Yoshio Taguma

Effect of Captopril on Heavy Proteinuria in Azotemic Diabetics

We investigated whether captopril, an angiotensin-converting-enzyme inhibitor, would reduce proteinuria in patients with advanced diabetic nephropathy. Captopril (37.5 mg given in divided doses three times daily) was administered to 10 azotemic diabetics with heavy proteinuria. Urinary protein decreased promptly within two weeks (from 10.6 +/- 2.2 to 6.1 +/- 1.4 g per day [mean +/- S.E.M.]; P less than 0.01). The decrease in proteinuria did not coincide with a fall in systemic blood pressure or in the blood glucose concentration. Serum creatinine and potassium values did not change in any of the patients except one. We suggest that captopril caused a decrease in intrarenal hypertension, which contributed to the reduction of urinary protein excretion. The therapeutic value of this intervention remains to be established.

Cohort Study of Advanced IgA Nephropathy: Efficacy and Limitations of Corticosteroids with Tonsillectomy

Background: Elevated serum creatinine is associated with poor outcome in IgA nephropathy (IgAN). The efficacy and limitations of corticosteroids in advanced IgAN (Cr ≧1.5 mg/dl), however, remains controversial. Methods: We retrospectively investigated 70 patients with advanced IgAN (Cr ≧1.5 mg/dl) classified into three groups according to their treatment regimens, that is, steroid pulse with tonsillectomy, conventional steroid, and supportive therapy. We evaluated the three groups to elucidate predictors for the endpoints ESRF and doubled serum creatinine from baseline. Results: Steroid pulse with tonsillectomy, conventional steroid and supportive therapy were performed in 30, 25 and 15 patients, respectively. During the mean follow-up period of 70.3 (12–137) months, 41.4% of patients reached ESRF (13.3 vs. 56.0 vs. 73.3%, p < 0.001) and 45.7% doubled serum creatinine from baseline (16.7 vs. 64.0 vs. 73.3%, p < 0.001). The incidence of ESRF in the patients treated by steroid pulse with tonsillectomy was significantly lower than the incidences in the patients treated by conventional steroid and supportive therapy at a baseline creatinine level of 1.5–2 mg/dl, but no statistical difference was observed at a level of >2 mg/dl. The Kaplan-Meier estimated probability of renal survival without ESRF was 89.2, 74.1 and 72.2% at 5 years and 82.8, 51.0 and 45.1% at 8 years, respectively (p = 0.017). The predictors for ESRF, identified in a Cox proportional hazards model, were baseline serum creatinine (p < 0.001) and interstitial infiltrate (p = 0.003). Steroid pulse with tonsillectomy also had a protective effect on the risk of reaching ESRF (p = 0.013). By target cross-stratification, the patients with baseline creatinine of 1.5–2 mg/dl who underwent steroid pulse with tonsillectomy showed a better renal survival rate than the others (p < 0.001). Conclusion: Steroid pulse therapy combined with tonsillectomy may be more effective than conventional steroid therapy in patients with a baseline creatinine level of ≤2 mg/dl.

A nationwide survey of rapidly progressive glomerulonephritis in Japan: etiology, prognosis and treatment diversity.

BackgroundThe etiology, prevalence, and prognosis of rapidly progressive glomerulonephritis (RPGN) including renal vasculitis vary among races and periods.MethodTo improve the prognosis of Japanese RPGN patients, we conducted a nationwide survey of RPGN in the nephrology departments of 351 tertiary hospitals, and found 1772 patients with RPGN (Group A: diagnosed between 1989 and 1998, 884 cases; Group B: diagnosed between 1999 and 2001, 321 cases; and Group C: diagnosed between 2002 and 2007, 567 cases). ANCA subclasses, renal biopsy findings, treatment, outcome and cause of death were recorded.ResultThe most frequent primary disease was renal-limited vasculitis (RLV) (42.1%); the second was microscopic polyangiitis (MPA) (19.4%); the third was anti-GBM-associated RPGN (6.1%). MPO-ANCA was positive in 88.1% of RLV patients and 91.8% of MPA patients. The proportion of primary renal diseases of RPGN was constant during those periods. The most frequent cause of death was infectious complications. The serum creatinine at presentation and the initial dose of oral prednisolone decreased significantly in Groups B and C compared to Group A. However, both patient and renal survival rates improved significantly in Groups B and C (survival rate after sixxa0months in Group A: 79.2%, Group B: 80.1%, and Group C: 86.1%. Six-month renal survival in Group A: 73.3%, Group B: 81.3%, and Group C: 81.8%).ConclusionEarly diagnosis was the most important factor for improving the prognosis of RPGN patients. To avoid early death due to opportunistic infection in older patients, a milder immunosuppressive treatment such as an initial oral prednisolone dose reduction with or without immunosuppressant is recommended.

