Isotopic Glomerular Filtration Rate Research Articles

177 Lu-DOTATATE PRRT Safety and Organ-at-Risk Dosimetry in Patients With Gastroenteropancreatic Neuroendocrine Tumors : Data From the Prospective Phase 2 LUMEN Study.

The aim of this study was to assess the association among toxicity, dosimetry of organs-at-risk, and disease progression in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with 177 Lu-DOTATATE. Thirty-seven patients with GEP-NETs underwent 177 Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) in a single-arm, prospective, phase 2 study, where patients were followed up with blood tests, isotopic glomerular filtration rate (iGFR), and imaging examinations (CT/MRI and PET) every 6 months until disease progression. Adverse events (AEs) graded per CTCAEv4.03 and occurring during treatment were collected and followed up until resolution. Dosimetry, including biologically effective doses (BEDs) to kidneys, BED to bone marrow, and absorbed dose (AD) to spleen, was performed after each PRRT cycle. Statistical analyses explored associations among dosimetry, toxicity, and patient progression free-survival. The most common AEs were anemia and lymphopenia (65%), followed by thrombocytopenia and fatigue (each 51%), alopecia (46%), and nausea (41%). The most common grade ≥3 AE was lymphopenia (43%). There was no grade ≥3 nephrotoxicity. The median iGFR % decrease was 11% ( P < 0.001), at a median follow-up of 23 months. iGFR %decrease and renal BED did not correlate (Spearman ρ = -0.09). Similarly, no significant association was found between bone marrow BED or spleen AD and the grades of hematological toxicities. We observed no association between progression free-survival and either the decline of renal function or the occurrence of hematological toxicities during PRRT. This study confirms the safety profile of 177 Lu-DOTATATE PRRT in patients with GEP-NETs irrespective of the dosimetry of organs at risk. Kidney, bone marrow, and spleen dosimetry measures were not associated with renal or hematological toxicity.

Fibroblast growth factor 23 but not copeptin is independently associated with kidney failure and mortality in patients with chronic kidney disease.

Copeptin and intact fibroblast growth factor 23 (iFGF23) increase early during chronic kidney disease (CKD) and may be predictive of unfavourable outcomes. The aim of this study was to evaluate their respective associations with renal and vital outcomes in CKD patients. We included CKD patients from the NephroTest cohort with concomitant measurements of plasma copeptin and iFGF23 concentrations and isotopic glomerular filtration rate measurement (mGFR). The primary endpoint was a composite outcome including kidney failure (KF) (dialysis initiation, pre-emptive transplantation or a 57% decrease of mGFR, corresponding to doubling of serum creatinine) or death before KF. Hazard ratios (HRs) of the primary endpoint associated with log-transformed copeptin and iFGF23 concentrations were estimated by Cox models. The slope of mGFR over time was analysed using a linear mixed model. A total of 329 CKD patients (243 men, mean age 60.3±14.6years) were included. Among them, 301 with an mGFR >15ml/min/1.73m2 were included in survival and mGFR slope analyses. During a median follow-up of 4.61years (quartile 1-quartile 3: 3.72-6.07), 61 KFs and 32 deaths occurred. Baseline iFGF23 concentrations were associated with the composite outcome after multiple adjustments {HR 2.72 [95% confidence interval (CI) 1.85-3.99]}, whereas copeptin concentrations were not [HR 1.01 (95% CI 0.74-1.39)]. Neither copeptin nor iFGF23 were associated with mGFR slope over time. Our study shows for the first time in population of CKD patients an independent association between iFGF23 and unfavourable renal and vital outcomes and shows no such association regarding copeptin, encouraging the integration of iFGF23 measurement into the follow-up of CKD.

P06 Improving renal function monitoring during chemotherapy- a role for cystatin C?

