Early intensive treatment improves outcomes in patients with glomerular hyperfiltration and type 2 diabetes.

BACKGROUND AND OBJECTIVE: Approximately 24-40% of patients with type 2 diabetes mellitus (T2DM) develop kidney damage. Our objective was to evaluate the long-term evolution of renal function using isotopic determination of GFR and urinary albumin excretion (UAE) in patients with T2DM undergoing intensive treatment for renal and cardiovascular risk factors. PATIENTS AND METHODS: This was a single-center, prospective study of 201 patients with T2DM and UAE who initiated intensive treatment. They were followed for 17.2±6.5 years. Patients were divided into three groups, according to renal function: 167(85.6%) had stable renal function, 16(8.2%) had creatinine levels that doubled and 12(6.2%) began renal replacement therapy (RRT). We performed periodic isotopic determinations of GFR using (125)I-iothalamate. RESULTS: There were significant differences between the three groups with respect to age, duration of T2DM at baseline, years of follow-up in the study and systolic blood pressure, serum creatinine, isotopic GFR, and UAE at baseline. Renal function evolution slopes were -1.55mL/min/1.73m(2)/year in patients with stable creatinine, -2.49mL/min/1.73m(2)/year in those with doubled creatinine, and -8.16mL/min/1.73m(2)/year in those requiring RRT. We also found that differences in renal events were determined by delayed initiation of intensive treatment. CONCLUSION: Patients with glomerular hyperfiltration who were undergoing treatment with renin angiotensin aldosterone system blockers exhibited a better evolution in renal function, possibly because these patients initiated intensive treatment earlier. Although diabetic nephropathy is associated with classic risk factors, early initiation of intensive treatment should be a priority in order to prevent worsening renal function.

Long-term changes in renal function and perfusion in heart failure patients with reduced ejection fraction.

INTRODUCTION: Little is known about the natural course of renal function and renal hemodynamics in heart failure patients with reduced ejection fraction (HFREF). METHODS AND RESULTS: We prospectively studied effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) in 73 HFREF patients with (125)I-iothalamate/(131)I-hippuran clearances with a mean follow-up of 34.6 ± 4.4 months. Fifteen percent were female, with age 58 ± 12 years and left ventricular ejection fraction (LVEF) 29 ± 10%. Baseline GFR was 81 ± 23 mL/min/1.73 m(2) and declined 0.6 ± 4.7 mL/min/1.73 m(2) per year. Baseline ERPF was 292 ± 83 mL/min/1.73 m(2) and declined 4.3 ± 19 mL/min/1.73 m(2) per year. Of the baseline variables, older age and high urinary kidney injury molecule-1 were the only variables associated with GFR decline (p < 0.05). Following stepwise backward analysis, only age (p < 0.001) remained significant. In addition, we found an association between change in GFR and changes in ERPF, N-terminal pro-brain natriuretic peptide and renovascular resistance. In the multivariable analysis, only the change in ERPF remained significantly associated with a change in GFR (p < 0.001). CONCLUSION: In this cohort of stable chronic HFREF patients, the average decline in GFR over time was small. The decline of GFR was associated with a higher age and a lower baseline GFR, and was strongly related to changes in renal perfusion.

The body composition and excretory burden of lean, obese, and severely obese individuals has implications for the assessment of chronic kidney disease.

