Parathyroid hormone suppression by intravenous 1,25-dihydroxyvitamin D. A role for increased sensitivity to calcium.

Numerous in vitro studies in experimental animals have demonstrated a direct suppressive effect of 1,25-dihydroxyvitamin D (1,25(OH)2D) on parathyroid hormone (PTH) synthesis. We therefore sought to determine whether such an effect could be demonstrated in uremic patients undergoing maneuvers designed to avoid changes in serum calcium concentrations. In addition, the response of the parathyroid gland in patients undergoing hypercalcemic suppression (protocol I) and hypocalcemic stimulation (protocol II) before and after 2 wk of intravenous 1,25(OH)2D was evaluated. In those enlisted in protocol I, PTH values fell from 375 +/- 66 to 294 +/- 50 pg (P less than 0.01) after 1,25(OH)2D administration. During hypercalcemic suppression, the "set point" (PTH max + PTH min/2) for PTH suppression by calcium fell from 5.24 +/- 0.14 to 5.06 +/- 0.15 mg/dl (P less than 0.05) with 1,25(OH)2D. A similar decline in PTH levels after giving intravenous 1,25(OH)2D was noted in protocol II patients. During hypocalcemic stimulation, the parathyroid response was attenuated by 1,25(OH)2D. We conclude that intravenous 1,25(OH)2D directly suppresses PTH secretion in uremic patients. This suppression, in part, appears to be due to increased sensitivity of the gland to ambient calcium levels.

Renal transplantation for systemic lupus erythematosus and recurrent lupus nephritis. A single-center experience and a review of the literature.

Prior to 1975 patients with systemic lupus erythematosus were generally not considered candidates for renal transplantation because of concern that immune complex deposition would rapidly destroy the allograft. However, recent evidence suggests that good patient and graft survival rates can be achieved comparable to other renal diseases. Between September 23, 1963 and July 31, 1990, 1070 renal transplants were performed at Washington University Medical Center (WUMC). During this period, 14 patients with SLE (12 female and 2 male) received 16 renal transplants (7 living-related donor [LRD], 1 living-unrelated donor [LURD], and 8 cadaver [CAD]). The mean age at the time of the first transplant was 32.5 +/- 10.3 years. The duration of disease prior to transplant was 88.0 +/- 45.9 months and the duration of hemodialysis prior to transplant was 36.0 +/- 33.7 months. Of these patients, 7/14 (50%) had negative and 3/14 (21%) positive SLE serology pre- and post-transplant, 3/14 (21%) had negative serology pretransplant that became positive posttransplant, and 1/14 (2%) was positive pretransplant and became seronegative posttransplant. Patient survival was 92.8% (13/14), and of the 16 kidneys transplanted 62.5% (10/16) are still functioning with a mean follow-up period of 43.7 +/- 45 months. The current mean serum creatinine was 1.4 +/- 0.26 mg/dl. One noncompliant patient developed recurrent lupus nephritis bringing the total number of cases reported in the literature to seven. The present study demonstrates that patients with SLE can be transplanted with excellent patient and graft survival and function and a low rate of recurrent lupus nephritis. From a review of the literature, there appears to be an association between positive SLE serology pre- and posttransplant and recurrent lupus nephritis.

Comparison of survival of an expanded polytetrafluoroethylene graft designed for early cannulation to standard wall polytetrafluoroethylene grafts.

