Creatinine Variables Research Articles

Obesos diabéticos tipo 2 submetidos à derivação gástrica em Y-de-Roux: análise de resultados e influência nas complicações

About 90% of type 2 diabetic patients are obese or overweight. The obvious clinical improvement observed with surgeries, such as Roux-en-Y gastric bypass, has opened space for research by different factors than only weight loss, as responsible for the return to euglycemia and reduction of medication use. To evaluate the efficacy and safety of surgical treatment of diabetes in obese patients with BMI above 35 kg/m2 underwent to gastric bypass, for the control of diabetes, weight loss, improvement of laboratory findings and complications of diabetes. The protocol was implemented in three stages: initial, after losing 10% of weight, and after a year. Seventeen patients who have lost weight in 10% were included in the surgical protocol. From the total, 11.8% continued needing medication (p <0.001). The time for weight loss was a month with significant reduction in fasting glucose, HOMA-IR index, insulin, HbA1c, hemoglobin, AST, urea and C-peptide and there was no variation in hematocrit, albumin, ALT and creatinine. With a year of monitoring, the surgical group showed a significant difference in weight, BMI, blood glucose, HbA1c, C-peptide, insulin and HOMA-IR. The percentage of patients with neuropathy (31.3%) was lower than the number of cases at baseline (52.9%) (p> 0.05). Gastric bypass with Roux-en-Y derivation is a safe procedure, with good results in control of diabetes type 2 in obese patients with BMI above 35 kg/m2.

Variation in Serum Creatinine Level Is Correlated to Risk of Type 2 Diabetes

BackgroundSkeletal muscle is well established as a major target organ of insulin action, and is associated with the pathogenesis of type 2 diabetes. Therefore, we attempted to determine whether a variation in serum creatinine is related to the development of type 2 diabetes and other risk factors for diabetes.MethodsA total of 2,676 nondiabetic subjects with stable and normal renal function (estimated glomerular filtration rate >60 mL/min/1.73 m2) were followed up for approximately 4.5 years. New onset diabetes was defined as fasting plasma glucose (FPG) ≥7.0 mmol/L, glycated hemoglobin (HbA1c) ≥6.5%, or subjects taking antidiabetic agents. Variation of serum creatinine (ΔCre) was defined as a difference between follow-up and baseline creatinine. In subgroup analysis, body composition was examined by bioelectric impedance analysis method.ResultsA total of 106 subjects were diagnosed with new-onset diabetes during the follow-up period. Baseline serum creatinine was not different between the new-onset diabetes and no diabetes groups. Negative ΔCre (ΔCre <0) showed an association with increased risk of type 2 diabetes after adjusting for age, sex, body mass index, systolic blood pressure, FPG, HbA1c, triglyceride, high density lipoprotein cholesterol, and γ-glutamyl transpeptidase (odds ratio, 1.885; 95% confidence interval, 1.127 to 3.153). Serum creatinine level demonstrated positive correlation with muscle mass and negative correlation with percentage of body fat in body composition analysis.ConclusionSerum creatinine reflected body muscle mass and the decrease of serum creatinine might be regarded as a risk factor for type 2 diabetes.

A prospective comparison of surgical and pathological outcomes obtained after robot‐assisted or pure laparoscopic partial nephrectomy in moderate to complex renal tumours: results from a French multicentre collaborative study

To prospectively compare the surgical and pathological outcomes obtained with robot-assisted laparoscopic partial nephrectomy (RAPN) or laparoscopic PN (LPN) for renal cell carcinoma in a multicentre cohort. Between 2007 and 2011, 265 nephron-sparing surgeries were performed at six French urology departments. The patients underwent either RAPN (n = 220) or LPN (n = 45) procedures. The operative data included operative duration, warm ischaemia time (WIT) and estimated blood loss (EBL). The postoperative outcomes included length of stay (LOS), creatinine variation (Modification of Diet in Renal Disease group), Clavien complications and pathological results. The complexity of the renal tumour was classified using the R.E.N.A.L. nephrometry scoring system. Student's t-test and chi-squared tests were used to compare variables. The median follow-ups for the RAPN and LPN groups were 7 and 18 months, respectively (P < 0.001). Age and American Society of Anesthesiology score were significantly higher in the LPN group (P = 0.02 and P = 0.004, respectively). These variables were lower in the RAPN group: WIT [mean (sd) 20.4 (9.7) vs 24.3 (15.2) min; P = 0.03], operative duration [mean (sd) 168.1 (55.5) vs 199.7 (51.2) min; P < 0.001], operating room occupation time [mean (sd) 248.3 (66.7) vs 278.2 (71.3) min; P = 0.008], EBL [mean (sd) 244.8 (365.4) vs 268.3 (244.9) mL; P = 0.01], use of haemostatic agents [used in 78% of RAPNs and 100% of LPNs; P < 0.001] and LOS [mean (sd) 5.5 (4.3) vs 6.8 (3.2) days; P = 0.05). There were no significant differences between pre- and postoperative creatinine levels, pathology report or complication rates between the groups. The main limitation was due to the study's non-randomised design. RAPN is not inferior to pure LPN for perioperative outcomes (i.e. EBL, operative duration, WIT, LOS). Only a randomised study with a longer follow-up can now provide further insight into oncological outcomes.

