Polymorphism of the ACE Gene in Dialysis Patients: Overexpression of DD Genotype in Type 2 Diabetic End-Stage Renal Failure Patients

The angiotensin-converting enzyme (ACE) gene DD homozygote has been suggested to be a significant risk factor for the progression of diabetic nephropathy. We analyzed clinical parameters and ACE genotype distribution between type 2 diabetic patients at the extremes of renal risk, i.e. an end-stage renal failure (ESRF) group (n = 103, group 1) who were on dialysis therapy due to progression of diabetic nephropathy, and a no progression group (n = 88, group 2) who had maintained normal renal function and normoalbuminuria for more than 15 years. There were no significant differences in age, sex, body mass index, HbA1c level, or lipid profiles between the two groups (p > 0.05). Group 1 had a significantly higher prevalence of hypertension [group 1: 82.5% (85/103) vs. group 2: 50.0% (44/88), p < 0.05] and diabetic retinopathy [group 1: 103/103 (100%) vs. group 2: 28/88 (31.8%), p < 0.05] than group 2. Daily urinary albumin excretion was also higher in group 1 than in group 2 [group 1: 2873 +/- 2176 mg/day vs. 12 +/- 7 g/day, p < 0.05]. The frequencies of the DD, ID, and II genotypes of the ACE gene in group 1 and group 2 were 26.2%, 47.6%, and 26.2%, and 7.9%, 57.9%, and 34.2%, respectively. The ACE genotype frequencies between the two groups were significantly different according to a chi-square test with Bonferroni's correction (p = 0.004). The presence of the DD genotype increased the risk of ESRF 4.286-fold compared to the II genotype [odds ratio 4.286, 95% CI 1.60- 11.42, p = 0.005]. The frequency of the D-allele was higher in both male and female patients in group 1 compared to group 2, but reached statistical significance only in males [male, group 1: 50.8% vs. group 2: 35.0%, p = 0.018, female, group 1: 48.8% vs. group 2: 39.5%, p = 0.231]. This study, although limited by sample size, showed that type 2 diabetic ESRF patients more frequently expressed the DD genotype. These findings may substantiate the previously noted relationship between the ACE DD genotype and the progression of diabetic nephropathy in Korean type 2 diabetic patients.

The Effect of Iodine Restriction on Thyroid Function in Patients with Hypothyroidism Due to Hashimoto's Thyroiditis

Lifelong thyroid hormone replacement is indicated in patients with hypothyroidism as a result of Hashimoto's thyroiditis. However, previous reports have shown that excess iodine induces hypothyroidism in Hashimoto's thyroiditis. This study investigated the effects of iodine restriction on the thyroid function and the predictable factors for recovery in patients with hypothyroidism due to Hashimoto's thyroiditis. The subject group consisted of 45 patients who had initially been diagnosed with hypothyroidism due to Hashimoto's thyroiditis. The subjects were divided randomly into two groups. One group was an iodine intake restriction group (group 1) (iodine intake: less than 100 microgram/day) and the other group was an iodine intake non-restriction group (group 2). The thyroid-related hormones and the urinary excretion of iodine were measured at the baseline state and after 3 months. After 3 months, a recovery to the euthyroid state was found in 78.3 % of group 1 (18 out of 23 patients), which is higher than the 45.5% from group 2 (10 out of 22 patients). In group 1, mean serum fT4 level (0.80 +/- 0.27 ng/dL at the baseline, 0.98 +/- 0.21 ng/dL after 3 months) and the TSH level (37.95 +/- 81.76 microIU/mL at the baseline, 25.66 +/- 70.79 microIU/mL after 3 months) changed significantly during this period (p < 0.05). In group 2, the mean serum fT4 level decreased (0.98 +/- 0.17 ng/dL at baseline, 0.92 +/- 0.28 ng/dL after 3 months, p < 0.05). In the iodine restriction group, the urinary iodine excretion values were higher in the recovered patients than in non-recovered patients (3.51 +/- 1.62 mg/L vs. 1.21 +/- 0.39 mg/ L, p=0.006) and the initial serum TSH values were lower in the recovered patients than in the non-recovered patients (14.28 +/- 12.63 microIU/mL vs. 123.14 +/- 156.51 microIU/mL, p=0.005). In conclusion, 78.3% of patients with hypothyroidism due to Hashimoto's thyroiditis regained an euthyroid state iodine restriction alone. Both a low initial serum TSH and a high initial urinary iodine concentration can be predictable factors for a recovery from hypothyroidism due to Hashimoto's thyroiditis after restricting their iodine intake.