BACKGROUND: Placement and maintenance of a well-functioning vascular access are essential for delivery of adequate hemodialysis. Newly placed polytetrafluoroethylene (PTFE) arteriovenous grafts require a period of wound healing and incorporation of fibrous tissue before use, a period typically lasting two to three weeks. An ideal PTFE graft would be one that can be used for vascular access immediately, obviating the need for temporary dialysis catheters. Recently an expanded PTFE (ePTFE) graft with a mesh cannulation segment (Diastat graft) has been proposed for early cannulation. STUDY DESIGN: This is a retrospective single-center study comparing ePTFE graft survival to contemporaneously placed standard wall PTFE (GORE-TEX) grafts. RESULTS: Forty-seven consecutive new or established patients receiving chronic hemodialysis had grafts (25 ePTFE, 22 standard PTFE) placed between November 1994 and July 1995. There were no significant differences between the groups in age, race, gender, incidence of diabetes mellitus, or peripheral vascular disease. By the end of the study, 21 of 25 ePTFE grafts had clotted, compared with 11 of the 22 patients receiving a standard PTFE graft. Median time to first clotting was 53 days for the ePTFE grafts and 164 days for the standard PTFE grafts (p < 0.0001). Nine patients with ePTFE grafts required a temporary catheter after their first clotting episode. CONCLUSIONS: The ePTFE grafts thrombosed at a significantly higher rate than standard wall PTFE grafts. Further experience with the Diastat graft might improve graft survival. However, early experience does not suggest that the avoidance of short-term temporary access outweighs the problem of high clotting rate, and its attendant morbidity.

The effect of comorbid conditions on hemodialysis access patency.

Vascular access complications are a continuing source of hospitalization and morbidity in chronic dialysis patients. Several factors have been identified that are associated with complications in patients with native vein and prosthetic bridge arteriovenous graft fistulas. Early failure of native vein arteriovenous fistulas most consistently are related to small blood vessels. It remains unclear whether other comorbid factors play a role in complications of this fistula type. Prosthetic bridge fistulas are frequently placed in the United States and are associated with frequent complications. Factors most consistently associated with higher complication rates are diabetes mellitus, older age, and black race. Antiphospholipid antibody-associated syndromes and erythropoietin therapy have also been suggested as contributing factors. In addition, elevated lipoprotein(a) and hypoalbuminemia have been found to be associated with an increase of prosthetic graft thrombosis in white and Hispanic dialysis patients. This information strongly suggests that fistula complications are multifactorial. An improved understanding of the mechanisms of these associations may aid in the delineation of the pathogenesis and an improvement in the outcome of this important problem.

Permanent vascular access: a nephrologist's view.

Vascular access complications are the greatest cause of morbidity in hemodialysis patients in the United States. Although arteriovenous fistulas have been recommended as the preferred mode of vascular access, recent data indicate that the majority of patients on hemodialysis in the United States have prosthetic graft fistulas. The most frequent complications of prosthetic graft fistulas are thrombosis and stenosis. Hospitalization rates for fistula complications are higher in patients with diabetes mellitus and of black race. Pathogenesis of intimal hyperplasia may include elaboration of platelet-derived growth factor and mechanical endothelial injury. Screening for stenosis and impaired blood flow in fistulas can be carried out with recirculation measurements, venous and intra-access pressure measurements, and Doppler ultrasound. A combination of the techniques is probably the best current strategy for fistula screening and further evaluation. Surgical thrombectomy and fistula revision remain the standard for comparison of newer approaches to management of complications. Percutaneous angioplasty with or without stent placement, thrombolysis, and use of atherectomy devices may play an increasing role in the treatment of complications, although comparative trials of these modalities need to be performed. No satisfactory long-term pharmacologic means of preventing thrombosis, stenosis, or restenosis have been found for graft arteriovenous fistulas. It is hoped that future directions in the field of vascular access placement and management will include better strategies for allowing primary arteriovenous fistula development, advances in graft materials, improved understanding of the pathogenesis of thrombosis and stenosis, and development strategies to prevent complications.

Hemodialysis prescription and delivery in a metropolitan community. The St. Louis Nephrology Study Group.

