Cerebral Microvascular Disease Predicts Renal Failure in Type 2 Diabetes

Abnormalities in small renal vessels may increase the risk of developing impaired renal function, but methods to assess these vessels are extremely limited. We hypothesized that the presence of small vessel disease in the brain, which manifests as silent cerebral infarction (SCI), may predict the progression of kidney disease in patients with type 2 diabetes. We recruited 608 patients with type 2 diabetes without apparent cerebrovascular or cardiovascular disease or overt nephropathy and followed them for a mean of 7.5 years. At baseline, 177 of 608 patients had SCI, diagnosed by cerebral magnetic resonance imaging. The risk for the primary outcome of ESRD or death was significantly higher for patients with SCI than for patients without SCI [hazard ratio, 2.44; 95% confidence interval (CI) 1.36 to 4.38]. The risk for the secondary renal end point of any dialysis or doubling of the serum creatinine concentration was also significantly higher for patients with SCI (hazard ratio, 4.79; 95% CI 2.72 to 8.46). The estimated GFR declined more in patients with SCI than in those without SCI; however, the presence of SCI did not increase the risk for progression of albuminuria. In conclusion, independent of microalbuminuria, cerebral microvascular disease predicted renal morbidity among patients with type 2 diabetes.Diabetes is estimated to increase the risk of ESRD by approximately 12-fold,¹ and 20% to 45% of patients with ESRD in most developed countries have type 2 diabetes mellitus.² Furthermore, the presence of nephropathy is known to seriously affect the prognosis of diabetes by increasing the likelihood of cardiovascular death.³ An association has also been reported between elevated urinary albumin excretion rate and diabetic nephropathy,³ and patients with microalbuminuria are defined as having incipient nephropathy.⁴ Nephropathy in type 2 diabetes progresses from microalbuminuria to macroalbuminuria, and from macroalbuminuria to an elevated serum creatinine (Cr) concentration or the need for renal replacement therapy. However, recent clinical studies have shown that renal insufficiency in the absence of microalbuminuria is relatively common in patients with type 2 diabetes.⁵ In addition, GFR was reported to be negatively correlated with the resistive index (RI) of the interlobular renal arteries ⁶ in patients with type 2 diabetes. These results have led to the suggestion that glomerular lesions and arteriosclerosis in the kidney independently play important roles in the development of ESRD in type 2 diabetes.Although small vessel diseases in the kidney may increase the risk of developing impaired renal function, there is still no established method to assess small vessel disease in the kidney. A linear relationship was observed between the RI and renal vascular resistance.⁷ However, RI is also affected by renal interstitial pressure, indicating that RI is increased in patients with increased interstitial fibrosis,^7,8 which occurs in various conditions such as chronic pyelonephritis, glomerulosclerosis, and ureteral obstruction. The vascular beds of the kidney and brain have similar hemodynamic properties⁹; therefore, silent cerebral infarction (SCI), small vessel disease in the brain, may be indicative of the presence of small vessel disease in the kidney.It is therefore possible that the presence of small artery diseases in the brain could indicate an increased risk for worsening kidney function. Accordingly, the goal of the study presented here was to investigate the association between the presence of SCI and renal prognosis in patients with type 2 diabetes.