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.

Primary Aldosteronism Complicated with Chronic Renal Failure / 대한신장학회잡지

Primary aldosteronism is a disease entity characterized by hypertension, hypokalemia, metabolic alkalosis and muscle weakness. Aldosteronoma is the most common cause of primary aldosteronism. The prevalence of primary aldosteronism in patients with hypertension appears to be low, less than 1%. However, primary aldosteronism is the one of common cause of secondary hypertension that is one of a few potentially curable forms of hypertension by surgical treament. The malignant hypertension in primary aldosteronism is very rare and the renal vascular damage due to hypertension seldom occurs. There has been no known reports about primary aldosteronism complicated with chronic renal failure in Korea. We report the rare case of primary aldosteronism in patient with hypokalemia, metabolic alkalosis complicated with chronic renal failure due to malignant hypertension with evident nephrosclerosis.

The Results of Renal Transplantation after Lymphocyte Cross-match Negative Conversion by Combination Therapy with Plasmapheresis, Intravenous Gamma Globulin and Potent Immunosuppresants in Patients with Positive LCM / 대한이식학회지

PURPOSE: It is well-known that kidney transplantation cannot be done if recipient has circulating antibodies showing positive lymphocyte cross-match (LCX) to organ donor. In the United States and European countries, the incidence of positive LCX to cadaveric donors in patients who are on the waiting list is up to 20~40%. Unfortunately, these patients also show high rate of positive LCX to live donors when they have donor candidates in their family members and have to be on dialysis until compatible donor comes up. Recently, Eugene J Schweitzer and his associates at the University of Maryland used the combination therapy with plasmapheresis, intravenous gamma globulin and potent immunosuppression to induce negative conversion of LCX in patients who were LCX positive to their living donors and reported the good results after the trial. We did the combination therapy in patients who had positive LCX to their living donors and reported the results. METHODS: Seven patients, four women and three men who showed positive LCX to their living donors, underwent the conversion trials between January 1 and July 31, 2002. The mean age of patients was 43.86 (35~60) and the duration of dialyses varies from 9 to 120 months. We used combination therapy with plasmapheresis, intravenous gamma globulin injection, tacrolimus, mycophenolate mofetil (MMF) and steroids. Plasmapheresis had been done on every other day up to 6 times to induce negative conversion of LCX. If patient continue to show positive LCX to donor after 6 times of plasmapheresis, we stopped the therapy. The numbers of plasmapheresis varies from two to six times. Kidney transplantations were preformed immediately after negative conversion of LCX as a semi-elective procedures. Five to ten day courses of ATG (or OKT3) were used as an induction immunosuppression after transplantation and tacrolimus, MMF, and steroids were used as a maintenance immunosuppression. RESULTS: We could achieve negative conversion of LCX in six out of seven patients, and kidney transplantations were performed in these 6 patients successfully. There was no hyperacute rejection during the operations, but three patients developed acute rejection episodes during their early postoperative periods. Steroid pulse therapies were used as a primary therapy to treat acute rejection and all three patients showed complete recovery of their graft function after the treatments. Baseline serum creatinine level varies from 1.0 mg/dl to 1.9 mg/dl with 3 to 6 months follow-up periods after transplantations. We could not induce negative conversion in one patient and he remained on hemodialysis. CONCLUSION: We did successful kidney transplantations in six patients who achieved negative conversion of LCX to their donors after the combination therapy with plasmapheresis and potent immunosuppression. All patients showed excellent graft function since their operations and did not have any significant complications except three reversible acute rejection episodes. According to the results, although it is preliminary, we recommend the use of the combination therapy in patient who has LCX positive living donor. Further long-term study with more numbers of patients is needed for the evaluation of the efficacy of this trial.