AimRenal toxicity causes major morbidity following chemotherapy- abnormal iGFRs may be detected in up to 73.7% of patients.1 Creatinine is universally used as a biomarker to track fluctuating function and to calculate surrogate glomerular filtration rate (GFR) in the form of estimating equations.2 There is concern regarding the suitability of creatinine as a biomarker in this population, and it is proposed that cystatin C as a biomarker alone and also included in estimating equations may offer improved clinical suitability and accuracy.3MethodsIn this prospective, longitudinal study over a period of 18 months, 132 combined isotope GFR (iGFR), creatinine and cystatin C measurements were taken from 48 paediatric oncology patients at a Northern Children’s Hospital. Correlation and agreement analysis was performed for both individual biomarkers and estimating equations. Sensitivity data, along with ROC curve analysis was performed for all biomarkers and estimating equations. Data from three identified patients was isolated to examine individual patient variation over time.ResultsCreatinine identified only 1/32 patients with an abnormal iGFR (&lt;90 ml/min/1.73 m2) compared to cystatin C which identified 12/32. Creatinine values and both estimating equations failed to change significantly over a period of declining iGFR though cystatin C did show a significant inverse increase (p&lt;0.05). Bland Altman analysis for both the creatinine and combined equation showed poor agreement (mean difference -64 ml/min/1.3 m2 and -20 ml/min/1.73 m2 respectively). All biomarkers and equations showed poor sensitivity to detect an abnormal iGFR either below 70 ml/min/1.73 m2 or 90 ml/min/1.73 m2. A transformation factor applied to the equations significantly improved the sensitivity and clinical applicability of all equations. The data from three individual patients failed to reveal any significant intra-patient relationships.ConclusionData from this study cannot support the use of creatinine or cystatin C as a single biomarker to monitor renal function in children undergoing chemotherapy. Newer cystatin C and creatinine combined equations, whilst offering statistical superiority, do not offer the clinical superiority to replace iGFR or provide a tool for accurate dose calculations. A transformation factor can be applied to the results gained from the estimating equations to significantly improve the detection of abnormal iGFR, though work in other patient cohorts is needed to support this. Previous work also supported the use of a transformation factor, though application of their transformation factor to this current cohort failed to replicate the 100% sensitivity findings previously demonstrated4. Three patients were identified from the cohort and their paired iGFR and estimated GFR were monitored prospectively, over a period of approximately a year. Significant variation was observed between iGFR and eGFR at each time point for all three patients and therefore personalisation of GFR estimation from baseline iGFR and demographic data could not be proposed. This requires exploration in a larger cohort with the possible inclusion of additional baseline variables.ReferencesCRUK Survival trends over time in Children’s Cancers. 1.2015. https://www.cancerresearchuk.org/health-professional/cancer-statistics/childrens-cancers/survival#heading-Two Accessed 28th March 2019.NICE ( 2013) CG169 Acute kidney injury: Prevention, detection and management of acute kidney injury up to the point of renal replacement therapy.Barnfield, MC, Burniston, MT, Reid, U, et al. Cystatin C in assessment of glomerular filtration rate in children and young adults suffering from cancer. Nuclear Medicine Communications 2013;34:609–614.Dodgshun, AJ, Quinlan, C, Sullivan, MJ. Cystatin C based equation accurately estimates glomerular filtration rate in children with solid and central nervous system tumours: enough evidence to change practice? Pediatric Blood and Cancer 2016;63:1535–1538.

Prediction of Nephrotoxicity Associated With Cisplatin-Based Chemotherapy in Testicular Cancer Patients.

BackgroundCisplatin-based chemotherapy may induce nephrotoxicity. This study presents a random forest predictive model that identifies testicular cancer patients at risk of nephrotoxicity before treatment.MethodsClinical data and DNA from saliva samples were collected for 433 patients. These were genotyped on Illumina HumanOmniExpressExome-8 v1.2 (964 193 markers). Clinical and genomics-based random forest models generated a risk score for each individual to develop nephrotoxicity defined as a 20% drop in isotopic glomerular filtration rate during chemotherapy. The area under the receiver operating characteristic curve was the primary measure to evaluate models. Sensitivity, specificity, and positive and negative predictive values were used to discuss model clinical utility.ResultsOf 433 patients assessed in this study, 26.8% developed nephrotoxicity after bleomycin-etoposide-cisplatin treatment. Genomic markers found to be associated with nephrotoxicity were located at NAT1, NAT2, and the intergenic region of CNTN6 and CNTN4. These, in addition to previously associated markers located at ERCC1, ERCC2, and SLC22A2, were found to improve predictions in a clinical feature–trained random forest model. Using only clinical data for training the model, an area under the receiver operating characteristic curve of 0.635 (95% confidence interval [CI] = 0.629 to 0.640) was obtained. Retraining the classifier by adding genomics markers increased performance to 0.731 (95% CI = 0.726 to 0.736) and 0.692 (95% CI = 0.688 to 0.696) on the holdout set.ConclusionsA clinical and genomics-based machine learning algorithm improved the ability to identify patients at risk of nephrotoxicity compared with using clinical variables alone. Novel genetics associations with cisplatin-induced nephrotoxicity were found for NAT1, NAT2, CNTN6, and CNTN4 that require replication in larger studies before application to clinical practice.

