Araki Tanaka

Effect of Granulocyte and Monocyte Adsorption Apheresis on Urinary Albumin Excretion and Plasma Endothelin-1 Concentration in Patients with Active Ulcerative Colitis

Background/Aim: Increases in microalbuminuria and endothelin (ET-1) are involved in the development of ulcerative colitis (UC) and in its progress. Because granulocyte and monocyte adsorption apheresis has proven to be useful in the treatment of UC, we examined whether urinary albumin excretion and plasma ET-1 concentrations are altered and whether granulocyte and monocyte adsorption apheresis affects the concentrations of these two factors in patients with active UC. Methods: Twenty patients with active UC and 20 age-matched healthy volunteers (our hospital staffs) were included in this study. UC patients were randomly divided into two treatment groups: a granulocyte and monocyte adsorption treatment group (n = 10) and a conventional treatment group (n = 10). The urine albumin/creatinine ratio, plasma ET-1 concentration and tumor necrosis factor (TNF)-α were determined before and after treatment and compared between 2 treatment groups. The 10 adsorption treatment patients underwent 5 consecutive weekly apheresis sessions, each of 60 min duration at a flow rate of 30 ml/min. Results: The urine albumin/creatinine ratio in UC patients (6.4 ± 2.2 mg/mmol) were higher than that in healthy subjects (1.0 ± 0.7 mg/mmol, p < 0.01). In addition, the plasma ET-1 level in UC patients (3.5 ±1.5 pg/ml) was higher than that in healthy subjects (0.8 ± 0.4 pg/ml, p < 0.01). Plasma TNF-α was detected in UC patients (18.8 ± 8.4 pg/ml), but not in healthy subjects. The urine albumin/creatinine ratio was highly correlated with the plasma ET-1 level (r = 0.62; p < 0.01) and plasma TNF-a level (r = 0.66, p < 0.01). Granulocyte and monocyte adsorption apheresis reduced the urine albumin/ creatinine ratio from 6.6 ± 2.4 to 1.8 ± 0.6 mg/mmol (p < 0.01), reduced the plasma ET-1 level from 3.7 ± 1.6 to 1.4 ± 0.6 pg/ml (p < 0.05) and reduced the plasma TNF-α from 19.2 ± 8.6 to 3.8 ± 1.2 pg/ml (p < 0.01). Conventional treatment did not affect these factors. Conclusion: Our data suggest that increases in the urine albumin/creatinine ratio, ET-1 and TNF-α play an important role in active UC and that granulocyte and monocyte adsorption apheresis is effective in ameliorating such increases.

Effect of Dilazep Dihydrochloride on Urinary Albumin Excretion in Patients with Autosomal Dominant Polycystic Kidney Disease

Proteinuria and microalbuminuria occur with a highly variable severity and are associated with progression of autosomal dominant polycystic kidney disease (ADPKD). Dilazep dihydrochloride, an antiplatelet drug, is effective in patients with immunoglobulin A nephropathy or diabetic nephropathy. We studied whether dilazep dihydrochloride affects the urinary albumin excretion (UAE) in normotensive and hypertensive patients with ADPKD. Twelve normotensive ADPKD patients with microalbuminuria were randomly assigned to two groups: a dilazep (300 mg/day) treatment group (n = 6, group A) and a placebo group (n = 6, group B). In addition, 10 hypertensive ADPKD patients with microalbuminuria were randomly assigned to two groups: a dilazep (300 mg/day) treatment group (n = 5, group C) and a placebo group (n = 5, group D). Treatment with dilazep was continued for a period of 6 months, at the end of which the UAE was reduced form 130 ± 52 to 46 ± 26 µg/min (p < 0.01) in group A. There was no reduction in group C. There were no changes in UAE in placebo groups B and D. These results suggest that dilazep dihydrochloride may be effective in reducing UAE in normotensive ADPKD patients with microalbuminuria.

Comparison between the Angiotensin II Receptor Antagonist Candesartan Cilexetil and the Angiotensin-Converting Enzyme Inhibitor Trandolapril in Microalbuminuria of Patients with Early Diabetic Nephropathy