Obesity could affect associations between creatinine generation, estimated body surface area, and excretory burden, with effects on chronic kidney disease assessment. We therefore examined the impact of obesity on the performances of estimated glomerular filtration rate (eGFR), the urine albumin:creatinine ratio (ACR), and excretory burden in 3611 participants of the Chronic Renal Insufficiency Cohort. Urine creatinine excretion significantly increased with body mass index (BMI) (34 and 31% greater at 40 kg/m(2) or more versus the normal of 18.5-25 kg/m(2)) in men and women, respectively, such that patients with a normal BMI and an ACR of 30 mg/g had the same 24-h albuminuria as severely obese patients with ACR 23 mg/g. The bias of eGFR (referenced to body surface area-indexed iothalamate (i-)GFR) had a U-shaped relationship to obesity in men but progressively increased in women. Nevertheless, obesity-associated body surface area increases were accompanied by a greater absolute (non-indexed) iGFR for a given eGFR, particularly in men. Two men with eGFRs of 45 ml/min per 1.73 m(2), height 1.76 m, and BMI 22 or 45 kg/m(2) had absolute iGFRs of 46 and 62 ml/min, respectively. The excretory burden, assessed as urine urea nitrogen and estimated dietary phosphorus, sodium, and potassium intakes, also increased in obesity. However, obese men had lower odds of anemia, hyperkalemia, and hyperphosphatemia. Thus, for a given ACR and eGFR, obese individuals have greater albuminuria, absolute GFR, and excretory burden. This has implications for chronic kidney disease management, screening, and research.

The impact of gender and NASH on chronic kidney disease before and after liver transplantation.

BACKGROUND & AIMS: Chronic kidney disease (CKD) after liver transplant (LT) is associated with increased long-term mortality. The impact of gender on CKD before and after LT is unknown. To further define risk factors and analyse gender differences in the incidence and progression of CKD after liver transplant. METHODS: Four hundred and fifty-five consecutive adult primary solitary LT recipients were included. Iothalamate clearance tests performed over time were analysed. RESULTS: Mean age was 51.4 ± 10.4 years with 63% males. A percentage of 29.1% of females and 21.1% of males had a GFR<60 ml/min/1.73 m(2) and 10.2% of females and 5.9% of males had GFR<30 ml/min/1.73 m(2) prior to transplant. At 1 year, 52.6% of recipients tested (69.6% females, 43.0% males) had GFR<60 ml/min/1.73 m(2) and 7.3% (11.6% females, 4.9% males) had GFR<30 ml/min/1.73 m(2) . Pre-LT GFR<60 ml/min/1.73 m(2) [OR 3.28, (1.76-6.10), P ≤ 0.001], female gender (OR 2.96, (1.72-5.10), P < 0.001) and age [OR 1.09, (1.05-1.12), P < 0.001] were independently predictive of stage ≥3 CKD at 1 year post-LT. Female gender [OR 2.52, (1.25-4.71), P = 0.004], age [OR 1.05, (1.02-1.08), P = 0.003] and NASH [OR 2.95, (1.06-8.21), P = 0.039] were independently predictive of ≥stage 3 CKD at 5 years post-LT. Pre-LT diabetes was associated with stage 4 CKD at 5 years [OR 2.91, (1.33-6.36), P = 0.008] post-LT. CONCLUSIONS: In addition to age and pre-LT CKD, female gender and NASH are independent predictors of ≥stage 3 CKD post-LT. Gender-based approaches to optimize modifiable risk factors are needed to improved post-transplant renal function.

Measurement of glomerular filtration rate in anesthetized and conscious rhesus monkeys (Macaca mulatta).

OBJECTIVE: To validate a method to assess glomerular filtration rate (GFR) in conscious monkeys via transcutaneous radiation detection after IV injection of technetium Tc 99m pentatate (99mTc-DTPA). ANIMALS: 4 healthy rhesus monkeys. PROCEDURES: On day 1, each monkey was anesthetized, lothalamate sodium I 125 (125l-iothalamate) was administered via continuous rate infusion (0.0037 MBq/min); blood and urine samples were obtained for determination of 125l-iothalamate plasma clearance variables and estimation of GFR. One dose of 99mTc-DTPA (74 MBq/kg, IV) was also administered during the 125l-iothalamate plasma clearance test, and transcutaneous measurements of technetium 99m-emitted radiation were obtained by use of an ambulatory renal monitor (ARM) applied to a brachium of each monkey. Determination of GFR by use of the ARM was repeated on days 8 and 45 in the same monkeys without anesthesia. RESULTS: Sensitivity, accuracy, and precision of the 2 methods were similar. By use of the ARM, GFR determined by use of the renal rate constant (κGFR) was calculated; the value obtained on day 1 under anesthesia was similar to values determined via 125l-iothalamate plasma clearance testing on the same day, but was 16% to 23% less than that measured on days 8 and 45 in conscious monkeys. CONCLUSIONS AND CLINICAL RELEVANCE: The ARM method for assessment of GFR was less invasive, faster, and more convenient than the standard clearance method, but yielded comparable results. The need to train animals and size restrictions of the device may limit the use of this technique in other nonhuman animals.