Assessing the impact of inadequate hydration on isotope-GFR measurement

Guidelines state that patients undergoing isotope glomerular filtration rate (GFR) tests should maintain adequate hydration, but pragmatically these tests can coincide with procedures requiring the patient not to eat or drink (‘nil-by-mouth’) for up to 12 hours beforehand. This study investigated the impact of a 12-hour nil-by-mouth regime on GFR measurement. Twelve healthy volunteers were recruited from our institution. Exclusion criteria included diabetes mellitus, being under 18 years of age and pregnancy. Isotope GFR measurements were carried out on these volunteers twice. One of the tests adhered strictly to the British Nuclear Medicine Society (BNMS) guidelines for GFR measurement and the other test was carried out after the volunteers had refrained from eating or drinking anything for 12 hours. The order of these tests was randomly assigned. The results show that after a nil-by-mouth regime, participants’ average absolute GFR fell from 108 ml/min to 97 ml/min (p < .01), while normalised GFR fell from 97 ml/min/1.73 m2 to 88 ml/min/1.73m2 (p < .01). Serum creatinine rose from 68 mmol/L to 73 mmol/L (p < .05). There were no changes in blood pressure, serum hydration markers or bio-impedance measured fluid status. Urine analysis showed statistically significant increases in urea, creatinine and osmolality levels after the nil-by-mouth regime. The results highlight the importance of following current guidelines recommending fluid intake during the procedure. Practitioners should consider what other outpatient appointments are being scheduled concurrently with a GFR test.

A Population Pharmacokinetic Model for 51Cr EDTA to Estimate Renal Function

51Cr EDTA clearance (CL) from plasma is used to estimate glomerular filtration rate (GFR). We propose that current methods for analysing the raw 51Cr EDTA measurements over-simplifies the disposition of 51Cr EDTA and therefore could produce biased GFR estimates. The aim of this study was to develop a population pharmacokinetic model for 51Cr EDTA disposition and to compare model-predicted GFR to other methods of estimating renal function. Data from 40 individuals who received ~7.4MBq of 51Cr EDTA, as an intravenous bolus, were available for analysis. Plasma radioactivity (counts/min) was measured from timed collection points at 2, 4, 6 and 24h after the dose. A population analysis was conducted using NONMEM® version 7.2. Model-predicted GFR was compared with other methods for estimating renal function using mean prediction error (MPE). A two-compartment pharmacokinetic model with first-order elimination best fit the data. Compared with the model predictions, creatinine CL from 24h urine data was unbiased. The commonly used 'slope-intercept' method for estimating isotopic GFR was positively biased compared with the model (MPE 15.5mL/min/1.73m2 [95% confidence interval {CI} 8.9-22.2]. The Cockcroft Gault, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equations led to negatively biased GFR estimates (MPE -19.0 [95% CI -25.4 to -12.7], -20.1 [95% CI -27.2 to -13.1] and -16.5 [95% CI -22.2 to -10.1] mL/min/1.73m2, respectively). The biased GFR estimates were most obvious in patients with relatively normal renal function. This may lead to inaccurate dosing in patients who are receiving drugs with a narrow therapeutic range where dosing is adjusted according to GFR estimates (e.g. carboplatin). The study is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), number: ACTRN 12611000035921.

Cystatin C Based Equation Accurately Estimates Glomerular Filtration Rate in Children With Solid and Central Nervous System Tumours: Enough Evidence to Change Practice?

Assessing the glomerular filtration rate (GFR) of paediatric patients receiving nephrotoxic chemotherapy is a vital element of clinical practice. Isotopically measured GFR is the gold standard in terms of accuracy but requires injection of tracer followed by several hours of blood tests. Estimation of GFR using creatinine is widely used but inaccurate, and there is increasing concern regarding its usage for paediatric oncology patients. Cystatin C (CysC) based equations are increasingly used in other paediatric specialities to estimate GFR, and their usefulness in paediatric oncology practice is becoming evident. We assessed the renal function of children with solid tumours and CNS tumours receiving nephrotoxic chemotherapy over a 1-year period using paired CysC and isotopic GFR. Fifty-six sets of measurements were reviewed with estimated GFR predicted using CysC-based and creatinine-based equations. The best performing equation was the 'new CKiD' equation, which estimated GFR within 30% of the measured GFR on 86% of occasions, outperforming the Schwartz equation. If estimated GFR using this equation was >100 ml/min/1.73 m(2) , all values of measured GFR were normal at >90 ml/min/1.73 m(2) , a category containing two-thirds of all measurements. The new CKiD equation predicts GFR in paediatric oncology patients with more accuracy than creatinine-based equations. When the estimated GFR is >100 ml/min/1.73 m(2) , isotopic GFR can be safely omitted.

