Measurement Of Filtration Rate Research Articles

Abstract 640: RGS2 Deficiency Impairs Renal Hemodynamics and Function

Regulator of G protein signaling 2 (RGS2) regulates signaling by acting as a GTPase-activating protein for Gq/11α and Gi/oα subunits of heterotrimeric G proteins. Certain single nucleotide polymorphisms and loss-of-function mutations of RGS2 have been linked to human hypertension. RGS2 deficiency in the kidney is sufficient to cause hypertension in mice; however, the renal pathophysiological mechanisms are unknown. Here, we assessed renal hemodynamics and function using renal blood flow (RBF) and glomerular filtration rate (GFR) measurements, and assessment of pressure natriuresis in wild type (WT) and RGS2 null (RGS2-/-) mice. GFR was measured by plasma clearance of FITC-inulin. Pressure natriuresis was determined by increasing renal perfusion pressure (RPP) stepwise by clamping the superior mesenteric and celiac arteries, and abdominal aorta, while total RBF was simultaneously recorded with flow probe. Baseline GFR was markedly decreased in RGS2-/- mice compared to WT controls (1.8 ± 0.1 vs. 1.1 ± 0.1 ml/min/g kidney weight, p=0.004). Renal conductance was reduced (70 ± 9 vs. 51 ± 3 μl/min/g kidney weight, p=0.006) while renal vascular resistance (RVR; 14.9 ± 2.2 vs. 20.2 ± 1.3 mmHg/ml/min/g kidney weight, p=0.002) was elevated in RGS2-/- compared to WT mice. The absence of RGS2 resulted in decreased sensitivity and magnitude of change in RVR (WT: 11.17 ± 1.94 vs. RGS2-/-: 6.87 ± 0.90 mmHg/ml/min/g) and conductance (WT: -25.69 ± 3.22 vs. RGS2-/-: -13.87 ± 2.40 ml/min/mmHg/g) after a step increase in RPP. The acute pressure-natriuresis curve shifted rightward in RGS2-/- relative to WT, with no change in the slope. Fractional sodium excretion was unaffected by RGS2 deficiency. We conclude that RGS2 deficiency impairs renal function and autoregulation by increasing renal vascular resistance and reducing effective renal blood flow. The findings provide a new line of evidence for renal vascular dysfunction as a primary cause of hypertension. Mutations or downregulation of RGS2 in the kidney may contribute to human hypertension by causing renal hypoperfusion and decreased GFR. Signaling pathways regulated by RGS2 may provide therapeutic targets in hypertension patients harboring mutations that potentially decrease expression and/or function of RGS2.

Structured clinical follow-up for CKD stage 5 may safely postpone dialysis.

The optimal timing of dialysis initiation is still unclear. We aimed to ascertain whether a strict clinical follow-up can postpone need for dialysis in chronic kidney disease (CKD) stage 5 patients. We reviewed records of all consecutive adult patients attending our conservative CKD stage 5 outpatient clinic from 2001 to 2010. Chronicity was defined as two consecutive estimated glomerular filtration rate (eGFR) measurements below 15 ml/min/1.73 m(2). Characteristics of subjects, including comorbidities, were assessed at baseline; blood pressure and serum markers of uremia were assessed both at first and last visit. GFR was estimated by the 4-variable Modification of Diet in Renal Disease (MDRD) formula. In the 312 patients analyzed baseline eGFR was 9.7 ± 2.7 ml/min, which declined by 1.93 ± 4.56 ml/min after 15.6 ± 18.2 months. Age was inversely related to eGFR decline (r -0.27, p = 0.000). During conservative follow-up 55 subjects (18%) died. In comparison with those eventually entering dialysis, deceased subjects were older and had a longer follow-up with no CKD progression. Multivariate analysis identified age, proteinuria and lower baseline K values as the only independent determinants of death. One hundred ninety-four subjects (66%) started dialysis with an average eGFR of 6.1 ± 1.9 ml/min. During 35.8 ± 24.7 months of dialysis follow-up, 84 patients died. Multivariate analysis identified age as the main determinant of death (hazard ratio [HR] for every year 1.07, 95% confidence interval [CI] 1.04-1.11, p 0.000). Patients starting dialysis with eGFR below the median, e.g. <5.7 ml/min, showed a better survival (HR for mortality 0.52, 95% CI 0.30-0.89, p 0.016) than the other group. A well-organized nephrological outpatient clinic for conservative follow-up of CKD stage five patients can delay dialysis entry as long as 1 year. Starting dialysis with eGFR lower than 6 ml/min does not confer any increased risk of death in selected early-referral patients.

