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

The excretion rates of albumin, IgG and beta 2-microglobulin were studied in insulin-dependent diabetic patients with (Albustix positive) and without (Albustix negative) clinical proteinuria and in a group of nondiabetic controls. In patients negative for clinical proteinuria, the mean excretion rate of albumin and IgG was increased but that of beta 2-microglobulin was normal. HbA1, a measure of excess glycemia, was positively correlated with both albumin and IgG urinary excretion rates. Vigorous correction of glycemic control significantly reduced IgG excretion in nine patients. In patients positive for clinical proteinuria, albumin and IgG clearances were inversely correlated with GFR, the filtration of IgG increasing relatively more than that of albumin as GFR declined. A negative hyperbolic correlation was found between GFR and beta 2-micro-globulin excretion. In this group HbA1 was unrelated to excretion rates or clearances of albumin and IgG. In clinically proteinuric patients, long-term correction of hyperglycemia by continuous subcutaneous insulin infusion failed to check the increasing albumin and IgG filtration. The microproteinuria of diabetes is glomerular in origin, is influenced by prevailing glycemia, and is reversible by vigorous glycemic control. In the clinically proteinuric phase, by contrast, selectivity is progressively lost and, as GFR falls, proteinuria becomes of a mixed glomerular and tubular origin. There is no evident association with prevailing glycemia, and metabolic near-normalization dose not appear to affect progression over the period of observation considered. This study suggests that clinical proteinuria denotes the installation of a self-maintaining process, largely independent of the diabetic metabolic disturbance which gave rise to it. Prevention of clinical diabetic nephropathy by metabolic correction may be achievable only in the phase of early microproteinuria.
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PMID:Proteinuria in diabetes mellitus: role of spontaneous and experimental variation of glycemia. 705 May 9

The diagnostic value of the measurement of quantitative proteinuria in patients with a creatinine clearance of less than 10 ml/min was determined in patients seen in a single center over a 5-year period. All 126 patients in whom a definitive renal diagnosis was possible were included. Patients with glomerular disease excreted 6.1 +/- 0.6 g/day and patients with interstitial disease 1.5 +/- 0.3 g/day (p less than 0.001). In individual patients with end-stage renal disease, however, measurement of urinary protein excretion excluded (with 95% confidence levels) patients with interstitial diseases only when greater than 2.9 g/day. To examine the natural history of proteinuria in progressive renal disease, urinary protein, absolute and factored for glomerular filtration rate (GFR; creatinine clearance), was determined at 10 ml/min decrements in GFR for patients with membranoproliferative glomerulonephritis, idiopathic membranous glomerulonephritis and focal glomerulosclerosis. Quantitative urinary protein excretion was relatively constant as GFR fell but did fall significantly at less than 10 ml/min but only to 4.8-7.0 g/day at even that level. Urinary protein excretion/GFR increased as GFR fell, particularly at end stage where a highly significant four-fold rise was seen; an increase also occurred in patients with primary interstitial disease. Similar data were obtained for 34 randomly selected patients after at least 1 year of chronic hemodialysis. Although a significant decline in absolute urinary protein excretion occurred during the year of dialysis to levels not different between glomerular and interstitial disease, urinary protein excretion/unit GFR remained elevated. Increased urinary protein excretion/unit GFR may result from a functional adaptation of remaining nephrons in response to declining renal mass.
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PMID:Quantitative urinary protein excretion in chronic renal failure. 714 93

To test whether angiotensin (AII) induces proteinuria via its effect on renal hemodynamics, or by another mechanism, two experimental approaches were used. In the first, it was found that AII was as effective in inducing proteinuria in nephrotic as in intact rats. In all AII augmented proteinurias, filtration fraction was increased. These effects plus electrophoretic profiles of AII proteinuria in intact rats suggested that hemodynamic changes underly the increased glomerular permeability to protein. In the second approach, the AII inhibitor, sar-ala-angiotensin, does not itself induce proteinuria or changes in GFR and RPF, but prevented the hemodynamic responses to AII and the proteinuric response as well.
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PMID:On the mechanism of angiotensin-induced proteinuria. I. Studies in aminonucleoside nephrotic rats and in saralasin blockade. 721 37

