Isotopic Glomerular Filtration Rate Research Articles

Comparison of cystatin C- and creatinine-based estimation of glomerular filtration rate according to glycaemic status in Type 2 diabetes

The influence of hyperglycaemia on the performance of glomerular filtration rate (GFR) estimating equations remains to be determined. We compared the performance of creatinine-based GFR with cystatin C-based GFR in patients with Type 2 diabetes according to glycaemic status. In a cross-sectional study of 210 patients with Type 2 diabetes, we staged glycaemic status by HbA(1c) tertiles [HbA(1c) ≤ 75 mmol/mol (9.0%) (n = 70), HbA(1c) 76-95 mmol/mol (9.1-10.8%) (n = 70), HbA(1c) >95 mmol/mol (10.8%) (n = 70)] and measured GFR. Isotopic GFR was measured using renal dynamic imaging with (99m) Tc-diethylene-triamine-penta-acetic acid. Estimated GFR (eGFR) was measured using creatinine-based formulae (Cockcroft-Gault-eGFR, the Modification of Diet in Renal Disease equation-eGFR and the Chronic Kidney Disease Epidemiology Collaboration formula-eGFR) and a cystatin C-based formula (cystatin C-eGFR). The isotopic GFR of all patients was 93.1 ± 34.1 ml min(-1) 1.73 m(-2). All methods for estimating GFR underestimated isotopic GFR [Cockcroft-Gault-eGFR (68.8 ± 38.6 ml min(-1) 1.73 m(-2) ) (P < 0.05), Modification of Diet in Renal Disease-eGFR (74.8 ± 31.3 ml min(-1) 1.73 m(-2) ) (P < 0.05), Chronic Kidney Disease Epidemiology Collaboration-eGFR (72.9 ± 26.6 ml min(-1) 1.73 m(-2)) (P < 0.05) and cystatin C-eGFR (83.5 ± 33.2 ml min(-1) 1.73 m(-2)) (P < 0.05)]. In all patient groups, cystatin C-eGFR was less biased and more accurate than the creatinine-based formulae, especially in the group with HbA(1c) > 95 mmol/mol (10.8%) where there was no difference between cystatin C-eGFR and isotopic GFR. Performance of cystatin C-eGFR was superior to creatinine-based GFR in patients with Type 2 diabetes with HbA(1c) >95 mmol/mol (10.8%).

Reverse cardiac remodelling and renal functional improvement following bilateral renal artery stenting for flash pulmonary oedema

Acute flash pulmonary oedema (AFPO) is a life-threatening syndrome almost unique to patients with atheromatous renovascular disease (ARVD). Although recurrent AFPO is a widely accepted indication to consider renal revascularization, this is based on a number of case reports/series describing a successful outcome post-procedure. There is limited literature on the pathophysiological mechanisms and treatment effects of revascularization to support this clinical decision making. We report the case of a 65-year-old lady who presented with three episodes of AFPO. Investigations revealed severe bilateral renal artery stenosis. Post-revascularization, she experienced substantial improvement in energy levels and New York Heart Association class, with improvement in her blood pressure and renal function. Post-procedure, there were dramatic improvements in her cardiac morphology and function that were sustained at 1 year (ejection fraction improved from 39 to 65%, left ventricular mass decreased from 161 to 116 g) as well as renal function (isotopic glomerular filtration rate increased from 22.4 to 34.2 mL/min). This report provides new insights into the pathophysiological relationships between renal and cardiac changes in AFPO; the extent of the cardiac morphological changes was striking and unexpected.