Correlation of Cystatin-C and radionuclidic measurement method of glomerular filtration rate in patients with lung cancer receiving cisplatin treatment

Objective: Cisplatin is a chemotherapeutic agent which affects renal functions adversely. The best indicator of renal functions is glomerular filtration rate (GFR) measurement. Cystatin-C appears to be a good alternative to existing methods of measuring GFR. However, it is controversial whether Cystatin-C demonstrates GFR correctly for patients receiving chemotherapy. This study aimed to investigate the correlation between GFR values calculated by Cystatin-C based formulas, radionuclidic method (multiple blood sampling) and blood Cystatin-C values in patients with lung cancer, receiving cisplatin treatment in both pre-treatment and post-treatment periods. Materials and methods: Thirty-six patients with lung cancer who were going to receive cisplatin treatment were included in this study. However, the evaluation was performed with 20 patients since 16 of them could not complete the treatment. Blood Cystatin-C values, GFR values calculated via Cystatin-C based formulas, and radionuclidic method were investigated before and after the cisplatin treatment. Results: After treatment significant decreases were detected in GFR values, obtained via radionuclidic measuring method. However, there was no significant difference in Cystatin-C values between pre-treatment and post-treatment periods. Also GFR values obtained by Cystatin-C based formulas were not significantly different in pre-treatment and post-treatment periods. There were meaningful correlations between radionuclidic method and Cystatin-C values and Cystatin-C based formulas before treatment. However, all correlations disappeared after the treatment. Conclusion: GFR values, calculated by Cystatin-C may not be reliable in following renal functions in patients receiving chemotherapy. When reliable monitoring of the renal functions is necessary radionuclidic method may be preferred in these patients.

Measuring GFR: A Systematic Review

No comprehensive systematic review of the accuracy of glomerular filtration rate (GFR) measurement methods using renal inulin clearance as reference has been published. Systematic review with meta-analysis of cross-sectional diagnostic studies. Published original studies and systematic reviews in any population. Index and reference measurements conducted within 48 hours; at least 15 participants studied; GFR markers measured in plasma or urine; plasma clearance calculation algorithm verified in another study; tubular secretion of creatinine had not been blocked by medicines. Endogenous creatinine clearance; renal or plasma clearance of chromium 51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA), diethylenetriaminepentaacetic acid (DTPA), iohexol, and iothalamate; and plasma clearance of inulin. Renal inulin clearance measured under continuous inulin infusion and urine collection. Mean bias <10%, median bias <5%, the proportion of errors in the index measurements that did not exceed 30% (P30) ≥80%, and P10 ≥50% were set as requirements for sufficient accuracy. Based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, the quality of evidence across studies was rated for each index method. Renal clearance of iothalamate measured GFR with sufficient accuracy (strong evidence). Renal and plasma clearance of 51Cr-EDTA and plasma clearance of iohexol were sufficiently accurate to measure GFR (moderately strong evidence). Renal clearance of DTPA, renal clearance of iohexol, and plasma clearance of inulin had sufficient accuracy (limited evidence). Endogenous creatinine clearance was an inaccurate method (strong evidence), as was plasma clearance of DTPA (limited evidence). The evidence to determine the accuracy of plasma iothalamate clearance was insufficient. With the exception of plasma clearance of inulin, only renal clearance methods had P30 >90%. The included studies were few and most were old and small, which may limit generalizability. Requirements for sufficient accuracy may depend on clinical setting. At least moderately strong evidence suggests that renal clearance of 51Cr-EDTA or iothalamate and plasma clearance of 51Cr-EDTA or iohexol are sufficiently accurate methods to measure GFR.

The clearance concept with special reference to determination of glomerular filtration rate in patients with fluid retention.

In subjects without fluid retention, the total plasma clearance of a renal filtration indicator (inulin, (99m) Tc-DTPA, (51) Cr-EDTA) is close to the urinary plasma clearance. Conversely, in patients with fluid retention (oedema, pleural effusions, ascites), there is a substantial discrepancy between the total plasma clearance and the urinary plasma clearance. This is owing to delayed indicator distribution to smaller or larger parts of the interstitial space, which in patients with ascites may simulate a peritoneal dialysator. In patients with fluid retention, urinary plasma clearance should be assessed to obtain a correct measurement of the glomerular filtration rate (GFR). In theory, total plasma clearance with late samples (24-h, 48-h) may be applied in patients with fluid retention, but validation hereof has not been performed. Until such studies are completed, it is recommended that patients with fluid retention have their GFR measured by a urinary plasma clearance technique with controlled quantitative urinary sampling within a few hours after indicator injection.

