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Query: UMLS:C0730345 (microalbuminuria)
 4,018 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The key change in diabetic glomerulopathy is accumulation of extracellular material. Basement membrane thickening and matrix expansion develop concomitantly. In insulin-dependent diabetic patients persistent microalbuminuria is associated with an early stage of glomerulopathy. Albuminuria in non-insulin-dependent patients does not always reflect glomerulopathy. Renal and glomerular hypertrophy in the early stages of insulin-dependent diabetes mellitus is unlikely to play a dominant role in the development of glomerulopathy. Loss of capillary surface, closely associated with loss of glomerular function, is only partly explained by mesangial expansion--glomerular occlusion plays an important role. Possible mechanisms of albuminuria are qualitative changes of the basement membrane, eg, loss of proteoglycans and excess glycosylation; epithelial cell changes; new vessel formation; remodeling of glomerular structures; and impeded function of juxtaglomerular arterioles. The interplay among abnormalities in individual compartments of the diabetic kidney should be explored.
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PMID:Renal pathology in diabetes mellitus. 792 8

Hyalinization of juxtaglomerular arterioles is prominent in advanced diabetic nephropathy and may have important functional consequences. We studied the early stages of diabetic renal disease using kidney biopsy material from insulin-dependent diabetic patients, 8 with normal albumin excretion rate (< 15 micrograms/min) and 16 with microalbuminuria (15-200 micrograms/min). Ten living non-diabetic kidney donors served as a control group. Median duration of diabetes was 9.5 years (range 5-31) in patients with normoalbuminuria, and 12 years (7-22) in patients with microalbuminuria (p = 0.27). The tissue was sectioned systematically, 1-micron thick sections for light microscopy at 10-micron intervals, and thin sections for electron microscopy taken at 60-micron intervals. The arterioles were identified as afferent or efferent, and total profiles were photographed (magnification 7500x), providing a systematic independent sample for measurements using standard stereological methods. Patients with microalbuminuria had significantly increased arteriole parameters compared with the control group: for afferent and efferent arterioles the volume fraction of matrix/media, means and (co-efficient of variation, CV), was 0.47 (0.16) vs 0.33 (0.19) (p = 0.0009), and 0.62 (0.14) vs 0.45 (0.23) (p = 0.0004) and matrix-T, expressing amount of matrix per unit arteriolar surface, 2.38 (0.38) micron vs 1.44 (0.30) micron (p = 0.004), and 1.62 (0.28) micron vs. 1.03 (0.34) (p = 0.0009). Patients with normoalbuminuria showed no significant differences from the control group, and had lower values than microalbuminuric patients for all parameters except the afferent matrix-T. In the normoalbuminuric group a correlation was found between parameters for afferent arterioles and those for glomerular structure. In conclusion there is arteriolar accumulation of extracellular material in the early phase of diabetic nephropathy, concomitant with early glomerulopathy.
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PMID:A quantitative ultrastructural study of juxtaglomerular arterioles in IDDM patients with micro- and normoalbuminuria. 858 42

A 15-year clinical follow-up is reported for a familial glomerulopathy characterized on light microscopy by the glomerular deposition of giant fibrillary deposits (Virchows Arch A Pathol Anat Histol 388:313-326, 1980). On electron microscopy, the deposits consist of randomly oriented fibrils (12 to 16 nm in width and 120 to 170 nm in length). These deposits show positive immunoreactivity for fibronectin. One hundred fifty-seven of 197 family members within five generations were investigated. The disease is characterized by the occurrence of albuminuria in the third to fourth decades of life and slow progression to end-stage renal disease over a period of 15 to 20 years with the occurrence of generalized distal tubular acidosis (renal tubular acidosis type IV), hypertension, and the nephrotic syndrome. The frequent occurrence of otherwise unexplained microalbuminuria in young individuals of generations IV and V could be indicative of incipient glomerular disease. In one affected male individual and in his unaffected sister, renal cell carcinoma was diagnosed, raising the possibility that this familial glomerulopathy might be associated with an increased risk to develop renal cell cancer by direct or indirect (associated genetic predisposition) mechanisms. The disease relapsed in one renal transplant, raising the possibility of the presence of a transferable factor that could be part of the deposited fibrillar material or, alternatively, interfere with the glomerular handling of the deposited material.
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PMID:Familial glomerulopathy with giant fibrillar (fibronectin-positive) deposits: 15-year follow-up in a large kindred. 915 3

