Reaching for Individualized Medicine in Diabetic Kidney Disease

In the US, an estimated 35.5 million people have chronic kidney disease (CKD), with 9 in 10 people unaware of the diagnosis. 1Albuminuria is both a marker of kidney disease and an independent risk factor for disease progression.Renin-angiotensin blockade with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers is the first-line standard of care for diabetic kidney disease therapy.Sodium-glucose cotransporter 2 (SGLT2) inhibitors can slow the progression of kidney disease and cardiovascular disease. 2 The 2025 American Diabetes Association Standards of Care in Diabetes recommends that SGLT2 inhibitors be used in all patients with CKD (estimated glomerular filtration rate 20 mL/min/1.73m 2 ) and type 2 diabetes regardless of the presence of albuminuria.Beernink and colleagues 3 tested whether the effect of the SGLT2 inhibitor dapagliflozin on albuminuria would be similar on re-exposure as well as the feasibility of remote clinical assessment in a research trial.Twenty adults with type 2 diabetes with moderate albuminuria were included in this randomized, double-blind, placebo-controlled crossover trial using an n-of-1 approach.Participants collected first-morning urine samples using a home device and sent them to a central laboratory for measurement of urinary albumin-to-creatinine ratio (UACR).Wearable and digital devices were used to collect vital sign measurements, such as blood pressure and body weight.Capillary blood samples were also collected at home to assess clinical values, such as creatinine and plasma glucose levels, and were compared with a venous blood sample.Overall, dapagliflozin reduced albuminuria by a mean of -15.1% (95% CI -28.2% to -3.3%; P = .01)compared with placebo, with marked variability in individuals' responses.Large ranges of UACR were found in both the dapagliflozin and the placebo periods; however, a significant correlation in individual UACR changes only occurred between dapagliflozin treatment periods (r = 0.50; P = .03).Reliable assessment of the UACR required assessing the mean of multiple samples, highlighting the importance of repeat measurement when assessing disease progression or treatment efficacy.A major strength of the study by Beernink and colleagues 3 is the n-of-1 crossover study design.Evidence-based medicine suggests that n-of-1 randomized clinical trials provide the strongest evidence of a treatment effect for an individual. 4Similar trial designs have been used in other settings, including hypertension trials, in the past. 5In contrast to population-level studies in which changes in albuminuria may be impacted by random day-to-day variation, the re-exposure design used in this study demonstrated a true pharmacological response at the individual level.Future research efforts are needed to determine the cause of the individual response variability.There are now several first-line therapies that delay progression of kidney disease in the context of type 2 diabetes, including SGLT2 inhibitors, nonsteroidal mineralocorticoid receptor antagonists, and glucagon-like peptide-1 receptor agonists.Each clinician would like to know which initial therapy would have the highest efficacy for the individual patient.While in the future, biomarkers may be identified to better guide decision-making, at this time, clinicians are using trial and error or a cumulative medication approach.Advances in technology have paved the way for more accessible home screening devices and clinical tools.Beernink and colleagues 3 used a urine home collection device, a validated tool for collecting and preserving small amounts of urine that was originally created in the Netherlands to collect urine samples from children.It consists of a small absorption pad, holder, and sample tube that can be refrigerated for days before analysis at a central laboratory.The authors found that the device was easy to implement, with 811 of 816 anticipated urine samples (99.4%) returned to the