Systemic sclerosis is an autoimmune disease characterized by inflammatory reactions and fibrosis. Myofibroblasts are considered therapeutic targets for preventing and reversing the pathogenesis of fibrosis in systemic sclerosis. Although the mechanisms that differentiate into myofibroblasts are diverse, transforming growth factor β (TGF-β) is known to be a key mediator of fibrosis in systemic sclerosis. This study investigated the effects of extracellular vesicles derived from human adipose stem cells (ASC-EVs) in an in vivo systemic sclerosis model and in vitro TGF-β1-induced dermal fibroblasts. The therapeutic effects of ASC-EVs on the in vivo systemic sclerosis model were evaluated based on dermal thickness and the number of α-smooth muscle actin (α-SMA)-expressing cells using hematoxylin and eosin staining and immunohistochemistry. Administration of ASC-EVs decreased both the dermal thickness and α-SMA expressing cell number as well as the mRNA levels of fibrotic genes, such as Acta2, Ccn2, Col1a1 and Comp. Additionally, we discovered that ASC-EVs can decrease the expression of α-SMA and CTGF and suppress the TGF-β pathway by inhibiting the activation of SMAD2 in dermal fibroblasts induced by TGF-β1. Finally, TGF-β1-induced dermal fibroblasts underwent selective death through ASC-EVs treatment. These results indicate that ASC-EVs could provide a therapeutic approach for preventing and reversing systemic sclerosis.

We report a rare case of the concurrent manifestation of central diabetes insipidus (CDI) and type 2 diabetes mellitus (DM). A 56 year-old man was diagnosed as a type 2 DM on the basis of hyperglycemia with polyuria and polydipsia at a local clinic two months ago and started an oral hypoglycemic medication, but resulted in no symptomatic improvement at all. Upon admission to the university hospital, the patient's initial fasting blood sugar level was 140 mg/dL, and he showed polydipsic and polyuric conditions more than 8 L urine/day. Despite the hyperglycemia controlled with metformin and diet, his symptoms persisted. Further investigations including water deprivation test confirmed the coexisting CDI of unknown origin, and the patient's symptoms including an intense thirst were markedly improved by desmopressin nasal spray (10 microg/day). The possibility of a common origin of CDI and type 2 DM is raised in a review of the few relevant adult cases in the literature.
Adult ; Blood Glucose ; Deamino Arginine Vasopressin ; Diabetes Insipidus, Neurogenic ; Diabetes Mellitus, Type 2 ; Diet ; Fasting ; Humans ; Hyperglycemia ; Metformin ; Polydipsia ; Polyuria ; Thirst ; Water Deprivation

Angioedema with eosinophilia is classified as the episodic and transient types according to the clinical course, the presence of recurrence and the response to treatment. Episodic angioedema with eosinophilia is characterized by recurrent angioedema, urticaria, periodical weight gain, peripheral eosinophilia and fever. The pathophysiologic mechanism is unknown, but it has been suggested that T-lymphocytes, eosinophils and cytokines may be the causes of this disorder. We report here on a 35-year-old woman with episodic angioedema and weight gain that she experienced about 3 days before the onset of menstruation.
Adult ; Angioedema ; Cytokines ; Eosinophilia ; Eosinophils ; Female ; Fever ; Humans ; Menstruation ; Recurrence ; T-Lymphocytes ; Urticaria ; Weight Gain

The impact of glucose-free icodextrin (ID) for overnight dwell as compared to conventional glucose-containing dialysate (GD) on potassium (K+) metabolism in continuous ambulatory peritoneal dialysis (CAPD) patients has not yet been investigated. Serum K+ in a total of 255 stable patients (116 on GD and 139 on ID) on CAPD for more than 6 months and in 139 patients on ID before and after ID use (Pre-ID and Post-ID) were observed along with nutritional markers in a 2-year study period (Jan. 2006 to Dec. 2007). The prevalence of hypokalemia was similar between patients on GD and ID (16.7% vs 17.3%), but was lower on Post-ID than Pre-ID (17.3% vs 20.5%) without statistic significance. The mean serum K+ level was higher on ID than on GD (P<0.05) as well as Post-ID than Pre-ID (P<0.001). In the multivariate analysis, serum K+ levels were positively correlated with serum albumin, and creatinine in all patients (P<0.05), and ID-use in younger patients (age< or =56, P<0.001). Serum albumin, creatinine, total CO2, and body mass index were significantly higher on Post-ID than Pre-ID. Icodextrin dialysate for chronic overnight dwell could increase serum K+ levels and lower the prevalence of hypokalemia compared to conventional glucose-containing dialysate. The improved chronic K+ balance in CAPD patients on icodextrin could be related to enhanced nutritional status rather than its impact on acute intracellular K+ redistribution.
Body Mass Index ; Creatinine ; Glucans ; Glucose ; Humans ; Hypokalemia ; Multivariate Analysis ; Nutritional Status ; Peritoneal Dialysis ; Peritoneal Dialysis, Continuous Ambulatory ; Potassium ; Prevalence ; Serum Albumin

