Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Uninephrectomy (UNX) results in a higher incidence of focal glomerular sclerosis (FGS) in young rats than it does in adults. The reason for this higher susceptibility in young animals is not fully understood, but this does suggest that UNX in young rats may represent a particularly promising model in which to study the development of FGS. In the present study 10-day-old rats were subjected to UNX. After 4, 12 and 24 weeks, glomerular hypertrophy, structural lesions and function were analyzed in comparison with sham-operated controls. Up to the twelfth week, remnant kidney growth and glomerular growth proceeded in parallel; thereafter, kidney growth ceased, whereas glomerular growth continued undiminished. Twenty-four weeks after UNX, glomerular tuft volume in experimental animals exceeded that in controls by 80%. Twelve weeks after surgery, total GFR in UNX rats was approximately 80% of that in controls, a value maintained until the end of the observation period. Twenty-four weeks after surgery, heavy proteinuria was present in UNX animals. Structural abnormalities in glomeruli of UNX animals were already encountered 12 weeks after surgery; they were present to a much lesser extent in controls. In UNX animals these proceeded to the FGS stage by the end of the observation period. Three major groups of glomerular lesions were observed: (1) changes in the width and shape of glomerular capillaries. (2) changes in podocyte structure, and (3) tuft adhesions to Bowman's capsule with or without segmental sclerosis. The structural changes are analyzed in this and an accompanying paper [1]. The present paper deals with the widespread formation of irregular, giant capillary loops. They occur predominantly at the tuft periphery with a clear predilection for the vascular pole region. They are not a result of compensatory growth, but rather an expansion of single capillaries due to failure of the mesangium. Local disconnection of the mesangium from its anchoring points at the GBM leads to bulging and "coalescence" of capillary loops, resulting in abnormally-shaped vascular channels. This process is associated with a rearrangement of the corresponding mesangium. In our view, the appearance of dilated capillaries represents a local event pivotal to the development of more severe lesions, such as tuft adhesions and FGS.
 ...
PMID:Glomerular damage after uninephrectomy in young rats. I. Hypertrophy and distortion of capillary architecture. 163 43

Clearances of uncharged dextrans of broad size distribution were used to evaluate the effects of a 30 day course of enalapril on glomerular barrier function in 10 patients with IgA nephropathy and proteinuria (from 1.4 to 5.6 g/day). Dextran clearance experiments were repeated three times: before enalapril therapy, after 30 days of enalapril and again 30 days after enalapril withdrawal. GFR, but not RPF, was significantly reduced by enalapril (basal 38.3 +/- 11.9, enalapril 30.2 +/- 12.6 ml/min/1.73 m2) and returned to basal values after enalapril withdrawal. Urinary protein excretion and fractional clearance of albumin were both significantly reduced by enalapril (basal 2.3 +/- 1.1 g/day and 102 +/- 90 x 10(-5), enalapril 1.2 +/- 0.6 g/day and 51 +/- 23 x 10(-5), respectively) and returned to basal values after enalapril withdrawal. Transglomerular passage of large dextrans (radii 54 to 62 A), but not of lower size (26 to 42 A) were significantly lowered by enalapril. When enalapril was withdrawn the dextran-sieving profile returned comparable to the baseline levels. A theoretical analysis of dextran-sieving profiles indicated that enalapril lowered the radius of largest membrane pores. This effect was independent from glomerular hemodynamic changes. We conclude that angiotensin converting enzyme inhibitors (CEI) in humans with IgA nephropathy reduces urinary protein excretion by a primary action on the intrinsic glomerular membrane properties enhancing barrier size-selective function. The hypofiltration associated with enalapril therapy in these patients, which was eliminated by its withdrawal, has to be taken into account as a possible undesired effect of CEI in long-term treatment.
 ...
PMID:Angiotensin converting enzyme inhibition improves glomerular size-selectivity in IgA nephropathy. 171 13

