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T D McKinney

Publications and source records attributed to T D McKinney.

At least 37 records · Page 2Linked to original sources
PubMed1985

In vivo and in vitro studies of urinary concentrating ability in potassium-depleted rabbits.

The factors responsible for the urinary concentrating defect associated with the potassium-depleted (KD) state are uncertain. The present studies were designed to, first, determine whether a urinary concentrating defect exists in potassium-depleted rabbits and, second, to use the technique of in vitro perfusion to evaluate directly the antidiuretic hormone (ADH) responsiveness of cortical collecting tubules (CCT) in this setting. Feeding female New Zealand White rabbits a potassium-deficient diet for 2 wk caused a significant fall in plasma potassium levels in both the ad-libitum and controlled water intake groups (P less than 0.001). Muscle potassium content after 2 wk of potassium restriction fell from 45.6 +/- 0.9 to 29.0 +/- 1.2 meq/100 g fat-free dry solids (P less than 0.001). Renal papillary sodium content fell significantly from a control value of 234.6 +/- 8.0 to 182.46 +/- 10.0 meq/kg H2O after 2 wk of potassium restriction. Maximal urinary osmolality measured after 12 h of dehydration and 1.25 U pitressin IM was significantly decreased in rabbits after 2 wk of potassium restriction in both the ad-libitum and controlled water intake groups (P less than 0.001). The relationship between plasma potassium concentration and maximum urinary osmolality was significantly correlated in both the ad-libitum and controlled water intake groups, r = 0.73 and 0.68 (P less than 0.001), respectively. In addition, refeeding KD rabbits with normal chow for 1 wk resulted in normalization of both plasma potassium levels and urinary concentrating ability. CCT from control and KD rabbits were perfused in vitro at 25 degrees C. The hydraulic conductivity coefficient, Lp, was significantly reduced at all doses of ADH tested in tubules from KD rabbits when compared with control tubules. In addition, the maximal hydraulic conductivity in tubules from KD rabbits when tested with 200 microU/ml ADH at 37.5 degrees C was only 23% of control values (P less than 0.05). Furthermore, this reduced ADH responsiveness persisted when the bath potassium was elevated from 5 to 20 mM. The reflection coefficient for NaCl when compared with raffinose was 0.91 in tubules from KD animals. Thus, these data suggest that the ADH-resistant urinary concentrating defect associated with potassium depletion is due, at least in part, to a diminished responsiveness of the CCT to ADH. Therefore, further studies were designed to investigate the cellular steps involved in this abnormal response. There was no difference in the 8-para-chlorophenylthio cyclic AMP induced hydroosmotic response between CCT from KD and control rabbits. Since the cAMP-induced hydroosmotic response was similar between KD and control CCT, experiments were performed to evaluate the contribution of phosphodiesterase (PDIE) activity by using the potent PDIE inhibitor isobutylmethylxanthine (10(-4) and 10(-3)M) in the presence of ADH (200 U/ml). Although Lp was increased by PDIE inhibition in CCT from both control and KD animals, the overall hydroosmotic response in CCT from KD rabbits was still significantly reduced when compared with controls. The final experiments used forskolin to evaluate further the adenylate cyclase complex. The resulting hydroosmotic response in CCT from KD rabbits was almost identical to that obtained in controls. In conclusion, these data suggest that the decreased responsiveness of CCT from KD rabbits to ADH involves a step at or proximal to the stimulation of the catalytic subunit of adenylate cyclase, and that PDIE activity makes no contribution to this abnormal hydroosmotic response.

Animals↗
PubMed1984

Further studies of organic base secretion by rabbit proximal tubules.

