Toxicity of materials and medications used in dialysis.
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Biomedical subjects
Publications and source records attributed to A R Hull.
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1. Erythrocyte 2,3-diphosphoglycerate (2,3-DPG) and adenosine triphosphate (ATP) were determined in normal individuals, uraemic patients on chronic haemodialysis and patients who underwent renal transplantation, and correlated with plasma phosphate and arterial blood pH. 2. Significant increases in the 2,3-DPG and ATP content were found in the uraemic patients and these persisted after transplantation in spite of marked hypophosphataemia. 3. No correlation was established with plasma phosphate for either of the compounds but 2,3-DPG had a significant correlation with arterial blood pH. 4. Normal values for ATP and 2,3-DPG were observed in post-transplant patients with normal haematological values. The high amounts of erythrocyte 2,3-DPG and ATP in the early post-transplant period are independent of the circulating concentration of inorganic phosphate, and might represent the response of erythrocyte glycolysis to changing arterial blood pH.
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Five patients who had injected intravenous (i.v.) phenmetrazine or methamphetamine developed marked prostration resembling septic shock, disseminated intravascular coagulation, rhabdomyolysis with myoglobinuria, and azotemia. Soon after injection, four noted chills, fever, sweats, nausea, and abdominal cramps. Within hours, they developed vomiting, myalgias, paresthesias, headache, and orthostasis. Cardiorespiratory arrest, accelerated bleeding, and noncardiac pulmonary edema were observed in one patient. From 4 to 11 litres of saline were required in the first 24 h to maintain blood pressure and urine output, suggesting that shock resulted from massive loss of intravascular volume into necrotic muscle. Recognition of this syndrome and treatment by aggressive volume replacement led to the recovery of all five patients.
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A 29-year-old black woman with malignant hypertension and anuria was treated with hemodialysis and antihypertensive drugs. Her renal function improved and her creatinine clearance was 28 ml/min after 4 1/2 months of treatment. Similar cases in the literature are reviewed.
Calcium absorption in 30-cm segments of small intestine was measured by constant perfusion of test solutions containing different concentrations of calcium gluconate. In both the jejunum and ileum, calcium absorption rates increased progressively as luminal calcium concentration was increased stepwise between 1 and 20 mM. Although calcium transport was not saturable within these limits, unidirectional flux ratios of calcium (47Ca) suggest that calcium absorption is active in both the jejunum and ileum. Calcium absorption in patients with chronic renal disease was markedly depressed in both regions of the small intestine. This was due to decreased flux out of the lumen; flux in the reverse direction was normal. Flux ratios in the renal disease patients showed no evidence for active calcium transport. Treatment of these patients for 1 wk within 2 mug/day of 1alpha-hydroxycholecalciferol [1alpha-(OH)-D3] restored net calcium absorption and unidirectional calcium flux out of the lumen to normal values in the jejunum; in the ileum, 1alpha-(OH)-D3 increased calcium absorption 60-83% of normal at the various luminal calcium concentrations. 1alpha(OH)-D3 had no effect on unidirectional calcium flux into the lumen or on xylose and electrolyte absorption in either area of the small intestine.
Magnesium absorption was studied in the normal human jejunum and ileum by in vivo intestinal perfusion, using test solutions containing from 0 to 20 mM Mg (as MgCl2). As luminal Mg concentration was increased, the rate of absorption in the jejunum rose progressively with a tendency towards saturation at the higher concentrations. The kinetics and rates of Mg absorption in the ileum were comparable to those in the jejunum, with the exception that at higher luminal concentrations the ileal absorptive process was fully saturated. Using test solutions containing various combinations of Ca and Mg, we found that Ca had little or no influence on Mg absorption, even through Mg depressed Ca absorption to a modest extent. Patients with end-stage renal disease, who had a reduced rate of Ca absorption (presumably due to deficiency of 1,25-dihydroxycholecalciferol) were found to have a severe depression of Mg absorption. On the other hand, patients with absorptive hypercalciuria and nephrolithiasis, who had an increased rate of Ca absorption, were found to absorb Mg normally. These results suggest that Mg absorption in the human is mediated by a transport process different from that which facilitates Ca absorption, and that normal Mg absorption may be dependent on vitamin D. Our results do not establish whether or not the normal intestine can absorb Mg against an electrochemical gradient.
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In patients with impaired renal function, careful adjustment of gentamicin dosage is required to achieve therapeutic yet nontoxic concentrations. Two regimens that differ in pharmacodynamic characteristics have been recommended for this purpose: prolonging the intervals between administration of equal doses (variable frequency regimen [VFR]) or administering a loading dose followed at the usual intervals by reduced maintenance doses (variable dosage regimen [VDR]). These regimens were compared in a prospective, randomized study of 20 seriously ill hospitalized patients, 10 on VFR and 10 on VDR. Wide variability in peak serum levels of gentamicin was observed both between patients and in individual patients after separate injections of the same dosage. As predicted by the design of these regimens, the trough serum levels of gentamicin correlated significantly with the serum creatinine concentrations in patients on the VDR but not in patients on the VFR. A gentamicin trough level of >/=4 mug/ml was the only variable among those tested that correlated significantly with development or progression of renal insufficiency during treatment with gentamicin, but such trough levels were observed frequently on both regimens. Whereas this study does not permit a direct comparison of the therapeutic efficacy of VDR and VFR, no difference in the risk of nephrotoxicity with these regimens was observed.
Chronic renal failure in man is associated with hyperglucagonemia that is not corrected by hemodialysis. Plasma glucagon concentrations were measured in nine patients before and after renal transplantation. Mean plasma glucagon concentration in eight patients with chronic renal failure before transplantation was 295 plus or minus 171 pg/ml (plus or minus SD). After successful transplantation, mean plasma glucagon concentration fell to 134 plus or minus 81 pg/ml (plus or minus SD) (P less than 0.001). Plasma glucagon concentration remained elevated in an additional patient who received a cadaveric graft that never functioned. Immunologic rejection of transplanted kidneys was associated with a dramatic increase of plasma glucagon concentration.
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10 patients with chronic renal disease on hemodialysis and 8 normals were studied by constant jejunal perfusion of calcium gluconate solutions, using polyethylene glycol as a nonabsorbable marker. Results in normals indicated that calcium absorption from 1 and 5 mM calcium solutions is mainly active. Absorption from 5, 15, and 20 mM solutions was a linear function of luminal calcium concentration, suggesting that the active transport carrier is saturated when luminal calcium concentration is greater than 5 mM and indicating that the increment in absorption at higher luminal concentrations is mainly the result of passive absorption. With 1 mM calcium, normals absorbed calcium against a concentration gradient, whereas the patients secreted calcium. Absorption in the patients was much less than normal with 5, 15, and 20 mM luminal calcium concentrations; however, the slope of this linear (passive) portion of the curve was normal. Unidirectional calcium fluxes were measured with calcium-47. Flux out of the lumen was depressed 2.5-fold in the patients, but flux into the lumen was normal. Xylose, urea, and tritiated water were absorbed normally, indicating no generalized abnormality of jejunal transport in these patients. Endogenous calcium secretion, estimated by the amount of calcium added to a calcium-free solution, was normal in the dialysis patients. These results indicate that active calcium absorption is markedly depressed in patients with chronic renal disease who are receiving hemodialysis therapy. On the other hand, passive calcium movement and endogenous calcium secretions are normal.