Comparative Study of Renal Replacement Therapy in Korean Diabetic End-Stage Renal Disease Patients: a Single Center Study

The number of diabetic ESRD patients has increased and death rates of diabetic patients on hemodialysis (HD), peritoneal dialysis (PD) and renal transplantation (RT) have remained higher than the death rate of non-diabetic patients. An attempt was made to compare the clinical characteristics, patients' cumulative survival, and technical survival among the three groups retrospectively according to the mode of renal replacement therapy (RRT), and to analyze the risk factors associated with mortality. A total of 229 diabetic ESRD patients diagnosed between 1986 and 1995 at the Severance Hospital who began dialysis or who underwent a kidney transplant were included and their medical charts were reviewed. Hypertension was the most common co-morbid disease in all study groups. The prevalence of cardiovascular disease was the only co-morbid condition that was significantly different among the three groups, which was highest in the PD group (24.4%) and lowest in the RT group (8%). In the analysis of a patient's cumulative survival rate not adjusted for age and sex, the RT group had the highest survival rate, and the cumulative survival rate of the HD and PD group were similar. The 5-year survival rate of the patients treated with HD, PD and RT was 28.8%, 19.8%, and 72.0%, respectively. No differences were observed in the patient's cumulative survival rate between the HD and PD patients even when it was adjusted for age. When adjusted for age, sex and risk factors, the relative death rate of the RT group was significantly lower in male patients younger than 60 years of age. With the exception of male patients younger than 60 years of age, the PD group showed a slightly lower relative death rate although it was not significant. The multiple Cox regression analysis of patient survival showed that age, serum albumin, BUN, mean hospital days, the presence of cardiovascular disease at the initiation of RRT were associated with mortality. The analysis of the technique survival rate revealed a better result in the HD group compared to PD group, but a limitation in being able to investigate the AVF function disturbed the accuracy of the analysis of technical survival rate. In conclusion, the survival rate between the PD and HD patients was not different and the RT group had the best survival rate. Therefore, kidney transplantation in diabetic ESRD patients should be considered positively if no other contraindicated condition for RT exit.

Clinical Features of Tuberculosis in Dialysis Patients / 대한신장학회잡지

BACKGROUND: A retrospective study of the clinical features of tuberculosis in patients undergoing maintenance dialysis was performed. METHODS: We reviewed medical records of patients. RESULTS: Among thirty-four patients, fourteen were on hemodialysis and twenty were on peritoneal dialysis. Mean age was 52.4 +/- 13.8 years, and interval between initiation of dialysis and onset of tuberculosis ranged from 1 to 146 months. There were 14 cases of pulmonary tuberculosis, 10 cases of tuberculous lymphadenitis, 4 cases of tuberculous peritonitis, 3 cases of miliary tuberculosis, 1 case of spinal tuberculosis, 1 case of tuberculous pericarditis, and 1 case of tuberculosis of thigh. Patients with pulmonary tuberculosis usually presented with dyspnea and malaise. But typical symptoms of tuberculosis such as fever, cough, sputum, and weight loss were rarely observed. Leukocytosis was absent but anemia, hypoalbuminemia and significant increase in acute phase reactants such as ferritin and C-reactive protein was obvious. Diagnosis was established by positive AFB in 3 patients, and in cases of extrapulmonaty tuberculosis, 13 among 20 patients were diagnosed by typical histologic characteristics on a tissue biopsy. Antituberculous treatment consisted of isoniazid, rifampicin, pyrazinamide, and occasionally ethambutol. And in several cases, incision and drainage, pericardiocentesis, or removal of peritoneal catheter were performed. Among the patients, just one recurrence was observed and four patients died while on antituberculous treatment. CONCLUSION: In dialysis patients, extrapulmonary tuberculosis is common and diagnosis of tuberculosis is difficult for its atypical manifestations. Therefore, early diagnosis and prompt initiation of treatment is needed in patients with high suspicion of tuberculosis.

