Correction: Using Automated HbA1c Testing to Detect Diabetes Mellitus in Orthopedic Inpatients and Its Effect on Outcomes.

[This corrects the article DOI: 10.1371/journal.pone.0168471.].

Using Automated HbA1c Testing to Detect Diabetes Mellitus in Orthopedic Inpatients and Its Effect on Outcomes.

AIMS: The prevalence of diabetes is rising, and people with diabetes have higher rates of musculoskeletal-related comorbidities. HbA1c testing is a superior option for diabetes diagnosis in the inpatient setting. This study aimed to (i) demonstrate the feasibility of routine HbA1c testing to detect the presence of diabetes mellitus, (ii) to determine the prevalence of diabetes in orthopedic inpatients and (iii) to assess the association between diabetes and hospital outcomes and post-operative complications in orthopedic inpatients. METHODS: All patients aged ≥54 years admitted to Austin Health between July 2013 and January 2014 had routine automated HbA1c measurements using automated clinical information systems (CERNER). Patients with HbA1c ≥6.5% were diagnosed with diabetes. Baseline demographic and clinical data were obtained from hospital records. RESULTS: Of the 416 orthopedic inpatients included in this study, 22% (n = 93) were known to have diabetes, 4% (n = 15) had previously unrecognized diabetes and 74% (n = 308) did not have diabetes. Patients with diabetes had significantly higher Charlson comorbidity scores compared to patients without diabetes (median, IQR; 1 [0,2] vs 0 [0,0], p<0.001). After adjusting for age, gender, comorbidity score and estimated glomerular filtration rate, no significant differences in the length of stay (IRR = 0.92; 95%CI: 0.79-1.07; p = 0.280), rates of intensive care unit admission (OR = 1.04; 95%CI: 0.42-2.60, p = 0.934), 6-month mortality (OR = 0.52; 95%CI: 0.17-1.60, p = 0.252), 6-month hospital readmission (OR = 0.93; 95%CI: 0.46-1.87; p = 0.828) or any post-operative complications (OR = 0.98; 95%CI: 0.53-1.80; p = 0.944) were observed between patients with and without diabetes. CONCLUSIONS: Routine HbA1c measurement using CERNER allows for rapid identification of inpatients admitted with diabetes. More than one in four patients admitted to a tertiary hospital orthopedic ward have diabetes. No statistically significant differences in the rates of hospital outcomes and post-operative complications were identified between patients with and without diabetes.

Elevated baseline glomerular filtration rate (GFR) is independently associated with a more rapid decline in renal function of patients with type 1 diabetes.

AIMS: Renal hyperfiltration is observed prior to the development of diabetic kidney disease (DKD) in patients with type 1 diabetes (T1DM); however its significance remains uncertain. Longitudinal data were used to investigate the association between measured baseline glomerular filtration rate (GFR) and renal function decline in patients with T1DM. METHODS: This study included 142 adult patients with T1DM and ≥2 measurements of glomerular filtration rate (mGFR; determined by diethylene-triamine-penta-acetic acid plasma clearance). Median follow up was 19 years. Patients were stratified by baseline mGFR quartile. The relationship between baseline mGFR and rate of renal function decline was assessed using random-effect generalized least squares regression, adjusted for age, duration of diabetes, HbA1c, blood pressure, renin-angiotensin-aldosterone system inhibitor therapy, LDL and BMI. RESULTS: The average rates of decline in renal function for the 2nd (baseline mGFR: 96.4-112.6 ml min-(1) 1.73 m-(2)), 3(rd) (baseline mGFR: 112.6-125.5 ml min- (1) 1.73 m-(2)) and 4th quartiles (baseline mGFR >125.5 ml min-(1) 1.73 m-(2)) were significantly faster than the first quartile (baseline mGFR: 60.9-96.4 ml min-(1) 1.73 m-(2)). In further detail, the average rates of decline in the 2nd (rate of decline 1.25 ml min- (1) 1.73 m-(2) per year, 95% CI: 0.97; 1.52, p=0.008), 3rd (rate of decline 1.35 ml min-(1) 1.73 m-(2) per year, 95% CI: 1.08; 1.62, p= 0.001) and 4th quartiles (rate of decline 1.6 ml min-(1) 1.73 m-(2) per year, 95% CI: 1.34, 1.88, <0.0001) were significantly faster when compared to the first quartile (rate of decline 0.67 ml min-(1) 1.73 m-(2) per year, 95% CI: 0.37; 0.96). Sub-analysis of quartile 4 revealed higher HbA1c measurements throughout follow-up in those with rapid mGFR decline (>3.0 ml min(-1)1.73 m(-2)/year). CONCLUSIONS: In patients with T1DM, higher baseline mGFR is associate ed with more rapid mGFR decline. Patients with high baseline mGFR who developed rapid mGFR decline had higher HbA1c measurements throughout the study. These findings are consistent with the concept that poor glycaemic control over time may be a determining factor for the rapid renal function decline observed in some hyperfiltering patients.

The Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation does not improve the underestimation of Glomerular Filtration Rate (GFR) in people with diabetes and preserved renal function.

BACKGROUND: Our hypothesis was that both the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) equations would underestimate directly measured GFR (mGFR) to a similar extent in people with diabetes and preserved renal function. METHODS: In a cross-sectional study, bias (eGFR - mGFR) was compared for the CKD-EPI and MDRD equations, after stratification for mGFR levels. We also examined the ability of the CKD-EPI compared with the MDRD equation to correctly classify subjects to various CKD stages. In a longitudinal study of subjects with an early decline in GFR i.e., initial mGFR > 60 ml/min/1.73 m(2) and rate of decline in GFR (ΔmGFR) > 3.3 ml/min/1.73 m(2) per year, ΔmGFR (based on initial and final values) was compared with ΔeGFR by the CKD-EPI and MDRD equations over a mean of 9 years. RESULTS: In the cross-sectional study, mGFR for the whole group was 80 ± 2.2 ml/min/1.73 m(2) (n = 199, 75 % type 2 diabetes). For subjects with mGFR >90 ml/min/1.73 m(2) (mGFR: 112 ± 2.0, n = 76), both equations significantly underestimated mGFR to a similar extent: bias for CKD-EPI: -12 ± 1.4 ml/min/1.73 m(2) (p < 0.001) and for MDRD: -11 ± 2.1 ml/min/1.73 m(2) (p < 0.001). Using the CKD-EPI compared with the MDRD equation did not improve the number of subjects that were correctly classified to a CKD-stage. No biochemical or clinical patient characteristics were identified to account for the under estimation of mGFR values in the normal to high range by the CKD-EPI equation. In the longitudinal study (n = 30, 66 % type 1 diabetes), initial and final mGFR values were 102.8 ± 6 and 54.6 ± 6.0 ml/min/1.73 m(2), respectively. Mean ΔGFR (ml/min/1.73 m(2) per year) was 6.0 by mGFR compared with only 3.0 by MDRD and 3.2 by CKD-EPI (both p < 0.05 vs mGFR) CONCLUSIONS: Both the CKD-EPI and MDRD equations underestimate reference GFR values > 90 ml/min/1.73 m(2) as well as an early decline in GFR to a similar extent in people with diabetes. There is scope to improve methods for estimating an early decline in GFR.

Estimating glomerular filtration rate in diabetes using serum cystatin C.

Chronic kidney disease (CKD) is a major public health problem, especially for people with diabetes. Not only is it a risk factor for end-stage renal disease (ESRD) but it is also a major cardiovascular disease (CVD) risk factor. Methods that accurately and simply estimate glomerular filtration rate (GFR) are therefore needed to optimise the detection and management of CKD in people with diabetes. One of the main failures of commonly used creatinine-based methods for estimating renal function is that they lack applicability across the full range of GFR values and underestimate GFR levels >60 mL/min/1.73m(2). Methods for accurately estimating an early pathological decline in GFR (i.e. ΔGFR >3.3 mL/min/year before reaching a GFR <60 mL/min/1.73m(2)) are especially needed as appropriate interventions have been shown to retard progression to ESRD and reduce CVD risk in people with diabetes. In contrast, recent studies have suggested that estimates of GFR based on serum cystatin C concentration might provide a simple and accurate method for detecting and monitoring an early decline in renal function.

Integrating albuminuria and GFR in the assessment of diabetic nephropathy.