We assessed the effects in isolated perfused rat kidneys of adding globulin or erythrocytes to Krebs-Henseleit bicarbonate perfusate with albumin as its principal source of colloid osmotic pressure during 3 h of perfusion. Colloid osmotic pressure varied between 11 and 58 mmHg. Bovine or human immunoglobulin substituted in part for albumin produced vasodilation, whereas rat erythrocytes added to albumin at a 5% hematocrit caused vasoconstriction. Inclusion of both globulin and erythrocytes in the perfusate was associated with an intermediate response. Kidneys perfused with albumin alone showed progressive decline in GFR, increasing vascular resistance, and increasing proteinuria correlating with kidney weight gain during perfusion. Onset of GFR and resistance changes were delayed and their magnitude decreased by increasing oncotic pressure. Estimated glomerular filtrate protein concentration of albumin-perfused kidneys progressively increased from 20 to 150 mg/dl. The presence of erythrocytes or globulin in the perfusate prevented the increase in vascular resistance and reduced the degree of decrease in GFR seen with albumin alone in the perfusate and reduced the time-dependent increase in proteinuria by 80%. The effects of globulin and erythrocytes on proteinuria were additive. The prevention of changes in hemodynamics, glomerular filtration, macromolecular clearance, subcapsular fluid accumulation, and organ weight gain for up to 5 h of perfusion by adding erythrocytes and globulins to the albumin perfusate suggest that these agents may be necessary for preventing interstitial edema and for maintaining renal function in vitro.
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PMID:Effect of erythrocytes and globulin on renal functions of the isolated rat kidney. 727 Jun 85

The aminonucleoside of puromycin induces proteinuria and renal damage when given to rats. Aminonucleoside of puromycin was administered to male Wistar-Furth rats as a single intravenous injection in a dose of 15 mg. per 100 gm. of body weight. The animals were studied 9 days later when the mean urinary protein was 175 mg. per 24 hours. Evidence of glomerular epithelial cell injury included massive obliteration of foot processes, appearance of microvilli, protein reabsorption droplets, extreme attenuation of cytoplasm with formation of blebs, and focal detachment of epithelial cells from glomerular basement membrane. An increase in both the amount of mesangial matrix and the number of mesangial cells was also observed. The fractional clearance (C/GFR) of anionic horseradish peroxidase had increased 18.5 times as compared to control values and was nearly equal to the C/GFR of neutral horseradish peroxidase in the experimental rats. The C/GFR of cationic horseradish peroxidase was decreased by one-third so that it approximated the C/GFRs of both anionic and neutral horseradish peroxidase. These findings indicate a nearly complete loss of the charge-selective barrier to filtration. In addition, C/GFRs of tritiated uncharged dextrans with a range of molecular radii from 18 to 58 Angstrom (A) were determined. The C/GFRs of dextrans (alpha e less than 30 A) were decreased in the experimental rats as compared to C/GFRs of dextrans of corresponding molecular size in control rats. However, the C/GFRs of dextrans (alpha e greater than 38A) were increased in experimental as compared to control rats. Further, both anionic and cationic ferritin (alpha e = 61 A) were observed in the urinary space near denuded areas of glomerular basement membrane. These results indicate that the size-selective properties of the glomerular barrier to filtration have been modified with decreased C/GFR of small molecules and increased C/GFR of large molecules. Thus, the proteinuria of aminonucleoside nephrosis in rats occurs secondary to alterations in both the charge- and size-selective barriers to glomerular filtration.
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PMID:Alterations in the charge and size selectivity barrier of the glomerular filter in aminonucleoside nephrosis in rats. 746 51