Risk Factors and Clinical Features of Ultrafiltration Failure in CAPD Patients; Case-control Study / 대한신장학회잡지

PURPOSE: Ultrafiltration (UF) failure is one of the most important causes of CAPD withdrawal accounting for up to 20% of CAPD catheter removal. Factors contributing to UF failure are; severe and multiple peritonitis, continuous exposure to nonphysiologic dialysis solution, and use of beta-blockers. We evaluated clinical features of patients with UF failure and assessed the risk factors for UF failure in CAPD patients. METHODS: CAPD data of our institution from Jan 1990 to Dec 2000 were analyzed and a subgroup of 191 patients whose CAPD catheters were removed were collected. Nineteen patients, whose CAPD catheters were removed due to UF failure, were selected from the subgroup as the case group. Seventy-six hospital controls without ultrafiltration failure matched for age, sex, and time of CAPD initiation who were currently maintained on CAPD were selected as the control group. Peritoneal equilibration test (PET) was done within 3 months of initiation of CAPD and at the diagnosis of UF failure, respectively. Peritoneal glucose load was estimated for the first two years. Incidence of peritonitis, accumulated days of peritoneal inflammation (APID), causative organisms of peritonitis, and history of beta-blocker use were evaluated. Peritoneal function was determined by daily net ultrafiltration and mass transfer area coefficient (MTAC) for creatinine. Serum albumin, normalized protein catabolic rate (nPCR) and Kt/Vurea were also evaluated. RESULTS: There was no difference between cases and controls in etiology of ESRD, peritonitis incidence, APID and causative organisms of peritonitis. The case group included more high transporters at the time of the diagnosis of UF failure. The patients with UF failure showed lower nPCR and higher CRP than controls. Serum albumin level was similar at start of CAPD, but decreased faster in UF failure group. Use of beta-blockers and decline in RRF were not different between the two groups. UF fail ure group had higher MTAC for creatinine and more peritoneal glucose load compared to control group. By logistic regression analysis, peritoneal glucose load and increment in glucose load were independent factors associated with UF failure. CONCLUSION: Peritoneal glucose load and increment of glucose load were found to be important risk factors for UF failure in our study. Therefore, various efforts to reduce peritoneal glucose load in CAPD patients are needed for prevention of UF failure.

The Long-term Nutritional Effects of Amino-Acid Based Dialysis Solution (IPAA) in Malnourished CAPD Patients : Comparison of Responders and Non-responders / 대한신장학회잡지

BACKGROUND: IPAA provide nutritional benefit, at least in the short term. However, the long-term efficacy of IPAA in PD patients remains unclear. An attempt was made to evaluate long-term efficacy of IPAA and to ascertain possible factors associated with improved nutritional status after IPAA. METHODS: The 46 malnourished CAPD patients were treated with IPAA (one exchange of Nutrineal daily) for one year. Various nutritional, boichemical variables, urea kinetic study and measurement of lean body mass based on creatinine excretion (LBMCr) were carried out at baseline, and at 3- month interval thereafter. Responders was defined as those patients who had an increment of mean LBMCr more than 2.0 kg and/or an increase in mean %LBMCr (LBMCr/Body weight) more than 5% during IPAA treatment. RESULTS: After administration of IPAA, BUN, Cr, LBMCr, %LBMCr, nPNA, SGA, and exercise capacity increased significantly. But, protein and albumin level showed no significant change. Increment of IGF-1 level was significant. At baseline, responders had a significantly higher hand grip and back lift strength compared to non-responders. IPAA treatment significantly increased in BUN, PNA and nPNA in both groups, but the increment of them was pronounced in responders. IPAA resulted in a significant increase in serum creatinine (10.6+/-2.1 vs. 11.8+/-2.6 mg/dL, p<0.05) and %LBMCr (70.8+/-8.9 vs. 76.4+/-9.2%, p<0.05), hand grip strength (23.2+/-7.3 vs. 24.3+/-7.7 kg, p<0.05) and back lift strength (67.0+/-27.4 vs. 75.3+/-26.6 kg, p<0.05) only in responders. Serum albumin level remained stable after IPAA treatment in responders. CONCLUSION: IPAA treatment for 12 months provided some nutritional benefits in malnourished CAPD patients. And, our data suggest that response to IPAA is more pronounced in CAPD patients with a better preserved nutritional status, especially in those patients with higher back lift and hand grip strength at baseline.

