Serum beta-2-microglobulin estimation as an indicator of the glomerular filtration rate

In 56 patients in whom the glomerular filtration rate (GFR) was estimated by the 51Cr-EDTA technique, serum creatinine and beta 2-microglobulin levels were also measured. In the 15 patients with a GFR of greater than or equal to 80 ml/min, both serum creatinine and beta 2-microglobulin levels were within the reference range. However, the beta 2-microglobulin level was elevated (greater than 2,3 mg/l) in all 41 patients with a GFR of less than 80 ml/min, while the serum creatinine level was increased (greater than 133 mumol/l) in only 35 patients. In the remaining 6 patients, the creatinine values ranged from 75 to 125 mumol/l. It would therefore seem that serum beta 2-microglobulin assay is a more sensitive test than creatinine assay for detecting impaired renal function.     

Prospective evaluation of renal function by serum cystatin-C: comparison with three other parameters of glomerular filtration rate]

Cystatin-C is a low-molecular-weight basic protein produced at a stable rate by all nucleated cells. It is freely filtered through the renal glomeruli and primarily catabolized in the proximal tubule cells. Since the serum cystatin-C concentration is not affected by muscle mass nor inflammation, it has been postulated to be an improved marker of glomerular filtration rate (GFR) compared with the serum creatinine level. To evaluate the clinical usefulness in terms of estimation of the glomerular filtration rate(GFR), we compared the serum cystatin-C concentration with other markers of GFR, such as serum levels of creatinine(SCr), alpha 1-microglobulin(alpha 1MG), and beta 2-microglobulin(beta 2MG). Their variations were analyzed based on 2-hour creatinine clearance (2hCCr) as a standard marker of GFR. The logarithmic value of serum cystatin-C level showed a stronger negative correlation(-0.959) with the logarithmic value of 2hCCr than that of other markers(-0.924, -0.942, -0.888; SCr, alpha 1MG, beta 2MG, respectively). Although beta 2MG showed the next strongest correlation with 2hCCr, it had a significantly lower sensitivity when detecting mild reduction of GFR. In addition, serum cystatin-C showed the greatest area under the curve of receiver-operating characteristic(ROC) of all GFR markers at both higher(90 ml/min.) and lower(70 ml/min.) cut-off value of 2hCCr. These data suggest that serum cystatin-C is useful for estimating GFR, even if the reduction of GFR is very mild.     

Rapid and accurate assessment of glomerular filtration rate in patients with renal transplants using serum cystatin C.

BACKGROUND: Assessment of renal function in patients with renal transplants is of great importance. Various studies have reported cystatin C as an easily and rapidly assessable marker that can be used for accurate information on renal function impairment. To date, no study is available to define the role of cystatin C in patients with renal transplants. METHODS: Thirty steady-state patients (50% male/50% female) with status post-kidney transplantation were studied. To assess renal function, cystatin C, creatinine clearance, serum creatinine, beta2-microglobulin (beta2M), and [125I]iothalamate clearance were determined. Correlations and non-parametric ROC curves for accuracy, using a cut-off glomerular filtration rate (GFR) of 60 ml/min, were obtained for the different markers allowing for calculations of positive predictive values (PPV), positive likelihood ratios (PLR), specificity and sensitivity, respectively. Further, to evaluate the usefulness of these markers for monitoring, intraindividual coefficients of variation (CVs) for cystatin C and creatinine measurements were compared in 85 renal transplant patients. Measurements consisted of at least six pairs of results, which were obtained at different time points during routine follow-up. RESULTS: Cystatin C correlated best with GFR (r=0.83), whereas serum creatinine (r=0.67), creatinine clearance (r=0.57) and beta2M (r=0.58) all had lower correlation coefficients. The diagnostic accuracy of cystatin C was significantly better than serum creatinine (P=0.025), but did not differ significantly from creatinine clearance (P=0.76) and beta2M (P=0.43). At a cut-off of 1.64 mg/l, cystatin C has a PPV of 93%, PLR of 6.4, specificity 89% and sensitivity 70%, respectively. For beta2M, PPV 83%, PLR 1.7, specificity 67% and sensitivity 75% was seen at a cut-off of 3.57 mg/l. Accordingly, at a cut-off of 125 micromol/l for serum creatinine, a PPV 76%, PLR 1.4, specificity 44% and sensitivity 80% was revealed. Finally, at a cut-off of 66 ml/min/1.73 m2 for creatinine clearance, the following characteristics were found: PPV 94%, PLR 7.7, specificity 89% and sensitivity 85%. The intraindividual variation of creatinine was significantly lower than that of cystatin C (P<0.001). With increasing concentrations, their ratios of CV tended towards a value of 1, demonstrating identical variability at low GFR. CONCLUSION: Together, our data show that in patients with renal transplants, cystatin C, in terms of PPV and PLR, has a similar diagnostic value as creatinine clearance. However, it is superior to serum determinations of creatinine and beta2M. The intraindividual variation of cystatin C is greater than that of creatinine. This might be due to the better ability of cystatin C to reflect temporary changes especially in mildly impaired GFR, most critical for early detection of rejection and other function impairment. Thus, cystatin C allows for rapid and accurate assessment of renal function (GFR) in renal transplants and is clearly superior to the commonly used serum creatinine.     