The National Cooperative Dialysis Study attempted to determine adequacy of hemodialysis based on kinetic modeling of urea. Based on this study, it has been recommended that a dimensionless term quantitating the amount of dialysis delivered (KT/V) be greater than 1.0 to avoid adverse outcomes. With the declining duration of dialysis treatments in the United States, there has been concern that a significant proportion of patients may be receiving inadequate therapy. The purpose of this study was to survey hemodialysis practices and treatment outcomes in our metropolitan area. Sixteen area nephrologists volunteered to study their outpatient hemodialysis patients (N = 617). Demographic data and urea kinetic modeling results were then analyzed at the lead center. The mean length of dialysis was 3.2 +/- 0.4 (SD) hours with dialysis blood flow rates of 333 +/- 74 ml/min. The mean KT/V was 1.03 +/- 0.25 with nearly half of patients failing to attain a KT/V of 1.0. In 55% of patients the reason for a low KT/V was the prescription of an insufficient amount of dialysis treatment. In the remainder, insufficient delivery of prescribed dialysis contributed to the low KT/V. Only 1 of 33 patients undergoing dialysis twice a week achieved the recommended quantity of treatment on a weekly basis. Patients undergoing dialysis in non-profit units had a higher KT/V than those treated in proprietary units (1.1 +/- 0.26 vs. 0.92 +/- 0.22, P less than 0.001). In addition, patients dialyzed in units that performed urea kinetic modeling on all or selected patients had a higher KT/V compared to those in units where urea kinetics were not done (1.12 +/- 0.25 vs. 0.95 +/- 0.23, P less than 0.001). If these findings reflect practices elsewhere in the United States, many hemodialysis patients fail to receive the current recommended quantity of treatment.

Impaired delivery of dialysis: diagnosis and correction.

Hemodialysis treatments yielding inadequate amounts of dialysis, as defined by urea kinetic modeling, are partially responsible for considerable mortality and morbidity in the United States. In almost 50% of dialysis treatments resulting in a Kt/V of < 1.0, the culprit is impaired delivery of the prescribed amount of dialysis. The factors involved in impaired delivery of dialysis are many and often elusive. If present and widespread, a search for the cause of the problem entails careful examination of the equipment and nursing procedures. If impaired delivery is a sporadic and infrequent event, a patient-specific investigation should be undertaken. In either circumstance, a clear understanding of the principles and practical aspects of hemodialysis greatly assists the nephrologist as a sleuth.

Glutamine transport in basolateral vesicles from dogs with acute respiratory acidosis.

It has been shown that acute respiratory acidosis in dogs results in enhanced renal extraction of L-glutamine from plasma and increased ammonia excretion per nephron. To determine whether a component of the enhanced L-glutamine extraction results from increased transport of L-glutamine across the basolateral membrane into the renal proximal tubular cell, we measured Na+ gradient-dependent L-[3H]glutamine transport in proximal tubular basolateral membrane vesicles isolated from kidneys of normal dogs and from kidneys of dogs following 2 h of acute respiratory acidosis. The initial rate of Na+ gradient-dependent L-[3H] glutamine uptake (15 s) was increased significantly in basolateral membrane vesicles from the acidotic compared with normal dogs. Increased uptake could be measured under conditions in which changes in membrane potential resulting from fluxes of solute were minimized. We conclude that an adaptation occurs in the basolateral membrane of the renal proximal tubular cell during acute respiratory acidosis that allows increased transport of L-glutamine across the membrane into the proximal tubular cell. This adaptation may permit increased ammonia production per nephron.

Prosthetic fistula survival and complications in hemodialysis patients: effects of diabetes and age.

Current trends in hemodialysis include increases in patient age, prevalence of diabetes, and use of high-efficiency dialysis. These patients often require prosthetic fistulas for vascular access. Little is known about fistula survival and complications in this setting. Hemodialysis patients at our center receiving new prosthetic fistulas between January 1, 1988 and January 1, 1991 were studied. Sixty-five prosthetic fistulas were placed in 50 nondiabetic and 73 in 51 diabetic patients. There were no differences in age, sex, race, or access type or location in patients with or without diabetes. Seventeen percent of fistulas were lost in nondiabetic compared with 32% diabetic patients (P less than 0.05). Life-table analysis showed 1- and 2-year graft survivals of 88% and 77% in nondiabetic patients and 70% and 67% in diabetic patients. A significant difference in graft survivals was found for the time interval from 100 to 600 days after fistula placement. There were 188 complications in 92 of the grafts. There was no difference in the distribution of thromboses, elevated recirculations, or infections causing the first complication in patients with or without diabetes, but complications occurred earlier in diabetic patients (175 +/- 26 v 286 +/- 36 days, P less than 0.01). Nondiabetic patients with prosthetic fistula complications were significantly older than those without complications (64 +/- 4 and 56 +/- 2 years, respectively, P less than 0.05). No impact of age on complications was found in diabetic patients. The probability of a first thrombosis at 6 and 12 months was 29% and 49% in nondiabetic and 55% and 72% in diabetic patients (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The short-term effects of a low-protein diet in stable renal transplant recipients.

