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Introduction: Our objective was to compare the bone and renal effects among HIV-infected patients randomized to abacavir or tenofovir-based combination anti-retroviral therapy., Methods: In an open-label randomized trial, HIV-infected patients were randomized to switch from zidovudine/lamivudine (AZT/3TC) to abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC). We measured bone mass density (BMD) and bone turnover biomarkers (osteocalcin, osteocalcin, procollagen type 1 N-terminal propeptide (P1NP), alkaline phosphatase, type I collagen cross-linked C-telopeptide (CTx), and osteoprotegerin). We assessed renal function by estimated creatinine clearance, plasma cystatin C, and urinary levels of creatinine, albumin, cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL). The changes from baseline in BMD and renal and bone biomarkers were compared across study arms., Results: Of 40 included patients, 35 completed 48 weeks of randomized therapy and follow up. BMD was measured in 33, 26, and 27 patients at baseline, week 24, and week 48, respectively. In TDF/FTC-treated patients we observed significant reductions from baseline in hip and lumbar spine BMD at week 24 (-1.8% and -2.5%) and week 48 (-2.1% and -2.1%), whereas BMD was stable in patients in the ABC/3TC arm. The changes from baseline in BMD were significantly different between study arms. All bone turnover biomarkers except osteoprotegerin increased in the TDF/FTC arm compared with the ABC/3TC arm, but early changes did not predict subsequent loss of BMD. Renal function parameters were similar between study arms although a small increase in NGAL was detected among TDF-treated patients., Conclusion: Switching to TDF/FTC-based therapy led to decreases in BMD and increases in bone turnover markers compared with ABC/3TC-based treatment. No major difference in renal function was observed., Trial Registration: Clinicaltrials.gov NCT00647244.

Objective: To investigate the relationship between serum cystatin C, serum creatinine, and (51)Cr-EDTA-clearance in patients with spinal cord injury., Setting: The Spinal Cord Unit, Viborg-Kjellerup County Hospital., Methods: Twenty-four men and seven women aged 20.3 to 68.0 years with motor complete spinal cord injury (ASIA A or B) were included. Serum cystatin C was measured by an automated particle-enhanced nephelometric immunoassay (Dade Behring), serum creatinine by an enzymatic method (Vitros 950), and (51)Cr-EDTA-clearance by a multiple plasma sample method., Results: A linear relationship was found between (51)Cr-EDTA-clearance and the reciprocal values of cystatin C and creatinine. The correlation coefficient between (51)Cr-EDTA-clearance and 1/cystatin C was 0.72 compared to the correlation coefficient between (51)Cr-EDTA-clearance and 1/creatinine being 0.26. Comparison of the area under the curves in the non-parametric receiver operating characteristics (ROC) plots for serum cystatin C (area under the curve (AUC)=0.912; SE=0.065), and serum creatinine (AUC=0.507; SE=0.115) revealed significant differences (P-values=0.0005)., Conclusion: In patients with spinal cord injury serum cystatin C is a better marker of the renal function compared to serum creatinine.

Cystatin C is a low molecular weight protein and the plasma level of cystatin C is mainly determined by glomerular filtration, making cystatin C an endogenous marker of glomerular filtration rate. The aim of the study was to elucidate the applicability of plasma cystatin C as a marker of renal function in patients with liver cirrhosis. Serum cystatin C and creatinine concentrations were compared with creatinine clearance. Thirty-six patients (14 females and 22 males aged between 33 and 81 years) with liver cirrhosis with normal to severely impaired kidney function were included. Plasma cystatin C was measured by an automated particle-enhanced nephelometric immunoassay (Dade Behring Diagnostics) and plasma creatinine by an enzymatic method. Plasma levels of cystatin C and creatinine were found to increase with decreasing values of creatinine clearance. The reciprocal values of cystatin C and creatinine were compared with those for creatinine clearance revealing an r2 of 0.37 and 0.18, respectively. Comparison of the areas under the curves (AUC) of the non-parametric receiver-operating characteristic plots for plasma cystatin C (AUC=0.7364; SE=0.0929) and plasma creatinine (AUC=0.6309: SF=0.1028) revealed a significant difference between plasma cystatin C and plasma levels of creatinine (p-value=0.03). The results demonstrate that the diagnostic accuracy of plasma cystatin C was better than plasma creatinine in identifying liver cirrhotic patients with reduced glomerular filtration rate.

