Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Abnormal renal diseases including nephrotic syndrome and chronic renal failure are associated with hyperlipidemia, significance of abnormal lipid metabolism has been thought to be limited in some inherited renal diseases. However, recent studies have postulated that glomerulosclerosis is induced by hyperlipidemia and is in common with atherosclerosis. This involvement is found in the progressive renal disorders, e.g., focal glomerular sclerosis, diabetic nephropathy and glycogen storage disease. Interaction between macrophages and mesangial cells may play an important role in such conditions. This evidence is supported by experimental models with hyperlipidemia. On the other hand, discovery and new hereditary metabolic disorders, such as type III hyperlipoproteinemia and lipoprotein glomerulopathy, shows that apolipoprotein (apo) E abnormalities are responsible for the glomerular lesions. Especially, lipoprotein glomerulopathy has specific features different from those of lipid-induced renal diseases. In this disease, apo E Sendai which results from new substitution (Arginine 145-->Proline) may induce intraglomerular lipoprotein thrombi characteristic of lipoprotein glomerulopathy.
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PMID:Abnormal lipid metabolism and renal disorders. 916 48

Proteinuria in chronic kidney transplant failure (CKTF) is due to an alteration of glomerular permselectivity and two major determinants can be characterized experimentally: (1) size selectivity, that is, the ability of the glomerular filter to progressively hinder the passage of macromolecules with increasing molecular radius and (2) charge selectivity, the ability to restrict filtration of negatively charged molecules more effectively than that of equally sized uncharged or cationic compounds. The fractional clearance values of neutral polydisperse dextran molecules create a sieving profile to describe size selectivity, and anionic dextransulfate is used to evaluate charge selectivity. We characterized permselectivity in renal transplants recipients with various degrees of proteinuria. Proteinuria < 1 g/day is caused by an isolated defect of glomerular charge selectivity, whereas nephrotic range proteinuria (characterized histologically by transplant glomerulopathy) is due to an additional impairment of glomerular size selectivity. This sequence is similar to the one observed in patients with chronic native kidney disease (such as diabetic nephropathy). It therefore can be speculated that therapeutic interventions which have been shown to reduce proteinuria in patients with chronic native kidney disease will also beneficially affect permselectivity in CKTF.
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PMID:Glomerular proteinuria in renal transplant patients: mechanisms and treatment. 940 28

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

There is little data on the spectrum of renal diseases in the United Arab Emirates. A renal diseases registry has been set up in an attempt to address this issue nationwide, and we report here the first outcome of this endeavor, a retrospective histopathologic analysis of 490 native kidney biopsies performed on adult patients presenting to four hospitals in the Emirate of Abu Dhabi from 1978 to June 1996. The most common indication for a biopsy was the nephrotic syndrome (54.0%), followed by asymptomatic urinary abnormalities (29.7%), and chronic renal failure (12.7%). Primary glomerular disease accounted for 77.1% of all biopsies. Chronic proliferative glomerulonephritis as a group was the predominant pathology (36.2%), followed by idiopathic membranous glomerulopathy (20.1%), focal segmental glomerulosclerosis (18.3%), minimal change nephropathy (18.3%), and IgA nephropathy (6.3%). Of the patients with secondary kidney diseases, 33 (40.7%) had systemic lupus erythematosis, 27 (33.3%) amyloidosis, 14 interstitial nephropathy, and seven diabetic nephropathy. Kidney biopsies of 187 patients with primary glomerular disease who presented with the nephrotic syndrome were analyzed. In this group idiopathic membranous glomerulopathy, proliferative glomerulonephritis, and minimal change glomerulopathy was found in almost equal proportions (28.3%, 26.6%, 26.2%) with focal segmental glomerulosclerosis (15.4%) accounting for the bulk of the remainder. Though the overall results of this analysis do not show any major differences in the spectrum of primary glomerulopathies in the United Arab Emirates compared with other countries, a slight tendency towards a higher frequency of focal segmental glomerulosclerosis among patients indigenous to the Arabian Peninsular (20.4%) deserves further evaluation.
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PMID:Analysis of 490 kidney biopsies: data from the United Arab Emirates Renal Diseases Registry. 965 Jan 23

