Satoru Fujimi

Controlled, prospective trial of steroid treatment in IgA nephropathy: a limitation of low-dose prednisolone therapy

BACKGROUND No accepted therapy has been established for progressive immunoglobulin A (IgA) nephropathy. METHODS A prospective, randomized, controlled trial of low-dose prednisolone therapy was performed in patients with IgA nephropathy with moderate histological characteristics. Forty-three patients in the steroid group and 47 patients in the control group were included in the study. The initial dose of prednisolone was 20 mg/d, gradually tapered to 5 mg/d during 2 years. RESULTS Baseline urine protein-creatinine ratio (UP-UCR) was significantly greater in the steroid group than in controls. Follow-up duration was 65 +/- 25 months in the steroid group and 64 +/- 23 months in controls. Changes in UP-UCR from baseline, ie, UP-UCR at last follow-up minus UP-UCR at baseline, were significantly lower in the steroid group than in controls (steroid group, -0.84 +/- 1.78; controls, 0.26 +/- 1.65; P = 0.0034). Kidney survival was similar in both groups. Patients were divided into two subgroups according to clinical course. There were 28 improved patients and 15 unimproved patients in the steroid group and 27 improved patients and 20 unimproved patients in the control group. In the steroid group, UP-UCR was significantly greater in the unimproved than improved subgroup (3.1 +/- 2.6 versus 1.8 +/- 1.5). CONCLUSION These data suggest that our protocol had an antiproteinuric effect, but could not improve kidney survival. Because the effect of steroid therapy to prevent the progression of IgA nephropathy is believed to be linked closely to reduction in urinary protein, an insufficient dose of prednisolone in our protocol may be the reason for the discrepancy between the effect on proteinuria and kidney survival.

An important role of glomerular segmental lesions on progression of IgA nephropathy : a multivariate analysis

The independent predictors of progression of IgA nephropathy (IgAN) were investigated by multivariate life table analysis, using Coxs proportional hazard model, in 225 patients with IgAN diagnosed by renal biopsy (Bx). There were 105 men and 120 women. Mean age at Bx was 32.5 years. The follow-up period following Bx was 4.0 +/- 2.6 yrs, ranging from 5 months to 11 yrs. The clinical parameters analyzed were age at the time of discovery of the disease, age at Bx, intervals from discovery to Bx, presence or absence of macrohematuria, and clinical data at Bx such as presence or absence of hypertension, the degree of hematuria, the amount of urinary protein excretion, serum creatinine and serum IgA concentration. The following immunopathological parameters were also examined; glomerular hypercellularity index, percentage of glomeruli associated with segmental lesions such as tuft adhesions, crescents and segmental sclerosis, percentage of obliterated glomeruli by global sclerosis, severity of interstitial infiltration, fibrosis, arterial wall thickening, arterial hyaline changes, and intensity of the depositions of IgG, IgA, IgM, C3, C1q and fibrinogen by immunofluorescent study. Among all clinical and pathologic parameters examined, the following parameters were proved to be significant independent predictors of progression of IgAN: serum creatinine exceeding 1.5 mg/dl in men and 1.3 mg/dl in women, proteinuria over 2 g/day, segmental lesions involving more than 25% of glomeruli and interstitial fibrosis occupying more than 25% of cortical area.(ABSTRACT TRUNCATED AT 250 WORDS)

Dialysis-Related Hypotension as a Cause of Progressive Frontal Lobe Atrophy in Chronic Hemodialysis Patients: A 3-Year Prospective Study

Background/Aim: Brain atrophy is known to develop more rapidly in hemodialysis (HD) patients than other individuals. The present study was designed to examine the role of HD-related hypotension in brain atrophy in patients on chronic HD. Methods: By using magnetic resonance imaging, whole brain atrophy was assessed by the ventricular-brain ratio (VBR; ventricular area/whole brain area). Frontal brain atrophy was assessed by the frontal atrophy index (FAI; frontal brain area/intracranial frontal space). The number of lacunae was also counted. We studied 32 HD patients without symptomatic neurological abnormalities or diabetes mellitus: male/female ratio 19/13; mean age ± SD 53 ± 10 (range 28–77) years; mean HD duration ± SD 11 ± 6 (range 1–22) years. Magnetic resonance imagings were taken in 1995 and 1998. All dialysis-related hypotension episodes during the same period were identified from the medical records and counted. Results: The VBR ranged from 8.8 to 18.7% in 1995 (12.8 ± 2.2%) and was not different in 1998 (13.1 ± 2.7%). However, the VBR increased by more than 5% in 14 patients, and their HD duration of 13 ± 6 years was significantly longer than that of 18 patients with stable VBR (p < 0.05). The FAI in 1995 was 62.2 ± 4.2% (range 55.8–71.3%) and decreased significantly to 59.7 ± 4.7% (range 50.2–70.9%) in 1998 (p < 0.05). The change in FAI correlated significantly with both the total number of dialysis-related hypotension episodes (r = 0.45, p < 0.05) and the increase in number of lacunae (r = 0.42, p < 0.05). Conclusion: Our results suggest that dialysis-related hypotension plays a role in progressive frontal lobe atrophy in HD patients.

