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S Morano

Publications and source records attributed to S Morano.

At least 19 recordsLinked to original sources
PubMed2006

Ultrasound imaging of the female perineum: the effect of vaginal delivery on pelvic floor dynamics.

OBJECTIVE: To assess the use of perineal ultrasound in the evaluation of the influence of vaginal delivery on urethral mobility and on the contraction strength of the levator ani muscles. METHODS: This was a prospective observational study of 70 nulliparous women. Each woman underwent perineal ultrasound assessment at 36-38 weeks' gestation and at 1 week and 3 months following delivery. During each examination we assessed: the posterior urethrovesical angle at rest, urethral mobility during Valsalva maneuver and movement of the anorectal angle and levator sling angle during contraction of the levator ani. RESULTS: The urethrovesical angle and the urethral mobility increased significantly after delivery (P < 0.0001). The levator sling excursion decreased proportionally. The anorectal excursion had decreased significantly by the examination 3 months after birth. CONCLUSIONS: Perineal sonography provides objective assessment criteria for urethral mobility and for contraction strength of the levator ani muscles and detects changes in the anatomy and function of the pelvic floor after vaginal delivery.

Adolescent↗
PubMed2004

Renal damage in vesico-ureteric reflux.

OBJECTIVE: To detect the different extent of renal parenchymal involvement in primary vesico-ureteric reflux (VUR), and to evaluate the relationship between VUR grade, patient age and different patterns of parenchymal damage. PATIENTS AND METHODS: This blinded retrospective study included 197 consecutive children (mean age 4.26 years, range 1 month to 13 years) with primary VUR detected by voiding cysto-urethrography (VCUG), 99mTc-dimercaptosuccinic acid (DMSA; 120 MBq/1.73 m2) renal scintigraphy, with scanning for 3 h after intravenous injection. An abnormal DMSA scan was classified into three subtypes: cortical defects as a single scar (SS), multiple cortical scarring (MS) and diffuse reduced uptake with small renal size. Renal absolute uptake (AU), and split-kidney relative uptake were evaluated in refluxing and nonrefluxing renal units, and correlated with parenchymal damage and patient age. Student's t-test and the chi-square test were used for the statistical analysis. RESULTS: In all, 282 refluxing and 112 nonrefluxing units were assessed. Renal damage was detected in 188 of 282 units with VUR (67%) and in 18 of 112 (16%) contralateral nonrefluxing kidneys. The mean AU was 18.7% in kidneys with VUR and 29% in nonrefluxing units (P < 0.001). The mean (SD) AU decreased from lower to higher grades of VUR, i.e. grade 0 VUR (group A), 28.97 (9.71); grade 1-3 (group B), 21.28 (8.33); grade 4-5 (group C), 14.78 (8.02). The differences were statistically significant (A vs B, B vs C, both P < 0.001). Renal damage was differently distributed in the three groups: 69 of 109 kidneys (63%) in group C (MS prevalent), 39 of 173 (22.5%) in group B (SS prevalent) and 17 of 112 (15.2%) in group A. There was no significant difference in the distribution of renal damage subtypes in patients aged < or > 2 years (SS 19.6% vs 17.9%, MS 29.6% vs 30.1%, small size 48.2% vs 46.3%). The VUR was severe (group C) in 65% of patients aged < 2 years and in 46% aged > 2 years (chi-square, P = 0.016). CONCLUSIONS: VUR is commonly associated with renal damage. Age (< or > 2 years) did not significantly influence the kidney lesion subtype. Reduced parenchymal function (AU) progressively decreased with the severity of VUR. Focal MS, reduced size and relative uptake were significantly more common in severe VUR, leading to multifocal lesions and hypo-dysplasia. Renal scarring was present in up to 15% of contralateral nonrefluxing kidneys. Severe VUR behaved differently from lesser VUR in the renal scan parenchymal uptake.

Adolescent↗
PubMed2004

The impairment of renal function is not associated to altered circulating vascular endothelial growth factor in patients with Type 2 diabetes and hypertension.