Cyclosporin A (CsA) can reduce proteinuria in various forms of human and experimental glomerulonephritis. This antiproteinuric effect of CsA may be the consequence of diminution of immunological damage, a drug-induced decrease of GFR, or changes in permselectivity of the glomerular basement membrane (GBM). We studied the antiproteinuric effect of CsA in the heterologous phase of a passively induced anti-GBM nephritis in the mouse. This passive model is characterized by acute exudative glomerular lesions and a dose-dependent albuminuria. Rabbit anti-mouse GBM antibodies were administered intravenously in C57B110 mice at day 4, after 3 days of pretreatment with either CsA (75 mg/kg body weight) (n = 15) or olive oil (OO, controls, n = 15) orally. CsA did not influence the severity of the histological lesions. Albuminuria was substantially reduced by CsA (CsA 1.6 +/- 1.8; OO 5.6 +/- 3.2 mg/18 h; P < 0.002). There was a considerable concomitant reduction of the GFR by CsA, as measured with a 51Cr-EDTA single-shot plasma clearance technique before (day-1) and during treatment (day 4): GFR ratio day 4/day-1 for CsA, 0.4 +/- 0.1; for OO controls, 1.1 +/- 0.6; P < 0.01. This drug-induced decrease of GFR was prevented by simultaneous treatment with phenoxybenzamine (PB) twice daily 45 micrograms orally for 4 days (GFR ratio day 4/day-1 for PB and CsA, 0.9 +/- 0.4; controls (PB and OO), 1.0 +/- 0.4; P = NS). Although the CsA-induced GFR reduction was prevented, CsA still reduced albuminuria significantly (PB and CsA, 2.2 +/- 1.8; controls (PB and OO), 5.6 +/- 1.8 mg/18 h; P = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyclosporin A reduces albuminuria in experimental anti-GBM nephritis independently from changes in GFR. 747 16

An earlier controlled trial showed that over an average of 26 months, enalapril slowed the progression of chronic renal failure. Following completion of the trial, the patients continued to receive antihypertensive treatment according to ordinary clinical criteria. All but four patients in the enalapril group remained on that drug, and two patients in the control group were switched to an angiotensin-converting enzyme (ACE) inhibitor. In the present study the fate of the 70 patients 44 months after termination of the trial was investigated, with a total follow-up of around 7 years. In the original enalapril group, 12 of the 35 patients (34%) were alive without renal replacement therapy versus five of the 35 patients (14%) in the control group. This difference of 20% in favour of having been in the enalapril group in the original trial was significant (P = 0.05; 95% confidence limits 0.5-39.5%). The influence of baseline proteinuria on clinical outcome was analysed. In the original control group, baseline renal clearances of albumin (Calb) and immunoglobulin G (CIgG) were significantly lower in patients surviving without renal replacement therapy at follow-up than in patients who ultimately developed end-stage renal failure (ESRF) (P < 0.05). In the original enalapril group, these baseline clearances were equal in the two renal outcome groups. In all patients, baseline Calb and CIgG were negatively correlated with the rate of change in GFR during the controlled trial (r = -0.37, P < 0.01 and r = -0.28, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Late outcome of a controlled trial of enalapril treatment in progressive chronic renal failure. Hard end-points and influence of proteinuria. 747 21

Fifty-five renal allografts (44 from living-related and 11 from cadaver donors) that have functioned for at least 20 years (mean 22.9 +/- 2.3, range 20.1 to 30.7 years) were evaluated in three groups based on renal function: group I (n = 26), with a GFR of > or = 60 ml/min/1.73 m2 or serum creatinine < or = 1.4 mg/dl and no proteinuria; group II (n = 9), with a GFR of > or = 60 ml/min/1.73 m2 or serum creatinine < or = 1.4 mg/dl but > 150 mg proteinuria/24 hr; and group III (n = 20), with a GFR < 60 ml/min/1.73 m2 and/or serum creatinine > 1.4 mg/dL with or without proteinuria. Allograft factors, including acute rejection (AR) in 62% (34/55) and delayed function (DF) in 55% (6/11) of the cadaver grafts, did not preclude 20-year success and the prospect of continued survival since they were not significantly more frequent in group I, II, or III. However, AR was confined to a limited period within the first three months posttransplant in 18/18 recipients in groups I and II but only in 7/16 of group III (P = 0.0002). In groups I and II AR was treated with IVMP in 14/18 cases and only 6/16 in group III (P = 0.035). Donor age < or = 50 years and recipient age < or = 40 years each occurred in 87% (48/55) of these transplants. One- or two-HLA haplotype matching was present in 98% (43/44) of living related transplants. Major risks to the recipient were coronary artery disease (11 cases and 3 deaths), malignancy (18 cases and 1 death), and severe infection and hepatitis (35 cases and 3 deaths, 2 of whom also had coronary artery disease). Hypertension occurred in 25 recipients and diabetes mellitus in 12. Potential open-end success was compromised by renal dysfunction in groups II and III, but appeared possible in 12 of the 26 patients in group I. There is no apparent "safe-haven" point of time for immunosuppressed renal allograft recipients, who remain at increased risk for eventual renal allograft dysfunction, as well as cardiovascular, neoplastic, infectious, and metabolic diseases. In order to clarify and standardize the words "long-term," a simple classification of long-term allograft survivals is proposed.
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PMID:The fate of renal allografts functioning for a minimum of 20 years (level 5A)--indefinite success or beginning of the end? A proposed classification of long-term allograft survivals. 748 35

