Eduardo Guimarães Camargo

Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Equation Pronouncedly Underestimates Glomerular Filtration Rate in Type 2 Diabetes

OBJECTIVE To evaluate the performance of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation to estimate glomerular filtration rate (GFR) in type 2 diabetic patients with GFR >60 mL/min/1.73 m2. RESEARCH DESIGN AND METHODS This was a cross-sectional study including 105 type 2 diabetic patients. GFR was measured by 51Cr-EDTA method and estimated by the MDRD and CKD-EPI equations. Serum creatinine was measured by the traceable Jaffe method. Bland-Altman plots were used. Bias, accuracy (P30), and precision were evaluated. RESULTS The mean age of patients was 57 ± 8 years; 53 (50%) were men and 90 (86%) were white. Forty-six (44%) patients had microalbuminuria, and 14 (13%) had macroalbuminuria. 51Cr-EDTA GFR was 103 ± 23, CKD-EPI GFR was 83 ± 15, and MDRD-GFR was 78 ± 17 mL/min/1.73 m2 (P < 0.001). Accuracy (95% CI) was 67% (58–74) for CKD-EPI and 64% (56–75) for MDRD. Precision was 21 and 22, respectively. CONCLUSIONS The CKD-EPI and MDRD equations pronouncedly underestimated GFR in type 2 diabetic patients.

Comparison between IDMS-traceable Jaffe and enzymatic creatinine assays for estimation of glomerular filtration rate by the CKD-EPI equation in healthy and diabetic subjects.

OBJECTIVES The aim of this paper was to compare the agreement between creatinine measured by Jaffe and enzymatic methods and their putative influence on eGFR as calculated by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation in healthy and diabetic individuals. DESIGN AND METHODS Cross-sectional study conducted in 123 adult southern Brazilians with GFR>60 mL/min/1.73 m² (53 patients with type 2 diabetes, 70 healthy volunteers). Mean age was 49±16 years (range of 19-86). Most were female (55%) and white (83%). Creatinine was measured by a traceable Jaffe method (Modular P, Roche Diagnostic) and by an enzymatic method (CREA plus, Roche/Hitachi 917). GFR was measured by the ⁵¹Cr-EDTA single-injection method. RESULTS Serum creatinine measured by the Jaffe and enzymatic methods was similar in healthy subjects (0.79±0.16 vs. 0.79±0.15 mg/dL, respectively, P=0.76), and diabetic patients (0.96±0.22 vs. 0.92±0.29 mg/dL, respectively, P=0.17). However, the correlation between the two methods was higher in the healthy group (r=0.90 vs. 0.76, P<0.001). The difference between Jaffe creatinine and enzymatic creatinine was <10% in 63% of cases in the healthy group and 40% of cases in the diabetes group (P=0.018). In the subset of patients with diabetes, eGFR based on enzymatic assay results showed better agreement with measured GFR than did eGFR based on Jaffe results. CONCLUSION Jaffe and enzymatic creatinine methods show adequate agreement in healthy subjects, but in the presence of diabetes, the enzymatic method performed slightly better.

Glomerular filtration rate estimation: performance of serum cystatin C-based prediction equations.

Abstract Serum creatinine measurement is a mainstay in the routine laboratory evaluation of renal function, despite of having several disadvantages. Cystatin C, on the other hand, suffers less influence of gender and muscle mass and has been proposed as a more sensitive marker for glomerular filtration rate. However, serum endogenous markers should not be used alone to assess glomerular filtration rate. Creatinine-based equations such as the modification of diet in renal disease (MDRD) and Cockcroft-Gault are widely used despite their limitations. A large number of cystatin C-based prediction equations were developed in recent years, in diverse populations, with different laboratory assays and methods. Several studies demonstrated that cystatin C-based equations are reliable markers of glomerular filtration rate and can be used for diagnosis, evaluation and follow-up of kidney disease. They are simpler than creatinine-based equations and have at least the same accuracy and precision for glomerular filtration rate estimation. In conclusion, diabetes mellitus, cystic fibrosis, kidney transplantation, HIV-infection, and cirrhosis are clinical situations where cystatin C-based equations can be useful. Extremes of age such as childhood and advanced age have also been evaluated with favorable results.

