Biomedical subjects

G Schulman

Publications and source records attributed to G Schulman.

At least 37 records · Page 2Linked to original sources

PubMed1997

Short-term effects of blood pressure control and antihypertensive drug regimen on glomerular filtration rate: the African-American Study of Kidney Disease and Hypertension Pilot Study.

The African-American Study of Kidney Disease and Hypertension pilot study randomized 94 nondiabetic black men and women (mean age, 53 years; 75% male) with presumed hypertensive nephrosclerosis and a baseline glomerular filtration rate (GFR) of 25 to 70 mL/min/1.73 m2 (mean, 52.3 mL/min/1.73 m2) to blood pressure control at either a low mean arterial pressure (MAP) goal of < or = 92 mm Hg or a usual MAP goal of 102 to 107 mm Hg and an antihypertensive drug regimen that included either a calcium antagonist (amlodipine), a beta-blocker (atenolol), or an angiotensin-converting enzyme (ACE) inhibitor (enalapril). After 3 months of follow-up (n = 90), the mean GFR was similar (53.0 mL/min/1.73 m2 v 53.7 mL/min/1.73 m2) to the baseline levels in participants randomized to the low MAP group (n = 44), whereas the mean GFR increased by 3.9 mL/min/1.73 m2 (P = 0.02) in participants randomized to the usual MAP group (n = 46). During the same period of time, the mean GFR increased significantly in participants randomized to the calcium channel blocker regimen (n = 28) (5.7 mL/min/ 1.73 m2; P = 0.01) but not in participants randomized to the beta-blocker regimen (n = 31) (1.7 mL/min/1.73 m2; P = 0.10) or the ACE inhibitor regimen (n = 31) (1.1 mL/min/1.73 m2; P = 0.52). Changes in GFR at 3 months were significantly different among the three treatment groups (P = 0.04). We conclude that the magnitude of short-term effects of blood pressure control and antihypertensive drug regimens on GFR should be considered when estimating sample size for clinical trials designed to evaluate the effects of these interventions on long-term changes in GFR slope.

Adolescent↗

PubMed1997

Care pathway reduces hospitalizations and cost for hemodialysis vascular access surgery.

Hemodialysis vascular access-related hospitalizations account for more than 20% of United States end-stage renal disease (ESRD) hospitalizations, with an annual cost approximating $675 million. Limiting access-related costs while delivering similar degrees of quality care thus would enhance alternative utilization of ESRD funding. We implemented a vascular access care pathway emphasizing coordinated patient evaluation and outpatient surgery to determine whether such an intervention affected outcomes associated with vascular access surgery. Data examining hospitalization and vascular access surgery charges, complications, and patient satisfaction (determined by questionnaire) were analyzed, comparing patients who underwent vascular access surgery in 1994 and 1995 as inpatients (non-care pathway patients) and patients who underwent vascular access surgery via the care pathway in 1995. Inpatient days declined in 1995 (1994: 582 days; 1995: 85 days; P < 0.03) and the average charges per patient for the care pathway cohort were significantly less than charges per patient in 1994 and charges for non-care pathway patients in 1995 (1994 patients: $10,524 +/- $5,209; 1995 non-care pathway patients: $11,196 +/- $5,806; 1995 care pathway patients: $4,686 +/- $2,912/patient; P < 0.02). Incidence rates for major (life-threatening) complications were not significantly different between 1994 patients and care pathway patients in 1995. However, the 1995 non-care pathway patients had a higher incidence of major complications (15.4%). Forty-seven repeat access procedures were performed in 29 patients in 1994 versus 35 repeat access procedures in 22 care pathway patients in 1995, and 12 repeat access procedures were performed in eight non-care pathway patients in 1995. Finally, a majority of the patients entered into the care pathway who responded to a survey stated that they were satisfied with access surgery via the care pathway. These data suggest that a vascular access care pathway can reduce hospital days and costs while achieving acceptable outcomes for access surgery.

Ambulatory Surgical Procedures↗

PubMed1997

Effect of dietary protein restriction on nutritional status in the Modification of Diet in Renal Disease Study.

