Renal Arteriolar Lesions Research Articles

Association between Hemoglobin A1c and Renal Arteriolar Sclerosis in Subjects Presenting without any Apparent Kidney Dysfunction.

Diabetic kidney disease is a major vascular complication in patients with diabetes mellitus (DM). However, the association between the hemoglobin (Hb)A1c levels, notably the prediabetic levels, and renal pathological changes remains unclear. We investigated the association between the HbA1c levels and renal arteriolar lesions in subjects without any apparent kidney dysfunction using a living kidney donor cohort. Between January 2006 and May 2016, 393 living kidney donors underwent a "zero-time" biopsy at Kyushu University Hospital. The patients were divided into four groups (HbA1c levels ＜5.6%, 5.6%-5.7%, 5.8%-6.4%, and ≥ 6.5%, or diagnosed with DM [DM group]). Renal arteriolar hyalinization and wall thickening were assessed using semi-quantitative grading. We then investigated the association between the HbA1c levels and renal pathological changes. 158 (40.2%) patients had arteriolar hyalinization and 148 (37.6%) showed wall thickening. A significant correlation was observed between the HbA1c levels and wall thickening (p for trend ＜0.001). An elevated HbA1c level was significantly associated with wall thickening according to a multivariable logistic analysis in subjects with HbA1c levels of 5.6%-5.7% and 5.8%-6.4%, and the DM group, compared with those with HbA1c levels of ＜5.6% (odds ratio [OR], 1.91; 95% confidence interval [CI]: [1.03-3.54] for 5.6%-5.7%, OR, 1.96; 95% CI: [1.09-3.53] for 5.8%-6.4%, and OR, 2.86; 95% CI: [0.91-9.01] for the DM group), whereas arteriolar hyalinization did not increase within the nondiabetic HbA1c levels. Elevated high-normal HbA1c levels are considered to be independent risk factors for arteriolar wall thickening. Subclinical renal arteriolar sclerosis may develop in patients with prediabetic HbA1c levels.

Association between serum uric acid level and renal arteriolar hyalinization in individuals without chronic kidney disease

Background and aimsRecent studies have reported an association between serum uric acid (SUA) and renal arteriolar changes in patients with chronic kidney disease (CKD). However, the association in individuals without CKD remains unclear. In this study, we investigated the relationship between SUA and renal arteriolar lesions in individuals without CKD from our living kidney donor cohort. MethodsBetween January 2006 and May 2016, 393 living kidney donors underwent “time-zero” biopsy at Kyushu University Hospital. Patients were divided into sex-specific quartiles of SUA before donation: Q1, Q2, Q3, and Q4 (male: <5.2,5.2–5.8,5.9–6.4, and ≥6.5 mg/dL, female: <3.8,3.8–4.3,4.4–5.0, and ≥5.1 mg/dL). Renal arteriolar hyalinization and wall thickening were assessed using a semiquantitative grading system. Predictive performance was compared between models with and without SUA by calculating the net reclassification improvement (NRI). ResultsIn total, 158 (40.2%) patients had arteriolar hyalinization, and 148 (37.6%) had wall thickening. High SUA was significantly associated with arteriolar hyalinization in multivariable logistic analysis (odds ratio [OR] per 1-mg/dL increase in SUA, 1.24; 95% confidence interval [CI], 1.00–1.53; p = 0.048. OR for Q4 vs. Q2, 2.22; 95% CI, 1.17–4.21; p = 0.01). We found no association between SUA and wall thickening. When SUA was incorporated into a predictive model with conventional atherosclerotic factors, the NRI was 0.21 (p = 0.04). ConclusionsHigh SUA was an independent risk factor for arteriolar hyalinization in individuals without CKD. SUA provided additional predictive value beyond conventional atherosclerotic factors in predicting arteriolar hyalinization.

Nephron number in patients with primary hypertension.

A diminished number of nephrons has been proposed as one of the factors contributing to the development of primary hypertension. To test this hypothesis, we used a three-dimensional stereologic method to compare the number and volume of glomeruli in 10 middle-aged white patients (age range, 35 to 59 years) with a history of primary hypertension or left ventricular hypertrophy (or both) and renal arteriolar lesions with the number and volume in 10 normotensive subjects matched for sex, age, height, and weight. All 20 subjects had died in accidents. Patients with hypertension had significantly fewer glomeruli per kidney than matched normotensive controls (median, 702,379 vs. 1,429,200). Patients with hypertension also had a significantly greater glomerular volume than did the controls (median, 6.50x10(-3) mm3 vs. 2.79x10(-3) mm3; P<0.001) but very few obsolescent glomeruli. The data support the hypothesis that the number of nephrons is reduced in white patients with primary hypertension.

Renoprotective effect of nisoldipine in rats with severe hypertension

To compare the protective effect against cardiac and renal damage of a beta-blocker, an angiotensin converting enzyme inhibitor and a calcium antagonist in severely hypertensive rats. Six-week-old male spontaneously hypertensive rats (n = 24) were given 100 mg/kg deoxycorticosterone and a 4% NaCl diet. They were then treated orally with vehicle, atenolol (70 mg/kg), enalapril (5 mg/kg) or nisoldipine (7 mg/kg) for 8 weeks. Control (vehicle-treated) rats developed marked hypertension after 8 weeks. The antihypertensive effect of the three drugs was similar, as were the reductions achieved in cardiac weight and aortic thickness. However, histological examination revealed that nisoldipine was significantly more effective than the other drugs in reducing renal arteriolar lesions and renal glomerular sclerosis. Only nisoldipine significantly improved plasma creatinine and the glomerular filtration rate. These findings suggest that calcium antagonists have a renoprotective effect in severely hypertensive rats, which may derive from the inhibition of arteriolar damage and glomerular sclerosis.

Platelet embolic injury; the healing process

The impaction of emboli composed mainly of platelets at the bifurcation of arterioles in the renal cortex has been shown previously to produce severe endothelial injury and lipid accumulation in arteriolar smooth muscle, followed by a marked thickening of the intima. In this study magnesium aluminum wire was inserted into the rabbit aorta as a source of emboli composed of platelet aggregates. The healing of renal arteriolar lesions produced by the emboli was examined at intervals from 3 to 21 days. The distinctive electron microscopic features of the mononuclear cells, endothelial cells, and smooth muscle cells were described. The mononuclear cells were found to remove fibrin, red cell and platelet remnants, and to produce a mucopolysaccharide matrix. Endothelium then grew into the matrix displacing the monocytes. Lipid in smooth muscle was always associated with myofilament fragmentation and mitochondrial vacuolization suggesting that the lipid accumulation is a result of injury. Plaques of concentric intimal thickening were found to consist of condensed matrix and myointimal cells. At each stage the cell types remained distinctive and there was no suggestion that monocytes are transformed to endothelial cells. These lesions serve as a model for some of the features of the encrustation concept of atherosclerosis, in that intimal thickening follows on thrombosis, in this case thromboemoblism and is associated with lipid accumulation in smooth muscle cells. The injury begins with endothelial damage and disruption. The subsequent intimal thickening resembles the vascular lesion in chronic allograft rejection and malignant nephrosclerosis and also involves the intertubular arterioles and small arteries of the kidney.