Different clinical outcomes for cardiovascular events and mortality in chronic kidney disease according to underlying renal disease: the Gonryo study

PurposeChronic kidney disease (CKD) can result from a wide variety of diseases, but whether clinical outcomes differ in the same CKD stages according to the underlying renal disease remains unclear. Clarification of this issue is important for stratifying risk of cardiovascular disease (CVD) and death in patients before dialysis.Patients and methodsThe study comprised 2,692 patients recruited from 11 outpatient nephrology clinics, classified by underlying disease of primary renal disease (PRD) (nxa0=xa01,306), hypertensive nephropathy (HN) (nxa0=xa0458), diabetic nephropathy (DN) (nxa0=xa0283), or other nephropathies (ON) (nxa0=xa0645). Risks of events such as ischemic heart disease, congestive heart failure, stroke, and all-cause mortality within 12xa0months were examined by logistic regression analysis in each group.ResultDuring the 12-months’ observation from recruitment, 200 cases were lost to follow-up, and 113 cases were introduced to chronic dialysis therapy. A total of 69 CVD events occurred (stroke in 27 cases), and 24 patients died. In total, increased odds ratios (OR) for the events by CKD stage (cf. CKD1xa0+xa02: unadjusted) were CKD3, 1.29 [95% confidence interval (CI), 0.70–2.17]; CKD4, 2.73 (1.55–4.83); and CKD5, 4.66 (2.63–8.23). Regarding events in respective groups, no significant differences were seen by CKD stage except for the group with HN, but significant differences were seen by underlying diseases (cf. PRD: adjusted for confounding factors, including estimated glomerular filtration rate): HN, 2.57 (1.09–6.04); DN, 12.21 (3.90–38.20); and ON, 4.14 (1.93–8.89).ConclusionRisk of CVD and mortality due to CKD needs to be stratified according to the underlying renal diseases.

Clinical effectiveness of steroid pulse therapy combined with tonsillectomy in patients with immunoglobulin A nephropathy presenting glomerular haematuria and minimal proteinuria

Aim:u2003 The effectiveness of steroid pulse therapy combined with tonsillectomy (ST) has been shown in immunoglobulin A nephropathy (IgAN) patients with moderate or severe urinary abnormalities. The present study aimed to clarify whether the effectiveness may be extrapolated to IgAN with minor urinary abnormalities, and whether the effectiveness may depend on the histological severity with minor urinary abnormalities.

Increased risk of cardiovascular events and mortality among non-diabetic chronic kidney disease patients with hypertensive nephropathy: the Gonryo study

To examine the clinical significance of hypertensive nephropathy (HN) among non-diabetic chronic kidney disease (CKD) patients. The study comprised 2692 CKD patients recruited from 11 outpatient nephrology clinics; these included 1306 patients with primary renal disease (PRD), 458 patients with HN, 283 patients with diabetic nephropathy (DN) and 645 patients with other nephropathies (ONs). All patients fulfilled the criteria of CKD, with a persistent low estimated glomerular filtration rate (eGFR) <60u2009mlu2009min−1 per 1.73u2009m2 or proteinuria as determined by a urine dipstick test. The risk factors for cardiovascular disease (CVD), such as ischemic heart disease, congestive heart failure and stroke; all-cause mortality; and progression to end-stage renal failure (dialysis induction) were analyzed using a Cox proportional hazards model in each group. During a mean follow-up period of 22.6 months from recruitment, 100 patients were lost to follow-up and 192 patients began chronic dialysis therapy. A total of 115 CVD events occurred (stroke in 37 cases), and 44 patients died. Regarding CVD events and death, there were significant differences in the hazard ratios (HRs) for the groups of patients with different underlying renal diseases as determined by both univariate and multivariate analysis adjusted for confounding factors including estimated glomerular filtration rate: PRD, 1.0 (reference); HN, 3.33 (95% confidence interval, 1.82–6.09); DN, 5.93 (2.80–12.52); and ON, 2.22 (1.22–4.05). However, there were no differences in the hazard ratio for dialysis induction for the groups of patients with different underlying renal diseases. HN is associated with an increased risk of CVD events and death among non-diabetic CKD patients, which highlights the clinical significance of HN.