BACKGROUND: Metabolic and haemodynamic factors concur in the development of diabetic nephropathy. Moreover, in diabetes, the presence of hypertension may accelerate the development of renal damage. Vascular endothelial growth factor (VEGF) stimulates microvascular permeability, endothelium-dependent vasodilation and angiogenesis and its synthesis is enhanced by hyperglycaemia, advanced glycation end-products (AGEs), tissue hypoxia and hypertension. VEGF appears to play a central role in mediating diabetic vasculopathy, and although VEGF and its receptors are expressed at renal level, its action in renal pathophysiology is unknown. The aim of this study was to elucidate whether presence and/or severity of renal dysfunction is related to circulating VEGF in patients with Type 2 diabetes and hypertension. DESIGN AND METHODS: Fifty hypertensive Type 2 diabetic patients and 20 non-diabetic patients were included in the study. Renal function parameters such as albumin excretion rate (AER), and glomerular filtration rate (GFR), and VEGF plasma levels were analysed in all subjects, whereas %HbA1c and AGEs levels were evaluated in diabetic patients. RESULTS: GFR was significantly decreased in diabetic patients compared with the control subjects (74.36 +/- 15.95 vs 111.5 +/- 17.0 ml/min, p<0.0001). Three diabetic patients showed AER abnormalities (53.8 +/- 2.3 mg/24h). VEGF in diabetic patients was higher than in the control group (77.95 +/- 65.98 vs 49.30 +/- 40.8 pg/ml), but not significantly. %HbA1c and AGE levels were 6.6 +/- 1.5% and 11.59 +/- 8.09 UAGE/ml, respectively. No correlation was found between renal function, circulating VEGF levels and metabolic control. CONCLUSION: Diabetes, in association with hypertension, significantly decreases renal function, but circulating VEGF may not reflect its concentration and action at renal level.

Aged↗
PubMed2003

Two polyclonal antisera detect different AGE epitopes in human plasma samples.

Advanced glycation end products (AGEs), involved in the pathogenesis of diabetic complications, comprise a series of related chemical structures which might possess dissimilar immunogenic characteristics. In this study the levels of AGE in plasma samples from normal subjects (N=41) and diabetic patients (N=44) were measured by ELISA using two polyclonal antisera (named CF5 and CF199, respectively, and immunologically characterized) raised using two different immunogens and immunization techniques. Age levels were significantly higher in diabetic than in normal plasma samples (P<0.0001) with both antisera. However, CF199 detected higher AGE levels than CF5 both in normal (P<0.0001) and diabetic (P<0.005) samples. Pre-incubation with AGE-bovine serum albumin (BSA) caused the loss of most the reactivity of both antisera. Pre-incubation with carboxy-methyl-lysine-BSA (an oxidation-derived AGE) induced the loss of nearly all CF5 reactivity while CF199 retained a significant amount of activity against AGE antigens. Moreover, CF5 lost over 90% of its reactivity against BSA incubated with high glucose under non-oxidative conditions, suggesting its recognition of mainly oxidation-derived AGE epitopes. The different AGE levels measured by the two antisera suggests, therefore, that one single antiserum is unable to recognize all the various AGE epitopes which might be present, at any time, in tissues and body fluids in health and disease.

Diabetes Mellitus↗
PubMed2003

Angiotensin-converting enzyme inhibition modulates high-glucose-induced extracellular matrix changes in mouse glomerular epithelial cells.