The evaluation of diabetic nephropathy from research and clinical viewpoints depends on the assessment of two continuous variables, albumin excretion rate (AER) and glomerular filtration rate (GFR). These two parameters form the basis of both the European classification of five stages of diabetic nephropathy, assessed according to changes in AER and GFR (hyperfiltration, normoalbuminuria, microalbuminuria, macroalbuminuria and end-stage renal disease), and the National Kidney Foundation classification of five stages of chronic kidney disease based on categories of estimated GFR. Although increases in AER generally precede a decline in GFR, some patients follow a non-albuminuric pathway to renal impairment. In addition, studies indicate that GFR decreases in a linear fashion from normal or above-normal levels. Whether hyperfiltration is part of the pathogenetic process leading to diabetic nephropathy remains unclear. Ideally, both AER and GFR should be assessed at an early stage in patients being evaluated for diabetic nephropathy. New methods such as the use of cystatin-C-based equations for estimating GFR should be considered because current creatinine-based estimates are inaccurate at normal or high GFRs. Serial assessments of both AER and GFR might allow diabetic nephropathy to be diagnosed at early stages of the disease process that are selectively responsive to new interventions. The successful integration of AER categories with the recently defined stages of GFR represents a new challenge in the management of diabetic nephropathy.

Thyrotoxicosis during sunitinib treatment for renal cell carcinoma.

CONTEXT: Sunitinib malate is an oral tyrosine kinase inhibitor used in the treatment of renal cell carcinoma (RCC) and gastrointestinal stromal tumours. Hypothyroidism has been observed in patients treated with sunitinib, but the mechanism whereby sunitinib induces hypothyroidism is unknown. OBJECTIVE: To describe a series of six patients who developed thyrotoxicosis while on sunitinib for metastatic RCC. SETTING: The study was conducted at Austin Health, a tertiary teaching hospital in Melbourne, Australia. RESULTS: Two patients developed severe thyrotoxicosis within 10 weeks after commencing sunitinib. In contrast, in the four patients who presented with later onset (16-30 weeks) thyrotoxicosis, the thyrotoxicosis was relatively mild, self-limiting and rapidly progressed to hypothyroidism. These patients experienced recurrent episodes of thyrotoxicosis in temporal relation to their cyclical sunitinib treatment. One patient had cytological evidence of lymphocytic thyroiditis. CONCLUSIONS: These findings suggest that sunitinib-induced hypothyroidism may be a consequence of preceding thyroiditis with associated transient thyrotoxicosis. As predictive factors are currently unknown, we suggest regular monitoring of thyroid function in all patients commenced on sunitinib. Clinicians treating patients with sunitinib or other similar kinase inhibitors should to be alerted to thyroid dysfunction as a potential toxicity of these agents.

Serial measurements of cystatin C are more accurate than creatinine-based methods in detecting declining renal function in type 1 diabetes.

OBJECTIVE: 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. RESEARCH DESIGN AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Lowering of proteinuria in response to antihypertensive therapy predicts improved renal function in late but not in early diabetic nephropathy: a pooled analysis.

In late diabetic nephropathy (DN) the initial lowering of albumin excretion rate (AER) with antihypertensive therapy is proportional to the degree of subsequent preservation of glomerular filtration rate (GFR). Whether a similar relationship exists between AER and GFR in early diabetes is not known. The present analysis has compared AER and GFR responses to antihypertensive therapy in 33 published studies (77 treatment groups) of early and late DN in type 1 (T1) and type 2 (T2) diabetes, analyzed on an intention-to-treat basis. Prospective trials were included if the initial change in AER during the first year of therapy and the change in GFR during at least 2 years of follow-up could be estimated from group mean data. The initial % decreases in AER were 5.9 +/- 4.3 (T1), 10.5 +/- 5.4 (T2, normotensive) and 18.4 +/- 6.2 (T2, hypertensive) in early DN and 7.6 +/- 11.1 (T1) and 20.8 +/- 5.5 (T2) in late DN. The corresponding annual % rates of decline of GFR were 2.0 +/- 0.5 (T1), 1.6 +/- 0.5 (T2, normotensive) and 2.1 +/- 0.3 (T2, hypertensive) in early DN and 9.8 +/- 1.5 (T1) and 9.2 +/- 1.1 (T2) in late DN. AER and GFR responses in each treatment group were closely correlated in late nephropathy (T1, r = -0.67, p = 0.03; T2, r = 0.57, p = 0.02) but not in early nephropathy. In contrast to late DN, the initial decrease in AER with antihypertensive therapy was not shown to predict the subsequent rate of decline of GFR in early DN. It follows that assessment of renoprotection during antihypertensive therapy in early nephropathy should be based not only on albuminuria but also on the GFR response.

The photon transport equation for turbid biological media with spatially varying isotropic refractive index.

Using the principle of energy conservation and laws of geometrical optics, we derive the photon transport equation for turbid biological media with spatially varying isotropic refractive index. We show that when the refractive index is constant, our result reduces to the standard radiative transfer equation and when the medium is lossless and free of scattering to the well known geometrical optics equations in refractive media.