Separate research groups offer two new methods for predicting which patients with chronic kidney disease are likely to progress to end-stage renal disease and other complications, according to studies published in the April 20 issue of JAMA.
Ultimately, the methods could help more accurately identify individuals who are at low and high risk for CKD progression, and allow for more appropriate use of health care resources for this population.
In the first report, a "triple-marker" approach using serum creatinine, serum cystatin C, and albuminuria levels yielded more accurate risk prediction than is achieved with current staging systems that are based primarily on creatinine-estimated glomerular filtration rates, said Dr. Carmen A. Peralta of the San Francisco VA Medical Center and her associates.
They assessed the triple-marker technique using a large, population-based cohort of adults (aged 45 years and older) who were participating in a stroke study. A subgroup of 26,643 of these subjects had undergone evaluation of kidney function as part of that study.
Patients in Dr. Peralta’s analysis had a mean age of 65 years. In all, 40% were black, more than half were women, 21% had diabetes, and 59% had hypertension. During a median follow-up of approximately 5 years, 177 subjects developed end-stage renal disease (ESRD) and 1,940 died of all causes.
Adding either the cystatin C or the albuminuria measures to creatinine-based estimated GFR greatly improved the ability to predict the development of ESRD as well as mortality. Using all three measures together improved it even further.
The rate of ESRD was 103-fold higher in subjects who were identified as being at risk via the triple-marker method than in those who were identified via creatinine level alone. Similarly, mortality was nearly eight times higher among those identified as being at risk via the triple-marker method than in those identified via creatinine level alone, the investigators said (JAMA 2011;305:1545-52).
Moreover, one in six subjects who were found to have CKD by the triple-marker method were not identified at all by creatinine level alone, suggesting that people could have occult CKD that would not be diagnosed according to standard methods.
In addition, 25% of subjects who were labeled as having CKD by creatinine-based GFR estimate alone were found not to have CKD when cystatin C and albuminuria levels were added into the risk stratification. This suggests that one-fourth of people screened by standard methods alone may be treated as though they’re at increased risk of ESRD or death when they are not.
Thus, using the triple-marker method "could both reduce unwarranted referrals and unnecessary work-ups for low-risk individuals and would prioritize specialty care and interventions to individuals at highest risk," Dr. Peralta and her colleagues said.
"Several groups are currently advocating new international guidelines that more accurately reflect prognosis of CKD and have proposed adding [albumin:creatinine ratio] to staging of CKD. Our results suggest that a triple-marker approach using both [albuminuria] and cystatin C to confirm CKD more accurately discriminates prognosis for death and progression to ESRD than creatinine and [albuminuria] alone," they added.
In the second report, investigators developed seven possible models for predicting CKD progression, using various combinations of more than 20 candidate variables that are known to affect renal function. To do so, they first assessed these variables in a Canadian cohort of 3,449 adults who were treated at nephrology clinics for stage 3-5 CKD.
These study subjects, who were followed from 2001 through 2008, helped determine which variables were best associated with CKD progression, said Dr. Navdeep Tangri of Tufts Medical Center, Boston, and his associates.
One of the seven models was particularly accurate at predicting CKD progression. It factored in patient age and sex, as well as the estimated GFR, albuminuria, serum calcium, serum phosphate, serum bicarbonate, and serum albumin levels. These are basic laboratory measurements "that are obtained routinely in patients with CKD," Dr. Tangri and his colleagues said (JAMA 2011;305:1553-9).
All seven models were tested in a validation cohort of 4,942 patients in a British Columbia registry who had stage 3-5 CKD. The same model was found to be the most accurate in predicting disease progression in that cohort.
"Using our models, lower-risk patients could be managed by the primary care physician without additional testing or treatment of CKD complications," whereas higher-risk patients could receive "more intensive testing, intervention, and early nephrology care," they said.
The models also could be used to triage patients with stage 4 CKD "regarding dialysis education, creation of vascular access, and preemptive transplantation"; to select stage 3 patients for public health interventions; and to select high-risk patients for enrollment in clinical trials, the researchers added.