BACKGROUND/AIM: Extracellular matrix alterations are involved in the pathogenesis of diabetic nephropathy. We evaluated the effects of high glucose concentrations and inhibition of angiotensin-converting enzyme on the laminin and fibronectin production by glomerular epithelial cells. METHODS: Glomerular epithelial cells were cultured in 5 and 30 mmol/l glucose, with and without enalaprilat (0.3 mmol/l). Laminin and fibronectin were measured (35S-methionine, immunoprecipitation), and their mRNA expression was evaluated (RT-PCR). RESULTS: The laminin concentration was higher in the cells than in the medium, where an increase of its content was observed under high-glucose conditions (p < 0.01). Fibronectin, found only in the medium, was not modified by the high glucose concentration. Following enalaprilat administration, the laminin concentration was decreased under high-glucose conditions, both in the cell and in the medium (p < 0.001), whereas the fibronectin concentration was increased under high-glucose conditions (p < 0.001). The mRNA expression of laminin and fibronectin under high-glucose conditions only slightly increased. Enalaprilat decreased the fibronectin mRNA synthesis dramatically (>50%, p < 0.0001) under high-glucose conditions. CONCLUSIONS: Enalaprilat normalizes the abnormal, high-glucose-induced concentration of laminin, while it decreases the fibronectin synthesis. The improvement of the renal function in diabetic patients treated with angiotensin-converting enzyme inhibitors may, in part, be due to a modulator effect on extracellular matrix content and composition.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2003

Pathophysiology of diabetic sexual dysfunction.

Sexual dysfunction is common in patients with diabetes mellitus. Vascular, neurological and hormonal alterations are involved in this complication. Many studies showed altered endothelium-dependent and neurogenic relaxations in corpus cavernosum from diabetic patients with erectile dysfunction (ED). This finding has been associated with a lack of nitric oxyde (NO) production and a significant increase in NO synthase (NOS) binding sites in penile tissues, induced by diabetes. Advanced glycation endproducts (AGEs) concur to diabetic vascular complications by quenching NO activity and by increasing the expression of mediators of vascular damage such as vascular endothelial growth factor (VEGF), possessing permeabilizing and neoangiogenic effects, and endothelin-1 (ET-1), with vaso-constricting and mitogenic action. Moreover, the differential gene expression for various growth factors in penile tissues may be involved in the pathophysiology of ED associated with diabetes. Neuropathy is also likely to be an important cause of diabetic ED: morphological alterations of autonomic nerve fibers in cavernosal tissue of patients with diabetic ED have been demonstrated. Finally, androgens enhance nNOS gene expression in the penile corpus cavernosum of rats, suggesting that they play a role in maintaining NOS activity. However, sexual dysfunctions in women with diabetes has received less attention in clinical research. Several studies suggest an increased prevalence of deficient vaginal lubrication, making sexual intercourse unpleasant. Sexual dysfunction is associated with lower overall quality of marital relation and more depressive symptoms in diabetic women.

Animals↗
PubMed2001

Advanced glycation end product levels in eye lenses, aorta, and tail tendon in transplanted diabetic inbred Lewis rats.

BACKGROUND: Pancreatic islet transplantation in diabetes, by restoring euglycemia, should in time correct the abnormal accumulation of advanced glycation end products (AGEs) over target tissues, thus delaying the development of late diabetic complications. METHODS: Homologous islet transplantation was performed in inbred Lewis rats 15 days (TA), 4 months (TB), and 8 months (TC) after streptozotocin diabetes. Group TA was studied for 12 months and groups TB and TC were studied for 4 months after transplantation. Normal (N) and diabetic (D) rats formed the control groups. Metabolic control in the transplant (T) groups was evaluated by oral glucose tolerance test. Blood glucose, glycated hemoglobin, and body weight were determined in all groups. AGE levels were determined by spectrofluorometry in eye lens proteins and by ELISA in aortic and tail tendon collagen. RESULTS: T groups showed normal oral glucose tolerance tests and metabolic parameters. The latter were altered in all D groups (P<0.005 to P<0.0001 versus N and T groups). AGEs were increased in the D groups (P<0.05 to P<0.001) versus the N groups. AGEs in the TA and TB groups were not different from those of the N groups but were significantly reduced (P<0.05 to P<0.001) when compared with those of the D groups. In the TC group, eye lens AGEs were significantly elevated (P<0.001) or significantly reduced (P<0.01) when compared with those of the N or D groups, respectively. Aortic collagen AGEs were elevated (P<0.01) by comparison with those of the N groups and not statistically different from those of the D groups. Tail tendon collagen AGE levels lay between those of the N and D groups, without reaching a statistical significance. CONCLUSIONS: These results indicate that primary and early secondary (groups TA and TB) but not late secondary (group TC) islet transplantations are capable of blocking or reducing an abnormal accumulation of AGEs, thus confirming the importance of preventive transplantation therapies.

