Investigation of end-stage kidney disease risk prediction in an ethnically diverse cohort of people with type 2 diabetes: use of kidney failure risk equation.

INTRODUCTION: The four variable kidney failure (KF) risk equation (KFRE) is recommended to estimate KF risk (ie, need for dialysis or kidney transplantation). Earlier referral to clinical kidney services for people with high-risk of kidney failure can ensure appropriate care, education and support are in place pre-emptively. There are limited data on investigating the performance of KFRE in estimating risk of end-stage kidney disease (ESKD) in people with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). The primary ESKD endpoint event was defined as estimated glomerular filtration rate (eGFR) <10 mL/min/1.73 m2 and secondary endpoint eGFR <15 mL/min/1.73 m2. RESEARCH DESIGN AND METHODS: We studied 7296 people (30% women, 41% African-Caribbean, 45% Caucasian) with T2DM and CKD (eGFR median (range) 48 (15-59) mL/min/1.73 m2) were included at two hospitals in London (median follow-up 10.2 years). Time to ESKD event was the endpoint and Concordance index (C-index) was used to assess KFRE's discrimination of those experiencing ESKD from those who did not. Mean (integrated calibration index (ICI)) and 90th percentile (E90) of the difference between observed and predicted risks were used as calibration metrics. RESULTS: Of the cohort 746 (10.2%) reached ESKD primary event (135 (1.9%) and 339 (4.5%) over 2 and 5 years, respectively). Similarly, 1130 (15.5%) reached the secondary endpoint (270 (3.7%) and 547 (7.5%) over 2 and 5 years, respectively). The C-index for the primary endpoint was 0.842 (95% CI 0.836 to 0.848) and 0.816 (95% CI 0.812 to 0.820) for 2 and 5 years, respectively. KFRE 'under-predicted' ESKD risk overall and by ethnic group. Likewise, the C-index for secondary endpoint was 0.843 (0.839-0.847) and 0.801 (0.798-0.804) for 2 and 5 years, respectively. KFRE performance analysis performed more optimally with the primary endpoint with 50% enhancement of the calibration metrics than with the secondary endpoint. KFRE recalibration improved ICI by 50% and E90 by more than 78%. CONCLUSIONS: Although derived for predicting KF, KFRE also demonstrated good discrimination for ESKD outcome. Further studies are needed to identify variables/biomarkers that may improve KFRE's performance/calibration and to aid the development of other predictive models to enable early identification of people at risk of advanced stages of CKD prior to onset of KF.

Ten years trajectories of estimated glomerular filtration rate (eGFR) in a multiethnic cohort of people with type 1 diabetes and preserved renal function.

OBJECTIVES: We aim to evaluate estimated glomerular filtration rate (eGFR) patterns of progression in a multiethnic cohort of people with type I diabetes mellitus and with baseline eGFR ≥45 mL/min/1.73 m2. DESIGN: Observational cohort. SETTING: People with a clinical diagnosis of type 1 diabetes, attending two university hospital-based outpatient diabetes clinics, in South London between 2004 and 2018. PARTICIPANTS: We studied 1495 participants (52% females, 81% white, 12% African-Caribbean and 7% others). PRIMARY AND SECONDARY OUTCOME MEASURES: Clinical measures including weight and height, systolic blood pressure, diastolic blood pressure and laboratory results (such as serum creatinine, urine albumin to creatinine ratio (ACR), HbA1c were collected from electronic health records (EHRs) and eGFR was estimated by the Chronic Kidney Disease-Epidemiology Collaboration. Ethnicity was self-reported. RESULTS: Five predominantly linear patterns/groups of eGFR trajectories were identified. Group I (8.5%) had a fast eGFR decline (>3 mL/min/1.73 m2 year). Group II (23%) stable eGFR, group III (29.8%), groups IV (26.3%) and V (12.4%) have preserved eGFR with no significant fall. Group I had the highest proportion (27.6%) of African-Caribbeans. Significant differences between group I and the other groups were observed in age, gender, HbA1C, systolic and diastolic blood pressure, body mass index, cholesterol and urine ACR, p<0.05 for all. At 10 years of follow-up, 33% of group I had eGFR <30 and 16.5%<15 (mL/min/1.73 m2). CONCLUSIONS: Distinct trajectories of eGFR were observed in people with type 1 diabetes. The group with the highest risk of eGFR decline had a greater proportion of African-Caribbeans compared with others and has higher prevalence of traditional modifiable risk factors for kidney disease.

People With Type 1 Diabetes of African Caribbean Ethnicity Are at Increased Risk of Developing Sight-Threatening Diabetic Retinopathy.

