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Kidney ; Kidney Diseases ; Paraproteinemias

BACKGROUND: The Korean Network for Organ Sharing (KONOS), which was established in December 31st, 1999, is a nationwide system of deceased donor detection and distribution. From its inception, KONOS has defined marginal donors and used this definition for over 15 years. However, this definition should be reevaluated to determine if it requires revision. This study was conducted to confirm the feasibility of the main study for revision of the marginal donor definition in deceased donor kidney transplantation. METHODS: This study is a retrospective meta-analysis of 786 patients who had deceased donor kidney transplant from six centers. After the data validation process, multivariable analysis was conducted to evaluate whether the marginal donor criteria of KONOS or UNOS expected adequately in terms of graft survival and delayed graft function (DGF). RESULTS: Neither the KONOS or UNOS criteria affected graft survival. Expanded criteria for donors of UNOS was a risk factor for DGF. However, KONOS criteria did not affect DGF. CONCLUSIONS: Based on this preliminary study, there is a need to conduct a study to revise the marginal donor criteria of KONOS in deceased donor kidney transplantation. Such a study should have large scale and long-term follow-up data.
Brain Death ; Delayed Graft Function ; Follow-Up Studies ; Graft Survival ; Humans ; Kidney Transplantation* ; Kidney* ; Retrospective Studies ; Risk Factors ; Tissue Donors*

Accelerated atherosclerosis is not only a frequent complication but also the most common cause of death in patients with chronic renal failure (CRF). Although mechanisms are unclear, disorder of lipid metabolism may be a major factor. Since apolipo-protein (apo) E is known to play a major regulatory role in lipid metabolism, we evaluated apo E genotype in 72 male patients with CRF and compared with that in 194 rnale normal controls. In addition, we measured plasma lipid and apolipoprotein concentrations and evaluated them according to apo E genotype in patients and controls. Apo E genotype was determined with the INNO-LiPA Apo E kit (Innogenetics, Belgium), which is based on reverse hybridization. The results are as follows ; 1) The distribution of the three major apo E alleles in patients with CRF ( e 2: 6.2%, e 3: 80.6%, e 4: 13.2%) was not different from that in controls ( e 2: 4.1%, e 3: 87.6%, e 4: 8.3%). 2) In patients with CRF, total cholesterol, lowdensity lipoprotein (LDL) and high-density lipoprotein (HDL) levels were significantly lower and the triglyceride and lipoprotein (a) levels were significantly higher than those in controls. 3) In controls, E 4/3 group had significantly lower levels of HDL than E 3/3 and E 3/2 groups. In patients with CRF, E 4/3 group had significantly higher levels of total cholesterol and apo B lipoprotein than E3/2 group. In conclusion, although there was no significant difference in the apo E genotype frequencies between male patients with CRF and controls, apo E polymorphism may play an important role in the determination of individual differences in plasma lipids in male patients with CRF.
Alleles ; Apolipoproteins B ; Apolipoproteins E ; Apolipoproteins* ; Atherosclerosis ; Cause of Death ; Cholesterol ; Genotype ; Humans ; Individuality ; Kidney Failure, Chronic* ; Lipid Metabolism ; Lipoprotein(a) ; Lipoproteins ; Male* ; Plasma* ; Triglycerides

Growth factor-stimulated phospholipase D (PLD) catalyzes the hydrolysis of phosphatidylcholine (PC), generating phosphatidic acid (PA) which may act as a second messenger during cell proliferation and survival. Therefore, PLD is believed to play an important role in tumorigenesis. In this study, a potential mechanism for PLD-mediated tumorigenesis was explored. Ectopic expression of PLD1 or PLD2 in human glioma U87 cells increased the expression of hypoxia-inducible factor-1alpha (HIF-1alpha) protein. PLD-induced HIF-1 activation led to the secretion of vascular endothelial growth factor (VEGF), a HIF-1 target gene involved in tumorigenesis. PLD induction of HIF-1alpha was significantly attenuated by 1-butanol which blocks PA production by PLD, and PA per se was able to elevate HIF-1alpha protein level. Inhibition of mTOR, a PA-responsive kinase, reduced the levels of HIF-1alpha and VEGF in PLD-overexpressed cells. Epidermal growth factor activated PLD and increased the levels of HIF-1alpha and VEGF in U87 cells. A specific PLD inhibitor abolished expression of HIF-1alpha and secretion of VEGF. PLD may utilize HIF-1-VEGF pathway for PLD-mediated tumor cell proliferation and survival.
Cell Line, Tumor ; Epidermal Growth Factor/metabolism ; Gene Expression Regulation, Neoplastic ; Glioma/genetics/*metabolism ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism ; Phosphatidic Acids/*metabolism ; Phospholipase D/genetics/*metabolism ; *Signal Transduction ; Transfection ; Vascular Endothelial Growth Factor A/*metabolism

