Soichi Sugahara

Effect of Angiotensin Receptor Blockers on Cardiovascular Events in Patients Undergoing Hemodialysis: An Open-Label Randomized Controlled Trial

BACKGROUND Cardiovascular disease is the leading cause of mortality in patients with kidney failure treated with hemodialysis (HD). Although angiotensin receptor blockers (ARBs) reduce cardiovascular disease (CVD) events in patients with diabetes and chronic kidney disease, their effect in patients with kidney failure on HD therapy is not known. STUDY DESIGN Open-labeled randomized trial. SETTING & PARTICIPANTS Patients aged 30 to 80 years receiving HD 2 to 3 times weekly for 1 to 5 years at 5 university-affiliated dialysis centers. INTERVENTIONS Treatment with ARBs (valsartan, candesartan, and losartan) versus without ARBs after stratification by sex, age, systolic blood pressure, and diabetes. OUTCOMES The primary end point is the development of fatal and nonfatal CVD events, defined as the composite of CVD death, myocardial infarction, stroke, congestive heart failure, coronary artery bypass grafting, or percutaneous coronary intervention. The secondary end point is all-cause death. RESULTS 366 subjects initially were randomly assigned to an ARB or no ARB (control), but after a run-in phase, 180 were retained in each group. Mean age was 60 years, 59% were men, 51% had diabetes, and mean predialysis systolic blood pressure was 154 mm Hg. There were 93 fatal or nonfatal CVD events (52%); 34 (19%) in the ARB group and 59 (33%) in the non-ARB group. After adjustment for age, sex, diabetes, systolic blood pressure, and center, treatment with an ARB was independently associated with reduced fatal and nonfatal CVD events (hazard ratio, 0.51; 95% confidence interval, 0.33 to 0.79; P = 0.002). There were 63 deaths (35%); 25 (14%) in the ARB group and 38 (21%) in the non-ARB group. After adjustment, all-cause mortality differed between the 2 groups (hazard ratio, 0.64; 95% confidence interval, 0.39 to 1.06; P = 0.1). LIMITATIONS Because of the small sample size of this trial, the large effect may be a spurious finding. Use of an open-label design and 3 different agents in the ARB group might have influenced results. CONCLUSION Use of an ARB may be effective in reducing nonfatal CVD events in patients undergoing long-term HD. A larger study is required to confirm these results.

A comparison of corticosteroid and warfarin therapy in IgA nephropathy with crescent formation: preliminary trial

AbstractBackground. No satisfactory treatment exists for IgA nephropathy (IgAN), especially in patients with severe histologic damage. Several trials using steroids combined with other therapies such as warfarin have demonstrated unremarkable results. We investigated the renoprotective effects of warfarin and steroids in IgAN patients with crescent formation. Methods. Fifteen Japanese patients with IgAN were followed for up to 3 years. Crescent formation was recognized in over half of their glomeruli from renal biopsy specimens. Treatments consisted of either 0.5 mg/kg per day of prednisolone, or warfarin monotherapy. Blood pressure was controlled with long-acting calcium channel blockers and alpha-beta blockers. Serum creatinine and urinary protein excretion were evaluated at least every 2 months for 36 months. Results. Ten of the 15 patients completed the study. The serum creatinine levels had increased in both groups by 3 years, but significantly more so in the group treated with warfarin. However, they were not significantly different between the two groups as measured at the beginning and end of the study. Blood pressure for all patients in the study was maintained below 130/85 mmHg. Excluded from the study were 5 patients who experienced either peptic ulcers (n = 2, steroid group) or bleeding problems (n = 3, warfarin group). Conclusions. These results suggest that corticosteroid therapy may assist in preventing deterioration of renal function in patients with IgAN accompanied by crescent formation. However, further study would be required to decide its usefulness.

