Gene/Protein Disease Symptom Drug Enzyme Compound
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9 patients were observed prospectively during 14-40 months 003 continuous ambulatory peritoneal dialysis (CAPD) treatment. From start of CAPD, each patient recorded dwell time, drained ultrafiltration volume (delta V), initial glucose concentration in dialysate, dialy fluid intake, body weight and blood pressure on a special form. These data, together with monthly values for albumin, urea, creatinin, phosphate, glucose and beta 2-microglobulin in plasma and in instilled dialysate, were later fed into a specially designed computer program to compare changes in the monthly mean (+/- SEM) values. During 5 episodes of peritonitis, daily changes in delta V were also computed. A long-term increase in delta V was found in 4 and a decrease in 5 patients. In all 9 patients delta V changed intermittently. All changes were most pronounced for long dwell times as compared to shorter dwell exchanges. The decrease in delta V started within the first 12 months of treatment. In the daily routine were aware of decreased ultrafiltration capacity in 3 patients only. Intermittent monthly changes in delta V could partly be correlated to changes in daily fluid intake. No correlations were found between long-term changes in delta V and fluid intake. All except 1 patient gained progressively in body weight, but without correlations to fluid balance, blood pressure and plasma albumin concentration. At the start of the observation period, most patients loosing delta V during this study appeared to have a more permeable membrane with a higher absorption rate of glucose and higher equilibration ratios for creatinine and beta 2-microglobulin in 5-hours drained dialysate as compared with the other patients. However, this was not statistically different between the two groups of patients. During the observation period, most patients with decreased delta V also increased transperitoneal solute transport, while the solute transport decreased in patients with increasing delta V, but these changes were only significant for some patients. During peritonitis, delta V decreased significantly 1 day before any other signs of peritonitis. All changes in delta V were most pronounced for long dwell times as compared with short dwell times. It is suggested that changes in ultrafiltration can be related to altered permeability of the peritoneal membrane, which appear earlier and more frequent than suggested by others, and any loss of delta V can be explained by a more permeable ('open') peritoneal membrane. It is also possible that different diseases act differently on the permeability of the peritoneal membrane.
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PMID:Long-term changes in transperitoneal water transport during continuous ambulatory peritoneal dialysis. 651 73

Kidney function and size were studied in seven normal male subjects before and after administration of highly purified human growth hormone for 1 week. Glomerular filtration rate, renal plasma flow (steady-state infusion technique with urinary collections using 125I-iothalamate and 131I-hippuran) kidney size (ultrasonic scanning) and urinary excretion rates of albumin and beta 2-microglobulin (radioimmunoassays) were measured. Highly purified growth hormone was injected subcutaneously, 2 IU in the morning and 4 IU in the evening. Glomerular filtration rate increased from (mean +/- SEM) 114 +/- 5 to 125 +/- 4 ml/min x 1.73 m2 (P less than 0.01) and renal plasma flow increased from 554 +/- 30 to 601 +/- 36 ml/min x 1.73 m2 (P less than 0.01). Kidney size and urinary excretion rates of albumin and beta 2-microglobulin did not change significantly. Our results show that raising plasma growth hormone into a range similar to that found in insulin-dependent diabetics enhances glomerular filtration rate and renal plasma flow, while kidney size remains unchanged. Increased renal plasma flow is the major determinant of growth hormone induced elevation in glomerular filtration rate. Growth hormone may thus contribute to the enhancement of glomerular filtration rate and renal plasma flow typically found in insulin-dependent diabetics.
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PMID:Kidney function and size in normal subjects before and during growth hormone administration for one week. 680 Aug 24

Various enzymatic urinary activities have been proposed to assess renal proximal tubule damage in children, including neonates. Nevertheless comprehensive knowledge on the developmental aspects of physiological enzymuria is limited, particularly with regard to lysosomal and brush border enzymuria. Urinary activities of two lysosomal enzymes, N-acetyl-beta-D-glucosaminidase (NAG) and beta-galactosidase (GAL), and of two brush border enzymes, alanine aminopeptidase (AAG) and gamma-glutamyltransferase (GGT) were comparatively investigated in normal prematures (n = 28), term neonates (n = 52), infants aged less than 2 years (n = 19) and children (n = 33), and compared to urinary excretion of beta 2-microglobulin (B2M). Enzymatic activities were assayed using either spectrophotometrical (NAG, AAP, GGT) fluorimetrical (GAL) or radioimmunological (B2M) methods, and were related to urinary creatinine excretion. Developmental profiles of both the studied lysosomal enzymes and of B2M were similarly characterized with significantly decreasing values from prematures (NAG 9.29 +/- 1.44, GAL 2.26 +/- 0.26 IU/mmol creatinine, indicated as mean +/- SEM) to term neonates (6,94 +/- 0.58 and 1.76 +/- 0.15 IU/mmol creatinine, respectively) and older infants and children. Lysosomal enzymatic urinary activities correlated linearly with a coefficient of r = 0.75, (p < 0.05), while correlations between each lysosomal enzymatic activity and B2M urinary excretion were weaker.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Specific developmental profiles of lysosomal and brush border enzymuria in the human. 772 20

