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)

The proteinuria in renal allograft recipients has been regarded as a sign of poor prognosis. The causes of post-transplant proteinuria include chronic rejection, chronic transplant glomerulopathy, glomerulonephritis (GN), acute rejection, and cyclosporine nephrotoxicity. Among them, chronic rejection is known to be most frequent. We analyzed the histopathologic findings of renal allograft biopsies in 197 Korean recipients with proteinuria. Among them, 26 patients developed proteinuria over 500 mg/d. All patients received baseline immunosuppression with cyclosporine. From 26 patients with post-transplant proteinuria, 29 biopsies were performed and their histologic diagnoses were immunoglobulin A nephropathy (IgAN) in 17, IgAN combined with chronic allograft nephropathy in 1, focal segmental glomerulosclerosis in 2, crescentic GN in 1, membranous GN in 1, diabetic nephropathy in 1, acute tubulointerstitial nephritis in 1, and chronic rejection in 3 biopsies. The remaining two biopsies showed nonspecific findings. The most common cause of post-transplant proteinuria was IgAN (62% of biopsies). The incidence of chronic rejection was relatively low and predominant cyclosporine-associated changes were not observed. In conclusion, our data suggest that the main causes of post-transplant proteinuria in Korea are primary glomerulonephritides rather than chronic rejection or cyclosporine nephrotoxicity, and the kidney allograft biopsies from patients with proteinuria should be handled as native kidney.
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PMID:Glomerulonephritis is the major cause of proteinuria in renal transplant recipients: histopathologic findings of renal allografts with proteinuria. 1104 96

In the treatment of diabetic nephropathy, ACE inhibitor therapy reduces albumin excretion and slows the rate of decline in glomerular filtration rate (GFR). Our study was designed to investigate whether these effects lay in amelioration of the underlying glomerular structural abnormalities. A total of 54 type 1 diabetic patients with albuminuria and blood pressure (BP) <150/90 mmHg were randomized to receive 10 mg enalapril once daily, 10 mg nifedipine retard twice daily, or placebo in a multicenter double-blind study of 3 years' duration. Renal biopsy was performed at baseline and follow-up, and tissue was analyzed by standard morphometric methods. BP, GFR, albumin excretion rate (AER), and HbA1c were measured every 6 months. Enalapril lowered AER after 6 months by 26% (P < 0.05); however, this reduction was not sustained at 3 years. There was no significant effect of nifedipine or placebo on AER. GFR decreased by a similar average rate of 4.1 ml x min(-1) x year(-1) (95% CI 2.6-5.6) in all three groups. BP and HbA1c were unchanged throughout the study in all groups. At baseline, nearly all biopsies showed classic appearances of diabetic glomerulopathy. There was no detectable effect of enalapril compared with either nifedipine or placebo on renal structure over 3 years. However, we found that patients with increased AER have established glomerulopathy and a progressive average decline in GFR of 4.1 ml x min(-1) x year(-1) in the absence of overt hypertension, and baseline AER appeared predictive of subsequent mesangial volume fraction (r = 0.20, P = 0.0018). In this small cohort of nonhypertensive patients studied for 3 years, disease evolution appears unaffected by treatment with either enalapril or nifedipine.
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PMID:Effect of 3 years of antihypertensive therapy on renal structure in type 1 diabetic patients with albuminuria: the European Study for the Prevention of Renal Disease in Type 1 Diabetes (ESPRIT). 1128 51

Membranous glomerulopathy (MGN) is characterized by subepithelial immune complex deposits and glomerular basement membrane (GBM) thickening. The majority of patients present with nephrotic syndrome and outcomes are variable. Pathologically, deposits at sites other than the subepithelial aspect of the GBM favor the presence of secondary forms of MGN which are seen most commonly in the setting of autoimmune disease, infection, neoplasia, and with certain therapeutic agents. MGN is the most common form of de novo glomerular disease seen in the renal allograft and may be seen concurrently with other forms of glomerular disease including focal segmental glomerulosclerosis, IgA nephropathy, diabetic nephropathy, and anti-TBM nephritis. This review emphasizes the detection of secondary forms and variants of MGN.
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PMID:Membranous glomerulopathy: emphasis on secondary forms and disease variants. 1134 36