Safety of meglumine gadoterate (Gd-DOTA)-enhanced MRI compared to unenhanced MRI in patients with chronic kidney disease (RESCUE study)

ObjectiveTo prospectively compare the renal safety of meglumine gadoterate (Gd-DOTA)-enhanced magnetic resonance imaging (MRI) to a control group (unenhanced MRI) in high-risk patients.MethodsPatients with chronic kidney disease (CKD) scheduled for MRI procedures were screened. The primary endpoint was the percentage of patients with an elevation of serum creatinine levels, measured 72 ± 24 h after the MRI procedure, by at least 25 % or 44.2 μmol/l (0.5 mg/dl) from baseline. A non-inferiority margin of the between-group difference was set at −15 % for statistical analysis of the primary endpoint. Main secondary endpoints were the variation in serum creatinine and eGFR values between baseline and 72 ± 24 h after MRI and the percentage of patients with a decrease in eGFR of at least 25 % from baseline. Patients were screened for signs of nephrogenic systemic fibrosis (NSF) at 3-month follow-up.ResultsAmong the 114 evaluable patients, one (1.4 %) in the Gd-DOTA-MRI group and none in the control group met the criteria of the primary endpoint [Δ = −1.4 %, 95%CI = (−7.9 %; 6.7 %)]. Non-inferiority was therefore demonstrated (P = 0.001). No clinically significant differences were observed between groups for the secondary endpoints. No serious safety events (including NSF) were noted.ConclusionMeglumine gadoterate did not affect renal function and was a safe contrast agent in patients with CKD.Key points • Contrast-induced nephropathy (CIN) is a potential problem following gadolinium administration for MRI. • Meglumine gadoterate (Gd-DOTA) appears safe, even in patients with chronic kidney disease. • Gd-DOTA only caused a temporary creatinine level increase in 1/70 such patients. • No case or sign of NSF was detected at 3-month follow-up.

500P - The Leeds Formula: A New, More Accurate and Widely Applicable Formula for Estimating Renal Function, Accounting for Variability in Creatinine Assay Measurement

ABSTRACT Introduction Many formulae are used to estimate renal function, but none account for the significant variation in creatinine (Cr) measurement between the 26 assays currently used in the UK. The UK National External Quality Assessment Service has published assay-specific Cr adjustors, but the calculated 'standardised Cr' (SCr) dangerously overestimates GFR when used in formulae such as Cockroft and Gault (CG r2 of 0.74) more accurately than alternative established GFR formulae e.g. C&G and W formulae (r2 0.4-0.6) . Prospective validation on a separate cohort of oncology patients (496 patients between 1/4/09 and 31/3/11) validated the Leeds formula with an r2 of 0.71 for correlation with iGFR. Conclusions The Leeds formula uses readily available clinical information to estimate GFR more precisely than existing formulae and has the advantage of being applicable to Cr results from any laboratory provided the assay type is known. Many oncologists do not appreciate the resultant effect of inter-Cr assay variability on estimated renal function (GFR) and hence chemotherapy dosing. Disclosure All authors have declared no conflicts of interest.

