PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “ARTERIOLOSCLEROSIS”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources

Quantitative ultrastructural study of afferent and efferent arterioles in IgA glomerulonephritis and benign nephrosclerosis.

Arteriolosclerosis frequently occurs in IgA nephritis (IgAN), and it is the hallmark of benign nephrosclerosis (BNS). The quantitative ultrastructure of juxtaglomerular arterioles is not known in these disorders. We examined afferent and efferent arterioles in renal biopsies from 25 adult patients with IgAN (hypertension at biopsy: 14 patients) and 9 patients with BNS. Six age-matched living renal transplant donors acted as controls. A systematic independent sample of profiles was obtained in thin sections taken at predetermined levels. The thickness of the media (myomedial cells plus the matrix) and the thickness of the medial matrix were estimated stereologically. From these estimates, the matrix/myomedia ratio was calculated. In IgAN with normotension or hypertension, the afferent media and its compartments did not exhibit significant thickening compared with the controls, whereas in BNS the afferent media and its layers were markedly and significantly thickened. The efferent media in IgAN and BNS displayed mild and significant thickening, with significant thickening of the matrix in BNS and IgAN with normotension. The matrix/myomedia ratio was not altered significantly in any group. The results indicate that the afferent arterioles are not the main sites of IgAN-related arteriolosclerosis, that arteriolosclerosis in IgAN and arteriolosclerosis in BNS are different lesions, and that increased efferent arteriolar thickness, demonstrated here for the first time in IgAN and BNS, might be a manifestation of angiotensin II-mediated autoregulatory efferent vasoconstriction exerted to maintain the glomerular filtration pressure.

Adolescent↗

Pathogenesis of diabetic nephropathy in non-insulin-dependent diabetes mellitus.

To elucidate the characteristics of diabetic nodular lesions and the process of progression of diabetic glomerulosclerosis, kidney specimens obtained from 185 patients with non-insulin-dependent diabetes mellitus (NIDDM) were observed using light, electron, and immunofluorescence microscopes. The results suggest the following. First, there are two distinct subtypes of nodular lesions: One is formed by the progression and expansion of diffuse lesions; the other, showing a concentrically layered structure, is probably formed in the process of reconstruction of mesangiolysis. Second, there are three phases in the process of progression of diabetic glomerulosclerosis: In the first phase, arteriolosclerosis and diffuse lesions appear; in the second phase, mesangiolysis and nodular lesions develop in association with moderately advanced arteriolosclerosis; and in the third phase, exudative lesions and hyalinized glomeruli appear in association with advanced arteriolosclerosis together with advanced interstitial lesions. In the progression of the phases and in the development of mesangiolysis and layered nodular lesions, disturbed blood flow into glomeruli in consequence of diabetic arteriolosclerosis could be essential.

Arteriosclerosis↗

Renal histopathology in hypertensive diabetic patients.

A total of 250 renal biopsy specimens from diabetic patients and from the kidneys of 400 autopsy cases were examined histologically and compared to kidneys from 160 autopsied nondiabetics. The morphological findings were assessed in relation to hypertension. There was a high prevalence of arteriolosclerosis, glomerulosclerosis, and pyelonephritis; in addition, early diabetic glomerulopathy and glomerulonephritis, particularly of the membranous type, were noted in a remarkably high percentage of diabetic patients. Ninety-three percent of patients with hypertension had arteriolosclerosis, and a good correlation existed between the extent of this lesion and the level of blood pressure. Even in 66% of normotensive patients, however, arteriolosclerosis was found. This fact and the involvement of the vas efferens argue against the notion of arteriolosclerosis being exclusively a sequela of hypertension. More than 70% of patients with glomerulosclerosis suffered from hypertension, compared to less than 50% of patients without either that condition or early diabetic lesions. The majority of diabetic patients with pyelonephritis and glomerulonephritis were hypertensive. We conclude that hypertension in diabetic patients with renal involvement may result from different renal lesions that can be differentiated only by histological examination.

Adult↗

[A 91-year-old man with a stroke, hypertension, and renal failure].