Human alpha 1-microglobulin and its relationship to renal function

To evaluate the clinical usefulness in terms of estimation for glomerular filtration rate (GFR), we determined the levels of alpha 1-microglobulin (alpha 1m) in the serum and urine of patients with various renal diseases and compared with those of beta 2-microglobulin (beta 2m) and creatinine. Serum and urinary alpha 1m levels were measured by using single-radial immunodiffusion method. 24-hour creatinine clearance (Ccr) was used as a indicator of GFR. There was a significant positive correlation between serum alpha 1m and creatinine levels (r = 0.75, p less than 0.001). Serum alpha 1m, beta 2m and creatinine inversely correlated and logarithmically correlated to Ccr as shown in the following equations: log alpha 1m = 2.30 - 0.42 X log Ccr (r = -0.74); log beta 2m = 2.06 - 0.91 X log Ccr (r = -0.92); log creatinine = 1.57 - 0.78 X log Ccr (r = -0.94). Both correlation coefficient and regression coefficient for alpha 1m were rather poor compared to those for beta 2m and creatinine. However, alpha 1m levels started to increase over normal range when Ccr fell below 80 liters/day, while beta 2m and creatinine remained within normal ranges. The daily urinary excretion of alpha 1m was increased in the patients whose Ccr was within normal limits compared to that of healthy control subjects (15.2 +/- 3.2 mg/day, n = 19, vs. 5.7 +/- 0.7, n = 7, p less than 0.001). Fractional clearance of alpha 1m increased proportionally to the decrease of Ccr. These data suggest that combined measurements of alpha 1m in the serum and urine seem to be useful to estimate GFR, especially to detect the mild reduction of CFR.     

Assessment of tumor-associated trypsin inhibitor (TATI) as a marker of renal function

BACKGROUND: Low molecular weight (LMW) proteins have been proposed for renal function assessment. This study aimed to ascertain the usefulness of tumor-associated trypsin inhibitor (TATI), a LMW protein (6.200 d), as a glomerular filtration rate (GFR) marker. The results were compared with those of beta2-microglobulin and of creatinine (Cr). METHODS: Renal handling of TATI labelled with 125I was first studied in rats. Then, in 198 patients, serum TATI levels and GFR (99mTc-DTPA clearance, bladder cumulative method) were determined. To evaluate urine excretion, the fractional TATI clearance was determined in 63 patients. RESULTS: In rats, total body scan showed a large amount of radioactivity in the kidneys, but not in other organs. The duration of radioactivity demonstrated a peak-time of 11 min. In human beings, the relationship between TATI and GFR was similar to that of beta2-microglobulin and Cr. The increase in TATI with declining renal function was statistically significant, vs. patients with GFR > 100 mL/min, already in the group with GFR 80-100 mL/min (p < 0.05, Bonferroni-Dunn test). The beta2-microglobulin increase was significant in the group with GFR 60-80 mL/min and of Cr in the group with GFR 40-60 mL/min. In patients with renal failure (GFR < 20 mL/min) TATI increased, vs. patients with GFR > 100 mL/min, 13x, beta2-microglobulin 8x and Cr 5x. Urinary excretion of TATI, expressed as fractional clearance, was very low increasing when GFR fell < 40 mL/min. CONCLUSIONS: The kidney plays an important role in the handling of TATI. When GFR fell, the increase in blood levels of TATI was sooner and higher than that of beta2-microglobulin and CR. Consequently, TATI can be added to the group of renal function markers.     

