The Causes of Early Death in End-stage Renal Disease Patients / 대한신장학회잡지

BACKGROUND: Despite improvements in dialysis care, the mortality of patients with end-stage renal disease(ESRD) remains high. Patients who die within the first 90 days after beginning dialysis are not included in mortality rates and may be absent from incidence count. Therefore, the identification of modifiable characteristics associated with the risk of death during the first 90 days of treatment could lead to improved survival during this interval. METHODS: We performed a retrospective analysis in 986 patients(at least 1 year survival from initiating dialysis were 920 patients, and 66 patients died within 90 days after dialysis) who were initiated renal replacement therapy first at Yonsei Medical Center from Jan 1994 to Jun 1999. RESULTS: The 1 year mortality rate of total patients was 10.4%, and early death rate was 6.9%. The mean survival duration was 28.9+/-23.0 days. Characteristics independently associated with increased risk of early death included older age, inflammation, nutritional impairment, more comorbid condition and previous history of cardiovascular disease at starting dialysis. But Diabetes was not increased early death rate. By multivariate logistic regression analysis, old age, combined comorbid conditions, especially malignancy and congestive heart failure, low serum album and elevated C-reactive protein level were the independent risk factors affecting early death. Other variables such as sex, dyslipidemia, hypertension and diabetes mellitus were not significant risk factors. The leading cause of death in early death group was infection rather than cardiovascular accidents. CONCLUSION: Proper treatment of infection and improved nutritional status by adequate predialytic managements may contribute to their prolonged survival on dialysis patients.

Comparative Prospective Study of Intravenously and Subcutaneously Administered Recombinant Human Erythropoietin(Epokine(R)) in End-Stage Renal Disease Patients : A Phase IV Single Center Study / 대한신장학회잡지

BACKGROUND: We evaluated the clinical efficacy and safety of recombinant human erythropoietin(Epokine(R)). METHODS: A comparative prospective study of intravenously and subcutaneously administrated Epokine(R) conducted 13 patients performing hemodialysis and 28 patients performing continuous ambulatory peritoneal dialysis with end-stage renal disease. Epokine(R) was given initially at a dosage of 100 unit/kg, subcutaneously, two times a week. The patients had achieved stable or more than 10 g/dL of hemoglobin level for 12 weeks and then we randomized switching intravenously or subcutaneously administrated Epokine(R) for another 12 weeks. RESULTS: Hemoglobin(g/dL) and hematocrit(%) increased significantly from baseline levels beginning from 2 weeks after Epokine(R) administration. In HD patients, hemoglobin increased significantly from 7.3 to 9.5 after 12 weeks and to 10.6 after 24 weeks. In CAPD patients, hemoglobin increased significantly from 6.8 to 10.2 after 12 weeks and then 10.8 after 24 weeks(p 0.05). In HD patients, intravenously administrated Epokine(R) group was more dosage than subcutaneously group(97.4+/-15.4 vs 145.4+/-2.9 U/kg/wk, p 0.05). The 9 cases(18.8%) were suffered from headache and flu-like syndrome, but these side effects were not severe and disappeared from conventional therapy. CONCLUSION: Epokine(R) administration is safe and effective in treating anemia of ESRD patients and subcutaneously administration is significantly more effective than intravenously.

Relationship between Inflammatory Markers and High Resolution B-mode Carotid Artery Ultrasonography in Continuous Ambulatory Peritoneal Dialysis(CAPD) Patients / 대한신장학회잡지

BACKGROUND: Continuous ambulatory peritoneal dialysis(CAPD) patients with low albumin(LA) and signs of inflammation reflected by increased C-reactive protein(CRP) level have an increased mortality, but the mechanism of this phenomenon is not clear yet. METHODS: To answer whether LA and inflammation also enhance cardiovascular risk in CAPD patients, we performed cross sectional study measuring carotid artery intima-media thickness(IMT), calculated intima-media area(cIM area) and the presence of plaque by high-resolution B-mode ultrasonography in 93 non-diabetic CAPD patients. RESULTS: Patients with coronary artery disease (CAD, n=8) had significantly increased IMT(0.79+/-0.21 mm vs. 0.60+/-0.11 mm, p or=0.8 mg/dL, n=18) had higher prevalence of carotid plaques (65.8% vs. 50.0%, p < 0.05) compared to those patients with CRP <0.8 mg/dL, but IMT and cIMT area were not different. By multivariate logistic regression analysis, old age, high CRP, history of CAD and low SA were the independent risk factors affecting IMT. CONCLUSION: Our study strongly suggests that low albumin and chronic inflammatory state of CAPD patients could be associated with increasing atherosclerotic cardiovascular disease.

