activation of the sympathetic nervous system, which is mediated by excessive synthesis and secretion of catecholamine into the blood. Tyrosine hydroxylase (TH), a rate-limiting enzyme in the synthesis of catecholamine, has been highlighted because genetic variations of TH could alter the activity of the sympathetic nervous system activity and subsequently contribute to the pathogenesis of hypertension. Here, we discuss the role of TH as a regulator of sympathetic activity and review several studies that investigated the relationship between genetic variations of TH and hypertension.
Genetic Variation* ; Hypertension* ; Polymorphism, Single Nucleotide ; Sympathetic Nervous System ; Tyrosine 3-Monooxygenase* ; Tyrosine*

BACKGROUND: Endocan, previously called endothelial cell–specific molecule-1, is a soluble proteoglycan that is secreted from vascular endothelial cells. Elevated plasma endocan levels were shown to be associated with poor cardiovascular outcomes in patients with chronic kidney disease (CKD). We investigated the clinical relevance of plasma and urine endocan levels in patients with immunoglobulin A nephropathy (IgAN). METHODS: Sixty-four patients with IgAN and 20 healthy controls were enrolled in this study. Plasma and urine endocan levels were measured. Clinical parameters, pathologic grades, and renal outcomes were compared among subgroups with different plasma and urine endocan levels. RESULTS: Both plasma and urine endocan levels were significantly higher in patients with IgAN than in controls. Elevated serum phosphorus and C-reactive protein were independent determinants for plasma endocan, and elevated C-reactive protein was also an independent determinant for urine endocan levels in multivariate analysis. Plasma endocan level was not significantly different across CKD stages, but patients with higher plasma endocan levels showed adverse renal outcome. Urine endocan levels were also elevated in patients with poor renal function. Cox proportional hazard models showed that high plasma endocan was an independent risk factor for CKD progression after adjusting for the well-known predictors of outcome in patients with IgAN. CONCLUSION: This study suggested that plasma endocan might be useful as a prognostic factor in patients with IgAN.
C-Reactive Protein ; Endothelial Cells ; Glomerulonephritis, IGA* ; Humans ; Immunoglobulin A* ; Immunoglobulins* ; Multivariate Analysis ; Phosphorus ; Plasma* ; Prognosis* ; Proportional Hazards Models ; Proteoglycans ; Renal Insufficiency, Chronic ; Risk Factors

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 m²/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.
Anaphylaxis ; Creatinine ; Disease Progression ; Follow-Up Studies ; Glomerular Filtration Rate ; Glomerulonephritis ; Glomerulonephritis, IGA* ; Hematuria ; Humans ; Immunoglobulin A* ; Immunoglobulin E* ; Immunoglobulins* ; Male ; Nephrotic Syndrome ; Proteinuria

We report the first case of Ramsay Hunt syndrome (RHS) diagnosed after kidney transplantation in Korea. RHS is a disease caused by latent varicella-zoster characterized to involve geniculate ganglion of the seventh cranial nerve. Patients who have undergone kidney transplantation can be easily affected by viral infections because of their immune-compromised status. A 35-year-old man with hypertensive end-stage renal disease underwent kidney transplantation. Two months after surgery, the recipient was diagnosed with RHS and treated with antivirals and steroids. However, after using the antiviral agents for the recommended duration, facial paralysis occurred as a new presentation and he required further treatment. Otalgia and periauricular vesicles improved, but the facial palsy remained.
Adult ; Antiviral Agents ; Earache ; Facial Nerve ; Facial Paralysis ; Geniculate Ganglion ; Herpes Zoster Oticus* ; Herpesvirus 3, Human ; Humans ; Kidney Failure, Chronic ; Kidney Transplantation* ; Kidney* ; Korea ; Steroids

BACKGROUND: Recent evidence demonstrates that high doses of epoetin-alpha (EPO-alpha) can be administrated at extended intervals, despite its relatively short serum half-life. However, no prospective randomized trials on the effects of extended dosing intervals of EPO-alpha compared with darbepoetin-alpha (DA-alpha) have been performed. This study was designed to investigate whether a single biweekly (Q2W) administration of a high dose of EPO-alpha is as effective as DA-alpha for anemia in chronic kidney disease (CKD) patients not receiving dialysis. METHODS: Sixty non-dialysis CKD patients were equally randomized to either Q2W subcutaneous EPO-alpha (10,000 unit) or DA-alpha (50microg) therapy groups for the first 6 weeks. After a 6-week washout period, the participants of the EPO-alpha and DA-alpha treatment groups switched to the alternate regimen for 6 weeks. The mean hemoglobin (Hb) levels after erythropoiesis stimulating agent (ESA) therapy and percentage change in Hb levels from baseline to the end of the study were analyzed. RESULTS: The mean Hb levels of postESA therapy increased significantly compared with those of preESA therapy in both ESA regimens. The percentage increase in Hb levels and erythropoietin resistance index did not show a significant difference between the different ESA regimens. No difference was observed between the regimens regarding mean Hb levels after ESA therapy. Additionally, there were no serious adverse effects leading to withdrawal from treatment. CONCLUSION: Biweekly high doses of EPO-alpha therapy may be equally as effective as Q2W DA-alpha therapy in maintaining target Hb levels in non-dialysis CKD patients.
Anemia ; Cross-Over Studies* ; Dialysis* ; Erythropoiesis ; Erythropoietin ; Half-Life ; Humans ; Renal Insufficiency, Chronic*

OBJECTIVE: To assess the umbilical nucleated red blood cell counts and perinatal outcomes according to umbilical artery Doppler end diastolic velocity in severe preeclampsia. MATERIALS AND METHODS: A prospective case-control study comparing 42 severe preeclampsia patients who had present umbilical artery end diastolic velocity with 7 severe preeclampsia patients who absent end diastolic velocity for umbilical nucleated red blood cell counts and perinatal outcomes. RESULTS: Those with absent end diastolic velocity did not have significantly greater nucleated red blood cell counts, but they had increased hemoglobin, hematocrit. These newborn had significantly lower birth weight, increased Cesarean section rate for fetal distress and been more frequently admitted to the neonatal intensive care unit. These newborn also had significantly increased intracranial hemorrhage,assisted ventilation and longer hospital days. CONCLUSION: No correlation with nucleated red blood cell counts and chronic fetal hypoxia were presented. However further study with more expanded cases for the role of nucleated red blood cell counts as a marker of fetal hypoxia will be needed.
Birth Weight ; Case-Control Studies ; Cesarean Section ; Erythrocyte Count* ; Erythrocytes* ; Female ; Fetal Distress ; Fetal Hypoxia ; Hematocrit ; Humans ; Infant, Newborn ; Intensive Care, Neonatal ; Pre-Eclampsia* ; Pregnancy ; Prospective Studies ; Umbilical Arteries ; Ventilation