Studies on serum and urinary alpha 1-microglobulin levels as parameter of the renal function--renal function observed after CDDP administration

To evaluate the clinical usefulness of alpha 1-microglobulin (alpha 1-MG) as parameter of renal function, we determined the levels of alpha 1-MG in the serum and urine of patients who had no malignant tumors, and compared them with the levels of beta 2-microglobulin (beta 2-MG), serum creatinine, urinary N-acetyl-beta-glucosaminidase (NAG) and 24-hour creatinine clearance (24 Ccr). There were significant positive correlations between alpha 1-MG in the serum and urine, and those of beta 2-MG levels. Serum alpha 1-MG and 24 Ccr were inversely correlated. Combined measurements of alpha 1-MG in the serum and urine seemed to be useful to estimate glomerular and tubular renal functions. The renal function in 8 patients with advanced urogenital cancers treated with cis-diammine-dichloroplatinum (CDDP) was examined by measuring 24 Ccr, alpha 1-MG, and beta 2-MG in serum and urine and urinary NAG. Determination of urinary alpha 1-MG was useful for early detection of tubular damage after CDDP administration.     

Assessment of renal function in renal transplant patients using cystatin C. A comparison to other renal function markers and estimates

To date, little evidence is available to define the role of cystatin C in patients with renal transplants. Thus, to assess, whether cystatin C (CysC) provides better information on renal function than other markers, CysC, creatinine clearance (CrCl), serum creatinine (SCr), beta2-microglobulin (beta2-M), and 125I-Iothalamate clearance were determined in 30 patients. Correlation and ROC curves were obtained and characteristics like sensitivity and specificity were calculated. Further, to evaluate the usefulness of these markers for monitoring, intraindividual coefficients of variation for CysC and SCr measurements were compared in 85 renal transplant patients. CysC correlated best with GFR, whereas SCr, CrCl and beta2-M all had lower correlation coefficients. CysC was superior to SCr, even when renal function equations of were used. The diagnostic accuracy of CysC was significantly better than SCr. but did not differ significantly from CrCl and beta2-M. Together, our data show that in patients with renal transplants, CysC has a similar diagnostic value as CrCl. However, it is superior to determinations of SCr. The intraindividual variation of CysC is significantly greater than that of SCr. This might be due to better ability of CysC to reflect temporary changes especially in mildly impaired GFR, most critical for early detection of rejection and other function impairment. In conclusion, CysC allows for easy and accurate assessment of renal function (GFR) in steady state renal transplant patients and is clearly superior to the commonly used serum creatinine.     

Usefulness of serum cystatin-C as a marker of the renal function: a comparative evaluation with beta 2-microglobulin, alpha 1-microglobulin and creatinine

We evaluated the usefulness of cystatin-C as a marker of renal function. Serum cystatin-C level was measured using latex agglutination tests in 885 patients with various forms of renal disease and 200 healthy subjects. In addition to cystatin-C, serum beta 2-microglobulin, alpha 1-microglobulin and serum creatinine (Scr) were measured concomitantly in the same sample. The serum cystatin-C level inversely correlated more closely with creatinine clearance (Ccr) (r = -0.90) than serum beta 2-microglobulin (r = -0.85), alpha 1-microglobulin (r = -0.74) and Scr (r = -0.78). In patients with mildly impaired renal function (defined as Ccr 71-90 ml/min), a significant increase in cystatin-C level was observed in 24% of patients, whereas elevated beta 2-microglobulin and Scr were seen in 8% and elevated alpha 1-microglobulin was seen in 17%. In patients with normal renal function (defined as Ccr > or = 100 ml/min), increased cystatin-C level was observed in 7% of patients, whereas beta 2-microglobulin was seen in 2%, Scr in 2% and alpha 1-microglobulin in 11%. These data suggest that cystatin-C is a better marker of glomerular filtration than beta 2-microglobulin, alpha 1-microglobulin and Scr. Moreover cystatin-C measurement offers improved clinical sensitivity as a screening test for early renal damage.     