Factors Affecting Malnutrition in Continuous Ambulatory Peritoneal Dialysis Patients: A Cross-sectional Study / 대한신장학회잡지

PURPOSE: Protein-calorie malnutrition is common in continuous ambulatory peritoneal dialysis (CAPD) patients and is associated with an increase in morbidity and mortality. This cross-sectional study was carried out to investigate prevalence of protein-calorie malnutrition in Korean CAPD patients. Other purposes were to ascertain relationship between various nutritional parameters and to evaluate factors independently associated with malnutrition in CAPD patients. METHODS: Subjects were clinically stable 127 patients who have been on CAPD for more than 3 months. Nutritional status was assessed by subjective global assessment (SGA), biochemical, anthropometric, and urea kinetic parameters. RESULTS: The mean age of the patients was 50.7+/-11.4 years with sex ratio (M : F) 1 : 1, and mean duration of dialysis was 67.3+/-39.7 months. Patients were divided into 3 groups according to SGA : group I (normal nutrition, n=75, 59.0%), group II (mild malnutrition, n=30, 23.6%) and group III (moderate to severe malnutrition, n=22, 17.4%). There were significant differences in age, CAPD duration, peritonitis rate and hospital-days per year between group I and group III. Among biochemical variables, serum creatinine, triglyceride, protein, albumin, prealbumin, IGF- 1, transferrin and leptin were significantly lower in group III compared to group I (p<0.05), and CRP, ferritin, and IL-6 were significantly higher in group III than group I. There were significant differences in serum albumin among all three groups. There were no differences in Kt/Vurea, nPNA and SCCr among three groups. However, there were significant differences in residual renal function (p<0.05) and PNA (p<0.05) between group I and group III. Among anthropometric variables, body weight, %IBW, BMI, %body fat mass, MAC, TSF, BSF, CAMA, and TBM were significantly lower in group III than the other two groups (p<0.05). But, there was no differences in exercise capacity and food intake among the three groups. To evaluate relationship between various parameters used for assessing malnutrition, we conducted Pearson's rank correlation test. Serum albumin (gamma=0.45), age (gamma=-0.29), %IBW (gamma=0.52), leptin (gamma=0.32), CRP (gamma=-0.24), TSF (gamma=0.45) and CAMA (gamma=0.41) significantly correlated with SGA. As a result of multiple regression analysis, albumin, leptin, and CRP were independent predictors of malnutrition (p<0.05). CONCLUSION: About 40% of CAPD patients were malnourished according to SGA, and multiple regression analysis revealed that serum albumin, leptin and CRP were independent predictors of malnutrition. These results suggest that acute and chronic inflammatory response plays an important role in the development of protein-calorie malnutrition in CAPD patients with comparable food intake and dialysis dose.

Selective Proteinuria Index as a Prognostic Index in IgA Nephropathy / 대한신장학회잡지

PURPOSE: Proteinuria is the hallmark of glomerular injury and results from alterations in glomerular permeability. The permeability of diseased glomerulus has been estimated by selectivity of proteinuria. Recently, some authors showed a significant relationship between selectivity of proteinuria and tubulointerstial damage. The present study examines the role of protein selectivity as a prognostic marker in patients with IgA nephropathy and its correlation with other prognostic indices. METHODS: The selective proteiuria index of 81 cases with IgA nephropathy diagnosed between 1990 and 2000 were reviewed, and each case was subclassified using the following : highly selective(SPI0.2). The mean age of the patients was 27+/-15 years with a follow-up period of 38+/-24 months. Six patients had highly selective proteinuria, thirty three patients had moderately selective proteinuria, and forty two patients had nonselective proteinuria. RESULTS: 1) A significant relationship was found between the SPI and Haas subclasess(p=0.01). With respect to clinical presentaion, hypertension(0, 4, 11 cases, p<0.05), proteinuria(0.52+/-0.35, 1.85+/-1.55, 2.79+/-2.51 g/day, p<0.05) were significant correlation.2) Chronic renal failure was significantly higher in patients with nonselective proteinuria in comparison with patients with selective proteinuria(p<0.05).3) Markers of renal failure by the Cox proportional hazards model were Cr(Exp(B)=4.2, p<0.001), Ccr (Exp(B)=2.1, p<0.05), SPI(Exp(B)=1.7, p<0.05), hypertension(Exp(B)=1.6, p<0.05). 4) In 28 patients of IgA nephropathy with nephrotic syndrome, 9 patients were moderately selective, 19 patients were nonselective. The response to therapy, evaluated retrospectively, was 67% and 16% in moderate and nonselective proteinuria(p=0.01). CONCLUSION: There is a significant relationship between selectivity of proteinuria and clinical para meters. Moreover, the selectivity of proteinuria has a predictive value on functional outcome.

