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Biomedical subjects

D W Windus

Publications and source records attributed to D W Windus.

18 recordsLinked to original sources

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)

Adult

Dialysis access grafts: anatomic location of venous stenosis and results of angioplasty.

PURPOSE: To determine the distribution of stenoses and results of angioplasty in patients with similar forearm dialysis grafts made of polytetrafluoroethylene (PTFE). MATERIALS AND METHODS: Diagnostic radiographs of the fistula obtained in 215 patients were reviewed; 90 patients had similar, unrevised forearm PTFE loop dialysis grafts. The location, morphology, and results of angioplasty were reviewed for each measurable stenosis. Surgical, radiologic, and dialysis records were reviewed to document the subsequent patency rate of each patient's dialysis access. RESULTS: On the initial diagnostic fistulogram, 93 stenoses were identified. The anatomic distribution included 47% at the venous anastomosis and 11% within 1 cm of the anastomosis. Life table analysis revealed a 6-month patency rate of 63% and a 1-year patency rate of 41% for the first angioplasty in a given graft, and a 6-month patency rate of 44% and a 1-year patency rate of 22% [corrected] for the second angioplasty. CONCLUSION: Performance of serial venous angioplasty procedures may help prolong the life of a graft, but the patency rates diminish with subsequent interventions.

Aged

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.

Aging

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)

Age Factors

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.

Aged

Calcium acetate as a phosphorus binder in hemodialysis patients.

Much interest is currently centered on the use of calcium acetate as a phosphorus binder in patients with renal failure. Therefore, this compound in subjects previously stable on calcium carbonate and undergoing high-efficiency hemodialysis with a dialysate calcium of 2.5 mEq/L was evaluated. Twenty subjects were switched from generic calcium carbonate to a single calcium carbonate preparation for a period of 2 months. This was followed by a phase (1 month) in which calcium acetate was substituted for calcium carbonate at a dose containing half the amount of elemental calcium. Subjects then continued calcium acetate for 6 months. It was found that calcium acetate allowed comparable control of immunoreactive parathyroid hormone, calcium, and phosphorus levels compared with calcium carbonate. This occurred with half the amount of elemental calcium ingested in the form of calcium acetate (349 +/- 25 versus 699 +/- 75 mmol/day; P less than 0.001). With this lower dose, the overall incidence of hypercalcemia was the same with each formulation. In the eight subjects concurrently receiving i.v. calcitriol, the incidence of hypercalcemia was significantly higher during the first month of calcium acetate compared with that in those not receiving this compound (P less than 0.05). Of those four subjects receiving the high dose of calcitriol (2 micrograms thrice weekly), all required either reduction in the dose or discontinuation of the drug. Thus, mineral metabolism could be controlled adequately with calcium acetate despite using half as much elemental calcium compared with calcium carbonate. This, however, did not result in a lower incidence of hypercalcemia, particularly in those receiving i.v. calcitriol.

Acetates

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)

Dietary Proteins

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.

Adult

Optimization of high-efficiency hemodialysis by detection and correction of fistula dysfunction.

Recirculation studies were performed in 103 patients treated with high-efficiency dialysis over a 14 month period. Fistulograms were performed on 22 out of 25 patients with greater than 0.15 fractional recirculation at a 400 ml/minute blood pump setting. Clinically significant abnormalities were found in 82% (N = 18) and treated in 17. Two patients had second episodes of elevated recirculations and were treated again within the period of follow-up. Treatment with angioplasty (N = 11) or surgical revision (N = 8) resulted in a fall in recirculation from 0.33 +/- 0.04 to 0.12 +/- 0.02 (P = 0.001). The fractional reduction of urea clearance due to recirculation fell from 0.20 +/- 0.03 to 0.08 +/- 0.02 (P = 0.001) and the effective urea clearance of the dialysis treatment rose by 16% from 193 +/- 7 ml/min to 224 +/- 6 ml/min (P = 0.001). Pre-dialysis BUN fell from 72 +/- 4 mg/100 ml to 62 +/- 3 mg/100 ml (P = 0.012). There was no correlation between venous pressure (VP) at 400 ml/min blood pump setting and recirculation (R2 = 0.04), although VP changed significantly comparing values before and after fistula repair (211 +/- 10 vs. 186 +/- 7 mm Hg, P = 0.012). Venous pressures in 20 of the patients in our dialysis unit with recirculations of less than 0.10 were 201 +/- 6 mm Hg (P = NS compared to patients with recirculation greater than or equal to 0.15 at 400 ml/min blood flow).(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriovenous Shunt, Surgical

Comparison of culture and serology for the diagnosis of cytomegalovirus infection in kidney and liver transplant recipients.

This study compared culture, including the shell vial procedure, with serology, including IgM cytomegalovirus (CMV) antibody testing, for the diagnosis of CMV infection in 42 subjects undergoing cadaveric renal or liver transplantation. Of 35 subjects who developed active CMV infection, 31 had positive cultures, while IgM CMV antibodies were detected in 29. Subjects with symptomatic CMV infection were more likely than asymptomatic subjects to have positive cultures of leukocytes (17/18 vs. 9/17, P = .01). In contrast, symptomatic and asymptomatic subjects did not differ in their IgG or IgM CMV antibody test responses. In subjects with symptomatic infection, viral shedding typically began early in the course of infection, often preceding symptoms, while the serologic response usually followed the appearance of symptoms. With the use of the shell vial procedure to facilitate detection of positive cultures, symptomatic CMV infections following kidney or liver transplantation can be recognized earlier and more reliably using viral culture than by serologic testing.

Adult

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.

Adult

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.

Creatinine

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.

Anuria

The effects of intraperitoneal calcitriol on calcium and parathyroid hormone.

Parathyroid suppression by intraperitoneal calcitriol (1,25(OH)2D3) during peritoneal dialysis. The purpose of this study was to determine if parathyroid hormone (PTH) suppression could be achieved by increasing calcium mass transfer (Ca MT) with high dialysate Ca (4 mEq/liter) or via intraperitoneal (i.p.) 1,25(OH)2D3 in patients undergoing continuous ambulatory peritoneal dialysis. Eleven patients were dialyzed for two months with standard Ca dialysate (3.5 mEq/liter) followed by two months with 4.0 mEq/liter Ca, then by three months of i.p. 1,25(OH)2D3. During the latter period, patients were randomized to groups whose dialysate contained either 3.5 mEq/liter or 4.0 mEq/liter Ca. We found that 4.0 mEq/liter Ca dialysate more than doubled Ca MT (37 +/- 17 mg/day to 84 +/- 6 mg/day) leading to a modest fall (P less than 0.05) in PTH levels (84 +/- 5.5% of controls). Ionized calcium levels did not change. With i.p. 1,25(OH)2D3, however, ionized calcium rose significantly (P less than 0.001) leading to a decline in PTH levels to 53.9 +/- 7.9% of control values. Serum 1,25(OH)2D3 levels rose from undetectable to 47.7 +/- 7.2 pg/dl (normal range 20 to 35). These studies indicate that increasing Ca MT using a 4.0 mEq/liter Ca dialysate leads to a small reduction in PTH concentrations. On the other hand, i.p. 1,25(OH)2D3 is well absorbed into the systemic circulation, raises ionized calcium levels, and leads to a marked suppression of PTH. Thus, i.p. 1,25(OH)2D3 may be a simple and effective means to suppress secondary hyperparathyroidism in patients undergoing CAPD.

Adult

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.

Adult

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.

Acid-Base Equilibrium

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.

Acidosis

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.

Acid-Base Equilibrium