The safety of dietary protein and phosphorous restriction was evaluated in the Modification of Diet in Renal Disease (MDRD) Study. In Study A, 585 patients with a glomerular filtration rate (GFR) of 25 to 55 ml/min/1.73 m2 were randomly assigned to a usual-protein diet (1.3 g/kg/day) or a low-protein diet (0.58 g/kg/day). In Study B, 255 patients with a GFR of 13 to 24 ml/min/1.73 m2 were randomly assigned to the low-protein diet or a very-low-protein diet (0.28 g/kg/day), supplemented with a ketoacid-amino acid mixture (0.28 g/kg/day). The low-protein and very-low-protein diets were also low in phosphorus. Mean duration of follow-up was 2.2 years in both studies. Protein and energy intakes were lower in the low-protein and very-low-protein diet groups than in the usual-protein group. Two patients in Study B reached a "stop point" for malnutrition. There was no difference between randomized groups in the rates of death, first hospitalizations, or other "stop points" in either study. Mean values for various indices of nutritional status remained within the normal range during follow-up in each diet group. However, there were small but significant changes from baseline in some nutritional indices, and differences between the randomized groups in some of these changes. In the low-protein and very-low-protein diet groups, serum albumin rose, while serum transferrin, body wt, percent body fat, arm muscle area and urine creatinine excretion declined. Combining patients in both diet groups in each study, a lower achieved protein intake (from food and supplement) was not correlated with a higher rate of death, hospitalization or stop points, or with a progressive decline in any of the indices of nutritional status after controlling for baseline nutritional status and follow-up energy intake. These analyses suggest that the low-protein and very-low-protein diets used in the MDRD Study are safe for periods of two to three years. Nonetheless, both protein and energy intake declined and there were small but significant declines in various indices of nutritional status. These declines are of concern because of the adverse effect of protein calorie malnutrition in patients with end-stage renal disease. Physicians who prescribe low-protein diets must carefully monitor patients' protein and energy intake and nutritional status.

Adolescent↗

PubMed1997

Comparison of methods to predict equilibrated Kt/V in the HEMO Pilot Study.

The ongoing HEMO Study, a National Institutes of Health (NIH) sponsored multicenter trial to test the effects of dialysis dosage and membrane flux on morbidity and mortality, was preceded by a Pilot Study (called the MMHD Pilot Study) designed to test the reliability of methods for quantifying hemodialysis. Dialysis dose was defined by the fractional urea clearance per dialysis determined by the predialysis BUN and the equilibrated postdialysis BUN after urea rebound is completed (eKt/V). In the Pilot Study the blood side standard for eKt/V was calculated from the predialysis, postdialysis, and 30-minute postdialysis BUN. Four techniques of approximating eKt/V that eliminated the requirement for the 30-minute postdialysis sample were also evaluated. The first adjusted the single compartment Kt/V using a linear equation with slope based on the relative rate of solute removal (K/V) to predict eKt/V (rate method). The second and third techniques used equations or mathematical curve fitting algorithms to fit data that included one or more samples drawn during dialysis (intradialysis methods). The fourth technique (dialysate-side) predicted eKt/V from an analysis of the time-dependent profile of dialysate urea nitrogen concentrations (BioStat method; Baxter Healthcare, Inc., Round Lake, IL, USA). The Pilot Study demonstrated the feasibility of conventional and high dose targets of about 1.0 and 1.4 for eKt/V. Based on the blood side standard method, the mean +/- SD eKt/V for patients randomized to these targets was 1.14 +/- 0.11 and 1.52 +/- 0.15 (N = 19 and 16 patients, respectively). Single-pool Kt/Vs were about 0.2 Kt/V units higher. Results were similar when eKt/V was based on dialysate side measurements: 1.10 +/- 0.11 and 1.50 +/- 0.11. The approximations of eKt/V by the three blood side methods that eliminated the delayed 30-minute post-dialysis sample correlated well with eKt/V from the standard blood side method: r = 0.78 and 0.76 for the single-sample (Smye) and multiple-sample intradialysis methods (N = 295 and 229 sessions, respectively) and 0.85 for the rate method (N = 295). The median absolute difference between eKt/V computed using the standard blood side method and eKt/V from the four other methods ranged from 0.064 to 0.097, with the smallest difference (and hence best accuracy) for the rate method. The results suggest that, in a dialysis patient population selected for ability to achieve an equilibrated Kt/V of about 1.45 in less than a 4.5 hour period, use of the pre and postdialysis samples and a kinetically derived rate equation gives reasonably good prediction of equilibrated Kt/V. Addition of one or more intradialytic samples does not appear to increase accuracy of predicting the equilibrated Kt/V in the majority of patients. A method based on dialysate urea analysis and curve-fitting yields results for equilibrated Kt/V that are similar to those obtained using exclusively blood-based techniques of kinetic modeling.