We report a 91-year-old man who had a stroke and died of renal failure. He had been treated for hypertension since 20 years before the onset of the present illness. In addition, he was operated on a gastric cancer 17 years previously. Otherwise he was doing well until May 29, 1991 (when he was 87-year-old) when he had sudden onset of dysarthria and right facial weakness. He was admitted to our hospital. On admission, general physical examination was unremarkable, and neurologic examination revealed a mentally sound man with slight dysarthria, right facial weakness, orolingual dyskinesia, and dysequilibrium in which he showed difficulty in tandem gait; however, no cerebellar ataxia was noted. A cranial CT scan revealed leukoaraiosis with multiple low density areas in the cerebral white matter. His BUN was 37 mg/dl and Cr 2.2 mg/dl. His neurologic symptoms cleared within the next few weeks and he was discharged with ticlopidine 100 mg q.d.. He had been doing well after the discharge except for gradual worsening of his renal function; his BUN was 65 mg/dl and Cr 3.27 mg/dl in April of 1994. On March 10, 1995, he fell down and hit his back; he became unable to walk because of pain, and he was admitted again on March 16, 1995. On admission, his blood pressure was 170/80 mmHg. There was an 1 + pitting pretibial edema; otherwise general physical examination was unremarkable. Neurologic examination revealed an alert and oriented man, however, Hasegawa's dementia scale was 23/30. Higher cerebral functions as well as cranial nerves were intact. He showed some unsteadiness of gait, however, no motor weakness or ataxia was noted. Deep tendon reflexes were diminished, but Chaddock sign was positive bilaterally. Vibration was diminished in the feet, however, pain and touch sensations were intact. Laboratory examination revealed a compression fracture of the twelfth thoracic vertebra. Blood count and chemistries were as follows; Hb 7.6 g/dl, Hct 23.3%, TP 6.0 g/dl, Alb 3.6 g/dl, BUN 87 mg/dl, Cr 4.53 mg/dl, T-Chol 174 mg/dl, HDL-Chol 49 mg/dl, Glu 156 mg/dl, Na 142 mEq/L, K 5.4 mEq/L, Cl 115 mEq/L. A urine specimen contained 1 + protein and 1 + glucose, and the sediments contained hyaline casts. A cranial CT scan was essentially same as that taken four years ago. His hospital course was complicated with pneumonia, congestive heart failure, and progressive renal failure. He was treated with intravenous fluid, chemotherapy, and other supportive measures, however, he expired from respiratory failure on April 30, 1995. He was discussed in a neurologic CPC, and the chief discussant arrived at the conclusion that the patient had Binswanger's disease in the brain, benign nephrosclerosis from arteriolosclerosis due to hypertension, congestive heart failure, and pneumonia. Opinions were divided regarding the question as to whether or not this patient had Binswanger's disease. Although his cranial CT scan revealed leukoaraiosis, his dementia and gait disturbance was only mild until his fall on March, 1995. Clinical features did not conform to those of Binswanger's disease. Postmortem examination of the right hemisphere revealed wide spread atherosclerosis and arteriolosclerosis. The kidney showed benign nephrosclerosis due to arteriolosclerosis. Sclerotic changes were also seen in the coronary arteries and the left middle cerebral artery with 70% stenosis. Myelin stain showed diffuse myelin pallor of the cerebral white matters with scattered small infarcts. Arterioles in the white matter showed arteriolosclerosis. Small infarcts were also seen in the putamen and in the thalamus. This patient appeared to have had circulatory disturbance of the white matter which is the basic abnormality causing Binswanger's disease. However, white matter changes in this patient were not quite severe enough to make a pathologic diagnosis of Binswanger's disease.

Aged↗

Morphometric study of arterioles and glomeruli in the aging kidney suggests focal loss of autoregulation.

