The long-term costs and effects of tubal flushing with oil-based versus water-based contrast during hysterosalpingography.

RESEARCH QUESTION: What are the long-term costs and effects of oil- versus water-based contrast in infertile women undergoing hysterosalpingography (HSG)? DESIGN: This economic evaluation of a long-term follow-up of a multicentre randomized controlled trial involved 1119 infertile women randomized to HSG with oil- (n = 557) or water-based contrast (n = 562) in the Netherlands. RESULTS: In the oil-based contrast group, 39.8% of women needed no other treatment, 34.6% underwent intrauterine insemination (IUI) and 25.6% had IVF/intracytoplasmic sperm injection (ICSI) in the 5 years following HSG. In the water-based contrast group, 35.0% of women had no other treatment, 34.2% had IUI and 30.8% had IVF/ICSI in the 5 years following HSG (P = 0.113). After 5 years of follow-up, HSG using oil-based contrast resulted in equivalent costs (mean cost difference -€144; 95% confidence interval [CI] -€579 to +€290; P = 0.515) for a 5% increase in the cumulative ongoing pregnancy rate compared with HSG using water-based contrast (80% compared with 75%, Relative Risk (RR) 1.07; 95% CI 1.00-1.14). Similarly, HSG with oil-based contrast resulted in equivalent costs (mean cost difference -€50; 95% CI -€576 to +€475; P = 0.850) for a 7.5% increase in the cumulative live birth rate compared with HSG with water-based contrast (74.8% compared with 67.3%, RR 1.11; 95% CI 1.03-1.20), making it the dominant strategy. Scenario analyses suggest that the oil-based contrast medium is the dominant strategy up to a price difference of €300. CONCLUSION: Over a 5-year follow-up, HSG with an oil-based contrast was associated with a 5% increase in ongoing pregnancy rate, a 7.5% increase in live birth rate and similar costs to HSG with water-based contrast.

Oil-based or water-based contrast for hysterosalpingography in infertile women: a cost-effectiveness analysis of a randomized controlled trial.

OBJECTIVE: To determine the cost effectiveness of the use of oil-based versus water-based contrast in infertile women undergoing hysterosalpingography (HSG). DESIGN: Economic evaluation alongside a multicenter randomized trial. SETTING: Hospitals. PATIENT(S): Infertile women with an ovulatory cycle, 18-39 years of age, low risk of tubal pathology. INTERVENTION(S): Use of oil-based versus water-based contrast during HSG. MAIN OUTCOME MEASURE(S): Costs per additional ongoing pregnancy and per live birth within 6 months of randomization, incremental cost-effective ratios (ICERs). RESULT(S): A total of 1,119 women were randomized to HSG (oil-based contrast, n = 557; water-based contrast, n = 562). After HSG, most women had no additional treatment; a minority had IUI or IVF. In the oil group, 39.7% women had an ongoing pregnancy within 6 months of randomization versus 29.1% women in the water group. There was a 10.7% increase in the live birth rate in the oil group. For ongoing pregnancy, the mean costs per couple were US$2,014 in the oil group and US$1,144 in the water group, with a corresponding ICER of US$8,198 per additional ongoing pregnancy. For live birth, the mean costs per couple were US$11,532 in the oil group and US$8,310 in the water group, with a corresponding ICER of US$30,112 per additional live birth. CONCLUSION(S): Hysterosalpingography with oil-based contrast results in higher 6-month ongoing pregnancy and live birth rate. If society is willing to pay US$8,198 for an additional ongoing pregnancy, HSG with oil-based contrast is a cost-effective strategy compared with HSG with water-based contrast for infertile, ovulatory women at low risk for tubal pathology. CLINICAL TRIAL REGISTRATION NUMBER: Dutch Trial Register, NTR 6577 (www.trialregister.nl).

Validity of estimated glomerular filtration rates for assessment of renal function after renal artery stenting in patients with atherosclerotic renal artery stenosis.