Blood Urea Nitrogen↗

PubMed1997

Predictive measures of vascular access thrombosis: a prospective study.

Malfunction of permanent vascular accesses remains a cause of frequent and costly morbidity in patients receiving chronic hemodialysis (CHD). Several recommendations for routine monitoring of these permanent vascular accesses for incipient failure have been proposed. In this study, multiple indicators of incipient vascular access dysfunction, including "venous" and "arterial" pressures at serial blood flows (200 ml/min, 300 ml/min, and 400 ml/min), percent urea recirculation, Doppler ultrasound, and access blood flow by ultrasound dilution technique were simultaneously evaluated in a total of 220 vascular accesses in 170 chronic hemodialysis patients in two separate study periods (6 months apart). The rate of thrombosis was determined within the subsequent 12 weeks of each study period to assess the short-term predictive power of access thrombosis. During the period of follow-up, there were 34 thrombotic events in 172 polytetrafluoroethylene (PTFE) grafts and only one thrombotic event in 48 arterio-venous fistulas (AVF). Therefore, the statistical analysis was limited to the PTFE grafts. When grafts with thromboses were compared to those without thrombosis by univariate analysis, access blood flow measured either by ultrasound dilution technique (875 +/- 426 ml/min with thrombosis vs. 1193 +/- 677 ml/min without thrombosis, P = 0.001) or by Doppler ultrasound (762 +/- 420 ml/min with thrombosis vs. 1171 +/- 657 ml/min without thrombosis, P = 0.001) were significantly different in the two groups. There was good correlation (r = 0.79, P = 0.0001) between the blood flows determined by both techniques. The grade of stenosis determined by ultrasound was also a statistically significant predictor (P = 0.02). "Venous" and "arterial" pressures were numerically similar and were not statistically different between the accesses that did and those that did not thrombose. When multivariate analysis was used, there was a significantly increased risk of thrombosis only with decreasing access blood flow determined by ultrasound dilution techniques after adjusting for other confounding variables. When the average blood flow of all grafts (1134 ml/min) is considered as the reference access blood flow (relative risk of 1.0), the relative risk of a PTFE thrombotic event within the subsequent 12 weeks was 1.23 at a blood flow 950 ml/min, 1.67 at a blood flow of 650 ml/min and to 2.39 at a blood flow of 300 ml/min. In summary, access blood flow measured by either Dilution or Doppler is a reliable indicator of subsequent short-term thrombosis risk. Other proposed methods of evaluating access dysfunction were not useful in our patients. If simple to use, cost-effective devices to measure dialysis access blood flow become readily available, the measurement of access blood flow will likely become the method of choice for screening of PTFE vascular access dysfunction in hemodialysis patients.

Aged↗

PubMed1997

Adequacy of dialysis.

Despite improvements in the delivery of dialysis, morbidity and mortality remain excessively high in end-stage renal disease patients. Multiple lines of evidence suggest that inadequate dialysis is responsible these trends. The limits of our understanding of the influence of dialysis dose on mortality and morbidity are discussed. In that context, the relationship between dialysis dose and nutritional status of dialysis patients is also reviewed. The best marker for adequacy of dialysis is yet to be determined. However, urea as a surrogate for small molecular weight solute clearance, has been demonstrated by many studies to be a parameter of adequacy, both in hemodialysis and peritoneal dialysis populations. The application of kinetic modeling of urea is discussed for hemodialysis. The new insights that will be forthcoming at the conclusion of the National Institute of Health HEMO study should help to define an optimal dose of dialysis.

Humans↗

PubMed1996

Atrial natriuretic peptide inhibits mineralocorticoid receptor function in rat colonic surface cells.