Advanced Glycation Urinary Protein-Bound Biomarkers and Severity of Diabetic Nephropathy in Man

Background/Aims: The formation of advanced glycation end products (AGEs) is accelerated in patients with diabetic nephropathy. The aim of this study was to ascertain if the urinary excretion of proteins modified by advanced glycation can be used as biomarkers for albuminuria in individuals with type 1 or type 2 diabetes. Methods: Community-based patients with type 1 (n = 68) or type 2 diabetes (n = 216) attending a diabetes clinic of a tertiary referral hospital were classified as having normoalbuminuria (Normo, albumin excretion rate (AER) <20 µg/min), microalbuminuria (Micro, AER 20–200 µg/min) or macroalbuminuria (Macro, AER ≧200 µg/min). Serum and urine AGE-modified proteins were measured. Results: In patients with both type 1 diabetes and type 2 diabetes, there was a clear association between the degree of albuminuria and urinary AGE-modified proteins (p < 0.0001). Exclusive to patients with type 1 diabetes, urinary excretion of the AGE carboxymethyllysine correlated with AER, whereas patients with type 2 diabetes and macroalbuminuria had an increase in urinary methylglyoxal, an AGE intermediate. These changes were independent of isotopic glomerular filtration rate levels. Serum concentrations of AGEs or soluble receptor for AGEs were not consistently associated with albuminuria in either type 1 or type 2 diabetes. Conclusions: Urinary excretion of proteins modified by AGEs may be useful biomarkers of albuminuria in individuals with type 1 and type 2 diabetes, warranting prospective investigation in larger diabetic cohorts.

Inaccuracies in estimated glomerular filtration rate in one Australian renal centre

Early identification of true renal disease (glomerular filtration rate (GFR) < 60 mL/min) results in better patient outcomes. There is now routine reporting in Australia of estimated GFR (eGFR) in all patients over age 18 who have serum creatinine measured, calculated by the Modification of Diet in Renal Disease (MDRD) formula, which was validated in an American Caucasian cohort. Significant clinical decisions and prognosis are often made on the basis of this calculation. To assess the accuracy of three estimates of GFR in an Australian population by comparing eGFR obtained by the abbreviated MDRD (aMDRD), Cockcroft-Gault corrected for body surface area (BSA) (CG) and Chronic Kidney Disease Epidemiology (CKD-Epi) formulae with a gold standard, isotopic (51) Cr-ethylenediaminetetra-acetic acid ((51) Cr-EDTA) GFR. Patients referred with an eGFR of <60 mL/min reported by the aMDRD formula underwent isotopic measurement of GFR (over 4 h) and had eGFR calculated using CG corrected for BSA, aMDRD and CKD-Epi formulae. Data were analysed using Bland-Altman plots and regression analysis to compare methods; bias, precision and the proportion of patients correctly stratified by stage of chronic kidney disease (CKD) were also compared according to the three estimates of GFR, using (51) Cr-EDTA GFR as the gold standard. A total of 139 patients were recruited (female 45%), mean age 64 years and mean serum creatinine 212 µmol/L. The mean GFR (SD) (mL/min per m(2) ) for isotopic, CG, aMDRD and CKD-Epi were 47 (28), 37 (20), 32 (17) and 33 (18) (P = 0.001). CG (57%) was more likely to correctly stage CKD than aMDRD (37%) or CKD-Epi (37%), and absolute bias was significantly lower using CG than either other method (P = 0.001). In this small Australian population the CG formula corrected for BSA agreed more closely with isotopic GFR and correctly staged patients with CKD more often than the aMDRD or CKD-Epi formulae. It is important that each renal Unit considers the accuracy of estimates of GFR according to their population demographics.

Correlation of estimated and measured glomerular filtration rate in patients with interposed bowel in the urinary tract