Laparoendoscopic Single-site Partial Nephrectomy Without Ischemia for Very Small, Exophytic Renal Masses: Surgical Details and Functional Outcomes

BackgroundLaparoendoscopic single-site surgery (LESS) has emerged as a natural progression from standard laparoscopy aiming to further minimize the morbidity of urologic procedures. ObjectiveTo describe our technique and report the surgical and functional outcomes of unclamped LESS partial nephrectomy (PN) in the treatment of small renal masses (SRMs). Design, setting, and participantsProspective evaluation of pre- and postoperative variables of patients undergoing the LESS-PN without ischemia between 2009 and 2012. The indications were single exophytic SRMs. Surgical procedureUnclamped LESS-PN was performed through a transperitoneal approach. A pararectal Hasson access technique was preferred. Single-port access was achieved via different single-port devices. A combination of straight and articulating laparoscopic instruments was used. The tumor was excised using bipolar scissors during normal renal perfusion. Hemostasis was achieved by bipolar electrocautery, parenchymal stitches, and hemostatic agents. Outcome measurements and statistical analysisDemographic, operative, postoperative, and pathologic outcomes data were recorded and analyzed. Results and limitationsA total of 21 LESS-PN were performed (operative time: 111±41min; blood loss: 196±195ml: tumor size: 2.0±0.3cm). Neither conversion to open surgery nor transfusions occurred. Three patients required conversion to standard laparoscopy. Postoperatively, three complications (Clavien grades 2, 3a, and 4) were recorded. Pathologic examination revealed 14 clear cell carcinomas, four renal cysts, two oncocytomas, and one angiomyolipoma. Hospital stay was 4.4±1.9 d. At the last follow-up (mean: 17±11.5 mo), no port-site, local, or distant recurrences were detected. No significant variation in serum creatinine and estimated glomerular filtration rate was observed. Subjective scar evaluation indicated 66% of patients were very satisfied/enthusiastic. Study limitations include the small sample size, the lack of a control group, the short follow-up period, and the arbitrary measure of patient's scar perception. ConclusionsUnclamped LESS-PN for selected SRMs is a safe and feasible procedure providing favorable postoperative outcomes and ensuring high levels of subjective, cosmetic satisfaction.

Prevention of renal ischemia/reperfusion injury in rats using acetylcysteine after anesthesia with isoflurane

To evaluate the effect of N-acetylcysteine, as a renoprotective agent, when administered early after anesthesia induction, against ischemia/reperfusion injury in rats anesthetized with isoflurane. Eighteen male Wistar rats weighing > 300 g were anesthetized with isoflurane. The internal jugular vein and the left carotid artery were dissected and cannulated. The animals were randomly divided into GAcetyl, receiving intravenous N-acetylcysteine, 300 mg/kg, and GIsot, isotonic saline. After 30 minutes, right nephrectomy was performed and the left renal artery was clamped during 45 minutes. The animals were sacrificed after 48 hours and blood samples were taken after anesthetic induction and upon sacrificing of the animals to evaluate blood creatinine. The kidneys were sent for histological analysis. The variation in serum creatinine was 2.33 mg/dL ± 2.21 in GAcetyl and 4.38 mg/dL ± 2.13 in GIsot (p=0.074). Two animals presented intense tubular necrosis in GAcetyl, compared to 5 in GIsot. Only GAcetyl presented animals free of tubular necrosis (two) and tubular degeneration (one). After renal ischemia/reperfusion, the rats which were given N-acetylcysteine presented less variation in serum creatinine and milder kidney injuries than the control group.

Circadian Rhythm and Response to an Acute Stressor of Urinary Corticosterone, Testosterone, and Creatinine in Adult Male Mice

In small laboratory species, steroid measures can be obtained more frequently and less invasively from urine than blood. Insofar as urinary levels reflect systemic levels, they could provide advantages particularly for measurement of glucocorticoids, whose blood levels react rapidly to handling and stress. In Experiment 1, urinary samples were collected from male mice every second hour over a 14:10 h light:dark cycle. Samples were analyzed via enzyme immunoassay for corticosterone, testosterone, and creatinine. Corticosterone had peak concentrations 1 h after light offset and a trough 1 h after light onset. Testosterone showed peak concentrations 5-7 h after light onset and lowest concentrations during the dark phase of the cycle. Creatinine showed some variation over the light-dark cycle, but steroid measures showed similar trends with and without adjustment for creatinine. In Experiment 2, mice were stressed via an injection at times close to the determined peak and trough levels of corticosterone. In urinary samples taken 90 min after injection, corticosterone was significantly higher in injected animals at both times relative to levels in control animals, but testosterone was unaffected by injection stress. In Experiment 3, serum and urine samples were collected from mice every sixth hour across the diurnal cycle. Corticosterone peaked in urine and serum immediately after light offset, and urinary measures predicted those in serum. These data indicate that urinary corticosterone reflects systemic levels in mice, document circadian variation in urinary testosterone, and indicate that circadian variation in creatinine is minimal, but potentially relevant in stressed animals.

