Measurement of Na+ and K+ in nanoliter droplets by ion-specific microelectrodes.
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Biomedical subjects
Publications and source records attributed to R J Hamburger.
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We considered the hypothesis that CAPD is a superior treatment to HD in patients with dialysis-refractory hypertension. We compared 12 HD patients to 22 CAPD patients entered to our program over a one year period. All had been treated for hypertension before dialysis. We found that systolic blood pressure decreased in CAPD patients compared to HD patients, even though medications were more commonly reduced in CAPD patients compared to HD patients. Ten CAPD patients required no medications after one year's treatment. These preliminary data in this small pilot study support the notion that CAPD is superior to HD in blood pressure management of hypertensive patients. A large, multicenter study may be warranted to determine if CAPD favorably influences the risk of cardiovascular complications in dialysis patients compared to HD.
The effect of dialyzer membrane and design on hemostatic parameters during hemodialysis were evaluated in a prospective controlled study. This study demonstrated that hemodialysis is associated with significant platelet activation and loss, which are influenced by both dialyzer configuration and membrane composition. In addition, use of the cuprophan membrane is associated with greater perturbations of the vascular endothelium, as reflected in changes in factor VIII-related von Willebrand factor and 6-keto-prostaglandin F1 alpha concentrations not seen with the polyacrylonitrile membrane. Of the dialyzers studied, the polyacrylonitrile membrane in a hollow-fiber configuration appears to minimize platelet loss and activation, and to minimize increases in factor VIII-related von Willebrand factor and 6-keto-prostaglandin F1 alpha.
We examined the effects of changes in volume flux, with or without changes in sodium flux, on phosphate reabsorption in the proximal convoluted tubule of the rabbit. Experiments were performed: before and after the addition of 10(-5) M ouabain, with a bath of 260, 290, or 320 mosm/kg and a perfusate of 290, and with change in perfusion rate from 15 to 5 nl/min. With the addition of ouabain, volume reabsorption was completely inhibited and phosphate flux decreased significantly. When volume flux was altered without a corresponding change in sodium flux by altering bath osmolality, no change in phosphate flux was noted even though volume flux increased with the hyperosmotic bath and decreased with the hypoosmotic bath. When perfusion rate was decreased from 15 to 5 nl/min, volume reabsorption decreased by 47% and phosphate reabsorption decreased by 45%. Under these circumstances net sodium flux would be expected to decrease. These results are consistent with a relationship between phosphate and sodium, but not fluid, reabsorption. Furthermore, the absence of a relationship between phosphate and volume flux driven by osmotic gradients would suggest that the paracellular pathway is not a significant route of phosphate flux.
To further define the pathophysiology of the syndrome of acquired isolated hypoaldosteronism, we determined plasma concentrations of active and inactive renin and urinary kallikrein and prostaglandin E2 excretion rates in 11 patients with the syndrome, 12 patients with similar serum creatinine levels, but without hyperkalemia, and in 12 normotensive patients with normal renal function and low plasma renin activities (PRA). Ten of 11 patients with the syndrome had low baseline PRA, and, unlike the control groups, six of 11 failed to double their PRA after furosemide stimulation. There were also consistent abnormalities in the percentage of inactive renin, no patient having a value less than and no control subjects having a value greater than 65%. Seven of 11 patients had prostaglandin E2 excretion rates lower than either control groups. Urinary kallikrein excretion rates in the patients with isolated hypoaldosteronism were significantly lower than in the control groups, but increased in response to therapy with fludrocortisone.
Zinc and prolactin levels were measured in 32 male haemodialysis patients; 12 were receiving 50 mg zinc per day as zinc acetate and 20 were not. Zinc-treated patients had significantly higher plasma zinc levels (134 +/- 10 micrograms/dl v 88 +/- 2 micrograms/dl) and lower serum prolactin levels (11 +/- 4 ng/ml v 29 +/- 7 ng/ml) than untreated patients. Plasma zinc and serum prolactin were inversely related in zinc-treated and untreated patients (r = -0.79, p less than 0.001).
