Geometric Distortion Correction of Renal Diffusion Tensor Imaging Using the Reversed Gradient Method.

ABSTRACT: Renal echo planar diffusion tensor imaging (DTI) has clinical potential but suffers from geometric distortion. We evaluated feasibility of reversed gradient distortion correction in 10 diabetic patients and 6 volunteers. Renal area, apparent diffusion coefficient, fractional anisotropy, and tensor eigenvalues were measured on uncorrected and distortion-corrected DTI. Corrected DTI correlated better than uncorrected DTI (r = 0.904 vs 0.840, P = 0.002) with reference anatomic T2-weighted imaging, with no significant difference in DTI metrics.

Risk factors for pregnancy outcomes in Type 1 and Type 2 diabetes.

BACKGROUND: Understanding the risk factors and pregnancy outcomes in women affected by Type 1 and Type 2 diabetes is important for pre-pregnancy counselling. AIM: To explore differences in pregnancy outcomes between women with Type 1 and Type 2 diabetes, and healthy controls, and to examine the relationships between potential adverse risk factors and pregnancy outcomes in this cohort of women. METHODS: This is a 10-year retrospective study of women with Type 1 diabetes (n = 92), Type 2 diabetes (n = 106) and healthy women without diabetes (controls) (n = 119) from a tertiary obstetric centre. Clinical and biochemical characteristics of women with Type 1 and Type 2 diabetes were determined and related to major obstetric outcomes using univariate analysis. RESULTS: Women with pre-existing diabetes had higher adverse pregnancy outcomes (preeclampsia, emergency caesarean section, preterm birth <32 and 37 weeks, large for gestational age, neonatal jaundice, Apgar score < 7 at 5 min, neonatal intensive care admission and neonatal hypoglycaemia) compared to controls. A higher birth weight gestational centile (97.4% vs 72.4%, P = 0.001) and large for gestational age rate (63.4% vs 35.8%, P = 0.001) were observed in Type 1 diabetes compared to Type 2 diabetes. There were no differences in other outcomes between women with Type 1 and 2 diabetes. CONCLUSION: In this exploratory study, risk factors for maternal adverse outcomes differ between Type 1 and Type 2 diabetes. Maternal and foetal adverse outcomes were higher in pregnancies affected by diabetes compared to healthy women but occurred with similar frequency in women with Type 1 and Type 2 diabetes.

A semi-automated "blanket" method for renal segmentation from non-contrast T1-weighted MR images.

OBJECTIVE: To investigate the precision and accuracy of a new semi-automated method for kidney segmentation from single-breath-hold non-contrast MRI. MATERIALS AND METHODS: The user draws approximate kidney contours on every tenth slice, focusing on separating adjacent organs from the kidney. The program then performs a sequence of fully automatic steps: contour filling, interpolation, non-uniformity correction, sampling of representative parenchyma signal, and 3D binary morphology. Three independent observers applied the method to images of 40 kidneys ranging in volume from 94.6 to 254.5 cm(3). Manually constructed reference masks were used to assess accuracy. RESULTS: The volume errors for the three readers were: 4.4% ± 3.0%, 2.9% ± 2.3%, and 3.1% ± 2.7%. The relative discrepancy across readers was 2.5% ± 2.1%. The interactive processing time on average was 1.5 min per kidney. CONCLUSIONS: Pending further validation, the semi-automated method could be applied for monitoring of renal status using non-contrast MRI.

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.

Functional MRI in assessment of diabetic kidney disease in people with type 1 diabetes.

AIMS: To compare levels of renal hypoxia measured by Blood Oxygen Level Dependent (BOLD) magnetic resonance imaging (MRI) with measured transverse relaxation rate (R2*) and renal structural changes including apparent diffusion coefficient (ADC) and fractional anisotropy (FA) in patients with type 1 diabetes and healthy controls. METHODS: Cohort study comparing MRI metrics in type 1 diabetes (n = 32, GFR 105 (77, 120) ml/min.1.73m2) and controls (n = 10). Renal function and selected inflammatory renal biomarkers were also measured. RESULTS: For BOLD, we found reduced cortical [14.7 (13.7,15.8) (1/s) vs 15.7 (15.1,16.6) (1/s), p < 0.001] and medullary [24.8 (21.8,28.2) (1/s) vs. 29.3 (24.3,32.4) (1/s), p < 0.001] R2*, indicating more oxygenated parenchyma, in type 1 diabetes vs. controls, respectively. We observed reduced cortical FA, indicating decreased structural integrity in type 1 diabetes -0.04 (-0.07, -0.01), (p = 0.02). We found reduced cortical ADC, reflecting reduced water diffusion, in non-hyperfiltering [2.40 (2.29,2.53) (103mm2/s)] versus hyperfiltering [2.61 (2.53,2.74) (103mm2/s)] type 1 diabetes patients. MRI parameters correlated with renal function and inflammatory renal biomarkers. CONCLUSIONS: MRI derived indices of renal function and structure differed between (i) type 1 diabetes and healthy controls, and (ii) between non-hyperfiltering and hyperfiltering type 1 diabetes patients, providing insight into the role of hypoxia and renal structural, and functional changes in DKD.

The association between maternal renal function and pregnancy outcomes in type 1 and type 2 diabetes.