BACKGROUND: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system. Secondary amyloidosis can occur as a complication of chronic systemic inflammatory and infectious diseases. Until now there has been no report of secondary amyloidosis associated with MS. We report herein a case of renal biopsy-proven secondary amyloidosis in a patient with MS. CASE REPORT: A 41-year-old woman with MS was hospitalized due to aggravated quadriparesis and edema in both lower extremities. Laboratory findings showed nephrotic-range proteinuria and hypoalbuminemia. A percutaneous renal biopsy procedure was performed, the results of which revealed secondary amyloid-A-type amyloidosis associated with MS. CONCLUSIONS: This is the first report of secondary amyloidosis associated with MS.
Adult ; Amyloidosis ; Biopsy ; Central Nervous System ; Communicable Diseases ; Demyelinating Diseases ; Edema ; Female ; Humans ; Hypoalbuminemia ; Lower Extremity ; Multiple Sclerosis ; Nephrotic Syndrome ; Proteinuria ; Quadriplegia

BACKGROUND: Triple immunosuppressant therapy including anti-metabolites is the representative immunosuppressive therapy after renal transplantation. This study is to evaluate the factors that influence Mycophenolate sodium (MPS, Myfortic, Novartis, Basel, Switzerland) dosage patterns in renal transplantation patients who take MPS as an inosine monophosphate dehydrogenase (IMPDH) among antimetabolites. METHODS: From May 2007 to April 2008, 16 clinical departments of 14 transplantation centers in Korea retrospectively performed a survey on 650 renal transplantation recipients taking MPS. This survey collected personal information, clinical factors related to transplantation and immunosuppressive therapy. RESULTS: The mean age of the patients was 43.0+/-12.0 (7~75) and the study included 364 males (56.0%) and 286 females (44.0%). The average follow up period after renal transplantation was 49.5+/-53.4 (1~307) months. There were 366 (56.3%) living related cases, 145 (22.3%) living non-related cases and 139 (21.4%) deceased donor cases. Cyclosporine was the most common calcineurin inhibitor (CNI) used in combination therapy with MPS (476 cases, 73.2%) followed by tacrolimus (169 cases, 26.0%). The mean daily dose of MPS was 909.7+/-336.3 (180~1,620)mg and the mean daily dose per kg was 15.3+/-5.9 (2.65~32.73)mg/kg. The daily dose showed significant positive correlation with patient body weight but the daily dose per kg showed negative correlation. The daily dose of MPS was significantly higher in the combination therapy with cyclosporine than that with tacrolimus. The daily dose and the dose per kg decreased with increment of recipient age and post-transplant period. CONCLUSIONS: Our study concluded that MPS dosages correlated with the combined type of CNI, post-transplant period and age.
Body Weight ; Calcineurin ; Cyclosporine ; Female ; Follow-Up Studies ; Humans ; Inosine Monophosphate ; Kidney Transplantation ; Korea ; Male ; Mycophenolic Acid ; Oxidoreductases ; Retrospective Studies ; Sodium ; Tacrolimus ; Tissue Donors ; Transplants

In hyponatremic patients, the assessment of extracellular fluid volume plays an essential step in diagnosing the etiology of hyponatremia and deciding how to manage it. Although various laboratory tests and diagnostic procedures have been developed for differential diagnosis of hyponatremia, there still are limits to the evaluation of the status of extracellular fluid volume due to the data that overlaps each other, leading to the difficulty in diagnosing between euvolemia and hypovolemia. Also, there is no consensus about how to guide the type and amount of fluid therapy despite many formulas including Adrogue-Madias and Barsoum-Levine formulas have been suggested. Hereby, we are reporting two hyponatremic patients (102 and 105 mEq/L) admitted simultaneously with indistinct volume status on initial clinical and laboratory examinations, but were clarified as euvolemic hyponatremia (syndrome of inappropriate antidiuretic hormone secretion) in one and hypovolemic hyponatremia in the other case after sequential intravenous saline (2 L over 24 hrs) and oral water (20 mL/kg) loading tests. When serum sodium values calculated by the above-mentioned two formulas were compared with actually measured ones during saline loading test in these cases, the Barsoum-Levine formula revealed almost no discrepancy between both the values while the Adrogue-Madias formula underestimated the measured value.
Consensus ; Diagnosis, Differential ; Extracellular Fluid ; Fluid Therapy ; Humans ; Hyponatremia ; Hypovolemia ; Inappropriate ADH Syndrome ; Sodium ; Water

