肾病患者内源性肾小球滤过率的实验室评价

目的 :评估肾病患者内源性肾小球滤过率 (GFR)。方法 :测定了 5 7例肾病患者和 39例健康对照血中CystatinC(CysC )、尿素、肌酐和肌酐清除率浓度。结果 :患者尿素、肌酐、肌酐清除率和CysC浓度与健康对照组间均存在明显差异 (P <0 .0 0 1 ) ;相关分析表明CysC和肌酐清除率之间 (P <0 .0 1 )、CysC和肌酐之间 (P <0 .0 1 )存在明显的相关关系。而肌酐和尿素之间 (P >0 .0 5 ) ,以及肌酐和肌酐清除率之间 (P >0 .0 5 )无明显相关关系存在。结论 :肾病患者血中CysC浓度增高 ,对GFR功能早期受损的评估优于尿素、肌酐和肌酐清除率。     

Serum cystatin C assay for the detection of early renal impairment in diabetic patients

The ability to assess renal function in diabetes patients rapidly and early is of major importance. This study was designed to determine whether cystatin C can replace serum creatinine as the screening marker for reduced glomerular filtration rate (GFR) in type 2 diabetes patients. The study was performed on 51 type 2 diabetic patients. GFR was estimated by the plasma clearance of (99m)Tc-DTPA. The correlation between (99m)Tc-DTPA clearance and levels of serum cystatin C, serum creatinine, and creatinine clearance was determined. Sensitivity and specificity for the diagnosis of renal impairment (defined as GFR<68 ml/min) were calculated by a receiver operating characteristic (ROC) curve for serum cystatin C, serum creatinine, and creatinine clearance. The correlation coefficients with (99m)Tc-DTPA clearance were -0.744 for serum cystatin C, -0.658 for serum creatinine, and +0.625 for creatinine clearance (P<0.001). With a cutoff value of 68 mL/min, the area under the ROC curve (AUC) was 0.891 for cystatin C, 0.77 for creatinine, and 0.753 for creatinine clearance. The AUC was statistically different between serum cystatin C and creatinine clearance (P<0.05). The ROC plot indicates that cystatin C is superior to serum creatinine and creatinine clearance for detecting impaired GFR. Serum cystatin C appropriately reflects GFR in diabetes, and is more efficacious than serum creatinine and creatinine clearance in detecting reduced GFR in type 2 diabetes patients.     

Relationships among serum cystatin C,serum creatinine,lean tissue mass and glomerular filtration rate in healthy adults

In an effort to increase our knowledge of the optimal use of serum cystatin C and creatinine as glomerular filtration rate (GFR) markers, these variables, as well as lean tissue mass and GFR, were determined in a population of 42 healthy young adults (men and women with normal GFR). Dual­energy X­ray absorptiometry and measurement of the plasma clearance of iohexol were used to measure lean tissue mass and GFR, respectively. Serum creatinine was significantly correlated to lean tissue mass (r=0.65; p&lt;0.0001) but not to GFR (1/creatinine vs. GFR: r=0.11; p=0.106). In contrast, serum cystatin C correlated with GFR (1/cystatin C vs. GFR: r=0.32; p=0.0387), especially in men (1/cystatin C vs. GFR: r=0.64; p=0.0055), but not to lean tissue mass. These results might explain previous observations that serum cystatin C seems to be a better marker for GFR than serum creatinine, particularly for individuals with small to moderate decreases in GFR. However, the results also show that the serum concentrations of both creatinine and cystatin C are determined not only by GFR, but also by other factors. Since these additional factors differ for cystatin C and creatinine, it seems justified to use serum creatinine and cystatin C in conjunction to estimate GFR, at least until it is known in what situations serum creatinine or cystatin C is the preferable marker.     