Evaluation of renal function in elderly patients

Measurement of the glomerular filtration rate (GFR) is recognized worldwide as the most accurate way of assessing kidney function. The prevalence of impaired renal function increases with advancing age. In this study we compared the clinical formulae Cockcroft-Gault (CG), isotope dilution mass spectrometry-modification of diet in renal disease (IMDS-MDRD) and chronic kidney disease epidemiology collaboration (CKD-EPI) with (99m)Tc-diethylene triamine pentaacetic acid ((99m)Tc-DTPA) in elderly patients over and under the age of 70 years in an attempt to establish which formula produces the best measurement of renal function in this population. Patients were randomly selected from two age groups [<70 years (n = 37) and ≥ 70 years (n = 39)]. Two plasma samples were collected at 60 and 180 min after injection of (99m)Tc-DTPA, and the GFR was calculated applying Charles D. Russell's two-sample method. In patients younger than 70 years, no statistically significant difference was found between GFR evaluated with (99m)Tc-DTPA and GFR obtained using the other methods.In patients aged at least 70 years, no statistically significant difference was found between GFR evaluated with (99m)Tc-DTPA and GFR evaluated using the CG real weight formula. Conversely, statistically significant differences were found between GFR evaluated with (99m)Tc-DTPA and GFR obtained using the CG normalized weight (P = 0.002), IMDS-MDRD (P = 0.024) and CKD-EPI (P = 0.028) formulae. In patients older than 70 years, the use of the two 'classical' formulae (IMDS-MDRD and CKD-EPI) overestimated GFR in stage III CKD (GFR 30-59 ml/min) when compared with the gold standard (99m)Tc-DTPA method. Thus, in patients aged 70 years and above only the CG real weight formula provided unbiased results comparable to (99m)Tc-DTPA. In conclusion, in elderly patients, GFR measured using CKD-EPI and IMDS-MDRD serum creatinine-based formulae may be overestimated compared with that measured using (99m)Tc-DTPA GFR.

Cystatin C-based glomerular filtration rate estimating equations in early chronic kidney disease.

To compare performance of combined creatinine and cystatin C-based equation with equations based on either cystatin C or creatinine alone, in early chronic kidney disease. Diagnostic accuracy study. Tertiary-care hospital. One hundred children with chronic kidney disease who underwent 99mTc diethylenetriamine pentaacetic acid (DTPA) glomerular filtration rate measurement. Estimating equations for glomerular filtration rate (GFR) based on serum cystatin C alone and in combination with serum creatinine were generated using regression analyses. These equations and the creatinine-based equation [0.42 x height/creatinine] were validated in 42 children with glomerular filtration rate between 60 and 90 mL/min/1.73 m2. Bias, precision and accuracy of estimating equations using DTPA glomerular filtration rate as gold standard. Cystatin C-based equation (GFR=96.9 - 30.4 x cystatin) overestimated while the combined cystatin C-and creatinine-based equation [GFR=11.45 x (height/creatinine) 0.356 x (1/cystatin) 0.188] underestimated the measured GFR. Cystatin C-based equation had less bias (1.9 vs. 12.4 ml/min/1.73 m2), and higher precision (13.1 vs. 25.6 mL/min/1.73 m2) and accuracy (92.1% vs. 75.7%) than creatinine-based equation. The combined cystatin C and creatinine equation had bias (-1.4 mL/min/1.73 m2) precision (15.2 mL/min/1.73 m2) and accuracy (91.2%) similar to cystatin C-based equation. Cystatin C-based equation has a better performance in estimating glomerular filtration rate than creatinine-based equation in children with early chronic kidney disease. Addition of creatinine equation does not improve the performance of the cystatin C-based equation.

Prediction of presence of kidney disease in a general patient population undergoing intravenous iodinated contrast enhanced computed tomography