Health-Related Quality of Life of Predialysis Patients with Chronic Renal Failure

Background: Health-related quality of life (HQOL) of predialysis patients with chronic renal failure (CRF) has received less attention than that of dialysis patients. We investigated changes in SF-36 over 1 year and examined associations between clinical parameters and SF-36 in predialysis CRF patients. Methods: Subjects were 471 predialysis CRF patients. SF-36 and clinical parameters were measured every 8 weeks for 48 weeks. Of the 471 subjects, 294 underwent one or more follow-ups. We analyzed the pooled dataset of the 294 CRF patients and 2002 subjects from Japanese general population using analysis of covariance. Results: After adjustment for age and sex, the 1-year declines in SF-36 domains were significantly greater in the predialysis patients than in the general population. For a 10% decline in hematocrit from the baseline survey value, the decline in vitality of SF-36 was 4.5 points (p = 0.003), while for a 10% increase in serum creatinine from the baseline survey value, respective declines in physical functioning, role-physical and mental health were 1.2 (p = 0.004), 1.9 (p = 0.035), and 1.0 points (p = 0.008). Conclusion: Among these predialysis CRF patients, the decline in HQOL was faster than that in the general population, and was associated with an increase in serum creatinine and decline in hematocrit.

Germanium dioxide-induced nephropathy: a new type of renal disease.

Chronic renal failure developed in 5 patients who were taking germanium dioxide (GeO2)-containing compounds. Renal functional deterioration was slow but progressive and dialysis treatment was necessitated temporarily in 2 patients. After the discontinuation of GeO2, the impaired renal function tended to improve but remained abnormal for an observation period of 10-40 months. The lack of proteinuria and hematuria was characterized as the clinical manifestations. Renal biopsy specimens revealed the tubular epithelial cell degeneration containing hematoxylin-positive fine granules on light microscopy, and electron-dense inclusions in the swollen mitochondria on electron microscopy. These findings localized mainly in distal segment of the tubules. In the rats given GeO2 orally for 10 weeks, similar histological lesions were evident, as manifested by marked weight loss, anemia, azotemia, and negative proteinuria. In the rats given carboxyethylgermanium sesquioxide, these changes were not observed and Ge concentration of kidney was significantly lower than in the rats given GeO2. The present study indicates that chronic GeO2 intake causes progressive renal dysfunction characterized by the degeneration of distal tubules.

The effect of azelastin hydrochloride on pruritus and leukotriene B4 in hemodialysis patients

Pruritus is a very common complication in chronic hemodialysis (HD) patients, however the exact mechanism for this affliction is still not known. Anti-histaminics usually failed to alleviate uremic pruritus. In others, an anti-allergic drug, which inhibits the release of chemical mediators, such as leukotrienes or histamine from mast cells, was reported to be effective. We evaluated the values of leukotriene B4 and interleukin 6 in HD patients with pruritus and the effect of an anti-allergic drug on these factors. Leukotriene B4, interleukin-6, C3a, C5a, the number of eosinophil and IgE at 0, 15 and 180 minutes after the start of regular HD in 11 HD patients suffering from pruritus and as well as in 11 HD patients without pruritus were examined. These HD patients in both groups showed significantly higher (p < 0.001) values of leukotriene B4 and C3a compared to healthy non-HD subjects. There was no difference in the leukotriene B4, interleukin-6, IgE, C3a and C5a levels between the patients with and without pruritus. Two mg/day of azelastin hydrochloride, an anti-allergic drug was orally given to the pruritus group for 3 weeks. In 5 of 11 patients, the pruritus symptoms disappeared, while in 4 of 11 they improved. Independent of the effect of the drug on pruritus, leukotriene B4 levels significantly decreased compared with those before the administration of this drug in the pruritus group (p < 0.01). Interleukin 6, C3a, C5a and the number of eosinophils demonstrated no significant change. In conclusion, although azelastin hydrochloride was effective in treating pruritus and also suppressed leukotriene B4 levels in hemodialysis patients, the high leukotriene B4 activity itself did not seem to be related to the development of pruritus in these patients.