The aim of the present studies was to further characterize the mechanisms responsible for the secretion of the organic base procainamide by measuring [3H] procainamide transport in superficial (SF) and juxtamedullary (JM) S2 segments of rabbit proximal tubules perfused in vitro. When perfusate pH was changed from 7.4 to 6.2, procainamide secretion increased by 227% in SF and by 159% in JM tubules. In the presence of ouabain the acidic perfusate caused only a minimal increase in procainamide secretion. When the perfusate pH was increased, procainamide secretion was reduced. Acetazolamide, 10(-5) M in the bath, reduced procainamide secretion in both SF and JM tubules. In SF tubules amiloride, 10(-4) M in the perfusate, inhibited procainamide secretion, whereas nonradioactive procainamide, quinidine, and cimetidine did not. When ambient sodium was reduced to 10 mM, the rate of procainamide secretion was low and was not affected by amiloride in the perfusate or acetazolamide in the bath. Amiloride in the bath caused a dose-related inhibition of procainamide secretion. The rate of procainamide secretion by cortical collecting tubules was very low and was not affected by acetazolamide. The mechanisms of renal organic base secretion are complex. Some of the present data are consistent with a mechanism involving organic base-proton exchange across the apical cell membrane. However, other data are not consistent with this being the major mechanism involved.

Acetazolamide↗
PubMed1983

Procainamide uptake by rabbit proximal tubules.

Procainamide is an organic cation and commonly prescribed drug that is actively secreted into the urine by renal proximal tubules. In order to elucidate further the mechanisms involved in this secretion, [3H]procainamide uptake into dissected S2 segments of superficial proximal tubule cells was studied. Uptake of [3H]procainamide was reduced by hypothermia and in a dose-related manner by the organic cations nonradiolabeled procainamide, cimetidine and quinidine and also by the carbonic anhydrase inhibitors acetazolamide and benzolamide, but not by ouabain. All these drugs were shown previously to inhibit transtubular secretion of [3H]procainamide in isolated perfused proximal tubules. The results of these and our previous studies suggest that 1) organic cations reduce the tubular secretion of each other, in part, by competing for uptake across the basolateral membrane of renal tubule cells, 2) acetazolamide and benzolamide reduce urinary excretion of organic cations, in part, by inhibiting proximal tubular secretion and 3) the potential difference across the basolateral cell membrane (due to activity of Na+-K+-dependent adenosine triphosphatase) is not the only driving force for uptake of organic cations into intact renal tubule cells.

Animals↗
PubMed1982

Effect of calcium and phosphate on bicarbonate and fluid transport by proximal tubules in vitro.

Previous studies in living animals have suggested that variations in the serum concentrations of calcium and phosphate directly affect renal tubular bicarbonate transport. To examine this area more directly, we measured the bicarbonate and the fluid transport in isolated rabbit proximal convoluted and straight tubules perfused in vitro. The concentration of calcium in the perfusate was varied between 0 and 5 mM and in the bath between 0.5 and 5 mM. In proximal convoluted tubules, 5 mM calcium in the perfusate and bath caused a significant increase in the rate of bicarbonate absorption, and removal of calcium from the perfusate inhibited both bicarbonate and fluid absorption. The concentration of phosphate in the perfusate and the bath was varied from 0.25 to 5 mM. In both convoluted and straight tubules, there was no significant change in bicarbonate or fluid absorption with changes in the ambient phosphate concentration. We conclude that changes in calcium concentration have significant effects on bicarbonate transport by proximal convoluted tubules but that wide variations in the concentration of phosphate have no significant effect on bicarbonate, sodium, or fluid transport by proximal tubules in vitro.

Absorption↗
PubMed1982

Cimetidine and procainamide secretion by proximal tubules in vitro.

Previous studies have shown that organic bases, including some drugs, are secreted by renal proximal tubules. The present studies examined the transport of the organic bases cimetidine and procainamide by rabbit proximal straight tubules perfused in vitro. Both drugs were secreted into the tubule lumen. [3H]cimetidine secretion was reduced by quinidine, procainamide, and N-acetylprocainamide. Previous studies showed that cimetidine secretion was reduced by other organic bases. Hypothermia and ouabain inhibited [3H]procainamide secretion as was shown previously for cimetidine secretion. [3H]procainamide secretion was also reduced by quinidine, cimetidine, procainamide, and N-acetylprocainamide but not by probenecid. High concentrations of cimetidine (10(-3) M) had no effect on the rates of fluid or total CO2 absorption. When analyzed in terms of Michaelis-Menten kinetics, the effect of cimetidine on procainamide secretion and procainamide on cimetidine secretion was consistent with competitive inhibition. The results suggest that both cimetidine and procainamide are secreted into the lumen of proximal straight tubules predominately by an organic base transport mechanism. These studies raise the possibility that some of these drugs might compete for a common secretory mechanism in renal tubules and reduce the elimination of each other.