The detection of overt albuminuria (> 300 mg/g creatinine) in the absence of azotemia was used to diagnose early nephropathy in 34 Pima Indians with NIDDM of 16 +/- 1 years duration. Differential solute clearances were performed serially to define the course of the glomerular injury over 48 months. At baseline, the GFR (107 +/- 5 ml/min), filtration fraction and sieving coefficients of relatively permeant dextrans (< 52 A) were all depressed below corresponding values in 20 normoalbuminuric Pima Indians with a similar duration of NIDDM. Over the ensuing 48 months the GFR (-34%) and filtration fraction (-13%) in the nephropathic patients declined further. The sieving coefficients of large, nearly impermeant dextrans (> 56 A radius) increased selectively and fractional clearances of albumin and IgG increased correspondingly by > 10-fold. Analysis of the findings with pore theory revealed: (1) a progressive decline in pore density and the ultrafiltration coefficient (Kf); and (2) broadening of glomerular pore-size distribution that resulted in greater prominence of large pores (> 70 A radius). We conclude that increasing loss of intrinsic ultrafiltration capacity is the predominant cause of the early and progressive decline in GFR that follows the development of nephropathy in NIDDM. We speculate that progressive impairment of barrier size-selectivity contributes to but does not fully account for the increasingly heavy proteinuria that is observed early in the course of this disorder.
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PMID:Progression of overt nephropathy in non-insulin-dependent diabetes. 754 61

These studies investigate glomerular hemodynamic responses to pregnancy in rats with 5/6th reduction of renal mass of four weeks duration. Both preglomerular and efferent arteriolar resistances (RA and RE) fell significantly at midterm although single nephron glomerular filtration rate (SNGFR) and glomerular plasma flow (QA) were unchanged versus virgins. In late pregnant rats with reduction of renal mass, the gestational fall in RA and RE was maintained and GFR, RPF, SNGFR and QA were higher compared to virgins. The gestational renal vasodilation was prolonged in this model of hypertension versus normals and a peripheral vasodilation is also indicated by the late fall in blood pressure. In virgins with 5/6th reduction of renal mass, PGC is elevated but in pregnant rats PGC fell towards term. The value of Kf was doubled in late pregnancy compared to virgins. All three groups of rats with reduction of renal mass showed similar proteinuria and similar levels of focal glomerular sclerosis, suggesting that pregnancy did not exacerbate the glomerular damage in this model of hypertension and renal disease. A decrease in hematocrit in late pregnancy compared with both virgin and midterm pregnancy indicated a plasma volume expansion. We conclude that when superimposed on hypertension with glomerular damage due to 5/6th reduction of renal mass, pregnancy induced gestational renal and peripheral vasodilation and plasma volume expansion. Since pregnancy was antihypertensive and lowered PGC, there was no hemodynamic basis for pregnancy-associated exacerbation of damage in this model of glomerular injury.
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PMID:Glomerular hemodynamic responses to pregnancy in rats with severe reduction of renal mass. 756 89


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