medwireNews: The results of two individual patient data meta-analyses support albuminuria as a surrogate marker of treatment response in patients with chronic kidney disease, particularly those with high baseline albuminuria.
“In our view, these results are particularly useful for diabetic kidney disease with high albuminuria at baseline,” write Lesley Inker (Tufts Medical Center, Boston, Massachusetts, USA) and co-authors of one of the analyses, in The Lancet Diabetes & Endocrinology.
“Diabetic kidney disease is highly prevalent and is associated with a high risk of progression to kidney failure, and few therapies are available, making it a condition with substantial unmet clinical need.”
The results are part of a regulatory authority-backed effort to identify surrogate endpoints for chronic kidney disease, because its long natural history makes large clinical trials with hard endpoints unfeasible.
The study by Inker and team draws on data from 29,979 participants (71% with diabetes) of 41 randomized trials, followed up for a median 3.4 years.
These data revealed that a 30% reduction in patients’ albumin-to-creatinine ratio (ACR) over 6 months was associated with a 27% reduction in their risk for developing end-stage kidney disease, doubling of serum creatine concentration, or an estimated glomerular filtration rate of less than 15 mL/min per 1.73 m2. The association was strongest for patients with a baseline ACR above 30 mg/g.
From this, the team calculated that to provide 97.5% confidence of a clinical benefit in a randomized trial, a treatment would need to produce an ACR reduction of between 21% and 31%, depending on the size of the trial and whether the population was restricted to patients with baseline ACR above 30 mg/g.
The companion study from Josef Coresh (Chronic Kidney Disease Prognosis Consortium Data Coordinating Center, Baltimore, Maryland, USA) and colleagues includes data from 693,816 individuals (80% with diabetes) in 28 observational cohorts.
It produced comparable results, with a 30% reduction in ACR over 2 years associated with around a 20% relative reduction in the risk for later end-stage renal disease, and a 1% reduction in the 10-year absolute risk. Again, the association was stronger if baseline ACR was higher.
“The similarity between the results from that report and ours provides reassurance about the robustness of the findings and the utility of changes in albuminuria to predict clinical prognosis,” say Inker and colleagues.
They note that the need for a treatment to produce a 20–30% ACR reduction “might appear to be excessively severe and not obtainable in many settings.” But they argue that this requirement increases “the probability of a significant treatment effect on the clinical endpoint, essentially making albuminuria a stronger surrogate.”
Use of a surrogate marker shortens trial duration, therefore increasing efficiency and reducing expense, they stress, adding that these could be further improved by increasing the number of albuminuria measurements.
medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group