The short-term effects of a low-protein diet were assessed in eight stable renal transplant recipients on maintenance immunosuppression 38 +/- 7 months following transplantation. Two-week baseline protein and caloric intakes derived from daily food records were 0.97 +/- 0.08 g/kg.d and 25.3 +/- 1.6 kcal/kg.d. A diet containing 0.6 g protein/kg.d and greater than or equal to 30 kcal/kg.d was then prescribed. Nitrogen balance was assessed for 3 weeks and final measurements were taken at 4 weeks. Body weight decreased from 76.4 +/- 3.8 to 74.8 +/- 3.5 kg (P = 0.028). Baseline inulin clearance was 40.9 +/- 6.2 mL/min.1.73 m2 and did not change following the dietary modification. There were no significant changes in plasma proteins, lipids, or in white blood cell counts. During the low-protein diet, mean protein intake was 0.62 +/- 0.02 g/kg.d (P less than 0.001 v baseline) and the mean caloric intake decreased to 20.8 +/- 1.2 kcal/kg.d (P = 0.036 v baseline). Mean baseline nitrogen balance was -62.8 +/- 81.4 mmol/d (-0.88 +/- 1.14 g/d) and remained negative, -113.5 +/- 35.7 mmol/d (-1.59 +/- 0.50 g/d), after 3 weeks of the protein-restricted diet. A positive correlation between caloric intake and nitrogen balance combining all periods was seen (r = 0.61, P less than 0.01, n = 32) with predicted neutral nitrogen balance occurring at a caloric intake of 28 kcal/kg.d. There was also a weak correlation (r = 0.42, P less than 0.05, n = 32) between protein intake and nitrogen balance.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of fasting on citrate transport by the brush-border membrane of rat kidney.

Fasting in rats decreases plasma citrate levels and reduces urinary citrate excretion by the kidney. After 72 h of fasting, the endogenous renal citrate clearance was decreased and the fractional citrate excretion was 0.026 +/- 0.008 compared with 0.218 +/- 0.030 in control fed rats. To determine whether these findings result from an adaptation in citrate transport across the plasma membrane of the renal tubular cell, Na+ gradient-dependent [14C]citrate uptake was examined in brush-border membrane vesicles (BBMW) prepared from kidneys of fed and 72-h fasted rats. The initial rate (10 s) of Na+ gradient-stimulated uptake of 100 microM citrate was significantly increased in BBMW from kidneys of fasted rats (380 +/- 24.9 pmol/mg prot) compared with fed rats (255 +/- 24.9 pmol/mg prot). Arterial acid-base parameters from conscious animals were similar between the two groups. There was no significant difference in Na+-independent citrate uptake or in L-glutamine uptake measured at 20 s in BBMV from the kidneys of fasted compared with fed rats. An adaptation occurs in the brush-border membrane of the renal tubular cell of fasting rats, unrelated to systemic acidosis, that may result in increased reabsorption of citrate.

The effects of hemodialysis on platelet deposition in prosthetic graft fistulas.