Animals↗
PubMed2000

Altered IgG(4) renal clearance in patients with inflammatory bowel diseases. Evidence for a subclinical impairment of protein charge renal selectivity.

BACKGROUND: A loss of intestinal glycosaminoglycans (GAGs) has been shown in inflammatory bowel diseases (IBD). Since GAGs are involved in the regulation of renal protein filtration and GAGs disruption is associated with anionic proteinuria, we examined whether changes in the selectivity of renal protein filtration occur in IBD. METHODS: From 46 patients with IBD (17 with Crohn's disease (CD), and 29 with ulcerative colitis (UC)) and 21 healthy subjects, urine and serum samples were obtained. Albumin, total IgG and IgG(4) clearances were measured using sensitive methods. Serum p-ANCA and TNF-alpha were tested. RESULTS: Median IgG(4) clearance was 0.041 ml/ min/10(-3) in patients with UC and 0.10 ml/ min/10(-3) in CD patients, both significantly higher than in controls (0.03 ml/min/10(-3)) (P<0.03). IgG(4) clearance was above the upper normal limit in 9/17 CD (53%) and in 10/29 UC (34.5%). Eighteen of 19 patients showing abnormal IgG(4) clearance were taking mesalazine. In patients on maintenance oral mesalazine, IgG(4) clearance was higher than that in patients off treatment (0.12 vs 0.03 ml/min/10(-3), P=0.04). No clinical/laboratory sign of renal dysfunction was documented in patients with altered IgG(4) clearance and maintained on mesalazine treatment. CONCLUSION: Renal protein charge permselectivity is impaired in 40% of patients with IBD with no overt proteinuria. Our data suggest that altered IgG(4) clearance may represent a subclinical marker of renal involvement in IBD.

Administration, Oral↗
PubMed1999

Effect of islet transplantation on neuroelectrophysiological abnormalities in diabetic inbred Lewis rats: comparison of primary versus secondary prevention.

BACKGROUND: Neuroelectrophysiological abnormalities in diabetes indicate nervous function failure. Restoration of euglycemia by islet transplantation may prevent or reverse these abnormalities. METHODS: Pancreatic islets were transplanted in inbred Lewis rats after 15 days (Ta12, primary prevention) or 8 months (Tb12, secondary prevention) from streptozotocin-induced diabetes. Transplanted and control (normal and diabetic) rats were followed for a total period of 12 months. Metabolic parameters, somato-sensory, brain-stem auditory, and visual evoked potentials were determined at the beginning and at the end of the study and before transplantation for secondary prevention. RESULTS: The metabolic parameters in transplanted animals were similar to those of normal animals. Ta12 and normal group somato-sensory conduction velocities did not vary and were always significantly higher than those of diabetic animals. By contrast, Tb12 group conduction velocities showed only a partial improvement, values lying between those of diabetic and normal rats. Brain-stem auditory (waves I, II, and III) latencies in Ta12 group were similar to those of normal rats and significantly lower than those of diabetic animals (wave I: P<0.01; waves II and III: P<0.05). Tb12 group wave I and II latency values remained altered (P<0.005 and P<0.01 versus normal values respectively). Visual evoked potentials-P1 wave latencies in transplanted rats were always higher than those of normal and diabetic animals. CONCLUSIONS: After primary prevention, central and peripheral neurological alterations were abolished. After secondary prevention, transplantation beneficial effects were partial, occurring mainly at peripheral level. These results highlight the importance of early transplantation to prevent hyperglycemia-dependent neuroelectrophysiological alterations.