Performance of CKD-EPI equation to estimate glomerular filtration rate as compared to MDRD equation in South Brazilian individuals in each stage of renal function

Abstract Background: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation seems to correct the overdiagnosis of chronic kidney disease (CKD) provided by Modification of Diet in Renal Disease (MDRD) equation. However, this point has not been tested in some ethnic groups. This study investigated the performance of MDRD and CKD-EPI equations in South Brazilian individuals. Methods: This cross-sectional study included 354 individuals including healthy volunteers, diabetic and non-diabetic individuals with or without CKD. Glomerular filtration rate (GFR) was measured by the 51Cr-EDTA single-injection method (51Cr-GFR). Accuracy (P30), bias, and Bland-Altman agreement plots were evaluated. Results: In the group as a whole, 51Cr-GFR was 87±37 (6-187), CKD-EPI eGFR, 82±30 (6-152), and MDRD eGFR, 77±28 (6-156) mL/min/1.73 m2 (p<0.001 for all comparisons). Analyzing the subset of individuals with 51Cr-GFR <60 mL/min/1.73 m2, P30 values were, respectively, 76% and 84% for MDRD and for CKD-EPI (p<0.001) while for 51Cr-GFR ≥60 mL/min/1.73 m2, P30 values were 57.5% for both equations (p=1.000). For MDRD and CKD-EPI, mean bias were negative for GFRs <60 (–11 vs. –12, p=0.221) and positive for values >60 (16 vs. 9, p<0.001). In multivariate analysis, absolute bias was unfavorably influenced by measured GFR >60 (for MDRD) and being diabetic or younger (for CKD-EPI). Conclusions: CKD-EPI reduces GFR underestimation in individuals with GFRs >60, but still presents a quite low accuracy at this GFR range. Moreover, it tends to overestimate GFR in subjects with GFRs <60 mL/min/1.73 m2. CKD stages 1 and 2, diabetes and young age had a negative influence on the performance of the equations.

Is there a role for inherited TR βmutation in human carcinogenesis

Resistance to thyroid hormone (RTH) is a rare autosomal dominant inherited disorder characterized by end-organ reduced sensitivity to thyroid hormone. This syndrome is caused by mutations of the thyroid hormone receptor (TR) β gene, and its clinical presentation is quite variable. Goiter is reported to be the most common finding. A close association of TRβ mutations with human cancers has become apparent, but the role of TRβ mutants in the carcinogenesis is still undefined. Moreover, higher TSH levels, described in RTH syndrome, are correlated with increased risk of thyroid malignancy, whereas TSH receptor stimulation is likely to be involved in tumor progression. We report here an illustrative case of a 29 year-old patient with RTH caused by a mutation in exon 9 (A317T) of TRβ gene, who presented multicentric papillary thyroid cancer. We review the literature on this uncommon feature, and discuss the potential role of this mutation on human tumorigenesis, as well as the challenges in patient follow-up.

Lack of interference of aspirin in HbA1c measured by ion-exchange HPLC in type 2 diabetic patients: a randomized, double-blind, placebo-controlled study.

Remarkable clinical trials, like the Diabetes Control and Complications Trial (DCCT) and United Kingdom Prospective Diabetes Study (UKPDS), have established that HbA1c is the cornerstone to predict the development of chronic vascular complications in diabetic subjects [1,2]. The American Diabetes Association (ADA) recommends HbA1c measurements at least twice a year, with target levels b7% [3]. However, it should be taken into account that many factors can influence the results, such as the analytical interference of some drugs, like aspirin (acetylsalicylic acid) [4–6]. This is an important issue, because low-dose aspirin is recommended for both primary and secondary cardiovascular disease prevention in diabetic patients [3]. Some in vitro and in vivo studies have suggested a potential interference of aspirin in HbA1c assays, especially in those that rely on the change of charge, like ion-exchange HPLC and electrophoresis [6–8]. Aspirin induces an acetylation of hemoglobin, giving it a negative charge and consequently increasing HbA1c levels in chromatographic assays [9]. There are no randomized clinical trials analyzing the possible effects of the antiplatelet agent on HbA1c values measured by ionexchange HPLC assay in diabetic patients. Therefore, the aim of this study was to evaluate the influence of low-dose aspirin on HbA1c levels measured by this method in type 2 diabetic patients. In this randomized, crossover, double-blind, placebocontrolled study, 14 type 2 DM patients received aspirin (300 mg/d) or an identical placebo for 8 weeks, with a 6week washout period. All patients signed a written informed consent approved by the Ethics Committee of the Hospital. The sample size calculation disclosed that a minimum of 12 patients was needed to detect an absolute change in HbA1c N0.5% (α=0.05 and β=0.20). The patients entered a run-in phase of 8 weeks, to stabilize metabolic control. All patients, except for 2 who received only insulin, used metformin, either alone or in combination