Selection of hemoperfusion therapy for patients with septic shock on the basis of the primary disease

The objective of this study was to analyze retrospectively the efficacy of polymyxin-B immobilized fiber (PMX-F) alone and in combination with continuous venovenous hemofiltration (CHF) on the prognosis of critically ill patients with sepsis using a retrospective chart review in a university hospital in Japan. A cohort of 246 patients meeting the criteria of sepsis, septic shock, or both, according to the American College of Chest Physicians/Society of Critical Care Medicine (ACCP/ACCM) Consensus Conference, were examined in this study. From these patients, 48 were selected who were found to have definitive causative bacteria and whose primary diseases were clearly identified. According to the charts, two major primary diseases were identified: one related to cardiovascular disease and the other to gastrointestinal disease. Other diseases were excluded from this study because of the small numbers of patients in categories such as malignant, hematological, genitourinary, and other diseases. Furthermore, patients who had levels of serum creatinine above 2.0 mg/dl were excluded. The prevalence of diabetes mellitus (up to 63%) was very high in both groups. There were no significant differences between the two groups in age or the Apache II scores at the start of hemoperfusion treatment; however, the gender ratio varied: 72% of the cardiovascular group were male, compared to 46% of the gastrointestinal group. The causative bacteria were markedly different between the two groups. For half of the gastrointestinal group the causative bacterium was Escherichia coli, while for half of the cardiovascular group the causative bacterium was Pseudomonas aeruginosa.The survival rate differed significantly between the two groups. The patients in the cardiovascular group survived longer than those in the gastrointestinal group. Moreover, for the patients with cardiovascular disease, there was no significant difference in the survival rate between treatment with PMX-F alone and with PMX-F and CHF in combination. In contrast, for the patients with gastrointestinal disease, there was a significant difference between treatment with PMX-F alone and with PMX-F and CHF in combination. When a patient with sepsis or septic shock is treated with hemoperfusion, the decision as to whether PMX-F should be given alone or in combination with CHF might be determined on the basis of the primary disease of the patient.

Salt and Excess Food Intake Produced Diabetic Nephropathy in Japan

The purpose of this study is to retrospectively analyze the clinical characteristics of patients with diabetes mellitus who started dialysis therapy. First, we reviewed 120 cases of end-stage renal failure due to diabetic nephropathy who started dialysis therapy in 1996 and 1997. Presenting features were as follows: men, 62.5%; mean age at starting dialysis, 57 +/- 1 year; and mean serum creatinine level, 7.3 +/- 0.2 mg/dl. To find any clinical characteristics in the population, we divided patients into three groups according to age, as follows: Young age group (<40 years old: 12 patients), Senior age group (>65 years: 32 patients) and Middle age group: 76 patients (>40 and <65 years). The Young age group, (mean age: 36 +/- 1 years) had lower serum creatinine levels (6.1 +/- 0.4 mg/dl) (p < 0.05) and greater cardio-thoracic ratio (61.1 +/- 1.3%) (p < 0.05), obtained from the chest X-ray film, than the other two groups. There were no significant differences between the Middle age group (59 +/- 1 year) and the Senior age group (72 +/- 1 year) in the levels of serum creatinine and cardio-thoracic ratio. To further analyze the clinical characteristics, the other 113 patients in 1998 and 1999 who were matched with the Middle age group in the former study, were retrospectively analyzed. The mean age was 61 +/- 2 years, and the proportion of men was 54% (62/113). The percentage of changes in body weights were as follows: 9.5 +/- 2.8% (p < 0.05) from teens to 20s and 19.2 +/- 3.2% (p < 0.05) from teens to 30s in men. The percentage of changes in body weight in women were as follows: 9.6 +/- 2.1% (p < 0.05) from teens to 30s and 18.6 +/- 2.4% (p < 0.05) from teens to 40s. The age at the start of dialysis therapy was 54 +/- 2 years old in men and 59 +/- 3 years in women. There was a significant difference (p < 0.05) between men and women. In summary, the study suggests that young patients with diabetic nephropathy received dialysis therapy because of hypervolemic symptoms compared to older patients, and that renal deterioration progressed more rapidly in male subjects than in female subjects with diabetic nephropathy. These differences should be borne in mind in clinical practice.

Acute Kidney Injury of Non-Septic Origin Requiring Dialysis Therapy

Acute kidney injury (AKI) requiring dialysis occurs frequently, and its pathogenesis involves multiple pathways within which hemodynamic, inflammatory and nephrotoxic factors overlap. Several studies have tried to assess the risk factors leading to AKI, and found, among other factors, that preoperative renal dysfunction is important. Currently, it is uncertain when dialysis therapy should start. However, AKI after cardiac surgery should be treated early by continuous hemodialysis.