Isotope glomerular filtration rate (GFR) measurement is invasive, time-consuming and expensive. Estimated glomerular filtration rate (eGFR) is used as a surrogate, but has not been validated in patients whose lower urinary tract (LUT) is replaced with bowel. This study aimed to evaluate the correlation between the Modification of Diet of Renal Disease (MDRD) eGFR andchromium-51 ethylenediamine tetra-acetic acid (Cr-EDTA) GFR in patients with LUT reconstruction/diversion. A retrospective chart review was undertaken of 75 consecutive patients with LUT reconstruction/diversion attending scheduled follow-up in a single institutional setting. Cr-EDTA GFR, serum creatinine and eGFR were compared. Routine patient demographics, type of bowel reconstruction/diversionand time since surgery were noted. The correlation between Cr-EDTA GFR and creatinine was poor (r (2) = 0.411) and the limits of agreement between variables were wide (-118 to +102, p = 0.053). The correlation between Cr-EDTA GFR and eGFR was slightly better (r (2) = 0.536), and the limits of agreement narrowed to -39 to +37 (p = 0.0003). The correlation was improved (r (2) = 0.623) when separating patients with renal failure (eGFR ≤ 60 ml/min per 1.73 m(2), n = 21), but the agreement between variables was poor (-20 to +16 ml/min per 1.73 m(2), p = 0.424).Study limitations include the heterogeneous/complex patient population and types of bowel interposition, and asynchronous eGFR and Cr-EDTA GFR measurement (although no clinical events were recorded between measures). These reflect the reality in which eGFR is often used. There is poor correlation between eGFR and Cr-EDTA GFR in patients with LUT reconstruction/diversion with bowel. eGFR should be used with caution as a surrogate marker for isotope GFR in these patients. Larger prospective studies controlling for the study limitations identified are indicated.

Low-dose sirolimus combined with angiotensin-converting enzyme inhibitor and statin stabilizes renal function and reduces glomerular proliferation in poor prognosis IgA nephropathy

There is a lack of new therapeutic strategies for IgA nephropathy. Low-dose sirolimus inhibits mesangial cell proliferation and renal fibrosis in animal models. We performed a pilot, randomized controlled trial to evaluate the efficacy and safety of low-dose sirolimus in patients with a high-risk IgA nephropathy. Twenty-three patients with a glomerular filtration rate (GFR) within 30-60 mL/min and/or proteinuria >1 g/day were randomly assigned to low-dose sirolimus plus enalapril and atorvastatin (SRL group, n = 14) or enalapril plus atorvastatin (CONTROL group, n = 9). Primary composite end point was variation of haematuria, proteinuria and blood pressure. Secondary end points were isotopic GFR, renal histology evaluated by Oxford classification and safety parameters evaluated at 6 and 12 months. Primary end point improved significantly in the SRL group at 12 months. Regarding isotopic GFR, patients included in the CONTROL group lost 8 mL/min/1.73 m(2), whereas those in the SRL arm improved 5 mL/min/1.73 m(2) (P = 0.03). Proteinuria decreased similarly in both study groups. At 1 year, SRL treatment was associated with a significant reduction of mesangial and endocapillary proliferation, whereas glomerular sclerosis, tubular atrophy and interstitial fibrosis were similar. Sirolimus was well tolerated; all patients remained on therapy at 12 months. The addition of low-dose sirolimus to enalapril and statin is safe, stabilizes renal function and reduces glomerular proliferative lesions in patients with poor prognosis IgA nephropathy.

Accuracy of GFR estimation by the Cockroft and Gault, MDRD, and Wright equations in Oncology patients with renal impairment

Estimation of renal function is crucial to guidance of systemic chemotherapy. With stable creatinine levels, the glomerular filtration rate (GFR) is often estimated from a single measurement of serum creatinine. We compared accuracy of the Cockroft and Gault (C&G), modifying diet in renal diseases (MDRD) and Wright estimates in Oncology patients with renal impairment. Analysis was carried out on the basis of monodentate platinum treatment as the nephrotoxic mechanism of these drugs may affect accuracy of these estimates. Sixty-two consecutive patients with stable creatinine levels who had isotopic GFR measurement of ≤ 60 ml min(-1) at a regional cancer center were reviewed. Twenty-nine were on monodentate platinum treatment. Isotopic GFR was compared with estimated GFR by the three equations. We defined three categories of estimate based on the fractional difference from isotopic GFR: 'perfect' (< 10%), 'reasonable' (≥ 10% but < 30%) and 'poor' (≥ 30%). There was a trend toward provision of more perfect estimates by the MDRD equation particularly in patients on monodentate platinum treatment. Similar numbers had poor estimates from either of these equations, particularly at extremes of body weight. The MDRD formula may be the most accurate of these equations in Oncology patients with renal impairment, particularly with monodentate platinum treatment.

