Relation of enzyme distribution in the kidney and increase pattern of urinary N-acetyl-beta-D-glucosaminidase (NAG) and gamma-glutamyl transpeptidase (gamma-GTP) activities following CDDP administration

Nephrotoxicity is the major side effect of CDDP and it develops renal tubular damage. In the present paper, we have studied acute effects of cis-dichlorodiamine platinum (CDDP, 20 mg daily for 5 days) on the renal tubule using urinary NAG and gamma-glutamyltranspeptidase (gamma-GTP) activities as indicators of the toxicity. Altogether 25 courses of chemotherapy in 15 patients who had malignant tumors were studied. Urinary enzyme activities consisting of N-acetyl-beta-D-glucosaminidase (NAG, lysosomal enzyme) and gamma-GTP (brush border enzyme) were measured for 11 days from the day before CDDP administration. In all cases, both urinary enzyme activities increased with CDDP administration. The increase of NAG activity was transient; the highest level was detected on the 5th day of chemotherapy and decreased after that. On the other hand, two peaks of gamma-GTP activity were observed in many cases, the first peak during chemotherapy and the second peak soon after the completion of CDDP administration. The differences in increase pattern of these two urinary enzyme activities, suggest that changes of brush border occur in an early stage and cellular tissue including lysosome of renal tubule is impaired afterwards.     

检测尿NAG活性对判断BPH患者早期肾功能损害的意义

目的 探讨测定尿N-乙酰-β-D氨基葡萄糖苷酶（NAG）活性在判断良性前列腺增生症（BPH）患者早期肾功能损害方面的应用价值。方法 检测65例BPH患者的尿NAG活性及血β2微球蛋白（β2-MG）、尿素氮（BUN）、肌肝（Cr）及最大尿流率（Qmax），并与80例年龄匹配的正常人群进行比较分析。同时对BPH患者手术前与术后1个月和3个月的NAG活性进行比较。结果BPH患者尿NAG活性明显高于正常对照组（P〈O．01），尿NAG活性与BPH患者最大尿流率呈显著正相关（P〈O．01）。术后3个月尿NAG活性下降明显，与术前相比有显著性差异（P〈O．01）。结论BPH患者最大尿流率较低时肾功能可能已有部分损伤，尿NAG活性水平可作为判断BPH患者早期肾功能损伤的监测指标以及手术指征之一。     

Acute changes in renal function following extracorporeal shock wave lithotripsy in patients with a solitary functioning kidney

Twelve consecutive patients with a solitary functioning kidney were treated for renal stone by extracorporeal shock wave lithotripsy (ESWL*) with the modified Dornier HM3 lithotriptor and studied for 3 days after treatment. Urinary excretion of electrolytes, N-acetyl-beta-glucosaminidase (NAG), alkaline phosphatase, kallikrein, glycosaminoglycans, albumin and beta 2-microglobulin, and clearances of creatinine, inulin and para-aminohippuric acid were determined, as were serum levels of creatinine, urea, beta 2-microglobulin and aldosterone, and plasma renin activity. Urinary flow rate, free water clearance, and urinary excretion of NAG, kallikrein and beta 2-microglobulin were significantly increased 0 to 24 hours after ESWL. The urinary excretions of alkaline phosphatase, albumin and glycosaminoglycans were unchanged. Glomerular filtration rate was significantly decreased and effective renal plasma flow was unchanged. Filtration fraction was stable. Serum lactic dehydrogenase increased significantly after ESWL and remained high through the period of observation. Serum levels of creatinine, beta 2-microglobulin and aldosterone were unaltered. A decrease in plasma renin activity immediately after treatment is explained by the water immersion and the extracellular volume expansion during treatment.     

Temporal changes of cytokines and nitric oxide products in urine from renal transplant patients

