Proteinuria in Patients with Cirrhosis: Relationship between Renal and Hepatic Function

1982 ◽  
Vol 63 (4) ◽  
pp. 387-392
Author(s):  
L. Milani ◽  
A. Gatta ◽  
C. Merkel ◽  
A. Ruol
Keyword(s):  
Liver Damage ◽  
Hepatic Function ◽  
Glomerular Permeability ◽  
Acid Glycoprotein ◽  
Β2 Microglobulin ◽  
Protein Excretion ◽  
Α2 Macroglobulin ◽  
Class B ◽  
Fractional Clearance ◽  
Renal Tubular

1. In 37 patients with cirrhosis of the liver of different severity (11 in class A, 18 in class B, and 8 in class C, according to Child's criteria modified by Hobbs), inulin and p-aminohippurate clearances, total fractional protein excretion and the fractional clearances of α1-acid glycoprotein, albumin, transferrin, α2-macroglobulin and β2-microglobulin (in 20 patients) were determined. 2. Inulin clearance was lower than 70 ml/min in 19 patients and p-aminohippurate clearance was lower than 300 ml/min in 20 patients. Total fractional protein excretion was above normal in 19 patients; α1-acid glycoprotein fractional clearance was above normal in 11, albumin fractional clearance in 10, transferrin fractional clearance in five, α2-macroglobulin fractional clearance in three, and β2-microglobulin fractional clearance in 10. 3. The increases in protein excretion were independent of any impairment of renal tubular function. An inverse relationship between protein excretion and the clearances of inulin and p-aminohippurate was found. No difference in protein excretion was found between the three groups of patients with different degrees of liver damage. 4. The results suggest that in cirrhosis an increase in glomerular permeability is frequent, though generally slight; it is correlated with an impairment of kidney function and is independent of the severity of the liver damage.

Anti-GBM antibody-induced proteinuria in isolated perfused rat kidney

1985 ◽  
Vol 249 (2) ◽  
pp. F241-F250 ◽  
Author(s):  
W. G. Couser ◽  
C. Darby ◽  
D. J. Salant ◽  
S. Adler ◽  
M. M. Stilmant ◽  
...  
Keyword(s):  
Rat Kidney ◽  
Sodium Reabsorption ◽  
Glomerular Permeability ◽  
Flow Rates ◽  
Fluorescent Markers ◽  
Protein Excretion ◽  
Perfusate Flow ◽  
Perfused Rat Kidney ◽  
Fractional Clearance ◽  
And Control

The effect of anti-GBM antibody on protein excretion was studied in isolated rat kidneys perfused with 20 mg of sheep anti-rat GBM (experimental) or nonantibody sheep IgG (control). Six control kidneys excreted 176 +/- 31 micrograms/min of BSA initially, rising to 296 +/- 111 micrograms/min at 2 h. Fractional clearance of BSA rose from 0.51 to 1.70%. Eight experimental kidneys excreted 211 +/- 56 micrograms/min of BSA, increasing to 1,924 +/- 804 micrograms/min at 2 h. Fractional BSA clearance increased from 0.56 to 11.49%. After 60 min, BSA excretion in anti-GBM-perfused kidneys exceeded controls by a factor of 6.5-7.9 (P less than 0.05) and fractional BSA clearance exceeded controls by a factor of 5.8-7.1 (P less than 0.05). Studies with fluorescent markers indicated proteinuria to be of glomerular origin in antibody-perfused kidneys. There were no significant differences between anti-GBM-perfused and control kidneys in perfusion pressures, perfusate flow rates, urine flow rates, inulin clearance, or sodium reabsorption. Antibody to GBM can induce a marked increase in glomerular permeability to BSA and IgG without participation of other systemic humoral or cellular mediation systems.