Validation of estimated renal function measurements compared with the isotopic glomerular filtration rate in an HIV-infected cohort

We performed a cross-sectional study to determine the best method for estimating the glomerular filtration rate (GFR) in HIV-infected subjects. Isotopic GFR was correlated with 24-h urine creatinine clearance, cystatin C levels, and 3 creatinine-based equations—the Modification of Diet in Renal Disease (MDRD), Cockcroft–Gault (CG), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)—in 15 patients. Cystatin C showed the strongest correlation with isotopic GFR ( r = −0.760, p = 0.001). When cystatin C was used as the reference variable for all 106 patients, CKD-EPI proved to be superior to the other equations ( r = −0.671, p < 0.001). Time with HIV infection, unsuppressed viral load, low CD4 T-cell counts, and use of protease inhibitors are related to an increased risk of renal impairment, leading us to recommend early initiation of antiretroviral therapy accompanied by a regular renal study.

The Sask Formula to Estimate Glomerular Filtration Rate in Renal Transplant Patients

The aim of this study was to develop a glomerular filtration rate (GFR) equation for renal transplant and compare its performance with Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and isotope dilution mass spectrometry (IDMS) equations. Using genetic symbolic regression analysis, the Sask equation was developed from a training sample of 772 isotope GFR (iGFR) scans performed in 99 transplanted patients. It was then validated in two other samples of 269 scans with the same number of patients. Standard methods including accuracy at 30% range from reference values were compared. In two validation samples, the Sask equation maintained the lowest bias of –0.7 ± 19.0 and 0.4 ± 18.4 ml/min/1.73 m² (p < 0.05) versus –3.1 ± 19.6 and –7.2 ± 18.8 ml/min/1.73 m² for CKD-EPI and –2.2 ± 19.2 and –6.5 ± 18.3 ml/min/1.73 m² for IDMS, respectively. In those with iGFR between 90 and 30 ml/min/1.73 m², the Sask equation demonstrated: (1) the lowest bias of –1.0 ± 15.7 and –0.4 ± 15.7 ml/min/1.73 m² (p < 0.05 vs. other tests); (2) an accuracy of 75.5 and 76.1% (p < 0.05 vs. other tests), and (3) a mean percentage error of 1.9 ± 30.5 and –4.1 ± 31.4 ml/min/1.73 m² (p < 0.05 vs. other tests). Analysis based on gender demonstrated improved performance in the total and subtotal female populations with GFR between 90 and 30 ml/min/1.73 m². The CKD-EPI and Sask equations performed better than IDMS. The Sask equation demonstrated improved bias over CKD-EPI, with iGFR between 90 and 30 ml/min/1.73 m², particularly in females.

Measurement Error in Estimated GFR Slopes across Transplant Chronic Kidney Disease Stages

Background: This study examines if transplant glomerular filtration rate (GFR) slope prediction is affected by the degree of transplant chronic kidney disease (CKDT) stage. Methods: Serial changes in estimated GFR (ΔeGFR) by Cockcroft-Gault (CG) and Modified Diet in Renal Disease-Isotope Dilution Mass Spectrometry (MDRD-IDMS) equations were compared to simultaneous changes in isotope GFR (ΔiGFR) in renal transplant patients who had at least four scans. Results: Total number of patients (iGFR scans) was 99 (772) while the corresponding numbers in CKDT stages 1–4 were 33 (103), 69 (239), 75 (316) and 37 (96), respectively. Measurement error [(ΔeGFR – ΔiGFR) × 100/ΔiGFR] (median ± IQR, interquartile range) estimated from CG and MDRD-IDMS slopes were –414.29 ± 276.16% and –342.86 ± 210.18% (stage 1); –350.00 ± 301.22% and –300.00 ± 525.00% (stage 2); –26.02 ± 404.38% and –26.58 ± 423.13% (stage 3); 10.26 ± 142.18% and –76.92 ± 145.64% (stage 4), respectively. The proportion of patients with CG measurement error ≤1-fold in stages 1 and 2 of 12 and 14.5% was significantly (p < 0.05) lower than that of 36.3 and 52.8% at stages 3 and 4, respectively. Similar measurement errors were observed for MDRD-IDMS. Conclusions: Transplant GFR slope prediction is affected by the degree of renal dysfunction. Errors in slope prediction are much higher in those with better function and thus add another limitation for eGFR use in longitudinal studies on progressive graft dysfunction.