Pathological changes in the urine sodium dodecyl sulphate gel electrophoresis (SDS PAGE) patterns often precede the occurrence of any sign of renal involvement in diabetes. However, data concerning the most frequent SDS PAGE pattern of the urine in early stages of type I diabetes mellitus are controversial. In the present study an SDS PAGE technique has been used that provides an adequate sensitivity for the detection of the abnormal pattern. Urinary proteins have been analyzed by SDS PAGE in twenty two diabetic adolescents and twenty four age matched controls. Albumin concentration, and N acetyl-beta-D-glucosaminidase (NAG) activity were also measured in the same samples. There was no significant difference in urine albumin concentration and NAG activity between diabetic children and controls. However twelve patients showed an electrophoretic pattern characteristic for glomerulopathy, two had a pattern indicating tubular dysfunction and another two patients had a mixed pattern. Among the twenty four controls only three showed abnormal electrophoretic patterns. The results support the view that early stages of diabetic nephropathy may involve both glomerular and tubular dysfunction. However the exact clinical and prognostic significance of the information provided by SDS PAGE analysis remains to be elucidated.
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PMID:Electrophoretic analysis of urinary proteins in diabetic adolescents. 1143 99

Genetic factors are important in conferring diabetic nephropathy (DN) risk. The insertion/deletion (I/D) polymorphism of the ACE gene has been described to be associated with DN risk and progression. The renal lesions underlying DN in type 2 diabetes are heterogeneous; only a subset of patients, characterized by a faster decline of renal function, have diabetic glomerulopathy. This study explored the relations between diabetic glomerulopathy and the ACE genotype distribution in 77 type 2 diabetic patients with an albumin excretion rate > or = 20 microg/min. Using morphometric analysis of kidney biopsies, mesangial and mesangial matrix fractional volumes [Vv(mes/glom) and Vv(MM/glom)] and glomerular basement membrane (GBM) width were estimated. We found that 13 patients were II, 30 were ID, and 34 were DD. Clinical features and renal function were similar in the three groups; in contrast, the DD patients had the highest Vv(MM/glom) and GBM width. Subdividing patients in tertiles of GBM width and Vv(MM/glom), from the lowest (I) to the highest (III) values, the DD carriers had an odds ratio of 6.11 (95% CI 1.84-20.3) and 10.67 (2.51-45.36), respectively, for the likelihood of being in tertile III than I for GBM width and Vv(MM/glom). Multiple regression analysis revealed the I/D polymorphism as an independent determinant of GBM thickening in addition to diabetes duration and HbA(1c). In conclusion, the ACE DD genotype is associated with diabetic glomerulopathy lesions, making the study of this polymorphism helpful in identifying those type 2 diabetic patients at higher risk of fast DN progression.
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PMID:The angiotensin-converting enzyme DD genotype is associated with glomerulopathy lesions in type 2 diabetes. 1175 50

Proteinuria is the hallmark of renal disease and proteinuria exceeding 1 gm a day in patients with renal disease augers a poorer prognosis. Proteinuria has been shown to be tubulotoxic and directly contributes to renal deterioration. Patients with non-selective proteinuria are more likely to have progressive renal disease. Diabetic patients with persistent microhaematuria have about 20 times the risk of developing diabetic nephropathy. In essential hypertension, the onset of de novo proteinuria after years of adequate BP control is a marker of subsequent decline in renal function. In glomerulonephritis, more severe proteinuria is associated with faster rate of progression. Even though the initial phase of proteinuria in patients with glomerulonephritis is usually of immunological origin, in the vast majority of patients with established disease, the latter progressive phase of proteinuric glomerulopathy is the result of glomerular hyperfiltration which shifts glomerular non-selective pores to larger dimensions resulting in excessive leakage of protein in the urine. Endothelial injury resulting from glomerular hyperfiltration causes increase in local generation of Angiotensin II in the kidney as part of the hemodynamic response. ACE inhibitors and angiotensin II receptor antagonists (ATRA) can improve glomerular pore-selectivity by remodelling the glomerular basement membrane. In addition, these agents also have beneficial effects by decreasing TGF-beta production therapy decreasing mesangial cell proliferation, hence ameliorating disease progression in patients with diabetic nephropathy and IgA nephropathy. A number of recent clinical trials have shown that ACEI and ATRA therapy can retard the progression of renal deterioration in patients with NIDDM and those with IgA nephropathy and even restore normal renal function in those with mild renal impairment. Treatment and control of proteinuria in patients with renal disease should be regarded as important as treatment of hypertension as it can prevent renal failure.
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PMID:Proteinuria: clinical signficance and basis for therapy. 1176 58