BACKGROUND: Acute rejection and urinary tract infection (UTI) both increase nitric oxide synthase (NOS) activity in urine from renal transplant patients. Also, with rejection, a regulatory interplay between nitric oxide (NO) and cytokines has been suggested. Thus, measurement of the temporal changes of NOS products and cytokines in urine will provide a strategy for the diagnosis of acute rejection and for its differentiation from UTI. METHODS: Soluble interleukins (ILs) and NOS-related products, cyclic GMP (cGMP), nitrate, and nitrite were measured in 192 urine samples consecutively collected from 13 patients within the first three months of transplantation. Sixty-seven additional urine specimens were collected randomly from 24 patients for follow-up analysis of the nitrate test. RESULTS: Among patients who experienced rejection, the percentage (%) binding of IL-2 increased within the first five days (P = 0.0004) after transplantation and one to five days prior to the clinical diagnosis (dx) of rejection (P = 0.02). Tumor necrosis factor-alpha, IL-6, and IL-8 increased at the time of rejection dx (P < or = 0.01). With UTI, IL-2 (P = 0.01) decreased one to five days prior to dx, and IL-10 (P = 0.003) increased one to five days after dx. Although cGMP and nitrate are dependent variables, cGMP increased (P < or =0.0009) with both rejection and UTI, and nitrate increased (P = 0.0001) with rejection and decreased (P = 0.0001) with UTI. Prior to formal dx (1 to 5 days), urine nitrate clearly differentiated rejection (3004 to 7451 micromol/L) from UTI (90 to 885 micromol/L) and controls (1059 to 3235 micromol/L). The additional 67 urines demonstrated that the sensitivity of the nitrate test for rejection and UTI was 100%. CONCLUSIONS: In renal transplant patients, specific temporal changes in urine cytokine levels do occur with acute rejection and UTI, but urine nitrate levels are the most precise at differentiating rejection from UTI.     

定期检测肾移植患者尿中供者细胞DNA的临床意义

目的 探讨肾移植患者尿中供者细胞的出现与急性排斥反应的相关关系及其临床意义。方法 以供者为男性、受者为女性或HLA—DB抗原有错配的80例肾移植患者为研究对象，定期收集尿液标本，从中提取DNA，利用聚合酶链反应及序列特异性引物—聚合酶链反应分别检测Y染色体上特异的基因片段DYZ—l和HLA-DR抗原的基因DRB1。结果 手术当天受者的尿中即有供者细胞出现，随着时间的推移，尿中供者细胞DNA的基因表达强度逐渐减弱，直至术后30d，仍有90．0％患者的尿中有供者细胞DNA的基因表达，其中8例(29．6％)发生了急性排斥反应；出院后发生急性排斥反应者，90．0％的尿液标本中能检测到供者细胞DNA，抗排斥治疗结束后2周，83．3％仍为阳性，治疗过程中尿中供者细胞DNA的基因表达强度逐渐减弱，直至3个月后，88．9％转为阴性；肾功能良好的稳定期患者，仅6．7％的患者尿中DYZ—l或HLA-DRB1基因阳性。结论 肾移植患者尿中供者细胞DNA的检测可以作为诊断急性排斥反应，并与药物性肾功能损伤进行鉴别的一种方法，其基因表达强度变化为定量评价排斥反应提供了可能性。     

Urinary FDP D-dimer and E fragments in renal transplantation

Both D-dimer and E fragments in urinary FDP were determined in renal transplantation patients. Urinary D-dimer fragments increased in 14 out of 20 acute rejections (70.0%) and in 6 out of 18 chronic rejections (33.3%). Urinary E fragments increased in 8 out of 9 acute rejections (88.9%) and in 4 out of 5 chronic rejections (80.0%). It is suggested that urinary FDP-E fragment is a better indicator to detect or predict rejection than the whole Urinary FDP. The appearance of D-dimer in the urine indicates intravascular coagulation in glomeruli followed by a secondary fibrinolysis in the course of the rejection reaction. The urinary D-dimer/FDP ratio which was used as the indicator of fibrinolytic activity in glomeruli was obtained in various conditions of renal transplants. The ratios were relatively high in the urines from well functioning grafts. This ratio deteriorated at the onset of rejection crisis and tended to go upward during the course of the recovery when the rejection was reversible. In the cases of irreversible acute rejection and chronic rejection, these ratios remained at a low level. D-dimer/FDP ratio might be useful indicator to predict the reversibility of rejection and the prognosis of renal allograft. Furthermore, these findings suggest that fibrinolytic and thrombolytic therapy by the tissue-type plasminogen activator (t-PA) along with immunosuppressive drugs might be more effective for the treatment of these rejections.     