Changing patterns of skin reactivity to inhalant allergens in asthmatic patients / 천식및알레르기

BACKGROUND: Skin prick test has been the primary diagnostic tool used to recognize causative allergens, and there is some evidence that skin reactivity to allergens can be altered by changes in the environment. OBJECTIVE: We performed this study to evaluate whether there are changes in skin reactivity to inhalant allergens among patients with bronchial asthma. MATERIALS AND METHOD: We reviewed the skin prick test results of 384 bronchial asthmatics tested in the early 1990s (June 1992-May 1994) with 52 common inhalant allergens and compared the results of 500 asthmatics tested in the mid 1980s (Jan 1984 - May 1987) with the same kinds of allergens provided by the same manufacturer. RESULTS: Of the 384 subjects tested in the early 1990s, 276 subjects(71.9%) had positive reaction to one or more inhalant allergens and the positive rate was not different from that of the mid 1980s(74%). But, skin reactivity to pollens was significantly increased. In individual allergens, house dust mite(D. farinae and D. pteronyssinus) was the most reactive allergen (52.3%, 43.2% respectively) in the early 1990s. Significant differences in skin reactivity to ragweed (10.0% vs 22.1%, p<0.05) and cockroach (12.7% vs 25.0%, p<0.05) were found when the results of the 1980s and the 1990s were compared. CONCLUSION: House dust mite was the most important allergen in asthmatics from the mid 1980s to the early 1990s. There was increased sensitization to cockroach and ragweed allergen in the early 1990s. Further prospective immunologic and environmental studies are recommended for proper interpretation of the changes in skin reactivity.

A Case of Massive Perirenal Hematoma in a Patient with Hemorrhagic Fever with Renal Syndrome / 대한신장학회잡지

Hemorrhagic fever with renal syndrome is characterized clinically by the triad of fever, hemorrhage and renal failure. The hemorrhage in hemorrhagic fever with renal syndrome(HFRS) varies from transient petechial lesions to fulminant and massive bleeding. The latter can be an important cause of death in HFRS. We here report a case of massive perirenal hematoma in a patient with HFRS. A 17-year-old male was admited to our hospital presenting with fever, sore throat, nausea and oliuria. Computed tomography was performed at the 2nd day of hospitalization due to abruptly developing right flank pain and anemia and showed perirenal hematoma on the right kidney. He was diagnosed as HFRS and treated with hemodialysis, fluid infusion, and transfusion. There was no evidence of further blood loss at the 7th day of hospitalization. After conservative treatment, he recovered from HFRS.

Study on the Prevalence of Coronary Heart Disease and Albuminuria in Type 2 Diabetic Patients / 대한신장학회잡지

There are opinions that microalbuminuria acts as an independent risk factor for cardiovascular diseases, related to other risk factors such as endothelial cell dysfunction, hypertension, insulin resistance, obesity, hyperlipidemia and platelet aggregation dysfunction in diabetic and non-diabetic patients. We examined the prevalence of microalbuminuria and macroalbuminuria and the relationship of microalbuminuria and macroalbuminuria to coronary heart disease in type 2 diabetic patients. Out of 798 type 2 diabetic patients who were hospitalized at Yonsei medical center from Oct. 1997 to Feb. 1999, we studied 181 patients who had normal renal function and were examined 24 hour urine albumin excretion. According to the amount of urine albumin excretion, 181 patients were categorized into three groups; normoalbuminuria(less than 30mg/24hour), microalbuminuria(30-300mg/24hour) and macroalbuminuria (more than 300mg/24hour). Patients were tested using treadmill test, stress thallium scan, echocardiography, and coronary angiography for the evaluation of coronary heart disease. The freguency of normoalbuminuria, microalbuminuria, and macroalbuminuria in our patients were 50.3%(91/181), 30.9%(56/181), and 18.3%(34/181), respectively. In each group, the prevalence of hypertension were 42.5%, 78.5%, and 82.3%, respectively and the prevalence of cardiovascular disease were 24.7%, 50.0%, and 46.0%, respectively. Microalbuminuria and macroalbuminuria groups showed statistically significant differences in the prevalence of hypertension and coronary heart disease compared with normoalbuminuria group(p<0.05). In addition, the prevalence of diabetic retinopathy were 37.3%, 58.9%, and 55.8%, respectively and microalbuminuria and macroalbuminuria groups showed statistically significant differences in the prevalence of diabetic retinopathy compared with normoalbuminuria group(p<0.05). We conclude that microalbuminuria and macroalbuminuria is a strong predictor of coronary heart disease in patients with type 2 diabetes.