The effect of aspirin on the antiproteinuric properties of enalapril in microalbuminuric type 2 diabetic patients: a randomized, double-blind, placebo-controlled study.

The concomitant use of angiotensin-converting enzyme inhibitors (ACEIs) and aspirin is recommended for any diabetic patient with microalbuminuria or macroalbuminuria because these drugs result in renal and cardiovascular benefits (1,2). However, a putative pharmacological interaction between these drugs is plausible, through their opposite effects on vasodilator prostaglandins (3). Therefore, the aim of this study was to analyze the possible interference of intermediate-dose aspirin (300 mg/day) on urinary albumin excretion (UAE) reduction properties of enalapril in microalbuminuric type 2 diabetic patients. In this randomized, crossover, double-blind, placebo-controlled …

Combined creatinine-cystatin C CKD-EPI equation significantly underestimates measured glomerular filtration rate in people with type 2 diabetes mellitus

AIM To evaluate the accuracy of creatinine and cystatin C (cysC) equations to estimate glomerular filtration rate (GFR) in type 2 diabetes mellitus (DM) patients and healthy adults. METHODS Case-control study including 84 patients with type 2 DM and 100 healthy adults with measured GFR (mGFR)≥60mL/min/1.73m2. GFR was measured by 51Cr-EDTA and estimated (eGFR) by the following equations using creatinine, cysC or both markers: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Caucasian Asian Pediatrics and Adults (CAPA), CKD-EPI creatinine-cystatin C (CKDEPI-CC), and CKD-EPI cystatin C (CKDEPIcysC). Agreement was evaluated by Bland & Altman analysis. RESULTS Healthy individuals were 66% females, aged 38±14years; they presented mGFR 112±19mL/min/1.73m2 and eGFR by CKD-EPI, CKDEPI-CC, CKDEPIcysC and CAPA equations, respectively, 108±17, 102±15, 97±16 and 93±16mL/min/1.73m2. DM group were 50% females, aged 59±19years and presented mGFR 104±27 and eGFR 87±19, 80±18, 74±20 and 73±18mL/min/1.73m2, respectively. All equations significantly underestimated mGFR, excepting creatinine-based CKD-EPI in the healthy group. The performance was considerably worse for GFRs above 120mL/min/1.73m2. CONCLUSION In both healthy and type 2 DM patients, cystatin C-based equations, including the combined CKD-EPI creatinine-cystatin equation, failed to improve the accuracy of GFR estimation, especially for normal and high normal GFR values.

Cavernous Sinus Thrombosis Mimicking Graves Ophthalmopathy in a Patient With Thyroid Storm

In patients with Graves disease, unilateral or markedly asymmetric ocular manifestations should raise suspicion of other ocular disorders. In the present report, we describe a patient with Graves disease who presented with a 24-hour history of severe left-sided headache and fever. Cranial computed tomography revealed pansinusitis, and the patient was treated with antibiotics and discharged. He returned 24 hours later with worsening of the headache and left eye proptosis with retrobulbar pain, periorbital swelling, conjunctival redness, and chemosis. There was also external ophthalmoplegia on lateral, upward and downward gaze of the left eye. A diagnosis of Graves ophthalmopathy was made. Later, based on computed tomography of the orbit, which revealed frontal sinusitis and thrombosis of the left cavernous sinus, and on clinical and laboratory data, a diagnosis of thyroid storm with septic thrombosis of the cavernous sinus was made. To our knowledge, this is the first report of an association between a benign condition, sinusitis, and potentially lethal septic thrombosis of the cavernous sinus and thyroid storm. The presence of sinusitis in patients with Graves disease should alert physicians to the possibility of cavernous sinus thrombosis.