BACKGROUND: In the past it was widely assumed that hyaline afferent arteriolosclerosis was responsible for ischemic glomerulosclerosis in the aging and hypertensive kidney. However, glomerular lesions of focal segmental glomerulosclerosis are now recognized in essential hypertension. Experimentally, such lesions are associated with loss of autoregulation of blood flow and glomerular hyperperfusion, as well as initial glomerular hypertrophy. These observations challenge the notion of ischemia as a unitary explanation for glomerulosclerosis. METHODS: A morphometric study was performed on normal portions of eight kidneys removed for tumors in aging, normotensive patients. Measurements were made of 126 pairs of afferent arterioles and their associated glomeruli. In addition, the amount of extracellular matrix (ECM) in the immediate periglomerular region was quantitated. RESULTS: Afferent arterioles were divided into three types according to the presence or absence of hyaline deposits and whether these did or did not obstruct the lumen. Arterioles with nonobstructive hyaline deposits had lumens over twice as large as those without deposits (482 +/- 240 micro2 vs. 204 +/- 160 micro2, P=0.0000). Their associated glomeruli had significantly greater total capillary area, particularly the hilar capillaries (1276 +/- 797 micro2 vs. 667 +/- 492 micro2, P=0.002), but with larger individual capillaries elsewhere as well (P=0.03). Arterioles with obstructive deposits differed from those with nonobstructive deposits by their smaller lumens (P=0.001) and walls (P=0.004), with a higher proportion of ECM in the periglomerular region (P=0.001), all consistent with a later stage of lesion. Glomeruli were divided into four basic types: normal, hypertrophic, glomeruli with features of focal segmental glomerulosclerosis (FSGS-type), and ischemic. Compared to normal glomeruli, hypertrophic glomeruli were larger, with greater total capillary area (P=0.0005), particularly the hilar capillaries (P=0.0000), and larger capillaries in the remainder of the tuft (P=0.003), but showed no evident lesions. FSGS-type glomeruli were also larger, with larger hilar capillaries (P=0.0005), but showed an increase in ECM due to sclerotic lesions (P=0.004). The remaining capillaries showed an inverse relation with the amount of mesangial matrix, showing a spectrum of sizes from enlarged to shrunken. As anticipated, ischemic glomeruli were significantly smaller than normal ones in every parameter measured. There was a strong association between hypertrophic/FSGS-type glomeruli and hyaline arteriolosclerosis, found in 90.3% of such glomeruli, versus 29.1% for the remaining glomeruli (P=0.0001). The great majority of hyaline deposits were of the nonobstructive variety (86.2%), but some were obstructive (13.8%), particularly in FSGS-type glomeruli, consistent with a more advanced lesion. CONCLUSIONS: We believe we have demonstrated in the aging kidney of humans the morphologic correlates of loss of autoregulation, occurring on a focal basis, with afferent arteriolar dilatation and increase in glomerular capillary size and subsequent focal segmental glomerulosclerosis. Hyaline arteriolosclerosis of the nonobstructive sort is strongly associated with these changes and may play a role in their pathogenesis.

Adult↗

Correlation between the resistive index by Doppler ultrasound and kidney function and histology.

BACKGROUND: Although duplex Doppler ultrasonography has been used widely, it still is unknown whether resistive index could be related directly to vascular or tubulointerstitial changes in the kidney. METHODS: Thirty-three patients who underwent renal biopsy were included in the present study. Clinical data, including sex; age; time from abnormal urinalysis result to biopsy; serum creatinine level; creatinine clearance; urinary excretion of protein, N-acetyl-beta-glucosaminidase, and urinary beta2-microglobulin; and presence of hypertension, were recorded at biopsy. Histopathologic data, including glomerular sclerosis, interstitial fibrosis/tubular atrophy, interstitial infiltration, and arteriolosclerosis, were evaluated separately by means of a quantitative or semiquantitative method. We examined whether resistive index at biopsy was related to these clinical and histopathologic parameters and, moreover, to renal outcome in patients followed up for more than 2 years. RESULTS: Age, creatinine clearance, urinary beta2-microglobulin excretion, and all histopathologic parameters showed statistically significant correlations with resistive index. However, stepwise multiple regression analysis showed that only arteriolosclerosis was chosen as an independent risk factor for increased resistive index. During the follow-up period of 57.5 +/- 15.6 months in 29 patients, 8 patients (27.6%) had progression of renal impairment, defined as an increase in serum creatinine level greater than 50%. They had a significantly increased resistive index at biopsy compared with patients without progression. CONCLUSION: We show a direct relationship between resistive index and arteriolosclerosis in damaged kidneys. Resistive index at renal biopsy may be useful as one of the prognostic markers for renal outcome.

Acetylglucosaminidase↗

Relationship between carotid artery stiffness and retinal arteriolar narrowing in healthy middle-aged persons.