OBJECTIVES: The purpose of this study was to evaluate the validity of estimates of glomerular filtration rate (eGFR) for assessing serial changes in renal function after renal artery stenting. BACKGROUND: eGFR are unreliable for assessing serial renal function in patients with atherosclerotic renal artery stenosis (RAS). eGFR have not been validated for assessment of serial renal function after renal artery stenting. METHODS: Serum creatinine (SCr) and (125)I-iothalamate GFR (iGFR) were measured in RAS patients before and after renal artery stenting. eGFR were calculated from Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Cockcroft-Gault (CG) formulas. Using iGFR as the reference standard, the sensitivity, specificity, and area under the receiver-operating characteristic curve (AUC) were determined for MDRD, CKD-EPI, and CG for assessing changes in GFR before and after intervention. RESULTS: Between 1998 and 2007, 84 patients underwent iGFR and eGFR before and after renal artery stenting. All eGFR demonstrated poor sensitivity and reliability for detecting ≥20% changes in iGFR, and poor agreement in the magnitude and direction of change in iGFR, before and after renal stenting. CONCLUSIONS: In RAS patients, eGFR demonstrate poor sensitivity and reliability for detecting meaningful changes in iGFR after renal artery stenting. eGFR should be abandoned as primary endpoints in major clinical trials assessing the impact of renal revascularization on renal function.

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.

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.

Renal function equations before and after living kidney donation: a within-individual comparison of performance at different levels of renal function.

BACKGROUND AND OBJECTIVES: The Modification of Diet in Renal Disease (MDRD) study equation and the Cockcroft-Gault (CG) equation perform poorly in the (near-) normal range of GFR. Whether this is due to the level of GFR as such or to differences in individual characteristics between healthy individuals and patient with chronic kidney disease (CKD) is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We evaluated the performance of MDRD, CG per BSA (CG/(BSA)) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations compared with measured GFR (mGFR; I-iothalamate) at 4 months before and 2 months after donation in 253 consecutive living kidney donors. RESULTS: mGFR declined from 103 ± 15 to 66 ± 11 ml/min per 1.73 m(2) after donation. All equations underestimated mGFR at both time points. Arithmetic performance analysis showed improved performance after donation of all equations, with significant reduction of bias after donation. Expressed as percentage difference, mGFR-estimated GFR (eGFR) bias was reduced after donation only for CG/(BSA). Finally, in 295 unselected individuals who were screened for donation, mGFR was below the cutoff for donation of 80 ml/min per 1.73 m(2) in 19 individual but in 166, 98, and 74 for MDRD, CDK-EPI, and CG/(BSA), respectively. CONCLUSIONS: A higher level of GFR as such is associated with larger absolute underestimation of true GFR by eGFR. For donor screening purposes, eGFR should be interpreted with great caution; when in doubt, true GFR should be performed to prevent unjustified decline of prospective kidney 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.

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.

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.

Assessment of PD treatment delivered by 125I-Iothalamate plasma disappearance.

The calculation of treatment delivered to PD patients requires the collection of PD effluent, plasma and urine samples. 125I-Iothalamate plasma disappearance, which eliminates the need for PD effluent collections, was tested as an alternate method to measure the weekly PD treatment delivered. Two protocols were designed. In protocol A, a 35 microCi dose of 125I-Iothalamate was injected in three subjects and allowed to equilibrate. A plasma sample was taken and patients returned on both of the following two days with timed labeled effluent bags and a 24-hour urine collection for each day. The timed PD effluent and 24-hour urine collections were measured for 125I-Iothalamate, urea and creatinine concentrations. 125I-Iothalamate and urea clearances were strongly correlated for both PD (R2 = 0.76, n = 24) and renal (R2 = 0.92, n = 6) clearances. In protocol B, thirteen subjects were given a 35 microCi injection of 125I-Iothalamate. A blood sample was taken one hour post injection and a second blood sample taken on day five. Kt/V were calculated from the 125I-Iothalamate plasma disappearance curve and compared to weekly Kt/V values extrapolated from one day's collections (Traditional Method). The comparison of Kt/V values found by 125I-Iothalamate Method vs. the "Traditional Method" yielded R2 = 0.79, n = 13. In conclusion, the plasma disappearance of 125I-Iothalamate is an alternate method of determining weekly Kt/V, over an extended period of time, which eliminates the need for PD effluent collections.