To assess which risk factors can be used to reduce superfluous estimated glomerular filtration rate (eGFR) measurements before intravenous contrast medium administration. In consecutive patients, all decreased eGFR risk factors were assessed: diabetes mellitus (DM), history of urologic/nephrologic disease (HUND), nephrotoxic medication, cardiovascular disease, hypertension, age > 60 years, anaemia, malignancy and multiple myeloma/M. Waldenström. We studied four models: (1) all risk factors, (2) DM, HUND, hypertension, age > 60 years; (3) DM, HUND, cardiovascular disease, hypertension; (4) DM, HUND, age > 75 years and congestive heart failure. For each model, association with eGFR < 60 ml/min/1.73 m(2) or eGFR < 45 ml/min/1.73 m(2) was studied. A total of 998 patients, mean age 59.94 years were included; 112 with eGFR < 60 ml/min/1.73 m(2) and 30 with eGFR < 45 ml/min/1.73 m(2). Model 1 detected 816 patients: 108 with eGFR < 60 ml/min/1.73 m(2) and all 30 with eGFR < 45 ml/min/1.73 m(2). Model 2 detected 745 patients: 108 with eGFR < 60 ml/min/1.73 m(2) and all 30 with eGFR < 45 ml/min/1.73 m(2). Model 3 detected 622 patients: 100 with eGFR < 60 ml/min/1.73 m(2) and all 30 with eGFR < 45 ml/min/1.73 m(2). Model 4 detected 440 patients: 86 with eGFR < 60 ml/min/1.73 m(2) and all 30 with eGFR < 45 ml/min/1.73 m(2). Associations were significant (p < 0.001). Model 4 is most effective, resulting in the lowest proportion of superfluous eGFR measurements while detecting all patients with eGFR < 45 ml/min/1.73 m(2) and most with eGFR < 60 ml/min/1.73 m(2). A major risk factor for contrast-induced nephropathy (CIN) is kidney disease. Risk factors are used to identify patients with pre-existent kidney disease. Evidence for risk factors to identify patients with kidney disease is limited. The number of eGFR measurements to detect kidney disease can be reduced.

Poorly Functioning Kidneys Recover from Ischemia after Partial Nephrectomy as Well as Strongly Functioning Kidneys

Poorly functioning kidneys may not recover from ischemia as well as strongly functioning kidneys. This could impact surgical approaches to partial nephrectomy. We analyzed the records of 155 consecutive patients treated with partial nephrectomy who underwent appropriate studies to facilitate analysis of function and parenchymal mass in the operated kidney, including computerized tomography and glomerular filtration rate measurement within 2 months preoperatively and 4 to 12 months postoperatively. Patients with a contralateral kidney also underwent renal scan in the same time frame to provide split renal function. Computerized tomography was done to measure functional parenchymal volume before and after partial nephrectomy. Recovery from ischemia, defined as percent glomerular filtration rate saved/percent volume saved, was considered 100% if all nephrons recovered from the ischemic insult. The median R.E.N.A.L. nephrotomy score was 8. Cold ischemia was used in 64 patients and limited warm ischemia was used in 91 (median 27 and 20minutes, respectively). The median percent glomerular filtration rate saved in the operated kidney was 80% and the median parenchymal volume saved was 83%. The overall median rate of recovery from ischemia was 95%, including 100% for cold ischemia and 92% for limited warm ischemia. Recovery from ischemia was approximately 100% and was similar for all strata ofpreoperative estimated glomerular filtration rates in the operated kidney (p=0.24), even in the warm ischemia subgroup. Our results suggest that the quantity of parenchyma preserved is the main determinant of the postoperative glomerular filtration rate after partial nephrectomy as long as limited warm ischemia or hypothermia is used. Even poorly functioning kidneys recover well from the ischemic insult proportionate tothe amount of parenchyma preserved.

Markers of and Risk Factors for the Development and Progression of Diabetic Kidney Disease

Diabetic kidney disease (DKD) occurs in 25%-40% of patients with diabetes. Given the dual problems of a significant risk of progression from DKD to end-stage renal disease (ESRD) and increased cardiovascular morbidity and mortality, it is important to identify patients at risk of DKD and ESRD and initiate protective renal and cardiovascular therapies. The importance of preventive therapy is emphasized further by worldwide increases in the incidence of diabetes. This review summarizes the evidence regarding the prognostic value and benefits of targeting established and novel risk markers for DKD development and progression. Family history of DKD, smoking history, and glycemic, blood pressure, and plasma lipid level control are established factors for identifying people at greatest risk of DKD development and progression. Absolute albumin excretion rate (AER) and glomerular filtration rate (GFR) measurements also are important, although AER categorization generally lacks the necessary specificity and sensitivity, and estimates of declining GFR are compromised by methodological limitations for GFRs in the normal-to-high range. Emerging risk markers for progressive loss of kidney function include markers of oxidation and inflammation, profibrotic cytokines, uric acid, advanced glycation end products, functional and structural markers of vascular dysfunction, kidney structural changes, and tubular biomarkers. Among these, the most promising are serum uric acid and soluble tumor necrosis factor receptor (type 1 and type 2) levels, especially in relation to GFR changes. At present, these can only be considered as risk markers because they only identify an individual at increased risk of progressive DKD and not necessarily related to the causal pathway promoting kidney damage. Further work is needed to establish whether modulating these factors improves the prognosis in DKD. Although change in urinary peptidome levels also is a promising marker, there currently is neither a clinical assay nor adequate studies defining its prognostic value. Until these or other novel markers become available for clinical use, predictive accuracy often may be increased with greater attention to established markers.