The effects of hemodialysis on the coagulation system are not completely understood. The purpose of these studies was to determine the effects of hemodialysis on platelet deposition in prosthetic graft fistulas. Nine patients with polytetrafluoroethylene graft fistulas and two with native vein fistulas were studied. Dialysis was performed thrice weekly with blood flow rates of 400 to 450 mL/min and regenerated cellulose hollow-fiber dialyzers. Platelets were labeled with oxine-111indium. Images of the fistula were obtained immediately after injection (baseline study), postdialysis the same day, the following morning, and before and after the next two routine treatments. Images were analyzed by drawing regions of interest, and activities were expressed as counts per pixel and percent baseline after correction for background and biologic clearance and physical decay. There was a marked dialysis-associated enhancement of platelet deposition in sites along the graft. More than a twofold increase in uptake was noted most frequently in the arterial anastomosis, arterial loop, midloop, venous loop, and venous anastomosis regions. The arterial loop and midloop regions were most consistently affected. The arterial side of the loop during the first dialysis treatment showed an increase from 15 +/- 3 counts/pixel (+/- SE) predialysis to 46 +/- 14 counts/pixel postdialysis (P = 0.03, Mann-Whitney). The uptake increased with dialysis in the midloop region from 12 +/- 2 counts/pixel to 40 +/- 11 counts/pixel (P = 0.04, paired t-test). The uptake was nearly reversed by the next dialysis treatment. Subsequent treatments had a similar pattern. No significant change in activity was found in the two patients with native vein fistulas.(ABSTRACT TRUNCATED AT 250 WORDS)

Flow in hemodialysis grafts after angioplasty: Do radiologic criteria predict success?

BACKGROUND: The anatomic success of percutaneous angioplasty of venous stenosis is determined by the improvement in cross-sectional diameter of the vessel. A successful outcome is defined as a residual stenosis of <30%. The purpose of this study was to determine whether the angiographic assessment of a venous stenosis correlates with the change in graft blood flow following angioplasty. METHODS: Twenty-two hemodialysis patients with decreased intragraft blood flow (<700 mL/min) underwent diagnostic fistulography and angioplasty. All grafts were patent at the time of the procedure. Intragraft blood flow was measured before and after angioplasty using the ultrasonic dilution technique. Change in graft blood flow after angioplasty was correlated to the morphologic changes of the treated stenosis. RESULTS: The mean preangioplasty and postangioplasty graft blood flows were 457 +/- 136 and 818 +/- 202 mL/min, respectively. The mean degree of stenosis before angioplasty was 74 +/- 15% and 18 +/- 14% after dilation (P < 0.001). The only variable that significantly correlated with postangioplasty blood flow was preangioplasty flow (r2 = 0.22, P < 0.001). The postangioplasty blood flow was not significantly different than the highest recorded blood flow measured in that graft (798 +/- 213 mL/min, P = NS). There was no significant correlation between the change in blood flow and the change in percentage of stenosis. CONCLUSION: Following angioplasty of a venous stenosis, the graft blood flow is most closely predicted by the preprocedural blood flow and is similar to the highest recorded blood flow ever measured in that graft. Angiographic criteria to assess the success of angioplasty are not predictive of changes in blood flow.

The effects of hemodialysis on platelet activation with new and reprocessed regenerated cellulose dialyzers.

Biocompatibility of dialysis membranes is defined, in part, by the tendency to activate the coagulation system. Methods for evaluating stimulation of the coagulation include analyses of markers of platelet activation. The purpose of these studies was to ascertain the effects of high blood flow rates and reprocessing on platelet activation during routine hemodialysis with regenerated cellulose membranes. The platelet alpha-granule protein, beta-thromboglobulin (BTG), was measured in patients undergoing routine chronic hemodialysis with regenerated cellulose dialyzers. Initial studies showed BTG levels to increase from 24 +/- 2 IU/mL at the baseline to 30 +/- 3 IU/mL at 120 minutes and postdialysis, respectively (P < 0.05). In contrast, BTG levels corrected for hemoconcentration with plasma protein concentrations showed no significant changes compared with baseline values. Further studies assessed the effects of two types of new and reprocessed regenerated cellulose dialyzers during four different treatments. Platelet counts at 10 and 30 minutes did not change compared with the baseline, while white blood cell counts decreased significantly. No significant changes in BTG levels occurred when corrected for hemoconcentration with either dialyzer. Additional studies with new and reprocessed regenerated cellulose dialyzers comparing 450 and 220 mL/min blood flow rates at 10 minutes showed no change in BTG. In summary, these studies show no evidence for platelet activation by routine hemodialysis with regenerated cellulose membranes. Differences from previous studies include correction of BTG for hemoconcentration due to ultrafiltration and pre-rinsing of dialyzers. Methods for assessment of cellular activation by dialysis membranes must account for hemoconcentration.

