Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q92565 (GFR)
 4,179 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In latent hereditary diabetes mellitus increased protein excretion has been found in male diabetic mice compared to controls. This proteinuria is partly due to an increased excretion of higher molecular weight proteins, which could be identified as deriving from plasma. The suggested glomerular proteinuria has been verified by an increase in the renal excretion of high molecular weight PVP. No changes in GFR occurred in this early stage of diabetic glomerulopathy. No changes in morphology could be detected, suggesting some changes in the biochemical membrane structure that cause the findings of increased permeability of the diabetic basement membrane for plasma proteins.
 ...
PMID:Functional and morphological study on the onset of proteinuria in experimental diabetes mellitus. 123 92

A number of risk factors associated with the development of diabetic nephropathy has been described, such as elevated blood pressure, poor metabolic control, hyperlipidemia, and smoking. Abnormal albuminuria also is associated with progression of renal disease, but has until recently been considered principally a marker of disease activity rather than a risk factor. This article discusses the role of elevated blood pressure versus abnormal albuminuria in a genesis and prediction of renal disease in diabetes. Controversy exists regarding parental disposition to hypertension and early blood pressure elevation in the course of diabetes, but all studies agree that elevated blood pressure--in the presence of abnormal albuminuria--constitutes a risk factor. Because abnormal albuminuria is associated with progression disease, it may itself be a risk factor because increased macromolecular traffic over the glomerular membrane may produce glomerulopathy. Problems related to blood pressure measurement are important, and 24-h recordings of blood pressure may be recommended in some situations. Regarding renal structure, preliminary results suggest that structural lesions precede blood pressure elevation. The solid end point for evaluation of renal disease progression is the fall rate of GFR, with abnormal albuminuria as an intermediate end point, also in drug trials. Abnormal albuminuria may constitute a new indication for antihypertensive treatment, being, as it is, a clear indicator of organ damage, whereas elevated blood pressure with normal AER may not increase risk substantially.
 ...
PMID:Blood pressure elevation versus abnormal albuminuria in the genesis and prediction of renal disease in diabetes. 139 16

Glomerular hemodynamics were measured in male Sprague-Dawley rats, aged 4 to 5 months (young) or 20 to 22 months (old). Body weight (BW) and left kidney weights (KW) were higher in old rats than young (BW: 507 +/- 12 g v 342 +/- 11 g, P less than 0.001; KW: 2.0 +/- 0.1 g v 1.3 +/- 0.1 g, P less than 0.001). Arterial blood pressure (AP) was slightly higher in old rats, but within the normotensive range (106 +/- 4 mm Hg v 94 +/- 4 mm Hg, P less than 0.05). Glomerular filtration rate (GFR; factored for KW) was lower in old versus young rats (0.67 +/- 0.05 mL/min/gKW v 1.00 +/- 0.08 mL/min/gKW, P less than 0.02). The cortical surface of the kidney in old (but not young) rats showed marked heterogeneity and single-nephron (SN)GFR was measured only in filtering nephrons and was higher and more variable in old versus young rats. Glomerular blood pressure (PGC) was unchanged in old compared with young rats (53 +/- 4 mm Hg v 55 +/- 2 mm Hg). There was a significantly greater level of glomerular sclerosis (in outer cortical glomeruli) in old versus young rats, and glomerular volume was substantially greater in old rats. This study suggests that age-related glomerulopathy is not primarily mediated by glomerular capillary hypertension.
 ...
PMID:The effect of aging on glomerular hemodynamics in the rat. 162 81

Diabetic nephropathy, clinically defined by overt albuminuria, hypertension and declining GFR, affects 25-35% of IDDM patients. The risk of nephropathy peaks during the second decade of IDDM and declines thereafter, suggesting that only a subset of IDDM patients is at risk for nephropathy. A role for hypertension in the progression of established renal damage in IDDM is now accepted; however the role of hypertension in the genesis of diabetic nephropathy is not yet clear. Mesangial expansion is a characteristic lesion of diabetic nephropathology and correlates with renal function. Functional studies are not indicative of underlying renal pathology except relatively late, when glomerular injury is advanced. Microalbuminuria in the 'predictive' range (greater than 30 micrograms/min) and associated with hypertension and/or declining GFR is a marker of established diabetic glomerulopathy. Only carefully designed longitudinal studies of renal morphology and function with accurate blood pressure monitoring beginning early in the course of IDDM will clarify the relationships between blood pressure and renal damage in IDDM. In NIDDM the frequent presence of non-diabetic renal lesions, of hypertension at or before the onset of diabetes, and the relative paucity of clinical-pathological correlations currently make it difficult to understand the role of hypertension in the genesis and progression of nephropathy. Again, longitudinal studies of blood pressure and renal structure and function are required in NIDDM patients. Finally, animal models of hypertension and diabetes may aid progress in these areas.
 ...
PMID:Hypertension and diabetic renal disease. 179 13