Urinary Excretion of Guanidinoacetic Acid in Rats with Diabetic Nephropathy

Urinary guanidinoacetic acid (GAA) is a sensitive marker for gentamicin nephrotoxicity in rats. This study assesses the usefulness of GAA concentrations in the diagnosis of renal tubular injury in diabetic nephropathy. Serum, urine, and renal cortex samples were obtained from rats 1, 2, and 3 weeks after streptozotocin injection (65 mg/kg body weight). Guanidinoacetic acid levels were measured by high-performance liquid chromatography. N-acetyl-β-D-glucosaminidase (NAG) activity in urine was determined by an enzymatic method. GAA levels in serum, urine, and renal cortex were significantly decreased in diabetic rats compared with those in control rats. In contrast, urinary NAG activity was significantly increased in diabetic rats. Decreases in serum, urine, and renal cortical GAA levels were attenuated by insulin treatment. These results indicate that a high serum glucose level may affect GAA synthesis in the renal cortex and that urinary GAA may be a clinically useful indicator of renal tubular injury in diabetic nephropathy.     

Acute change in urinary NAG activity following CDDP administration

In the present paper, the acute change of urinary NAG activities following CDDP administration was studied in 8 patients with urological malignant tumors. The activities were measured for 11 days from the day before CDDP administration and were expressed as U/day. According to the NAG activity and creatinine clearance (CCr), the patients were divided into 4 types. In type I (normal NAG activity and normal CCr), the increase of the NAG activity following CDDP administration was transient. In type II (normal NAG activity and low CCr), the NAG activity increased and decreased as in type I, but in type II, the NAG activity rebounded a few days after the completion of CDDP administration. In type III (high NAG activity and normal CCr) and in type IV (high NAG activity and low CCr), the increase of the NAG activities continued longer than in type I, II; especially in type IV, the increase and the prolongation of the NAG activity was prominent. The timing of CDDP administration is considered important to avoid renal toxicity of CDDP.     

Urinary excretion of guanidinoacetic acid in rats with diabetic nephropathy

Urinary guanidinoacetic acid (GAA) is a sensitive marker for gentamicin nephrotoxicity in rats. This study assesses the usefulness of GAA concentrations in the diagnosis of renal tubular injury in diabetic nephropathy. Serum, urine, and renal cortex samples were obtained from rats 1, 2, and 3 weeks after streptozotocin injection (65 mg/kg body weight). Guanidinoacetic acid levels were measured by high-performance liquid chromatography. N-acetyl-beta-D-glucosaminidase (NAG) activity in urine was determined by an enzymatic method. GAA levels in serum, urine, and renal cortex were significantly decreased in diabetic rats compared with those in control rats. In contrast, urinary NAG activity was significantly increased in diabetic rats. Decreases in serum, urine, and renal cortical GAA levels were attenuated by insulin treatment. These results indicate that a high serum glucose level may affect GAA synthesis in the renal cortex and that urinary GAA may be a clinically useful indicator of renal tubular injury in diabetic nephropathy.     

Effects of high energy shock wave exposure on renal function during extracorporeal shock wave lithotripsy for kidney stones.

In order to study the effects of high energy shock wave exposure on the kidney in extracorporeal shock wave lithotripsy (ESWL) using Dornier HM3, renal hemodynamics and renal function before and after ESWL were analyzed by 99mTc-DTPA renoscintigraphy. Various urinary enzyme activities (LDH, GOT, GPT, NAG, gamma-GTP) and low molecular protein concentrations (alpha 1-microglobulin, beta 2-microglobulin) before and after ESWL were also compared. In the early phase of the renoscinitgram obtained in the 1st min after injection of 99mTc-DTPA, the time required to reach maximum radioactivity was significantly prolonged after ESWL in both the affected and contralateral kidney. This indicated that renal blood flow decreased in both the affected and contralateral kidney immediately after ESWL. An analysis of the 30-min renoscintigram showed that urinary clearance was delayed in the affected kidney in spite of no overt obstruction due to stone fragments. As for urinary enzyme activities and low molecular protein concentrations, they were standardized by urinary creatinine concentration measured at the same time. Urinary LDH, GOT, GPT and NAG activities remarkably increased on the day of ESWL followed by a decrease close to pretreatment levels on the 4th day, though these levels were still significantly higher than pretreatment levels. Urinary gamma-GPT activity was significantly higher than the pretreatment level only on the day of ESWL. Urinary alpha 1-microglobulin and beta 2-microglobulin concentrations significantly increased on the day of ESWL and were still high on the 4th day.(ABSTRACT TRUNCATED AT 250 WORDS)     