Animals↗
PubMed1999

Autoimmune markers and neurological complications in non-insulin-dependent diabetes mellitus.

To verify whether autoimmune markers related to nervous system structures and other autoimmunity indexes present in diabetes mellitus are associated with subclinical neuropathy, we examined 48 non-insulin-dependent diabetic patients with and without neuroelectrophysiological alterations. Nerve conduction velocity at the external sciatic-popliteal nerve, at the sural nerve, at the median and ulnar nerves level has been evaluated. Autoimmunity was investigated by evaluating glutamic acid decarboxylase (GAD-Ab), insulin (IAA), GM3, GD3 and GT1b gangliosides, pancreatic islet cell (IC-A) and anti-nervous-tissue autoantibody presence. Nerve conduction velocities were decreased in 72.9% of diabetic patients. Anti-insulin antibodies were detected in seven non-insulin created diabetic patients and in higher amount in subjects with (17.1%) than in those without (7.7%) asymptomatic neuropathy. Anti-GM3 antibodies were detected in four diabetic patients all of whom presented neurological complication. A significant correlation has been found between neurological damage and presence of anti-insulin antibodies (p<0.05). In the case of GM3 autoantibody, a similar result was obtained, but the data failed to reach statistical significance. Our data demonstrate that autoimmunity might play a role in the development of peripheral neuropathy.

Aged↗
PubMed1998

Reduction of advanced glycation end-product (AGE) levels in nervous tissue proteins of diabetic Lewis rats following islet transplants is related to different durations of poor metabolic control.

Advanced glycation end-products (AGEs) are irreversible compounds which, by abnormally accumulating over proteins as a consequence of diabetic hyperglycaemia, can damage tissues and thus contribute to the pathogenesis of diabetic complications. This study was performed to evaluate whether restoration of euglycaemia by islet transplantation modifies AGE accumulation in central and peripheral nervous tissue proteins and, as a comparison, in proteins from a non-nervous tissue. Two groups of streptozotocin diabetic inbred Lewis rats with 4 (T1) or 8 (T2) months disease duration were grafted into the liver via the portal vein with 1200-1500 islets freshly isolated from normal Lewis rats. Transplanted rats, age-matched control and diabetic rats studied in parallel, were followed for a further 4-month period. At study conclusion, glycaemia, glycated haemoglobin and body weight were measured in all animals, and an oral glucose tolerance test (OGTT) performed in transplanted rats. AGE levels in cerebral cortex, spinal cord, sciatic nerve proteins and tail tendon collagen were measured by enzyme-linked immunosorbent assay (ELISA). Transplanted animal OGTTs were within normal limits, as were glycaemia and glycated haemoglobin. Diabetic animal AGEs were significantly higher than those of control animals. Protein AGE values were reduced in many transplanted animals compared to diabetic animals, reaching statistical significance in spinal cord (P < 0.05), sciatic nerve (P < 0.02) and tail tendon collagen (P < 0.05) of T1 animals. Thus, return to euglycaemia following islet transplantation after 4 months of diabetes with poor metabolic control reduces AGE accumulation rate in the protein fractions of the mixed and purely peripheral nervous tissues (spinal cord and sciatic nerve, respectively). However, after a double duration of bad metabolic control, a statistically significant AGE reduction has not been achieved in any of the tissues, suggesting the importance of an early therapeutic intervention to prevent the possibly pathological accumulation of AGEs in nervous and other proteins.

Animals↗
PubMed1996

Antineutrophil cytoplasmic antibodies are present in long standing type 1 diabetics but do not correlate with selective proteinuria.