Factors affecting delivery of high-efficiency dialysis using temporary vascular access.

The effectiveness of hemodialysis depends, in part, on the delivery of the prescribed rate of blood flow and the amount of blood recirculation. Studies evaluating the magnitude of recirculation in double-lumen catheters at blood flow rates > or = 300 mL/min have not been performed. We therefore examined the effects of prescribed blood flow rate and placement site on measure blood flow, recirculation and effective clearance using double-lumen catheters in 17 patients. Double-lumen catheters were placed in the internal jugular (12.5 cm), subclavian (20 cm), and femoral veins (15 cm and 24 cm). Recirculation studies were performed in triplicate with a two-needle method at blood flow rates of 250, 300, 350, and 400 mL/min. Blood flow rate was measured with an ultrasonic flow meter placed on the venous line. The arterial line pressure was continuously monitored. Mean arterial line pressure was -105 +/- mm Hg at 250 mL/min and -231 +/- mm Hg at 400 mL/min prescribed blood flow rates in the internal jugular, subclavian, and 15-cm femoral vein catheters. Patients with 24-cm femoral catheters had a mean arterial line pressure of -196 +/- mm Hg at 250 mL/min and -327 +/- mm Hg at 400 mL/min. In spite of the change in arterial line pressure, measured blood flow rate increased appropriately at all set blood flows and with all catheter sites studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Severe dialyzer dysfunction undetectable by standard reprocessing validation tests.

It is generally accepted that careful monitoring of total cell volume and ultrafiltration rates will ensure adequate function of reprocessed dialyzers. During routine urea kinetic measurements we noted that the percent of patients with clearances less than 200 ml/min increased from 5% to 48% despite adherence to these validation tests. As these patients did not have evidence of recirculation in the vascular access, possible causes of dialyzer dysfunction were investigated. Injection of methylene blue into the dialysate port revealed non-uniform flow of dialysate in dialyzers from patients with markedly reduced clearances. In vitro studies of dialyzers subjected to sequential daily reprocessing, without patient exposure, demonstrated that in vitro clearances declined in one lot but not another. The initial clearances of 218 +/- 4 ml/min fell progressively to 112 +/- 18 (P less than 0.001) after 15 reuses. No effects of reprocessing were found in a different lot (230 +/- 2 vs. 226 +/- 4 ml/min). Soaking the dialyzers from the affected lot in either the disinfectant or dialysate solution caused a decline in the clearances which was less than that of serial reuse. Although the magnitude of the problem of dialyzer malfunction with reuse is unknown, careful attention to dialyzer function is warranted in patients treated with reprocessed dialyzers.

The effects of atrial peptide in humans with chronic renal failure.

The role of atrial peptide in humans with chronic renal insufficiency is uncertain. Therefore, the effects of synthetic atrial peptide (atriopeptin III, 24 amino acids) infusion on renal function and solute excretion were examined in 16 subjects with chronic renal insufficiency of diverse etiologies. After a two-hour baseline period, atrial peptide was infused for four hours in doses ranging from 0.005 to 0.1 micrograms/kg/min. When all doses were combined, absolute and fractional excretions of sodium increased significantly from baseline values (130 +/- 15 to 231 +/- 28 microEq/min and 3.57 +/- 0.57 to 6.03 +/- 1.26%, respectively, P less than 0.05). Significant increases in urinary excretion of chloride, calcium, and phosphorus were also seen during atrial peptide infusion. Increased absolute and fractional phosphorus excretion persisted during the two-hour postinfusion period, while excretion of other solutes returned to baseline. Glomerular filtration rate (GFR) increased by greater than 20% in five of 16 subjects. Two subjects with severe renal insufficiency (GFR = 9 and 12 mL/min) had no apparent response to atrial peptide infusion. Subjects receiving doses of 0.05 and 0.1 microgram/kg/min had significant falls of mean arterial pressure by the last hour of infusion. A dose-dependent effect of atrial peptide on sodium excretion was suggested, but not statistically significant. No apparent dose-dependent effect was seen on GFR or other solute excretions. Despite the presence of chronic renal insufficiency, atrial peptide increased renal solute excretion in most subjects. The demonstration that atrial peptide retains its diuretic and natriuretic effect in the presence of renal insufficiency supports the hypothesis that atrial peptide plays an important adaptive role in sodium homeostasis of the failing kidney.