A rate of albumin excretion rate above 20 micrograms/min is a predicting factor of overt nephropathy in Type I diabetes. It has not yet been established whether this is the case also for Type II diabetes, where microalbuminuria is antecedent to general and cardiovascular mortality but not to end-stage renal disease. The reasons accounting for this discrepancy between Type I and Type II diabetes have not been fully elucidated. In principle two different hypotheses can be postulated to explain these findings. Firstly it can be suggested that overt proteinuria is not detected with similar incidence rates in microalbuminuric patients with the two types of diseases because Type II diabetics are older and more prone to develop cardiovascular events. Therefore these patients would die frequently before developing overt proteinuria not because microalbuminuria is not a predicting factor of End-stage Renal Disease, but rather because the follow-up period is not long enough to monitor the patients till the very moment they develop renal complications. Alternatively it is possible that microalbuminuria reflect a systemic, endothelial and vascular disorder rather than glomerular structural abnormalities in these patients. We have recently described a clustering of clinical features encompassing microalbuminuria, hypertension, peripheral extrahepatic insulin resistance, renal and cardiac hypertrophy and altered cation membrane transport systems, not in the overall Type II diabetic population, but only in a cohort of these patients. Evidences in keeping with a strict association between insulin resistance, hypertension and microalbuminuria in a subgroup of Type II diabetic patients have been recently reported by several authors both in cross-sectional and longitudinal studies. However the hypothesis that microalbuminuria reflects a systemic endothelial and vascular disorder in Type II diabetic patients, does not rule out the possibility that these systemic disturbances are also associated with histologic abnormalities of the kidney. With regard to the characteristics of renal histology in Type II diabetic patients with and without microalbuminuria, preliminary data from our laboratory demonstrate that there is no evidence of any renal disorder other than diabetes in microalbuminuric Type II diabetic patients. More particularly in this subset of patients we observed typical features of diabetic nephropathology (glomerular, tubulo-interstitial and arteriolar changes), while a substantial number of patients with increased albumin excretion rate exhibited either marked tubulo-interstitial lesions or arteriolar hyalinosis or both, in absence of significant glomerular changes. These findings suggest that it is not true that Type II diabetic patients with microalbuminuria show quite often normal renal histology, but rather than hyperglycemia may cause different patterns of renal injury as compared to Type I Diabetes. Furthermore always with regard to renal histology, it has been pointed out that in Type I diabetes glomerulopathy (especially mesangial) is the crucial change, whereas recent studies found considerable structural heterogeneity amongst proteinuric Type II diabetic patients with relatively high incidence of renal diseases other than diabetes. However parallel studies in a small group of micromacroalbuminuric Type II diabetic patients reported the typical glomerular changes, usually shown by Type I diabetic patients with similar patterns of renal damage. The issue of the relationships between microalbuminuria, hypertension and the development of overt nephropathy in Type II diabetes has been also examined in Pima Indians. The clinical scenario found in these patients does closely resemble that of Caucasian Type I diabetic patients.
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PMID:Relationships among microalbuminuria, insulin resistance and renal-cardiac complications in insulin dependent and non insulin dependent diabetes. 928 31

Onset of hypertension and nephropathy after 1,2, and 4 weeks of exposure to cadmium chloride (1 mg/kg, ip) was studied in rats by measuring changes in blood pressure and renal function (urinary output, electrolytes, serum creatinine, inulin clearance and Na+K+ ATPase). Significant decrease in body weight and rise in blood pressure were observed as early as one week of exposure while microalbuminuria was detected in 50% of the animals after 2 weeks. Na+K+ ATPase, a renal tubular enzyme, was depressed after 1 week with maximum lowering occurring after 4 weeks. There were no detectable changes in fluid intake, urine output, electrolytes, inulin clearance and serum creatinine even after 4 weeks. It is concluded that hypertension and tubular lesion set in earlier than glomerulopathy as indicated by microalbuminuria and the latter could be the consequence of rise in blood pressure.
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PMID:Cadmium induced nephrotoxicity in rats. 931 23