Atrial natriuretic peptide (ANP) inhibits and aldosterone (ALDO) stimulates Na conductive transport. Therefore, the effects of ANP and its second messenger cGMP on mineralocorticoid receptor (MR) function in rat colon surface and crypt cells were examined. 100 nM 8-Br-cGMP decreased surface [3H]ALDO binding by 42 +/- 4% but increased crypt [3HvALDO binding by 52+/-16%. ANP decreased surface [3H]ALDO binding by approximately 50% after a 2.5-h lag period but had no effect on crypt ALDO binding. ANP and cGMP rapidly (< 15 min) inhibited surface cell ALDO-induced MR nuclear translocation but did not affect crypt MR nuclear translocation. Inhibition of cGMP-dependent protein kinase with KT5823 blocked the inhibitory effects of ANP and 8-Br-cGMP on surface cell ALDO binding and MR nuclear translocation. In crypt, KT5823 increased baseline [3H]ALDO binding but did not inhibit the stimulatory effect of exogenous cGMP. DEAE-cellulose chromatography and gel mobility shift assay showed that ANP did not inhibit surface MR activation. ANP inhibited ALDO stimulated short circuit current in distal colon. These data demonstrate cell-specific regulation of MR function. In surface cells, ANP rapidly inhibits MR nuclear translocation and ALDO-induced short circuit current. ANP inhibition of MR function may be an additional mechanism of ANP antagonism of Na reabsorption.

Aldosterone↗

PubMed1996

Effective hemodialysis and hemofiltration driven by an extracorporeal membrane oxygenation pump in infants with hyperammonemia.

Two infants with urea cycle disorders had life-threatening hyperammonemia within the first 5 days of life. Both patients were small for dates, poorly oxygenated, and hemodynamically unstable. We employed a combination of extracorporeal oxygenation and hemodialysis to provide high-flow filtration in a controlled system to rapidly detoxify both patients.

Ammonia↗

PubMed1996

Prevalence of hypertension in 1,795 subjects with chronic renal disease: the modification of diet in renal disease study baseline cohort. Modification of Diet in Renal Disease Study Group.

The Modification of Diet in Renal Disease Study was a multicenter trial of the effect of protein restriction and strict blood pressure control on the progression rate of chronic renal failure of multiple causes. At the first baseline visit, 1,795 screened patients with renal disease had blood pressure measured, antihypertensive medications recorded, glomerular filtration rate (GFR) determined by 125I-iothalamate clearance, a nutritional assessment, and a 24-hour urine collection to determine sodium and potassium levels. A total of 1,494 patients in this cohort were classified as hypertensive (83%) and the remainder (301 patients) as nonhypertensive. Ninety-one percent of the hypertensive subjects were on treatment, 54% being controlled to a blood pressure of < or = 140/90 mm Hg. To better understand the factors that contribute to the development of hypertension in chronic renal disease, some determinants of the prevalence of hypertension in this cohort were investigated. Compared with normotensive subjects, hypertensive patients were older (51.2 +/- 12.7 years v 46.6 +/- 13.1 years [mean +/- SD]), had a higher body mass index (BMI; 27.5 +/- 4.7 kg/m2 v 25.4 +/- 4.2 kg/m2), and had a lower GFR (37.8 +/- 19.6 mL/min/1.73 m2 v 50.1 +/- 25 mL/min/1.73 m2). All these differences were significant (P < 0.01). The prevalence of hypertension was significantly higher for men than for women (86% v 80%; P = 0.001), and for blacks than for whites (93% v 81%; P < 0.001). The prevalence of hypertension was higher in subjects with glomerular disease than in those with tubulointerstitial disease (85% v 62.6%; P < 0.001). The prevalence of hypertension varied inversely with GFR (from 66% at a GFR of 83 mL/min/1.73 m2 to 95% at a GFR of 12 mL/min/1.73 m2). The prevalence of hypertension varied directly with BMI (from 70% with a BMI at the 10th percentile to 94% with a BMI at the 97th percentile). This relationship was independent of GFR. Multiple logistic regression analysis showed five predictors in decreasing order of significance as determined by chi-square values: GFR, 83.2; BMI, 36.7; black race, 19.9; increasing age, 14.5 (all P < 0.001); and male gender, 5.1 (P = 0.024). Salt intake was not a determinant of blood pressure status. These results confirm previous reports indicating that hypertension in renal disease is determined by the level of renal function. For the first time, three factors known to predict blood pressure levels in populations with normal renal function were also shown to be determinants of blood pressure in renal disease: BMI, black race, and age. In addition, the data suggest that hypertension is inadequately treated in more than half of patients with chronic renal disease in the United States.