A Case of Penicillium merneffei CAPD Peritonitis / 대한신장학회잡지

P. marneffei is a fungus that causes life-threatening disseminated infection in a geographically distinct areas of the world. Following the first case of human infection in 1959, the incidence of this infection has risen markedly during the past 5 years. However, even in the midst of such rapid increase, the infection has always occurred only in a limited geographic distributions or in persons who have visited this limited geographic areas. These areas include Myanmar, Hong Kong, Indonesia, Laos, Malaysia, Singapore, Taiwan, Thailand, Vietnam, and the Guangxi province of southern China. P. marneffei infection occurs mostly in immunocompromised patients, particularly AIDS patients. P. marneffei infection commonly presents with skin and subcutanous tissue infection, fungemia, diarrhea, bone marrow infection, and generalized lymphadenopathy with hepatosplenomegaly. We report the case of continuous ambulatory peritoneal dialysis-associated peritonitis caused by P. marneffei. The case occurred in Korea, a non-endemic area of P. marneffei, in a non-AIDS patient who has not been exposed to any of the endemic areas. This warrants further consideration in determining the yet unknown transmission route of this fungal organism. P. marneffei was diagnosed without delay by 18sRNA PCR and sequencing, and was later confirmed by culture. PCR and sequencing may contribute to the early diagnosis of the P. marneffei infection, which is important given this infection's ability to progress to a systemic infection with high mortality rate when diagnosis and management are delayed.

The validity of random urine specimen albumin measurement as a screening test for diabetic nephropathy

To assess the validity of urine albumin concentration (UAC) and the urine albumin:creatine ratio (UACR) in a random urine specimen (RUS) for screening diabetic nephropathy in Korea, a total of 105 ambulatory diabetes mellitus patients (male:female, 52:53), ages 40-75 years (median 59 years) collected 105 RUSs after completing a timed 24 hour urine collection. Albumin was measured by immunonephelometry. According to the timed urinary albumin excretion rate (UAER) measured in the 24 hour collection (criterion standard), samples were classified normoalbuminuric (UAER 200 micrograms/min; n = 25). The receiver operating characteristics (ROC) curve of UAC and UACR in a RUS for screening of microalbuminuria (normo- and microalbuminuric samples; n = 80) and macroalbuminuria (micro- and macroalbuminuric samples; n = 55) were plotted. Pearson's coefficients of correlation of 24 hour UAER vs. UAC and UACR were 0.81 and 0.75, respectively (P < 0.001). The point of intersection with a 100%-to-100% diagonal for microalbuminuria were as follows: 31.0 mg/l for UAC and 32.5 mg/g for UACR; for macroalbuminuria 181 mg/l for UAC and 287.3 mg/g for UACR. The sensitivity and specificity of the cut-off points for microalbuminuria were 77% and 82% for UAC and 77% and 92% for UACR. The sensitivity and specificity of the cut-off points for macroalbuminuria were 84% and 90% for UAC and 88% and 90% for UACR. In present study, no difference was observed when comparing the performance of UAC and UACR based on a statistical comparison by McNemar test. The repeated measurements of UAC and UACR in the same individual were statistically similar and were correlated with each other. Based on these results, albumin measurements (UAC and UACR) in a RUS were considered as a valid test for screening diabetic nephropathy.

A Case of Nutcracker Syndrome in a Patient with Gross Hermaturia / 대한신장학회잡지

Nutcracker syndrome(renal vein entrapment syndrome) is probably more common than previously suspected. The nutcracker phenomenon refers to compression of left renal vein between aorta and superior mesenteric artery that results in elevation of pressure in left renal vein and develoment of collateral veins. This syndrome occurs in relatively young and previously healthy patients and is characterized by intermittent gross hematuria due to left renal vein hypertension, at times associated with flank pain, abdominal pain or varicocele. We report a 17 years-old male patient with this syndrome presented with flank pain, abdominal pain, and intermittent gross hematuria for 3 months. Urinalysis revealed protein(-), blood(+++), many RBC with only 1% of dysmorphic RBC. IVP and cystoscopy showed no remarkable finding but doppler ultrasonography and abdominal spiral CT revealed compression of left renal vein between aorta and superior mesenteric artery. Renal venography showed compression of left renal vein and collateral circulation to left gonadal vein and the pressure gradient between left renal vein and inferior vena cava was 11mmHg. The nutcracker syndrome should be considered as one of the causes of nonglomerular hematuria. All patients with unexplained severe left flank or abdominal pain, or unilateral hematuria from the left on cystoscopy, should be studied by selective renal venography and pressure measurement in inferior vena cava and renal veins. The patient with this typical syndrome could be treated surgically, by transposition of left renal vein and resection of collateral veins as the procedure of choice to correct the underlying pathologic process and eliminate these troublesome symptoms.