The clinical course of diabetic nephropathy may be described in stages; the normo-, micro- and macroalbuminuric stage. The basis for its development is the diabetic glomerulopathy in which accumulation of basement membrane (BM) material is pivotal. Normoalbuminuric patients have normal or slightly increased BM thickness; microalbuminuric patients show further BM thickening and mesangial expansion, formation of new capillaries, arteriolar and interstitial changes. The degree of diabetic glomerulopathy may be predicted by long-term glycemic control, diabetes duration and glomerular filtration rate (GFR). A slight decline in GFR in microalbuminuric patients is associated with increases in BM thickness, capillary diameter and interstitial volume fraction. In turn, the degree of early diabetic glomerulopathy may predict the level of microalbuminuria several years later. Improved metabolic control, even to not normal levels, retards the increase of BM thickness and matrix volume in microalbuminuric adolescents. If matrix accumulation may be prevented diabetic nephropathy will not develop. Morphometric analyses may thus be useful in evaluating the effect of intervention, also during shorter periods and at early stages.
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PMID:Diabetic glomerulopathy in young IDDM patients. Preventive and diagnostic aspects. 967 92

Our purpose was to elucidate the hypothesis that paracrine-produced transforming growth factor (TGF)-beta1 regulates the accumulation of extracellular matrix (ECM) in renal glomeruli, a hallmark of diabetic nephropathy. To produce TGF-beta1 from the juxtaglomerular apparatus in mouse kidneys, we cloned a mouse Ren-1c promoter fragment (-4.100 to +6 base pairs) upstream of porcine TGF-beta1 (pTGF-beta1) cDNA, mutated to ensure secretion of biologically active TGF-beta beta1. The resulting transgenic mice had significantly more TGF-beta1 in their kidneys than was in those of nontransgenic controls, as confirmed by immunohistochemistry, and the production of TGF-beta1 was enhanced in vivo by captopril-induced stimulation of the Ren-1c promoter. Overproduction of pTGF-beta1 close to the glomerulus resulted in a local accumulation of ECM, composed partly of collagen type IV and laminin, and thickening of the basement membrane, characteristic features of diabetic nephropathy. Interstitial accumulation of ECM and signs of tubular atrophy were present only in older mice (>5 months of age). Results from in situ hybridization and immunohistochemistry suggest that pTGF-beta1 stimulated the production of endogenous TGF-beta1 along collecting ducts and connecting tubules. The increased amount of biologically active TGF-beta1, transgenic as well as endogenous, was corroborated by heightened proteoglycan synthesis from incubated kidney slices. This transgenic model demonstrates that sustained local expression of TGF-beta1 leads to glomerulopathy. We conclude that autocrine- or paracrine-produced TGF-beta1 may play a role in the development of glomerular diseases, such as diabetic nephropathy.
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PMID:Under control of the Ren-1c promoter, locally produced transforming growth factor-beta1 induces accumulation of glomerular extracellular matrix in transgenic mice. 989 41

We reviewed the clinical and pathological characteristics of seven patients with collapsing glomerulopathy (CG) in renal allograft biopsy specimens. All patients underwent biopsies for graft dysfunction. Two patients had nephrotic proteinuria (protein, >3.5 g/24 h), whereas all others had only modest or insignificant proteinuria. In five of seven patients, additional pathological processes, including microvascular injury, acute rejection, recurrent diabetic nephropathy, and immune complex glomerulonephritis, were present, each of which likely contributed to graft dysfunction and proteinuria. None of the patients in this series had nephrotic syndrome solely attributable to CG. Three biopsy specimens had features consistent with chronic rejection. The development of CG in renal allograft biopsy specimens was associated with graft dysfunction and a high rate of graft loss. These findings emphasize the prognostic significance of CG in renal allografts and suggest that CG may result from diverse pathogenic mechanisms.
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PMID:Collapsing glomerulopathy in renal allografts: a morphological pattern with diverse clinicopathologic associations. 1019 29

A 41-yr-old patient with non-insulin-dependent diabetes mellitus (NIDDM), before and after ABO-incompatible renal transplant, is reviewed using serial protocol biopsy. Although she recovered from delayed hyperacute rejection (DHAR) immediately post-transplantation, her graft function deteriorated gradually. A mild acute transplant glomerulitis, noted at the 155th day post-transplantation, progressed to pronounced chronic transplant glomerulopathy over 5 yr. In the specimen of the last biopsy, at 5 yr post-transplantation, glomeruli demonstrated an exudative hyaline lesion, which was characteristic of diabetic nephropathy in addition to chronic transplant glomerulopathy. Therefore, we made a diagnosis of this glomerular lesion as chronic transplant glomerulopathy complicated by diabetic glomerulopathy. Considering the result of this case, the protocol biopsy is a useful procedure to diagnose an accurate cause of graft dysfunction in individual cases. It is concluded that the protocol biopsy is apparently useful for the detection of various pathological processes occurring in allograft and may contribute to a strategy for improvement of graft survival.
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PMID:A case of ABO-incompatible renal transplant patient with non-insulin-dependent diabetes mellitus; long-standing observation of serial glomerular change by protocol biopsy. 1075 Oct 56