Estimation of Renal Function — What is Appropriate in Cancer Patients?

Aims To compare the accuracy of renal assessment in patients with cancer using radioisotope glomerular filtration rate (GFR), urine collection for creatinine clearance, Cockroft–Gault, Modification of Diet in Renal Disease (MDRD) and Wright formulae. Materials and methods Measurements of isotope GFR from 367 patients were compared with estimates from the described methods (Cockroft–Gault, MDRD, Wright). An analysis including a further 252 patients with an isotope GFR ≤ 50 ml/min was also carried out. Results The Wright formula was the most accurate form of estimating renal function for the first study group. The formulae were similar in accuracy in the second study group. Conclusions The Wright formula is the most accurate form of estimation of renal function in comparison with the isotope GFR for cancer patients. When there is a large proportion of patients with a low isotope GFR (≤50 ml/min), the formulae have similar accuracy.

Is the New Mayo Clinic Quadratic Equation Useful for the Estimation of Glomerular Filtration Rate in Type 2 Diabetic Patients?

OBJECTIVE—To test the Mayo Clinic Quadratic (MCQ) equation against isotopic glomerular filtration rate, compared with the Modification of Diet in Renal Disease (MDRD) and the Cockcroft-Gault formulas, in type 2 diabetes.RESEARCH DESIGN AND METHODS—Based on values obtained with iothalamate, 118 type 2 diabetic patients were divided into three groups according to renal function: hyperfiltration (26), normal function (56), or chronic kidney disease (CKD) stages 3–4 (36). ANOVA, the Bland-Altman procedure, and Lins coefficient (Rc) were performed to study accuracy.RESULTS—In the hyperfiltration and normal function groups, all prediction equations significantly underestimated the value obtained with isotopic glomerular filtration rate (P < 0.05). In the CKD group, all equations also presented significant differences with the isotopic method. However, MDRD had a bias of −5.3 (Rc 0.452), Cockcroft-Gault formula −0.2 (Rc 0.471), and the MCQ −4.5 (Rc 0.526).CONCLUSIONS—The MCQ and prediction equations proved inaccurate (excessive underestimation) in type 2 diabetic patients with hyperfiltration or normal renal function. With regard to CKD, the results obtained provided no evidence of superiority of the MCQ over the MDRD or the Cockcroft-Gault formula.

MRI in patients with chronic obstructive uropathy and compromised renal function: a sole method for morphological and functional assessment

The aim of this study was to assess the role of MRI as a single modality for anatomical and functional evaluation of obstructed kidneys in patients with compromised renal function. The study included 96 adults with unilateral or bilateral chronic obstructive hydronephrosis and compromised renal function (serum creatinine >or=1.8 mg dl(-1)). Patients were subjected to gadolinium-enhanced MRI (Gd-MRI), which determined the anatomy of both renoureteral units, as well as their function, through selective calculation of the glomerular filtration rate (GFR) of each kidney. All patients underwent a technetium-99m diethylenetriamine-pentaacetic acid renal scan. Moreover, a correlation was made between the GFR determined by Gd-MRI and the isotope GFR. The study comprised 59 males and 37 females. A comprehensive MRI study detected the cause of obstruction in all kidneys with non-calcular obstruction (sensitivity of 100%) and in 21 kidneys with calcular obstruction (sensitivity of 70%). The overall sensitivity of MRI combined with plain X-ray of the abdomen and ultrasound in the detection of various causes of obstruction was 97%. A comparison between the isotope GFR of the obstructed kidneys and the corresponding magnetic resonance urography (MRU) GFR showed perfect correlation. In conclusion, combined static and dynamic MRU is a promising technique that allows anatomical and functional evaluation of obstructed kidneys in patients with impaired renal function but, owing to the possible risk of nephrogenic systemic fibrosis in patients with a GFR <30 ml min(-1), the lowest possible dose of the most stable Gd-macrocyclic chelates should be used if a functional MRI study is required.