To identify the specific in vivo renal effect of reactive oxygen species (ROS), hydrogen peroxide (H2O2) was infused directly into the left renal artery in Munich-Wistar rats. H2O2 (5 to 50 mumol over 1 h) induced a dose-dependent increase in urine protein excretion rate in infused kidneys, reaching a maximum at the dose of 35 mumol (on average, a 60-fold increase from baseline). The H2O2 (35 mumol)-induced proteinuria peaked over 1 h and completely normalized by 24 h after the infusion. Electrophoresis revealed that the urine protein is primarily of glomerular origin. Fractional clearances of graded-size neutral dextran of larger molecular radii, an index of glomerular size selectivity, were significantly and substantially elevated immediately but normalized by 24 h after the infusion. GFR and RPF rate remained unchanged throughout the entire time course examined. The H2O2-induced proteinuria was largely prevented by pretreatment with catalase (20 mg, iv) or deferoxamine (30 mg/100 g body wt, iv). Thus, iron-dependent metabolites of hydrogen peroxide appear to be involved in this proteinuria and glomerular size-selective defect. Light and electron microscopy, including determination of anionic site density at lamina rara externa of glomerular capillary wall by polyethyleneimine staining, did not reveal any appreciable abnormality throughout the study period, including at the peak of proteinuria. Thus, ROS can cause massive, reversible proteinuria by inducing a molecular size-selectivity defect of the glomerular capillary wall without apparent ultrastructural abnormalities. The results raise the possibilities: (1) that persistent proteinuria of a variety of renal diseases may reflect persistence of pathogenic ROS acting on glomeruli because the potent proteinuric effect of ROS can be transient (2) that the light and electron microscopy abnormalities in glomeruli of ROS-induced renal injuries reported thus far may have no direct causal linkage to proteinuria; and, finally, (3) ROS-induced reversible proteinuria may relate to the mechanism of clinical functional proteinuria, which involves increased oxygen and ROS metabolism, e.g., exercise-induced proteinuria.
 ...
PMID:Reactive oxygen metabolites cause massive, reversible proteinuria and glomerular sieving defect without apparent ultrastructural abnormality. 172 53

Circulating anticardiolipin antibodies are associated with recurrent thrombosis, fetal loss and thrombocytopenia. We have identified four patients with SLE or lupus-like disease who have high circulating levels of ACLA, repeated thrombosis and evidence of renal disease. Their clinical signs and symptoms of lupus activity were minimal, yet all had renal insufficiency with GFR 50 ml/min or less despite no history nor evidence of overt nephritis (proteinuria less than 0.5 g/day and no haematuria). Renal biopsy specimens showed focal ischaemic lesions with no evidence of active lupus nephritis. We describe a new lesion of renal ischaemia secondary to non-inflammatory vascular pathology associated with circulating ACLA.
 ...
PMID:Insidious loss of renal function in patients with anticardiolipin antibodies and absence of overt nephritis. 174 95

The renal impairments were studied clinicopathologically in 57 patients with progressive systemic sclerosis (scleroderma). Proteinuria, hematuria, azotemia and hypertension, used as markers for renal involvements, were observed in 3 (5.3%), 4 (7.0%), 2 (3.5%) and 6 patients (10.5%) respectively, at the initial examination. Hypertension was increased 2.6 times at the last observation, although the incidence of other three markers have not changed during the follow-up period. Finally, 17 out of 57 patients (29.8) revealed more than one of these clinical markers throughout the study. The decrease of GFR (CThio) was noticed in 3 out of 36 cases (8.3%), however that of RPF (CPAH) in 11 of 36 patients (30.6%), including 5 without abnormal clinical markers. Histological studies were performed in 12 patients. One showed crescentic glomerulonephritis, two membranous nephropathy, and the remaining 9 minor glomerular abnormalities. On the other hand, the vascular changes such as intimal proliferation of interlobular arteries were frequently observed. The frequency of pulmonary involvements, skin ulcer and gastro-intestinal involvement in the patients with renal lesions were not significantly different from that of the non-renal group. The level of RPF was significantly lower in the patients with skin ulcer than that of those without skin ulcer. No significant difference was noticed in the frequency of renal involvements between the patients with or without anti-Scl-70 antibody.
 ...
PMID:[Clinicopathological studies of renal disorders in patients with progressive systemic sclerosis]. 174 19