Osteopontin expressed by renal tubular epithelium mediates interstitial monocyte infiltration in rats

2000 ◽  
Vol 278 (1) ◽  
pp. F110-F121 ◽  
Author(s):  
Hirokazu Okada ◽  
Kenshi Moriwaki ◽  
Raghuram Kalluri ◽  
Tsuneo Takenaka ◽  
Hiroe Imai ◽  
...  
Keyword(s):  
Target Genes ◽  
Renal Plasma Flow ◽  
Mrna Level ◽  
Antisense Oligodeoxynucleotide ◽  
Tubular Epithelium ◽  
Rt Pcr ◽  
Goodpasture Syndrome ◽  
Renal Tubular Epithelium ◽  
Protein Excretion ◽  
Renal Tubular

In this study, we have shown that intravenously administered antisense oligodeoxynucleotide (ODN) was demonstrated to be taken up by tubular epithelium, after which it blocked mRNA expression of target genes in normal and nephritic rats. Therefore, we injected osteopontin (OPN) antisense ODN to Goodpasture syndrome (GPS) rats every second day between days 27 and 35, the time when renal OPN expression increased and interstitial monocyte infiltration was aggravated. In parallel to blockade of tubular OPN expression, this treatment significantly attenuated monocyte infiltration and preserved renal plasma flow in GPS rats at day 37, compared with sense ODN-treated and untreated GPS rats. No significant changes were observed in OPN mRNA level by RT-PCR and histopathology of the glomeruli after ODN treatment, which was compatible with an absence of differences in the urinary protein excretion rate. In conclusion, OPN expressed by tubular epithelium played a pivotal role in mediating peritubular monocyte infiltration consequent to glomerular disease.

PLATELET ACTIVATING FACTOR (PAF) AS A MEDIATOR OF PROTEINURIA IN ISOLATED PERFUSED KIDNEY (IPK).

1987 ◽  
Author(s):  
F Delani ◽  
M Tagliaferri ◽  
D Macconi ◽  
C Lupini ◽  
N Perico ◽  
...  
Keyword(s):  
Platelet Activating Factor ◽  
Sprague Dawley ◽  
Cationic Protein ◽  
Glomerular Permeability ◽  
Urine Protein Excretion ◽  
Protein Excretion ◽  
Sprague Dawley Rats ◽  
Vehicle Injection ◽  
Stabilization Period ◽  
Krebs Henseleit Buffer

PAF amplifies tissue damage in glomerulonephritis and can promote proteinuria stimulating platelet and neutrophil cationic protein release. We used IPK to establish whether PAF directly causes proteinuria. Kidneys were isolated from male Sprague-Dawley rats and perfused at constant pressure (100 mmHg) in a closed circuit with a Krebs-Henseleit buffer containing glucose urea creatinine, BSA (1%), Ficoll 70 (3.5%) and amino acids. After 25 min stabilization period, a basal 10 min clearance period was followed by PAF (1.8 nM f.c. n = 6) or vehicle (n = 5) injection into the renal artery. As seen in the figure PAF but not vehicle significantly (p<0.01) increased urine protein excretion. No significant changes in GFR (as creatinine clearance) were observed after PAF or vehicle injection (Basal: 0.786 ± 0.075 PAF: 0.658 ± 0.070. Basal 0.653 ± 0.081, vehicle 0.639 ± 0.074 ml/min/g kidney). The data indicate that PAF may directly increase glomerular permeability to proteins.

Longitudinal Study of Proteins in Plasma and Dialysate during Continuous Ambulatory Peritoneal Dialysis (CAPD)

1990 ◽  
Vol 10 (4) ◽  
pp. 257-261 ◽  
Author(s):  
Gerald A. Young ◽  
Albert Taylor ◽  
Steven Kendall ◽  
Aleck M. Brownjohn
Keyword(s):  
Peritoneal Dialysis ◽  
Longitudinal Study ◽  
Membrane Permeability ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Plasma Proteins ◽  
Complement C3 ◽  
Acid Glycoprotein ◽  
Β2 Microglobulin ◽  
Male Patients