Comparison of glomerular function tests in children with cancer

Evaluation of renal function should be performed as part of the follow-up during and after chemotherapy in pediatric cancer patients. The aim of this study was to compare an isotope clearance method [isotope glomerular filtration rate (iGFR)] with alternative methods to determine GFR in such patients. Isotope GFR [(99m)Tc-labeled diethylene triaminopentoacetic acid (DTPA) or (51)Cr-labeled ethylenediaminetetra-acetate (EDTA)] was measured in 36 children (112 studies) and compared with simultaneously measured creatinine clearance (CrCl), serum creatinine (SCr), and cystatin C (CysC) concentrations, as well as the results of Schwartz, Counahan-Barratt, and Cockroft-Gault formulae, using general linear mixed models. Our results showed a significant association between iGFR and CysC concentrations (p < 0.001). No linear relationship was observed between CrCl and iGFR (p = 0.7). As expected, the results of height-based formulae (Counahan-Barratt and Schwartz) had significantly (p = 0.004) better correlation to iGFR than the results of a formula based on weight (Cockroft-Gault) (p = 0.19). Despite significant linear correlation, intraclass correlation coefficients showed poor agreement. Tests of similarity between iGFR estimates showed differences between average values of GFR. Therefore, determination of iGFR remains the method of choice in estimation of GFR in cancer patients. In our study population, assay of serum CysC was the most reliable alternative method to measure glomerular function.

Serial Measurements of Cystatin C Are More Accurate Than Creatinine-Based Methods in Detecting Declining Renal Function in Type 1 Diabetes

Cystatin C-and creatinine-based methods were compared with (99m)-technetium-diethylene-triamine-penta-acetic acid ((99m)Tc-DTPA) plasma clearance (isotopic glomerular filtration rate [iGFR]) for detecting declining renal function. Glomerular filtration rate (GFR) was monitored over a mean of 10.1 years in 85 subjects with type 1 diabetes (with an average of 5.6 measurements per individual). Baseline mean +/- SD iGFR of the cohort was 106.1 +/- 2.6 ml/min per 1.73 m(2). The rates of decline in GFR (DeltaGFR) were derived using linear regression. In 19 of 85 subjects with declining renal function (i.e., DeltaiGFR >3.3 ml/min per 1.73 m(2) per year), DeltaGFR (ml/min per 1.73 m(2) per year) was 6.5 by iGFR, 4.2 by 10(4)/creatinine, 3.6 by Cockcroft-Gault formula, 3.4 by the Modification of Diet in Renal Disease (MDRD)-6 equation, and 3.5 by the MDRD-4 variable equation (P < 0.01 vs. iGFR). In comparison, DeltaGFR was 6.1 using the formula Cys-GFR = (86.7/cystatin C concentration) - 4.2 (not significant). Cystatin C was more accurate in detecting decline in renal function than creatinine-based methods in this population of subjects with type 1 diabetes and a normal mean baseline GFR.

Accuracy to Estimate Rates of Decline in Glomerular Filtration Rate in Renal Transplant Patients

We examined the use of the Cockroft Gault (C-G) test, Modified Diet in Renal Disease 2 (MDRD2) test, and inverse serum creatinine (Delta1/Scr) to estimate rates of decline in renal transplant function using isotope glomerular filtration rate (GFR) as a reference test. Percent changes in estimated GFR (DeltaeGFR) were compared to simultaneous changes in isotope GFR (DeltaiGFR) in 72 patients. The number of iGFR was 508 with a mean of 7.15+/-3.15 scans per patient. There was a decline in iGFR of 16.14+/-21.37 ml/min over the study duration of 88.9+/-57.6 months. DeltaeGFR and Delta1/Scr correlated significantly with DeltaiGFR. Accuracy to predict DeltaiGFR from the eGFRs was limited to <65% concordance within 30% range from changes in iGFR. Slope analyses showed a significantly lower percent annual loss in mean iGFR of 6.03% than that of the C-G of 8.62% and MDRD2 of 8.96% (P<0.001). The within patient variability measured from the standard deviation (ml/min) of root mean square of 4.69 for iGFR was significantly higher than that for C-G and MDRD2 of 2.46 and 2.94, respectively. iGFR and eGFR at first observation correlated significantly (P<0.001) with last observation. iGFR is significantly more variable within patient than the other predictors, and the two estimators predict the iGFR with a high sensitivity but low specificity. This is a clinically reasonable combination. Predicted percent of annual loss in iGFR appears to be smaller than that using the two estimators.