In the present paper, longitudinal studies in non-insulin-dependent diabetes mellitus (NIDDM) dealing with risk factors, especially microalbuminuria, blood pressure, and glycemic control, and the course of the kidney function are addressed. The definition of microalbuminuria, limits for abnormal albuminuria, and possible causes of microalbuminuria in NIDDM are discussed. Microalbuminuria is a major independent risk marker for early mortality, and new studies indicate that even "high normoalbuminuria" carries a risk. Furthermore, risk markers agreed on among various studies include apart from abnormal albuminuria, age and preexisting cardiovascular disease, whereas there is some inconsistency concerning glycemic control, lipoproteins, and even hypertension. People with microalbuminuria, NIDDM patients as well as nondiabetics, share an increased prevalence of atherosclerosis and its risk factors as well as an increased TER(alb). Albuminuria in NIDDM may thus have two different causes: general vascular disease and diabetic glomerulopathy. The clinical course of renal function is with large interindividual variation in both patients with or without overt proteinuria. Systolic blood pressure, glycemic control, and level of albuminuria appear to determine the deterioration in kidney function and progression of albuminuria, and to influence the overall prognosis, thus being obvious items for intervention. Long-term intervention studies demonstrating improved survival are, however, still awaited.
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PMID:Microalbuminuria, blood pressure, metabolic control, and renal involvement: longitudinal studies in white non-insulin-dependent diabetic patients. 932 21

We have recently described heterogeneity in renal structure in non-insulin-dependent diabetic patients (NIDDM) with microalbuminuria (MA; defined as albumin excretion rate from 20 to 200 micrograms/min). Thus, at variance with IDDM patients, "typical" diabetic glomerulopathy by light microscopy is observed only in a third of NIDDM with MA (Category II, CII). Further, despite persistent MA, 30% of NIDDM have normal or near normal renal structure (Category I, CI). Another one-third shows "atypical" patterns of renal injury with absent or mild diabetic glomerular changes, associated with disproportionately severe tubulointerstitial lesions and/or arteriolar hyalinosis and global glomerular sclerosis (Category III, CIII). The aims of this study were to evaluate whether similar patterns of renal lesions could be confirmed in a larger group of NIDDM with MA and to investigate tubular function in order to understand the mechanisms underlying MA in NIDDM patients. Renal biopsies were performed in 53 NIDDM with MA. Categories I, II and III were found in 41%, 26% and 33% of NIDDM with MA, respectively. All 8 patients with proliferative diabetic retinopathy were in CII. We also studied the urinary daily excretion rate of alpha 1-microglobulin (alpha 1 m), a low molecular weight protein, which is a useful indicator of tubular function. alpha 1 m was markedly increased only in CII patients (CI vs. CII vs. CIII: 6.2 +/- 1.2 vs. 13.7 +/- 2.1 vs. 7.3 +/- 0.9 mg/day, ANOVA, P < 0.01). In conclusion, we confirm that there is heterogeneity in renal structure in NIDDM patients with MA. This heterogeneity is not due to renal diseases other than diabetes. Increased alpha 1 m and proliferative retinopathy are useful indicators of the subgroup of MA NIDDM patients with typical diabetic glomerulopathy. It is suggested that diabetic microangiopathy explains the simultaneous occurrence of typical diabetic glomerulopathy, proliferative retinopathy and tubular dysfunction in a subgroup of NIDDM patients with MA.
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PMID:Renal structure and function in non-insulin dependent diabetic patients with microalbuminuria. 940 19

Microalbuminuria (MA) is associated with microangiopathy (renal and retinal lesions) in insulin-dependent diabetic (IDDM) patients. In contrast MA does not reflect microvascular damage in a substantial number of non-insulin-dependent diabetic (NIDDM) patients. MA predicts cardiovascular disease in NIDDM patients with increased von Willebrand factor (vWF) plasma levels which are hypothesized to reflect endothelial dysfunction. However, it is not known whether MA is consequent to generalised endothelial dysfunction or to renal injury. Thus, this study evaluated vWF plasma levels in relation to renal and retinal structural abnormalities in NIDDM patients with MA. Kidney biopsies, fundoscopy and measures of vWF plasma levels were performed in 32 NIDDM patients with MA. These patients were allocated to two renal structural categories: A) Without renal structural abnormalities (C I, n = 10): normal or near-normal renal structure, and B) With renal structural abnormalities (n = 22), further divided into: C II (n = 12) with typical diabetic nephropathology, predominantly glomerulopathy, and C III (n = 10) with atypical patterns of renal injury (more advanced tubulo-interstitial and arteriolar than glomerular changes). vWF plasma levels were significantly higher in category B (C II: 195+/-49% and C III: 161+/-46%) than in category A (C I: 119+/-42%), (chi-square, p < 0.05). Diabetic retinopathy was also related to vWF plasma levels (ANOVA, p < 0.05). These data suggest that there are two types of MA in NIDDM: one associated with increased vWF levels, established renal injury and frequently retinopathy, and the other characterized by normal vWF levels, normal renal structure and absent or mild diabetic retinopathy. We propose that vWF plasma levels in NIDDM patients with MA may help to identify patients with important renal structural changes, increased retinopathy risk and, perhaps, generalised endothelial dysfunction. Whether vWF plasma levels predict end-stage renal disease and cardiovascular events deserves longitudinal studies.
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PMID:Heterogeneous nature of microalbuminuria in NIDDM: studies of endothelial function and renal structure. 949 59

