The changes in renal function over time as surrogate endpoints for new drug trials are complicated by many factors, including the often-expected initial decrease in estimated glomerular filtration rate when a new drug is started. Two articles in the journal address this challenge, but multiple other challenges are explored in this commentary. To maximize the benefits of expensive new drugs that may slow decline in renal function, these drugs should be reserved for those patients who have a high probability of rapid loss of kidney function.