Adolescent↗

PubMed1996

Effects of recombinant human growth hormone on plasma and dialysate amino acid profiles in CAPD patients.

Protein and calorie malnutrition is common in chronic dialysis patients. Several interventions have been proposed to prevent and/or to treat malnutrition including the use of recombinant human growth hormone (rhGH) as an anabolic agent. We have previously reported a significant decrease in net urea nitrogen appearance along with modest but statistically significant decrements in several blood chemistries including serum potassium, phosphorus, albumin and a small increase in creatinine concentration during rhGH administration in CAPD patients. In order to evaluate the underlying mechanism of these changes, we systematically evaluated the plasma and dialysate amino acid profiles in blood and dialysate samples of the same patients during their participation in the study. The design of the study was prospective, cross-over with the patients serving as their own controls. There were three study periods: baseline (preGH), treatment (Tx), and follow-up (PostGH). During the seven days Tx period, patients self-administered 5 mg/day s.c of rhGH. Compared to PreGH period, administration of rhGH resulted in a significant decrease in essential amino acids (EAA), in both plasma (935 +/- 243 mumol/liter vs. 801 +/- 186 mumol/liter; P < 0.05) and dialysate (623 +/- 244 mumol/liter vs. 415 +/- 122 mumol/liter; P < 0.05). This decrease was evident in 8 out of 10 individual EAA, and the extent of decrease ranged from 15% to 28% for plasma EAA and from 30% to 45% for dialysate EAA. On the other hand, plasma non-essential AA levels increased significantly during treatment (2537 +/- 776 mumol/liter vs. 3177 +/- 1259 mumol/liter; P < 0.05). All changes returned to baseline values after discontinuation of rhGH. Our findings suggest that the net anabolic processes induced by rhGH reflect a shift in AA metabolism towards peripheral muscle tissues.

Adult↗

PubMed1996

Nephrotoxicity of antiviral therapies.

An ever-increasing variety of antiviral medications are being used clinically for an array of viral infections ranging from hepatitis to HIV. Some of these medications, such as acyclovir and foscarnet, have significant nephrotoxicity, whereas others are associated only rarely with renal failure. The spectrum of renal lesions associated with antiviral nephrotoxicity suggests that these medications may cause renal failure by affecting tubular cells or glomeruli. In most instances of antiviral-related nephrotoxicity, discontinuation of the offending agent results in a rapid return to normal renal function.

Acquired Immunodeficiency Syndrome↗

PubMed1996

Nitrogen balance in hospitalized chronic hemodialysis patients.

Malnutrition is an important factor in the increased morbidity and mortality of chronic hemodialysis (CHD) patients. Dietary protein intake necessary to maintain neutral nitrogen balance appears to be higher in CHD patients due to various catabolic effects of the hemodialysis procedure, including nutrient losses and increased energy expenditure. Dietary intake may be further decreased in hospitalized CHD patients. We examined this issue in 18 CHD patients (9 male, 9 female) who were admitted to a regular ward. Daily protein intake (DPI) and daily caloric intake were measured for each patient. In addition, protein catabolic rate (PCR) calculated from interdialytic changes in BUN were calculated. Our results showed that mean (+/- SD) DPI was 0.79 +/- 0.41 g/kg/day, while PCR was 0.93 +/- 0.38 g/kg/day. Dietary protein and energy intake were 66% and 50% of suggested values, respectively, and DPI accounted for only 85% of PCR. Mean nitrogen balance was negative by -2.11 +/- 2.77 g of nitrogen/day (range -9.91 g of nitrogen/day to +3.89 g of nitrogen/day). Biochemical nutritional parameters such as serum albumin, cholesterol, prealbumin and transferrin obtained one week following admission were also indicative of undernutrition (3.16 +/- 0.39 g/dl, 132 +/- 30 mg/dl, 20 +/- 7.4 mg/dl, 154 +/- 49 mg/dl, respectively). We conclude that hospitalized CHD patients have inadequate protein and energy intake and this is evidenced by a significant deterioration in nutritional parameters during hospitalization. More aggressive nutritional interventions may be needed for this group of patients to prevent the adverse effects of hospitalization on nutritional status.

