Satoru Kuriyama

Diabetic nephropathy has been increasing in prevalence in recent years, and it is now the dominant cause of end-stage renal disease (ESRD) worldwide. Because diabetes is frequently associated with multiple complications, nephrologists must be alert to the selection of dialysis modality so as to reduce the accompanying risks. The present review addresses whether the benefits of peritoneal dialysis are greater than its disadvantages in diabetic patients. The answer is quite positive: for most diabetic patients, peritoneal dialysis offers multiple benefits.

Correction of anemia by erythropoietin (EPO) is often associated with a rise in blood pressure (BP; EPO-induced hypertension). Most studies regarding EPO-induced hypertension have involved evaluation using office/clinic BP (OBP). However, recent investigations suggest that BP measured at home (HBP) may be of more importance for clinical practice in hypertension. In this context, the present study addressed whether or not HBP measured in the morning could be useful to predict EPO-induced hypertension. The study involved patients with mild to moderate renal impairment who had renal anemia requiring EPO treatment. BP control was evaluated based on the relationship between OBP and HBP in the morning. The BP categories used were well-controlled BP, poorly controlled BP, hypertension with a white-coat effect (white-coat hypertension), and masked hypertension. Comparison was made of the BP categories before and after EPO treatment. Before EPO treatment, 38% of patients had well-controlled BP, 30% had poorly controlled BP, 20% had masked hypertension, and 12% had white-coat hypertension, revealing a predominance of morning hypertension (poorly controlled BP plus masked hypertension). Following EPO treatment, the prevalence of morning hypertension in patients with masked hypertension and poorly controlled BP increased significantly, by 5% (HBP in those with masked hypertension increased from 152 +/− 18 mmHg to 162 +/− 25 mmHg, and HBP in those with poorly controlled BP increased from 157 +/− 18 mmHg to 168 +/− 25 mmHg; P < 0.05 by paired t-test). And there was a significant decrease in the prevalence of the well-controlled category, by 8%, with an increased level of morning HBP (from 128 +/− 14 mmHg to 137 +/− 16 mmHg; P < 0.05 by paired t-test). In contrast, OBP remained unchanged in all groups. The development of EPO-induced hypertension was effectively predicted by HBP in the morning (from 62% to 72% before and after EPO treatment; P = 0.0031 by Wilcoxon's analysis), but not by OBP (from 42% to 47% before and after treatment; P = 0.1399). The present study indicates that, despite receiving concurrent antihypertensive therapy, the majority of patients with renal disease had morning hypertension. Furthermore, HBP in the morning can be more useful than OBP to predict the development of EPO-induced hypertension in patients with renal anemia.

A 77-year-old man with a history of hypertension and hyperuricemia was admitted to our hospital complaining of limb weakness, persistent constipation, and worsening hypertension. He had been taking a Chinese herbal remedy for allergic rhinitis for the past 10 years, together with an angiotensin-converting enzyme inhibitor (ACE-I; enalapril, 20 mg daily). After the dosage of enalapril had been reduced to 10 mg daily about 1½ years before the current admission, he had developed persistent constipation. Therefore, he had started taking another traditional Chinese herbal remedy, a laxative, for the constipation, about 4 months prior to this hospitalization. Laboratory data on admission demonstrated marked metabolic alkalosis with severe hypokalemia associated with urinary wasting of potassium and chloride. A diagnosis of pseudoaldosteronism was made based upon his past history of exposure to various traditional Chinese medicines containing glycyrrhizin. Discontinuation of the Chinese remedies and supplementation of potassium successfully normalized the electrolyte imbalance and relieved all symptoms within a short time. The present case describes the occurrence of pseudoaldosteronism induced by a patient taking two traditional Chinese herbs, both containing glycyrrhizin, resulting in an overdose of this causative chemical agent. The development of pseudoaldosteronism appeared to be of particular interest with regard to the interaction of the renin-angiotensin-aldosterone (RAA) system with glycyrrhizin, in which an ACE-I retarded the development of pseudoaldosteronism.