Cardiovascular Effects of Unilateral Nephrectomy in Living Kidney Donors.

There is a robust inverse graded association between glomerular filtration rate (GFR) and cardiovascular risk, but proof of causality is lacking. Emerging data suggest living kidney donation may be associated with increased cardiovascular mortality although the mechanisms are unclear. We hypothesized that the reduction in GFR in living kidney donors is associated with increased left ventricular mass, impaired left ventricular function, and increased aortic stiffness. This was a multicenter, parallel group, blinded end point study of living kidney donors and healthy controls (n=124), conducted from March 2011 to August 2014. The primary outcome was a change in left ventricular mass assessed by magnetic resonance imaging (baseline to 12 months). At 12 months, the decrease in isotopic GFR in donors was -30±12 mL/min/1.73m(2). In donors compared with controls, there were significant increases in left ventricular mass (+7±10 versus -3±8 g; P<0.001) and mass:volume ratio (+0.06±0.12 versus -0.01±0.09 g/mL; P<0.01), whereas aortic distensibility (-0.29±1.38 versus +0.28±0.79×10(-3) mm Hg(-1); P=0.03) and global circumferential strain decreased (-1.1±3.8 versus +0.4±2.4%; P=0.04). Donors had greater risks of developing detectable highly sensitive troponin T (odds ratio, 16.2 [95% confidence interval, 2.6-100.1]; P<0.01) and microalbuminuria (odds ratio, 3.8 [95% confidence interval, 1.1-12.8]; P=0.04). Serum uric acid, parathyroid hormone, fibroblast growth factor-23, and high-sensitivity C-reactive protein all increased significantly. There were no changes in ambulatory blood pressure. Change in GFR was independently associated with change in left ventricular mass (R(2)=0.28; P=0.01). These findings suggest that reduced GFR should be regarded as an independent causative cardiovascular risk factor. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01028703.

37 Cardiovascular Effects of Unilateral Nephrectomy in Human Kidney Donors

<h3>Introduction</h3> There is a graded association between chronic kidney disease and cardiovascular (CV) risk but proof of causality is lacking and the pathophysiological mechanisms responsible for this relationship remain unclear. We hypothesised that the reduction in glomerular filtration rate (GFR) accompanying nephrectomy in live kidney donors causes increased left ventricular (LV) mass, impaired LV function and increased aortic stiffness. <h3>Methods</h3> This was a multicentre, parallel group, blinded end point study of live kidney donors and healthy controls (n = 124). The primary outcome was change in LV mass assessed by MRI (baseline to 12 months). Pre-specified secondary outcomes included changes in: isotopic GFR; LV strain; blood pressure (BP); aortic pulse wave velocity (PWV) and distensibility; and cardiac biomarkers. <h3>Results</h3> When compared to controls, LV mass (+7 +/- 10 g vs. −3 +/- 8 g; P &lt; 0.001), LV mass-volume ratio (+0.06 +/- 0.12 g/ml vs. −0.01 +/- 0.09 g/ml; P &lt; 0.01) and PWV (+0.5 +/- 0.9 m/s vs. −0.1 +/- 0.7 m/s; P &lt; 0.001) were increased in donors. Aortic distensibility (−0.29 +/- 1.38 × 10^–3 mmHg^-1vs. +0.28 +/- 0.79 × 10^–3 mmHg^-1; P = 0.03) and global circumferential strain (−1.1 +/- 3.8% vs. +0.4 +/- 2.4%; P = 0.04) were reduced in donors. The decrease in GFR (−30 +/- 12 mL/min/1.73 m²) in donors was accompanied by increases in uric acid (+56 +/- 35 micromol/L vs. +2 +/- 33 micromol/L; P &lt; 0.001), parathyroid hormone (+1.1 +/- 1.6 pg/mL vs. +0.4 +/- 1.3 pg/mL; P = 0.03) and hs-CRP (+1.7 +/- 5.3 mg/dl vs. -0.7 +/- 5.2 mg/dL; P &lt; 0.01), with greater risks of developing detectable hs-Troponin T (21% vs. 2%; OR 16.2; P &lt; 0.01) and microalbuminuria (7% vs. 0%; OR 3.74; P = 0.04). There were no significant changes in circulating levels of renin or aldosterone and no changes in brachial or central BP. Change in GFR was an independent predictor of the change in LV mass after adjustment for age, sex, baseline LV mass, and 12-month changes in BP, uric acid and parathyroid hormone (Beta = −0.3, R² = 0.31, P = 0.002). <h3>Conclusions</h3> A modest reduction in GFR causes increased LV mass, LV systolic dysfunction, increased aortic stiffness and adverse changes to CV biomarkers. Reduced GFR should be regarded as an independent causative CV risk factor.