Accurate, fast, and convenient measurement of glomerular filtration rate in potential renal transplant donors.

BACKGROUND: Measurement of glomerular filtration rate (GFR) is essential in the risk evaluation of potential kidney donors. The optimal method of measuring GFR involves using clearance techniques. However, clearance techniques are technically complex and time consuming. The goal of this study is to evaluate a different method of measuring GFR, one that retains the accuracy of a clearance technique and adds the convenience of a plasma creatinine measurement. METHODS: Fifty subjects, including both normal and patients with different degrees of renal dysfunction, were included in the initial validation study. GFR was measured simultaneously using a continuous infusion of I-iothalamate and external radioactivity measurement after a single intravenous injection of Tc-labeled diethylenetriaminepentaacetic acid (Tc-DTPA). After validation, the renal function of 80 potential renal transplant donors was measured using only external radiation detection. RESULTS: External radioactivity decreases versus time with first-order kinetics. The rate of clearance of Tc-DTPA was measured as the slope (kappa) of the natural logarithm of external radioactivity corrected for radioactive decay versus time. There was an excellent correlation between kappa and simultaneous GFR measurements done with I-iothalamate. Nonlinear regression analysis of kappa GFR values obtained in potential renal transplant donors versus frequencies indicates a mean value and variance similar to normal reported values obtained with clearance techniques. Estimated GFR and 24-hr plasma creatinine clearance underestimate GFR with greater variance. CONCLUSIONS: Measurements of external whole tissue radioactivity after intravenous injection of Tc-DTPA represents an accurate, fast, and convenient way to measure total and individual kidney GFR, addressing an important concern during the risk evaluation of potential renal transplant donors.

[Assessment of the new CKD-EPI equation to estimate the glomerular filtration rate]. / Valoración de la nueva ecuación CKD-EPI para la estimación del filtrado glomerular.

INTRODUCTION: A recent report by the CKD-EPI Chronic Kidney Disease Epidemiology Collaboration) group describes a new equation to estimate the glomerular filtration rate (GFR). This equation has been developed from a population of 8,254 subjects who had the GFR measured by iothalamate clearance (mean 68 mL/min/1.73 m2, SD 40 mL/min/1.73 m2). It includes variables such as serum creatinine, age, sex and race with different formula according to race, sex and creatinine value. The CKD-EPI equation improved the accuracy and precision results of the current first-choice MDRD-IDMS (Modification of Diet in Renal Disease-Isotopic Dilution Mass Spectrometry) formula, specially for GFR > 60 mL/min/1.73 m2 in a group of 3,896 subjects. METHODS: The goal of our study was to compare the estimated GFR by using the new equation CKD-EPI with MDRD-IDMS in a wide cohort of 14,427 patients (5,234 women and 9,193 men), and to analyze the impact of the new CKD-EPI formula on the staging of patients with CKD. RESULTS: Mean estimated GFR was 0.6 mL/min/1.73 m2 higher with CKD-EPI as compared to MDRD-IDMS for the whole group, 1.9 mL/min/1.73 m2 higher for women and 0.2 mL/min/1.73 m2 lower for men. The percentage of CKD staging concordancy between equations varied from 79.4 % for stage 3A and 98.6% for stage 5. For those patients younger than 70 years, 18.9 % and 24 % MDRD-IDMS stages 3B and 3A were reclassified as CKD 3A and 2 by CKD-EPI, respectively. For the same stages in the group younger than 70 years, the percentage of reclassified patients increased up to 34.4% and 33.4%, respectively. CONCLUSION: The new CKD-EPI equation to estimate the GFR reclassifies an important number of patients to higher CKD stages (higher GFR), specially younger women, classified as CKD stage 3 by MDRD-IDMS.