Combined antihypertensive therapy plays a crucial role in achieving targeted blood pressure reductions and renoprotection. We therefore compared the antihypertensive and antiproteinuric effects of combined therapy with either a calcium channel blocker (CCB) plus an angiotensin II receptor blocker (ARB) or an angiotensin converting enzyme inhibitor (ACE-I) plus an ARB in patients with type 2 diabetes mellitus complicated by overt nephropathy and mild to moderate hypertension. After a 12-week dietary control period, diabetic patients with mildly to moderately impaired renal function were randomly assigned to either a CCB (amlodipine 5 mg once daily) or an ACE-I (temocapril 2 mg once daily) for 12 weeks (monotherapy period). Both groups then received add-on therapy with an ARB (candesartan 4 mg once daily) for an additional 12 weeks. During the monotherapy period, blood pressure was decreased equally well in both groups. Daily urinary protein excretion remained unchanged in the CCB-treated group (control period, 4.0±1.8 g/day vs. CCB period, 4.1±1.9 g/day; ns; n =8), but decreased in the ACE-I-treated group (control period, 4.3±1.8 g/day vs. ACE-I period, 3.5±1.7 g/day; p <0.05; n =9). After the combined therapy period, blood pressure was decreased to the same degree in both groups. Although ARB plus CCB significantly reduced urinary protein excretion (to 3.5±1.5 g/day; p <0.05 vs. control period; n =8), a more profound reduction was achieved with ARB plus ACE-I (to 2.6±1.3 g/day; p <0.01 vs. control period; n =9). Monotherapy with the ACE-I increased the serum potassium concentration, and this elevation was sustained after addition of the ARB. In contrast, the serum potassium concentration was not influenced by monotherapy with the CCB, but was significantly increased after addition of the ARB. A decreased hematocrit was observed in the ARB plus ACE-I group. The present study suggests that combined antihypertensive therapy with either a CCB plus an ARB or an ACE-I plus an ARB exerts an antiproteinuric effect in patients with type 2 diabetic nephropathy with mildly impaired renal function. Although the latter combination had a more profound effect, it was associated with an increased serum potassium concentration and worsening of renal anemia. Thus, the combination of a CCB and an ARB should be the first line antihypertensive therapy in those with overt diabetic nephropathy. The long-term efficacy of these combined antihypertensive therapies will need to be further addressed in a future study. (Hypertens Res 2002; 25: 849-855)

The association of the angiotensinogen (AGT) gene variation at codon 235, the T235 variant, with hypertension induced by erythropoietin (Epo) was investigated in patients with progressive renal disease requiring treatment for renal anemia with Epo. The subjects for the study were patients with renal diseases with serum creatinine concentration exceeding 2 mg/dl and a hematocrit (Ht) of less than 30%. During the run-in period, blood pressure was well controlled with an appropriate salt restricted diet and/or antihypertensive treatment. The patients were then given 6,000 lU of Epo once a week until the Ht rose by 5%. For the overall patient group, AGT gene polymorphism analysis revealed T235T (T/T) in 31 cases (61%), M235T (M/T) in 19 cases (37%), and M235M (M/M) in 1 case (2%). In response to treatment with Epo, hypertension (defined as an increase in mean blood pressure greater than 10 mmHg) was found in 11 cases (22%), all of who carried the homozygous T allele (T/T). On the other hand, the frequency of T/T in patients who did not develop hypertension was 50% (T/T:T/M=20:19 cases), indicating a significant difference (p=0.003 by Chi-square). Variables estimated to be associated with Epo-induced hypertension were the T allele, gender (male), and the degree of increase in Ht, in descending order. Our preliminary research indicates that individuals who carry two copies of the T allele, i.e., who are homozygous for T, are highly susceptible to development of hypertension when subjected to Epo. These results suggest that the AGT T235 variant may be the primary gene responsible for the development of Epo-induced hypertension. (Hypertens Res 2001; 24: 501-505)