Evaluation of the clinical application of cystatin C, a new marker of the glomerular filtration rate, for the initial dose-setting of arbekacin

Objective:  Recent studies have shown that serum cystatin C is a better marker for measuring the glomerular filtration rate (GFR) than the conventional method, using serum creatinine concentration. The purpose of this study is to evaluate the clinical application of serum cystatin C as a marker of GFR to determine the initial dosage of arbekacin, an antibiotic primarily excreted via the kidneys. In this study, the predictability of serum arbekacin peak and trough concentrations were assessed using estimated population mean GFR values calculated from either serum creatinine (Cockcroft–Gault equation) or cystatin C (Sjöström equation) concentrations. Method:  Ninety‐five patients treated with arbekacin for methicillin‐resistant Staphylococcus aureus infection were divided into three groups according to their GFR values estimated by the serum cystatin C concentration as follows: normal to mild (GFR > 70 mL/min, n = 40), moderate (30 ≤ GFR ≤ 70 mL/min, n = 41) and severe (GFR < 30 mL/min, n = 14) renal impairment. Result:  The mean GFR (±SD) of 95 patients predicted by serum cystatin C concentration (64·6 ± 30·6 mL/min) was significantly lower (P < 0·001) than predicted by serum creatinine concentration (77·4 ± 43·9 mL/min). Prediction (difference of mean prediction error, ΔME) of the serum arbekacin concentration using the estimated GFR based on the serum cystatin C concentration was significantly less biased at the peak and trough concentrations than those determined using serum creatinine concentration. The accuracy of prediction (difference of the mean absolute error, ΔMAE) using serum cystatin C concentration was significantly better than with serum creatinine for both serum peak and trough concentrations in patients with moderately decreased GFR. However, there were no significant differences in the ΔMAE of normal to mild and severe renally impaired patients. Conclusion:  These results suggest that serum cystatin C is a useful marker of GFR for determining the initial dosage of arbekacin, especially in patients with moderate impairment of renal function.     

Kidney function estimating equations in patients with chronic kidney disease

Background: The current guidelines emphasise the need to assess kidney function using predictive equations rather than just serum creatinine. The present study compares serum cystatin C‐based equations and serum creatinine‐based equations in patients with chronic kidney disease (CKD). Methods: Seven hundred and sixty‐four adult patients with CKD were enrolled. In each patient serum creatinine and serum cystatin C were determined. Their glomerular filtration rate (GFR) was estimated using three serum creatinine‐based equations [Cockcroft–Gault (C&G), modification of diet in renal disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration equation (CKD‐EPI)] and two serum cystatin C‐based equations [our own cystatin C formula (GFR = 90.63 × cystatin C^?1.192) and simple cystatin C formula (GFR = 100/cystatin C)]. The GFR was measured using ⁵¹CrEDTA clearance. Results: Statistically significant correlation between ⁵¹CrEDTA clearance with serum creatinine, serum cystatin C and all observed formulas was found. The receiver operating characteristic curve analysis (cut‐off for GFR 60 ml/min/1.73 m²) showed that serum cystatin C and both cystatin C formulas had a higher diagnostic accuracy than C&G formula. Bland and Altman analysis for the same cut‐off value showed that all formulas except simple cystatin C formula underestimated measured GFR. The accuracy within 30% of estimated ⁵¹CrEDTA clearance values differs according to stages of CKD. Analysis of ability to correctly predict patient’s GFR below or above 60 ml/min/1.73 m² showed statistically significant higher ability for both cystatin C formulas compared to MDRD formula. Conclusion: Our results indicate that serum cystatin C‐based equations are reliable markers of GFR comparable with creatinine‐based formulas.     

Analysis of glomerular filtration rate, serum cystatin C levels, and renal resistive index values in cirrhosis patients.

BACKGROUND: The aim of this study was to evaluate the relation of glomerular filtration rate (GFR) to serum cystatin C levels, renal resistive index (RRI), serum creatinine and creatinine clearance in patients with different stages of cirrhosis. METHODS: The study sample was 25 cirrhotic patients (10 females and 15 males; mean age 57.3+/-2.04 years), 10 in the compensated stage without ascites and 15 in the decompensated stage with new-onset ascites. None had azotemia nor were on diuretic treatment. The control group comprised 25 healthy adults (11 female and 14 men; mean age 56.56+/-1.91 years). Serum cystatin C, RRI, serum creatinine and creatinine clearance were measured. GFR was determined by technetium(99m)-diethylene triamine pentaacetic acid renal scintigraphy. RESULTS: Cirrhosis cases had lower mean scintigraphic GFR than controls (64.5+/-4.03 vs. 87.96+/-4.16 mL/min, p<0.05). Serum cystatin C and RRI were significantly higher in the cirrhotic group compared to controls (1.16+/-0.09 mg/L and 0.68+/-0.01 vs. 0.86+/-0.03 mg/L and 0.64+/-0.01, respectively; p<0.05). Subgroup comparative analysis showed that only two parameters, scintigraphic GFR and serum cystatin C, were significantly different between compensated and decompensated cirrhotics (75.62+/-4.9 mL/min and 0.89+/-0.07 mg/L vs. 57.23+/-5.14 mL/min and 1.34+/-0.13 mg/L, respectively; p<0.05). Scintigraphic GFR showed significant correlation with cystatin C, but not with serum creatinine or creatinine clearance (r=-0.877, p<0.05) in decompensated patients. No correlation was observed between scintigraphic GFR and RRI or between serum cystatin C and RRI in all subjects. A receiver operator characteristics curve showed that cystatin C at a cutoff value of 1.01 mg/L can significantly differentiate patients with GFR <70 mL/min with 80% sensitivity and 80% specificity. CONCLUSIONS: Serum cystatin C, but not serum creatinine or RRI measurement, correlates with GFR in each stage of liver failure and has a significant diagnostic advantage in detecting lower GFR in such cases.     