AIMS: To investigate the prognostic value of estimated glomerular filtration rate (eGFR) and albuminuria in determining pregnancy outcomes in women with type 1 and type 2 diabetes. METHODS: An observational study of pregnant women with type 1 (n = 92) and type 2 diabetes (n = 106) who delivered between 2004 and 2014 at a single tertiary obstetric centre. Clinical and biochemical characteristics were determined and related to major obstetric outcomes: preeclampsia, preterm birth <32 and <37 weeks, and neonatal intensive care admission. We used univariate analyses and multivariable logistic regression models with eGFR using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and albuminuria as covariates. RESULTS: In the pooled diabetes cohort, multivariable logistic regression with eGFR and albuminuria status demonstrated that the presence of albuminuria (albumin-to-creatinine ratio ≥ 3.5 mg/mmol) (OR, 2.7; 95% CI, 1.42-4.99; P = 0.002) was associated with preeclampsia, whilst an eGFR of < 120 mL/min/1.73 m2 was associated with preterm birth < 32 weeks (OR, 1.04; 95% CI, 1.00-1.09; P = 0.02). CONCLUSIONS: Despite its recognized limitations in pregnancy, lower eGFR values were associated with increased risk of adverse outcomes. Our exploratory data suggest eGFR, along with albuminuria, can aid in identifying women at high risk of developing adverse obstetric outcomes.

Biomarkers for Macrosomia Prediction in Pregnancies Affected by Diabetes.

Large birthweight, or macrosomia, is one of the commonest complications for pregnancies affected by diabetes. As macrosomia is associated with an increased risk of a number of adverse outcomes for both the mother and offspring, accurate antenatal prediction of fetal macrosomia could be beneficial in guiding appropriate models of care and interventions that may avoid or reduce these associated risks. However, current prediction strategies which include physical examination and ultrasound assessment, are imprecise. Biomarkers are proving useful in various specialties and may offer a new avenue for improved prediction of macrosomia. Prime biomarker candidates in pregnancies with diabetes include maternal glycaemic markers (glucose, 1,5-anhydroglucitol, glycosylated hemoglobin) and hormones proposed implicated in placental nutrient transfer (adiponectin and insulin-like growth factor-1). There is some support for an association of these biomarkers with birthweight and/or macrosomia, although current evidence in this emerging field is still limited. Thus, although biomarkers hold promise, further investigation is needed to elucidate the potential clinical utility of biomarkers for macrosomia prediction for pregnancies affected by diabetes.

Use of Readily Accessible Inflammatory Markers to Predict Diabetic Kidney Disease.

Diabetic kidney disease is a common complication of type 1 and type 2 diabetes and is the primary cause of end-stage renal disease in developed countries. Early detection of diabetic kidney disease will facilitate early intervention aimed at reducing the rate of progression to end-stage renal disease. Diabetic kidney disease has been traditionally classified based on the presence of albuminuria. More recently estimated glomerular filtration rate has also been incorporated into the staging of diabetic kidney disease. While albuminuric diabetic kidney disease is well described, the phenotype of non-albuminuric diabetic kidney disease is now widely accepted. An association between markers of inflammation and diabetic kidney disease has previously been demonstrated. Effector molecules of the innate immune system including C-reactive protein, interleukin-6, and tumor necrosis factor-α are increased in patients with diabetic kidney disease. Furthermore, renal infiltration of neutrophils, macrophages, and lymphocytes are observed in renal biopsies of patients with diabetic kidney disease. Similarly high serum neutrophil and low serum lymphocyte counts have been shown to be associated with diabetic kidney disease. The neutrophil-lymphocyte ratio is considered a robust measure of systemic inflammation and is associated with the presence of inflammatory conditions including the metabolic syndrome and insulin resistance. Cross-sectional studies have demonstrated a link between high levels of the above inflammatory biomarkers and diabetic kidney disease. Further longitudinal studies will be required to determine if these readily available inflammatory biomarkers can accurately predict the presence and prognosis of diabetic kidney disease, above and beyond albuminuria, and estimated glomerular filtration rate.

Clinical predictive factors in diabetic kidney disease progression.

Diabetic kidney disease (DKD) represents a major component of the health burden associated with type 1 and type 2 diabetes. Recent advances have produced an explosion of 'novel' assay-based risk markers for DKD, though clinical use remains restricted. Although many patients with progressive DKD follow a classical albuminuria-based pathway, non-albuminuric DKD progression is now well recognized. In general, the following clinical and biochemical characteristics have been associated with progressive DKD in both type 1 and type 2 diabetes: increased hemoglobin A1c, systolic blood pressure, albuminuria grade, early glomerular filtration rate decline, duration of diabetes, age (including pubertal onset) and serum uric acid; the presence of concomitant microvascular complications; and positive family history. The same is true in type 2 diabetes for male sex category, in patients following an albuminuric pathway to DKD, and also true for the presence of increased pulse wave velocity. The following baseline clinical characteristics have been proposed as risk factors for DKD progression, but with further research required to assess the nature of any relationship: dyslipidemia (including low-density lipoprotein, total and high-density lipoprotein cholesterol); elevated body mass index; smoking status; hyperfiltration; decreases in vitamin D, hemoglobin and uric acid excretion (all known consequences of advanced DKD); and patient test result visit-to-visit variability (hemoglobin A1c, blood pressure and high-density lipoprotein cholesterol). The development of multifactorial 'renal risk equations' for type 2 diabetes has the potential to simplify the task of DKD prognostication; however, there are currently none for type 1 diabetes-specific populations. Significant progress has been made in the prediction of DKD progression using readily available clinical data, though further work is required to elicit the role of several variables, and to consolidate data to facilitate clinical implementation.

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.