Reappraisal of serum beta2-microglobulin as marker of GFR

INTRODUCTION: Beta 2 microglobulin (beta2M) is filtered by the glomeruli and reabsorbed by the proximal tubular cells where it is metabolized. Its plasma concentration increases with decreasing renal function. AIM: To compare serum creatinine (Cr) and serum beta2M as markers of GFR. PATIENTS AND METHODS: In 160 adult patients, with various kidney diseases and different GFR, serum Cr (autoanalyzer), serum beta2M (RIA) and GFR (bladder cumulative method using 99mTc-DTPA as glomerular tracer) were measured in the same day. RESULTS: A linear relationship was observed between In GFR and both In serum Cr (lnCr=3.112-0.716 lnGFR; r=0.92) and ln serum beta2M (lnbeta2M= 4.274-0.814 lnGFR; r = 0.90). With decreasing GFR the increase in serum beta2M was higher than that of serum Cr (see regression coefficients that are significantly different). The normal upper limit of serum Cr corresponds to a GFR 48.1 mL/min while that of serum beta2M to a GFR 65.0. With decreasing GFR the increase of serum beta2M occurs before than that of serum Cr. CONCLUSIONS: With declining renal function, serum beta2M increases more and before than serum Cr. Serum beta2M is a good endogenous marker of GFR, better than serum Cr.     

Acute changes in kidney function following extracorporeal shock wave lithotripsy for renal stones

Seventeen patients were subjected to analysis of various renal functional parameters before and after extracorporeal shock wave lithotripsy (ESWL) for renal stones. Thirteen patients were observed at 2 weeks and 3 months. Glomerular filtration rate (GFR) was not influenced by ESWL as based on unchanged serum levels of creatinine, beta 2-microglobulin and creatinine clearance. A significant increase in urinary excretion of beta 2-microglobulin, N-acetyl-beta-glucosaminidase and alkaline phosphatase, with return to pre-treatment values within 4 to 5 days, reflected transient disturbances in proximal tubular function. Urinary albumin excretion was increased 0-24 h after ESWL. No significant alterations were observed in plasma renin activity or serum aldosterone due to ESWL. Serum lactic dehydrogenase remained significantly increased for 2 weeks. In addition, significant changes in several blood and urine parameters were caused by immersion in water and intravenous infusions during treatment and were not specifically due to ESWL.     

Serum cystatin C as an index of renal function in kidney transplant patients

Management of renal transplant patients requires periodic measurement of renal function, which is usually assessed by measuring the glomerular filtration rate (GFR). The most commonly used marker for GFR is serum creatinine, although muscle wasting and tubular secretion may lead to overestimation of the actual GFR. Serum concentrations of the low-molecular-weight proteins, cystatin C and beta(2)-microglobulin (B(2)M), may afford useful markers to determine a reduced GFR. We investigated whether these molecules provide reliable indicators of renal function in 75 renal transplant patients. Cystatin C and B(2)M correlated significantly with creatinine (r =.648, P <.05 and r =.578, P <.05, respectively). Inverse serum creatinine was superior to inverse cystatin C and inverse B(2)M when renal function equations were used (r =.95, P <.05, according to MDRD; r =.87, P <.05, according to Cockroft-Gault). Receiver operating characteristic (ROC) analysis was performed to quantitate the accuracy of the different markers to detect reduced GFR using a cutoff value of 70 mL/min. No significant difference between the areas under the ROC curves comparing cystatin C and B(2)M was observed; however, serum creatinine demonstrated a significantly greater value than cystatin C (.981 vs.724, P =.001). We conclude that serum creatinine is a more efficacious marker than serum cystatin C to assess renal function.     