Potassium transport in the isolated proximal convoluted tubule (PCT) of the rabbit was studied to determine the importance of concentration-dependent passive processes in potassium reabsorption. Net potassium flux was measured with an initial perfusate potassium concentration of 4 mM and bath potassium concentration of 2, 4, or 6 mM. When bath concentration was 6 mM, there was net potassium secretion in both superficial (SF) and juxtamedullary (JM) PCT. When bath concentration was 2 mM, there was net reabsorption in both groups of tubules. The apparent permeability coefficients were found to be significantly higher in JMPCT (2.96 +/- 0.37 pmol X mm-1 X min-1 X mM-1) than in SFPCT (1.94 +/- 0.34 pmol X mm-1 X min-1 X mM-1). We also attempted to uncover an active potassium reabsorption process by inhibiting water flux, but not other transport processes, by the imposition of a transtubular osmotic gradient. When the perfusate was made 30 mosmol/kg H2O hypertonic to the bath, there was net fluid entry of 0.38 +/- 0.09 nl/min, accompanied by a significant decline in net potassium flux. The collected fluid-to-perfusate potassium concentration ratio was not significantly less than zero, thereby not providing evidence for active potassium reabsorption. These studies suggest that a primary mode of potassium reabsorption in this segment is due to its movement along a transepithelial gradient established by fluid reabsorption. We have been unable to identify an active component of potassium reabsorption.
As part of a general safety study of iopamidol, a nonionic iodinated contrast agent, urine N-acetyl-beta-glucosaminidase enzyme assays were done to compare the renal toxicity of iopamidol with that of iothalamate and diatrizoate. In a randomized study of 30 patients for computed body tomography and another 30 patients for angiography, 10 in each group were injected with iopamidol, 10 with iothalamate, and 10 with diatrizoate. After computed tomography or angiography with the three agents, there was no significant difference in urinary enzyme levels among the groups. The nephrotoxicity of iopamidol appears equivalent to that of diatrizoate and iothalamate.
The surgical considerations pertaining to 173 continuous ambulatory peritoneal dialysis catheters were reviewed in 140 patients from 1979 through 1983. All catheters were inserted in the operating suite by an open technique. Local anesthesia was used in the majority of patients (59%). Catheter peritonitis was the most frequent complication, 228 episodes/2407 patient months. Twenty-three percent of the patients accounted for 51% of catheter-related peritonitis. Sixteen catheters were removed because of an inability to clear the infection. Intra-abdominal catastrophes were noted in four patients and differentiation from continuous ambulatory peritoneal dialysis peritonitis was based on serial examinations, bacteriologic cultures, and/or a progressive increase in free abdominal air. Surgically-related catheter complications were designated either early (less than 1 month) or late (greater than 1 month) in relation to catheter placement. Frequent early complications were mechanical flow problems and dialysate leaks. Five of 11 mechanical flow difficulties required catheter replacement while none of the dialysate leaks required surgical intervention, and all healed spontaneously. Common late complications included 35 tunnel infections, 23 of which were associated with peritonitis. Nine of these catheters (25%) were removed. Cuff extrusion was also associated with a high incidence (83%) of catheter attrition. Thirty-six patients underwent renal transplantation and in no instance did the catheter increase patient or renal allograft morbidity rates.
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The tubuloglomerular feedback (TGF) response was studied in control rats and after either hypotensive hemorrhage or aortic clamping (AC). TGF was assessed both by differences in proximally and distally determined single nephron glomerular filtration rate (SNGFR) and by proximally determined SNGFR responses to orthograde microperfusion at 0 or 36 nl/min. Hypotensive hemorrhage was induced by the removal of blood equivalent to 0.5-1% of body weight. In control rats, proximal SNGFR was 29.74 +/- SE 0.87 nl/min and distal SNGFR was 28.64 +/- 0.82 nl/min, values not significantly different from each other. After moderate hemorrhagic hypotension (MH: BP = 86 +/- 1 mm Hg) or AC (BP = 70 +/- 4 mm Hg), both proximal and distal SNGFR decreased, with no significant differences between the values in either group. After severe hemorrhagic hypotension (SH; BP = 70 +/- 1 mm Hg), proximal SNGFR was 25.23 +/- 2.07 nl/min and distal SNGFR was 19.69 +/- 1.50 nl/min, values significantly different from each other and consistent with an enhanced feedback response. Using orthograde microperfusion, a significant reduction in SNGFR at a perfusion rate of 36 nl/min was observed under all circumstances. However, with SH hypotension the percent change in SNGFR at the two perfusion rates was significantly increased to 35.0 +/- 5.5%, compared to 21.6 +/- 6.6% in controls. In contrast, AC with reduction in renal perfusion pressure to a degree comparable to SH hypotension did not augment the relative decrease in SNGFR, the percentage change being 22.2 +/- 7.2%. Neither was TGF enhanced after MH hypotension when similar volumes of blood were removed but a similar decrease in BP was not obtained. These results suggest that some factor related to severe systemic hypotension enhanced the TGF response.