Evaluation of serum cystatin C and chromogranin A as markers of nephropathy in patients with type 2 diabetes mellitus

Nephropathy is a significant cause of morbidity and mortality in patients with diabetes mellitus (DM). The condition is characterized by persistent albuminuria and years of progressive renal structural changes associated with decline in the glomerular filtration rate (GFR). This study evaluates whether serum concentrations of the endogenous markers of GFR, cystatin C and chromogranin A could be used as indicators of nephropathy in 77 patients with Type 2 DM. On the basis of early morning urine microalbumin:creatinine ratio, patients were divided into patients without diabetic nephropathy (DN) who were normoalbuminuric (n = 27) and patients with DN who were microalbuminuric (n = 8) or macroalbuminuric (n = 42). Patients with reduced GFR or elevated serum cystatin C did not show the expected increase in serum chromogranin A. Twenty-six percent of the patients with normoalbuminuria and 6% of those with DN had serum chromogranin A below the detection limit of the assay (< 2 U/L). In patients with DN, serum chromogranin A showed significant correlation with serum cystatin C, but not with serum creatinine and creatinine clearance. Serum cystatin C and creatinine showed poor correlation with duration of DM and HbA1c. Serum cystatin C and creatinine were significantly higher in patients with DN than in normoalbuminuric patients. Serum cystatin C showed significant correlation with serum creatinine (rs = 0.45, p = 0.002), but not with creatinine clearance (rs = 0.23, p = 0.17) in patients with DN. Four of nine patients with creatinine clearance between 50 and 80 mL/min had increased (> or = 1.4 mg/L) serum cystatin C compared with only two patients with increased serum creatinine concentration. Twenty of 50 (40%) patients with DN had elevated serum cystatin C compared with 6 of 50 (12%) with elevated serum creatinine. If microalbuminuria is regarded as the "gold-standard" test, serum cystatin C has a sensitivity of 40% and specificity of 100% for the detection of DN. However, further studies are required to confirm the usefulness of serum cystatin C estimation as a screening test and as an early indicator and predictor of the development of DN.     

异常凝血酶原和唾液酸在慢性肾功能不全患者血清中的表达及临床意义

目的观察慢性肾功能不全对血清异常凝血酶原(PIVKA-Ⅱ)和唾液酸(SA)水平的影响。方法用化学发光法和酶法分别检测127例慢性肾功能不全、32例肾功能正常肾脏疾病患者、57例体检健康者和120例肝细胞癌(HCC)患者血清PIVKA-Ⅱ和SA水平。分别测定上述受试者血清尿素(Urea)和肌酐(Cr)水平,并估算肾小球滤过率值(eGFR)。结果健康对照组、肾功能正常疾病组和肾功能不全疾病组三组间血清PIVKA-Ⅱ水平没有统计学差异(H=2.902,P0.05),且明显低于HCC组(U值分别为319.50、203.00、665.50,P均0.001)。肾功能不全疾病组中各期之间血清PIVKA-Ⅱ水平也没有统计学差异(H=3.991,P0.05)。血清SA水平在健康对照组、肾功能正常疾病组和肾功能不全疾病组之间(H=63.685,P0.001),以及在肾功能不全疾病组各期之间(H=64.689,P0.001)均有统计学差异。血清SA水平与eGFR呈负相关(r=-0.705,P0.001),与Urea、Cr水平呈正相关(r=0.599、0.704,P0.001)。HCC组血清SA水平较CKD1~4期均明显升高(U值分别为126.00、163.50、247.00、715.00,P均0.001),较CKD5期无明显变化(U=419.00,P0.05)。结论肾功能不全对血清PIVKA-Ⅱ表达无明显影响,但可明显提高血清SA的表达水平,并与肾功能损害程度密切相关。可见血清SA水平升高不仅对HCC及其他多种恶性肿瘤有辅助诊断价值,还可较好地反映慢性肾功能不全患者的肾功能状态。     