Structural changes underlying diabetic nephropathy in Type 1 diabetes are prodominant in the glomerulus [thickening of glomerular basement membrane (GBM) and mesangial expansion], but also include arteriolar, tubular and interstitial lesions. The structural measure that correlates best with all renal functional parameters in Type 1 diabetes is mesangial fractional volume [Vv(mes/glom)], an estimate of mesangial expansion. Structural-functional relationships in Type 2 diabetes are much less known. These studies investigated renal structure in the early stages of nephropathy [microalbuminuria (MA)] in patients with Type 1 and Type 2 diabetes. Diabetic glomerulopathy was quite advanced in Type 1 diabetic patients with MA, and both Vv (mes/glom) and GBM width were increased as compared to normoalbuminuric (NA) patients when the albumin excretion rate (AER) was > 30 microgram/min. Serial renal biopsies were performed 5 years apart in 11 Type 1 diabetic patients to evaluate whether glomerular and interstitial lesions progress jointly. AER increased significantly in 5 years, while the glomerular filtration rate remained unchanged. All structural parameters were initially abnormal. Vv(mes/glom) and mean glomerular volume increased significantly, whereas GBM width and the interstitial volume fraction were unchanged. Moreover, the change in Vv (mes/glom) was correlated with the change in AER (r =0.64, p <0.05). Thus, at the disease stage during which some patients progress to MA or proteinuria, continuing mesangial expansion is the main variable, whereas further interstitial expansion does not occur. A large number of Type 2 patients were also studied. Early diabetic glomerulopathy was detected by electron microscopy in NA patients and found to be more advanced in those with MA and proteinuria. However, lesions were milder than in Type 1 diabetic patients, and there was considerable overlap between groups. Morphometric results by electron microscopy were similar to those by light microscopy, demonstrating the heterogeneity of renal structure in Type 2 diabetic patients. In fact, only 30% of MA patients had typical diabetic glomerulopathy, while 40% had more advanced tubulo-interstitial and/or vascular lesions and 30% had normal renal structure.
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PMID:Structural involvement in type 1 and type 2 diabetic nephropathy. 1092 68

Peritubular capillaries (PCs) with a circumferentially multilayered basement membrane have been suggested as an ultrastructural indicator of chronic renal allograft rejection (CR). The authors validated this lesion as a marker for CR, by analyzing its quantitative features, specificity, and sensitivity in 169 renal biopsy specimens. The mean number of circumferential layers (PCcirc) and the incidences of the grades (mild: 2 to 4, moderate: 5 to 6, severe: 7 or more layers) were investigated in biopsy specimens involving CR (CR(Bx), n = 46), acute rejection (n = 11), normal kidneys (n = 20), psoriatics treated with cyclosporine (n = 13), renal transplants with chronic cyclosporine toxicity (n = 12), native kidney diseases (NKD, n = 56), and transplant nephrectomies attributable to CR (Cr(nephr), n = 11). CR was diagnosed with regard to the clinical features and the presence of intimal fibrosis in 41 biopsy specimens or transplant glomerulopathy in 35 biopsy specimens (cg; identified only by electron microscopy in 10 cases). NKD included chronic glomerulonephritis, chronic tubulointerstitial nephritis, benign nephrosclerosis, thrombotic microangiopathy, diabetic nephropathy, and renal disease in elderly patients (median age, 72 years). All PCs around glomeruli were sampled (median, 14 profiles per case). PCs with a moderate/ severe lesion appeared as serrated profiles with a thick, ribbon-like basement membrane layer in semithin plastic sections. The numbers of circumferentially multilayered PCs were significantly characteristic of CR (PCcirc in CR(Bx): 2.87+/-1.83 SD; range, 0 to 7.36; P < .001 v other groups). A severe lesion occurred exclusively in CR (in 12% of the PCs in CR(Bx), and in 38% in CRnephr). A moderate lesion was observed in 0.6% of the PCs in NKD, 16% in CR(Bx), and 21% in CRnephr. Three or more PCs with a moderate lesion were encountered only in CR. A mild lesion was not suggestive of CR at all. In CR(Bx), 27 cases showed a severe lesion or 3 or more PCs with a moderate lesion (cpc; sensitivity: 59%). Four of the 27 cases lacked cg. The cumulative incidence of cpc and cg was 85%. In transplants with cyclosporine toxicity, the presence of cpc verified the coexistence of CR in 7 specimens. In conclusion, cpc is a specific marker of CR. The incidence of cpc increases as CR progresses. The lesion may be caused by a low-grade rejection injury to the PCs. Careful analysis of semithin sections promotes the better sampling of cpc. An ultrastructural demonstration of cpc and cg defines CR more precisely than does light microscopic evaluation per se.
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PMID:Peritubular capillaries in chronic renal allograft rejection: a quantitative ultrastructural study. 1101 82


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