Oncological and Functional Outcome of Radical Cystectomy in Patients With Bladder Cancer and Obstructive Uropathy

We present our experience with the perioperative, functional and oncological outcomes of radical cystectomy in patients with bladder cancer and obstructive uremia. From 1998 to June 2006, 58 patients with bladder cancer, and concomitant obstructive uropathy and azotemia presented to our institution. Mean +/- SD serum creatinine at presentation was 9.2 +/- 4.5 mg% (range 2.4 to 16.5). Radical cystectomy, bilateral pelvic lymphadenectomy and urinary diversion were performed after stabilizing renal function with and without percutaneous nephrostomy in 28 and 8 patients, respectively. Various preoperative variables were evaluated for predicting long-term treatment failure and renal deterioration. Mean followup was 34 months. Mean serum creatinine at surgery was 1.85 mg%. An ileal conduit was used in 32 patients and cutaneous ureterostomy was used in 4. One patient died of chest infection in the perioperative period. All patients had muscle invasive disease, while 15 had positive lymph nodes. At the mean followup 15 patients (41.6%) were free of disease and 21 had treatment failure. Of the factors evaluated pathological tumor stage, grade and lymph node involvement predicted the long-term oncological outcome, while serum creatinine greater than 2.5 mg% at surgery and ileal conduit diversion predicted long-term renal deterioration. Patients with bladder cancer who have obstructive uremia usually present with locally advanced disease. Radical cystectomy is not associated with additional morbidity, provided that patients are adequately prepared before surgery by optimizing renal function. An adequate number of these patients achieve long-term disease-free survival after radical cystectomy. As the urinary diversion of choice, an ileal conduit appears to be safe in patients with serum creatinine less than 2.5 mg% at surgery.

New Predictive Equations Improve Monitoring of Kidney Function in Patients With Diabetes

The Cockcroft-Gault and Modification of Diet in Renal Disease (MDRD) equations poorly predict glomerular filtration rate (GFR) decline in diabetic patients. We sought to discover whether new equations based on serum creatinine (the Mayo Clinic Quadratic [MCQ] or reexpressed MDRD equations) or four cystatin C-based equations (glomerular filtration rate estimated via cystatin formula [Cys-eGFR]) were less biased and better predicted GFR changes. In 124 diabetic patients with a large range of isotopic GFR (iGFR) (56.1 +/- 35.3 ml/min per 1.73 m2 [range 5-164]), we compared the performances of the equations before and after categorization in GFR tertiles. A total of 20 patients had a second determination 2 years later. The Cockcroft-Gault equation was the least precise. The MDRD equation was the most precise but the most biased according to the Bland-Altman procedure. By contrast with the MDRD and, to a lesser extent, the MCQ, three of the four Cys-eGFRs were not biased. All equations overestimated the low GFRs, whereas only the MDRD and Rule's Cys-eGFR equations underestimated the high GFRs. For the subjects studied twice, iGFR changed by -8.5 +/- 17.9 ml/min per 1.73 m2. GFR changes estimated by the Cockcroft-Gault (-4.5 +/- 6.8) and MDRD (-5.7 +/- 6.2) equations did not correlate with the isotopic changes, whereas new equation-predicted changes did: MCQ: -8.7 +/- 9.4 (r = 0.44, P < 0.05) and all four Cys-eGFRs: -6.2 +/- 7.4 to -7.3 +/- 8.4 (r = 0.60 to 0.62, all P < 0.005), such as 100/cystatin-C (r = 0.61, P < 0.005). The new predictive equations better estimate GFR than the Cockcroft-Gault equation. Although the MDRD equation remains the most accurate, it poorly predicts GFR decline, as it overestimates low and underestimates high GFRs. This bias is lesser with the MCQ and Cys-eGFR equations, so they better predict GFR changes.

