Albuminuria and Rapid Kidney Function Decline as Selection Criteria for Kidney Clinical Trials in Type 1 Diabetes Mellitus

Key Points Severely increased urinary albumin excretion rate is an effective criterion to select persons with type 1 diabetes at high risk of GFR decline for enrollment in clinical trials. A history of rapid GFR decline is less effective but can be used to extend clinical trials to person with normoalbuminuric diabetic kidney disease. These findings have immediate implications for the design of clinical trials of novel renoprotective interventions in type 1 diabetes. Background The optimal criteria to select individuals with type 1 diabetes mellitus and albuminuric or normoalbuminuric diabetic kidney disease, who are at risk of rapid kidney function decline, for clinical trials are unclear. Methods This study analyzed data from the Preventing Early Renal Loss in Diabetes clinical trial, which investigated whether allopurinol slowed kidney function decline in persons with type 1 diabetes mellitus and early-to-moderate diabetic kidney disease. Rates of iohexol GFR (iGFR) and eGFR decline during the 3-year study were compared by linear mixed effect regression between participants enrolled based on a history of moderately or severely increased albuminuria ( n =394) and those enrolled based on a recent history of rapid kidney function decline (≥3 ml/min per 1.73 m 2 per year) in the absence of a history of albuminuria ( n =124). The association between baseline albuminuria and iGFR/eGFR decline during the trial was also evaluated. Results Rates of eGFR decline during the trial were higher in participants with a history of albuminuria than in those with a history of rapid kidney function decline (−3.56 [95% confidence intervals (CIs), −3.17 to −3.95] versus −2.35 [95% CI, −1.86 to −2.84] ml/min per 1.73 m 2 per year, P = 0.001). The results were similar for iGFR decline, although the difference was not significant ( P = 0.07). Within the history of albuminuria group, the rate of eGFR decline was −5.30 (95% CI, −4.52 to −6.08) ml/min per 1.73 m 2 per year in participants with severely increased albuminuria as compared with −2.97 (95% CI, 2.44 to −3.50) and −2.32 (95% CI, −1.61 to −3.03) ml/min per 1.73 m 2 per year in those with moderately increased or normal/mildly increased albuminuria at baseline ( P < 0.001). Conclusions Severely increased albuminuria at screening is a powerful criterion for selecting persons with type 1 diabetes mellitus at high risk of kidney function decline. A history of rapid eGFR decline without a history of albuminuria is less effective for this purpose, but it can still identify individuals with type 1 diabetes mellitus who will lose kidney function more rapidly than expected from physiological aging. Clinical Trial registry name and registration number: NCT02017171.