The prevalence and associated risk factors of renal artery stenosis in patients undergoing cardiac catheterization

Renal artery stenosis may be a cause of hypertension and a potential contributor to progressive renal insufficiency. However, the prevalence of renal artery disease in a general population is poorly defined. The purposes of this study were to evaluate the prevalence of angiographically-determined renal artery narrowing in a patient population undergoing routine cardiac catheterization, and to identify the risk factors for renal artery stenosis. After left ventriculography, abdominal aortography was performed to screen for the presence of renal artery stenosis. A total of 427 patients (274 males, 153 females) were studied and the mean age was 59 years. Renal artery narrowing was identified in 10.5% of patients. Significant (> or = 50% diameter narrowing) renal artery stenosis was found in 24 patients (5.6%) and insignificant stenosis was found in 21 patients (4.9%). Significant unilateral stenosis was present in 4.2% of patients and bilateral stenosis was present in 1.4%. The stem of the renal artery was a more common site of stenosis in 62.2% of patients than in the ostium (37.8%), but the severity of stenosis was not significantly different according to the site of stenosis. By univariate and multivariate logistic regression analysis, the association of clinical variables with renal artery stenosis was assessed. Multivariable predictors included age, hypertension and peripheral vascular disease (p < 0.05). The variables such as sex, smoking history, hyperlipidemia, renal insufficiency, as well as the presence of obesity, severity of coronary heart disease and D.M., were not associated. In conclusion, the prevalence of angiographically-determined renal artery narrowing in a patient population undergoing cardiac catheterization is 10.5%. Old age, hypertension and evidence of peripheral vascular disease represent the predictors of renal artery stenosis.

Comparison between Oral Pulse and Daily Calcitriol (Calcio(R)) Therapy in Continuous Ambrlatory Peritoneal Dialysis (CAPD) Patients with Secondary Hyperparathyroidism / 대한신장학회잡지

The most widely used method for treatment of secondary hyperparathyroidism(SH) in CAPD patients has been the administration of calcitriol by oral route. In this study, we compared the efficacy and safety of daily low dose calcitriol therapy with those of intermittent high dose pulse therapy. The study group consisted of 38 patients undergoing CAPD with serum intact PTH level of more than 200pg/ mL. Twenty patients were randomly administered daily low dose calcitriol(0.25 microgram/day for 1 month followed by 0.5 microgram daily dose for the next 3 mon-ths) while 18 patients were given intermittent pulse therapy (0.5 microgram-0.5 microgram-0.75 microgram 3 times a week for 1 month, increased to 1.0 microgram-1.25 microgram-1.25 microgram 3 times a week for the next 3 months). Thirty five patients completed the study : 17 on daily oral calcitriol (M: F=0.7:1, mean age=47.3+/-10.6 years, mean duration of CAPD=48.9+/-41.1 months), and 18 on oral pulse calcitriol (M:F=1.6:1, mean age=41.5+/-12.7 years, mean duration of CAPD=49.2+/-41.6 months). The baseline serum levels of calcium, phosphorus, i-PTH, alkaline phosphatase, and total CO2 were not different between daily and pulse group(9.5+/-0.8 vs 9.3+/-0.9mg/dL, 5.8+/-1.3 vs 5.1+/-1.2mg/dL, 443.1+/-162.5 vs 546+/-385.9pg/mL, 91.8+/-47.7 vs 108.9+/-66.5IU/L, 23.7+/-1.9 vs 25.5+/-2.0mEq/L, p>0.05, respectively). The i-PTH level decreased significantly in daily calcitriol group after 1 month (332.8+/-214.8pg/mL, p0.05). The serum calcium increased similarly in both groups after treatment (daily=10.6+/-0.8 vs pulse=l0.1+/-1.0mg/dL, p>0.05). Hypercalcemia(>11.0mg/dL) was rarely observed in all patients (daily=5, pulse=8 episodes). In conclusion, both daily and pulse calcitriol therapy were similarly effective and safe in control of SH.