GFR determined by nonradiolabeled iothalamate using capillary electrophoresis.

Traditional measurements of glomerular filtration rate (GFR) in clinical practice include the measurement of serum creatinine or creatinine clearance. Increasing evidence concerning the limitation of these measurements in clinical practice and clinical trials has resulted in efforts to develop technologies that improve measurement of GFR. Recent efforts in that regard have used radioisotopic labeling of markers of GFR, such as 125I-iothalamate, and 51Cr-ethylenediaminetetraacetic acid. Limitations of these technologies include radiation exposure as well as cost considerations for the management of radioisotopes, including safety, disposal, mailing, and deteriorating activity that results in short shelf life. We report a test that used 0.5 mL Conray dye injected subcutaneously and subsequent measurement of the nonisotopic (cold) iothalamate by capillary electrophoresis in blood and urine. GFR using cold iothalamate compared with standard clearance using 125I-iothalamate was 0.99. The method is cost-effective and allows for avoiding exposure to isotopes, as well as problems such as the disposal and short shelf life of isotopes. This technology could allow for replacement of 125I-iothalamate as a marker for GFR.

Constant infusion clearance is an inappropriate method for accurate assessment of an impaired glomerular filtration rate.

Recently renewed interest has been focused on constant infusion clearance to assess GFR accurately. In this study we compared GFR and ERPF calculated from the constant infusion method (CIM = I x V/P) with that calculated from the standard method (StM = U x V/P), in 100 patients with renal disease who were subdivided in four groups according to their GFR-StM (< 30; 30-60; 60-90; > 90 ml/min). After a priming dose, a constant infusion of 125I-iothalamate (= GFR) and 131I-hippurate (= ERPF) was started at 9 a.m. The infusion rates were individually adjusted to the GFR which was approximated from the serum creatinine concentration. After a 90-min equilibration period, GFR-StM and ERPF-StM were determined for two 2-h periods. These values were compared with GFR-CIM and ERPF-CIM calculated from the plasma concentration of the respective tracers at the end of each 2-h period (= 210 and 330 min). In the patient group with GFR-StM < 30 ml/min, the 125I-iothalamate plasma concentration increased progressively over time. Consequently, average GFR-CIM at 210 min (34.2, SE +/- 2.1 ml/min) was higher than the GFR-CIM at 330 min (31.9, SE +/- 2.0 ml/min; P < 0.001). In addition both values were significantly higher than the corresponding GFR-StM values (18.1 +/- 2.4 and 15.3 +/- 1.6 ml/min respectively). In the two patient groups with GFR-StM > 60 ml/min, the 125I-iothalamate plasma concentration decreased progressively over time.(ABSTRACT TRUNCATED AT 250 WORDS)

[Adverse reactions to high osmolarity contrast media. A comparative-prospective study]. / Reacciones adversas a medios de contraste de alta osmalaridad. Estudio comparativo--prospectivo.

The purpose of this study was to verify and compare the different types of reactions to iodinated contrast media available at the Social Security Metropolitan Hospital Complex: Conray 60%, Vascoray and Uromiron. These are ionic, high osmolality compounds. The authors found that, in 400 patients not only the osmolality had an important role in the reactions observed, but that the intrinsic nature of the molecule of the contrast medium used was the determining factor.