血清胱抑素C在危重患者急性肾功能障碍监测中的应用

目的探讨血清胱抑素C在危重患者急性肾功能障碍监测中的应用。方法测定72例危重患者血清胱抑素C、肌酐及肾脏内生肌酐清除率水平,并分析其差异。结果危重患者血清胱抑素C水平与肾脏内生肌酐清除率水平呈明显负相关,且高于血清肌酐。在急性肾功能障碍检出率上,血清胱抑素C检出率78.94%(30/38)高于血清肌酐检出率21.05%(8/38),差异有统计学意义(P<0.05)。结论血清胱抑素C是较精准的肾小球率监测指标,检测胱抑素C有助于危重患者急性肾功能障碍的监测。     

Oral antiviral drugs in experimental herpes simplex keratitis

Serum kinetics of amikacin were investigated in 17 severely ill patients. During both the first and last dose intervals of therapy, the serum concentration time course of every patient was documented by 17 blood samples. Six of the patients had moderate to severe renal insufficiency (serum creatinine greater than 1.5 mg/100 ml). In this group of patients, a pronounced rise in serum half-life of amikacin was observed, increasing from a mean of 11.2 to 21.5 h for the first and last interval, respectively. In contrast, mean half-life remained stable in the group of 11 patients with normal renal function. No change in mean serum creatinine occurred in either group, when data from the beginning and the end of therapy were compared. Therefore, the increase of amikacin half-life is apparently not due to a reduction of the glomerular filtration rate, but rather to a decrease of the ratio of amikacin to creatinine clearance. Indeed, a significant reduction of this ratio could be shown in the seven patients in which 24-h creatinine clearance was determined during the first and last day of therapy. This phenomenon is discussed in the context of aminoglycoside accumulation in deep compartments. We conclude that the daily dose of amikacin has to be reduced during therapy in patients with impaired, but stable, renal function.     

The efficacy and toxicity of two dosing-regimens of amikacin in neonates with sepsis

What is known and objective: Neonatal sepsis is one of the most common reasons for admission to neonatal units in developing countries. Aminoglycosides widely used in its treatment are usually administered two or three times a day. Less frequent doing may be more convenient and as effective. We aim to compare the efficacy and safety (nephrotoxicity) of once daily vs. twice daily dosing of amikacin in neonates with suspected or proven sepsis and report on the drug’s pharmacokinetics in these subjects. Methods: Thirty neonates of gestational age ≥36 weeks and body weight ≥2500 g with suspected or proven sepsis were randomized to receive amikacin either at a dose of 15 mg/kg once per day; group I (n = 15), or a dose of 7·5 mg/kg twice per day, group II (n = 15). All neonates received classical treatment of sepsis including antibiotics, hemodynamic support, inotropic support based on blood pressure levels and size of the heart in chest X‐ray, if needed. Amikacin was infused over 1 h. Peak and trough serum samples for amikacin were measured for all infants at steady state. Nephrotoxicity was assessed by serum creatinine and urinary N‐acetyl β‐d ‐glucosaminidase before and 7 days after therapy. Clinical efficacy was compared using both observation of clinical status and normalization of laboratory tests. Results: All the patients in group I had achieved a trough level <10 μg/mL and two patients had trough concentration >10 μg/mL in group II. No significant difference between group I and group II in either baseline or day 7 serum creatinine was demonstrated (P > 0·05). No significant difference was found between the two groups in clinical efficacy or renal toxicity. The calculated pharmacokinetic parameters were in group I and II, respectively: clearance =63·8 ± 15·9 mL/kg/h and 73·5 ± 18·1 mL/kg/h; volume of distribution =0·54 ± 0·09 L/kg and 0·61 ± 0·13 L/kg, half‐life =6·1 ± 1·0 h and 5·95 ± 1·1 h. What is new and conclusion: As expected, amikacin given once every 24 h to septic neonates of ≥36 weeks of gestation achieved higher peak levels and lower trough concentrations than the twice daily regimen. Treatment with once daily regimen did not lead to more nephrotoxicity than with a twice‐daily regimen, and showed comparable efficacy.     