In an attempt to clarify the influence of pregnancy on the natural course of the chronic glomerulonephritis with impaired renal function (glomerular filtration rate: GFR less than or equal to 70 ml/min), the courses of 14 pregnancies occurring in 10 patients (seven with IgA nephropathy, one with membranoproliferative glomerulonephritis, one with membranous nephropathy and one with hereditary nephropathy) were studied. In 8 patients GFR measured before pregnancies ranged from 46 to 70 ml/min and in the other two creatinine clearance estimated in the first trimester of pregnancies was 62 and 49 ml/min, respectively. The pregnancies resulted in 10 live births, one spontaneous abortion, one artificial abortion and 2 neonatal deaths. In 2 out of 10 live births fetal weight was less than 2500 g. In 3 of 11 pregnancies there was neither increase in urinary protein nor elevation of blood pressure during pregnancies, while seven (64%) had increased proteinuria during the third trimester, and 4 of them were also complicated with hypertension. In 6 of 10 patients, there was no decrease in GFR during pregnancies. In three patients GFR was decreased from 70 to 36 ml/min, 70 to 58 ml/min and 62 to 48 ml/min, respectively. However, these reductions were considered to go with the natural course of respective patients because the reduction slopes were almost the same or rather mild in comparison with those estimated before or after pregnancies. The other patient also had a transient increase in serum creatinine level during two pregnancies, but the reciprocals of serum creatinine concentration before and after the pregnanciesdeclined linearly with time. These data suggest that pregnancy might have little influence on the natural course of the chronic glomerulonephritis even if complicated with renal functional impairment defined as GFR of 70 ml/min or less.
 ...
PMID:[Influences of pregnancy on the natural course of chronic glomerulonephritis with impaired renal function]. 177 Jun 39

Although the renal clearance of 99mTc-MAG3 is about 60% of the 131I-hippurate clearance, 99mTc-MAG3 clearance may be useful to estimate ERPF. In one study, however, proteinuria seemed to influence the MAG3/hippurate clearance ratio. In order to establish whether proteinuria or serum albumin level has influence on this ratio, a comparison was made between 99mTc-MAG3 clearance and 131I-hippurate clearance in 14 patients. There was a good linear correlation between MAG3 and hippurate clearance, although the standard error of estimate of ERPF from MAG3 was relatively large, which remained unexplained. No correlation was found between proteinuria and MAG3/hippurate clearance ratio nor between serum albumin level, GFR, FF, ERPF and the MAG3/hippurate clearance ratio. We therefore conclude that there is no correlation between proteinuria and albumin level and the MAG3/hippurate ratio. A reasonable estimation of ERPF with MAG3 can be made in patients with proteinuria and lowered serum albumin levels although the estimation may be less accurate.
 ...
PMID:Technetium-99m-MAG3 clearance as a parameter of effective renal plasma flow in patients with proteinuria and lowered serum albumin levels. 183 39