Absorption↗
PubMed1982

Heterogeneity of organic base secretion by proximal tubules.

Rabbit renal tubules were perfused in vitro to characterize the secretion of the organic base procainamide by proximal tubules. When [3H]-procainamide was added to the bath it was secreted into the tubule lumen. In tubules from superficial nephrons secretory rates were greatest in S1, intermediate in S2, and lowest in S3 segments. In juxtamedullary tubules secretory rates were greatest in S1 and S2 and lowest in S3 segments. Secretory rates of p-aminohippurate were greatest in S2 and lowest in S1 and S3 segments of both superficial and juxtamedullary nephrons. The results indicate that there is both axial and internephronal heterogeneity for the secretion of this organic base by rabbit proximal tubules. The segmental secretion of procainamide differs from that of p-aminohippurate.

Aminohippuric Acids↗
PubMed1982

Serum aluminum levels in dialysis dementia.

Serum aluminum concentrations were measured in 7 normal persons, 47 chronic hemodialysis patients and in 10 patients with the dialysis dementia syndrome. The concentrations were (mean +/- 1 SEM): 35 +/- 3.7, 109.3 +/- 10.6, and 369 +/- 51.6 micrograms/l, respectively. These results are consistent with the theory that aluminum is involved in the pathogenesis of this syndrome. In contrast to most previous reports dialysate contaminated with aluminum could not be implicated in our patients.

Aluminum↗
PubMed1981

Cancer and the kidney: complications of neoplasms.

Various renal complications occur during the course of neoplastic disease. The therapeutic and prognostic implications differ according to the reversibility of both the underlying malignancy and the superimposed complications in the kidney. Since the mechanisms of renal failure vary significantly in patients with different types of malignancy, it is essential to avoid generalizations about etiologic factors or likely outcomes of the disease processes. The pathophysiologic abnormalities should be determined in each patient, and the reversibility of both the neoplastic and problems assessed before therapeutic decisions are made. This often requires a team effort by the internist, oncologist, nephrologist, urologist and, most importantly, the patient.

Amyloidosis↗
PubMed1981

Hypersensitivity pneumonitis and mesangiopathic glomerulonephritis: an unusual pulmonary-renal syndrome.

A broad range of disorders can manifest themselves as pulmonary-renal syndromes; the etiology and pathophysiology of most of these remain unknown. Although the occurrence of classic hypersensitivity pneumonitis with glomerulonephritis is rare, there is the possibility of at least some commonality of pathologic mechanisms. We present a case of mesangiopathic glomerulonephritis with renal failure complicated by a hypersensitivity-type pneumonitis, both of which were responsive to corticosteroids. The differential diagnostic considerations and alternate explanations for this syndrome are presented, as is the possibility that the renal and pulmonary abnormalities in this case represent a single disorder.

Alveolitis, Extrinsic Allergic↗
PubMed1981

Cimetidine secretion by rabbit renal tubules in vitro.