The Study on the Mechanism Regulating the Production of Extracellular Matrix in Renal Tubular Epithelial Cells Cultured in High Glucose Concentration / 대한신장학회잡지

Thickening of tubular basement membrane and progressive tubulointerstitial fibrosis has been reported as important components of diabetic nephropathy, In order to investigate the mechanisms of tubulinterstitial changes in diabetic nephropathy, we evaluated the effects of a high concentration of glucose(25mM; 450mg/dL) on glucose transporter GLUT1 level, fibronectin production and tissue inhibitors of metalloproteinases (TIMP)-1 concentration in renal tubular(LLC-PK1) cells. As the effect of high glucose-induced alteration in LLC-PK1 cells, the expression of facilitative glueose transporter, GLUT1 was decreased after longer than 24-hours exposure to 25mM glucose, compared to control(5.6mM). The administration of protein kinase C (PKC) inhibitor GF109203X(10 microM) did not show significant effect on high glucose-induced decrease of GLUT1 level. On western blot analysis of fibronectin production, The exposure of LLC-PK cells to 25mM glucose for 48 hours significantly increasc4 fibro- nectin production, dose-dependently. The addition of GF102903X at the concentration of 10pM induced the significant increase of fibronectin level in LLC-PK1cells under glucose-free condition, whereas there was no significant effect on the high glucose-induced increase of fibronectin production. The addition of anti-TGF-beta antibody at 30 microgram/mL partly inhibited the high glucose-induced increase of fibronectin production. Concerning the changes of tissue inhibitor of metallo-proteinase(TIMP)-1 levels in the presence of high glucose, the exposure to high glucose for 24 and 43 hours increased TIMP-1 levels in culture supernatant of LLC-PK1 cells, dose-dependently. The TIMP-1 levels of 48-hour exposure to 15 and 25mM glucose were also significantly higher than those of 24-hourexposure. The treatment with 10 microM GF102903X or 30 microgram/mL anti-TGF-Beta antibody had no significant effects on TIMP-1 levels measured under the high glucose culture condition. In conclusion, the expression of facilitative glucose transporter, GLUT1 is inhibited and the production of fibronectin is increased in renal tubular cells cultured in the presence of high concentration of glucose, which is partly mediated by TGF-beta. The TIMP-1 level is also increased under high glucose culture condition. The enhanced productions of fibronectin and TIMP-1 of renal tubular cells under high glucose concentration may contribute to tubulointerstitial fibrosis that occurs in diabetic nephropathy.

Factors Affecting Accurate Quantitation of Proteinuria Using Protein/Creatinine Ratio in Random Urine Specimen / 대한신장학회잡지

It's well known that protein/creatinine ratio(P/C ratio) in random urine samples reflects 24-hour urine protein. However, the factors affecting accurate quantitation of proteinuria using random urine P/C ratio are not fully evaluated. The aim of this study is to evaluate factors affecting accurate quantitaion of proteinuria using random urine P/C ratio. 118 patients admitted in Yonsei university medical center during June 1998 and Dec. 1998 were assessed for the measurement of random urine protein/creatinine ratio from second voided urine. 118 patients(mean age 41.5year, male: female 2.36: 1) had mean creati-nine level 1.83+/-1.78mg/dL, 24-hour pmteinuria 6.06+/-7.64g/day and P/C ratio 4.80+/-4.48, All the patiient.s were divided into A, B, C, I, II, K, IV according to serum creatinine level and 24-hour proteinurim amount. The correlation coefficient(R value) between proteinuria and P/C ratio are shown that in all pa- tients is 0.875, group A(Cr*

Clinical Outcome and Prognostic Factors of Biopsy-proven Diffuse Proliferative Lupus Nephritis / 대한신장학회잡지