The 99mTc-DTPA Urinary Clearance Method May Be Preferable to the Plasma Disappearance Method for Assessing Glomerular Filtration Rate in Diabetic Nephropathy

Background: Isotopic glomerular filtration rate (iGFR) measurement is comparable to the inulin method. In this study, we compared urinary and plasma iGFR methodologies in patients with diabetic nephropathy. Methods: A total of 147 patients from 3 sites in the Diabetic Intervention with Vitamins to Improve Nephropathy (DIVINe) trial provided 213 sets of urine and blood collections, at baseline, 18 and 36 months. Results: The mean (with standard deviation) plasma iGFR of 60.7 (24.9) ml/min/1.73 m² compared to urinary iGFR of 52.0 (28.0) ml/min/1.73 m² was statistically significant (p value <0.001). Although plasma and urinary iGFRs were highly related (R² = 0.86), plasma iGFR increasingly overestimated urinary iGFRs at lower GFRs. In contrast to the cross-sectional analyses, the two measures of iGFR were weakly related (R² = 0.32) in regard to patients' change over 18 months of follow-up. Conclusion: Plasma iGFR may not be a suitable method for accurately measuring GFR in patients with advancing degrees of chronic kidney disease from diabetic nephropathy.

Evaluation of Serum Cystatin C as a Marker of Early Renal Impairment in Patients with Liver Cirrhosis

Background. Serum cystatin C (CysC) was proposed as an effective reflection of the glomerular filtration rate (GFR). However, its role in patients with liver cirrhosis has not been extensively verified especially in the detection of early RI. Patients and Methods. Seventy consecutive potential candidates for living donor liver transplantation with serum creatinine (Cr) <1.5 mg/dL were included. CysC, Cr, and estimated GFR [creatinine clearance (CCr), Cockcroft-Gault formula (C-G), MDRD equations with 4 and 6 variables, CKD-EPI-Cr, CKD-EPI-CysC, and CKD-EPI-Cr-CysC] were all correlated to isotopic GFR. Early RI was defined as GFR of 60–89 mL/min/1.73 m2. Results. Patients were 25.7% and 74.3% Child-Pugh classes B and C, respectively. GFR was ≥90, 60–89, and 30–59 mL/min/1.73 m2 in 31.4%, 64.3%, and 4.3% of the patients, respectively. All markers and equations, except C-G, were significantly correlated to GFR with CKD-EPI-Cr-CysC formula having the highest correlation (r = 0.474) and the largest area under the ROC curve (0.808) for discriminating early RI. At a cutoff value of 1.2 mg/L, CysC was 89.6% sensitive and 63.6% specific in detecting early RI. Conclusion. In patients with liver cirrhosis, CysC and CysC-based equations showed the highest significant correlation to GFR and were measures that best discriminated early RI.

Determining appropriate ambient lighting levels in Radiology reporting rooms

Determining appropriate ambient lighting levels in Radiology reporting rooms

Performance of formulae based estimates of glomerular filtration rate for carboplatin dosing in stage 1 seminoma