How Reliable Is Estimation of Glomerular Filtration Rate at Diagnosis of Type 2 Diabetes?

The Cockcroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) equations previously have been recommended to estimate glomerular filtration rate (GFR). We compared both estimates with true GFR, measured by the isotopic (51)Cr-EDTA method, in newly diagnosed, treatment-naïve subjects with type 2 diabetes. A total of 292 mainly normoalbuminuric (241 of 292) subjects were recruited. Subjects were classified as having mild renal impairment (group 1, GFR <90 ml/min per 1.73 m(2)) or normal renal function (group 2, GFR >/=90 ml/min per 1.73 m(2)). Estimated GFR (eGFR) was calculated by the CG and MDRD equations. Blood samples drawn at 44, 120, 180, and 240 min after administration of 1 MBq of (51)Cr-EDTA were used to measure isotopic GFR (iGFR). For subjects in group 1, mean (+/-SD) iGFR was 83.8 +/- 4.3 ml/min per 1.73 m(2). eGFR was 78.0 +/- 16.5 or 73.7 +/- 12.0 ml/min per 1.73 m(2) using CG and MDRD equations, respectively. Ninety-five percent CIs for method bias were -11.1 to -0.6 using CG and -14.4 to -7.0 using MDRD. Ninety-five percent limits of agreement (mean bias +/- 2 SD) were -37.2 to 25.6 and -33.1 to 11.7, respectively. In group 2, iGFR was 119.4 +/- 20.3 ml/min per 1.73 m(2). eGFR was 104.4 +/- 26.3 or 92.3 +/- 18.7 ml/min per 1.73 m(2) using CG and MDRD equations, respectively. Ninety-five percent CIs for method bias were -17.4 to -12.5 using CG and -29.1 to -25.1 using MDRD. Ninety-five percent limits of agreement were -54.4 to 24.4 and -59.5 to 5.3, respectively. In newly diagnosed type 2 diabetic patients, particularly those with a GFR >/=90 ml/min per 1.73 m(2), both CG and MDRD equations significantly underestimate iGFR. This highlights a limitation in the use of eGFR in the majority of diabetic subjects outside the setting of chronic kidney disease.

Bone loss in diabetic patients with chronic kidney disease

We investigated whether loss of bone is detectable during follow-up of diabetic patients with chronic kidney disease (CKD). In 40 initially non-dialysed diabetic patients with CKD (isotopic glomerular filtration rate < 60 ml/min/1.73 m(2) or albumin excretion rate > 30 mg/24 h), body composition (DEXA scan) and glomerular filtration rate (GFR determined from (51)Cr-EDTA clearance) were measured at a 2-year interval, and compared by paired t-tests. The 40 patients, mainly with Type 2 diabetes (n = 28), were men (n = 28), aged 65 +/- 11 years, with diabetes duration 18 +/- 11 years. GFR was initially 38.0 (range 8-89) ml/min/1.73 m(2). CKD progressed during follow-up: eight started haemodialysis and GFR declined in the 32 others (P < 0.05 vs. initial). T-scores for total body (initial -0.61 +/- 1.11, final -1.11 +/- 1.40; P < 0.001) and femoral neck (initial -1.88 +/- 0.15, final -2.07 +/- 0.15; P < 0.05) declined. Ten patients were osteopaenic at baseline (no osteoporosis), whereas most were osteopaenic (n = 21, P < 0.05) and five were osteoporotic at final assessment. The 16 patients who became osteopaenic or osteoporotic during follow-up did not differ from the others for the type of diabetes, age, GFR, albumin excretion rate, HbA(1c), GFR reduction and the requirement for dialysis during follow-up. They were all men (P < 0.01 by chi-squared test), with reduced initial total body T-score (-1.20 +/- 0.82, others -0.32 +/- 1.13; P < 0.05) and a lower body mass index (24.6 +/- 4.3; others 27.7 +/- 4.3; P < 0.05). Bone loss, especially in the femoral neck, is progressive in diabetic patients with CKD.