A method for measuring the peritoneal dialysis capacity (PDC) of the individual patient has been developed as an aid to treatment of patients with renal failure and peritoneal dialysis. The patient collects the data him or herself during an almost normal CAPD day using a carefully designed protocol whereby the nursing time is kept to a minimum. The three-pore model is used to describe the PDC with three physiological parameters: (1.) the 'Area' parameter (A0/delta X), which determines the diffusion of small solutes and the hydraulic conductance of the membrane (LpS); (2.) the final reabsorption rate of fluid from the abdominal cavity to blood (JVAR) when the glucose gradient has dissipated; and (3.) the large pore fluid flux (of plasma, JVL), which determines the loss of protein to the PD fluid. In the adult PD population (age 60, N = 97) the normal 'Area' parameter was 23,600 cm/1.73 m2, with an SEM of 650. The JVAR was 1.49 ml/min/1.73 m2 and JVL was 0.078 ml/min/1.73 m2. The PDC parameters were reproducible and could adequately predict the concentrations of the test solutes as well as that of beta 2-microglobulin. The results in terms of clearance, 'UF volume' and nutritional consequences were presented on easily understandable graphs, whereby patient compliance was improved. These physiological parameters are highly dynamic, as evidenced by the marked increases observed during peritonitis. It seems safe to conclude that PDC is a useful tool to achieve adequate dialysis and to enhance the understanding of PD exchange.
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PMID:Assessing the peritoneal dialysis capacities of individual patients. 778 18

Enhanced extracorporeal removal of beta 2-microglobulin (beta 2m) may prevent the development of dialysis-related amyloidosis (DRA). One mechanism of beta 2m removal is membrane adsorption. Therefore, we fundamentally characterized beta 2m adsorption to the highly permeable polyacrylonitrile (PAN) membrane. Porous and nonporous PAN fragments were incubated in buffer containing 125I-beta 2m. Over a concentration range of 8 to 60 mg/liter, the equilibrium adsorption isotherm was linear (r = 0.99) for porous PAN while the isotherm for nonporous PAN suggested either multilayer binding or adsorption of proteins with differing orientations. In kinetic analyses, the approach to equilibrium versus (time)1/2 was evaluated. For both porous and nonporous PAN, this relationship was linear (r = 0.99), consistent with a diffusion-controlled process. Adsorption reversibility was assessed by comparing the amount bound at varying residence times (0 to 4 hr) to the amount remaining adsorbed after a subsequent incubation in buffer. The fractions remaining bound at 60, 120, and 240 minutes (0.34 +/- 0.02, 0.36 +/- 0.06, and 0.44 +/- 0.03; mean +/- SEM) were significantly greater (P < 0.05) than the value at five minutes (0.23 +/- 0.01). This suggests membrane-induced conformational changes in adsorbed beta 2m. This investigation permits the comparison of beta 2m adsorptive properties of PAN to those of other membrane-based and nonmembrane-based therapies designed to prevent DRA.
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PMID:Membrane adsorption of beta 2-microglobulin: equilibrium and kinetic characterization. 786 9