The concomitant use of meloxicam and methotrexate does not clearly increase the risk of silent kidney and liver damages in patients with rheumatoid arthritis

We investigated whether the concomitant use of meloxicam and methotrexate might induce kidney and liver damages in patients with rheumatoid arthritis (RA). We enrolled 101 RA patients with normal kidney and liver functions taking meloxicam and methotrexate concomitantly for more than 6 months. Blood and urine tests were performed. Estimated glomerular filtration rate (eGFR) and liver stiffness measurement (LSM) were used for evaluating silent kidney and liver damages. Ultrasonography was also performed to exclude structural abnormalities. We adopted 90 mL/min/1.73 mm(2) and 5.3 kPa as the cutoff for an abnormal eGFR and LSM. The mean age (85 women) was 51.9 years. The mean eGFR was 97.0 mL/min/1.73 m(2) and the mean LSM was 4.7 kPa. The mean weekly dose of methotrexate was 13.4 mg. The mean weekly dose of methotrexate did not correlate with eGFR or LSM. Neither the cumulative dose of meloxicam or methotrexate nor the mean weekly dose of methotrexate showed the significant odds ratio or relative risk for abnormal eGFR and LSM values. The use of higher-dose MTX, above 15 mg per week, with meloxicam did not significantly increase the risk for abnormal LSM and eGFR (RR = 2.042, p = 0.185; RR = 0.473, p = 0.218). The concomitant use of meloxicam and MTX did not clearly increase the risk of silent kidney or liver damage in RA patients with normal laboratory results taking MTX and meloxicam concurrently for over 6 months.

Preparation of Ga-68-NOTA as a renal PET agent and feasibility tests in mice

Positron emission tomography (PET) may provide more accurate quantification of kidney function such as glomerular filtration rate (GFR) than gamma imaging. The purpose of these experiments was to prepare and evaluate Ga-68 complexes as potential PET agents for measurement of GFR. We labeled EDTA, DTPA, DOTA, and NOTA with Ga-68 obtained from a Ge-68/Ga-68-generator and measured the binding to serum and red blood cells. Biodistribution study was performed in male BALB/c mice after intravenous injection together with Cr-51-EDTA as the standard for glomerular filtration rate (GFR) measurement. Animal-PET study was performed using BALB/c mice. All the tested chelating agents except DTPA showed quantitative labeling yields (>99%). Among them, Ga-68-NOTA showed consistently low binding to both human and mouse RBC and serum protein. Biodistribution study showed no significant difference between Ga-68-NOTA and Cr-51-EDTA groups by one-way analysis of variance (ANOVA) (p>0.05). Furthermore, the GFR values obtained by Ga-68-NOTA and Cr-51-EDTA were almost same (0.26±0.04 and 0.25±0.04mL/min, respectively). Animal-PET study showed almost the same GFR (0.25mL/min) with the values obtained by biodistribution study. We proved that an easy-to-prepare agent Ga-68-NOTA is ideal for renal PET as well as for GFR measurement.

Kidney Transplant Donor Glomerular Filtration Rate by Iohexol Clearance During Computerized Tomographic Angiography of the Kidneys

BackgroundPre-transplantation living-donor kidney function determines remaining donor kidney function and significantly affects post-transplantation allograft function in the recipient. Few transplantation centers perform donor kidney function measurement owing to patient burden. A simplified method of glomerular filtration rate (GFR) measurement after angiographic procedures may facilitate more precise measurement of donor kidney function. MethodsWe evaluated the agreement between a simplified method of GFR measurement after renal computerized tomographic (CT) angiography (index GFR, 100 mL iohexol [350 mg/mL iodine]) and the reference GFR measurement with the use of iodinated radiocontrast media (5 mL bolus of iohexol [300 mg/mL iodine]) among 19 potential living kidney transplant donors. The 24-hour creatinine clearance and GFR estimation equations were additionally examined. Kidney lengths and total and segmented cortical kidney volumes were also measured. ResultsThe index CT angiography GFR performed best with respect to the reference GFR with minimal bias (mean difference, −4 mL/min/1.73 m2), good precision (SD of the difference, 9.8 mL/min/1.73 m2), coefficient of determination (R2) of 0.74, narrow mean coefficient of variation (5% [range 1%–15%]), and high accuracy, with 100% of the values for the index test within 30% of the reference test. The 24-hour urine creatinine clearance values performed poorly. Kidney volumes and length did not significantly correlate with measured GFR. ConclusionsThe CT angiographic GFR measurement could be a useful and more convenient method of donor kidney function evaluation and maintains minimal bias, high precision, and accuracy compared with the reference GFR measurement.