Functional immunoassay technology (FIT), a new approach for measuring physiological functions: application of FIT to measure glomerular filtration rate (GFR).

This is the first description of functional immunoassay technology (FIT), which as a diagnostic tool has broad application across the whole spectrum of physiological measurements. In this paper, FIT is used to measure the renal clearance of an ultra low-dose administration of a clinically available contrast reagent for the purpose of obtaining an accurate glomerular filtration rate (GFR) measurement. Biomarker-based GFR estimates offer convenience, but are not accurate and are often misleading. FIT overcomes previous analytic barriers associated with obtaining an accurate GFR measurement. We present the performance characteristics of this diagnostic test and demonstrate the method by directly comparing GFR values obtained by FIT to those obtained by an FDA approved nuclear test in 20 adults. Two subjects were healthy volunteers and the remaining 18 subjects had diagnosed chronic kidney disease, with 12 being kidney transplant recipients. Measured GFR values were calculated by the classic UV/P method and by the blood clearance method. GFR obtained by FIT and the nuclear test correlated closely over a wide range of GFR values (10.9-102.1 ml.min(-1).1.73 m(-2)). The study demonstrates that FIT-GFR provides an accurate and reproducible measurement. This nonradioactive, immunoassay-based approach offers many advantages, chiefly that most laboratories already have the equipment and trained personnel necessary to run an ELISA, and therefore this important diagnostic measurement can more readily be obtained. The FIT-GFR test can be used throughout the pharmaceutical development pipeline: preclinical and clinical trials.

Feasibility and impact of the measurement of extracellular fluid volume simultaneous with GFR by 125I-iothalamate.

The feasibility, validity, and possible applications of the assessment of extracellular fluid volume (ECFV) simultaneous with glomerular filtration rate (GFR) were assessed in a series of validation studies using the constant infusion method of (125)I-iothalamate (IOT). In 48 subjects with a broad range of GFR, distribution volume (V(d)) of IOT corresponded well with V(d) bromide (16.71 +/- 3.0 and 16.73 +/- 3.2 l, respectively, not significant), with a strong correlation (r = 0.933, P < 0.01) and without systematic deviations. Reproducibility assessment in 25 healthy male subjects showed coefficients of variation of 8.6% of duplicate measurement of V(d) IOT during strictly standardized (50 mmol Na(+)/d) sodium intake. An increase in dietary sodium intake (200 mmol Na(+)/d) induced a corresponding rise in V(d) IOT of 1.11 +/- 1.5 l (P < 0.01). In 158 healthy prospective kidney donors, the impact of indexing of GFR to ECFV was analyzed. Age, gender, height, and body surface area (BSA) were determinants of GFR. Whereas GFR, GFR/BSA, and GFR/height were gender-dependent, GFR/ECFV was gender-independent and not related to height or BSA. This supports the potential of normalizing GFR by ECFV. Thus, ECFV can be simultaneously assessed with GFR by the constant infusion method using IOT. After appropriate validation, also other GFR tracers could be used for such a simultaneous estimation, providing a valuable resource of data on ECFV in renal studies and, moreover, allowing GFR to be indexed to the body fluid compartment it clears: the ECFV.

Decreased incidence of acute rejection in adolescent kidney transplant recipients using antithymocyte induction and triple immunosuppression.

BACKGROUND: Acute rejection is a frequent event in pediatric renal transplantation; it can diminish allograft function and affect long-term outcome. Recent data from the North American Pediatric Renal Transplant Cooperative Study indicates that the rate of acute rejection remains high despite current immunosuppressive regimens. METHODS: In this retrospective series, we examined 37 pediatric renal transplant recipients who received induction doses of antithymocyte globulin combined with maintenance immunotherapy using tacrolimus, mycophenolate mofetil, and prednisone. The postoperative course was reviewed for initial and total hospital stay, number of rehospitalizations, evidence of posttransplant complications, graft fibrosis, and overall patient and graft survival. RESULTS: Three episodes of acute rejection (8.1%) were recorded in the first year posttransplant. The median initial hospital stay for patients receiving a kidney transplant was 8 days. Patient and graft survival were 100% and 91.9% at 1 year, respectively. The incidence of viral infection (cytomegalovirus, BK virus, and Epstein-Barr virus) and posttransplant lymphoproliferative disease remained low. Urinary tract infection and fluid and electrolyte complications were the main causes of posttransplant hospitalization. CONCLUSIONS: We conclude that induction with antithymocyte globulin and maintenance immunosuppression with tacrolimus, mycophenolate, and prednisone should be considered a valuable tool in the management of children undergoing renal transplantation.

