According to the most recent NHANEs data, 15.5 million Americans have CKD III, a figure that has increased by over 40% in less than a decade. CKD III is primarily a marker of global health outcomes, and affected patients are at increased risk for overall mortality, cardiovascular disease and hospitalization. Although many may be referred, few (less than 5%) will ever progress to the point of needing dialysis or transplantation. In fact, in the Tromso study, a 10-year prospective follow-up of patients with CKD III, only 2% reached ESRD compared with a third dying from other causes, mostly cardiovascular disease. A major challenge for Nephrologists, if we are not to be swept away by a massive tide of referrals, is to develop tools which permit the identification of individuals who will develop progressive kidney disease. These may be referred for specialist Nephrology follow-up, while people at low-risk for progression could be managed by primary care.
Renal stress testing is not a new idea. It has been primarily studied in the pediatric setting and, while a little cumbersome in its present form, has potential. The most frequently studied version involves measurement of GFR augmentation after oral protein loading. The relative increase in GFR – normally around 20% – is taken to reflect renal reserve. This reserve is often reduced or absent in hyperfiltration states such as early diabetic nephropathy but, interestingly, often not in uninephrectomized patients (a group who tend to do well). Theoretically, patients without renal reserve are at the limit of their renal autoregulatory capacity, and are at greatest risk for progressive CKD (and AKI). Unfortunately, there are no quality follow-up studies of these patients. A typical protocol can be found in the methods of this article.
A second method tests tubular function as opposed to reserve GFR. Patients are given a large creatinine bolus (88.4 mmol/kg), targetting a serum creatinine of 4-6 mg/dL, and urinary creatinine excretion is measured. An impaired tubular secretory response to a creatinine load appears to be a more sensitive index of reduced functioning renal mass than serum creatinine or GFR. Again, a prospective study is lacking, but the results are stimulating. Seems like an interesting side-project for a renal fellow with some spare time on his or her hands – do such creatures exist?