BackgroundSingle cycle carboplatin, dosed by glomerular filtration rate (GFR), is standard adjuvant therapy for stage 1 seminoma. Accurate measurement of GFR is essential for correct dosing. Isotopic methods remain the gold standard for the determination of GFR. Formulae to estimate GFR have improved the assessment of renal function in non-oncological settings. We assessed the utility of these formulae for carboplatin dosing. MethodsWe studied consecutive subjects receiving adjuvant carboplatin for stage 1 seminoma at our institution between 2007 and 2012. Subjects underwent 51Cr-ethylene diamine tetra-acetic acid (EDTA) measurement of GFR with carboplatin dose calculated using the Calvert formula. Theoretical carboplatin doses were calculated from estimated GFR using Chronic Kidney Disease-Epidemiology (CKD-EPI), Management of Diet in Renal Disease (MDRD) and Cockcroft–Gault (CG) formulae with additional correction for actual body surface area (BSA). Carboplatin doses calculated by formulae were compared with dose calculated by isotopic GFR; a difference <10% was considered acceptable. Results115 patients were identified. Mean isotopic GFR was 96.9ml/min/1.73m2. CG and CKD-EPI tended to overestimate GFR whereas MDRD tended to underestimate GFR. The CKD-EPI formula had greatest accuracy. The CKD-EPI formula, corrected for actual BSA, performed best; 45.9% of patients received within 10% of correct carboplatin dose. Patients predicted as underdosed (13.5%) by CKD-EPI were more likely to be obese (p=0.013); there were no predictors of the 40.5% receiving an excess dose. ConclusionsOur data support further evaluation of the CKD-EPI formula in this patient population but clinically significant variances in carboplatin dosing occur using non-isotopic methods of GFR estimation. Isotopic determination of GFR should remain the recommended standard for carboplatin dosing when accuracy is essential.

Alemtuzumab Induction in Renal Transplantation Permits Safe Steroid Avoidance with Tacrolimus Monotherapy

The use of alemtuzumab as induction immunosuppression for renal transplantation introduces the possibility of long-term tacrolimus monotherapy, avoiding maintenance with both corticosteroids and mycophenolate mofetil (MMF). We conducted a single-center, prospective, open-label, randomized controlled trial comparing two steroid avoidance regimens between December 2006 and November 2010. One hundred and sixteen adult patients were randomized to either basiliximab induction followed by tacrolimus and MMF maintenance or to alemtuzumab induction followed by tacrolimus monotherapy. The primary endpoint was noninferiority of isotopic glomerular filtration rate at 1 year; secondary endpoints included patient and graft survival, incidence of delayed graft function, and incidence and severity of biopsy-proven acute rejection. The two groups were well matched for all baseline demographics. Isotopic glomerular filtration rate was comparable between the groups at 1 year (57±26 mL/min for alemtuzumab group and 53±21 mL/min for basiliximab group; P=0.42). Secondary endpoints were also similar between the groups. The rate of biopsy-proven acute rejection by 12 months was lower in the alemtuzumab group (n=6 vs. n=14 in basiliximab arm) just reaching statistical significance (P=0.049); however, a single extra case in the alemtuzumab arm included when considering clinically treated rejection removes this significance (P=0.082). Similar rates of cardiovascular, infective, and neoplastic complications were observed in both groups. Forty-seven (81.0%) of the patients in the alemtuzumab group remained on tacrolimus monotherapy at 12 months. Renal transplantation with alemtuzumab induction followed by tacrolimus monotherapy leads to good graft and patient outcomes, with no major differences detected compared with basiliximab induction and tacrolimus/MMF maintenance at 1 year.

Weight-loss diets in people with type 2 diabetes and renal disease: a randomized controlled trial of the effect of different dietary protein amounts

Higher-protein weight-loss diets (defined as >25% of energy as protein) are not recommended for individuals with type 2 diabetes because of their potential adverse effect on renal function. We aimed to examine the effect of such diets on renal function over 12 mo in people with type 2 diabetes and early renal disease. Overweight and obese people with type 2 diabetes were screened to identify those with an albumin:creatinine ratio from 3 to 30 mg/mmol. Seventy-six subjects were randomly assigned to either a moderate-protein weight-loss diet or a standard-protein weight-loss diet for 12 mo. The primary endpoint was the change in renal function as assessed by the isotope glomerular filtration rate (GFR), estimated GFR, and cystatin C. Forty-five subjects (moderate protein: n = 21; standard protein: n = 24) completed the study. The mean (±SE) weight loss was not different between diets at 9.7 ± 13.4 kg for the moderate-protein diet and 6.6 ± 7.1 kg for the standard-protein diet. There were no changes in renal function or albuminuria or blood pressure, although glycated hemoglobin was lowered with both diets. Changes in renal function were related to the baseline estimated GFR. Patients with stage 1-3 renal disease (<120 mL · min(-1) · 1.73 m(-2); n = 33) had an improvement in renal function, whereas patients with hyperfiltration (>120 mL · min(-1) · 1.73 m(-2); n = 12) had a decrease in the GFR. After adjustment for weight loss, the baseline GFR remained a significant predictor of outcomes with no effect of dietary treatment. An average difference in protein intake between diets of 19 ± 6 g/d was achieved. Weight loss improved renal function, but differences in dietary protein had no effect. This trial was registered at the Australian and New Zealand Clinical Trial Register as ACTRN12608000045314.