Glutamine transport in renal basolateral vesicles from dogs with metabolic acidosis.

To determine whether the increased ammonia production per nephron in chronic metabolic acidosis is accompanied by augmented L-glutamine transport across the basolateral membrane of the renal cortical cell and consequent increased availability of this ammoniagenic amino acid, we measured L-[3H]glutamine transport in basolateral membrane vesicles (BLMV) isolated from kidneys of normal and acidotic dogs. Na+ -dependent electrogenic transport of L-[3H]glutamine was demonstrated in BLMV from kidneys of normal dogs that exhibited saturability over the concentration range of 25 microM to 2 mM L-glutamine. The apparent Km was 416 +/- 114 microM and Vmax was 536 +/- 129 pmol X mg protein-1 X 15 s-1. The initial rate of Na+ -dependent L-[3H]glutamine transport was increased in BLMV from kidneys of acidotic dogs, as reflected by an increased apparent Vmax. We conclude that an adaptation resulting in greater uptake of L-glutamine across the basolateral membrane of the renal cortical cell may underlie, in part, the increased rate of ammonia production per nephron seen in chronic metabolic acidosis.

Fatal Rhizopus infections in hemodialysis patients receiving deferoxamine.

Four hemodialysis patients receiving deferoxamine for metal overload had fatal rhinocerebral rhizopus infections. Serious fungal infections are not commonly seen in patients on dialysis, and none of these patients had the usual risk factors for rhizopus infection. Deferoxamine is being used with increased frequency in dialysis patients for aluminum and iron overload states. We propose that there is a link between the deferoxamine therapy and this unusual infection. Deferoxamine may serve as a specific growth factor for Rhizopus species or may alter host immune function. We suggest searching for fungal organisms in patients with unexplained illnesses receiving deferoxamine.

Effects of antiplatelet drugs on dialysis-associated platelet deposition in polytetrafluoroethylene grafts.

Hemodialysis is associated with platelet deposition in polytetrafluoroethylene (PTFE) graft fistulas. We determined whether aspirin or ticlopidine would modify this response. Patients on chronic hemodialysis with forearm loop PTFE fistulas were studied. Platelets labeled with 111indium were injected and a baseline scan of the fistula arm was made with a large field of view gamma camera. After a routine dialysis treatment, a second scan was performed within 1 hour. Four weeks later, a repeat labeled platelet study was conducted after taking either aspirin 325 mg/d or ticlopidine 250 mg/d orally for 7 days. Images were computer analyzed by drawing seven standardized regions along each graft. The counts per second per pixel in postdialysis images were compared with predialysis images for each region and a percent uptake compared with the predialysis image was calculated. Regions with dialysis-induced uptake of more than 1.5-fold compared with the predialysis image before antiplatelet drug therapy were compared with these same regions after therapy. Six patients were studied before and after aspirin therapy. Uptakes larger than 1.5-fold over predialysis images were found in 12 of 40 regions and were 292% +/- 50% (+/-SEM) before and 193% +/- 25% of predialysis values after aspirin (P = 0.02, paired t-test). Uptakes in the remaining regions were 107% +/- 4% before and 115% +/- 6% after aspirin (P = NS). A second group was studied before and after ticlopidine (n = 5). Uptakes increased by more than 1.5-fold compared with predialysis images in 19 of 30 regions and had a median of 286% increased uptake (mean, 785% +/- 374%) before and 160% (153% +/- 10%) after drug therapy (P < 0.001, Wilcoxon). Uptakes in the remaining regions were 116% +/- 5% before and 134% +/- 13% after drug therapy (P = NS). Platelet aggregation studies suggested compliance with both drugs. These studies show that these antiplatelet drugs reduce, but do not completely prevent, dialysis-associated radiolabeled platelet deposition in PTFE grafts.