Satoru Kuriyama

2008 Japanese Society for Dialysis Therapy: guidelines for renal anemia in chronic kidney disease.

The Japanese Society for Dialysis Therapy (JSDT) guideline committee, chaired by Dr Y. Tsubakihara, presents the Japanese guidelines entitled “Guidelines for Renal Anemia in Chronic Kidney Disease.” These guidelines replace the “2004 JSDT Guidelines for Renal Anemia in Chronic Hemodialysis Patients,” and contain new, additional guidelines for peritoneal dialysis (PD), non‐dialysis (ND), and pediatric chronic kidney disease (CKD) patients.

Pseudoaldosteronism due to the concurrent use of two herbal medicines containing glycyrrhizin: interaction of glycyrrhizin with angiotensin-converting enzyme inhibitor

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.

Effect of Cilazapril on Hyperdipsia in Hemodialyzed Patients

To investigate whether angiotensin-converting enzyme inhibitor (ACE-I) potentially alleviates hyperdipsia, the effect of cilazapril on dialysis-associated excessive thirst was studied by evaluating various dipsogenic parameters in patients undergoing chronic hemodialysis (HD) who manifest an excessive interdialysis body weight gain of more than 5%, and show simultaneous severe-to-moderate hyperdipsia. An initial single dose of 1 mg of cilazapril given at the end of the HD session produced a marked improvement in the interdialysis thirst scores and a simultaneous reduction in plasma angiotensin II (AII) concentration due to the inhibition of ACE activity. The interdialysis body weight gain in the cilazapril treatment period was significantly smaller than that in the nontreatment period. None of the other parameters including blood pressure, plasma osmolarity, and serum Na and K concentration were different in the treatment vs. the nontreatment period. The present data help to explain the potential pharmacological action of AII in the physiology of thirst and suggest that cilazapril may effectively alleviate dialysis-associated hyperdipsia at least on some occasions. The mechanism by which ACE-I exerts an antidipsogenic action may, in part, be accounted for by the reduction in plasma concentration of AII, as a result of the ACE inhibition.

Carpal Tunnel Syndrome in Patients Undergoing CAPD: A Collaborative Study in 143 Centers

Patients undergoing continuous ambulatory peritoneal dialysis (CAPD) who developed carpal tunnel syndrome (CTS) were retrospectively studied in 143 centers in Japan. Among the total 5,050 patients undergoing CAPD between 1980 and 1993 only 7 patients (0.14%) given CAPD developed CTS. Five of these 7 patients treated solely with CAPD developed CTS 12-108 months after starting CAPD. The remaining 2 patients who were initially treated with HD for 7-9 years and then switched to CAPD developed this complication 9 years after starting CAPD. All 7 patients were women, ranging in age from 32 to 70 (average 52) years. We detected the presence of amyloid deposits in 2 of 5 specimens and beta 2-microglobulin in 2 of 4 specimens from these patients. It was concluded that CAPD minimizes the emergence of CTS although constant surveillance is necessary to detect CTS in patients during CAPD.

Successful Treatment of Tumoral Calcinosis Using CAPD Combined with Hemodialysis with Low-Calcium Dialysate

Successful treatment of tumoral calcinosis using continuous ambulatory peritoneal dialysis (CAPD) combined with hemodialysis is described. A 32-year-old male patient with a 2-year history of CAPD rapidly developed multiple metastatic calcification (tumoral calcinosis) adjacent to his fingers, elbows, and knee joints. Tests showed severe hyperphosphatemia, moderate hypercalcemia, and increased Ca-P product without elevation of intact parathyroid hormone. An enlarged parathyroid gland was not found by echography. In order to rapidly lower the excessive Ca and P levels, a combined therapy with CAPD and vigorous transient hemodialysis using a low-Ca dialysate was performed. In parallel, the patient was given calcitonin, bisphosphonate, and short-term Al to ameliorate the metastatic calcifications more effectively. The result was dramatic with disappearance of the tumoral calcinosis as well as improvement in subjective symptoms within a few months. The present case suggests that combined therapy with hemodialysis and CAPD using a low-Ca dialysate, together with Ca-modulating agents, can be effective in ameliorating tumoral calcinosis in patients on CAPD.

Morning blood pressure at home predicts erythropoietin-induced hypertension in patients with chronic renal diseases

BackgroundCorrection 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.MethodsThe 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.ResultsBefore 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 Wilcoxons analysis), but not by OBP (from 42% to 47% before and after treatment; P = 0.1399).ConclusionsThe 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.

Angiotensin II effect on 22Na+ transport in vascular smooth muscle cells.

