Laurent Dinh

Estimating Glomerular Filtration Rate in Kidney Transplantation: A Comparison between Serum Creatinine and Cystatin C–Based Methods

Accurate measurement of GFR is critical for the evaluation of new therapies and the care of renal transplant recipients. Although not accurate in renal transplantation, GFR is often estimated using creatinine-based equations. Cystatin C is a marker of GFR that seems to be more accurate than creatinine. Equations to predict GFR based on the serum cystatin C concentration have been developed, but their accuracy in transplantation is unknown. GFR was estimated using four equations (Filler, Le Bricon, Larsson, and Hoek) that are based on serum cystatin C and seven equations that are based on serum creatinine in 117 adult renal transplant recipients. GFR was measured using radiolabeled diethylenetriaminepentaacetic acid (99mTc-DTPA), and the bias, precision, and accuracy of each equation were determined. The mean (99m)Tc-DTPA GFR was 58 +/- 23 ml/min per 1.73 m(2). The cystatin C-based equations of Filler and Le Bricon had the lowest bias (-1.7 and -3.8 ml/min per 1.73 m2), greatest precision (11.4 and 11.8 ml/min per 1.73 m2), and highest accuracy (87 and 89% within 30% of measured GFR, respectively). The cystatin C equations remained accurate even when the measured GFR was >60 ml/min per 1.73 m2. The creatinine-based equations were not as accurate, with only 53 to 80% of estimates within 30% of measured GFR. Cystatin C-based equations are more accurate at predicting GFR in renal transplant recipients than traditional creatinine-based equations. Further prospective studies with repetitive measurement of cystatin C are needed to determine whether cystatin C-based estimates of GFR will be sufficiently accurate to monitor long-term allograft function.

Estimating GFR using serum beta trace protein: accuracy and validation in kidney transplant and pediatric populations

The limitations of estimates of glomerular filtration rate (GFR) based only on serum creatinine measurements have spurred an interest in more sensitive markers of GFR. Beta-trace protein (BTP), a low-molecular-weight glycoprotein freely filtered through the glomerular basement membrane and with minimal non-renal elimination, may be such a marker. We have recently derived two GFR estimation equations based on BTP. To validate these equations, we measured BTP and the plasma clearance of (99)mTc-DTPA in 92 adult kidney transplant recipients and 54 pediatric patients with impaired kidney function. GFR was estimated using the serum creatinine-based Modification of Diet in Renal Disease (MDRD) Study equation for adults, the Schwartz and updated Schwartz equations in children, and 4 novel BTP-derived equations (our 2 equations and 2 proposed by Poge). In adults, our BTP-based equations had low median bias and high accuracy such that 89-90% of estimates were within 30% of measured GFR. In children, the median bias of our 2 equations was low and accuracy was high such that 78-83% of estimates were within 30% of measured GFR. These results were an improvement compared to the MDRD and Schwartz equations, both of which had high median bias and reduced accuracy. The updated Schwartz equation also performed well.

Effect of Clinical Variables and Immunosuppression on Serum Cystatin C and Beta-Trace Protein in Kidney Transplant Recipients

BACKGROUND Cystatin C and beta-trace protein (BTP) are low-molecular-weight proteins that have generated interest as alternative endogenous markers of glomerular filtration rate (GFR). Studies examining the effect of demographic, biometric, clinical, and biochemical variables on cystatin C levels have yielded conflicting results, perhaps because of the reliance on inferior methods of GFR determination. The aim of this study is to examine the independent effect of various clinical parameters on serum concentrations of creatinine, cystatin C, and BTP in kidney transplant recipients. STUDY DESIGN Cross-sectional study. SETTING & PARTICIPANTS 207 kidney transplant recipients with stable kidney function. PREDICTORS GFR, age, race, sex, body mass index, albumin level, proteinuria, smoking status, prednisone, and calcineurin inhibitor and mycophenolate mofetil use. OUTCOMES & MEASUREMENTS Multiple linear regression analysis was used to examine the relationship between predictor variables and cystatin C, BTP, and creatinine levels. GFR was measured by using technetium 99m-radiolabeled diethylenetriaminepentaacetic acid clearance. RESULTS After adjusting for GFR, cystatin C and BTP levels were significantly lower in women compared with men. Greater albumin concentration was associated with significantly lower cystatin C and BTP concentrations. There was a statistically significant, but clinically small, association between body mass index and cystatin C level, but no association between the other demographic variables or medications analyzed. LIMITATIONS Predominantly white population; results may not be applicable to other racial groups. CONCLUSION Important nonrenal factors can influence BTP and cystatin C concentrations and need to be considered when interpreting BTP and cystatin C values in kidney transplant patients.

Restoration of strength despite low stress and abnormal imaging after Achilles injury.