Improved measurement of the glomerular filtration rate from Tc-99m DTPA scintigraphy in patients following nephrectomy

ObjectiveWe aimed to improve Tc-99m DTPA glomerular filtration rate (GFR) scintigraphy (Gates’ method) in a prospective study using Cr-51 EDTA GFR test as a gold standard.MethodsFifty-seven Tc-99m DTPA GFR scintigrams in 45 subjects (male/female = 33:12, age = 45.9 ± 17.6 years, 14 healthy volunteers and 31 nephrectomised patients) were compared using Cr-51 EDTA GFR tests. Using the %renal uptake of Tc-99m DTPA and Cr-51 EDTA GFR, a revised equation for GFR was established through linear regression analysis.ResultsThe revised equation for improved GFR was GFR(mL/min) = (%renal uptake × 11.7773) − 0.7354. Gates’ original GFRs (70.1 ± 20.5 mL/min/1.73 m2) were significantly lower than Cr-51 EDTA GFRs (97.0 ± 31.9 mL/min/1.73 m2; P < 0.0001), but the improved GFRs (98.0 ± 26.3 mL/min/1.73 m2) were not different from (P = 0.7360) and had a significant correlation with (r = 0.73, P < 0.0001) the Cr-51 EDTA GFRs. The revised GFR equation effectively demonstrated perioperative GFR changes in kidneys that were operated on and the contralateral kidneys at 3 and 6 months post-partial nephrectomy (n = 25).ConclusionsGFR measurement using Tc-99m DTPA scintigraphy could be significantly improved by a revised equation derived from the comparison with Cr-51 EDTA GFR.Key Points• Measurement of glomerular filtration rate is difficult following nephrectomy.• Measurements can be significantly improved by new renal sctintigraphic methods.• This helps physicians to measure kidney function of patients following nephrectomy.• Management of renal tumour patients should become more effective.

Height-Independent Estimation of Glomerular Filtration Rate in Children: An Alternative to the Schwartz Equation

To compare the diagnostic performance of 2 height-independent equations used to calculate estimated glomerular filtration rate (eGFR), those of Pottel (eGFR-Pottel) and the British Columbia Children's Hospital (BCCH) (eGFR-BCCH), with the commonly used Schwartz equation (eGFR-Schwartz). We externally validated eGFR-Pottel and eGFR-BCCH in a well-characterized pediatric patient population (n = 152) and compared their diagnostic performance with that of eGFR-Schwartz using Bland-Altman analysis. All patients underwent glomerular filtration rate measurement using the gold standard single-injection inulin clearance method (GFR-inulin). Median GFR-inulin was 92.0 mL/min/1.73 m² (IQR, 76.1-107.4 mL/min/1.73 m²). Compared with GFR-inulin, the mean bias for eGFR-Schwartz was -10.1 mL/min/1.73 m(2) (95% limits of agreement [LOA], -77.5 to 57.2 mL/min/1.73 m(2)), compared with -12.3 mL/min/1.73 m² (95% LOA, -72.6 to 47.9 mL/min/1.73 m(2)) for eGFR-Pottel and -22.1 mL/min/1.73 m² (95% LOA, -105.0 to 60.8 mL/min/1.73 m(2)) for eGFR-BCCH. eGFR-Pottel showed comparable accuracy to eGFR-Schwartz, with 77% and 76% of estimates within 30% of GFR-inulin, respectively. eGFR-BCCH was less accurate than eGFR-Schwartz (66% of estimates within 30% of GFR-inulin; P < .01). The performance of eGFR-Pottel is superior to that of eGFR-BCCH and comparable with that ofeGFR-Schwartz. eGFR-Pottel is a valid alternative to eGFR-Schwartz in children and could be reported by the laboratory if height data are not available.

