So-called silent strokes, visible on cerebral MRI scans, predict kidney failure in patients with Type 2 diabetes, researchers said.
After an average follow-up of 7.5 years, diabetic patients with evidence of small cerebral infarctions at baseline later suffered death or kidney failure at more than twice the rate seen in patients who had not had silent strokes, reported Takashi Uzu, MD, of Shiga University of Medical Sciences in Shiga, Japan, and colleagues.
Silent strokes are a consequence of cerebral microvascular disease and thus may logically accompany the development of similar abnormalities in renal blood vessels, ultimately leading to kidney failure, the researchers explained. “It is important to identify individuals who are at risk of progression of diabetic renal disease,” Uzu and colleagues wrote.
The current standard prognostic test is the albumin-creatinine ratio, but it is not entirely adequate for the purpose, they suggested: “Recent clinical studies have shown that renal insufficiency can occur in the absence of microalbuminuria in patients with Type 2 diabetes.”
But they acknowledged that brain MRI scans would be too expensive and inconvenient for routine prognostic testing.
“New strategies are needed to determine the presence of renal and/or extrarenal microvascular diseases,” Uzu and colleagues wrote. Their study involved 608 patients with Type 2 diabetes who had no clinical signs of cerebrovascular or cardiovascular disease or overt nephropathy. Their mean age at baseline was about 60 and the average glycated hemoglobin level was about 8.6%.
Participants underwent cerebral MRI scans at baseline, with 177 showing evidence of silent cerebral infarctions, defined as focal lesions of at least 3 mm in diameter with low signal intensity on T1-weighted images and high intensity with T2 weighting. Dilated perivascular spaces were distinguished from infarcts with proton density scans. Patients with positive findings who had a history of stroke or transient ischemic attack were excluded.
Those with silent infarctions at baseline differed significantly from other participants according to several parameters. Not surprisingly, patients with cerebral infarcts on average were somewhat older (63 versus 57), had had diabetes for a longer period of time (9.8 years versus 7.6), had higher blood pressure (146.8 mm Hg systolic versus 136.5 ), and were more likely to have a history of smoking (58% versus 46%). All differences were significant at P<0.01.
On the other hand, baseline fasting plasma glucose and glycated hemoglobin levels were both significantly lower in the patients who’d had silent infarctions: mean 163 mg/dL versus 176 for glucose and 8.3% versus 8.7% for HbA1c (P≤0.01 for both).
Patients were followed for up to 10 years, with a mean of 7.5. The primary outcome was end-stage renal disease or death, and Uzu and colleagues chose a secondary outcome combining dialysis with doubling of serum creatinine.
Kaplan-Meier curves for the patients with and without silent infarctions at baseline indicated that the primary outcome occurred at equal rates through the first four years of follow-up, but then the curves diverged abruptly. At year eight, approximately 6% of the noninfarcted group had experienced the primary outcome, compared with 21% of those who’d had silent strokes (P<0.0001), according to Uzu and colleagues.
Curves for the secondary outcome began diverging by year three. At year eight, about 6% of the noninfarct participants had gone to dialysis or had serum creatinine levels double, whereas these endpoints occurred in nearly 30% of the infarct group (P<0.0001). Overall, the hazard ratio associated with baseline silent cerebral infarctions for the primary outcome during follow-up was 2.44 (95% CI 1.36 to 4.38).
The hazard ratio for death alone was somewhat smaller (1.61, 95% CI 0.71 to 3.62), indicating that most of the risk measured by the primary outcome was actually in end-stage renal disease. For the secondary outcome, the hazard ratio was 4.79 (95% CI 2.72 to 8.46).
All the hazard ratios reflected adjustments for age, sex, duration of diabetes, body mass index, smoking status, HbA1c, blood pressure, serum lipids, and standard lab indices of kidney function at baseline.
Estimated glomerular filtration rate (eGFR) during follow-up also decreased faster in patients with silent strokes. After five years, mean eGFR had fallen by 8 ml/min/m2 in the patients without silent infarcts at baseline compared with 10.5 ml/min/m2 in those with cerebral microvascular disease.
- Explain to interested patients that the long-term complications of diabetes include so-called microvascular diseases, which are abnormalities in small blood vessels leading to dysfunction in the eyes, kidneys, and peripheral nerves as well as small strokes in the brain.
- Explain that maintaining good glycemic control through diet, exercise, and medication is believed to reduce progression of such complications.
Journal of the American Society of Nephrology, Uzu T, et al “Cerebral microvascular disease predicts renal failure in Type 2 diabetes” J Am Soc Nephrol 2010; DOI: 10.1681/ASN.2009050558