BACKGROUND AND PURPOSE: Both carotid atherosclerosis and cerebral arteriolosclerosis are associated with stroke. However, the relationship between carotid atherosclerosis and cerebral arteriolosclerosis is unknown. We examined the association between carotid artery stiffness, a marker of early atherosclerosis, and retinal arteriolar narrowing, a marker of arteriolosclerosis, in healthy middle-aged people. METHODS: This population-based, cross-sectional study involved 8031 men and women 45 to 64 years of age. Carotid arterial stiffness was estimated from high-resolution ultrasonic echo tracking of the left common carotid artery and was defined as adjusted arterial diameter change (AADC, micro, adjusted for diastolic blood pressure, pulse pressure and pulse pressure squared, and diastolic arterial diameter and height, with smaller AADC reflecting greater arterial stiffness). Generalized retinal arteriolar narrowing was estimated from measurements of diameters of retinal vessels from digitized retinal photographs and summarized as the arteriole-to-venule ratio (AVR, with smaller AVR indicating greater retinal arteriolar narrowing). RESULTS: After controlling for age, sex, ethnicity, hypertension, diabetes, and cigarette smoking, decreasing AADC was associated with decreasing AVR. The mean AADCs, comparing the lowest and highest quartiles of AVR, were 394 (SE, 4) and 409 (SE, 4) micro, respectively (P<0.01). The pattern of the graded association between carotid arterial stiffness and generalized retinal arteriolar narrowing was similar among persons with and without hypertension. CONCLUSIONS: Greater stiffness of the carotid arteries is related to generalized narrowing of the retinal arterioles independent of blood pressure and other vascular factors. This supports a relationship between macrovascular and microvascular disease processes important in stroke pathogenesis.

Arterioles↗

APOE, vascular pathology, and the AD brain.

OBJECTIVE: To use neuropathologic data to examine the association between APOE genotype and cerebrovascular lesions commonly found in Alzheimer disease (AD), as well as neuritic senile plaque (SP) and neurofibrillary tangle (NFT) burden. METHODS: The sample comprised brains from 96 men and 3 women who fulfilled NIA-Reagan criteria for intermediate to high likelihood of AD. Region-specific and global measures of gross cerebrovascular disease, arteriolosclerosis, white matter lesions, microinfarcts, amyloid angiopathy, neuritic SP, and NFT burden were compared among those who had at least one APOE-epsilon4 vs those who did not. Pairwise rank-order correlations between measures were calculated. The association between APOE epsilon4 status and measures of vascular and AD pathology, adjusting for age at death, sex, brain weight, and Braak stage, were evaluated. RESULTS: APOE-epsilon4 was not associated with gross cerebrovascular pathology. Compared to those who were negative, brains from epsilon4 individuals had a greater degree of small vessel arteriolosclerosis (p = 0.04) and perivascular macrophage infiltration (p = 0.06), but not other markers of small vessel disease or white matter myelin loss. Microinfarcts in the deep nuclei were associated with epsilon4 (p = 0.009), whereas cortical and subcortical microinfarcts were not. There was a trend toward association between APOE genotype and amyloid angiopathy (p = 0.08), and epsilon4 was associated with neuritic SP burden, but not NFT. CONCLUSION: APOE-epsilon4 is associated with small vessel arteriolosclerosis, microinfarcts of the deep nuclei, neuritic senile plaque density, and amyloid angiopathy in patients with autopsy-proven Alzheimer disease (AD). These results suggest a role for epsilon4 in some of the microvascular changes commonly found in AD and are consistent with a potential amyloidogenic role for epsilon4.

Age Factors↗

Hypertensive encephalopathy in cats with reduced renal function.

The clinical, hemodynamic, and pathologic features of hypertensive encephalopathy in two cats with reduced renal mass are described. The cats developed a progressive syndrome of lethargy, ataxia, blindness, stupor, and seizures following an abrupt increase in blood pressure associated with a surgical reduction in renal mass. The cats had severe gross brain edema, evidenced by cerebellar changes of caudal coning and cranial displacement over the corpora quadrigemina and cerebral changes of widening and flattening of the gyri. Histologically, interstitial edema was most pronounced in the cerebral white matter. Hypertensive vascular lesions were present as hyaline arteriolosclerosis in one cat and hyperplastic arteriolosclerosis in the other. Rare foci of parenchymal microhemorrhages and necrosis were also observed. Systemic hypertension (especially severe or rapidly developing) accompanied by neurologic signs and the pathologic findings of diffuse brain edema with cerebral arteriolosclerosis are consistent with an etiologic diagnosis of hypertensive encephalopathy.