Adult↗

PubMed1995

Current standards for dialysis adequacy.

Multiple lines of evidence suggest that inadequately prescribed or delivered dosage of hemodialysis is associated with increased morbidity and mortality. Conversely, retrospective studies indicate that increased levels of hemodialysis reverse this trend of poor outcome. The results of the National Cooperative Dialysis Study (NCDS), a prospective and randomized trial, suggested that urea kinetic modeling was a valid method of quantifying the dose of hemodialysis delivered and also identified a level of treatment below which a number of adverse events occurred. In the ensuing years, urea kinetic modeling has been increasingly applied to quantitate dialysis. The application of the NCDS results as well as the limitations of the study are reviewed, and the modifications in applying urea kinetic modeling due to urea rebound are discussed. To assess the impact of newer membranes and higher levels of dialysis on an older hemodialysis population with more comorbid conditions than the subjects studied in the NCDS, a 5-year, multicenter, prospective and randomized trial, the HEMO Study, has recently been initiated.

Evaluation Studies as Topic↗

PubMed1994

Effects of dose of dialysis on morbidity and mortality.

The annual mortality rate of patients on hemodialysis in the United States is 24.3%, substantially higher than the mortality of age-matched patients in Europe and Japan. Differences in the dose of dialysis received by US patients has been proposed as an important factor contributing to this high mortality rate. We undertook a prospective effort to increase the dose of dialysis delivered to 130 patients treated at an urban dialysis center affiliated with Vanderbilt University. From 1988 to 1991 the dose of dialysis, represented by the urea kinetic modelling parameter Kt/V (K = dialyzer clearance, t = dialysis time, V = volume of distribution of urea), has been gradually increased from a dose of 0.82 +/- 0.32 to 1.33 +/- 0.23. Concurrent with this increase, there was a reduction of the gross annual mortality rate from 22.8% in 1988 to 9.1% in 1991. To account for potential differences in patient characteristics during those years, we also calculated the number of expected deaths, based on data from the United States Renal Data System. The ratio of observed to expected deaths, termed the "standardized mortality rate," decreased from a value of 1.03 in 1988 to a value of 0.611 in 1991. In addition, the number of hospital days per patient per year decreased from 15.2 d/patient/yr to 10.3 d/patient/yr. We conclude that increasing the dose of delivered dialysis decreases the hospitalization and mortality rates of hemodialysis-dependent patients.

Adult↗

PubMed1994

Effects of recombinant human erythropoietin on renal function in chronic renal failure predialysis patients.

A study was undertaken to ascertain the effects of recombinant human erythropoietin (r-HuEPO) on renal function in chronic renal failure predialysis patients. The effect of improvement of anemia by r-HuEPO on the rate of decline in renal function in predialysis patients has not been previously studied prospectively in a large number of patients using reliable measures of glomerular filtration rate (GFR). To investigate the efficacy, safety, and impact of r-HuEPO therapy in chronic renal insufficiency patients, a 48-week, randomized, open-label, multicenter study was initiated in 83 anemic, predialysis (serum creatinine 3 to 8 mg/dL) patients. Serial GFRs were measured using 125I-iothalamate clearance. Forty patients were randomized to the untreated arm and 43 patients to the treatment arm (50 U/kg r-HuEPO subcutaneously three times weekly). Baseline characteristics were comparable for the r-HuEPO-treated and untreated groups. During this 48-week study, GFR, mean arterial blood pressure, and daily protein intake were not significantly different between the two groups. There was a statistically significant increase in hematocrit for the r-HuEPO-treated group that was not associated with acceleration of deterioration in residual renal function. This was demonstrated by the lack of a significant (P = 0.376) between-group difference in mean change in GFR from baseline to last available value for the r-HuEPO-treated (-2.1 +/- 3.2 mL/min) and untreated (-2.8 +/- 3.5 mL/min) groups. This study concludes that r-HuEPO therapy improves anemia in predialysis patients and does not accelerate the rate of progression to end-stage renal disease.

Adult↗

PubMed1994

Hemodialysis membrane biocompatibility in acute renal failure.