Early diagnosis of rejection. Correlation of enzymuria and histological findings after renal transplantation in the rat

One hundred renal transplants were performed between different rat strain combinations. Posttransplant renal function was monitored using serum creatinine levels, creatinine clearance rates, and N-acetyl-beta-D-glucosaminidase (NAG) enzymuria. These biochemical measurements were compared with the morphological appearances of the transplanted kidney. Rises in NAG enzymuria proved to be useful diagnostic indicators of graft rejection with a false positive rate of only 6%. In 78% of the rejection episodes, the urinary NAG level rose 2 days before any elevation in serum creatinine concentration. There was a close correlation among increasing NAG enzymuria, decreasing renal function, and the structural events of rejection--indicating that the routine measurement of tubular enzymuria would be of value in the prediction and diagnosis of renal allograft rejection.     

Immunohistological analysis of renal allograft biopsies from cyclosporin-treated patients

Differentiation of cyclosporin nephrotoxicity from renal allograft rejection is often difficult. Induction of tubular HLA-class II antigens and elevated levels of leucocyte infiltration are associated with allograft rejection but their association with cyclosporin nephrotoxicity is unclear. In order to determine these relationships, transplant biopsies (n=32) from patients considered to have cyclosporin nephrotoxicity, allograft rejection or stable graft function were stained with monoclonal antibodies specific for HLA-class II antigens and infiltrating leucocytes. Leucocyte infiltration was elevated during rejection but not in cyclosporin nephrotoxicity or stable graft function. While HLA-class II antigen expression was induced in 71% of the biopsies obtained during clinical rejection, no increased expression was found in the other 29%. Induced antigens were detected in five of the nine biopsies obtained in the presence of cyclosporin nephrotoxicity 90 days after transplantation. In four of these, induction was attributed to prolongation of increased class II expression following previous rejection episodes. Thus, the presence of induced class II antigens in the renal allograft does not exclude a diagnosis of cyclosporin nephrotoxicity.     

Immunohistological analysis of renal allograft biopsies from cyclosporin-treated patients: Induced HLA-class II antigen expression does not exclude a diagnosis of cyclosporin nephrotoxicity

Abstract. Differentiation of cyclosporin nephrotoxicity from renal allograft rejection is often difficult. Induction of tubular HLA-class II antigens and elevated levels of leucocyte infiltration are associated with allograft rejection but their association with cyclosporin nephrotoxicity is unclear. In order to determine these relationships, transplant biopsies ( n =32) from patients considered to have cyclosporin nephrotoxicity, allograft rejection or stable graft function were stained with monoclonal antibodies specific for HLA-class II antigens and infiltrating leucocytes. Leucocyte infiltration was elevated during rejection but not in cyclosporin nephrotoxicity or stable graft function. While HLA-class II antigen expression was induced in 71% of the biopsies obtained during clinical rejection, no increased expression was found in the other 29%. Induced antigens were detected in five of the nine biopsies obtained in the presence of cyclosporin nephrotoxicity 90 days after transplantation. In four of these, induction was attributed to prolongation of increased class II expression following previous rejection episodes. Thus, the presence of induced class II antigens in the renal allograft does not exclude a diagnosis of cyclosporin nephrotoxicity.     

Urinary NAG and gamma-GTP activities as indicators of CDDP renal toxicity: effect of fosfomycin on CDDP renal toxicity

Using urinary N-acetyl-beta-D-glucosaminidase (NAG) and gamma-glutamyl transpeptidase (gamma-GTP) activities as the indicator of renal toxicity, the effect of fosfomycin (FOM) on cisdichlorodiamineplatinum (CDDP) renal toxicity was studied in 10 patients with urological malignant tumors. Regimen of chemotherapy was daily 20 mg of CDDP and 800 mg of administered by drip infusion for 5 days and 40 mg of adriamycin injected in one-push on day 1. FOM was not used at 1st cure. At 2nd cure, daily 2 g X 2 of FOM was administered for eleven days from the day before CDDP administration. Urinary NAG and gamma-GTP were measured for eleven days continuously in both 1st and 2nd cure. Effect of FOM on CDDP renal toxicity was discussed by comparison of the urinary NAG and gamma-GTP activities between 1st and 2nd cure. The results showed that urinary NAG and gamma-GTP activities following CDDP administration were deeply influenced by these activities before CDDP administration and the combined therapy of FOM had tendency to reduce CDDP renal toxicity when urinary NAG and gamma-GTP activities before CDDP administration were in the normal range.     