The aim was to evaluate plasma proteins during continuous ambulatory peritoneal dialysis (CAPD) in relation to dialysis losses, membrane permeability, renal insufficiency, and time on CAPD. Ten male patients, established on CAPD for at least 14 months, were studied every 8 weeks for 56 weeks. Blood and dialysate from the morning exchange were analysed for urea, creatinine, and 7 proteins, and used to calculate dialysate to plasma concentration ratios (DIP). These ratios were not significantly changed suggesting that permeability remained constant. However, there was a trend for β2-microglobulin, creatinine, and urea to increase progressively. After 56 weeks, β2-microglobulin had increased from 27.9 to 31.3 mglL (p < 0.05) and creatinine 1006 to 1099 μmoLIL (p < 0.05) and both correlated with time on CAPD (p < 0.001). Plasma α1-acid glycoprotein, albumin, transferrin, IgG, IgA, and complement C3 were not significantly changed, although IgA and complement C3 were each negatively correlated with time on CAPD (r = −0.70 and −0.67, respectively), creatinine (r = 0.51 and −0.54), and urea (r = −0.61 and −0.61) (p < 0.001 for all). It is concluded that increases in β2-microglobulin, creatinine, and urea are not due to loss of membrane permeability but reflect a slight increase in uraemia. Long-term decreases in immunological proteins may be caused by uraemia or progressive depletion.

Glomerular size selectivity in nephrotic rats exposed to diets with different protein content

1987 ◽  
Vol 253 (2) ◽  
pp. F318-F327
Author(s):  
A. Remuzzi ◽  
C. Battaglia ◽  
L. Rossi ◽  
C. Zoja ◽  
G. Remuzzi
Keyword(s):  
High Protein Diet ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
High Protein ◽  
Protein Diet ◽  
Standard Diet ◽  
Size Selectivity ◽  
Protein Excretion ◽  
Fractional Clearance ◽  
Glomerular Size

Glomerular size-selective properties in animals made nephrotic by adriamycin (ADR) injection and fed standard (20% protein) or high-protein (35% protein) diets were investigated using dextran fractional clearances. To interpret filtration and dextran-sieving data, a theoretical approach previously developed for analysis of experimental data in healthy and nephrotic humans was used. Four types of hypothetical pore-radius distributions were compared in order to establish the best tool for describing membrane pore structure in normal and nephrotic rats. This analysis revealed that a spread distribution of pores, the lognormal probability distribution, is the most adequate in representing membrane intrinsic characteristics. ADR animals on standard diet developed massive proteinuria and a lower glomerular filtration rate (GFR) than control animals. High-protein feeding in ADR rats induced a further increase in urinary protein excretion and in GFR. Dextran fractional clearance was more elevated for larger dextran fractions (greater than 46 A) in ADR animals on the standard diet than in control rats. No differences were observed in dextran-sieving curves between ADR rats on the standard and high-protein diet. Theoretical analysis of filtration and fractional clearance data revealed comparable changes in the intrinsic parameters of glomerular size selectivity in the two groups of nephrotic animals. These observations indicate that increased traffic of plasma proteins through the glomerular capillary wall does not imply, in our experimental condition, a further loss of glomerular size-selective properties. The greater urinary protein excretion of ADR animals on high-protein diet than ADR animals on a standard diet cannot be explained by further impairment of glomerular size selectivity but more likely reflects hemodynamic changes.

scholarly journals Effects of Proximal Tubule Shortening on Protein Excretion in a Lowe Syndrome Model

2019 ◽  
Vol 31 (1) ◽  
pp. 67-83 ◽  
Author(s):  
Megan L. Gliozzi ◽  
Eugenel B. Espiritu ◽  
Katherine E. Shipman ◽  
Youssef Rbaibi ◽  
Kimberly R. Long ◽  
...  
Keyword(s):  
Cell Division ◽  
Proximal Tubule ◽  
Cell Lines ◽  
Kidney Development ◽  
Lowe Syndrome ◽  
Multinucleated Cells ◽  
Protein Excretion ◽  
Pt Cell ◽  
Renal Tubular ◽  
Endocytic Traffic

