medwireNews: Researchers have developed a novel model for predicting the risk for kidney disease progression in patients with type 2 diabetes and identifying those who may benefit from treatment with sodium-glucose cotransporter (SGLT)2 inhibitors.
“[T]he objective of this study was to generate a clinical stratification tool that would be more widely implemented and thus based on readily accessible clinical markers used in routine management of patients with [type 2 diabetes],” they explain in Diabetes Care.
Marc Sabatine (Brigham and Women’s Hospital, Boston, USA) and team’s risk prediction tool consists of eight highly significant, independent risk factors for kidney disease progression, defined as a sustained 40% or greater decrease in estimated glomerular filtration rate (eGFR), end stage kidney disease (defined as dialysis for ≥90 days, kidney transplantation, or sustained eGFR <15 mL/min per 1.73 m2), or kidney death.
The eight candidate risk factors are baseline eGFR, urine albumin-to-creatinine ratio (UACR), hemoglobin and glycated hemoglobin (HbA1c) levels, duration of type 2 diabetes, systolic blood pressure, atherosclerotic cardiovascular disease, and heart failure.
These were selected by multivariable Cox regression from a possible 23 variables assessed in 41,204 patients with type 2 diabetes from four Thrombolysis in Myocardial Infarction (TIMI) trials – DECLARE-TIMI 58, SAVOR TIMI 53, FOURIER (TIMI 59), and CAMELLIA-TIMI 61.
The patients were followed up for a median of 2.4 years, during which time kidney disease progression occurred in 481 patients.
The final risk prediction tool – The TIMI Risk Score for Kidney Disease Progression in Type 2 Diabetes – showed good discrimination when used in 28,842 (70%) patients comprising the derivation cohort, with a Harrell c-index of 0.798. At baseline, the patients (34% women, 21% non-White) had a median age of 64 years, a median HbA1c of 7.5% (58 mmol/mol), a median diabetes duration of 9.2 years, and 36% were receiving insulin therapy.
In addition, the cohort had a median eGFR of 76 mL/min per 1.73 m2, 77.6% of patients had preserved kidney function (eGFR ≥60 mL/min per 1.73m2), and a median UACR of 13.3 mg/g (67.0% had normal or mildly increased UACR <30 mg/g).
Sabatine et al point out that the same level of discrimination (0.798) was also seen when the tool was used in the remaining 12,362 (30%) patients – the validation cohort – whose baseline characteristics were very similar to those of the derivation cohort.
Each of the individual components of the model showed similarly good discrimination and the tool was able to predict kidney disease progression whether the patients had baseline eGFR above or below 60 mL/min per 1.73 m2, and in those with and without baseline albuminuria, the researchers report.
Moreover, good calibration was demonstrated, with the 2-year cumulative incidence of kidney disease progression falling within the predefined 2-year predicted risk categories of low (<0.5%), intermediate (0.5 to <2.0%), and high (≥2.0%).
The team also assessed reductions in the risk for kidney disease progression with dapagliflozin according to predicted 4-year risk (low <1%, intermediate 1–4%, and high ≥4%) among included patients from the DECLARE-TIMI 58 trial.
Relative risk reductions for kidney disease progression with dapagliflozin were generally consistent across the higher risk categories (15.0%, 49.0%, and 47.0% respectively). However, the investigators note that the absolute risk reductions increased significantly in line with the risk categories (0.2%, 1.0%, and 3.5%, respectively), showing that patients “with a higher baseline risk of kidney disease progression experience a greater magnitude of benefit from [SGLT2] inhibition.”
Sabatine et al acknowledge that other kidney disease risk scores exist, such as the kidney failure risk equation, the chronic kidney disease (CKD) Prognosis Consortium risk equation for incident CKD, and the CKD Prognosis Consortium risk model for decline in kidney function. However, the current model differs in that it was developed using people with type 2 diabetes rather than a general population, predictions were broader and not limited to an eGFR below 60/mL/min per 1.73 m2 and focused on an earlier outcome rather than kidney failure.
“Despite performing well in predicting kidney end points in our own cohort, these risk scores were not superior to the TIMI Risk Score for Kidney Disease Progression in Type 2 Diabetes,” they stress.
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