Avaliação do ritmo de filtração glomerular / Assessment of glomerular filtration rate

A medida do ritmo de filtração glomerular (RFG) é a prova laboratorial mais utilizada na avaliação da função renal. Para tanto, usam-se marcadores indiretos, como as determinações de creatinina e cistatina C no sangue, ou procede-se à determinação do RFG propriamente dito, com indicadores como inulina; contrastes iodados, marcados ou não; e outras substâncias. O exame mais solicitado para avaliação do RFG no laboratório de patologia clínica é a dosagem da creatinina sérica. Em algumas condições, entretanto, o resultado encontrado da creatinina sérica deve ser corrigido (através da utilização de fórmulas que levam em consideração características próprias do indivíduo) para ser devidamente interpretado. De fato, a inulina ainda é vista como marcador ideal de filtração glomerular, mas seu uso não se destina à prática clínica, de modo que ainda hoje persiste a busca por testes adequados para uso rotineiro.

Glomerular filtration rate (GFR) determination is the most frequently used laboratorial test to evaluate renal function. Indirect markers as blood determination of creatinine and cystatin C are used with this purpose, as well as the direct determination of GFR, with indicators like inulin; iodated contrasts, radioactive or not; and others. Serum creatinine is the test that is most commonly performed in order to evaluate GFR in the clinical pathology laboratory. However, in some conditions, aiming at the adequate interpretation of the test, the result of serum creatinine must be corrected (by using formulas that include individual characteristics of the subjects). In fact, inulin is still seen as the ideal marker of glomerular filtration, but its use is not directed to clinical practice; then the search for appropriate tests for routine use continues.

Impact of creatinine calibration on performance of GFR estimating equations in a pooled individual patient database.

BACKGROUND: Variation in performance of glomerular filtration rate (GFR) estimating equations is related to variation in calibration of the creatinine assay across clinical laboratories. STUDY DESIGN: Cross-sectional analysis. SETTING & PARTICIPANTS: 6 research studies and 4 clinical populations including 5,504 participants who had GFR measured using urinary clearance of iothalamate. MEASUREMENTS: Standardized serum creatinine values obtained by means of calibration to the Cleveland Clinic Research Laboratory using frozen specimens, a calibration panel, and/or survey results from the College of American Pathologists. PREDICTOR: Noncalibrated serum creatinine assayed in research and clinical laboratories compared with standardized serum creatinine. OUTCOME: Difference between measured GFR versus GFR estimated from the Modification of Diet in Renal Disease (MDRD) Study and Cockcroft-Gault equations. RESULTS: For a noncalibrated serum creatinine value of 1 mg/dL (88.4 micromol/L), standardized serum creatinine value was 0.07 mg/dL (6.2 micromol/L) less than noncalibrated values. In the pooled data set, for the MDRD Study equation, calibration improved median percentage of difference between measured and estimated GFR from 9.0% (interquartile range [IQR], 28%) to 5.8% (IQR, 28%) and improved the percentage of estimates within 30% of measured GFR (P30) from 80% to 83%. The effect of calibration was greater at higher levels of GFR and varied across studies. For the Cockcroft-Gault equation, calibration worsened the median percentage of difference from -2.0% (IQR, 38%) to -11.4% (IQR, 39%), and the P30, from 74% to 69%. LIMITATIONS: College of American Pathologist samples were used for calibration of clinical populations; calibration factors do not account for drift over time in the serum creatinine assay; calibration cannot account for variation in assay performance among individuals. CONCLUSION: Calibration improves the performance of the MDRD Study equation. After calibration, larger errors remain for GFR estimates greater than 60 mL/min/1.73 m2 (>1 mL/s/1.73 m2).