Hyperfiltration is a very characteristic feature in insulin-dependent diabetes. Hyperfiltration is to some extent associated with long-term glycemic control but the correlation is not very strong. Long-term hyperfiltration may play a role in the genesis of late diabetic nephropathy, but it is difficult to distinguish effects of hyperfiltration per se from effects of poor metabolic control. Long-term hyperfiltration without diabetes does not produce nephropathy. It is hypothesized that IDDM patients who do not show considerable hyperfiltration in spite of poor metabolic control may be those who are to some extent protected against late diabetic nephropathy, but other mechanisms may also be involved in the renal protection of these patients, who survive long-term diabetes without nephropathy. On the other hand, those with poor metabolic control combined with hyperfiltration are likely to develop nephropathy. In addition, it is suggested that the metabolic aberrations in diabetes, with the subsequent changes in the biochemistry of the glomerular wall, are permissive and absolutely required for the development of diabetic nephropathy. Of note, diabetic glomerulopathy in NIDDM occurs without significant hyperfiltration and extreme hyperfiltration in the one-kidney-model (without diabetes) does not produce nephropathy. Nonglycemic modalities of intervention, resulting in reduced hyperfiltration, e.g., low-protein diet or administration of somatostatin analogues, deserves interest as new potential ways of preventing or postponing diabetic nephropathy. Also intervention with aldose-reductase inhibitors may be an important therapeutic modality for those patients in whom good metabolic control is not obtainable. It is now well-established that antihypertensive treatment, including ACE-inhibition, reduces rate of decline in GFR in patients with already established nephropathy. In addition, protein excretion is diminished in IDDM patients with incipient diabetic nephropathy by antihypertensive treatment where GFR is well-preserved during treatment. No data are available for NIDDM.
 ...
PMID:Comparative renal pathophysiology relevant to IDDM and NIDDM patients. 306 56

Diabetic glomerulopathy is characterized by a very slow development of basement membrane (BM) accumulation, manifested as thickening of the peripheral BM and increased volume of the mesangial BM-like material (BMLM) with mesangial expansion. The initiation of the process is probably at the onset of diabetes since the BM thickening is detectable after a few years. The BM accumulations at the two sites (PBM and BMLM) in the glomerular tuft are considered as two different expressions of a fundamental BM abnormality. The two locations present different conditions for quantitation, may have a different biochemical make-up, and immediate functional implications of the abnormalities may differ as well. In the long run, however, the two in concert lead to the ultimate solidification of the glomerular tuft with loss of capillary surface. The end-stage is glomerular closure, with elimination of glomerular function. A very close correlation has been found between the total remnant surface area of the glomerular capillaries and the level of GFR. Along with the classical changes of the diabetic glomerulopathy, changes in glomerular size are detectable. In early diabetes during the stages of glomerular hyperfunction, hypertrophy develops acutely at the onset of diabetes, leading to an increase in capillary surface corresponding to the increase in filtration rate. In the advanced stages when glomerular closure involves a proportion of the nephrons compensatory hypertrophy develops, thereby probably helping to preserve capillary surface for a period of time. The exact mechanisms that may influence these developments are not known, but underlying them all are the metabolic abnormalities of diabetes.
 ...
PMID:Structural changes in the diabetic kidney. 353 98

The earliest manifestations of clinical diabetic nephropathy, including proteinuria, hypertension, and declining GFR, represent very advanced diabetic glomerulopathy with especially prominent mesangial expansion. Mesangial expansion, by restricting glomerular capillary filtration surface and lumenal volume, stimulates compensatory mechanisms analogous to those resulting from a marked reduction in nephron number. These compensatory mechanisms involve alterations in glomerular hemodynamics designed to maintain glomerular filtration but which ultimately injure the kidney. These hemodynamic perturbations are not specific to diabetes but represent a final common pathway toward endstage renal failure that also characterizes the remnant kidney. This thesis concludes that the onset of clinical diabetic nephropathy augurs inevitable decline in kidney function, and that only studies and interventions exercised before clinical nephropathy develops can influence understanding and outcome of diabetic nephropathy.
 ...
PMID:Diabetic nephropathy. A perspective. 640 Jun 68