Prevention, detection and management of early chronic kidney disease: A systematic review of clinical practice guidelines

In response to the increase in Chronic Kidney Disease (CKD) worldwide, several professional organizations have developed clinical practice guidelines to manage and prevent its progression. This study aims to compare the scope, content and consistency of published guidelines on CKD stages I-III. Electronic databases of the medical literature, guideline organizations, and the websites of nephrology societies were searched to November 2011. The Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument and textual synthesis was used to appraise and compare recommendations. One consensus statement and 15 guidelines were identified and included. Methodological rigour across guidelines was variable, with average domain scores ranging from 24% to 95%. For detection of CKD, all guidelines recommended estimated glomerular filtration rate measurement, some also recommended serum creatinine and dipstick urinalysis. The recommended protein and albumin creatinine ratios and proteinuria definition thresholds varied (>150-300 mg/day to >500 mg/day). Blood pressure targets ranged (<125/75 to <140/90 mmHg). Angiotensin converting enzyme inhibitor and angiotensin receptor blockers were recommended for hypertension, as combined or as monotherapy. Protein intake recommendations varied (no restriction or 0.75 g/kg per day-1.0 g/kg per day). Salt intake of 6 g/day was recommended by most. Psychosocial support and education were recommended by few but specific strategies were absent. CKD guidelines were consistent in scope but were variable with respect to their recommendations, coverage and methodological quality. To promote effective primary and secondary prevention of CKD, regularly updated guidelines that are based on the best available evidence and augmented with healthcare context-specific strategies for implementation are warranted.

Reliability of Transcutaneous Measurement of Renal Function in Various Strains of Conscious Mice

Measuring renal function in laboratory animals using blood and/or urine sampling is not only labor-intensive but puts also a strain on the animal. Several approaches for fluorescence based transcutaneous measurement of the glomerular filtration rate (GFR) in laboratory animals have been developed. They allow the measurement of GFR based on the elimination kinetics of fluorescent exogenous markers. None of the studies dealt with the reproducibility of the measurements in the same animals. Therefore, the reproducibility of a transcutaneous GFR assessment method was investigated using the fluorescent renal marker FITC-Sinistrin in conscious mice in the present study. We performed two transcutaneous GFR measurements within three days in five groups of mice (Balb/c, C57BL/6, SV129, NMRI at 3–4 months of age, and a group of 24 months old C57BL/6). Data were evaluated regarding day-to-day reproducibility as well as intra- and inter-strain variability of GFR and the impact of age on these parameters. No significant differences between the two subsequent GFR measurements were detected. Fastest elimination for FITC-Sinistrin was detected in Balb/c with significant differences to C57BL/6 and SV129 mice. GFR decreased significantly with age in C57BL/6 mice. Evaluation of GFR in cohorts of young and old C57BL/6 mice from the same supplier showed high consistency of GFR values between groups. Our study shows that the investigated technique is a highly reproducible and reliable method for repeated GFR measurements in conscious mice. This gentle method is easily used even in old mice and can be used to monitor the age-related decline in GFR.

Radiotherapy of abdomen with precise renal assessment with SPECT/CT imaging (RAPRASI): design and methodology of a prospective trial to improve the understanding of kidney radiation dose response

BackgroundThe kidneys are a principal dose-limiting organ in radiotherapy for upper abdominal cancers. The current understanding of kidney radiation dose response is rudimentary. More precise dose-volume response models that allow direct correlation of delivered radiation dose with spatio-temporal changes in kidney function may improve radiotherapy treatment planning for upper-abdominal tumours.Our current understanding of kidney dose response and tolerance is limited and this is hindering efforts to introduce advanced radiotherapy techniques for upper-abdominal cancers, such as intensity-modulated radiotherapy (IMRT). The aim of this study is to utilise radiotherapy and combined anatomical/functional imaging data to allow direct correlation of radiation dose with spatio-temporal changes in kidney function. The data can then be used to develop a more precise dose-volume response model which has the potential to optimise and individualise upper abdominal radiotherapy plans.Methods/designThe Radiotherapy of Abdomen with Precise Renal Assessment with SPECT/CT Imaging (RAPRASI) is an observational clinical research study with participating sites at Sir Charles Gairdner Hospital (SCGH) in Perth, Australia and the Peter MacCallum Cancer Centre (PMCC) in Melbourne, Australia. Eligible patients are those with upper gastrointestinal cancer, without metastatic disease, undergoing conformal radiotherapy that will involve incidental radiation to one or both kidneys. For each patient, total kidney function is being assessed before commencement of radiotherapy treatment and then at 4, 12, 26, 52 and 78 weeks after the first radiotherapy fraction, using two procedures: a Glomerular Filtration Rate (GFR) measurement using the 51Cr-ethylenediamine tetra-acetic acid (EDTA) clearance; and a regional kidney perfusion measurement assessing renal uptake of 99mTc-dimercaptosuccinic acid (DMSA), imaged with a Single Photon Emission Computed Tomography / Computed Tomography (SPECT/CT) system. The CT component of the SPECT/CT provides the anatomical reference of the kidney’s position. The data is intended to reveal changes in regional kidney function over the study period after the radiotherapy. These SPECT/CT scans, co-registered with the radiotherapy treatment plan, will provide spatial correlation between the radiation dose and regional renal function as assessed by SPECT/CT. From this correlation, renal response patterns will likely be identified with the purpose of developing a predictive model.Trial registrationAustralian New Zealand Clinical Trials Registry: ACTRN12609000322235