Alteration in renal organic anion transporter 1 after ischemia/reperfusion in cadaveric renal allografts.

We have previously shown that postischemic injury to renal allografts results in profound impairment of p-aminohippuric acid (PAH) extraction. To elucidate the cellular integrity of the human organic anion transporter 1 (hOAT1) in postischemic acute renal failure (ARF), immunohistochemical analysis of hOAT1 was performed in cadaveric renal allografts using confocal microscopy for three-dimensional reconstruction of serial optical images. Biopsy samples were obtained from 10 cadaveric renal allografts 1 hr after reperfusion during transplant operation. Control tissues were obtained from four living donors of healthy kidneys immediately before an arterial clamp was applied to the renal artery. Control tissues demonstrated hOAT1 distributed to basolateral membrane of proximal tubule cells. In contrast, maldistribution of hOAT1 to cytoplasm and/or diminution of the protein was noted in cadaveric allografts. Characteristics of maldistribution were variable: disappearance of lateral distribution, diffuse cytoplasmic aggregates, apical cytoplasmic aggregates, and disappearance of the staining. In addition, iothalamate and PAH clearances were performed on posttransplant days 3-7 in 18 recipients of a cadaveric renal allograft. PAH clearance was depressed <250 ml/min in all but three subjects. We conclude that reperfused, transplanted kidneys exhibit maldistribution of hOAT1 in proximal tubule cells, resulting in impairment of PAH clearance. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials.

Reproducibility of renal function measurements in adult men with diabetic nephropathy: research and clinical implications.

BACKGROUND/AIM: Measurement of the renal function is critical to follow progression of kidney disease. Short-term and long-term variabilities in these measurements have significant impacts on clinical decision making and clinical trials. The goal of this study was to describe the variability in these measurements and to calculate minimum sample size estimates over varying time frames for clinical trials. METHODS: We studied 44 elderly men with diabetic nephropathy who participated in a clinical trial. Glomerular filtration rate and renal plasma flow were measured by continuous infusion technique with five urine collection periods on two occasions 4 months apart. Protein and creatinine excretion rates were measured in the same specimens. In addition, two consecutive 24-hour specimens every month for 4 months were collected to analyze urine protein, creatinine, urea nitrogen, and electrolytes. A hierarchical random effects model was used to analyze the reproducibility from hour to hour, from day to day, and from month to month. RESULTS: A total of 824 urine specimens were analyzed, of which 412 constituted specimens collected in the short term and 412 were 24-hour urine collections. Hour-to-hour variation accounted for 45% for urinary clearance of iothalamate, but for only 0.5% of the variability in plasma clearance of iothalamate. Day-to-day variability in 24-hour urinary excretion rates for creatinine was 46% and for protein 10%. Month-to-month variability in 24-hour excretion rates for creatinine was 11% and for protein 19%. The urine protein/creatinine ratio had a day-to-day variability of 2% and a month-to-month variability of 19%. Sample size requirements can be reduced by correcting for urine creatinine for some but not all urinary analytes. CONCLUSIONS: In nephrotic men with diabetic nephropathy, the coefficient of variation in the month-to-month protein excretion rate is 36%. Approximately 28 patients in each arm of two groups are needed to detect a difference in protein excretion rate of 28% (1 g/day in this study). The coefficient of variation in plasma iothalamate clearance over 4 months is 16%. To detect a 10% change in glomerular filtration rate between two groups, 44 patients per group are needed. To be deemed statistically significant, a change in daily protein excretion rate of at least 72% over month(s) is needed in individual patients.

[Renal radionuclide scintigraphy in the evaluation of radiopaque substances on renal function].