Estimation of renal function in diabetic nephropathy. Comparison of five methods

Plasma as well as renal clearance of 51Cr-EDTA, serum creatinine, plasma beta-2-microglobulin and endogenous creatinine clearance were compared and evaluated in patients with diabetic nephropathy and in control patients with renal disease of other origin. The difference between the plasma clearance and the renal clearance of 51Cr-EDTA, that is the extrarenal clearance, was found to be higher in diabetics than in control patients (7.0 vs. 3.5 ml/min; p less than 0.001). The serum creatinine correlated well with the glomerular filtration rate (GFR), but in the individual case the GFR was not at all predictable from serum creatinine. The plasma beta-2-microglobulin did not correlate better than serum creatinine to 51Cr-EDTA clearance, and did not permit an earlier diagnosis of renal insufficiency. Endogenous creatinine clearance overestimated GFR by 0-180%. Due to residual urine, the coefficient of variation was higher in diabetic patients than in controls, but the effect of this imperfection was reduced by using multiple collection periods. In conclusion, the renal clearance of 51Cr-EDTA was found to be preferable to the other methods.     

Fetal serum beta2-microglobulin predicts postnatal renal function in bilateral uropathies

BACKGROUND: Predicting postnatal renal function is crucial for the prenatal evaluation of fetal bilateral uropathies. Prenatal ultrasound can identify intrauterine terminal renal failure, but is not sensitive enough to identify those infants who would survive with an impaired renal function. Because it reflects fetal glomerular filtration, fetal serum beta2-microglobulin is a potential predictor of postnatal renal function. METHODS: Fetal serum beta2-microglobulin (beta2m) was assayed in 61 cases of bilateral or low obstructive uropathy, 74 controls, and 17 cases of bilateral renal agenesis, and was correlated with renal function. RESULTS: Fetal serum beta2m was 3.2 mg/L (range 1.5 to 4.7) in controls (N = 74), 9.5 mg/L (range 6.7 to 11.3) in bilateral renal agenesis (N = 17), 7 mg/L (5.1 to 10.6) in uropathy in which terminal renal failure resulted in termination of pregnancy (N = 26), and 3.7 mg/L (range 2.3 to 11.2) in live births with uropathy (N = 35). In the latter subgroup, fetal serum beta2m was significantly and positively correlated (r2 = 0.91) with postnatal serum creatinine. All survivors with a postnatal serum creatinine < or =50 micromol/L ha a fetal serum beta2m lower than 5 mg/L. Four of 6 survivors with a postnatal serum creatinine> 50 micromol/L had a fetal serum beta2m greater than 5 mg/L. CONCLUSION: Fetal serum beta2-microglobulin is a marker for renal function and predicts postnatal serum creatinine in bilateral or low fetal obstructive uropathy.     

Beta 2-microglobulin levels in patients with renal insufficiency

beta 2-microglobulin (beta 2M) has been implicated in the pathogenesis of amyloidosis in long-term dialysis patients. beta 2M levels were measured in patients with chronic renal failure: before and after conventional hemodialysis in 30, before and after high-flux (HF) hemodialysis in 35, and during the first hemodialysis treatment in five patients, as well as in the serum and peritoneal fluid of 13 patients who were receiving continuous ambulatory peritoneal dialysis (CAPD) and in the serum and urine of three patients who had received kidney transplants. Dialysis patients had markedly elevated beta 2M levels; prehemodialysis values were not significantly different for patients receiving conventional v HF hemodialysis. Most of these patients were functionally anephric, and the beta 2M levels did not correlate with age, sex, or time on dialysis. In patients receiving conventional hemodialysis using cellulose acetate membrane, beta 2M levels increased 25.4% after hemodialysis, whereas in patients receiving HF hemodialysis using polysulfone membrane, beta 2M levels decreased significantly (43.0%) after hemodialysis. End-stage renal disease patients dialyzed for the first time had beta 2M values significantly lower than the other two groups because of residual glomerular filtration rate (GFR). CAPD patients also had lower values because they had an estimated loss of 80.4 mg/d of beta 2M in the dialysate fluid. In patients with chronic renal failure, beta 2M levels paralleled the increase in serum creatinine. Patients who received kidney transplants had a dramatic decrease in beta 2M levels that correlated with improvement in GFR. beta 2M correlated with the residual GFR, and its removal was membrane-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)     