Hemodialysis is a lifesaving procedure for patients with acute renal failure. Nevertheless, the institution of hemodialysis may result in a continued or accelerated decline in renal function. Loss of osmotic drive and hypotension may be partially responsible for this observation. However, multiple lines of evidence suggest that the nature of the hemodialysis membrane also influences renal function following acute renal failure. The cellulosic hemodialysis membrane activates humoral pathways and the cellular elements of blood. The inflammatory responses entrained from the activation result in hypersensitivity reactions attributable to anaphylatoxin generation, hypoxemia, increased susceptibility to infection, and catabolic events. In addition, recent studies indicate that the use of bioincompatible membranes delays recovery from acute renal failure. Increased numbers of neutrophils are found in the glomeruli following exposure to cellulosic membranes, suggesting that inflammatory events induced by complement activation may mediate continuing renal injury and prolonged recovery from acute renal failure. Membrane choice for patients with acute renal failure is emerging as an important therapeutic consideration, just as it is for those patients on long-term dialysis.

Acute Kidney Injury↗

PubMed1994

Short-term effects of recombinant human growth hormone in CAPD patients.

Protein and calorie malnutrition is common in chronic dialysis patients. Several interventions have been proposed to prevent and/or to treat malnutrition. Recombinant human growth hormone (rhGH) is a drug with anabolic properties and has been used in several catabolic conditions, such as patients with severe burns as well as in pediatric patients with chronic renal failure. In this study, we evaluated the short-term effects and safety of rhGH on urea kinetics and commonly measured biochemical parameters in 10 stable adult continuous ambulatory peritoneal dialysis (CAPD) patients. The design of the study was prospective, cross-over with the patients serving as their own controls. There were three study periods: baseline (PreGH), treatment (Tx), and follow-up (PostGH). During the seven day Tx period, patients self-administered 5 mg/day s.c. of rhGH. During this time, there was a significant decrease in blood urea nitrogen (BUN) (54 +/- 15 to 40 +/- 12 mg/dl), as well as in the combined dialysate and urine urea nitrogen excretion rate (5.69 +/- 1.86 to 4.04 +/- 1.13 g/day), and protein catabolic rate (0.82 +/- 0.13 to 0.67 +/- 0.09 g/kg/day), (all P < 0.001). Serum phosphorus (4.8 +/- 1.6 to 4.4 +/- 1.8 mg/dl) and potassium (4.0 +/- 0.4 to 3.6 +/- 0.2 mEq/liter) levels also showed a small but statistically significant decrease, in conjunction with a statistically significant increase in serum creatinine levels (12.2 +/- 5.7 to 12.9 +/- 5.7 mg/dl). Dietary protein intake, determined by dietary recall, did not change during the study (66.1 +/- 20.5 vs. 75.8 +/- 22.1 grams/day).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Mineralocorticoid and glucocorticoid receptor steroid binding and localization in colonic cells.

In rat colon epithelium glucocorticoids and mineralocorticoids regulate Na transport by binding to distinct receptors and stimulating different pathways. The distribution and intracellular localization of mineralocorticoid (MR) and glucocorticoid (GR) receptors in colonic Na-absorbing surface cells and Cl-secreting crypt cells is unknown. Surface and crypt cells were sequentially isolated from rat distal colon by EDTA chelation and mechanical dissociation. Cell viability was confirmed by trypan blue exclusion and low rates of 2',7'-bis(2-carboxyethyl)-5(6)-carboxylfluorescein leak. Histologic examination, alkaline phosphatase activity, and rates of [3H]leucine incorporation confirmed separation of surface from crypt cells. Scatchard analysis of [3H]aldosterone and [3H]triamcinolone acetonide binding demonstrated that the number of MR decreased from 7,228 +/- 1,067 in surface to 2,299 +/- 434 receptors/cell in crypt cells, whereas the number of GR increased from 20,857 +/- 4,241 in surface to 58,598 +/- 8,207 receptors/cell in crypt cells. The dissociation constants were 2.8 +/- 0.4 nM for the MR and 12 +/- 3 nM for the GR. Indirect immunofluorescence using the specific anti-MR antibody hMRsN and the anti-GR antibody BuGR-2 demonstrated that both unliganded receptors were cytoplasmic and translocated to the nucleus after hormone binding. These data indicate that both surface and crypt cells are potentially responsive to mineralocorticoids and glucocorticoids and that both the MR and GR require hormone for nuclear translocation.

Aldosterone↗