Lupus nephritis is a major cause of morbidity and mortality arising from systemic lupus erythematous. It is generally acknowledged that the presence of diffuse proliferative lupus nephritis(DPLN) is highly predictive of a poor prognosis in terms of renal and patient out- come on survival. The objective of this study was to evaluate the clinicopathologic characteristics, renal out- come according to therapeutic regimen, and prognostic factors of biopsy-proven diffuse proliferative lupus nephritis. Among the biopsy-proven lupus nephritis patients who were admitted to Yonsei University Medical Center from January 1986 to June 1997, 36 patents who were diagnosed DPLN by renal biopsy and treated for at least 6 months and regularly followed-up for at least 12 months were included. We retrospec-tively reviewed the medical recorders. Patients were treated with steroid regimen with or without cyclo-phosphamide. According to the therapeutic response, patients were divided into two groups : a therapeutic response group(n=24), and a therapeutic non-response group

Factors Affecting the Response to Oral Calcitriol Therapy in CAPD Patients with Secondary Hyperparathyroidism / 대한신장학회잡지

Calcitriol therapy is an important treatment for the prevention and control of secondary hyperparathyroidism in continuous ambulatory peritoneal dialysis (CAPD) patients. However, this often has been limited by the associated hypercalcemia and hyperphosphatemia due to increase in intestinal calcium and phosphorus absorption. Many studies reported that these limitations could be avoided by changing routes, frequency and dose of calcitriol treatment. But, there are still controversy about each methods and the results on the PTH response to conventional calcitriol treatment in CAPD patients. This study was performed to evaluate the factors affecting the response to oral calcitriol in CAPD patients. A retrospective study was done in 92 CAPD patients with secondary hyperparathyroidism(intact PTH level >200pg/ml) on oral calcitriol treatment. After baseline study of serum calcium, phosphorus, alkaline phosphatase, BUN, creatinine and intact PTH, calcitriol therapy was begun via oral rou- te, daily. Serum calcium, phosphorus, alkaline phosphatase, BUN, creatinine, intact FI'H and other bio- chemical markers were checked at 3 month, 6 month after treatment. Parathyroid gland ultrasonography was performed to detect parathyroid hypertrophy and nodule and to measure the diameter of parathymid gland. All the patients were divided into two groups according to percent reduetion of i-PTH(initial PTH PTH after 3, 6 months)X100/initial PTH(%),deltaPTH during oral calcitriol therapy for 3 and 6 months(group I ; delta PTH >30%, group II ; delta PTH <30%). RESULT: 1) All 92 patients(mean age 46.5 11.3yr, M: F 45: 47, mean CAPD duration 51.3 39.4 months) were administered oral calcitriol, daily. Mean calcitriol dose during 3 month was 0.43 0.22Mg and during 6month 0.43 0.24Mg. 2) After 3-month treament, there were significant differences in initial i-PTH, the diameter of parathyroid gland, initial phosphorus, intial total alkaline phosphatase and duration of CAPD between group I and II(406.7+/-196.5 vs. 871.0+/-478Apglml, 6.2+/-2.6 vs. 13.1+/-5.2mm, 5.0+/-1.3 vs. 5.7+/-1.3mg/dl, 93.7+/-4L1 vs. 171.9+/-137.6IU/L, 40.1+/-34.9 vs. 73.5+/-37.8months, p< 0.05, respectively). 4) After 6-month treament, there were significant differences in initial i-PTH, the diameter of parathyroid gland, intial total alkaline phosphatase and duration of CAPD between group I and II(474.1+/-266.6 vs. 889.7+/-485.4pg/ml, 6.4+/-2.7 vs. 14.5+/-5.1mm, 107.9+/-80.1 vs. 180.7+/-121.5IU/L, 40.5+/- 32.9 vs. 81.8+/-35.3months, p<0.05, respectively). 5) The significant negative correlation was shown between deltaPTH and the duration of peritoneal dialysis, the diameter of parathyroid gland, initial PTH level and PTH response during 3-month and 6-month oral calcitriol treatment. The response to oral calcitriol was poor when i-PTH level more than 500pg/ml(kappa 0.429, p value <0.01), the diameter of parathyroid gland more than 10.0mm(kappa 0.641, p value<0.01), the duration of CAPD more than 55months(kappa 0.524, p value< 0.01). These data suggested that initial i-PTH level, the diameter of parathyroid gland size and the duration of CAPD were independent risk factors of the poor response to oral calcitriol therapy in CAPD patients with secondary hyperparathyroidism.