Animals↗

Vascular pathology in three cases of progressive cognitive deterioration.

The clinical condition known as vascular dementia remains poorly defined. Few studies have attempted a correlative link between the clinical syndrome and the structural abnormalities of the brain. Classically the clinical progression of the vascular dementing process is thought to be a multi-step process punctated by repeated episodes of ischemia, that are clinically expressed as strokes. In most instances it has been assumed that the substrate of vascular dementias consists of atherothrombotic infarcts. The objective of this report is to illustrate 3 cases of progressive (rather than stepwise) cognitive deterioration without clinical evidence of stroke, evolving over a period of several years, in which there were prominent vascular lesions. A complete autopsy and detailed neuropathologic examination demonstrated cerebral vascular lesions involving small arterial vessels (< 200 microns in diameter). The lesions consisted of moderate-to-severe arteriolosclerosis in two cases, and mild-to-moderate arteriolosclerosis in a case of Alzheimer's disease with severe cerebral amyloid angiopathy. Parenchymal lesions consisted of small cortical and subcortical infarcts, most of them smaller than 0.1 cm in average diameter, and subcortical leukoencephalopathy severe in two cases and mild-to-moderate in the third case. Severe atherosclerosis not accompanied by large infarcts was also present in one case. Arterial changes affecting small, distal branches causing sometimes small parenchymal lesions in association with diffuse cerebral white matter disease, appear to be the anatomical substrate that accompanies progressive cognitive impairment in some patients who are frequently diagnosed with Alzheimer's disease because in their clinical records there is neither history of strokes nor stepwise progression of symptoms.

Aged↗

Cause of residual hypertension after adrenalectomy in patients with primary aldosteronism.

The cause of residual hypertension after adrenalectomy for primary aldosteronism (PA) is unknown. The purpose of this study is to investigate the characteristic pathological kidney features associated with PA. Between 1977 and 1999 at our hospital, 26 patients with PA caused by a unilateral adrenal cortical adenoma (Conn's syndrome) underwent unilateral adrenalectomy with concurrent open-wedge renal biopsy. Patients were categorized into two groups: (1) those with normotension with diastolic blood pressure less than 90 mm Hg who were not administered antihypertensive drugs, and (2) those with residual hypertension with diastolic blood pressure of 90 mm Hg or greater who were administered medication for 6 months after surgery. Thirteen patients were cured of hypertension postoperatively, and 12 patients were administered antihypertensive medications. Glomerulosclerosis, renal arteriolosclerosis, and preoperative left ventricular mass (LVM) index were worse in the group with residual hypertension than in that with normotension (17.8% +/- 7.8% versus 9.6% +/- 3.8%; P = 0.01; 2.5 +/- 0.5 versus 1.6 +/- 0.4, Bader's grade; P = 0.005; and 165 +/- 31 versus 139 +/- 24 g/m(2); P = 0.02, respectively). Severity of tubulointerstitial injury, preoperative duration of hypertension, preoperative severity of proteinuria, plasma aldosterone level, and serum potassium concentration were not significantly different between the two groups. In conclusion, severity of glomerulosclerosis and arteriolosclerosis and LVM are related to blood pressure after adrenalectomy in patients with PA.

Adenoma↗

Pathology of small blood vessel disease in hypertension.

A pathogenic role for arterioles in hypertension has been postulated for many decades. Renal arteriolonecrosis, myointimal hyperplasia, and hyaline arteriolosclerosis are anatomic correlates of hypertension. The pathogenesis of these lesions is discussed as is contribution of these lesions to the perpetuation of hypertension. The importance of the extracellular matrix in the initiation and development of hyaline arteriolosclerosis is presented and correlated with the hemodynamic and pathophysiologic consequences of increased transmural pressure. The possibility of aiming therapy at arresting or ameliorating arteriolar disease is presented.

Arterioles↗

Congenital abnormalities of the conduction system in sudden death in young adults.