Pulse wave velocity (PWV) is a main parameter for arterial stiffness. In patients with end-stage renal disease (ESRD), PWV is known to be associated with increased mortality. But factors related to the increased PWV in ESRD patients are not well defined. In addition, the carotid-femoral PWV (cfPWV) measurement, which traditionally has been used to evaluate arterial stiffness, has low reproducibility. Recently, brachial-ankle PWV (baPWV) measurement, which can be performed more easily than cfPWV measurement, has become available as a means of measuring PWV. The aim of this study is to investigate the clinical factors associated with increased baPWV in ESRD patients. BaPWV was examined for 65 ESRD patients on maintenance hemodialysis during the period between the 7th to the 11th of February in 2005 using VP-1000. The clinical factors included age, sex, smoking history, blood pressure, diabetes, body mass index, interdialytic weight gain, duration of dialysis, lipid profile, uric acid, albumin, creatinine, C-reactive protein, calcium, phosphate, intact parathyroid hormone, and hematocrit were analyzed regarding associations (or to determine associations) with baPWV. The median age was 53.8+/-12.0, 31 males and 34 females. BaPWV was 18.9+/-5.2 m/s and there was no significant difference between gender (18.1+/-4.4 m/s vs 19.4+/-5.9 m/s, p=NS). In multiple regression models, age, predialysis systolic blood pressure, and diabetes were independent variables. In conclusion, age, systolic blood pressure, and diabetes were correlated with baPWV in ESRD patients. Thus baPWV measured by simple, noninvasive methods may become available for screening high risk groups in ESRD patients, although further longitudinal studies are necessary.
Atherosclerosis ; Blood Pressure ; Body Mass Index ; C-Reactive Protein ; Calcium ; Creatinine ; Dialysis ; Female ; Hematocrit ; Humans ; Kidney Failure, Chronic ; Male ; Mass Screening ; Parathyroid Hormone ; Pulse Wave Analysis ; Renal Dialysis ; Smoke ; Smoking ; Uric Acid ; Vascular Stiffness ; Weight Gain

On view of the absent or minimal osmotic diuresis in end stage renal disease, hyperglycemia on maintenance hemolysis as compared to nonketotic hyperosmolar status without underlying advanced renal failure has been noted to show a wide clinical spectrum form severe manifestations by hypertonicity to no clinical manifestations at all. We experienced a 60-year-old man with a known history of type 2 diabetes mellitus on maintenance hemodialysis for 2 years, who was admitted 4 times within 1 year with hyperglycemia (>500 mg/dL) accompanied by recurrent nausea and vomiting at each admission. However, the calculated effective osmolality (tonicity) in this case ranged only from 286 to 303 mOsm/kg H2O. During the past 6 months following meticulous education for the importance of compliance to medication, especially prokinetics for diabetic gastroparesis, he developed no further episode of hyperglycemia or nausea and vomiting.
Compliance ; Diabetes Mellitus, Type 2 ; Diuresis ; Gastroparesis ; Hemolysis ; Humans ; Hyperglycemia ; Kidney Failure, Chronic ; Middle Aged ; Nausea ; Osmolar Concentration ; Renal Dialysis ; Renal Insufficiency ; Vomiting

PURPOSE: This prospective study aimed to evaluate the safety and efficacy of potassium-exchange resin (PER, Kalimate(R) or Argamate(R)) for managing hyperkalemia induced by Renin-Angiotensin System (RAS) blockers in chronic kidney disease (CKD) patients without their discontinuation. METHODS: Besides conservative remedies including low-potassium diet, all hyperkalemic CKD patients (n=21, [K] > or =5.6 mEq/L) received PER added on angiotensin-converting enzyme inhibitor (Moexipril, n=2) or angiotensin-receptor blocker (Irbesartan, n=19) with, at least, weekly monitoring of serum [K] if its level remains more than 5.5 mEq/L for more than 2 months (mean+/-SD, 6.8+/-5.9 mon; range, 2-26 mon). RESULTS: Baseline serum [K] on RAS blocker alone (5.1+/-0.4 mEq/L; 4.2-6.3 mEq/L) increased to 6.0 +/-0.4 mEq/L (p<0.05) before adding PER, and then it was significantly decreased to 5.3+/-0.6 mEq/L at the first clinic visit (p<0.05) and to 5.0+/-0.7 mEq/L at the last clinic visit (p<0.05) following the administration of PER added on RAS blocker. During the study period, GFR, serum creatinine and urinary protein excretion didn't change significantly. CONCLUSION: The development of hyperkalemia on RAS blockers in CKD patients doesn't necessarily lead to withdrawal of RAS blockers when the cautious add-on therapy of potassium-exchange resin with other conservative remedies launches, unless severe refractory hyperkalemia persists.
Ambulatory Care ; Angiotensin II Type 1 Receptor Blockers ; Angiotensin-Converting Enzyme Inhibitors ; Creatinine ; Diet ; Humans ; Hyperkalemia ; Prospective Studies ; Renal Insufficiency ; Renal Insufficiency, Chronic* ; Renin-Angiotensin System*