Time course of serial cystatin C levels in comparison with serum creatinine after application of radiocontrast media

BACKGROUND: The delayed increase of creatinine after radiocontrast application is a potential reason for overlooking radiocontrast nephrotoxicity. Cystatin C may be more useful to rapidly assess a decrease in glomerular filtration rate (GFR). We compared cystatin C and creatinine to examine their kinetics after application of radiocontrast media. PATIENTS AND METHODS: Forty-one patients (60.8 +/- 8.8 years, 68% males) with normal to subnormal GFR scheduled for coronary angiography (27% with angioplasty), were studied for serum cystatin C and creatinine levels before, 5 h, 24 h and 48 h after angiography. Furthermore, alpha1-microglobulin was checked for evidence of tubular damage. RESULTS: At 5 hours after angiography, there was no significant change compared to baseline in either serum creatinine nor cystatin C. In comparison with the value immediately before coronary angiography, the increase of cystatin C achieved a maximum at 24 h after the application of the contrast agent (+7.2%). Within 48 h, cystatin C decreased to the level before angiography. Serum creatinine increased at 24 h (+7.7%) and continued to increase at 48 h (+11.3%). CONCLUSION: Cystatin C increases earlier after radiocontrast application compared with creatinine. Therefore, cystatin C needs to be investigated as a potential early marker for nephrotoxicity, especially in the upcoming setting of short-time hospitalizations for coronary angiographies and interventions. Thus, further studies in patients with renal failure undergoing radiocontrast application are warranted to assess the usefulness of cystatin C in respect of an earlier detection of radiocontrast nephrotoxicity.     

Diagnostic sensitivity of serum cystatin for impaired glomerular filtration rate

Recently, the reciprocal of cystatin C (Cys-C), a non-glycosylated 13-kilodalton protein that is produced by all investigated nucleated cells, was found to correlate closely with glomerular filtration rate (GFR). In order to determine the diagnostic validity in children for the detection of impaired GFR, venous blood samples from 381 children (aged 1.7–18 years) with various renal pathology referred for ⁵¹Cr-EDTA clearance investigations were obtained for measurement of Cys-C as well as β₂-microglobulin (β2-MG) and serum creatinine. Two hundred and sixteen children with clearance values >90 ml/min per 1.73 m² constituted a control group, with a normal GFR. In the control group, Cys-C values were normally distributed with a mean of 0.94±0.27 mg/l and an upper reference limit (97.5th percentile) of 1.47 mg/l. In all children, there was a positive correlation between ⁵¹Cr-EDTA clearance and the reciprocal of Cys-C (r=0.64, P<0.0001), β₂-MG (r=0.59, P<0.0001), creatinine (r=0.55, P<0.0001), and the height/creatinine ratio (r=0.73, P<0.0001). Receiver-operating characteristics analysis showed that there were no significant differences between these three parameters for discriminating between patients with normal and reduced GFR, although there was a tendency towards the best diagnostic sensitivity of the GFR estimate according to the Schwartz formula. We conclude that for the detection of mildly impaired GFR, a full clearance study cannot be replaced by measurement of serum Cys-C or β2-MG concentrations. Received: 15 June 1998 / Revised: 22 September 1998 / Accepted: 23 September 1998     

Serum beta 2-microglobulin in spinal cord injury patients--its efficacy as a screening test of renal function

We evaluated the reliability of serum beta 2-microglobulin (beta 2-MG) in comparison with serum creatinine, blood urea nitrogen and creatinine clearance in 164 patients with spinal cord injury. The value of serum beta 2-MG demonstrated the highest correlation coefficient (r = -0.927) in relation to creatinine clearance. The beta 2-MG value reflected the severity of hydronephrosis on excretory urography, with very few false negative values. The value of beta 2-MG is concluded to be one of the best screening tests in evaluating renal function in spinal cord injury patients.     