Idiopathic Membranous Glomerulonephritis Associated with Diabetes mellitus

The present study described 3 patients with idiopathic membranous glomerulonephritis associated with diabetes mellitus. Clinical characteristics of the 3 patients contrasted with diabetic glomeruloscl

Efficacy and safety of oral falecalcitriol in reducing parathyroid hormone in hemodialysis patients with secondary hyperparathyroidism

Abstract: Based on research conducted so far, active vitamin D3 is known to suppress the secretion of parathyroid hormone (PTH), which is stimulated by chronic renal failure. We investigated the effect and safety of falecalcitriol, a new type of active vitamin D3, in patients with secondary hyperparathyroidism accompanied by chronic renal failure in a multicenter study. In a double-blind study, 121 patients were randomly assigned to a falecalcitriol group (63 patients) or a placebo group (58 patients). They received daily oral falecalcitriol or placebo for 8 weeks. The change rates of intact PTH (i-PTH) , midregion PTH (m-PTH), and carboxy-terminal PTH (c-PTH) were determined as major evaluation parameters. The falecalcitriol group showed a significant suppression (P < .01) of 34.8% in i-PTH; in contrast, the placebo group recorded a significant rise (P < .01) of 12.4%, with a significant difference (P < .01) between the groups. The results for m-PTH and c-PTH were similar to those for i-PTH. Serum calcium, meanwhile, rose significantly (P < .01) in the falecalcitriol group after 2 weeks. The mean values, however, remained within the normal range, and the change rate was within 10%. Apart from the rise in serum calcium, there were no differences in adverse reactions from the placebo group. The results suggest that falecalcitriol is an effective drug against secondary hyperparathyroidism with chronic renal failure because it significantly inhibits a rise in i-PTH under conditions that cause no large changes in serum calcium.

Association between Serum Phosphate Levels and Stroke Risk in Patients Undergoing Hemodialysis: The Q-Cohort Study

Background and Purpose— The contribution of serum phosphate levels to stroke risk in dialysis patients remains unclear. The present study aimed to elucidate the respective association between serum phosphate levels and the risk of brain hemorrhage or infarction in patients undergoing hemodialysis. Methods— A total of 3437 patients undergoing hemodialysis were followed up for a median of 3.9 years. The primary outcome was the occurrence of brain hemorrhage or infarction. Patients were divided into 4 groups based on their baseline serum phosphate levels (Q1–Q4). Stroke risk was estimated using a Cox proportional hazards model. Results— During the follow-up period, 75 patients experienced brain hemorrhage and 139 experienced brain infarction. The risk of brain hemorrhage was significantly higher in the highest (Q4) compared with the lowest quartile (Q1) as the reference value (multivariate-adjusted hazard ratio [95% confidence intervals]: Q1, 1.00; Q2, 1.76 [0.79–4.18]; Q3, 1.99 [0.92–4.67]; and Q4, 2.74 [1.27–6.47]; P=0.077 for trend; hazard ratio for every 1 mmol/L increase in serum phosphate level, 2.07 [1.10–3.81]; P=0.025). In contrast, the risk of brain infarction was significantly higher in Q1 (P=0.045) compared with Q3 as the reference value (Q1, 1.65 [1.01–2.73]; Q2, 1.35 [0.82–2.25]; Q3, 1.00; and Q4, 1.30 [0.77–2.20]). Conclusions— Higher serum phosphate levels were associated with an increased risk of brain hemorrhage, whereas low levels were associated with an increased risk of brain infarction in hemodialysis patients. These results suggest the importance of managing serum phosphate levels within an appropriate range in hemodialysis patients. Clinical Trial Registration— URL: http://www.umin.ac.jp/. Unique identifier: UMIN000000556.

Effects of the Methylprednisolone Pulse Therapy on Renal Function

The effect of the methylprednisolone (MP) pulse therapy on renal function was examined in 15 patients with renal or collagen disease. Three nephrotic patients who had reduced renal function and active renal disease with progressive deterioration of renal function prior to the use of MP developed transient renal failure following an MP pulse therapy. The renal failure in each case was reversed by discontinuation of MP and/or by forced diuresis using albumin and furosemide. We examined the correlations between the individual changes in serum creatinine (Scr), body weight (BW) and urine volume (UV) before and after the pulse therapy and other laboratory data such as Scr, total serum protein and albumin. There were significant correlations between a change in Scr on the one hand and changes in BW and UV, Scr and serum albumin on the other. These findings mean that the effect of the MP pulse therapy on renal function depends on the clinical state of the patient and that renal deterioration after the pulse therapy may be more marked in patients who are more nephrotic and more impaired in renal function and suggest that increasing sodium and water retention during an MP therapy and the associated renal interstitial edema, proposed as one of the mechanisms of acute renal failure occurring in patients with minimal-change nephrotic syndrome, may be responsible for the MP-induced transient renal failure.