We recently observed that the course of glomerular filtration rate (GFR) rapidly declines in a subgroup of Type 2 diabetic patients (D) with abnormalities of albumin excretion rate (AER) and typical diabetic nephropathy, despite tight blood pressure control. The aim of this study was to evaluate whether amelioration of blood glucose control, using insulin, improves the course of GFR. GFR decay was measured by spline modeling analysis of the plasma clearance rate of 51CR-EDTA, assessed every 6 months. We identified two groups of D using morphometric analysis of renal biopsy, who had values of glomerular basement membrane (GBM) and fractional mesangial volume (Vv mes/glom) respectively below (Group A: 38) or above (Group B: 50) the mean+2SD of values found in 27 kidney donors (GBM: 389 nm; Vv mes/glom: 0.25), as previously described in detail. Median AER was similar at base line in the 2 groups (109 microg/min, 29-1950, in Group A, 113 microg/min, 37-1845, in Group B; n.s.). Conventional metabolic therapy (sulphonylureas and/or biguanides) was used both in Group A and B during a 3 year follow-up period (Period 1). Group B was further divided in two subgroups with body mass index below (Group B, a) and above (Group B, b) the value of 30 kg/m2. Mean +/- SD HbA1c was 8.2 +/- 1.6% in Group A, 8.3 +/- 1.7% in Group B (a) (n.s.) and 9.1 +/- 1.7% in Group B (b) (n.s.). Tight blood pressure control was achieved and maintained using angiotensin converting enzyme inhibitors and/or beta blockers and/or calcium antagonists and/or thiazides. The mean arterial blood pressure (MAP) was 92 +/- 3 mmHg in Group A and 91 +/- 4 mmHg in Group B (n.s.). GFR decay was significantly greater in Group B than in Group A (Group A vs B: +1.21 +/- 0.71 vs -5.86 +/- 1.61 ml/min/1.73 m2/year). Median AER significantly rose in Group B (177 microg/min, p<0.05 vs base line) but not in Group A (134 microg/min, n.s.) during the third year of follow-up. Groups A and B were then followed over 4.1 years (range 3.1-4.4) (Period 2) maintaining the above described antihypertensive regimen, resulting in MAP values similar to those described during Period 1. Group A patients were treated with the same conventional glycemic control during Period 2. Group B (a) was conversely treated with intensive insulin therapy to achieve a HbA1c value below 7.5% (3 daily injections of regular and 1 or 2 daily injections of intermediate acting insulin associated with metformin 500 mg twice daily in 64% of the patients). Group B (b) patients were only treated by metformin (850 mg thrice daily) to achieve a HbA1c value below 7.5%. HbA1c decreased below the 7.5% target value in Group B (a) (7.0 +/- 1.6%, p<0.01 vs Period 1), but not in Group B (b) (8.0 +/- 1.6%, p<0.05 vs Period 1) and in Group A (8.3 +/- 1.7%, n.s. vs Period 1). The GFR decay of Group B, a during Period 2 was lower than that during Period 1 (Period 1 vs Period 2: -5.9 +/- 1.8 vs -1.8 +/- 0.7 ml/min/1.73 m2/year, p<0.01). GFR decay during Period 2 was similar to that observed during Period 1 in Group A (Period 1 vs Period 2: +1.21 +/- 0.71 vs +0.7 +/- 0.6 ml/min/1.73 ml/year, n.s.) and in Group B (b) (Period 1 vs Period 2: -4.4 +/- 0.71 vs -4.2 +/- 0.6 ml/min/1.73 m2/year, n.s.). Median AER did not significantly change in the fourth year of Period 2 , either in Group A or B (Group A vs B: 141 vs 152 microg/min, n.s.). In conclusion, our findings seem to suggest that amelioration of blood glucose control is attained both by insulin and metformin intensive treatment, but only insulin decreases and maintains HbA1c levels below 7.5%. These pattens of HbA1c appear to be a threshold value in order to significantly blunt GFR decay in a subgroup of Type 2 diabetic patients with typical diabetic glomerular lesions, who are less responsive to tight blood pressure control alone. Conversely, the cohort of patients with less severe diabetic glomerulopathy steadily show constant GFR patterns, despite similar abnormalities of albumin excretion rate, and HbA1c average values above 7.5%.
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PMID:Evidence of a threshold value of glycated hemoglobin to improve the course of renal function in type 2 diabetes with typical diabetic glomerulopathy. 1178 2

