Taihei Yanagida

Localization of TGF-β and Its Receptors in the Kidney

This paper reviews the expression and localization of proteins of the TGF-β system in the kidney, i.e. TGF-β isoforms, latent TGF-β binding protein, and receptors. There is heterogeneity of TGF-β isoforms, binding proteins and receptors. TGF-βs are more evenly distributed among different segments of the nephron than TGF-β receptors, and are expressed by almost all cell types in the kidney. The spatial distribution of TGF-β and its signaling receptor may help to better understand the biologic function of TGF-β in the kidney.

Early effects of parathyroidectomy on erythropoietin production in secondary hyperparathyroidism

BACKGROUND Secondary hyperparathyroidism (2-HPT) has an adverse effect on renal anemia and may cause a hyporesponsiveness to recombinant human erythropoietin (rHuEpo) in patients with chronic renal failure. The early effects of parathyroidectomy (PTx) on renal anemia, erythropoietin production, and nutritional state were examined. METHODS Twenty-nine patients under hemodialysis therapy received a PTx for 2-HPT. They were prospectively studied regarding hematological parameters, rHuEpo use, plasma erythropoietin levels, and nutritional condition until 12 months after PTx. RESULTS The hemoglobin level showed a significant increase from 3 months after PTx (10.2% +/- 1.5% to 11.2% +/- 1.3%; P <0.01), associated with a consistent increase of the reticulocyte count. These changes lasted until 12 months after PTx. The plasma erythropoietin level showed a gradual increase of up to about 5 times the level of the preoperative value, until 12 months after PTx (22.6 +/- 10.1 to 106.3 +/- 112.1 mU/mL; P <0.001). The weekly dose of rHuEpo administration decreased after 3 months. The serum levels of albumin and total protein also significantly and gradually improved until 12 months after PTx. CONCLUSIONS PTx caused a significant early improvement in renal anemia in patients with secondary hyperparathyroidism. This effect may be caused by an enhanced erythropoietin production and may also be partially due to the improved nutritional state after PTx.

Impaired Taste Acuity in Patients with Diabetes mellitus on Maintenance Hemodialysis

Aims: It has been reported that taste acuity for the four primary tastes, sour, sweet, salty and bitter, is impaired in hemodialysis (HD) patients. However, there have been no studies reported on taste acuity of diabetic HD patients. The present study aimed to quantify and compare the taste acuity of diabetic and non-diabetic HD patients, and further to determine if there were correlations between diminished taste acuity and certain blood serum parameters typically askew in hemodialysis patients. Methods: In a test group of 24 diabetic and 24 non-diabetic HD patients matched for age, body mass index and duration of HD, taste acuity for the four tastes was determined by asking patients to identify them at varying concentrations. Results: Statistical analyses indicate that bitter and total taste acuity were significantly impaired in diabetic HD patients. In diabetic HD patients, correlation was found between sweet, salty or total taste acuity and blood urea nitrogen or normalized protein catabolic rate. Conclusions: We conclude that taste acuity is partially impaired in diabetic HD patients, and suggest this contributes to reduced appetite, leading to malnutrition and poor prognoses.

Roles of TGF-β and Latent TGF-β-Binding Protein in Glomerulosclerosis Induced by Two Consecutive Injections of Monoclonal Antibody 1-22-3 in Rats

The present study demonstrated the elevated synthesis and gene expressions of transforming growth factor β (TGF-β) or latent TGF-β binding protein (LTBP) in an irreversible glomerulosclerosis rat mode

A huge fecalith associated with dialysis-related gastrointestinal amyloidosis

A 60-year-old man who had been receiving dialysis for more than 30 years was admitted for treatment of cellulitis in his right thigh on November 7, 2003. He suffered from an ileus on December 14 and was found to have a huge, 7-cm-diameter, well-circumscribed fecalith, incarcerated at the splenic flexure of the colon. It was proving difficult to pass this naturally and surgical removal was thought to be too risky. Using a colonoscope and a water-jet probe, the fecalith was broken up; the ileus then improved and the patient was able to take oral fluids. Unfortunately, he died of cardiac failure on February 13, 2004. We conducted an autopsy, with his familys consent, and found generalized amyloidosis. Deposits of amyloid were seen in all layers of the colon. Because of this, we hypothesized that peristalsis had been poor and this had led to paralytic ileus due to stasis, which, in turn, had led to the formation of the huge fecalith. In Japan it is not rare for a patient to be on dialysis for more than 25 years and it may be that this is a cause of generalized amyloidosis. There have been no such cases of fecalith associated with gastrointestinal amyloidosis described previously, which is why we decided to report this case here.