The sudden death of four apparently healthy young people, three men aged 25, 24 and 21 years, respectively, and one woman aged 20 years, was investigated. The heart was of normal size in two and was slightly enlarged in two. The conduction system in all hearts was serially sectioned. In all hearts the His bundle showed loop formation. In two, the branching bundle was left-sided with the right bundle branch intramyocardial. In the other two, the His bundle was markedly fragmented. Two had myocarditis, and three had arteriolosclerosis of the summit of the ventricular septum. These findings suggest the following: autopsy may be otherwise normal or show minimal findings in cases of sudden death in young people, with significant abnormalities seen only in the conduction system. The common denominator in the conduction system may be a congenital abnormality of the His bundle (in two hearts it was fragmented, in two it was left-sided and there was loop formation in all). Acquired changes may be present, such as arteriolosclerosis of the summit of the ventricular septum (three cases), myocarditis (two cases), and fatty infiltration in the atria (all four cases), a congenital abnormality of the His bundle with or without other findings (congenital or acquired) may cause reentrant phenomena or increased automaticity, ventricular arrhythmias and sudden death.

Adult↗

Mesangiolysis in diabetic glomeruli: its role in the formation of nodular lesions.

In order to elucidate a participation of the mesangiolysis in the formation of diabetic nodular lesions, 355 kidney specimens obtained from 327 patients with primary diabetes mellitus were studied. Mesangiolyses begun by focal and segmental disintegration of the pivotal structure of the mesangium ("torn off phase"), resulting in cystic or aneurysmal dilatation of the involved tuft, were found in 56 specimens (16%). The dilated tufts were filled with lysed mesangial matrix, which showed a reticular or fibrillar arrangement ("structureless phase"), being followed by a concentrical re-arrangement ("reconstructive phase") and by the ultimate formation of diabetic nodules. The mesangiolysis of various phases was frequently found concomitant with severe diabetic arteriolosclerosis and, in the reconstructive phase, the lysed mesangial matrix near the recanalized capillary along the inner aspect of glomerular basement membrane was observed to be rearranged in a layered structure. These results suggest the hypothesis that: 1) the mesangiolysis is the initial lesion occurring in glomeruli in the process of diabetic nodule formation, and disturbed blood flow into glomeruli, caused by diabetic arteriolosclerosis, may be implicated in the development of the mesangiolysis; and 2) concentric compression of the lysed mesangial matrix by recanalized capillaries forms layered structures and ultimate completed diabetic nodules.

Diabetes Mellitus, Type 1↗

Severity of tubulointerstitial inflammation and prognosis in immunoglobulin A nephropathy.

Many risk factors for progression in immunoglobulin A nephropathy (IgAN) have been found. We focused on renal leukocyte infiltrations and cytokines in IgAN. The subjects were 204 IgAN patients. Renal histopathological changes were semiquantitatively graded. Expression of tubulointerstitial Leukocyte common antigen (LCA), CD3, CD68, interleukin (IL)-1beta, and IL-10 was evaluated by immunohistochemistry. These parameters were correlated with progression of IgAN. The significance of these correlations was tested by a multivariate analysis. Glomerulosclerosis, tubular atrophy, interstitial inflammation, and hyaline arteriolosclerosis correlated with progression in all patients and also in patients with initially normal serum creatinine. Tubulointerstitial LCA, CD3, CD68, and IL-1beta expression correlated with progression. CD3 had the strongest correlation. In the multivariate analysis, tubulointerstitial CD3, hypertriglyceridemia, elevated serum creatinine concentration, and interstitial fibrosis were independently associated with progressive disease in all patients, and tubulointerstitial CD3 expression and hyaline arteriolosclerosis in patients with initially normal serum creatinine. We found parameters reflecting tubulointerstitial inflammation to predict deterioration of renal function in IgAN. This was also seen in patients whose serum creatinine was normal at the time of renal biopsy. Our findings show that, an immunohistochemical evaluation of tubulointerstitial inflammation seems to be a useful tool in determining the prognosis in IgAN.

Adolescent↗

Primary IgA nephropathy with low histologic grade and disease progression: is there a "point of no return"?