Diagnostic value of serum cystatin C for evaluation of hepatorenal syndrome

BACKGROUND: The evaluation of renal function in patients with decompensated cirrhosis is important for prognosis, dosage assessment of potentially nephrotoxic drugs and recognition of changes in glomerular filtration rate (GFR) to decide paracentesis and diuretic therapy. Patients with many different disorders of hepatic function can present with various abnormalities of renal function in the absence of other known causes of renal failure which has been called hepatorenal syndrome (HRS). Some reports have pointed out that serum creatinine levels frequently failed to rise above normal levels even when glomerular filtration rate (GFR) is very low in cirrhotic patients with hepatorenal syndrome. The aim of this study was to determine if estimation of serum cystatin C could replace creatinine clearance in routine GFR determinations for patients with cirrhosis. METHODS: Serum cystatin C, creatinine clearance (Clcr), and 99mTc-DTPA clearance were determined in 26 patients with cirrhosis. According to Child-Pugh's classification, 21 patients were in group C and 5 were in Group B. RESULTS: Pearson correlation analyses showed that correlation between serum cystatin C and 99mTc-DTPA clearance was r=-0.522, p=0.006, between serum creatinine and 99mTc-DTPA was r=-0.373, p=0.06. The results of our study demonstrated that neither serum creatinine nor creatinine clearance (Clcr) were good indicators of hepatorenal syndrome because the mean value for Clcr was found to be higher than Tc-DTPA clearance, and there was no correlation between these two parameters (r=0.059). Additionally, the mean value of serum creatinine was found to be within the normal range, whereas the mean DTPA clearance level was lower than normal range. CONCLUSIONS: This finding could be explained by the fact that cirrhotic patients with poor nutrition may have decreased protein intake, low muscle mass and lack of converting capacity of creatine to creatinine. Thus, we suggest that serum cystatin C assay, which has good analytical performance, could replace or at least be added to creatinine measurement for GFR assessment in patients with cirrhosis.     

Relationships among serum cystatin C, serum creatinine, lean tissue mass and glomerular filtration rate in healthy adults

In an effort to increase our knowledge of the optimal use of serum cystatin C and creatinine as glomerular filtration rate (GFR) markers, these variables, as well as lean tissue mass and GFR, were determined in a population of 42 healthy young adults (men and women with normal GFR). Dual-energy X-ray absorptiometry and measurement of the plasma clearance of iohexol were used to measure lean tissue mass and GFR, respectively. Serum creatinine was significantly correlated to lean tissue mass (r=0.65; p < 0.0001) but not to GFR (1/creatinine vs. GFR: r=0.11; p=0.106). In contrast, serum cystatin C correlated with GFR (1/cystatin C vs. GFR: r=0.32; p=0.0387), especially in men (1/cystatin C vs. GFR: r=0.64; p=0.0055), but not to lean tissue mass. These results might explain previous observations that serum cystatin C seems to be a better marker for GFR than serum creatinine, particularly for individuals with small to moderate decreases in GFR. However, the results also show that the serum concentrations of both creatinine and cystatin C are determined not only by GFR, but also by other factors. Since these additional factors differ for cystatin C and creatinine, it seems justified to use serum creatinine and cystatin C in conjunction to estimate GFR, at least until it is known in what situations serum creatinine or cystatin C is the preferable marker.     

Predictors of renal function in diabetic and non-diabetic renal disease

Forty-two patients with renal disease due to diabetic nephropathy (14 patients), tubulointerstitial disease (14 patients) and glomerular disease (14 patients) underwent measurement of glomerular filtration rate (GFR) by the 51Cr-EDTA 'one-shot' method and simultaneous serum beta 2-microglobulin, serum creatinine and creatinine clearance estimation. Serum creatinine was a significantly better predictor of GFR than serum beta 2-microglobulin in patients with diabetic nephropathy, whereas both methods were equally useful predictors of GFR in non-diabetic renal disease. Serum creatinine measurement remains the best method for detecting early reduction of GFR on a serum sample.     