Background: Cystatin C is a proteinase inhibitor with a low molecular weight. The serum levels of cystatin C are mainly dependent on glomerular filtration rate (GFR) making cystatin C an endogenous parameter of GFR. The aim of the study was to elucidate the applicability of serum cystatin C as a parameter of GFR in patients with normal to moderately impaired kidney function and to estimate a reference interval for serum cystatin C., Patients and Methods: Forty-six patients (25 males and 21 females) aged 22 to 83 years with various kidney diseases and 250 blood donors (164 males and 86 females) aged 19 to 64 years were included. Cystatin C was measured by an automated particle-enhanced nephelometric immunoassay, serum creatinine by an enzymatic and by Jaffé method, urine creatinine by an enzymatic method, and GFR by 99mTc-DTPA clearance., Results: Serum levels ofcystatin C and creatinine showed increments with decreasing values of 99mTc-DTPA clearance and a linear relationship was found between 99mTc-DTPA clearance and l/serum cystatin C, l/serum creatinine (enzymatic method), and creatinine clearance. Comparison of the non-parametric receiver-operating characteristic (ROC) plots for serum cystatin C (area under the curve (AUC) = 0.996; SE = 0.005), serum creatinine (enzymatic method) (AUC = 0.899; SE = 0.044), serum creatinine (Jaffé method) (AUC = 0.870; SE = 0.051), measured creatinine clearance (AUC = 0.959; SE = 0.025), and estimated creatinine clearance (0.950; SE = 0.029) revealed significant differences for serum cystatin C and serum creatinine (enzymatic and Jaffé method) (p values: 0.03 and 0.01). No significant differences were demonstrated between serum cystatin C and measured and estimated creatinine clearance (p value: 0.14 and 0.12). The non-parametric reference interval for serum cystatin C was calculated to be 0.51-1.02 mg/l (median: 0.79 mg/l; range: 0.33 - 1.07 mg/l)., Conclusion: Serum cystatin C seems to be a better parameter of GFR than serum creatinine in adults with various types of kidney disease with normal to moderately impaired kidney function.

Since 1985, cystatin C has been suggested to be a marker of the renal function. Cystatin C is a proteinase inhibitor with a low molecular weight (M(r) = 13359). It is produced at a constant rate in all nucleated cells investigated to date, freely filtered in the renal glomeruli and reabsorbed and catabolised in the proximal tubules. The concentration of serum cystatin C is mainly determined by glomerular filtration, which makes cystatin C an endogenous marker of glomerular filtration rate (GFR). There are few data describing the influence of various factors on the production and elimination of cystatin C. Fully automated assays using particle-enhanced turbidimetry or particle-enhanced nephelometry are available and the assays are precise, rapid and usable in clinical routine practice. Reference intervals have been determined for cystatin C in adults and in children older than one year. It has been suggested that the same reference interval can be used in children older than one year and in adults without gender differences, on the assumption that the same method with the same standardisation is used. Several studies including adults and children with different renal diseases with various kidney function have suggested serum cystatin C to be a better marker of GFR than serum creatinine.

The protease inhibitor cystatin C is a non-glycosylated low molecular weight protein (Mr=13359) which is produced by all nucleated cells at a constant rate, freely filtered by the renal glomeruli, and catabolized in the tubuli. The aim of the study was to elucidate the applicability of serum cystatin C as a marker of glomerular filtration rate (GFR) in patients with various kidney diseases with a wide range of renal function and in dialysis patients. Seventy-six patients with various kidney diseases (aged 20 to 79 years) and 61 dialysis patients (aged 21 to 82 years) were included. Serum cystatin C was measured by automated particle-enhanced immunoturbidimetry, serum and urine creatinine by an enzymatic method, and GFR by 99mTc-DTPA-clearance using a single plasma sample method. Serum cystatin C in patients with various kidney diseases was 1.90+/-0.98 mg/L (mean+/-SD) and in dialysis patients 7.14+/-1.91 mg/L. In the non-dialysis patients a linear relationship was found between 99mTc-DTPA-clearance and 1/serum cystatin C (r=0.91, p-value<0.0001), 1/serum creatinine (r=0.89, p-value<0.0001), and creatinine-clearance (r=0.88, p-value<0.0001). Comparison of the non-parametric ROC plots for serum cystatin C (area under the curve (AUC)=0.9665; SE=0.0169), serum creatinine (AUC=0.9554; SE=0.0205), and creatinine-clearance (AUC=0.9731; SE=0.0160) revealed no significant differences (p-values: 0.50, 0.78, and 0.49). In conclusion, cystatin C may be a likewise good marker of the GFR as serum creatinine and creatinine-clearance, cystatin C having the advantage being independent of gender and muscle mass.