Acute Kidney Injury Network Criteria as a Predictor of Hospital Mortality in Cirrhotic Patients With Ascites

Acute kidney injury (AKI) is frequent in cirrhotic patients but its best definition is unclear. Recently, the Acute Kidney Injury Network (AKIN) proposed criteria to define AKI. The aims of this study were to apply AKIN criteria to cirrhotic patients with ascites and to evaluate its association to hospital mortality. In this retrospective study, cirrhotic patients with ascites admitted to a university hospital in Brazil between November 2003 and December 2007 were included. AKIN criteria were applied in the first 48 hours of hospitalization, considering 2 values of creatinine in this period. Association of AKI at admission and hospital mortality was analyzed. Of the 198 patients in the study, 91 (46%) presented AKI at hospital admission. Overall hospital mortality was 40.4%. Patients without AKI had a hospital mortality rate of 29.9%, whereas the same rate for patients with this complication was 52.7% (odds ratio=2.6; 95% confidence interval, 1.5-4.7; P=0.001). In a logistic regression analysis, 4 variables were independently associated to hospital mortality: infection, hepatic encephalopathy, Child score, and AKI. A receiver operating characteristic curve analysis revealed that the variation in creatinine proposed by AKIN had the best combination of sensitivity and specificity in relation to hospital mortality. In cirrhotic patients with ascites, prevalence of AKI at hospital admission is high. Patients with renal dysfunction defined by AKIN have significant higher hospital mortality. AKIN criteria are useful in cirrhotic patients with ascites, as it identifies earlier patients with worse prognosis.

Variation of serum and urinary neutrophil gelatinase associated lipocalin (NGAL) after strenuous physical exercise

Strenuous exercise may trigger acute complications, such as exertional rhabdomyolysis and gastrointestinal complaint. As less is known about the potential renal impairment after long distance running, we assessed creatinine and neutrophil gelatinase associated lipocalin (NGAL) in serum (sNGAL) and urine (uNGAL) before and after an ultramarathon. The study population consisted of 16 trained male athletes who ran a 60 km ultramarathon. Blood and spot urine samples were collected 20 min before and immediately after the run. Creatinine was assessed by Jaffe assay on Beckman Coulter AU5800 and renal function was expressed as estimated glomerular filtration rate (eGFR) by MDRD formula. NGAL was measured by fully-automated immunoassay NGAL Test™ on AU 5800. Serum and urinary creatinine increased significantly by 38% and 78%, respectively. The eGFR contextually decreased by 31%. sNGAL, uNGAL and uNGAL/creatinine ratio increased by 1.6-fold, 7.7-fold and 2.9-fold. In six of 16 athletes (38%), the acute post-exercise increase of serum creatinine met the criteria of acute kidney injury. No significant relationship was found between pre-exercise, post-exercise values and post-exercise variation of sNGAL, uNGAL and uNGAL/creatinine ratio. A significant correlation was found between pre- and post-exercise changes of serum creatinine and sNGAL, but not with either uNGAL or uNGAL/creatinine ratio. The acute variations of serum creatinine and uNGAL attest that renal impairment is likely to develop after long distance running. The uNGAL seems more independent from creatinine variation and extra-renal sources, and thereby more reliable for monitoring the renal involvement in these types of kidney impairment.

