This review summarizes recent progress in elucidating the chloride-transporting mechanisms in kidney epithelia, focusing particularly on those which act through the newly identified chloride channels. A family of chloride channel proteins (ClC chloride channels) consisting of at least 9 members (ClC-1, 2, 3, 4, 5, 6, 7, K1 and K2) has recently been identified in mammals. Although all of these ClC channels, except for skeletal muscle-specific ClC-1, are expressed in the kidney, only ClC-K1 and K2 are kidney-specific ClC chloride channels, suggesting that they play an important role in the kidney. The functional properties and intrarenal localization of these chloride channels are summarized, and their involvement in certain tubular dysfunctions and physiological roles are discussed in this report.

抄録全体を表示

A 26-week experiment was designed to determine the effect of an oral adsorbent, AST-120 (Kremezin^TM), in rats with cisplatin-induced interstitial nephropathy. We found that creatinine clearance during the 24th week of the experiment was significantly higher in the AST-120-treated rats (n=11) than in the control animals (n=11) (1.09 ±0.14, vs. 0.63 ±p<0.12 ml/min; p<0.05). Furthermore, the kidneys, which were examined morphometrically using a computerized image scan, revealed that the AST-120-treated rats had a significantly lower ratio of the tubular cross-sectional area over the cortex and outer medulla cross-sectional area than the control group (0.26±0.03 vs. 0.38V0.02; p<0.05). An aditional experiment was conducted to see if the oral adsorbent affects absorption and excretion of intraperitoneally administered cisplatin. There was no difference between the control group (n=12) and the AST-120-treated group (n=12) in serum concentration or urinary excretion of cisplatin during a 72-hour period after the injection. The results of our experiments suggest that the oral absorbent, AST-120, blunts progressive deterioration of renal function and nephron architecture in cisplatin nephropathy.

抄録全体を表示

To evaluate the relationship between Jaffe rate assay (Jaffé assay) and creatinine amidohydrolase enzymatic method (enzymatic method), we measured serum and urine creatinine concentrations in 100 serum and 100 urine samples by two methods in patients with renal disease. Comparison of Jaffé(X) and enzymatic(Y) measurements of serum and urine creatinine levels revealed a high correlation (r2=0.9991 in serum, r2=0.9995 in urine). The creatinine concentrations in serum and urine determined by Jaffé assay were significantly (p<0.01) higher than those assayed by the enzymatic method. The relationship between Jaffé and enzymatic analyses of creatinine clearance (Ccr) was obtained mathematically using regression lines (Y=0.977X - 0.199 in serum, Y = 0.999X -1.872 in urine). Ccr values obtained by both methods were almost the same at high serum creatinine levels. However, Ccr determined by Jaffe assay was much lower than that obtained by the enzymatic method when the serum creatinine concentration was under 2.0mg/dl. We present here the equation for conversion of clearance values determined by both methods to obtain an accurate evaluation of renal function in many clinical studies.

抄録全体を表示

Thrombomodulin (TM) is a thrombin receptor found on endothelial cells. TM acts as a cofactor for the thrombin-catabolized activation of protein C and protects these cells from the formation of thrombi. We hypothesized that the soluble form of TM which reflects the damage of the endothelial cells and that simultaneously, soluble TM will be affected by renal excretion because a significant positive correlation has been found between soluble TM and serum creatinine (sCr) in the renal failure state. However, there have been no reports on the relationship between plasma TM and clinical parameters except for sCr in primary glomerulonephritis (PGN). Plasma TM (pTM) and urinary TM (uTM) were measured in 107 patients with PGN using a one-step sandwich enzyme immunoassay. These values were assessed together with other laboratory and histological findings. We were able to divide all subjects into two groups: an sCr-dependent group whose sCr level was over 1.2mg/dl and an sCr-independent group whose sCr level was under 1.2mgldl. In the sCr-independent group, patients who suffered from nephrotic syndrome (NS) had a much higher pTM level than patients who did not suffer from NS. Histological findings and other parameters were not correlated with pTM or uTM. Therefore, the two patients who suffered from NS with very high pTM levels and normal sCr level at the time of admission exhibited a decrease in their pTM value as their condition improved. We concluded that in our patients, pTM was affected not only by renal excretion of TM, but also by renal damage with heavy proteinuria and may have been associated with an ongoing disease process in PGN.

抄録全体を表示

Since red blood cell survival time is shortened in patients with diabetes mellitus (DM) on hemodialysis (HD), it is unlikely that indices of glycemic control accurately reflect the glycemic state of these individuals. In this study, in order to determine the best index of glycemic control in diabetic patients on HD, we measured HbA1c, 1, 5-anhydroglucitol (1, 5-AG), fructosamine (Fr) and glycated albumin (GA) in 31 diabetic patients on HD (20 males and 11 females, mean age: 66.9 years), and examined the correlation between each index and predialysis plasma glucose level. Since the mean values of predialysis plasma glucose during the final 2 and 4 weeks before the study were best correlated with HbA1c, this parameter was considered to be the most reliable index of glycemic control in diabetic patients on HD. GA was more closely correlated with mean values of predialysis plasma glucose during the final 2 and 4 weeks, than any other index of glycemic control, followed by HbA1c. In conclusion, HbA1c is considered to be the most reliable index of glycemic control in diabetic patients on HD.

抄録全体を表示

Parathyroidectomy (PTX) is one of the treatments of choice for secondary hyperparathyroidism in chronic dialysis patients. Due to the large increase in long-term dialysis patients, hyperparathyroidism is becoming a common clinical problem. Several studies on PTX have reported various surgical procedures, but limited information is available on the incidence and risk factors of the surgery. The Okinawa Dialysis Study (OKIDS) registry is a community-based dialysis registry. It covers the entire area of Okinawa from when the use of chronic dialysis began in 1971. By the end of 1990, a total of 1, 986 chronic dialysis patients were registered and 128 of these had undergone PTX by the end of 1993. The cumulative incidence of PTX was 4.3 in DM and 15.2 in non-DM per 1, 000 patient-years. About half of the PTX patients underwent the surgery within 10 years of dialysis. By logistic analysis, the risk of PTX was seen to increase significantly with the duration of dialysis, P<0.0001. Other clinical variables such as sex, age at the start of dialysis and the presence of diabetes mellitus were not significant predictors of PTX. The probability of PTX increased linearly with the duration of dialysis (r=0.83, p<0.001). After the introduction of active vitamin D in 1981, the probability of PTX was significantly decreased (p<0.05) compared to the pre-vitamin D period ('71-'80). With prolongation of the duration of dialysis, the risk of PTX increased steadily and was estimated to be 10 percent in 10 years and 20 percent in 20 years. Other uremic factors determining a pathological transformation of parathyroid tissue from reactive to autonomous growth remained to be investigated.

抄録全体を表示