Sung-Kyu Ha

ACE gene polymorphism and progression of diabetic nephropathy in Korean type 2 diabetic patients: effect of ACE gene DD on the progression of diabetic nephropathy

BACKGROUNDnPathophysiological causes of the development and progression of diabetic nephropathy are not well known, but the angiotensin-converting enzyme (ACE) gene polymorphism has been proposed to be involved in its development and progression.nnnMETHODSnThe impact of insertion/deletion (I/D) genotypes on the progression of diabetic nephropathy in 239 Korean patients with type 2 diabetes (99 patients with stable renal function, group 1; 140 patients with declining renal function, group 2) was investigated by retrospective review of clinical data.nnnRESULTSnThe frequency of the DD genotype was significantly greater in group 2 compared with group 1 (30.7% versus 9.1%; P < 0.05). There were no significant differences in age, blood pressure, hemoglobin A(1c) levels, or lipid profiles among ACE genotype groups. However, the prevalence of retinopathy was significantly greater in patients with the DD genotype (DD, ID, and II, 90.4%, 71.2%, and 70.6%, respectively; P < 0.05). Patients with the DD genotype reached the end point (serum creatinine > 2.0 mg/dL [176.8 micromol/L]) faster than those with the other genotypes (DD, 11.38 +/- 4.08 years; ID, 13.85 +/- 4.04 years; II, 14.04 +/- 4.06 years, respectively; P < 0.05) and took significantly less time to reach dialysis therapy (DD, 13.10 +/- 4.45 years; ID, 16.21 +/- 4.74 years; II, 15.13 +/- 4.09 years, respectively; P < 0.05). In multiple logistic regression analysis, systolic blood pressure and DD genotype showed significant correlations with the progression of diabetic nephropathy. In patients with the DD genotype, the odds ratio was 3.881 (95% confidence interval, 1.564 approximately 9.628; P = 0.003) compared with those with the II genotype.nnnCONCLUSIONnIt is suggested that the ACE gene DD genotype might be a significant risk factor for the progression of diabetic nephropathy.

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 Bonferronis 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.

Safety and Efficacy of Tolvaptan in Korean Patients with Hyponatremia Caused by the Syndrome of Inappropriate Antidiuretic Hormone

Background The aim of this multicenter study was to evaluate the safety and efficacy of tolvaptan (TLV) in Korean patients with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Methods Of 51 enrolled patients with SIADH, 39 patients (16 female patients, aged 70.8 ± 11.3 years) were included in an intention to treat analysis. All patients received 15 mg/day as the initial dose, and the dose was then increased up to 60 mg/day (as needed) until day 4. Results Serum sodium increased significantly from baseline during the first 24 hours (126.8 ± 4.3 vs. 133.7 ± 3.8 mmol/L, P < 0.001), rose gradually between days 1 and 4 (133.7 ± 3.8 vs. 135.6 ± 3.6 mmol/L, P < 0.05), and then plateaued until day 11 (136.7 ± 4.5 mmol/L). The correlation between the change in serum sodium for the first 24 hours and initial serum sodium concentration was significant (r = −0.602, P < 0.001). In severe hyponatremia (< 125 mmol/L), the change was significantly higher (11.1 ± 4.8 mmol/L) than in moderate (6.4 ± 2.5 mmol/L, P < 0.05) or mild hyponatremia (4.3 ± 3.3 mmol/L, P < 0.01). In addition, logistic regression analysis showed that body weight (odds ratio [OR], 0.858; 95% confidence interval [CI], 0.775–0.976; P = 0.020) and body mass index (BMI) (OR, 0.692; 95% CI, 0.500–0.956; P = 0.026) were associated with rapid correction. No serious adverse events were reported, but in 13% of patients hyponatremia was overcorrected. Conclusion TLV is effective in correcting hyponatremia and well-tolerated in Korean patients with SIADH. However, those with low body weight, low BMI or severe hyponatremia, could be vulnerable to overcorrection with the initial dose of 15 mg TLV.