PURPOSE To determine the usefulness of clinical imaging in predicting the mechanical properties of rabbit Achilles tendons after acute injury. METHODS We created a 2 x 7-mm full-thickness central tendon defect in one Achilles tendon of healthy rabbits. Rabbits in groups of 10 were killed immediately and 4 and 8 wk after surgery (n = 30). We then performed magnetic resonance (MR) imaging, ultrasonography (US), bone mineral densitometry (BMD), and mechanical testing to failure using a dual-cryofixation assembly on experimental and contralateral tendons. The main outcome measures included tendon dimensions, optical density (OD) of T1-weighted, proton density (PD), and T2-weighted MR sequences, US focal abnormalities, BMD of the calcaneus, and stress and peak load to failure. RESULTS On MR imaging and US, all dimensions of the injured tendons after 2 wk and more were greater than those of the contralateral tendons (P < 0.05). The mean T1-weighted OD was greater at 4 wk (256 +/- 53) and 8 wk (184 +/- 24) than immediately after surgery (149 +/- 15). Mechanical stress was markedly lower in the experimental than in the contralateral tendons at both 4 wk (39 +/- 9 vs 77 +/- 16 N x mm(-2)) and 8 wk (58 +/- 6 vs 94 +/- 26 N x mm(-2); P < 0.05). Mean peak load to failure was significantly lower immediately after surgery (332 +/- 128 N) than at 4 and 8 wk (712 +/- 106 and 836 +/- 90 N, respectively). Both high T1-weighted OD (r = -0.73) and PD OD (r = -0.69) correlated with lower mechanical stress (P < 0.05). In the experimental tendons, higher T1-weighted OD correlated with lower peak load (r = -0.46; P < 0.05). CONCLUSIONS Normal peak loads 4 wk after injury were withstood by an enlarged tendon of lower stress. These findings support progressive physical loading 4 wk after an Achilles tendon injury. T1-weighted OD constituted a marker of tendon mechanical recovery.

A randomised controlled trial of cemented and cementless femoral components for metal-on-metal hip resurfacing: a bone mineral density study

The primary purpose of this study of metal-on-metal (MoM) hip resurfacing was to compare the effect of using a cementless or cemented femoral component on the subsequent bone mineral density (BMD) of the femoral neck. This was a single-centre, prospective, double-blinded control trial which randomised 120 patients (105 men and 15 women) with a mean age of 49.4 years (21 to 68) to receive either a cemented or cementless femoral component. Follow-up was to two years. Outcome measures included total and six-point region-of-interest BMD of the femoral neck, radiological measurements of acetabular inclination, neck-shaft and stem-shaft angles, and functional outcome scores including the Harris hip score, the Western Ontario and McMaster Universities Osteoarthritis Index and the University of California at Los Angeles activity scale. In total, 17 patients were lost to follow-up leaving 103 patients at two years. There were no revisions in the cementless group and three revisions (5%) in the cemented group (two because of hip pain and one for pseudotumour). The total BMD was significantly higher in the cementless group at six months (p < 0.001) and one year (p = 0.01) than in the cemented group, although there was a loss of statistical significance in the difference at two years (p = 0.155). All patient outcomes improved significantly: there were no significant differences between the two groups. The results show better preservation of femoral neck BMD with a cementless femoral component after two years of follow-up. Further investigation is needed to establish whether this translates into improved survivorship.

Peri-acetabular bone mineral density in total hip replacement

Objectives To quantify and compare peri-acetabular bone mineral density (BMD) between a monoblock acetabular component using a metal-on-metal (MoM) bearing and a modular titanium shell with a polyethylene (PE) insert. The secondary outcome was to measure patient-reported clinical function. Methods A total of 50 patients (25 per group) were randomised to MoM or metal-on-polyethlene (MoP). There were 27 women (11 MoM) and 23 men (14 MoM) with a mean age of 61.6 years (47.7 to 73.2). Measurements of peri-prosthetic acetabular and contralateral hip (covariate) BMD were performed at baseline and at one and two years’ follow-up. The Western Ontario and McMaster Universities osteoarthritis index (WOMAC), University of California, Los Angeles (UCLA) activity score, Harris hip score, and RAND-36 were also completed at these intervals. Results At two years, only zone 1 showed a loss in BMD (-2.5%) in MoM group compared with a gain in the MoP group (+2.2%). Zone 2 showed loss in both groups (-2.2% for MoM; -3.9% for MoP) and zones 3 and 4 a gain in both groups (+0.1% for MoM; +3.3% for MoP). No other between-group differences were detected. When adjusting for BMD of the contralateral hip, no differences in BMD were observed. The only significant differences in functional scores at two years were higher UCLA activity (7.3 (sd 1.2) vs 6.1 (sd 1.5); p = 0.01) and RAND-36 physical function (82.1 (sd 13.0) vs 64.5 (sd 26.4); p = 0.02) for MoM bearings versus MoP. One revision was performed in the MoM group, for aseptic acetabular loosening at 11 months. Conclusions When controlling for systemic BMD, there were no significant differences between MoM and MoP groups in peri-acetabular BMD. However, increasing reports of adverse tissue reactions with large head MoM THR have restricted the use of the monoblock acetabular component to resurfacing only.