Antineutrophil cytoplasmic antibodies (ANCA) are present in systemic vasculitis with or without renal involvement and in inflammatory bowel diseases, conditions which share damage in proteoglycan content of basal membrane. In diabetes, there is a reduction in proteoglycans in the kidney basal membrane, responsible for the decrease in fixed anionic charges and, consequently, for the prevalent anionic proteinuria (albumin, IgG4) even in the early preclinical stage of nephropathy. The aims of this study were to search for the presence of ANCA in long-standing type 1 diabetic patients and to evaluate possible correlations with size- and/or charge-selective proteinuria. Twenty-two type 1 diabetic patients (duration of diabetes 24 years, range 9-30) selected and grouped according to albumin excretion rate values, were studied together with 21 age and sex comparable normal subjects. ANCA, albumin excretion rate, and the clearances of albumin, of prevalently cationic total IgG (IgG) and of anionic IgG4 were evaluated. ANCA were measured using ELISA and indirect immunofluorescence methods; albumin, IgG and IgG4 were tested with RIA or ELISA methods developed in our laboratory. ANCA were found in five patients, three of whom showed proteinuria. 33.3% and 18.2% of patients with normal IgG and albumin clearances respectively had elevated IgG4 clearance. This study shows for the first time the presence of ANCA in long-standing type 1 diabetic patients and confirms a prevalent anionic protein excretion in these patients, but does not show a correlation between the presence of ANCA and proteinuria, even if the presence of ANCA in diseases sharing alterations in proteoglycan content of vascular basal membrane is noteworthy.

Adult↗
PubMed1996

Peripheral, but not central, nervous system abnormalities are reversed by pancreatic islet transplantation in diabetic Lewis rats.

Neuroelectrophysiological recordings represent a non-invasive and reproducible method of detecting central and peripheral nervous system alterations in diabetes mellitus. In order to evaluate whether the normalization of metabolic control obtained by pancreatic islet transplantation could reverse diabetic neuroelectrophysiological alterations, or prevent further deterioration, we used an experimental model in which pancreatic islets (n = 1200) were injected into the portal vein of inbred Lewis rats (used as islet donors as well as recipients). Islets were injected 4 months after diabetes induction, since previous work had shown functional but not morphological damage at the nervous tissue level at this stage of the disease. Visual (V), brainstem auditory (BA) and somatosensory (S) evoked potentials (EPs) were measured in streptozotocin-induced, islet-recipient diabetic rats (n = 7), streptozotocin-induced diabetic rats (n = 16) and non-diabetic control rats (n = 12). Metabolic parameters and electrophysiological recordings were evaluated before diabetes induction, before transplantation and 4 months later. After transplantation, glycaemic levels returned to normal values within 1 week and remained so until the end of the study, as confirmed by a normal oral glucose tolerance test and by an increase in body weight. Electrophysiological recordings were altered in diabetic animals before transplantation. Four months after transplantation EP recordings improved, with a detectable gradient from the peripheral to the central structures. SEPs were significantly improved in the peripheral tarsus-L6 tract and the L6-cortex tract (P < 0.005 and P < 0.01 versus diabetic rats) and were ameliorated without achieving statistical significance in the central L6-cortex tract. BAEP latency values tended to improve in transplanted rats, but the differences versus non-transplanted diabetic animals failed to reach significance. VEP values remained clearly pathological and even deteriorated after transplantation. These results show that normalization of metabolic control by pancreatic islet transplantation can reverse some of the already established neuroelectrophysiological alterations at the peripheral nervous system level, but does not affect other alterations at the central nervous system level.

Animals↗
PubMed1995

Role of advanced glycation end-products (AGE) in late diabetic complications.