OBJECTIVE: There is limited information on the effect of ethnicity on the development of referable sight-threatening diabetic retinopathy (STDR) in people with type 1 diabetes. This study describes the risk factors for STDR in a diverse cohort of people with type 1 diabetes attending a regional diabetes eye screening service. RESEARCH DESIGN AND METHODS: Clinical and digital retinal imaging data from 1,876 people with type 1 diabetes (50% women, 72.1% Caucasian, 17.3% African Caribbean, 2.9% Asian, and 7.6% other) with no retinopathy at baseline, attending surveillance eye screening were reviewed. Referable STDR was defined as the presence of any moderate to severe nonproliferative or preproliferative diabetic retinopathy or proliferative diabetic retinopathy or maculopathy in either eye as per U.K. National Diabetic Eye Screening criteria. Median follow-up was 6 years. RESULTS: The median (interquartile range) age of the cohort was 29 (21, 41) years. Of the cohort of 1,876 people, 359 (19%) developed STDR. People who developed STDR had higher baseline HbA1c, raised systolic blood pressure (SBP), longer diabetes duration, and were more often of African Caribbean origin (24% vs. 15.6%; P < 0.05 for all). In multivariable Cox regression analyses, African Caribbean ethnicity (hazard ratio [HR] 1.39, 95% CI 1.09-1.78, P = 0.009), baseline SBP (HR 1.01, 95% CI 1.00-1.01, P = 0.033), and baseline HbA1c (HR 1.01, 95% CI 1.00-1.01, P = 0.0001) emerged as independent risk factors for STDR. CONCLUSIONS: We observed that people with type 1 diabetes of African Caribbean ethnicity are at significantly greater risk of STDR. Further research is required to understand the mechanisms that explain this novel observation.

African Caribbean Ethnicity Is an Independent Predictor of Significant Decline in Kidney Function in People With Type 1 Diabetes.

OBJECTIVE: The aim of the study was to identify the demographic and clinical features in an urban cohort of people with type 1 diabetes who developed a ≥50% decline in estimated glomerular filtration rate (eGFR). RESEARCH DESIGN AND METHODS: We evaluated 5,261 people with type 1 diabetes (51% female, 13.4% African Caribbean) with baseline eGFR >45 mL/min/1.73 m2 between 2004 and 2018. The primary end point was an eGFR decline of ≥50% from baseline with a final eGFR <30 mL/min/1.73 m2. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. RESULTS: Of the cohort, 263 (5%) reached the primary end point. These individuals were more likely to be of African Caribbean ethnicity, be older, have a longer duration of diabetes, have higher systolic blood pressure and HbA1c, have more prevalent retinopathy, and have higher albuminuria (all P < 0.05). In multivariable Cox regression models, African Caribbean ethnicity emerged as a significant risk factor for the primary end point (hazard ratio 1.57, 95% CI 1.19, 2.08) compared with other ethnicities and independent of established risk factors (P < 0.01). The incidence rate for the primary end point in African Caribbean people was double that in non-African Caribbean people (16 vs. 7.7 per 1000 patient-years, P < 0.001). A similar significant independent impact of African Caribbean ethnicity for secondary end points (≥40% and ≥30% fall in eGFR) was observed. CONCLUSIONS: We report a novel observation that African Caribbean ethnicity increased the risk of kidney function loss in people with type 1 diabetes, an effect that was independent of traditional risk factors. Further studies are needed to examine the associated pathophysiology that may explain this observation.

Symptoms of Anxiety and Depression Are Independently Associated With Impaired Awareness of Hypoglycemia in Type 1 Diabetes.

OBJECTIVE: We tested the hypothesis that impaired awareness of hypoglycemia (IAH) is independently associated with symptoms of anxiety and depression in type 1 diabetes. RESEARCH DESIGN AND METHODS: In this cross-sectional observational study in 950 adults with type 1 diabetes, associations were examined using multiple regression models, adjusting for sociodemographic and clinical characteristics. RESULTS: Prevalence for probable anxiety, depression, and IAH were 9.4%, 9.8%, and 22.6%, respectively. When included in separate regression models, both depression and anxiety were independently associated with an increased odds of IAH and robust to adjustment (odds ratio 3.64 [95% CI 2.19-6.04] and 2.46 [1.46-4.14], respectively). Further analysis demonstrated a dose-response relationship between increased severity of probable mental disorder and increased odds of having IAH (P < 0.001). CONCLUSIONS: The robust independent relationship between probable anxiety and depression with IAH demonstrates the need for routine psychological assessment and management of people with type 1 diabetes and IAH.