Histologic low-grade chronic renal lesions in 144 adults with primary immunoglobulin A (IgA) nephropathy were correlated with clinical parameters of disease progression over a median follow-up of 93 months. Using chronicity-based histologic grading, 50, 59, and 35 patients were glomerular grade (GG) 1a, GG1b, and GG2; 83 and 61 patients were tubulointerstitial grade (TIG) 1 and TIG2; and 25 patients had hyaline arteriolosclerosis. On follow-up, GG and TIG were predictive of disease progression by impairment of renal function, development of hypertension, and significant proteinuria (>1 g/d). Hyaline arteriolosclerosis correlated only with the development of hypertension. Histologic lesions GG1a or TIG1 predicted a significant low risk for disease progression compared with other renal lesions, regardless of the renal manifestation at the time of biopsy. Combined GG1a, TIG1, and isolated hematuria at the time of biopsy enhanced the sensitivity to determine early IgA nephropathy and to define a nonearly cohort with a higher risk of disease progression appropriate for recruitment into clinical therapeutic trials within realistic time frames. The significant risk of progression in other low-grade lesions, such as GG1b or TIG2, suggests that the point of no return in IgA nephropathy may occur much earlier than perceived and that delayed biopsy in these patients no longer may be justified.

Adolescent↗

Uric acid correlates with the severity of histopathological parameters in IgA nephropathy.

BACKGROUND: Immunoglobulin-A nephropathy (IgAN) is the most common chronic glomerulonephritis worldwide. Many clinical and histopathological risk factors for progression have been found previously. Recently, metabolic risk factors, such as hyperuricaemia and hypertriglyceridaemia, also have been associated with the progression of IgAN. METHODS: In the present study we correlated clinical and metabolic risk factors with histopathological parameters in 202 patients with IgAN. Morphological changes in glomerular, tubulointerstitial and vascular tissue were semiquantitatively graded into three classes. Mesangial proliferation activity and the amount of inflammatory cells were also evaluated by immunohistochemical staining of Ki-67 (MIB-1), CD45 (LCA) and CD68 stainings. Serum uric acid, triglycerides and cholesterol, urine protein excretion (UPE), blood pressure and body mass index (BMI) were measured. Smoking habits and occurrence of diabetes mellitus also were evaluated. The independent role of serum uric acid in the development of renal morphological changes was evaluated in multivariate analysis. RESULTS: Serum uric acid and UPE level correlated with several histological parameters. Uric acid level showed the strongest correlation with tubulointerstitial changes and UPE with glomerulosclerosis. The level of serum triglycerides correlated with interstitial fibrosis and hyaline arteriolosclerosis. Blood pressure correlated with hyaline arteriolosclerosis, glomerulosclerosis and tubulointerstitial changes. BMI and diabetes mellitus correlated with both tubulointerstitial and vascular changes. We found no significant correlations between histopathological parameters and smoking habits or serum cholesterol level. Serum uric acid had independent associations with the presence of tubular atrophy and interstitial fibrosis and inflammation. CONCLUSIONS: We conclude that many metabolic factors are univariately associated with renal morphological findings in IgAN. These same factors are central in the metabolic or insulin resistance syndrome and may have a pathogenetic role in the progression of IgAN. Serum uric acid may have an independent role in development of tubulointerstitial lesions as well as being associated with inflammation in renal tissue of patients with IgAN.

Adolescent↗

Antihypertensive and vasculo- and renoprotective effects of pioglitazone in genetically obese diabetic rats.

Although an improvement of insulin sensitivity has been shown to be a new therapeutic approach for treating diabetes mellitus, details of effects of this treatment on the cardiovascular system and possible renal complications remain unknown. In the present study, we investigated the effects of a thiazolidine derivative, pioglitazone, and examined the insulin-sensitizing action on blood pressure, nephropathy, and vascular changes in genetically obese diabetic Wistar fatty (WF) rats. Pioglitazone (3 mg.kg-1.day-1) was orally administered for 13 wk starting at the age of 5 wk, and the results were compared with those of vehicle-treated WF rats. At the age of 18 wk, vehicle-treated WF rats were associated with mild hypertension, nephropathy with proteinuria histological glomerular injury, and renal arteriolosclerosis in addition to hyperglycemia, hyperinsulinemia, and hyperlipidemia. Treatment with pioglitazone significantly improved glucose and lipid metabolism. In addition, it lowered blood pressure, decreased proteinuria, and prevented glomerular injury, renal arteriolosclerosis, and aortic medial wall thickening, whereas body weight, food intake, sodium balance, and urinary norepinephrine excretion were significantly increased. These results suggest that the insulin-sensitizing agent pioglitazone is effective in correcting not only glucose and lipid metabolism but also cardiovascular and renal complications in non-insulin-dependent diabetes mellitus.

Animals↗