Cimetidine, a drug in widespread use in the treatment of peptic ulcer disease, is eliminated primarily via urinary excretion. We examined cimetidine transport by rabbit proximal straight tubules perfused in vitro. [3H]Cimetidine in the bath was actively secreted into the tubule lumen. There was a curvilinear relationship between the rate of cimetidine secretion and the concentration of bath cimetidine. Cimetidine secretion was inhibited by hypothermia and ouabain. Quinine, tolazoline, probenecid, phloridzin, creatinine, p-aminohippurate, and cimetidine sulfoxide inhibited cimetidine secretion in a dose-related manner. At low cimetidine concentrations lumen-to-bath transport rates were only 11-18% of bath-to-lumen secretory rates. High performance liquid chromatographic analysis of collected tubular fluid showed a predominance of cimetidine and a small amount of cimetidine sulfoxide in ratios similar to those of the bath. These studies show that cimetidine is actively secreted into the lumen of rabbit proximal straight tubules in vitro. Secretion probably occurs via the organic base and to a lesser extent the acid transport systems.

Animals↗
PubMed1980

PTH inhibition of bicarbonate transport by proximal convoluted tubules.

These studies examined the effect of parathyroid hormone (PTH), dibutyryl cyclic AMP DBcAMP, and 8-bromo-cyclic AMP BrcAMP on HCO3- transport by rabbit superficial proximal convoluted tubules perfused in vitro. Bicarbonate was estimated as total CO2 measured microcalorimetrically. At slow perfusion rates with 25 mM HCO3- in the perfusate and bath, PTH (0.1 U/ml in the bath) caused the total CO2 in tubular fluid to rise from 10.2 to 19.9 mM. The hormone had no effect on the total CO2 concentration in tubules perfused with HCO3(-)-free perfusates. With HCO3(-) in the perfusate and bath, PTH reduced the rates of fluid and total CO2 absorption to 57 and 48% of control values, respectively. PTH had no effect on the rates of fluid absorption and total CO2 secretion when HCO3(-)-free perfusates were used. The effects of DBcAMP and BrcAMP (10(-7) M in the bath) were similar to those of PTH. 5'-AMP (10(-6) M in the bath) did not alter the total CO2 concentration of tubular fluid when the tubules were perfused at slow rates with HCO3- in the perfusate and bath. Ouabain (10(-5) M in the bath) caused the total CO2 concentration in tubules perfused at slow rates with HCO3--free perfusates to rise from 8.9 to 12.7 mM. PTH caused no further change in the total CO2 concentration in the presence of ouabain.

Animals↗
PubMed1979

Hemodialysis and renal transplantation in progressive systemic sclerosis: report of 2 cases.

Renal failure is a common cause of death in patients with progressive systemic sclerosis (PSS). The present paper describes two patients with chronic renal failure secondary to PSS whom we have treated by a combination of chronic hemodialysis and renal transplantation. Also reviewed are reports of six additional patients who have undergone renal transplantation. We conclude that chronic hemodialysis and renal transplantation are successful life-sustaining treatment modalities in some patients with end-stage renal disease due to PSS.

Adult↗
PubMed1979

Spurious hyperbilirubinemia in uremic patients on propranolol therapy.

Chronic, low-grade, unexplained increases of total serum bilirubin concentration were observed in 16 of 132 (12%) chronic dialysis patients. Cessation of antihypertensive medication in four patients resulted in disappearance of hyperbilirubinemia. Propranolol was the only antihypertensive drug common to all 16 patients. Daily dosage varied among the patients, but the mean dose was 308 mg (+/- 51 SEM). Serial determinations of sera from individual patients given different doses and from the group as a whole demonstrated a linear relationship between propranolol dose and apparent total serum bilirubin concentration with continuous-flow analysis. When serum specimens from uremic patients receiving propranolol were treated with diazotized fulfanilic acid and examined spectrophotometrically, an absorbance peak distinct from but overlapping that of bilirubin was consistently demonstrated. The material producing the peak disappeared when the drug was stopped, did not dialyze, and was not reproduced by the in vitro addition of propranolol to uremic serum. We postulate that a metabolite(s) of propranolol is retained in uremic serum and interferes with the bilirubin determination.

Bilirubin↗
PubMed1978

Bicarbonate absorption by rabbit cortical collecting tubules in vitro.