Accessible online at: www.karger.com/journals/nef Dear Sir, Experimental and clinical studies show that in various kinds of glomerular diseases, angiotensin II (AngII) contributes to the appearance of proteinuria and that angiotensin-converting enzyme inhibitors (ACEIs) significantly reduce proteinuria [1]. Intervention trials have demonstrated that ACEIs have a particular beneficial effect over other antihypertensive drugs in retarding the development and progression of diabetic nephropathy, implicating the renin-angiotensin system in its pathogenesis [2]. AngII receptor antagonists have recently been introduced as a new class of therapeutic drugs for the treatment of hypertension. AngII receptor antagonists have a more direct mechanism of action than other drugs affecting the renin-angiotensin system [3]. Recently, Russo et al. [1] reported that an ACEI (enalapril) and an AngII receptor antagonist (losartan), when administered alone, reduced proteinuria to the same extent in normotensive patients with IgA nephropathy. Candesartan cilexetil is a potent, highly selective AngII receptor antagonist devoid of agonist activity. It has a distinctive receptorbinding property characterized, in current pharmacologic terms, as being insurmountable [4]. Noda et al. [5] have reported that candesartan cilexetil shows potent and longterm preventive effects against the progression of renal injury in rats. Trandolapril is a fairly new, orally active, long-acting nonsulfhydryl ACEI, suitable for a once-daily regimen [6]. We recently compared the antimicroalbuminuric effects of candesartan cilexetil and trandolapril in patients with early diabetic nephropathy. Thirty patients with microalbuminuria were divided into two groups at random. Group A patients (10 men and 5 women, age 52.6 B 10.4 years) were treated with 8 mg candesartan cilexetil once daily. Group B patients (9 men and 6 women, age 51.6 B 9.8 years) were treated with 2 mg trandolapril once daily. After 8 weeks, microalbuminuria was reduced to the same extent in each group: from 124.6 B 66.2 to 38.2 B 16.4 Ìg/min (p ! 0.01) in the candesartan cilexetil group and from 132.2 B 70.8 to 40.6 B 18.4 Ìg/min (p ! 0.01) in the trandolapril group. A significant change in blood pressure was not seen in either group (from 124.6 B 12.8 to 116.8 B 10.8 mm Hg in group A and from 122.8 B 13.6 to 117.6 B 12.2 mm Hg in group B). Candesartan cilexetil may have a renoprotective effect similar to that of trandolapril and not related to the decrease in blood pressure in normotensive microalbuminuric patients with early diabetic nephropathy. It would be of interest to evaluate whether combination therapies have an additional renoprotective effect in patients with diabetic nephropathy. References

Effect of dilazep dihydrochloride on serum cardiac troponin T levels in hemodialysis patients

Background/Aim: Cardiac troponin T is a highly sensitive marker for the detection of myocardial injury. We studied whether dilazep dihydrochloride affects cardiac troponin T levels in hemodialysis patients. Methods: Our study included 60 hemodialysis patients without symptoms of acute myocardial ischemia. We measured serum cardiac troponin T levels by the Elecsys® troponin T assay and randomized 40 hemodialysis patients with left ventricular hypertrophy (LVH) into two treatment groups: a dilazep dihydrochloride group (300 mg/day, n = 20) and a placebo group (n = 20). Treatment was continued for 12 months. Results:There were no significant differences between pre- and postdialysis cardiac troponin T levels before treatment. LVH was noted in 40 patients out of 60 hemodialysis patients (67%). Cardiac troponin T levels were significantly higher in these patients (0.23 ± 0.08 µg/l) than in hemodialysis patients without LVH (0.09 ± 0.03 µg/l). Cardiac troponin T levels were reduced from 0.24 ± 0.08 to 0.12 ± 0.06 µg/l (p < 0.01) in patients treated with dilazep dihydrochloride. There were no change in cardiac troponin T levels in patients receiving placebo (from 0.21 ± 0.08 at baseline to 0.20 ± 0.07 µg/l). Conclusion: Dilazep dihydrochloride may be effective in ameliorating myocardial damage in hemodialysis patients.

Late Relapse in a Case of Mesangioproliferative Glomerulonephritis

A case of atypical proliferative glomerulonephritis (PGN) without mesangial immunoglobulin (Ig) A deposition (so-called non-IgA PGN) showing exacerbation of heavy proteinuria under long-term observation is reported. Examinations of first renal biopsy specimens revealed membranoproliferative glomerulonephritis (MPGN)-like findings. Urinary protein excretion completely disappeared after treatment with prednisolone (PSL) and an antiplatelet drug, i.e., dipyridamole. Negative reaction for urinary protein continued for more than 10 years. Fourteen and a half years after the first biopsy, the patient had heavy proteinuria again. Results of the second renal biopsy showed marked proliferation of glomerular mesangial cells. Under electron microscopy, lobulation and double contours of the glomerular capillary walls were also observed segmentally. Depositions of IgG, IgM, IgA, and C3 were observed mainly in the glomerular capillary walls, but not in the mesangial areas; however, these findings were not compatible with IgA nephropathy or MPGN. No hypocomplementemia was observed during the clinical course. The patient was treated with 30 mg of PSL and 75 mg of dipyridamole daily and showed a good response to such treatment. It appears that this patient had a rare case of atypical non-IgA PGN.