It is well established that angiotensin II (AII) rapidly increases free cytosolic Ca2+ in vascular smooth muscle cells (VSMCs). Several studies have indicated that the hormone also plays a role in Na+-K+ regulation of these cells. In this study, we explored the mechanism of AII effect on 22Na+ transport in cultured rat VSMCs. The 22Na+ washout from these cells was described by three exponents with exponential factors k1 greater than k2 greater than k3. In 1.8 mM Ca2+ medium, AII (10(-9)-10(-6) M) increased (in a dose response manner) the k1 value, and consequently the initial washout rate constant (kei) for the isotope. AII had no effect on kei in Ca2+-deficient medium or in the presence of ouabain. Amiloride (10(-3) M) and verapamil (10(-5) M) abolished the AII induced increase in kei. These findings are consistent with angiotensin II stimulation of an amiloride-sensitive Na+ transport, which is likely to represent the Na+/H+ antiport. In cultured VSMCs, the sustained stimulation by AII of this transport system requires the presence of extracellular Ca2+ and its influx into these cells.

Increased atrial natriuretic factor receptor density in cultured vascular smooth muscle cells of the spontaneously hypertensive rat.

To explore the role of the atrial natriuretic factor (ANF) system in the pathophysiology of hypertension we examined the binding kinetics of synthetic ANF to cultured vascular smooth muscle cells (VSMCs) derived from the spontaneously hypertensive rat (SHR) and two normotensive controls-the Wistar Kyoto (WKY) and American Wistar (W). The number of maximal binding sites (Bmax) per cell (mean +/- SEM; X10(3] were: SHR = 278.0 +/- 33.0, WKY = 28.3 +/- 7.1 and W = 26.6 +/- 4.2. The differences between the SHR and normotensive strains were significant at p less than 0.001. The equilibrium dissociation constant (Kd; X 10(-9)M) was higher in SHR VSMCs (0.94 +/- 0.14) than in WKY (0.22 +/- 0.09; p less than 0.01) and W (0.39 +/- 0.14; p less than 0.02) cells. The plasma levels of the immunoreactive ANF were higher in SHR than the normotensive controls. We suggest that the relatively greater ANF receptor density in cultured VSMCs of the SHR represents a response to the in vitro environment which is relatively more deficient in ANF for VSMCs of the SHR as compared with the normotensive rats. Thus, the capacity of the SHR VSMC to regulate ANF receptor density appears to be independent of the blood pressure level.

Incidence of peripheral arteriosclerotic complications of the lower extremities in diabetic patients with chronic renal failure.

Abstract:  Patients with diabetes mellitus are at high risk of arteriosclerotic complications. The same is true for those with chronic renal failure (CRF). The present study evaluated clinical factors on the occurrence of peripheral arterial diseases. The severity of peripheral arterial disease was defined as mild (plaque, calcifications) or severe (70% stenosis, obstructions) based upon ultrasonographical examination. Overall in diabetic patients, mild ultrasonographical findings such as plaque and calcification were observed in 25% (17/69) of predialysis patients and in 18% (7/38) of those on hemodialysis (HD). Severe arteriosclerotic findings such as stenosis and obstruction were seen in 42% (29/69) of predialysis patients and in 50% (19/38) of those on HD. The incidence is identical between predialysis patients and patients on HD, regardless of the severity of peripheral arterial diseases. In an attempt to compare diabetics with non‐diabetics, the incidence of mild abnormal findings was found in 22% (24/107) of diabetics and in 30% (11/37) of non‐diabetics. Similarly, the percentage of patients with severe arteriosclerotic findings was found in 45% (48/107) in diabetics and 11% (4/37) in non‐diabetics. The incidence of the severe type findings in the diabetics is significantly more frequent than that in the non‐diabetics (P < 0.01, by the χ2 test). In non‐diabetic predialysis patients, the incidence of mild arteriosclerotic findings was observed in 30% (7/23), and 29% (4/14) of non‐diabetic patients on HD. Similarly, the percentage of severe type was 9% (2/23) in non‐diabetic predialysis patients, and 14% (2/14) in non‐diabetic patients on HD. These data are not only supportive of previous data that diabetes is a risk factor for arteriosclerosis, but also suggestive that, even before the initiation of dialysis, patients with CRF are already susceptible to arteriosclerotic assault of peripheral arterial complications.

The effects of vasoactive agents on the proliferation of vascular smooth muscle cells grown in vitro.

The present study was designed to investigate the effect of vasoactive agents on cellular proliferation in serially passed cultured vascular smooth muscle cells (VSMC). A substantial reduction in the number of vascular smooth muscle cells was observed with the addition of nifedipine, nicorandil, bunazocine and labetalol compared with that in a control sample. Furthermore, noradrenaline significantly increased the number of vascular smooth muscle cells. In contrast, neither propranolol nor captopril had any effect on number of vascular smooth muscle cells. The cell size, measured as water volume of vascular smooth muscle cells based on the equilibrium distribution of 3-O-(14C-methyl)-D-glucose, did not differ between treatments with the above-mentioned agents. It is suggested that in addition to a known calcium-mediated mechanism, an α-receptor-mediated property could be involved in the proliferation of vascular smooth muscle cells and that clinical use of a calcium antagonist or an α-blocker might be useful to prevent the hyperproliferation of vascular smooth muscle cells commonly seen in the vascular walls of patients with hypertension.