The rate of transport of bicarbonate was studied in isolated perfused rabbit cortical collecting tubules that were absorbing bicarbonate in vitro. Acetazolamide completely inhibited bicarbonate absorption, as was previously observed with isolated proximal tubules. Therefore, carbonic anhydrase probably is important for bicarbonate absorption in both the proximal tubules and collecting tubules. Inhibition of sodium transport by ouabain or elimination of its transport by completely removing the sodium did not cause a decrease in bicarbonate absorption by the collecting tubules. We previously found that inhibition of sodium transport caused a great decrease in bicarbonate absorption by proximal tubules. Therefore, absorption of bicarbonate is not directly related to sodium transport in collecting tubules, but it probably is related to sodium transport in isolated perfused rabbit proximal tubules. Amiloride inhibited bicarbonate absorption by the collecting tubules consistent with previous observations that the drug inhibits urinary acidification. Although amiloride also inhibits sodium transport and reduces the transepithelial voltage across the collecting tubules, the effect of the drug on bicarbonate transport apparently is independent of the other effects.

Absorption↗
PubMed1978

Bicarbonate secretion by rabbit cortical collecting tubules in vitro.

We previously reported that rabbit renal cortical collecting tubules can secrete bicarbonate in vitro (i.e., there can be net transport from bath to lumen, causing the concentration in the lumen to increase). Net bicarbonate secretion was observed most often when rabbits had been pretreated with NaHCO(3) and were excreting alkaline urine before being killed for experiments. The purpose of the present studies was to elucidate the mechanism involved by testing the effects of ion substitutions and drugs on collecting tubules that were secreting bicarbonate. Acetazolamide inhibited net bicarbonate secretion, suggesting that the process is dependent upon carbonic anhydrase. Net bicarbonate secretion also decreased when sodium in the perfusate and bath was replaced by choline, but not when chloride was replaced by nitrate or methylsulfate. Ouabain had no significant effect. Amiloride caused net bicarbonate secretion to increase. The rate of net secretion did not correlate with transepithelial voltage. The results are compared to those in turtle urinary bladders that also secrete bicarbonate. There are no direct contradictions between the results in the two tissues, i.e., in turtle bladders acetazolamide also inhibited bicarbonate secretion and ouabain had no effect. Nevertheless, it seems unlikely that net secretion of bicarbonate by collecting tubules involves specific exchange for chloride, as has been proposed for turtle bladders, because replacement of chloride by other anions did not inhibit bicarbonate secretion by collecting tubules. It was previously shown that the collecting tubules in vitro also may absorb bicarbonate, especially when the rabbits have been treated with NH(4)Cl and are excreting acid urine before being killed. The effects of drugs on net bicarbonate secretion found in the present studies are compared to their previously reported effects on net bicarbonate absorption and the possibility is discussed that bicarbonate absorption and secretion are independent processes, as was previously proposed for turtle bladders.

Acetazolamide↗
PubMed1977

Biocarbonate and fluid absorption by renal proximal straight tubules.

Rabbit proximal straight tubules from superficial nephrons were perfused in vitro in order to elucidate the mechanism of fluid and bicarbonate absorption. Both processes were greatly inhibited when sodium was replaced in the perfusate and bath by other cations, when ouabain was added to the bath, or when potassium was removed from the bath. We infer that these experimental manipulations inhibit active sodium tranport, and that active sodium transport is a primary process leading to fluid and bicarbonate absorption. Fluid absorption also decreased (but only by 22 to 36%) when bicarbonate was replaced by chloride in the perfusate and bath or when acetazolamide (10(-3)M) was added, suggesting that fluid and sodium transport depend in part on bicarbonate. We infer that the links between fluid, sodiu, and bicarbonate transport are complex and involve at least two mechanisms: 1) a sodium for hydrogen ion exchange mechanism located in the brush border membrane and 2) the transepithelial concentration difference for bicarbonate, which results from its absorption and which acts as an additional driving force for fluid and sodium absorption. Finally, bicarbonate absorption was unaltered when chloride was replaced by nitrate in the perfusate and bath, suggesting that chloride is not necessary for acidification in this nephron segment.

Acetazolamide↗