To evaluate the nephrotoxic effect of radiopaque substances (ROS) by renal radionuclide scintigraphy, 47 patients were examined before and after coronary ventriculography. Iohexol, iobitridole, and ioxythalamate were used as ROS in 15, 18, and 14 patients, respectively. The parameters of renal filtration and excretory function were calculated during study. Ioxythalamate was shown to have a less pronounced nephrotoxic effect.

Are prediction equations for glomerular filtration rate useful for the long-term monitoring of type 2 diabetic patients?

BACKGROUND: The aim of this study was to compare the accuracy of prediction equations [modification of diet in renal disease (MDRD), simplified MDRD, Cockcroft-Gault (CG), reciprocal of creatinine and creatinine clearance] in a cohort of patients with type 2 diabetes. METHODS: A total of 525 glomerular filtration rates (GFRs) using (125)I-iothalamate were carried out over 10 years in 87 type 2 diabetic patients. Accuracy was evaluated at three levels of renal function according to the baseline values obtained with the isotopic method: hyperfiltration (GFR: >140 ml/min/1.73 m(2); 140 isotopic determinations in 27 patients), normal renal function (GFR: 140-90 ml/min/1.73 m(2); 294 isotopic determinations in 47 patients) and chronic kidney disease (CKD) stages 2-3 (GFR: 30-89 ml/min/1.73 m(2); 87 isotopic determinations in 13 patients). The annual slope for GFR (change in GFR expressed as ml/min/year) was considered to ascertain the variability in the equations compared with the isotopic method during follow-up. Student's t-test was used to determine the existence of significant differences between prediction equations and the isotopic method (P < 0.05 with Bonferroni adjusted for five contrast tests). RESULTS: In the subgroup of patients with hyperfiltration, a GFR slope calculated with (125)I-iothalamate -4.8 +/- 4.7 ml/min/year was obtained. GFR slope in patients with normal renal function was -3.0 +/- 2.3 ml/min/year. In both situations, all equations presented a significant underestimation compared with the isotopic GFR (P < 0.01; P < 0.05). In the subgroup of CKD stages 2-3, the slope for GFR with (125)I-iothalamate was -1.4 +/- 1.8 ml/min/year. The best prediction equation compared with the isotopic method proved to be MDRD with a slope for GFR of -1.4 +/- 1.3 ml/min/year (P: NS) compared with the CG formula -1.0 +/- 0.9 ml/min/year (P: NS). Creatinine clearance presented the greatest variability in estimation (P < 0.001). CONCLUSIONS: In the normal renal function and hyperfiltration groups, none of the prediction equations demonstrated acceptable accuracy owing to excessive underestimation of renal function. In CKD stages 2-3, with mean serum creatinine > or =133 micromol/l (1.5 mg/dl), the MDRD equation can be used to estimate GFR during the monitoring and follow-up of patients with type 2 diabetes receiving insulin, anti-diabetic drugs or both.

Assessing glomerular filtration rate by estimation equations in kidney transplant recipients.

Surveillance of glomerular filtration rate (GFR) is crucial in the management of kidney transplant recipients. With special emphasis on serum creatinine (SCr) calibration assay, we assessed the performance of estimation equations as compared to iothalamate GFR (iGFR) in 209 patients using the modification of diet in renal disease (MDRD), Nankivell and Cockcroft-Gault methods. Fifty-five percent of patients were treated with a calcineurin inhibitor (CNI) and all were taken trimethroprim-sulfametoxazole at the time of SCr measurement. The mean iGFR was 44 +/- 26 mL/min/1.73 m2. The MDRD equation showed a median difference of 0.9 mL/min/1.73 m2 with 53% of estimated GFR within 20% of iGFR. Median differences were 7.5 and 7.0 mL/min/1.73 m2 for Nankivell and Cockcroft-Gault formulas, respectively. The accuracy of the Nankivell and Cockcroft-Gault formulas was such that only 38% and 37% of estimations, respectively, fell within 20% of iGFR. The performance of all equations was not uniform throughout the whole range of GFR, with some deterioration at the extremes of GFR levels. In addition, good performance of the MDRD equation was seen in subjects taking CNI. In conclusion, the overall performance of the MDRD equation was superior to the Nankivell and Cockcroft-Gault formulas in renal transplant recipients including subjects treated with CNI.