A prospective comparison of the pathologic and surgical outcomes obtained after elective treatment of renal cell carcinoma by open or robot-assisted partial nephrectomy

ObjectiveTo prospectively compare surgical and pathologic outcomes obtained by elective robot-assisted (RAPN) or open partial nephrectomy (OPN) for small renal cell carcinoma (RCC). Materials and methodsBetween 2008 and 2010, after protocol design and patient consent, we prospectively collected clinical data for 100 patients who concurrently underwent either OPN (58) or RAPN (42) by an individual experienced surgeon. Clinical data included age, BMI, and past medical history. Operative data included operative time, warm ischemia time (WIT), and estimated blood loss (EBL). Postoperative outcomes included hospital stay (LOS), creatinine variation, Clavien complications, pathologic results, and survival. We stratified the complexity of the renal tumor using the R.E.N.A.L Nephrometry score. ResultsOf note, RAPN was superior to OPN in terms of EBL (median 143 mL vs. 415; P < 0.001) and LOS (median 3.8 days vs. 6.8; P < 0.0001). The median WIT for the RAPN group was 17.5 minutes (vs. 17.1 OPN; P = 0.3)) and the mean strict operative time was 134.8 minutes (vs. 128.4 OPN; P = 0.097). Regarding immediate, early, and short-term complications, variation of creatinine levels, and pathologic margins, the rates were equivalent for both groups (P > 0.05). According to the R.E.N.A.L nephrometry scores, both groups (RAPN/OPN) had similar rates (%) of low (81/72.4) and intermediate (19/20.7) complexity tumors, though there were 4 high complexity tumors in OPN group (vs. 0; P = 0.03). ConclusionWe found that RAPN is superior to the reference standard (OPN) surgical treatment of small RCCs in terms of blood loss and length of hospital stay with equivalent complications, warm ischemia time, and effect on renal function. Larger randomized trials with longer follow-up will give us further information and insight into the oncologic equivalence.

Plasma creatinine in dogs: intra- and inter-laboratory variation in 10 European veterinary laboratories

BackgroundThere is substantial variation in reported reference intervals for canine plasma creatinine among veterinary laboratories, thereby influencing the clinical assessment of analytical results. The aims of the study was to determine the inter- and intra-laboratory variation in plasma creatinine among 10 veterinary laboratories, and to compare results from each laboratory with the upper limit of its reference interval.MethodsSamples were collected from 10 healthy dogs, 10 dogs with expected intermediate plasma creatinine concentrations, and 10 dogs with azotemia. Overlap was observed for the first two groups. The 30 samples were divided into 3 batches and shipped in random order by postal delivery for plasma creatinine determination. Statistical testing was performed in accordance with ISO standard methodology.ResultsInter- and intra-laboratory variation was clinically acceptable as plasma creatinine values for most samples were usually of the same magnitude. A few extreme outliers caused three laboratories to fail statistical testing for consistency. Laboratory sample means above or below the overall sample mean, did not unequivocally reflect high or low reference intervals in that laboratory.ConclusionsIn spite of close analytical results, further standardization among laboratories is warranted. The discrepant reference intervals seem to largely reflect different populations used in establishing the reference intervals, rather than analytical variation due to different laboratory methods.

Creatinine in Spot Urine Samples: Sources of Variation and the Adjustment of Urinary Biomarkers Among Roofers Exposed to Asphalt

PP-30-056 Background/Aims: Urinary biomarkers of environmental exposures and early effects are often reported with respect to levels of urinary creatinine. This study investigates sources of variation of urinary creatinine and the effects of adjustment on urinary 1-hydroxypyrene (1-OHPyr) and 8-hydroxy-2′-deoxyguanosine (8-OHdG). Methods: Urine samples were collected from 19 roofers in South Florida before and after 6 hours of work. 1-OHPyr was analyzed though LC-MS/MS, 8-OHdG was analyzed by enzyme-linked immunosorbent assay, and creatinine was analyzed using a colorimetric kit. Statistical tests were performed after natural logarithmic transformation. Results: When compared to the Hispanics, African American roofers had higher levels of urinary creatinine before (220.3 vs. 78.7 mg/dL, P = 0.06) and after the work (395.0 vs. 123.6 mg/dL, P = 0.01). A negative correlation was observed between creatinine in urine and amount of alcoholic drinks consumed within the last 24 hour (Pearson r = −0.470 and −0.515 for before and after the work, respectively, P < 0.05 for both). In linear regressions models of urinary creatinine, African American race explained 38.2% of the variation before the work, and 44.8% of the variation after the work. Linear regression models of urinary (after work) 8-OHPyr and 1-OHPyr were compared with and without creatinine adjustment. When 8-OHdG levels were adjusted, the model explained 17.2% less of the variation (71.3% vs. 88.5%) and had twice the estimated error variance (0.202 vs. 0.107) than the model without adjustment. When 1-OHPyr levels were adjusted, only levels of 1-OHPyr before work remained in the model explaining 78.4% of the variation. The model without adjustment included other variables (gloves, burn due to work) and explained 82.1% of the variation. Conclusion: Our results show that urinary creatinine levels may vary greatly because of individual factors, such as race and alcohol consumption. Routine adjustments of urinary biomarkers may introduce additional error into analyses.