肾移植术后血清IL—6水平的动态监测及临床意义

目的：观察肾移植术后发生急性排斥反应、感染、CsA中毒时血清IL-6的变化,以探讨IL-6在急性排斥反应的早期诊断、鉴别诊断中的意义。方法：采用双抗体夹心酶联免疫吸附法,对106例肾移植患者血清IL-6活性水平于肾移植手术前后进行动态监测。结果：肾移植术前,IL-6与对照组比较差别无显著性意义。术后第1天明显升高,2周左右基本降至术前水平。发生急性排斥反应前1-3天。血清IL-6即有升高,峰值出现在抗排斥反应治疗的当天,经甲基本降至术前水平,发生急性排斥反应前1-3天,血清IL-6即有升高,峰值出现在抗排斥反应治疗的当天,经甲基泼尼松尼（MP）冲击有效后迅速下降,治疗无效者,血清IL-6持续在高水平,并发感染时,IL-6也显著升高,与急性排斥反应组相比差别无显著性意义;而CsA中毒时,IL-6变化不明显。结论：动态监测IL-6可以作为急性排斥反应的早期诊断,鉴别诊断的免疫生物学指标。     

Elevated serum activity of N-acetyl-beta-glucosaminidase in essential hypertension: diagnostic value and reversal to normal values after antihypertensive therapy

Previous studies have shown that urinary N-acetyl-beta-glucosaminidase (NAG) is elevated in patients with hypertension, even without renal disease. To elucidate the value of measuring NAG, both in urine and serum of hypertensive patients, we measured NAG activity in the serum, plasma, and 24-hour urine by the fluorimetric method in 84 patients with uncomplicated essential hypertension before and after 6 months of effective treatment. NAG activities of these hypertensive patients were compared with those of 102 healthy normotensive subjects and 97 patients with various renal diseases and controlled hypertension. Serum NAG activity was clearly greater in patients with essential hypertension (427 +/- 124 U/mL) than in normotensive subjects (380 +/- 109 U/mL) or patients with renal disorders (393 +/- 115 U/mL) (P less than or equal to 0.004). The greater was the diastolic pressure in the hypertensive group, the greater was serum NAG activity (r = +0.30, P = 0.004). Hypertensive patients with high serum NAG activity were further characterized by a more exaggerated increase in systolic pressure (34 +/- 16 v 25 +/- 15 mm Hg, P = 0.051) and total peripheral resistance (19% +/- 18% v 12% +/- 13%, P = 0.042) in response to the cold pressor test and by a greater increase in systolic pressure (56 +/- 15 v 45 +/- 13 mm Hg, P = 0.009) and diastolic pressure (11 +/- 7 v 6 +/- 9, P = 0.043) in response to bicycle exercise testing than the group with low serum NAG activity. In contrast, urinary NAG activity tended to be only slightly higher in patients with essential hypertension than in the normotensive control group (33 +/- 31 v 23 +/- 29 U/mg creatinine [cr], P = 0.062), whereas patients with renal diseases had clearly increased urinary NAG activity (87 +/- 105 U/mg cr) (P less than 0.001). Following effective antihypertensive therapy, serum NAG activity decreased in patients with essential hypertension to values of normotensive control subjects (from 427 +/- 124 U/mL to 386 +/- 106 U/mL, P less than 0.01). A significant decrease in serum NAG activity was observed in patients with both initially high as well as low pretreatment serum NAG activities (P less than 0.001 and P less than 0.02, respectively). Urinary NAG activity overall was unchanged by antihypertensive treatment. We conclude that in patients with mild essential hypertension, serum NAG activity was already elevated (whereas urinary NAG activity was not) and was normalized by effective antihypertensive treatment.(ABSTRACT TRUNCATED AT 400 WORDS)     

Urinary polyamines as markers of cardiac allograft rejection. A clinical evaluation