T-lymphocytic infiltration of the exocrine pancreas and liver in patients with chronic pancreatitis has suggested that cell mediated immune mechanisms may play a part in the pathogenesis of this disease. As expression of major histocompatibility (MHC) antigens is a prerequisite for organ specific autoimmunity, the expression of HLA class I (beta 2-microglobulin) and class II (HLA-DR) determinants have been analysed, together with the presence of T-lymphocytes, in 93 patients (64 men and 29 women, mean age 40.6 years) having an operation for chronic pancreatitis. Ethanol (63 patients), recurrent acute pancreatitis (12), congenital lesions (2), and unknown (16) were suggested to be the causes of the disease. Immunohistochemical staining of formalin fixed and paraffin wax embedded tissue sections used conventional immunohistochemical techniques with specific anti-serum samples. No MHC expression was identified in 10 histologically normal pancreatic control specimens or in four cases of chronic pancreatitis secondary to obstruction by neuroendocrine tumours within the head of the pancreas. beta 2-microglobulin expression by pancreatic exocrine epithelial cells was seen in 76 chronic pancreatitis specimens (82%) while HLA-DR was present in 61 (66%). Simultaneous expression of both class I and II determinants was seen in 53 (57%) of cases. MHC determinant expression was not found in 10 cases (11%) of chronic pancreatitis. In the positive specimens, expression was confined to ductal and ductular (interlobular and intralobular) epithelium with no staining of acinar cells. Staining was not related to the suspected cause of the disease or age. T-lymphocytes were more prominent in chronic pancreatitis mean (SEM) (131 (15) cells per high powered field) than controls (5 (1), p < 0.01). Aberrant MHC expression by exocrine pancreatic epithelial cells occurring in the presence of an appreciable T-cell infiltration confirmed that the appropriate cellular conditions were present for cell mediated cytotoxicity to contribute to the pathogenesis of chronic pancreatitis.
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PMID:Expression of major histocompatibility antigens in human chronic pancreatitis. 779 37

Increased biocompatibility and lower cost are the two major arguments favoring routine dialyzer reprocessing. The impact of longer-term reprocessing is critical to the practical use of polysulfone membranes (PMs), because of the possibility of decreasing efficiency and performance, especially in the removal of beta 2-microglobulin (beta 2M), a protein that has been implicated in the development of dialysis-associated amyloidosis (DDA). In this study, we examine urea clearance (Kd), urea mass transfer coefficient (h0), ultrafiltration coefficient (K(uf)), and percent removal of beta 2M up to 24 uses. The study involved 11 patients on hemodialysis for 5.27 +/- 4.6 years, with a mean age of 62.5 +/- 9.7 years and average run-time treatment of 2.78 +/- 0.3 hours. PMs were tested after being reprocessed manually using bleach and formaldehyde. The efficacy of the dialyzer was examined on uses 1, 5, 10, 15, 20, and 24, and the percent removal of beta 2M was determined except in the twentieth use and corrected for ultrafiltration. The Kd obtained through 24 uses showed no significant change, although h0 was significantly increased in the fifteenth use, and K(uf) was significantly increased in the 10th and 20th use (P < 0.05). The percent removal of beta 2M increased significantly from 44.1 +/- 2.8 (mean +/- SEM) in the first use to 59.4 +/- 2.19 (P < 0.05) in the 10th use, and 62.1 +/- 4.07 and 63.1 +/- 4.27 in the 15th and 24th uses, respectively (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of dialyzer reprocessing on performance and beta 2-microglobulin removal using polysulfone membranes. 846 21

The purpose of this study was to investigate the usefulness of urinary endothelin-1 (ET-1) as a marker of renal disease. We measured urinary excretion of ET-1 in 28 patients with glomerulonephritis (GN), 22 patients with chronic renal failure (CRF), 40 patients with end-stage renal disease (ESRD), and 17 healthy volunteers. There was no significant difference in 24-hour urinary ET-1 excretion among the four groups (mean +/- SEM, 0.49 +/- 0.22 ng in controls, 0.79 +/- 0.37 ng in GN patients, 0.39 +/- 0.18 ng in CRF patients, and 0.28 +/- 0.11 ng in ESRD patients). The 24-hour urinary excretion of ET-1 in patients with GN or CRF showed significant correlation with the urinary excretion of sodium (r = 0.27, p < 0.05). The 24-hour urinary beta 2-microglobulin (beta 2M) excretion in patients with CRF (18.4 +/- 2.6 mg) or ESRD (9.7 +/- 1.1 mg) was significantly higher than in normal control subjects (0.23 +/- 0.11 mg). Serum creatinine concentration was positively correlated with the 24-hour urinary excretion of beta 2M in patients with GN or CRF (r = 0.50, p < 0.001). These findings indicate that urinary ET-1 is not as good a marker of renal disease as urinary beta 2M. However, it may be responsible for urinary sodium excretion in patients with GN or CRF.
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PMID:Urinary endothelin-1 in patients with renal disease. 983 Feb 75


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