Metastatic calcification is rare; it is found during autopsy in patients who underwent hemodialysis. Diffuse calcium precipitation of small and medium-sized cutaneous vessels, known as calciphylaxis, can result in progressive tissue necrosis secondary to vascular calcification. This condition most commonly involves the skin; however, a rare occurrence of visceral calciphylaxis has been reported. Here we report on an autopsy case. Despite a thorough evaluation, and even performing an autopsy, the underlying cause of acute-onset hypercalcemia, resulting in the production of pulmonary calciphylaxis and metastatic renal calcification associated with acute respiratory and renal failure, could not be determined. Metastatic calcification often lacks specific symptoms, and the degree of calcification is a marker of the severity and chronicity of the disease. This unusual autopsy case emphasizes the importance of rapidly progressing visceral calciphylaxis, as well as its early detection.
Autopsy ; Calciphylaxis ; Calcium ; Humans ; Hypercalcemia ; Necrosis ; Renal Dialysis ; Renal Insufficiency ; Vascular Calcification

There have been controversies on the effect of albumin in treating edema in nephrotic syndrome patients. We evaluated the additive diuretic effect of coadministration of furosernide with albumin in the six patients with nephrotic syndrome. We administered 160mg of furosemide intravenously for 1 hour with 100rnl of 20% albumin or 5% dextrose by random cross-over design. The urine and plasma furosemide concentrations were measured by HPLC. After the administration of furosemide alone, urine volume, urinary excretions of sodium and chloride were increased significantly compared to those of basal state (P<0.05). But, coadministration of furose-mide with albumin did not increase significantly the urine voume (2285+/-445ml vs. 3023+/-715ml), urinary excretions of sodium (194+/-58rnmol/day vs. 282+/-85 mmol/day) and chloride (213+/- 54mmoVday vs. 286+/- 74mmoVday) comparing to those of furosemide only cases. Addition of albumin to furosemide did not significantly changed pharmacokinetic parameters such as AUC (28.3+/-5.5ug/ml hr vs 36.0+/-6.7ug/ml hr), total plasma clearance (115+/-30mVmin vs 108+/-41ml/min), volume of distribution (0.13+/-0.02L/kg vs 0.10+/- 0.01L/kg), elirnination half life (1.4+/-0.3hr vs 1.5+/-0.3hr), and urine furosemide excretion (44+/-8% vs 43+ 10%). We concluded that albumin infusion did not enhance the diuretic action of furosemide pharmacodynamically and pharmacokinetically in patients with nephrotic syndrome.
Area Under Curve ; Chromatography, High Pressure Liquid ; Cross-Over Studies ; Diuretics ; Edema ; Furosemide* ; Glucose ; Half-Life ; Humans ; Nephrotic Syndrome* ; Pharmacokinetics ; Plasma ; Sodium