The large interindividual variation in diabetes duration until the onset of nephropathy is partly unexplained. This study was performed to compare renal structure in insulin-dependent (IDDM) patients who had developed signs of nephropathy after a short or long duration of diabetes. Renal biopsies were obtained from 17 IDDM patients, with albumin excretion rate 20-300 microg/min and normal blood pressure. Six patients had <25 years duration ("short-term", early onset of microalbuminuria) and eight patients had duration >30 years ("long-term", late onset of microalbuminuria). Biopsies were obtained 18 months after entry into a study testing the effect of low-dose antihypertensives. Parameters characterizing diabetic glomerulopathy were significantly increased in IDDM patients compared with those in 17 living donors: Basement membrane thickness, mean and (CV): 591 nm (0.17) vs 320 nm (0.12), mesangial volume fraction per glomerulus 0.27 (0.19) vs 0.19 (0.10), matrix volume fraction per glomerulus 0.16 (0.20) vs 0.097 (0.22), matrix star volume 38.5 microm3 (0.43) vs 13.9 microm3 (0.31), (p<10(-4) for each). Comparison of short vs long-term patients showed no significant differences in glomerulopathy parameters, glomerular volume or extracellular material per glomerulus, whereas the fraction of occluded glomeruli was significantly increased in long-term patients. A close correlation obtained between fraction of occluded glomeruli and glomerular filtration rate (r=0.72, p= 0.001). Glomerular occlusion occurred unrelated to the severity of diabetic glomerulopathy. It is suggested that diabetic macroangiopathy and arteriolar hyalinization may play an important role in the renal function of patients with slow development of nephropathy.
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PMID:Renal structural changes in insulin-dependent diabetic patients with albuminuria. Comparison of cases with onset of albuminuria after short or long duration. 954 24

Urinary samples were concentrated rapidly and efficiently and were used to develop several protein assays that may be of value in monitoring individuals with progressive renal disorders. Transforming growth factor-beta1 (TGF-11) and retinol binding protein (RBP) were measured with modification of commercially available methods used to assay serum specimens; type 3 collagen (T3C) was measured with a new immunonephelometric assay. The precision characteristics of these assays are comparable with those reported for microalbuminuria. The clinical utility of measuring a panel of these markers was demonstrated in urine samples from 16 control subjects and from 46 individuals with insulin-dependent diabetes mellitus (IDDM) with various albumin excretion rates (AERs). TGF-beta1 and T3C were used as markers of cytokine expression and of the renal fibrogenic process, whereas RBP excretion served as a marker of tubular injury or dysfunction. Compared with controls, T3C excretion was significantly increased in 18 normoalbuminuric and further increased in 13 microalbuminuric (AER 20 < or = 200 microg/min) IDDM subjects. RBP excretion was increased in macroalbuminuric IDDM subjects (AER >200 microg/min, overt nephropathy). Significant correlations were also found between AER and RBP in all but macroalbuminuric individuals, whereas TGF-beta1 correlated with T3C excretion in controls and in normoalbuminuric diabetic subjects. Urinary RBP but not AER was an excellent predictor of diabetic nephropathy as defined by serum creatinine (P = 0.0001). This underscores the importance of an early tubulopathy in the subsequent development of glomerulopathy and overt nephropathy. The data suggest that longitudinal monitoring of a panel of urinary markers such as that used in the current study may better define their relevance in progressive glomerulosclerosis and may also provide greater insight into the mechanisms underlying such process.
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PMID:Urinary measurement of transforming growth factor-beta and type IV collagen as new markers of renal injury: application in diabetic nephropathy. 959 Mar 67


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