Effect of High Glucose on Nitric Oxide Production in Culteured Rat Mesangial Cells / 대한신장학회잡지

Diabetic nephopathy is one of the leading causes of end-stage renal disease and characterized pathologically by the glomerular mesangial expansion and increased extracellular matrix(ECM) formation. Glomerular hyper-filtration and increased vascular permeability observed in the early stage of diabetic nephropathy have been proposed to play a significant pathophysiologic role in the eventual development of glomerulosclerosis of dia-betic nephropathy. Some studies have suggested that this glomerular hyperfiltration is mediated by increased nitric oxide(NO) production via the constitutive nitric oxide synthase(cNOS) pathway present in endothelial cells under the high glucose environment. However, the exact role of the inducible NOS(iNOS) pathway present in mesangial cells in the pathogenesis of diabetic neph-ropathy is not clearly established. The present study was carried out to examine whether NO production via the iNOS pathway is mo-dulated in cultured rat mesangial cells exposed to the high glucose environment and underlying mechanism of this modulation. For this purpose, the production of the stable metabolite of NO(nitrite), intracellular cyclic gu-anosine monophosphate(cGMP), iNOS mRNA expression and iNOS protein synthesis were examined under different glucose concentrations. Rat mesangial cells cultured in high glucose concen- tration(30mM D-glucose) increased significantly nitrit#e/ nitrate production and intracellular cGMP levels upon stimulation with lipopolysaccharide(LPS) plus interfer-on-r (IFN-r ) compared with control glucose concen- tration(5.6mM D-glucose). Mesangial iNOS mRNA expression and protein synthesis also increased signifi- cantly in response to high glucose. This enhanced iNOS mRNA expression induced by high glucose concentration was significantly suppressed by protein kinase C(PKC) inhibitor, calphostin C, and the aldose reductase inhibitor, 6-bromo-l, 3-dioxo-1H- benz[d, elisoquinoline-2(3H)-acetic acid. These results indicate that high glucose in combination with stimulation by LPS plus IFN- r enhances NO production from mesangial cells by the iNOS pathway, and that the activation of PKC and the polyol pathway may play a role in this enhancement.

Patients' Referral Pattern and Dialysis Initiation Practice: Single Center Experience / 대한신장학회잡지

Despite improvements in dialysis care, the mortality of patients with end-stage renal disease(ESRD) remains high. One factor that has so far received little attention, but which might contribute to morbidity and mortality, is the timing of referral to the nephrologist. We performed a retrospective analysis in 358 patients(male 275, female 151) who were initiated renal replacement therapy first at this hospital from Jan 1995 to Dec 1996. Patients were defined by the time of first nephrology as early referral(E, n=163) encountered after more than 8 weeks; late early referral(LE, n=19) encountered between 8 weeks and 4 weeks; late referral(L, n=55) encountered from 1 week to 4 weeks; urgent referral(U, n= 121) encountered less than 1 week. There were no differences in age, gender, primary renal disease, cause of dialysis, and renal replacement therapy modalities. However, there were significant differences in rnean arterial pressure and serum phosphate levels between these 4 groups. The mean arterial pressures (mmHg) were 109.15 +/- 17.16, 105.37+/-18.76, 117.24 +/- 27.24 and 116.98+/-24.26 for E, LE, L and U, respectively(p0.05). In the E group, there was more controlled blood pressure and serum phosphate levels compared to the U group at initiation of renal replacement therapy, but other parameters were not significantly different among the 4 groups. Delays in initiation of renal replacement therapy may result in patients entering dialysis in a compromised state, therefore adequate long-term predialysis care by a nephrologist is important. Socioeconomic - and medical factors respon-sible for late referral and late initiation of dialysis need to be evaluated and corrected to further improve the outcome of these patients.