Renal handling of beta-2-microglobulin in renal disorders: with special reference to hepatorenal syndrome

A study of serum beta 2-microglobulin and urinary beta 2-microglobulin in patients with liver and/or kidney disease was done to determine if such information is of diagnostic help. Serum concentrations and beta 2M/Cr clearance ratios are higher in patients with primary tubular disorders than in those with glomerular diseases, a finding unaltered by hepatic disease. These data suggest either an increased production or decreased tubular degradation of beta 2M, independent of the glomerular filtration rate (GFR), in primary tubular disorders. The marked increase in urinary beta 2-microglobulin that followed insertion of the peritoneal-jugular shunt is evidence that this procedure resulted in improvement of the GFR, in previously underperfused nephrons.     

The beta2-microglobulin/cystatin C ratio--a potential marker of post-transplant lymphoproliferative disease

BACKGROUND: As a consequence of more intensified immunosuppression, post-transplant lymphoproliferative disease (PTLD) is increasingly observed in patients after solid-organ transplantation. Beta2-microglobulin, a low-molecular weight protein (MW 11.8 kDa), is produced by all nucleated cells as part of the HLA complex. Its serum concentration is directly correlated with prognosis in patients with lymphatic neoplasms. Like other low-molecular weight proteins, beta2-microglobulin is eliminated by glomerular filtration. This complicates its use as a tumor marker in renal insufficiency. Cystatin C, a low-molecular weight protein of 13.3 kDa, is a new marker of kidney function largely unaffected by extrarenal disease. We, therefore, sought to assess the potential of the beta2-microglobulin/cystatin C ratio (beta2M/Cys) as a marker of lymphoproliferation. PATIENTS AND METHODS: Beta2M/Cys was determined by particle-enhanced immunonephelometry in sera from 132 children with different degrees of renal insufficiency, 5 of whom had lymphoproliferative disease. Renal function was assessed using the Schwartz formula. RESULTS: Beta2M/Cys was constant between 1.2 and 2.4 mg/mg for Schwartz GFR > or = 40 ml/min x 1.73 m2. With lower GFR, beta2M/Cys rose progressively, maximum values being found in the hemodialysis patients (4.85-11.73). Healthy renal transplant recipients had beta2M/Cys comparable to controls. With acute lymphoproliferative disease, all but one patient had significantly elevated beta2M/Cys between 2.68 and 3.68 mg/mg, which returned to normal in remission (1.67-2.35 mg/mg). The sensitivity of a beta2M/Cys ratio > 2.4 mg/mg for the detection of PTLD was 80%, the specificity 100%, positive predictive value 100%, negative predictive value 90%. CONCLUSION: The beta2-microglobulin/cystatin C ratio is a promising parameter of lymphoproliferation in patients with normal or mildly impaired renal function.     

血清半胱氨酸蛋白酶抑制剂C在慢性肾脏病肾功能中的应用

目的以放射性核素99Tcm-DTPA清除率测定的肾小球滤过率为标准,比较血清胱抑素C和肌酐评价GFR的准确性和特异性。方法以99Tcm-DTPA清除率法测定38例慢性肾脏病患者GFR,并同时测定Scr浓度和Cys-C浓度。运用ROC分析曲线分析SCysC和Scr评价GFR的准确性、敏感性和特异性。结果 38例慢性肾脏病患者SCys-C浓度为（1.67±0.25）mg/L,Scr浓度为（198.77±98.01）μmol/L,GFR为（50.55±35.62）mL/（min.1.73m2）。SCys-C与Scr、GFR呈明显负相关,相关系数分别为-0.74和-0.6（1P〈0.05）;分别以GFR〈90mL（/min.1.73m2）、GFR〈60mL（/min.1.73m2）和GFR〈30mL/（min.1.73m2）为界点,Cys-C的Roc曲线下面积（AUC）分别为0.822、0.857、0.920;Scr的Roc曲线下面积分别为0.775、0.801和0.922。结论在慢性肾病患者中与Scr比较,Cys-C是评价GFR的一个良好内源性指标,且能更好地反映GFR的早期改变。