To evaluate accumulation of advanced glycation end-products (AGE) in diabetes and its possible correlation with late diabetic complications, AGE levels were measured by spectrofluorimetry in eye lens and sciatic nerve proteins and isolated tail tendon collagen of rats with experimental diabetes of 3- and 6-month duration. The values obtained were compared to those from age-matched control rats and correlated with cataract presence and somatosensory evoked potential (SEP) alterations. Diabetic animals had increased AGE levels in all tissues at both times; cataract developed in 29% of diabetic rats at 3 months and in 57% at 6 months; SEP conduction velocity was reduced in diabetic animals both at 3 (54.5 +/- 1.8 S.E.M. m/s vs. 73.9 +/- 1.0, P < 0.0001) and 6 months (59.5 +/- 1.4 vs. 71.5 +/- 1.6, P < 0.0001) from diabetes induction. No eye lens AGE level differences were observed when cataract presence was considered. Interestingly, in diabetic rats, increased sciatic nerve AGE levels were associated with reduced SEP. These data show that: (1) AGE levels are increased as early as 3 months from development of hyperglycemia; (2) other factors, in addition to an enhanced rate of fluorescent AGE formation, might play important roles in the pathogenesis of diabetic cataract; (3) increased peripheral nerve AGE levels are associated with SEP alterations.

Animals↗
PubMed1994

Characteristics of proteinuria in experimental diabetes mellitus.

An impairment of protein charge selectivity has been invoked to explain the initial anionic proteinuria in diabetic nephropathy. The aims of this work were to investigate charge and size protein perm-selectivity abnormalities in experimental diabetes and to monitor these changes over time after diabetes induction. Diabetes was induced in 56 Sprague-Dawley male rats by streptozotocin; the control group was represented by 38 normal rats. Blood glucose, body weight, urine volumes, and proteinuria in 24-h urine collections were evaluated at 3, 6, 9, and 12 months of diabetes. The Bradford method and mono- and bidimensional gel electrophoresis were used to determine and characterize proteinuria. Body weight increase was lower (P < 0.05, P < 0.0001, P < 0.05 at 3, 6, and 12 months, respectively), urine volumes were greater (P < 0.001, P < 0.005, P < 0.05 at 6, 9, and 12 months, respectively) and the proteinuria was significantly increased (P < 0.05 at 3 months, P < 0.001 at 6 months, P < 0.01 at 9 months, and P < 0.05 at 12 months) in diabetic rats compared with the control group. When the charge and the size of urine proteins were considered, small (30 kDa) and anionic proteins were found to be mainly excreted in diabetic rats, at 3 months of the disease; at 6 months, higher amounts of albumin and cationic proteins with higher molecular weight (50 kDa) were also found in the urine; at 9 and 12 months the changes previously described were associated with an excretion of proteins weighing about 75 kDa.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗
PubMed1993

A charge selectivity impairment in protein permselectivity is present in type 2 diabetes.

A possible loss in kidney charge permselectivity of proteins before any manifestation of nephropathy has been sought in type 2 (non-insulin-dependent) diabetes by assessing the clearances of proteins differing in charge and/or size (anionic and cationic immunoglobulins, albumin). Eighty-five consecutive outpatients with type 2 diabetes were studied and compared with 101 normal subjects. Of the patients, 14.1% were microalbuminuric and 2.3% macroalbuminuric. A significant increase in protein clearances was observed in diabetic patients in comparison with normal subjects: the median of albumin clearance was 0.09 ml/min, interquartile range (IR) 0.04-0.31 (P < 0.01 vs normals); that of anionic immunoglobulins (IgG4) 0.02 ml/min, IR 0.04-0.05 (P < 0.005 vs normals); and that of neutral/cationic immunoglobulins (IgG) 0.13 ml/min, IR 0.07-0.19 (P < 0.01 vs normals). The anionic/cationic immunoglobulin ratio median was 0.22, IR 0.11-0.43, and exceeded the upper limit of normal values in 29.4% of all patients. IgG4 clearance was positively correlated with albumin clearance (r = 0.72) and with IgG clearance (r = 0.98). Nevertheless anionic immunoglobulin clearance was increased in a number of patients (17.3%) with normal IgG excretion and even in patients (15.1%) with normal albumin clearance. Clearances of IgG4 and IgG, but not that of albumin, were correlated with the duration of diabetes. Thus, an increased anionic/cationic IgG ratio in type 2 diabetes highlights a charge selectivity defect in protein permselectivity; this selective proteinuria may reflect more accurately than does microalbuminuria an early kidney abnormality in this form of diabetes.

Adult↗