Diuretic therapy for the treatment of edema in patients with end-stage renal disease (ESRD) is unsatisfactory, and a combination of thiazide and loop diuretics may produce better clinical effects. To evaluate the influence of thiazide on loop diuretic therapy for ESRD, we performed a crossover study of furosemide versus hydrochlorothiazide plus furosemide treatment. The diuretic effects of furosemide (160 mg i.v.) alone versus a combination of hydrochlorothiazide (100 mg p.o.) and furosemide were studied in ten ESRD patients with proteinuria greater than 1 g/day. The diuretic effects were compared for 24 h urine volume and electrolyte excretion. To detect the influence of thiazide that may have been obscured in the widely dispersed data, pharmacodynamic analysis of urine furosemide excretion rate versus fractional excretion of sodium (FeNa) was also performed using mixed-effect modeling. Combination therapy was not significantly different from furosemide monotherapy in terms of 24 h urine volume, chloride, or sodium excretion. Hydrochlorothiazide was not a significant covariate in the furosemide effect for the pharmacodynamic model. In patients with ESRD and severe proteinuria (>1,000 mg/day), the combination of hydrochlorothiazide with furosemide therapy did not increase the diuretic effect of furosemide.
Cross-Over Studies ; Diuretics ; Edema ; Furosemide ; Humans ; Hydrochlorothiazide* ; Kidney Failure, Chronic* ; Proteinuria ; Sodium ; Sodium Potassium Chloride Symporter Inhibitors

BACKGROUND: This study describes a novel analytical method for simultaneously determining sarpogrelate and its metabolite (M-1) in human plasma, using liquid chromatography coupled with tandem mass spectrometry, with electrospray ionization in the positive ion mode. METHODS: Sarpogrelate, M-1, and labeled internal standard (d3-sarpogrelate) were extracted from 50 microL of human plasma by simple protein precipitation. Chromatographic separation was performed by using a linear gradient elution of a mobile phase involving water-formic acid (99.9:0.1, v/v) and acetonitrile-formic acid (99.9:0.1, v/v) over 4 min of run time on a column, with a core-shell-type stationary phase (Kinetex C18, 50 mm x 2.1 mm i.d., 2.6-microm particle size, Phenomenex, USA). Detection of the column effluent was performed by using a triple-quadruple mass spectrometer in the multiple-reaction monitoring mode. RESULTS: The developed method was validated in human plasma, with lower limits of quantification of 10 ng/mL for sarpogrelate and 2 ng/mL for M-1. The calibration curves of sarpogrelate and M-1 were linear over the concentration ranges of 10-2,000 and 2-400 ng/mL, respectively (R2>0.99). The carry-over effect, precision, accuracy, and stability of the method met the criteria for acceptance. CONCLUSIONS: A simple, fast, robust, and reliable analytical method was successfully developed and applied to the high-throughput determination of sarpogrelate and its metabolite in real plasma samples in a pharmacokinetic study of healthy subjects.
Calibration ; Chromatography, Liquid ; Humans ; Mass Spectrometry* ; Particle Size ; Plasma* ; Tandem Mass Spectrometry

We evaluated gastric emptying time (GET) by using Tc99m-sulfur colloid gastric emptying scintigraphy in 11 patients with CAPD (6 male, 5 female) and 14 healthy volunteers. We investigated the effect of dialysate dwelling on GET by studying twice, once without dialysate in the abdomen (drained) and once with 2 L of dialysate in the abdomen (full), and the relationship between body surface area (BSA) and delayed gastric emptying. 1) The mean of gastric emptying rate in 120 minute in patients with CAPD when drained (67.8+/-13.4%) was not different from that in healthy volunteers (65.4+/-8.6%) 2) The mean of gastric emptying rate in 120 minute when full (55.6+/-14.6%) was significantly lower than that when drained (67.8+/-13.4%) (P<0.05). In four of the 11 patients (36.4%), gastric emptying was extremely delayed from normal to abnormal range when full. 3) The BSA (1.5+/-0.11m2)of patients who had extremely delayed GET from normal to abnormal range was smaller than that (1.74+/-0.22m2) of patients who had minimal delayed or unchanged GET when full. This study showed the patient with CAPD had normal gastric emptying when drained, and that gastric emptying was delayed by dialysate dwelling, especially in the patients who has less than 1.5m2 of body surface area. Therefore, we suggest that intermittent nocturnal peritoneal dialysis or a small volume of dialysate may be considered for the patient with small body surface area based on the adequacy.
Abdomen ; Body Surface Area ; Colloids ; Gastric Emptying* ; Healthy Volunteers ; Humans ; Male ; Peritoneal Dialysis ; Peritoneal Dialysis, Continuous Ambulatory* ; Radionuclide Imaging