Experimental evidence suggests that pharmacological manipulations of glomerular haemodynamics may affect the progression of chronic renal insufficiency and scarring. In this study, we have investigated the short-term (4 weeks) renal haemodynamic effects of nifedipine and nitrendipine (10 mg/thrice daily) in two separate groups of 6 patients with stable chronic renal failure (CRF) (glomerular filtration rate, GFR: 9.7-47.8 ml/min/1.73 m2). Patients were studied on three occasions: (1) before the administration of the calcium antagonist, (2) after 4 weeks of treatment and (3) 4 weeks after the discontinuation of the drug. Mean arterial pressure fell significantly on nifedipine: from 116.33 +/- 12.25 to 107.22 +/- 18.67 mm Hg, p less than 0.05, and on nitrendipine: from 112.22 +/- 10.04 to 102.22 +/- 13.77 mm Hg, p less than 0.05. There was no significant effect of either calcium antagonist on GFR, effective renal plasma flow (ERPF), proteinuria or natriuresis. Consequently, renal vascular resistance (RVR) fell in both experimental groups, nifedipine: from 51.40 +/- 28.77 to 44.97 +/- 30 dyn s cm-5 x 10(3) (mean +/- SD), and nitrendipine: from 37.04 +/- 18.46 to 30.47 +/- 15.56 dyns s cm-5 x 10(3), p less than 0.05. These results show that calcium antagonists reduce systemic blood pressure whilst GFR and ERPF are maintained. The fall in the RVR of patients with CRF treated with calcium antagonists may confer on these agents a therapeutic advantage in the management of progressive renal insufficiency.
 ...
PMID:Short-term effects of calcium antagonists on renal haemodynamics in patients with chronic renal failure. 185 83

Twenty-four patients with idiopathic membranous nephropathy, long-lasting nephrotic syndrome and serum creatinine less than 2 mg/dl ate sequentially, in a randomized cross-over design, a normal protein diet containing 1.1 +/- 0.3 g/kg/day of proteins and a low protein diet containing 0.7 +/- 0.1 g/kg/day of protein, each diet for a period of 3 months. Both diets were low in fat (less than 30% of total calories) and cholesterol (less than 200 mg/day) content and rich in polyunsaturated fatty acids and in linoleic acid (10% of energy). Random assignment to one of the two 3 month diet periods was done after a RUN-IN period of at least one month on the hypolipidic normal protein diet. Glomerular filtration rate (inulin clearance), 24 hour urinary protein loss and serum albumin concentration did not significantly differ at the end of the two diet periods, indicating that long-term restriction of protein intake does not modify GFR or urinary protein loss in nephrotic patients. Serum total and LDL-cholesterol and daily proteinuria were significantly lower at the end of both diet periods than at the beginning and at the end of the RUN-IN period. We suggest that these changes were a consequence of the manipulation of dietary fat intake.
 ...
PMID:Effect of dietary proteins and lipids in patients with membranous nephropathy and nephrotic syndrome. 187 36

Genetic predisposition to essential hypertension, as indicated by increased maximal velocity of Na+/Li+ countertransport in red cells, has been suggested as a marker for the risk of developing diabetic nephropathy. To evaluate the validity of this concept in non-insulin-dependent diabetics, we measured the maximal velocity of Na+/Li+ countertransport in red cells in 18 male diabetics suffering from proteinuria due to biopsy proven diabetic glomerulosclerosis (GFR: 51 [range 27 to 146] ml/min/1.73 m2), 17 male diabetics with normoalbuminuria, and in 18 sex-, age-, and body mass index-matched healthy control subjects. Na+/Li+ countertransport was identical in patients with and without diabetic nephropathy, 0.43 (0.24 to 0.92) versus 0.44 (0.20 to 0.83) mmol/(liter cells x hr), but was elevated compared to control subjects, 0.32 (0.09 to 0.73; P less than 0.05). Arterial blood pressure was elevated in patients with nephropathy (162/92 +/- 21/9 mm Hg) compared to normoalbuminuric patients (132/82 +/- 15/7) and control subjects (133/83 +/- 14/7 mm Hg; P less than 0.001). Our study does not support the hypothesis that the risk of diabetic nephropathy in non-insulin-dependent diabetes is associated with a genetic predisposition to hypertension. Diabetes per se seems to enhance Na+/Li+ countertransport activity.
 ...
PMID:Red cell Na+/Li+ countertransport in non-insulin-dependent diabetics with diabetic nephropathy. 200 27


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>