Histologic evaluation of endomyocardial biopsy specimens is the current method of monitoring rejection after cardiac transplantation. Unfortunately, this technique gives a discontinuous evaluation of the recipient immunologic status. A noninvasive marker of immunologic activation and of allograft rejection that would permit a more continuous monitoring than the biopsy technique would be clinically useful. Urinary polyamine excretion reflects cellular proliferation or degeneration and, as a marker of cellular metabolic activity, may also reflect lymphocyte proliferation and organ rejection. From July 1985 to December 1986, urinary polyamines were studied in 18 patients during hospitalization for heart and heart-lung transplantation. Endomyocardial biopsy was performed twice a week and histologic rejection was characterized by standard criteria. Urinary specimens were collected daily and analyzed for polyamines by high-pressure liquid chromatography. Concentrations of acetylputrescine and total urinary polyamines were significantly higher before the 20 rejection episodes than before the 80 biopsies yielding negative results. So that their clinical usefulness could be evaluated, an elevation of polyamines and a daily level variability of 28% or more was chosen to indicate increased metabolic cellular activity and to predict rejection in the next 8 days. On the basis of these definitions, the sensitivity of polyamine assays to predict rejection was 85%, the specificity 88%, and the positive predictive value 79%. Therefore, serial measurements of urinary polyamines may provide daily information on the recipient's immunologic status after cardiac transplantation.     

肾移植受者外周血白细胞淋巴细胞功能相关抗原-1表达的意义

目的　监测肾移植前、后外周血白细胞淋巴细胞功能相关抗原１（ＬＦＡ１） 的表达水平,了解其变化规律, 探讨其在肾移植排斥反应中的意义。方法　应用单克隆抗体流式细胞仪荧光抗体技术监测肾移植受者外周血白细胞的ＬＦＡ１ 表达水平。结果　肾移植术后ＬＦＡ１ 表达水平较术前显著降低, 并维持在低水平, 发生排斥反应时显著升高; 排斥时的ＬＦＡ１ 表达水平与术后无排斥时及排斥反应控制后比较, 差异有显著性, 与术前比较, 差异无显著性。结论　ＬＦＡ１ 在白细胞上的表达与排斥反应密切相关; 监测ＬＦＡ１ 的表达水平有助于肾移植排斥反应的诊断。     

肾移植术后肝细胞生长因子的动态监测及临床意义

目的:探讨肝细胞生长因子(HGF)在急性排斥反应的早期诊断、鉴别诊断中的意义。方法:采用双抗体夹心酶联免疫吸附法,对50例肾移植受者血清HGF水平在手术前后进行动态监测。观察肾移植术后发生急性排斥反应(AR)、急性肾小管坏死(ATN)、环孢素(CsA)中毒时血清HGF的变化。结果:术前组HGF水平与对照组相比有统计学意义(P<0.05)。稳定组术后前3天HGF下降明显,2周左右降至对照组水平。AR组在典型症状出现及血Cr升高前1~3d,HGF即有升高,且峰值出现在抗排斥治疗的当天。经甲基泼尼松龙冲击后AR逆转者HGF迅速下降。ATN组HGF升高,与AR组相比有统计学意义(P<0.05)。CsA中毒组HGF水平升高,与AR相比有统计学意义(P<0.05),但与ATN组相比无统计学意义(P>0.05)。结论:动态监测HGF可能作为急性排斥反应的早期诊断敏感指标,并且对ATN、CsA中毒的鉴别诊断也具有一定临床应用价值。     

Studies of urinary proteins, FDP (fibrinogen degradation products), and NAG (N-acetyl-beta-D-glucosaminidase) in renal transplanted patients

The urinary proteins, FDP (fibrinogen degradation products), and NAG (N-acetyl-beta-D-glucosaminidase) in renal transplanted patients were studied. SDS (sodium dodecyl sulphate) electrophoresis was used for the differentiation of urinary proteins according to their molecular size. In the azathioprine-treated patients with stable renal function, most of the urinary proteins were albumin. However, the low molecular weight (LMW) proteins, which were suggestive of tubular proteins, appeared in the urine of the ciclosporin-treated patients with stable renal function. During the rejection episodes of the ciclosporin-treated patients, the fraction of LMW proteins increased. The elevation of urinary FDP and NAG index (urinary NAG/urinary Cr) were detected in association with rejection episodes. Urinary NAG index increased in proportion to the elevation of serum Cr. However, the elevation of urinary NAG index was found in some ciclosporin-treated patients with normal serum Cr. The elevation of NAG index without the elevation of urinary FDP occurred in ciclosporin nephrotoxicity. The SDS electrophoresis of urinary proteins, urinary FDP, and urinary NAG index can be useful parameters for monitoring ciclosporin nephrotoxicity.