We recently demonstrated that recombinant hGH exacerbates renal functional and structural injury in chronic puromycin aminonucleoside (PAN) nephropathy, an experimental model of glomerular disease. Therefore, we examined whether recombinant human (rh) IGF-I is a safer alternative for the treatment of growth failure in rats with chronic PAN nephropathy. The glomerulopathy was induced by seven serial injections of PAN over 12 wk. Experimental animals (n = 6) received rhIGF-I, 400 micrograms/d, whereas control rats (n = 6) received the vehicle. rhIGF-I improved weight gain by 14% (p < 0.05), without altering hematocrit or blood pressure in rats with renal disease. Urinary protein excretion was unaltered by rhIGF-I treatment in rats with chronic PAN nephropathy. After 12 wk, the inulin clearance was higher in rhIGF-I-treated rats, 0.48 +/- 0.08 versus 0.24 +/- 0.06 mL/min/100 g of body weight in untreated PAN nephropathy animals, p < 0.05. The improvement in GFR was not associated with enhanced glomerular hypertrophy or increased segmental glomerulosclerosis, tubulointerstitial injury, or renal cortical malondialdehyde content. In rats with PAN nephropathy, administration of rhIGF-I increased IGF-I and GH receptor gene expression, without altering the steady state level of IGF-I receptor mRNA. In normal rats with intact kidneys, rhIGF-I administration (n = 4) did not alter weight gain, blood pressure, proteinuria, GFR, glomerular planar area, renal cortical malondialdehyde content, or glomerular or tubulointerstitial damage, compared with untreated animals (n = 4). rhIGF-I treatment reduced the steady state renal IGF-I mRNA level but did not modify gene expression of the IGF-I or GH receptors. We conclude that: 1) administration of rhIGF-I improves growth and GFR in rats with chronic PAN nephropathy and 2) unlike rhGH, long-term use of rhIGF-I does not worsen renal functional and structural injury in this disease model.
 ...
PMID:The effect of recombinant human insulin-like growth factor-I on chronic puromycin aminonucleoside nephropathy in rats. 882 80

We characterized glomerular function in adults with sickle cell anemia (SSA): 12 with normal renal function (SSA-controls), and 15 with renal insufficiency (SSA-CRF). GFR was similar in SSA-controls and healthy-controls, however, renal plasma flow was increased in SSA-controls. In SSA-CRF, the albumin and IgG excretion rates were enhanced. The fractional clearances of all dextran sizes (26 to 64 A) were significantly increased in both SSA-controls and SSA-CRF versus healthy-controls. In SSA-CRF, the fractional clearance of dextrans > 58 A was enhanced. Analysis with an "isoporous+shunt" model revealed an increase in the mean restrictive pore radius (ro) by 5 A in SSA-controls and SSA-CRF, versus healthy-controls. In SSA-CRF, the total number of membrane pores was reduced > 70%, and the shunt parameter increased twofold. We conclude that SSA patients have a distinct pattern of glomerular dysfunction with generalized increased permeability to dextrans, resulting from an increase in pore radius. When CRF develops, the total number of membrane pores is reduced, and a size-selectivity defect occurs. The changes in dextran permeability cannot be attributed to purely hemodynamic changes (increased RPF or low filtration fraction), or to known modulators of membrane porosity. These findings suggest that unique mechanism(s) are implicated in the pathogenesis of sickle glomerulopathy.
 ...
PMID:Sickle cell anemia causes a distinct pattern of glomerular dysfunction. 906 17

Renal interstitial expansion is now considered a useful marker of progression of several nephropathies. This study describes a multicenter, prospective, double-blind, placebo-controlled, randomized trial of the effects of Perindopril (4 mg/d) on kidney structure and function over 2 yr in 26 type 2 diabetic patients with proteinuria ranging from 70 to 4210 mg/d and relatively preserved GFR (creatinine clearance >60 ml/min). All patients underwent baseline renal biopsy, but four (15%) were not randomized because of the presence of nondiabetic nephropathy. The remaining 22 were randomized ( 11 to Perindopril [PE], 11 to placebo [PO]), and 19 (9 PE, 10 PO) underwent follow-up biopsy at 2 yr. BP was controlled equally in both groups throughout. Proteinuria increased in PO patients (+1562 mg/d) but declined in PE patients (-156 mg/d) (P < 0.05). Morphometric analysis was performed by light microscopy using a Biocom computer. Over the 2 yr, mean cortical interstitial fractional volume identical at baseline increased significantly in PO patients (31.7 +/- 5.3 versus 40.2 +/- 11.1%; P = 0.001) but was unchanged in PE patients (33.8 +/- 4.9 versus 34.7 +/- 6.6%; P = 0.50). It is concluded that: (1) nondiabetic nephropathy is present in approximately 15% of albuminuric type 2 diabetic patients; and (2) Perindopril prevents interstitial expansion in hypertensive patients with biopsy-proven diabetic glomerulopathy. These results support a role of angiotensin II in the progression of interstitial changes in type 2 diabetic patients with nephropathy.
 ...
PMID:Expansion of cortical interstitium is limited by converting enzyme inhibition in type 2 diabetic patients with glomerulosclerosis. The Diabiopsies Group. 1036 63


1 2 Next >>