Lymphocytapheresis to treat rapidly progressive glomerulonephritis: a randomised comparison with steroid-pulse treatment

Rapidly progressive glomerulonephritis (RPGN) may progress to end-stage renal failure within weeks and to death from organ damage induced by systemic vasculitis or from immune system failure due to immunosuppressive therapy. Death or the need for dialysis has variously been reported to occur in 17% to 73% of patients treated for RPGN. The need exists for a means promptly to stop disease activity without compromising the patient’s immune system. Macrophages and cytotoxic T cells play a central role in the glomerular injury of RPGN, and the removal of these cells by lymphocytapheresis is effective in the treatment of rheumatoid arthritis. We investigated the efficacy of lymphocytapheresis for treatment of RPGN, in comparison with steroid-pulse treatment. 24 patients with RPGN proven by biopsy were enrolled in RESEARCH LETTERS

Involvement of neutrophil elastase in crescentic glomerulonephritis

To elucidate the role of neutrophils in the tissue damage of crescentic glomerulonephritis (GN), we examined neutrophils infiltrated in renal tissues and the localization of neutrophil elastase (NE), as a neutrophil-derived tissue destructive mediator, using an immunohistochemical technique with antibodies specific for neutrophils and neutrophil elastase; the enzyme histochemical technique (chloroesterase staining) also was used to detect neutrophils. In normal controls, neutrophil infiltration was scarce, and NE was localized in neutrophil cytoplasm. Neutrophils were abundant in crescentic GN and infiltrated in the glomerulus and interstitium; the infiltrating neutrophils were often aggregated. NE was localized in the cytoplasm of neutrophils and also appeared extracellularly (in granular or diffuse patterns) in glomerular necrotizing lesions, crescents, ruptured portions of Bowmans capsules, and in periglomerular and perivascular sites of the interstitium. Moreover, urinary concentration of NE measured by enzyme-linked immunosorbent assay (ELISA) in crescentic GN patients was significantly higher than in normals (93.6 +/- 13.3 v 1.4 +/- 0.5 microg/g x Cr, respectively; P < .001). These data suggest that NE plays a significant role in renal tissue damage, especially in the formation of glomerular necrotizing and crescentic lesions and in periglomerular interstitial lesions of crescentic GN.

Night-time blood pressure is associated with the development of chronic kidney disease in a general population: the Ohasama Study.

Objective: Ambulatory blood pressure (BP) is reportedly associated with target organ damage. However, whether ambulatory BP carries prognostic significance for the development of chronic kidney disease (CKD) has not been confirmed. Method: We measured ambulatory BP in 843 participants without CKD at baseline from a general Japanese population and examined the incidence of CKD defined as positive proteinuria or an estimated glomerular filtration rate (eGFR) less than 60u200aml/min per 1.73 m2 at health checks. The association between baseline ambulatory BP and CKD incidence was examined using the Cox proportional hazard regression model adjusted for sex, age, BMI, habitual smoking, habitual alcohol consumption, diabetes mellitus, hypercholesterolemia, a history of cardiovascular disease, antihypertensive medication, eGFR at baseline, the number of follow-up examinations, and the year of the baseline examination. Results: The mean age of the participants averaged 62.9u200a±u200a8.1 years, 71.3% were women and 23.7% were under antihypertensive medication. During a median follow-up of 8.3 years, 220 participants developed CKD events. The adjusted hazard ratios for CKD in a 1-standard deviation increase in daytime and night-time SBP were 1.13 [95% confidence interval (CI) 0.97–1.30] and 1.21 (95% CI 1.04–1.39), respectively. When night-time and daytime BP was mutually adjusted into the same model, only night-time BP persisted as an independent predictor of CKD. Conclusion: Night-time BP is a better predictor of CKD development than daytime BP in the general population. Ambulatory BP measurement is considered useful for evaluating the risk of progression to CKD.

Significance of the duration of nephropathy for achieving clinical remission in patients with IgA nephropathy treated by tonsillectomy and steroid pulse therapy

BackgroundBecause of the well-established annual urinalysis screening system in Japan, the duration of nephropathy (DN) can be estimated in more than half of all patients with IgA nephropathy (IgAN). Treatment using a combination of tonsillectomy and steroid pulse (TSP) therapy has been reported as an effective method for obtaining clinical remission (CR), defined as negative hematuria and proteinuria, in IgAN patients. The present study aims to identify the correlation between DN and CR rate in IgAN patients treated by TSP therapy.MethodsWe retrospectively investigated 830 IgAN patients who were followed up for 81.6xa0months after TSP therapy. DN could be estimated in 495 of the 830 patients.ResultsThe CR rate among patients with DN ≤36xa0months was 87.3% (295/338 patients). The CR rate among patients with DN of 37–84xa0months was 73.3% (63/86 patients), while that among patients with DN ≥85xa0months was 42.3% (30/71 patients). The CR rate among the remaining 335 patients in whom DN could not be estimated because of missing annual urinalysis results was 43.6% (146/335 patients). A multivariate Cox regression model using data from the former group of 495 patients showed that DN ≤36xa0months was a significant predictor of CR (hazard ratio 1.839; 95% confidence interval 1.410–2.398; Pxa0<xa00.001).ConclusionShorter DN is associated with higher likelihood of clinical remission in IgAN patients treated by TSP therapy.