Reacciones adversas a medios de contraste de alta osmalaridad. Estudio comparativo--prospectivo / Adverse reactions to high osmolarity contrast media. A comparative-prospective study

The purpose of this study was to verify and compare the different types of reactions to iodinated contrast media available at the Social Security Metropolitan Hospital Complex: Conray 60%, Vascoray and Uromiron. These are ionic, high osmolality compounds. The authors found that, in 400 patients not only the osmolality had an important role in the reactions observed, but that the intrinsic nature of the molecule of the contrast medium used was the determining factor

Assessment of renal function by serum creatinine and creatinine clearance: glomerular filtration rate estimated by four procedures.

We compared creatinine concentrations in serum and urine and creatinine clearances determined by two Jaffé (Beckman's "Astra," Boehringer Mannheim Diagnostics) and two enzymatic (Kodak, Boehringer Mannheim Diagnostics) methods. Serum creatinine and creatinine clearances determined by each method were also compared with the glomerular filtration rate as measured with use of sodium [125I]iothalamate in patients with a wide range of renal function. Results between methods correlated excellently, but we saw clear method-dependent biases of up to 2.9 mg/L for serum. The highest serum creatinine values and the lowest creatinine clearances were obtained with Boehringer Mannheim Diagnostics' Jaffé method. The reciprocal of the serum creatinine and the creatinine clearance also correlated well with the glomerular filtration rate, but all methods over-estimated the glomerular filtration rates to varying degrees. Appropriate standardization of methods appears to be as important as method principle for establishing an accurate relationship between creatinine determinations and glomerular filtration rate.

Variability in arteriographic assessment of the carotid bifurcation.

We evaluated interobserver and intraobserver variability in the arteriographic assessment of the carotid bifurcation. Two neuroradiologists evaluated area stenosis and lumen surface morphology for 60 biplane carotid arteriograms in two reading sessions. Absolute interobserver differences for area stenosis averaged 8.8%, and interobserver differences were statistically significant for arteries of at least 50% stenosis. Analysis of observations for lumen surface morphology revealed statistically significant interobserver differences, averaging 29.5% disagreement. Intraobserver differences were not statistically significant. Observer variability for arteriography should be considered in the process of evaluating patients for carotid endarterectomy.

Safer, more expensive iodinated contrast agents: how do we decide?

The advantages of the new, safer, but more expensive iodinated contrast agents are discussed, and opinions on which patient groups should receive the agents are presented.

Assessment of compensatory renal function and [125I]iothalamate clearance in sheep.

Compensatory renal function and sodium [125I]iothalamate clearance were studied in 4 adult Merino ewes. Renal clearances of inulin (CIN), iothalamate (CIOT), and p-aminohippurate (CPAH) were used to measure renal function before and 7 and 170 days after 50% and 75% reductions in renal mass. Renal mass reduction to 50% of normal was achieved by ligation of the right renal artery, and to 25% of normal by ligating the right renal artery and branches of the left renal artery. Renal function (CIN and CPAH) after 50% renal mass reduction was 78% of normal on postligation day (PLD) 7 and 64% of normal on PLD 170. This decrease in renal function between PLD 7 and 170 was significant (P less than 0.05). Renal function (CIN and CPAH) after 75% renal mass reduction was 55% of normal on PLD 7 and 48% on PLD 170; however, this decrease in renal function between PLD 7 and 170 was not significant. Results indicated that, shortly after 50% renal mass reduction by renal arterial ligation, renal function in ewes was greater than that previously reported after unilateral nephrectomy and that a further decrease in renal function developed within 6 months after ligation. The mean CIOT in healthy ewes was 2.46 ml/min/kg of body weight. In healthy ewes and in ewes after renal mass reduction, regression of the simultaneous CIOT and CIN was CIOT = 0.276 + 1.05 CIN. The CIOT was higher than the corresponding CIN, and remained significantly (P less than 0.01) and consistently higher. Therefore, iothalamate can be used to estimate glomerular filtration rate in sheep, although a correction factor is required.