BackgroundLowe syndrome (LS) is an X-linked recessive disorder caused by mutations in OCRL, which encodes the enzyme OCRL. Symptoms of LS include proximal tubule (PT) dysfunction typically characterized by low molecular weight proteinuria, renal tubular acidosis (RTA), aminoaciduria, and hypercalciuria. How mutant OCRL causes these symptoms isn’t clear.MethodsWe examined the effect of deleting OCRL on endocytic traffic and cell division in newly created human PT CRISPR/Cas9 OCRL knockout cells, multiple PT cell lines treated with OCRL-targeting siRNA, and in orcl-mutant zebrafish.ResultsOCRL-depleted human cells proliferated more slowly and about 10% of them were multinucleated compared with fewer than 2% of matched control cells. Heterologous expression of wild-type, but not phosphatase-deficient, OCRL prevented the accumulation of multinucleated cells after acute knockdown of OCRL but could not rescue the phenotype in stably edited knockout cell lines. Mathematic modeling confirmed that reduced PT length can account for the urinary excretion profile in LS. Both ocrl mutant zebrafish and zebrafish injected with ocrl morpholino showed truncated expression of megalin along the pronephric kidney, consistent with a shortened S1 segment.ConclusionsOur data suggest a unifying model to explain how loss of OCRL results in tubular proteinuria as well as the other commonly observed renal manifestations of LS. We hypothesize that defective cell division during kidney development and/or repair compromises PT length and impairs kidney function in LS patients.

Kinetics of α2-macroglobulin and α1-acid glycoprotein in rats subjected to repeated acute inflammatory stimulation

2010 ◽  
Vol 44 (2) ◽  
pp. 150-154 ◽  
Author(s):  
Toshio Honjo ◽  
Takashi Kuribayashi ◽  
Mariko Matsumoto ◽  
Shunsuke Yamazaki ◽  
Shizuo Yamamoto
Keyword(s):  
Acid Glycoprotein ◽  
Α2 Macroglobulin ◽  
Kinetics Of

scholarly journals Temporal characterization of the development of renal injury in FHH rats and FHH.1BN congenic strains

2011 ◽  
Vol 300 (2) ◽  
pp. F330-F338 ◽  
Author(s):  
Jan Michael Williams ◽  
Marilyn Burke ◽  
Jozef Lazar ◽  
Howard J. Jacob ◽  
Richard J. Roman
Keyword(s):  
Renal Injury ◽  
Transforming Growth Factor ◽  
Renal Perfusion ◽  
Chromosome 1 ◽  
Brown Norway ◽  
Glomerular Permeability ◽  
Congenic Strains ◽  
Protein Excretion ◽  
And Control ◽  
Progression Of Renal Disease

The present study examined the effect of transfer of portions of chromosome 1 that includes (FHH.1BN AR+ strain) or excludes (control FHH.1BN AR− strain) a 4.3-Mb region from the Brown Norway (BN) rat that restores the autoregulation (AR) of renal blood flow (RBF) on the development of hypertension and renal injury in congenic strains of Fawn Hooded Hypertensive (FHH) rats. FHH and control AR− rats exhibited poor autoregulation of RBF, and glomerular capillary pressure (Pgc) rose by 19 ± 2 mmHg in FHH rats when renal perfusion pressure (RPP) was increased from 100 to 150 mmHg. In contrast, RBF was well autoregulated in the AR+ strain, and Pgc only increased by 3 ± 1 mmHg when RPP was increased over this range. Baseline mean arterial pressure (MAP) at 12 wk of age was similar in all strains and averaged 122 mmHg. MAP increased significantly in FHH rats and was significantly higher by 12 mmHg in 21-wk-old FHH rats than in the FHH.1BN congenic strains. Protein excretion rose from 5 ± 1 to 397 ± 29 mg/day in 6- vs. 21-wk-old FHH rats. In contrast, protein excretion only increased to 139 ± 21 mg/day in the control AR− strain, and it did not increase significantly in the AR+ strain. Glomerular permeability to albumin was similar in all strains at 6 wk of age. It increased significantly in 9-wk-old FHH and control AR− rats, but not in the AR+ strain. The levels of matrix metalloproteinase (MMP)-2 and transforming growth factor (TGF)-β2 protein were significantly higher in the renal cortex of 9-wk-old FHH rats compared with the levels seen in the AR+ strain. These data indicate that transfer of a 4.3-Mb region of BN chromosome 1 into the FHH genetic background improves autoregulation of RBF, normalizes Pgc, and slows the progression of renal disease.

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