Renal extraction of cystatin C vs 125I-iothalamate in hypertensive patients.

BACKGROUND: Several markers are available to estimate the glomerular filtration rate (GFR) in patients. Cystatin C is a relatively new marker and has been suggested as an alternative for creatinine. Numerous studies have been performed to evaluate the usefulness of cystatin C to estimate GFR. The aim of this study is to compare the renal extraction of cystatin C with that of 125I-iothalamate in hypertensive patients. METHODS: Forty hypertensive patients with unilateral renal artery stenosis, and who used at least two antihypertensive agents, were studied. For the determination of the renal extraction ratio, blood samples were drawn simultaneously from the renal vein and the abdominal aorta. The renal extraction ratio was calculated as ([A]-[V])/[A], in which A is the plasma concentration of the compound from the abdominal aorta, and V is the plasma concentration of the compound from the renal vein. RESULTS: The mean difference between the renal extraction ratio of cystatin C and that of 125I-iothalamate was 0.002. The 95% confidence interval (CI) for the mean difference was -0.036 to 0.032, which was not statistically significant. However, the limits of agreement were large (-0.271 and 0.267). CONCLUSIONS: Despite a lower reported glomerular sieving coefficient of cystatin C, the mean renal extraction of cystatin C was equal to the mean renal extraction of 125I-iothalamate in hypertensive patients, suggesting tubular secretion of cystatin C. Combined with the large variation in the renal extraction of cystatin C, these findings cast doubts on its usefulness as a glomerular filtration marker.

Performance of the Cockcroft-Gault and modification of diet in renal disease equations in estimating GFR in ill hospitalized patients.

BACKGROUND: Estimating glomerular filtration rate (GFR) in severely ill inpatients is clinically important for therapeutic interventions and prognosis, but notoriously difficult to do accurately. The Modification of Diet in Renal Disease (MDRD) equation and Cockcroft-Gault (CG) formula are widely used to estimate renal function in sick hospitalized patients; however, neither method has been validated in this setting. METHODS: Iodine 125-iothalamate clearances (iGFR) performed in 107 sick inpatients with renal dysfunction were compared with estimated GFRs (eGFRs) from the 6- and 4-variable MDRD (MDRD eGFR) and CG (CG eGFR) equations. RESULTS: Mean serum creatinine (SCr) level was 3.5 +/- 2.0 mg/dL (309 +/- 177 micromol/L), and mean iGFR was 17.1 +/- 17.9 mL/min/1.73 m2 (0.29 +/- 0.30 mL/s/1.73 m2). Six-variable MDRD eGFR was 22.5 +/- 17.4 mL/min/1.73 m2 (0.38 +/- 0.29 mL/s/1.73 m2), 4-variable MDRD eGFR was 23.9 +/- 16.3 mL/min/1.73 m2 (0.40 +/- 0.27 mL/s/1.73 m2), and CG eGFR was 26.0 +/- 17.1 mL/min/1.73 m2 (0.43 +/- 0.29 mL/s/1.73 m2). Blood urea nitrogen (BUN)/SCr ratios greater than 20 were seen in 58% of patients. Overall, the CG and MDRD equations overestimated iGFR, with poor agreement. Overestimation of at least 25% of measured iGFR was seen in 63%, 67%, and 70% of all inpatients when using the 6-variable MDRD, 4-variable MDRD, and CG equations, respectively. Accuracy of eGFR within 50% of measured iGFR was 55% for the 6-variable MDRD equation, 49% for the 4-variable MDRD equation, and 40% for the CG formula. The performance of both methods deteriorated further in patients with a BUN/SCr ratio greater than 20. CONCLUSION: Estimation equations are performed poorly compared with iGFR and are not reliable measures of actual level of function in sick hospitalized patients, especially those with a high BUN/SCr ratio. Although use of the 6-variable MDRD equation provides a better estimation of GFR, it still is unsuitable for clinical application in this population.