A randomized prospective control study of low dose prednisolone therapy for IgA nephropathy: Its usefulness and limitations

To clarify whether low dose prednisolone therapy for patients with IgA nephropathy (IgAN) is effective or not, this prospective control study was performed. Eightyeight patients with IgAN of glomerular scores ranging 4 to 7 were studied. A glomerular score is a semiquantitative index of histological severity of glomerular changes such as proliferation, crescent and sclerosis in IgAN, ranging from 1 to 12. The patients were randomized and divided into steroid and control group. There were 43 patients (15 men and 28 women) in steroid group and 45 patients (21 men and 24 women) in control groups. The mean age at biopsy was 33.6 ± 13.4 years in steroid group and 32.4 ± 11.1 years in the control group. The interval from discovery of the disease to biopsy was 4.9 ± 4.5 years and 5.1 ± 6.7 years, respectively. The protocol of steroid therapy was as follows. Prednisolone was given as 20, 15, 10 mg for 1 month each and 7.5 mg for 3 months and 5 mg for 18 months. Anti-platelet drug was given in both groups. The duration from biopsy to the last follow up was 4.1 ± 1.5 years in steroid group and 4.2 ± 1.6 years in control group. There was no significant difference in blood pressure and body surface area between two groups. Urinary protein/creatinine ratio (UP/UCR) was significantly larger in steroid group than in control group, 2.3 ± 2.1 g/day versus 1.1 ± 0.8 g/day. Mean serum creatinine was 0.9 ± 0.2 mg/dL in both groups. Creatinine clearance was 90.8 ± 27.3 mL/min per 1.73 m in steroid group and 89.9 ± 27.2 mL/min per 1.73 m in control group. Serum IgA was significantly higher in steroid group than in conrol group, 409 ± 110 mg/dL versus 350 ± 127 mg/dL, respectively. The index of cell proliferation was significantly higher in steroid group than in control group, 2.3 ± 0.4 versus 2.1 ± 0.3, respectively. There was no difference in the severity of other glomerular lesions, tubulo-interstitial and vascular changes between the two groups. UP/UCR was 2.31 ± 2.01 before treatment in steroid group and significantly decreased to 1.70 ± 1.96 after steroid therapy for 24 months. In control group, UP/UCR was 1.1 ± 0.80 before treatment and 1.1 ± 1.30 after antiplatelet therapy for 24 months (no significant change). The severity of urinary occult blood significantly decreased after 2 years of treatment than those before treatment in both groups, from 2.46 ± 0.76 to 1.50 ± 1.20 in steroid group and from 2.26 ± 0.96 to 1.61 ± 1.06 in the control group. The reciprocal of serum creatinine (1/Cr) significantly increased from 1.17 ± 0.30 to 1.31 ± 0.38 in the steroid group. In control groups 1/Cr was 1.20 ± 0.30 before treatment and 1.28 ± 0.43 after 2 years treatment (no significant difference). The patients in steroid group were subdivided according to their response to steroid. After steroid therapy, UP/UCR decreased in 27 cases, two of which also showed decrease in serum creatinine. Another two patients showed trace proteinuria before treatment and the degree of urinary occult blood decreased after steroid therapy. These 29 patients were entered in the responsive group. Massive proteinuria was continued in seven patients, three of which showed increase in serum creatinine. UP/UCR increased in other seven cases. These 14 cases were classified to non-responsive group. Male to female ratio showed significant differences betwen two groups, 6 : 23 in responsive group and 9 : 5 in non-responsive group. UP/UCR before treatment was significantly larger in non-responsive group than it was in the responsive group, 3.2 ± 2.8 versus 1.8 ± 1.5. Among 29 patients in the responsive group, steroids were discontinued after around 2 years in 21 cases. Fourteen cases showed no increase in UP/UCR after discontinuation of steroid (no-rebound group). In seven patients in the responsive group, UP/UCR re-increased after cessation of steroid (rebound group). The mean duration from discontinuation of steroids to last follow up was 26.2 ± 15.2 months in the no-rebound group and 26.6 ± 15.6 months in the rebound group. There were tendencies of difference in UP/UCR before steroid treatment between the rebound group and the no-rebound group, 2.7 ± 0.5 versus 1.3 ± 0.8. This low dose steroid therapy seems to be not effective in men and patients with a UP/UCR of more than 3. Low dose steroid therapy seemed to be effective in cases whose UP/UCR was less than 3. However, the cases with UP/UCR exceeding 2, re-increase in UP/UCR was observed after discontinuation of steroid. Thus, 2 years treament was not enough in such cases. A randomized prospective control study of low dose prednisolone therapy for IgA nephropathy: Its usefulness and limitations