Simple Method for Vancomycin Dosage Adjustment Based on Serum Creatinine Variation

Simple Method for Vancomycin Dosage Adjustment Based on Serum Creatinine Variation

Early Creatinine Shifts Predict Contrast-induced Nephropathy and Persistent Renal Damage after Angiography

Purpose The purpose of this study was to evaluate incidence and predictors of contrast-induced nephropathy after coronary angiography and interventions, and to assess renal function at 30 days. The prognostic value of any early shift of serum creatinine compared with baseline was investigated; such measurement, being a delta, is largely independent of creatinine variations. Methods There were 216 patients at risk for contrast-induced nephropathy prospectively evaluated at baseline and at 12, 24, and 48 hours after exposure to contrast media, and 190 (88%) evaluated 1 month after discharge. Results Contrast-induced nephropathy occurred in 39 patients (18%), and 30-day renal damage was detected in 15 (7%). Contrast media/kg volume predicted contrast-induced nephropathy ( P = .002), and percentage change of creatinine 12 hours from baseline was significantly higher in patients with nephropathy ( P <.001). At multivariate analysis, percentage change of creatinine 12 hour-basal was the best predictor of nephropathy ( P <.001). A 5% increase of its value yielded 75% sensitivity and 72% specificity (area under the curve 0.80; odds ratio 7.37; 95% confidence interval, 3.34-16.23) for early contrast-induced nephropathy detection. Furthermore, it strongly correlated with the development of renal impairment at 30 days ( P = .002; sensitivity 87%, specificity 70%; area under the curve 0.85; odds ratio 13.29; 95% confidence interval, 2.91-60.64). Conclusion Minimal elevations of serum creatinine at 12 hours are highly predictive of contrast-induced nephropathy and 30-day renal damage after exposure to contrast media.

Twenty-four-hour profiles of urinary excretion of calcium, magnesium, phosphorus, urea, and creatinine in healthy prepubertal boys

Objectives Available data on 24-h urinary solute excretion in healthy children are sparse. We thus documented the daily and overnight variations of urinary electrolytes (calcium, magnesium, and phosphorus), urea, and creatinine in prepubertal (Tanner stage I) boys. Design and methods Nine voluntary healthy prepubertal boys aged 10.8 ± 0.11 years participated in this study. Concentrations of variables were quantified in daytime samples (collected between 07:00 h ± 30 min and 21:00 h ± 30 min) and nighttime samples (collected between 21:00 h ± 30 min and 07:00 h ± 30 min) in spring, during a period of 24-h every 3 h. Results Significant differences were found between daytime and nighttime excretion of calcium ( p < 0.05), magnesium ( p < 0.001), phosphorus ( p < 0.01), and urea ( p < 0.05), with high concentrations during the night. The 24-h solute/creatinine ratio was 0.072 ± 0.008 mg/mg for calcium, 0.069 ± 0.008 mg/mg for magnesium, 0.698 ± 0.070 mg/mg for phosphorus, and 0.017 ± 0.001 g/mg for urea. Statistically significant correlation analyses showed that urea and creatinine were positively associated with body mass index (BMI) ( R = 0.790, p = 0.0113 for urea; R = 0.889, p = <0.0013 for creatinine) and weight ( R = 0.717, p = 0.0297 for urea; R = 0.978, p = < 0.001 for creatinine). The other urinary variables were independent of BMI and body mass. Conclusion These data are of interest for the diagnosis of certain renal disease in prepubertal children.