Glomerulopathy, characterized by thickening of the glomerular basement membrane (GBM) and mesangial expansion, is the most important renal structural change in type 1 diabetic patients with diabetic nephropathy. Morphological lesions develop concomitantly in the arterioles, tubules and interstitium. Mesangial fractional volume [Vv(mes/glom)], an estimate of mesangial expansion, is the structural parameter that best correlates with glomerular filtration rate (GFR) and it is also closely related to the presence of proteinuria and hypertension. Diabetic glomerulopathy has also been described in type 2 diabetic patients, but glomerular lesions are milder than in type 1 diabetic patients. In type 2 diabetes glomerular structural parameters are, on average, altered. However, despite persistent microalbuminuria or proteinuria, several patients have normal glomerular structure. Renal structure is, in fact, heterogeneous in type 2 diabetic patients: only a subset has typical diabetic glomerulopathy, while a substantial proportion has more advanced tubulo-interstitial and vascular rather than glomerular lesions, or has normal or near normal renal structure. Also in type 2 diabetes mesangial expansion is related to renal functional parameters, but although significant, these structural-functional relationships are less precise than in type 1 diabetes. Thus, both in type 1 and in type 2 diabetes, mesangial expansion is the most important structural change. Finally, we have recently demonstrated that, the lesions of diabetic glomerulopathy can be reversed in humans. This amelioration in glomerular structure was observed after long-term normoglycemia obtained by pancreas transplantation. This is a new concept in nephrology, and the understanding of the mechanisms involved in the glomerular architectural remodelling might have important clinical and therapeutic implications.
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PMID:Role of mesangial expansion in the pathogenesis of diabetic nephropathy. 1179 46

Diabetic glomerulosclerosis is the most frequent cause of renal disease in patients with type II diabetes mellitus (DM), sometimes accompanied by vascular lesions. However, other glomerular pathologies are important in these patients. The aim of this study was to evaluate the prevalence of non-diabetic nephropathy (NDN) in selected patients with type II DM, and to identify clinical markers that may predict its presence in this population. We reviewed 20 renal biopsies performed on twenty patients with type II DM. Nine of them showed diabetic nephropathy (DN) (45%), whereas eleven showed NDN (55%): 1 IgA nephropathy, 3 vasculitis and 7 membranous nephropathy. We found no differences between the two groups with regard to sex, duration of DM, insulin therapy, glycosylated haemoglobin, proteinuria, presence of nephrotic syndrome, hypertension, serum IgA level or renal size. The NDN group had haematuria in 63.6%, whereas the patients with NDN had it in 44.4% (NS). Body mass index was higher in NDN patients (30 +/- 6.7 vs 22 +/- 2.9; p < 0.01), The same was true for creatinine clearance (82.2 +/- 51.4 ml/m vs 40.4 +/- 19.6 ml/m; p < 0.05). The age at the moment of diagnosis was higher in ND patients (67 +/- 11.2 vs 54.3 +/- 4.6; p < 0.05). The 3 patients who had diabetic retinopathy were found to have DN on renal biopsy (diagnostic specificity = 100%), although 66.7% of the patients with diabetic glomerulopathy had no retinopathy. We conclude that patients with type II DM with renal findings suggesting non-diabetic renal disease frequently it have NDN, and a renal biopsy must be performed. The presence of retinopathy has a predictive value of 100% in predicting DN, therefore its existence may make this diagnostic procedure unneccesary.
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PMID:[Renal histological lesions in patients with type II diabetes mellitus]. 1208 17

Diabetic glomerulopathy is a well-recognized consequence of both type I and type II diabetes. Occasionally, pathologic diagnosis may be challenging for the pathologist. These circumstances include atypical light microscopy or diabetic change with a second superimposed glomerulopathy (dual disease). We have compiled a selection of 12 renal biopsies from diabetic patients that show either an unusual pattern of nephropathy or "dual disease," as well as 2 cases in which the patient had no history of diabetes but had renal biopsies exhibiting changes consistent with diabetic nephropathy. The salient diagnostic features are discussed. To accurately assess these biopsies, immunofluorescence and electron microscopy become essential, and a broadened differential diagnosis must be considered.
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PMID:Diabetic glomerulopathy: unusual patterns and dual disease. 1218 Jun 36


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