Clinical value of serum cystatin C by ELISA for estimation of glomerular filtration rate

The search for whether endogenous markers of changes in glomerular filtration rate (GFR) by serum cystatin C assay and serum cystatin C compare with creatinine clearance by the Cockeroft-Gault formula and the evaluation of its clinical significance as a marker of GFR is important in clinical practice at present. Serum cystatin C was determined by sandwich enzyme immunoassay using a kit. Control blood samples were collected from 70 healthy subjects and 168 patients with various kidney diseases. Creatinine clearance (Cockeroft-Gault formula) as a measure of GFR, in 168 patients with various kidney diseases, depends on the creatinine clearance; GFR parameters were used to divide patients into two groups. The GFR was >80 mL/min in 38 patients (group A) and <80 mL/min in 130 patients (group B). The two groups were analyzed by correlation coefficient and diagnostic sensitivity and specificity were assessed by the receiver-operating characteristic (ROC) plots (area under the curve). Of the 70 healthy control individuals, the serum level of cystatin C was measured as normal value range and a reference interval of 1.05+/-0.18 micro g/mL (mean+/-1.96 SD, 95% confidence limits for the upper references limit is 1.4 microg/mL). In group A, serum cystatin C had no correlation to the creatinine clearance (r=0.171, P>0.05) and in group B, serum cystatin C was closely correlated to the creatinine clearance (r=-0.771, P<0.001). Diagnostic sensitivity and specificity were assessed by the ROC plots for serum cystatin C (area under the curve=0.8461, SE=0.057) and creatinine clearance (area under the curve=0.7642, SE=0.068). These data suggest that combined measurement of serum cystatin C is useful to estimate GFR, especially to detect the reduction of GFR. Further studies are required to evaluate the whether serum cystatin C as a more sensitive marker of early renal injury might be extremely useful, particularly in nonproteinuric or unapparent renal disease.     

光抑素C与血肌酐对2型糖尿病患者肾小球滤过功能评价比较

目的 比较光抑素C(Cystatin C)和血清肌酐及8小时肌酐清除率，评价其对2型糖尿病患者肾小球滤过率(GFR)的判断价值。方法 选择80例2型糖尿病患者，检测其血肌酐、肌酐清除率、尿微量白蛋白排泌率(UAER)及Cystatin C水平，同时通过^99mTc-DTPA排泌率，应用Gates法计算GFR。结果 Cystatin C水平随GFR下降逐渐升高。相关性分析示Cystatin C与GFR呈相关性(r=-0．663，p=0．000)，明显高于肌酐(r=-0．444，P=0．009)及8小时肌酐清除率(r=0．300，P=0．000)。ROC曲线分析示Cystatin C具有更大的曲线下面积(AUC)，敏感性(82％)、特异性(96％)均好，而肌酐特异性好(98％)、敏感性差(20％)，8小时肌酐清除率敏感性(68％)、特异性(79％)均不理想。Cystatin C诊断精确性(80％)明显高于肌酐(63％)。结论 Cystatin C是反映GFR的更敏感指标，可更早、更准确地反映2型糖尿病患者GFR的变化。     

Effects of moderate-dose versus high-dose trimethoprim on serum creatinine and creatinine clearance and adverse reactions.

The effects of a 10-day course of moderate-dose (10 mg/kg/day) or high-dose (20 mg/kg/day) trimethoprim therapy on serum creatinine, measured creatinine clearance, urinary creatinine excretion, and serum folate were studied in 20 healthy volunteers. Serum creatinine concentrations increased significantly during trimethoprim therapy, began to decrease near day 10, and returned to baseline during the washout phase at both dosage levels. At the same time, measured creatinine clearance and urine creatinine changed in the opposite direction. No clinical or statistical differences were noted between changes in the moderate- versus the high-dose phases. Serum folate concentration decreases during high-dose trimethoprim therapy were statistically significant. Adverse drug reactions in the two groups were statistically different during the first study period, with the high-dose group having a 75% incidence rate and the moderate-dose group having an 11% incidence rate (P < 0.02). Serum creatinine, measured creatinine clearance, and urinary creatinine excretion demonstrated statistically, but not clinically, significant changes during trimethoprim therapy. In addition, high-dose trimethoprim caused significantly more adverse drug reactions than moderate-dose trimethoprim in normal volunteers.     

