Can proteins in the blood predict an early death?

Certain measures of kidney health may predict who is likely to die prematurely, according to a study appearing in an upcoming issue of the Journal of the American Society Nephrology (JASN). The findings suggest that some markers of kidney function are better than others at predicting an individual's prognosis.

22 dec 2011--A person's level of kidney function often indicates how likely they are to develop kidney failure and other conditions. Kidney function is most accurately represented by the kidneys' filtration rate, but this is difficult to measure. Therefore, blood levels of a protein called creatinine are commonly used to assess kidney function, but levels of two other blood components—cystatin C and beta trace protein—are newly proposed markers that may be better predictors of individuals' future health. It's thought that these markers may go beyond indicating kidney health to include other aspects of an individual's well being.

To see how well these markers predict people's future health, Navdeep Tangri, MD, Mark Sarnak, MD MS (Tufts Medical Center), and their colleagues analyzed data from the Modification of Diet in Renal Disease Study, which provided levels of these markers for 816 kidney disease patients who were then followed for an average of 16.6 years.

The researchers found that, independent of the kidneys' filtration rate, participants with higher creatinine had a higher risk of developing kidney failure, but a lower risk of dying. Those with higher cystatin C and beta trace protein had a higher risk of both kidney failure and death.

These results suggest that creatinine, beta trace protein, and cystatin C may be predictive of aspects of health that go beyond the kidneys. Beta trace protein and cystatin C appear to provide more consistent prognostic information than creatinine.

Future studies should investigate whether a panel of markers of kidney function would provide a better prediction of an individual's prognosis than any one marker alone.

More information: The article, entitled "Filtration Markers Have Prognostic Value Independent of Glomerular Filtration Rate" will appear online on December 15, 2011, doi: 10.1681/ASN.2011070663

Provided by American Society of Nephrology

Serum Uric Acid May Herald Kidney Failure in Type 1 Diabetes

By Michael Smith
BOSTON, March 21 -- For patients with type 1 diabetes, a serum uric acid concentration in the high-normal range may be an early signal of kidney failure, researchers here said.
Such increases can appear before there is any change in urinary albumin excretion rate, according to Elizabeth Rosolowsky, M.D., of the Joslin Diabetes Center, and colleagues.
The findings raise the possibility that manipulating serum uric acids levels might help slow or prevent kidney deterioration in these patients, Dr. Rosolowsky and colleagues said in the May issue of the Clinical Journal of the American Society of Nephrology.
The discovery still needs to be confirmed, she said, but "we have the hope of having a means to thwart the loss of kidney function while function is still in a relatively preserved stage."
Dr. Rosolowsky and colleagues enrolled 675 type 1 Joslin patients, excluding those with frank proteinuria, and divided them according to urinary albumin to creatinine ratio.
The study had 364 patients with normoalbuminuria and 311 patients with microalbuminuria, with an average glomerular filtration rate of 119 and 99 mL/min, respectively.
But mildly or moderately impaired renal function -- defined as less than 90 mL/min -- was seen in 10% of those with normoalbuminuria and 36% of those with microalbuminuria.
Overall, 22% of the study group had impaired renal function, the researchers noted. "Our research showed that loss of kidney function takes place even in the absence of albuminuria in patients with type 1 diabetes," Dr. Rosolowsky said.
The researchers found:
The median urinary albumin excretion rate was lower in those with normoalbuminuria (at 15.0 mcg/min) compared with those with microalbuminuria (at 70.8). The difference was part of the study design.
The average serum uric acid was higher in those with microalbuminuria, at 5.2 mg/dL versus 4.2. The difference was significant at P<0.0001.
The average glomerular filtration was lower in those with microalbuminuria, at 98.7 mg/min versus 118.8. The difference was significant at P<0.0001.
In a multivariate analysis, Dr. Rosolowsky and colleagues showed that the glomerular filtration rate (GFR) decreased steadily with increasing albumin excretion rate and with increasing serum uric acid.
But the two were independent -- even if there was no increase in albumin excretion, increased serum uric acid implied worsening kidney function, the researchers said.
Dividing subjects into uric acid tertiles (in mg/dL) revealed the following values for adjusted mean GFR (in mL/min):
First, ≤4.0; 117.4
Second 4.1 to 5.2; 108.1
Third, ≥5.3; 97.5
P values for difference between tertiles were <0.0001.
In fact, "the serum concentration of uric acid in these patients varied in a manner consistent with its having played a role in this early loss of kidney function," Dr. Rosolowsky said.
Other studies have suggested that increased serum uric acid levels may play a role in kidney damage, the researchers noted, raising the possibility that modulating uric acid in these patients may prevent kidney disease.
"The serum uric acid concentration is modifiable by drugs or by decreasing the intake of dietary protein, the main source of uric acid," Dr. Rosolowsky said.
She and colleagues are currently conducting follow-up studies to see whether serum uric acid concentration predicts the course of early decline in kidney function.
If those studies pan out, she said, that would justify clinical trials to test whether modifying serum uric acid concentration also modifies the course of renal function decline in type 1 diabetic patients.
The study was supported by the NIH, the Agency for Healthcare Research and Quality and the American Diabetes Association. The researchers reported no conflicts.
Primary source: Clinical Journal of the American Society of NephrologySource reference:Rosolowsky ET, et al "High-normal serum uric acid is associated with impaired glomerular filtration rate in nonproteinuric patients with type 1 diabetes" Clin J Am Soc Nephrol 2008; 3: DOI: 10.2215/CJN.04271007.