Effect of Early Stage Kidney Disease on Cardiac Mass: Comparison to Post-Donation Renal Function

Background/Aim: In chronic renal failure the increase in cardiovascular risk is in part related to the high prevalence of left ventricular hypertrophy. The aim of the present monocentric retrospective study was to evaluate the influence of the presence of parenchymal kidney disease on left ventricular geometry in normotensive (arterial pressure <140/90 mm Hg) patients (KD+, n = 50, mean age 39 ± 19 years) with mild to moderate renal failure (stage 2-3 chronic kidney disease). Methods: Left ventricular geometry was estimated by echocardiography and compared to a group of healthy subjects with similarly reduced renal function as a consequence of renal donation (KD-, n = 63, mean age 52 ± 12 years). Results: Subjects with and without kidney disease had similar blood pressure, body mass index and isotopic glomerular filtration rate. Left ventricular mass (LVM) indexed to body surface area was greater in KD+ as compared to KD- subjects and the difference was more pronounced in women than in men. The increase in LVM in KD+ patients was associated with lower albuminemia and hematocrit, and a higher plasma renin activity and aldosterone as compared to KD- subjects. In multivariate analysis, kidney disease emerged as an important determinant of LVM index independently of age, gender and blood pressure. Conclusion: This observation suggests that the presence of kidney disease has an independent amplifying effect on LVM which could be related to volume overload and/or prohypertrophic factors such as aldosterone.

Cystatin C in assessment of glomerular filtration rate in children and young adults suffering from cancer

The study objective was to establish the diagnostic efficacy of cystatin C in the assessment of glomerular filtration rate (GFR) in paediatric oncology patients by investigating the relationships between serum cystatin C, serum creatinine and isotope clearance and determining whether these relationships are different from those seen in a group of patients of similar age with renal disease. This was a cohort study in which patients were divided into two groups: group A comprised renal patients and group B comprised oncology patients. All patients were referred for isotopic GFR assessment as part of routine clinical management and concurrently also had assessments made of their serum creatinine and cystatin C levels, together with height and weight measurements. Reciprocals of cystatin C correlate well with isotopic GFR; correlation coefficients from linear regression were 0.83 and 0.66 for the renal and oncology groups, respectively. However, when GFR was assessed from serum creatinine and cystatin C, levels of agreement were still very high (95% levels of agreement: -33 and 31 ml/min/1.73 m for cystatin C and -46 and 30 ml/min/1.73 m for the Counahan serum creatinine estimate). Receiver-operator characteristic curve analysis demonstrated that cystatin C has improved diagnostic utility for identifying patients with GFRs both below normal (90 ml/min/1.73 m) and below the point at which chemotherapy dose reduction may be considered (60 ml/min/1.73 m). Levels of intrapatient variability were similar for both tracers. Cystatin C was shown to be a better indicator of renal function compared with serum creatinine in oncology patients as demonstrated by receiver-operator characteristic curve and Bland-Altman analyses; however, sensitivity of the tracer to mild reductions in GFR is still low.

1416 ARE WE EVALUATING PROPERLY THE RENAL FUNCTION WITH THE MODIFICATION OF DIET IN RENAL DISEASE (MDRD) IN PATIENTS WITH ORTHOTOPIC ILEAL NEOBLADDER?