Polyarteritis nodosa developed in one of 34 patients undergoing long-term maintenance hemodialysis with persistent hepatitis B surface antigenemia. Exacerbation of the baseline hypertension and progressive peripheral neuropathy during the recovery phase of hepatitis B surface antigen hepatitis were the initial features. Poor response to aggressive corticosteroid and immunosuppressive therapy in this patient was in contrast to recent experience in patients undergoing long-term hemodialysis and the general population.
The efficacies of low-dose heparin and low-dose heparin plus ticlopidine as anticoagulants during hemodialysis in acutely uremic dogs were compared and evaluated. Heparin was administered as a bolus at a dose of 100 U/kg. In preliminary experiments it was determined that dogs dialyzed with ticlopidine alone demonstrated gross clotting of the artificial kidney within 2.5 hr. Ticlopidine was administered by gavage at a dose of 50 mg/kg/day starting 72 hr prior to hemodialysis and continuing throughout the period of hemodialysis (4 days). Each dog was dialyzed four times with either heparin alone or heparin plus ticlopidine. Each hemodialysis lasted 3.5 hr. Parameters followed included dialysis clearance of urea and creatinine, ultrafiltration rate, residual blood volume, gross clotting episodes, platelet count, and levels of fibrinogen and thromboxane B2. A lesser degree of hemodialysis-associated thrombocytopenia, a lower residual blood volume, fewer episodes of gross clotting, no reduction in fibrinogen levels, and no increase in thromboxane B2 levels were observed in the heparin plus ticlopidine group as compared to the heparin group alone. Although ticlopidine at the dosage employed should not be used as the sole anticoagulant for hemodialysis, it may be useful when added to low-dose heparin. The salutary effects demonstrated in this study suggest clinical benefits of the combination.
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A comparison of the efficacy of prostacyclin and heparin as anticoagulants during hemodialysis in uremic dogs was evaluated. Prostacyclin was infused continuously into the arterial limb of the dialyzer (100 ng/kg/min) while heparin was administered as a 5000 unit bolus at the beginning of dialysis. Prostacyclin and heparin were alternated and a total of 4 dialyses/dog were performed. Parameters followed to assess the efficacy of dialyses included: dialysance (ml/min) of urea, creatinine, ultrafiltration rate (ml/hr), residual volume and platelet count (% of baseline). A lesser degree of hemodialysis associated thrombocytopenia, and a higher ultrafiltration rate were observed with prostacyclin. These studies demonstrate that prostacyclin can be used alone as an anticoagulant in a uremic dog model, and in contrast to heparin it maintains the platelet count and improves the ultrafiltration rate during hemodialysis.
The proximal renal tubules have a marked affinity for gentamicin; they also are the major site of nephrotoxicity caused by this drug. The uptake of radiolabeled gentamicin in separated, viable renal tubules prepared by enzymatic digestion of rabbit kidneys was studied. The preparations showed rapid initial uptake of gentamicin followed by continued slower uptake. Accumulation was not affected by pH, but was significantly inhibited by ouabain, dinitrophenol, anoxia, and hypothermia in the absence of evident cellular damage. At gentamicin concentrations of greater than 50 microgram/ml in the medium, there was competition for drug uptake. Gentamicin efflux in tubules that were taken from a medium containing antibiotic and placed into antibiotic-free fluid was slow and incomplete. From these data it appears that gentamicin uptake by separated renal tubules occurs by a process that requires metabolic energy; thereafter, the drug resides in a poorly exchangeable cellular pool.
The effects on juxtaglomerular apparatus (JGA) renin activity of maneuvers known to acutely alter renin secretory rates were studied in rats. Five groups of rats were studied: group I: control; group II: 1% volume expansion; group III: 10% volume expansion; group IV: hypotensive hemorrhage; and group V: aortic clamping. Superficial (S) JGA renin activity was decreased in group II and further decreased in group III. Deep (D) JGA renin activity did not change. After hypotensive hemorrhage both S- and D-JGA renin activity increased. Similar results were seen after aortic clamping, although the increase in D-JGA renin activity was significantly less. These results indicate that S- and D-JGA renin activity may be under the control of different stimuli and may vary independently. They also support the concept that acute changes in renin secretion may be related to changes in renin synthesis.