Evaluation of Residual Renal Function of Chronic Renal Failure at the Initiation of Dialysis / 대한신장학회잡지

The decision to initiate dialysis in a patient with progressive renal disease often depends on the physician's assessment of the patient's subjective symptoms of uremia. Decreased residual renal function and malnutrition at the initiation of dialysis is a strong predictor of subsequent increased relative risk of death on dialysis. In this context, to investigate the residual renal function and nutritional parameters of chronic renal failure patients at the initiation of dialysis, 103 patients with chronic renal failure patients were studied. The residual renal function(estimated GFR) was ascertained by measuring simultaneously the 24-h creatinine and urea clearances and averaging the two values and Krt/V. Nutritional parameters were ascertained by measuring the nPNA, %LBM and serum albumin. The mean estimated GFR was 5.97+/-2.88ml/min, the mean weekly Krt/V was 1.24+/-0.80, the mean %LBM was 61.66+/-22.41 and the mean nPNA was 0.89+/-0.30 g/day/kg. We knew that the time of initiation of dialysis, which was based on the manifestation of symptoms of certain patients in conjunction with selected laboratories indices, was delayed than that of NKF- DOQI recommendation. This study suggests that the timely initiation of dialysis is determined by not clinical symptoms and signs but estimated GFR, krt/V and nPNA.

A Case of microscopic pulmonary metastasis of papillary thyroid carcinoma / 대한내과학회지

Although the papillary thyroid carcinoma generally follows an indolent course characterized by slow growth and abscence of distant metastasis, distant metastases to extrathyroid organ may occur in the lung, bone and brain in about 5% of patients. The lung metastases are usually diagnosed by plain X-ray, chest CT and 131I whole body scan. However, we present a case of papillary thyroid carcinoma with microscopic pulmonary metastasis that could not be detected by conventional method, such as chest X-ray, chest CT and 131I whole body scan. A 62-year-old female visited due to traumatic hemopneumothorax. In the pathology of resected tissues from lacerated lung parenchyme, metastatic papillary carcinoma was diagnosed without evidence of abnormality in radiologic examination and we diagnosed and treated an asymptomatic papillary thyroid carcinoma.

2 Cases of Peripheral Nerve Tumors of Anterior Neck Simulating Thyroid Nodule / 대한내분비학회지

Peripheral nerve tumors are mostly benign and can arise on any nerve trunk or twig. Although peripheral nerve tumors can occur anywhere in the body, including the spinal roots and cauda equina, many cases are subcutaneous in location and present as a soft swelling, sometimes with a purplish discoloration of skin. There are two major catagories, schwannoma(neurilemmoma), and neurofibroma. Schwannomas are usually solitary and grow in the nerve sheath, rendering them relatively easy to dissect free. In contrast, neurofibromas tend to be multiple, grow in the endoneural substance, which renders them difficult to dissect, may undergo malignant changes, and are the hallmark of von Recklinghausens neurofibromatosis. Masses in the anterior part of neck may be initially thought to be thyroid nodule and then other cervical masses should be considered. The diagnosis rests on clinical suspicion and diagnostic support may be obtained by CT scan, magnetic resonance imaging(MRI) and substraction angiography in the literature. After imaging, fine needle aspiration for cytology may be helpful. If they are resected unrecognized and/or without regard to their nerve origin, major and permanent nerve defects can unnecessarily occur. We experienced 2 cases of peripheral nerve tumors of anterior neck simulating a thyroid nodule.