You have accessJournal of UrologyUrinary Diversion: Bladder Reconstruction, Augmentation, Substitution, Diversion (II)1 Apr 20131416 ARE WE EVALUATING PROPERLY THE RENAL FUNCTION WITH THE MODIFICATION OF DIET IN RENAL DISEASE (MDRD) IN PATIENTS WITH ORTHOTOPIC ILEAL NEOBLADDER? Mathieu Rouanne, Yann Neuzillet, Dominique Eladari, Thierry Lebret, and Henry Botto Mathieu RouanneMathieu Rouanne Suresnes, France More articles by this author , Yann NeuzilletYann Neuzillet Suresnes, France More articles by this author , Dominique EladariDominique Eladari Paris, France More articles by this author , Thierry LebretThierry Lebret Suresnes, France More articles by this author , and Henry BottoHenry Botto Suresnes, France More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2770AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Few studies assessing prospectively the renal function changes after orthotopic ileal bladder substitution are available.The aim was to evaluate the accuracy of Modification of Diet in Renal Disease (MDRD) formulae as a substitute for the gold standard measure of glomerular filtration rate (GFR) using chromium 51 EDTA. METHODS Seventeen consecutive patients underwent radical cystectomy (RC) from July 2011 to December 2011 for muscle-invasive bladder cancer were included in this prospective protocol. Exclusion criteria were chronic kidney disease (CKD) and neoadjuvant chemotherapy. Bias and precision of estimated GFR (eGFR) were compared with isotopic GFR (iGFR). Chromium-51 ethylenediamine tetra-acetic acid (51 Cr-EDTA) was used to measure the glomerular filtration rate of both kidneys. 51Cr-EDTA GFR was performed preoperatively and 6 mo postoperatively. In addition, technetiumTc99m-diethylenetriaminepentaaceticacid (Tc99m-DTPA) renal scintigraphy was used to determine the glomerular filtration rate (GFR) of each kidney individually. RESULTS Mean preoperative GFR values were 84 ml/min per 1.73 m2 (range to 61-116) and 75 ml/min per 1.73 m2 (range to 60-117) using eGFR and 51 Cr-EDTA GFR respectively. At 6 mo, the mean GFR values were 77 ml/min per 1.73 m2 (range to 60-117) and 68 ml/min per 1.73 m2 (range to 60-102) using eGFR and iGFR respectively. At 6 mo, the difference between 51 Cr-EDTA GFR and eGFR was statistically different (p = 0.035). In addition, 51 Cr-EDTA GFR values were statistically different between preoperative time and at 6 mo ((p=0.025) whereas no statistical significant difference was found using eGFR (p > 0.05). CONCLUSIONS There is poor correlation between eGFR and 51Cr-EDTA GFR in patients with ileal neobladder reconstruction. eGFR should be used with caution as a surrogate marker for isotope GFR in these patients. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byRouanne M, Lebret T and Courbebaisse M (2018) Re: Long-Term Renal Function Outcomes after Radical CystectomyJournal of Urology, VOL. 193, NO. 3, (1066-1067), Online publication date: 1-Mar-2015. Volume 189Issue 4SApril 2013Page: e580 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mathieu Rouanne Suresnes, France More articles by this author Yann Neuzillet Suresnes, France More articles by this author Dominique Eladari Paris, France More articles by this author Thierry Lebret Suresnes, France More articles by this author Henry Botto Suresnes, France More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Comparisons between validated estimated glomerular filtration rate equations and isotopic glomerular filtration rate in HIV patients

Comparisons between validated estimated glomerular filtration rate equations and isotopic glomerular filtration rate in HIV patients

Comparisons between validated estimated glomerular filtration rate equations and isotopic glomerular filtration rate in HIV patients

Understanding how best to measure renal function in HIV-infected patients is critical because estimated glomerular filtration rate (eGFR) in HIV-infected patients can be affected by ethnicity and body composition. We validated the available eGFR equations and compared them to the plasma Tc-diethylenetriaminepentaacetic acid (Tc-DTPA) clearance in HIV-infected patients. Test of diagnostic accuracy. One hundred and ninety-six HIV-infected patients underwent measuring of Tc-DTPA plasma clearance, five creatinine-based eGFR equations, cystatin-C GFR, and 24-h urine creatinine clearance (CrCl). Mean (SD) Tc-DTPA GFR was 117.7 ± 29.2 ml/min per 1.73 m. The re-expressed Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), re-expressed MDRD formula with Thai racial correction factor, Thai eGFR equation, Cockcroft-Gault equation, cystatin-C GFR, and 24-h urine CrCl underestimated the reference GFR. The bias estimated by the mean of differences (SD) for the re-expressed MDRD equation, CKD-EPI, re-expressed MDRD formula with Thai racial correction factor, Thai eGFR, Cockcroft-Gault equation, cystatin-C, and 24-h urine CrCl can be expressed as 18.9 ± 27.3, 11.1 ± 25.5, 6.2 ± 28.8, 15.4 ± 27.0, 30.4 ± 28.0, 3.2 + 36.1, and 5.0 ± 12.1 ml/min per 1.73 m, respectively. The available eGFR equations underestimated GFR in HIV-infected adults. However, the eGFR by cystatin-C GFR was the most precise and accurate. Among creatinine-based eGFR equations, re-expressed MDRD formula with Thai racial correction factor was the most precise and accurate. The racial factor for each ethnicity is important and the existing eGFR equation should be validated before using it in the HIV population.