Hepcidin在慢性肾脏病不同分期患者血清中的检测及意义

【目的】探讨hepcidin在判定慢性肾脏病（CKD）不同分期患者机体铁贮存和功能性缺铁方面的价值以及对促红细胞生成素（EPO）治疗反应的影响。【方法】检测70例CKD不同分期患者血清Hepcidin水平以及血液铁代谢指标、高敏C反应蛋白（hsCRP）和相关生化指标。【结果】患者血清Hepcidin水平随着肾小球滤过功能减退,逐渐升高,CKD5期血透组Hepcidin水平最高（120．81±6．65μg／L）（P〈0．001）。血透组Hepcidin水平与血清铁蛋白和转铁蛋白饱和度呈正相关。在不考虑cKD分期的情况下,血清hepcidin水平与hsCRP呈正相关,与肾小球滤过率（GFR）,外周红细胞计数和红细胞压积呈负相关。在血透组A、B亚组中,EPO≥9000IU的A组血清hepcidin水平高于EPO〈9000IU的B组（P〈0.001）。【结论】慢性肾脏病时随着GFR的下降,血清hepcidin水平增加,这可能与肾脏清除hepcidin减少和CKD时存在微炎症状态有关。血清hepcidin升高引起功能性铁缺乏,贮存铁利用障碍和EPO低反应,最终使贫血难以纠正。     

Serum cystatin C: A useful marker of kidney function in very old people

Abstract

Background: Serum creatinine-based estimates of GFR may be inaccurate in the elderly and there is need for improvement. Serum Cystatin C, not being influenced by muscle volume, may be more accurate. Material and methods: GFR was measured with plasma clearance of iohexol in 50 elderly persons aged >70 years. Blood tests were drawn for analysis of creatinine, albumin and urea. Cystatin C was analysed on frozen specimens using the Dade Behring method. GFR estimates based on cystatin C were compared to estimates based on serum creatinine, using earlier published equations. Results: Significant increase with age was found with cystatin C (rs=0.62, p<0.0001) and urea (rs=0.43, p=0.0018) but no correlation with creatinine (rs=0.05, p=0.7502). All equations underestimated GFR with a bias ranging from ?2.2 to ?31%. The equation with the greatest accuracy was the Hoek equation (Cystatin C based) with 98% of estimates within 30% of mGFR and confidence interval 89–100%. Estimated GFR using the MDRD Study equations (creatinine based) showed accuracy of 94% with 4 or 6 factors used. There was a gender difference with an accuracy higher among males (p<0.002). The Cockcroft Gault equation was not found useful with high bias and a low accuracy. Conclusion: S-cystatin C seems a useful marker for kidney function in the elderly. Two equations based on serum cystatin C as well as the two MDRD equations seem adequate for estimating kidney function.     

Serum hepatocyte growth factor levels in patients with chronic renal disease - effect of GFR and pathogenesis

Hepatocyte growth factor (HGF) is a growth-promoting peptide that appears to act in a renotropic and nephroprotective manner during acute renal damage. Recent studies suggest that HGF is also of importance in chronic renal diseases. The serum HGF level is correlated with serum creatinine, and it has been suggested that glomerular and tubular diseases affect serum HGF differently. In the present study, levels of serum HGF were determined and correlated to glomerular filtration rate (GFR) in 118 patients with various chronic renal diseases. GFR was determined by 99m Tc-DTPA clearance, and the GFR values were evenly distributed in the interval 5-155 mL/min/1.73 m 2 . Serum HGF levels increased slightly with decreasing GFR; the Pearson correlation coefficient being 0.49 (p < 0.0001). In 21 additional patients with end-stage renal disease treated with continuous ambulatory peritoneal dialysis, there was a more marked increase in the serum levels of HGF. The effect of glomerular and tubular diseases on serum HGF was examined by comparing the HGF levels in two groups of patients with similar GFR values: 57 patients with mainly glomerular disorders (diabetic nephropathy with micro- or macroalbuminuria or glomerulonephritis) and 14 patients with mainly tubular disorders (polycystic kidney disease). There was no significant difference between the HGF levels of the two groups (p = 0.30). In conclusion: Serum HGF levels are correlated with GFR (for GFR &#85 5 mL/min/1.73 m 2 ) in patients with chronic renal diseases, and glomerular and tubular disorders seem to affect the HGF level similarly.