A Case of Drug-Induced Chylous Ascites in a Patient Undergoing Continuous Ambulatory Peritoneal Dialysis / 대한신장학회잡지

A chylous ascites, especially drug-induced, is very rare complication in CAPD. The diagnostic criteria for the drug-induced chylous peritoneal dialysate include 1) turbid dialysate developed within Chrs after the administration of causative drug, 2) no clinical symptoms being suggestive of peritoneal inflammation, 3) the fluid containing normal leukocyte counts and being negative for bacterial and fungal culture, and 4) it disappeared spontaneously after the withdrawal of the assumed causative agent and never recurred thereafter. We report a case of chylous ascites emerging after use of manidipine, dihydropyridine calcium channel blocker, in a patient undergoing CAPD. The chylous ascites in that patient was improved after discontinuation of manidipine.

Comparison between Lamivudine alone and Lamivudine and Steroid Combination in Treatment of Nephrotic Syndrome Associated with Hepatitis B / 대한신장학회잡지

Treatment of nephrotic syndrome associated with hepatitis B are controversial, but some patients may respond to interferon therapy. Steroid therapy in these patients could be limited, because it may aggravate hepatitis with the acute viral replication. Lamivudine may also be effective in reducing viral burden and may convert patients from HBsAg and HBeAg positive to negative. But there was no report for the usefulness of lamivudine in treatment of these patients. We performed a randomized comparative study to assess the usefulness of lamivudine and the effect of steroid in the use of lamivudine in treatment of B-viral associated nephrotic syndrome. Twelve patients(M:F=1:0.2, mean age 34.3 years, MCD 1, MPGN 5, MGN 6 patients) suspected to have the acute viral replication with nephrotic syndrome were included. They were randomly assigned to receive lamivudine and steroid combination therapy(group I, 150mg of lamivudine with high-dose steroid, 1mg/kg/day, orally once daily in 6 patients) or lamivudine alone therapy(group II, 150 mg of lamivudine orally once daily alone in 6 patients). The duration of lamivudine use was 6 months in both groups, and that of steroid use was 6 weeks in group 1. Then, lamivudine and steroid were tapered according to the amount of proteinuria and serum HBV-DNA titer. All patients were closely monitored every 2 months with clinical, bioche mical, and serological parameters for 10 months. The rate of negative sero-conversion of HBV- DNA were 91.7%(11/12) at 2 months of lamivudine therapy in all patients, and there was no difference between group I and II(83.3% vs. 100%, p>0.05). In group I, there were a significant decreases of mean serum HBV-DNA values(899.2+/-711.9 vs. 31.4+/-32.7, 12.7+/-27.6, and 137.2+/-278.1pg/ml, p<0.05, respectively), proteinuria(11.0+/-3.6 vs. 3.9+/-2.3, 2.1+/-2.3, and 2.5+/-3.1g/d, p<0.05, respectively), and SGPT (57.7+/-18.9 vs. 30.5+/-12.4, 23.8+/-10.2, and 26.0+/-10.4 IU/L, p<0.05, respectively) measured at 2, 6, and 10months compared to before therapy, and serum albumin levels were significantly increased at 2, 6, and 10months compared to before therapy(2.2+/-0.5 vs. 3.1+/-0.5, 3.9+/-0.8, and 3.9+/-0.9g/dL, p<0.05, respectively). In group II, serum HBV-DNA was significantly decreased at 2, 6, and 10 months compared to before therapy(358.8+/-369.3 vs. 19.1+/-27.0, 0.0+/-0.0, and 0.0+/-0.0pg/ml, p<0.05, respectively), and proteinuria and SGPT were significantly decreased at 6 and 10 months compared to before therapy(8.5+/-5.5 vs. 2.6+/-1.3 and 2.1+/-2.3g/d, p<0.05; 67.5+/-43.0 vs. 25.3+/-11.6 and 31.5+/-9.2IU/L, p<0.05, respectively). Serum albumin levels were significantly increased at 10 months compared to before therapy(2.8+/-0.8 vs. 4.3+/-0.1g/dL, p<0.05). Serum HBV-DNA levels rebounded in two patients of group I, but none was observed in group II. No serious adverse events were observed in all the patients. In conclusion, lamivudine and steroid combination therapy may more rapidly decrease proteinuria than lamivudine alone in B-viral associated nephrotic syndrome, but may induce the rebound of serum HBV-DNA.

Hereditary influence in determinig peak bone mass / 대한내분비학회지

No abstract available.