Population Pharmacokinetics of Tenofovir in AIDS Patients

The interindividual variability of tenofovir pharmacokinetics in HIV+ patients is quite large, but the sources of variability are incompletely understood. Intraindividual variability has not been characterized, although it may have an impact on efficacy and therapeutic drug monitoring. The aims of the study were to estimate intraindividual variability of tenofovir clearance and to assess interactions with associated antiviral drugs. Tenofovir concentrations (median 2; range, 1-5) were measured in 175 patients during several dosing intervals. Covariates and dosing regimen of associated antiretroviral drugs were recorded prospectively. The data were analyzed by a population approach. The final model was a 2-compartment model with first-order absorption rate. The elimination clearance was found to be related to the ratio of body weight to serum creatinine. Among the 15 drugs coadministered, no interaction on tenofovir kinetics was significant. The global variability of CL/F, after accounting for variability to variation of body weight and serum creatinine, was about 50%, with 20% due to interindividual variability and 30% due to interoccasion variability. In a few patients, clearance (and AUC) could vary by a factor of 2 between occasions. The interoccasion variability was not related to the delay between occasions. In the context of drug monitoring, for a given patient, the dose should not be adapted unless the variation of concentration between 2 occasions is large, or the 24-hour trough concentration at steady state is lower than 12 microg/L.

Variation of Serum Creatinine, Cystatin C, and Creatinine Clearance in Healthy Persons

Variation of Serum Creatinine, Cystatin C, and Creatinine Clearance in Healthy Persons

Cystatin C and contrast-induced nephropathy

Sir, The paper by Kimmel et al. [1] concludes that cystatin C blood level variations are a more reliable parameter than serum creatinine increments for the diagnosis of contrastinduced nephropathy (CIN). However, this conclusion does not seem sufficiently supported by the data to us. Since the definition of CIN is based on serum creatinine variations, it is not clear what the meaning is of the cystatin C increase when the former does not occur. Does it reflect a true GFR reduction or some other condition, i.e. the release of cystatin C from atherosclerotic vascular lesions during arterial catheterization [2] or the biological variability of the parameter [3]? We are also puzzled with the variability of cystatin C in the period d-1/d0. Looking at Figure 1, our feeling is that it is quite large. As a matter of fact, it was reported that the critical difference for sequential values is 37% for serum cystatin C—a value that includes the cystatin C levels plotted in Figure 1—and only 14% for serum creatinine [3]. The authors state that the temporary increase in GFR possibly due to the peri-procedural hydration does not translate into a cystatin C decrement because of its slower kinetics vis-a-vis serum creatinine. However, what is the evidence for such a statement? Is it just speculation to explain the dichotomic trends between serum cystatin C and creatinine levels? The issue is very important, since if cystatin C really has a delayed progression with respect to serum creatinine, we might suspect that the interval d0/d2, 48 h, is too long to grasp mild, transient serum creatinine variations occurring inbetween. We think that, although cystatin C is an attractive biomarker of GFR, before concluding that it should be the preferred biomarker for the development of CIN, an experimental design with a more strict timing in sampling and a much larger case population is necessary.

Variation of serum creatinine, cystatin C, and creatinine clearance tests in persons with normal renal function

Background To determine the potential sensitivity of several renal function tests for detecting early changes in renal function, we compared the within-individual (W-I) variation over 5 months of serum creatinine, serum cystatin C, and creatinine clearance. Methods On 31 healthy subjects, blood and timed urine specimens were collected once each month to get 6 collections. Creatinine (enzymatic) in serum and urine and cystatin C (immunonephelometric) in serum were measured and glomerular filtration rate (GFR) by creatinine clearance and the Modification of Diet in Renal Disease (MDRD) equation were calculated. To compare W-I variations between different creatinine methods, we also measured creatinine by both enzymatic and kinetic alkaline picrate methods on 15 sets of frozen samples. Results For the 31 volunteers, the mean W-I variations for serum creatinine (5.8%) and cystatin C (5.4%) were both much lower than the W-I variation of creatinine clearance (18.7%). As expected, the MDRD GFR had a similar W-I variation (6.7%) to that of serum creatinine and its values were markedly different than GFR by creatinine clearance. On the 15 sets of frozen samples, the W-I variation of creatinine measured by the enzymatic method (CV 5.2%) was slightly less than by the picrate method (CV 6.2%). Conclusions The low W-I variation of both serum cystatin C and serum creatinine suggests that serial measurements of either would detect a changes in renal function earlier than would GFR by creatinine clearance or MDRD equation, which allows reporting only for GFRs < 60 ml/min/1.7 m 2. While we measured only creatinine clearance, the large variability, difficulty, and cost of all clearance measurements make them impractical for routine monitoring of patients.