Improving evidence-based primary care for chronic kidney disease: study protocol for a cluster randomized control trial for translating evidence into practice (TRANSLATE CKD).

BackgroundChronic kidney disease (CKD) and end stage renal disease (ESRD) are steadily increasing in prevalence in the United States. While there is reasonable evidence that specific activities can be implemented by primary care physicians (PCPs) to delay CKD progression and reduce mortality, CKD is under-recognized and undertreated in primary care offices, and PCPs are generally not familiar with treatment guidelines. The current study addresses the question of whether the facilitated TRANSLATE model compared to computer decision support (CDS) alone will lead to improved evidence-based care for CKD in primary care offices.Methods/DesignThis protocol consists of a cluster randomized controlled trial (CRCT) followed by a process and cost analysis. Only practices providing ambulatory primary care as their principal function, located in non-hospital settings, employing at least one primary care physician, with a minimum of 2,000 patients seen in the prior year, are eligible. The intervention will occur at the cluster level and consists of providing CKD-specific CDS versus CKD-specific CDS plus practice facilitation for all elements of the TRANSLATE model. Patient-level data will be collected from each participating practice to examine adherence to guideline-concordant care, progression of CKD and all-cause mortality. Patients are considered to meet stage three CKD criteria if at least two consecutive estimated glomerular filtration rate (eGFR) measurements at least three months apart fall below 60 ml/min. The process evaluation (cluster level) will determine through qualitative methods the fidelity of the facilitated TRANSLATE program and find the challenges and enablers of the implementation process. The cost-effectiveness analysis will compare the benefit of the intervention of CDS alone against the intervention of CDS plus TRANSLATE (practice facilitation) in relationship to overall cost per quality adjusted years of life.DiscussionThis study has three major innovations. First, this study adapts the TRANSLATE method, proven effective in diabetes care, to CKD. Second, we are creating a generalizable CDS specific to the Kidney Disease Outcome Quality Initiative (KDOQI) guidelines for CKD. Additionally, this study will evaluate the effects of CDS versus CDS with facilitation and answer key questions regarding the cost-effectiveness of a facilitated model for improving CKD outcomes. The study is testing virtual facilitation and Academic detailing making the findings generalizable to any area of the country.Trial registration Registered as NCT01767883 on clinicaltrials.gov NCT01767883

Prevalence of preclinical renal dysfunction in obese Egyptian patients with primary knee osteoarthritis, preliminary data

Aim of the workObesity and the related metabolic syndrome cluster of cardiovascular risk factors have been associated with chronic kidney disease (CKD). Patients with knee osteoarthritis (OA) are frequently obese and due to the combined effects of obesity and the chronic use of non-steroidal anti-inflammatory drugs (NSAIDs); they may represent a high risk group for renal dysfunction. We aimed to detect preclinical renal involvement in obese patients with knee OA. Patients and methodsForty patients with knee OA and a body mass index (BMI)⩾30 (mean age 43.5±3.7years) not on chronic NSAID use and forty age and sex matched non-obese controls were enrolled in this study. For all subjects anthropometric measures were taken. Laboratory assessment included fasting blood sugar, serum triglycerides, high density lipoprotein cholesterol (HDL), serum uric acid, urea, creatinine and microalbuminuria assay. For patients with knee OA, knee radiographs were done and the disease severity was assessed according to Kellgren–Lawrence (K–L) scale. Tc-99m DTPA was used for the measurement of the glomerular filtration rate (GFR) and the results were classified into normal and CKD according to Kidney–Dialysis Outcomes and Quality Initiative stages. ResultsAmong the patients’ group, 26/40 (65%) had CKD compared to 12/40 (30%) subjects among the controls (P=0.001). GFR correlated positively with HDL (r=0.4; P=0.02) and inversely with microalbuminuria and the severity of knee OA (r=−0.4; P=0.02 for each). ConclusionsObese patients with knee OA represent a high risk group for renal dysfunction.