Kiyoshi Hirano

A Case of Acute Tubulointerstitial Nephritis and Uveitis Syndrome with a Dramatic Response to Corticosteroid Therapy

A 23-year-old female with acute renal failure associated with acute tubulointerstitial nephritis and uveitis is reported. Renal tubular acidosis and inflammatory reactions consisting of markedly increased erythrocyte sedimentation rate and high serum immunoglobulin levels were seen on admission. Light microscopy revealed infiltration of mononuclear cells in the interstitium. Immunofluorescence of renal tissues was negative in staining for immunoglobulins, fibrinogen, and complement components. Bone marrow specimens did not show any granulomatous lesions. The etiology of this tubulointerstitial nephritis and uveitis syndrome was not clear. Immunological evaluation showed a slight decrease of the OKT4/OKT8 ratio in the peripheral blood. OKT8- and OKM1-positive cells had infiltrated diffusely into the renal interstitium. Acute tubulointerstitial nephritis and uveitis responded dramatically to steroid therapy. It was suggested that immunological factors might correlate with the onset and/or development of this syndrome. It is indicated that high-dose steroid therapy might be useful for patients with acute interstitial nephritis and uveitis.

Adaptation of Low-Phosphate Diet in Renal Brush Borders of Spontaneously Hypertensive Rats

A LPD seems to increase the Pi uptake by vesicles of the BBM of the renal cortex. This study was done to find if there was adaptation to a LPD in the BBM vesicles from the superficial or deep cortex in SHR, with WKY rats as control. The fractional excretion of Pi of SHR on the LPD was higher than that of WKY rats (p less than 0.01). The Vmax of Pi uptake in BBM vesicles from superficial cortex of WKY rats on the LPD was greater (p less than 0.05) than in such rats on a diet with a normal level of phosphate. Thus, the adaptation to a LPD was normal in WKY rats. However, in BBM vesicles from the superficial cortex of SHR kidneys, the difference in this Vmax depending on diet was insignificant. In BBM vesicles of the deep cortex of SHR kidneys, this Vmax was higher (p less than 0.01) on the LPD. The apparent Km was not significantly different in different groups or parts of the renal cortex. These results suggest that BBM vesicles in the superficial cortex of SHR kidneys did not adapt to the LPD. The less adaptation in SHR in vivo indicates that there may be a defect in Pi transport in BBM vesicles of the superficial cortex of SHR kidneys.

Effects of endothelin 1 on phosphate transport in brush border membrane vesicles

Endothelin is the most potent vasoconstrictive agent released from endothelial and many other types of cells. It has been reported that endothelin has physiological effects on the rat kidney, especially on the renal proximal tubules. We investigated the role of endothelin 1 in the renal brush border membrane. The V(max) of P(i) uptake by brush border membrane vesicles (BBMV) in the endothelin-1-treated group was significantly greater than that in the control group. There were no significant changes in apparent K(m) values between the two groups. To define the direct effect of endothelin 1 on P(i) transport of BBMV, BBMV from normal rats were incubated with endothelin 1 in vitro. The P(i) uptake by BBMV incubated with endothelin 1 did not differ from that by BBMV incubated with a salt solution as a control. These results suggested the probability of the presence of endothelin 1 receptor in the proximal tubules. Administration of the endothelin 1 might increase the P(i) reabsorption by BBMV according to changes in the capacity of the transporter.

Effect of Acarbose on Blood Glucose and Proteinuria in Patients with Diabetic Nephropathy

Accessible online at: www.karger.com/journals/nef Dear Sir, A study of the effect of Acarbose on decreases in the levels of fasting blood glucose and urinary protein excretion in patients with diabetic nephropathy is described. The importance of strict control of hyperglycemia in diabetes mellitus is now well accepted. Acarbose (·-glucosidase inhibitor), a complex oligosaccharide, is a potent competitive inhibitor of sucrase and decreases postprandial hyperglycemia when administered with food [1, 2]. Lee [3] reported that glomerular mesangial thickening and mesangial immunoglobulin deposition were significantly reduced in ab/ab mice receiving highdose Acarbose (40 mg/100 g food). We recently determined the levels of fasting blood glucose, glycohemoglobin A1c (HbA1c) and urinary protein excretion after treatment with Acarbose (Glucobay®) for 24 months in diabetic patients with or without nephropathy. Non-insulin-dependent diabetes mellitus type 2 was diagnosed according to the criteria of the 75-gram oral glucose tolerance test of the Japanese Diabetic Research Council [4]. Blood and urine samples were obtained from 33 diabetic patients with or without nephropathy in our outpatient clinic. Thirteen patients who showed more than 300 mg of urinary albumin per gram creatinine (Cr) were included in this study. Levels of fasting glucose and HbA1c in the peripheral blood were measured by ordinary laboratory examination before and 24 months after initiation of the treatment. Oral doses of 150–300 mg/day of Acarbose (Glucobay) were administered for 24 months. Levels of fasting glucose 24 months after initiation of treatment with Acarbose (152 B 44 mg/dl; mean B SD) were significantly lower than those before treatment (212 B 96 mg/dl; p ! 0.001). The levels of HbA1c 24 months after initiation of treatment (7.7 B 0.9%) were also significantly lower than those before treatment (9.8 B 2.6%; p ! 0.001). The mean levels of urinary protein excretion 24 months after initiation (400 mg/g Cr) were lower than those before the treatment (540 mg/g Cr), but the difference was not statistically significant. It appears that mild glycemic control, rather than strict control, might not improve proteinuria in patients with diabetic nephropathy. It is necessary to decrease markedly the levels of blood glucose to improve proteinuria and vice versa. References

Effects of acute and chronic parathyroidectomy on phosphate transport in brush border membrane vesicles

Acute parathyroidectomy (PTX) is associated with an increase in phosphate (Pi) uptake by renal cortical brush border membrane (BBM). We investigated the response to acute and chronic PTX in the renal BBM. Kinetic studies of Pi uptake were carried out in 5 groups of rats as follows; control, acute PTX (1h), chronic PTX (20h and 72h), and chronic PTX (20h) treated with 10 IU of parathyroid hormone (PTH). The Na+-dependent Pi transport in BBMV was significantly increased 1h after PTX. However, this increase was not retained 72h after PTX. The Vmax of Pi uptake was significantly increased and the apparent Km was significantly decreased in acute PTX. In chronic PTX, the Vmax and the apparent Km returned to control leyels. The treatment with PTH increased the apparent Km and decreased Vmax significantly 20h after PTX. These results suggested an adaptive response to hyperphosphatemia in chronic PTX rats.