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Biomedical subjects

N S Bricker

Publications and source records attributed to N S Bricker.

At least 37 records · Page 2Linked to original sources
PubMed1977

Reversibility of the "salt-losing" tendency of chronic renal failure.

We examined the salt-losing tendency of chronic renal failure in five patients with glomerular filtration rates varying from 5.2 to 16.0 ml per minute. When the studies began, patients were in sodium balance on metabolic diets containing 58 to 342 meq of sodium daily. The sodium content of the diet was then reduced in stages at intervals of at least one week over four to 14 weeks with careful clinical and laboratory monitoring. In four of the patients a salt-losing tendency developed, temporarily requiring intravenous salt replacement in two. At the completion of the studies all the patients remained in sodium balance while ingesting a mean (+/- S.D.) of 5.0 +/- 2.9 meq of sodium per day. There was no change in renal function. Thus, the salt-losing tendency of chronic renal failure is reversible and appears to be a manifestation of the long-term adaptation for sodium excretion.

Adaptation, Physiological↗
PubMed1976

Influence of volume expansion on NaC1 reabsorption in the diluting segments of the nephron: a study using clearance methods.

Whether volume expansion influences NaC1 reabsorption by the diluting segment of the nephron remains a matter of controversy. In the present studies this question has been examined in normal unanesthetized dogs, undergoing maximal water diuresis. Free water clearance (CH2O/GFR) has been used as the index of NaC1 reabsorption in the diluting segment. Three expressions have been employed for "distal delivery" of NaC1: a) V/GFR, designated as the "volume term"; b) (CNa/GFR + CH2O/GFR), the "sodium term;" and c) (CC1/GFR + CH2O/GFR), the "chloride term". The validity of these terms is discussed. Three techniques were used to increase distal delivery: 1) the administration of acetazolamide to dogs in which extracellular fluid (ECF) volume was not expanded (grop 1); 2) "moderate" volume expansion (group 2); and 3) "marked" volume expansion (group 3). CH2O/GFR increased progressively with rising values for "distal delivery" regardless of which term was used to calculate the latter. With all three delivery terms, differences in distal NaC1 reabsorption emerged between the two volume-expanded groups, though only with the "chloride" term did substantial differences also emerge between the nonexpanded group 1 dogs and both volume-expanded groups. In group 1, values for CH2O/GFR increased in close to a linear fashion up to distal delivery values equal to 24% of the volume of glomerular filtrate. However, at high rates of distal delivery the rate of rise of CH2O/GFR was less in group 2 than in group 1 and the depression of values was even greater in group 3. Within the limits of the techniques used, the data suggest that volume expansion inhibits fractional NaC1 reabsorption in the diluting segment of the nephron in a dose-related fashion. The "chloride" term was found to be superior to the "volume" and "sodium" terms in revealing these changes.

Acetazolamide↗
PubMed1976

Bicarbonate reabsorption in the dog with experimental renal disease.

Renal bicarbonate reabsorption (expressed per unit of glomerular filtration rate, GFR) has been reported to be diminished in uremic man and uremic rats. Both the increases in parathyroid hormone concentrations and in natriuretic forces have been considered to play a role in this change. The increased kaliuresis per nephron observed in chronic uremia could theoretically also contribute to inhibition of bicarbonate reabsorption. Despite the common use of normal dogs in studying bicarbonate reabsorption and of uremic dogs in studying alterations of renal function in disease, few studies of bicarbonate reabsorption in uremic dogs have been performed. In the present studies we have examined bicarbonate reabsorption in normal dogs and in dogs with experimental renal disease using a conventional bicarbonate titration technique. In unanesthetized normal dogs, the threshold for bicarbonaturia was 24.8 mEq/liter of GFR. A maximal reabsorptive rate (Tm/GFR) of 34.0 mEq/liter of GFR was obtained. In a second group of dogs, GFR was decreased to one-fifth normal. FENa was increased 16.9-fold over normal values: UKV/100 GFR and FEP were increased 5.8-fold and 10.9-fold, respectively. The threshold for bicarbonaturia in these dogs was increased to 30.5 mEq/liter of GFR and the maximal reabsorptive rate was increased to 41.2 mEq/liter of GFR. Thus, the capacity to reabsorb bicarbonate was increased despite the presence of high fractional excretion rates for sodium, potassium and phosphate. This increased reabsorptive capacity could not be accounted for by the effects of other known determinants of bicarbonate reabsorption.

Animals↗
PubMed1976

Enhanced end-organ responsiveness of the uremic kidney to the natriuretic factor.

In chronic renal disease, the addition of a fixed quantity of Na to the extracellular fluid (ECF) will evoke a natriuretic response per nephron which is inversely proportional to the glomerular filtration rate (GFR). One factor that could contribute to this "magnification" phenomenon is an increased sensitivity of residual nephrons to physiologic natriuretic forces. The present studies were designed to examine this possibility. Natriuretic urine fractions from uremic patients, infused into one renal artery of normal rats, produced a small but significant unilateral natriuresis. Infusion of the same fractions in identical amount into remnant kidneys of stage II nonuremic rats (i.e., rats with a contralateral normal kidney in situ) produced a natriuresis in the remnant kidney only which was equivalent to that observed in the normal kidneys. The i.v. infusion of natriuretic fractions into stage II rats produced comparable increments in the fractional excretion of sodium (FENa) bilaterally. However, when the natriuretic fractions were infused into remnant kidneys of stage III rats (no contralateral kidney), deltaFENa was significantly greater than in the foregoing groups. Because stage III rats have increased control values for FENa, baseline FENa was increased to an equivalent level in normal rats by unilateral renal denervation. Natriuretic factor was administered into the ipsilateral renal artery. Although the natriuretic response was increased, it was significantly less than in the stage III remnant kidneys. The data support the view that the uremic state per se is associated with an enhanced responsiveness of the residual nephrons to the natriuretic factor found in the urine (and blood) of uremic patients.

Animals↗
PubMed1976

On the influence of the natriuretic factor from patients with chronic uremia on the bioelectric properties and sodium transport of the isolated mammalian collecting tubule.

A gel filtration fraction of urine from patients with chronic renal disease (natriuretic factor) has been shown previously to cause natriuresis in rats and to inhibit sodium transport in the isolated toad bladder. The effect of this fraction on transtubular potential difference and sodium transport was examined on the isolated perfused cortical collecting tubule of the rabbit. A rapid inhibition of potential difference from -22.5 mV to -12 mV (P less than 0.001) was observed when the fraction was applied to the peritubular surface. This effect was accompanied by a decrease in net sodium flux from 6.29 to 3.21 pmol/cm per s (P less than 0.001). Unidirectional fluxes using isotopic sodium revealed that the inhibition of net sodium transport was due to a decrease in flux from the lumen to the peritubular surface, i.e., an inhibition of active sodium transport. There was no change in sodium flux in the reverse direction. These changes were all rapidly reversed by removal of the fraction from the peritubular surface. The addition of the fraction to the lumen had no effect on potential difference or net sodium flux. Control studies using the same fraction from the urine of normal subjects had no effect on any of the parameters studies. Where both a uremic and a normal fraction were sequentially applied to the peritubular surface of the same tubule, inhibition of potential difference was obtained only with the former. In the light of evidence implicating the collecting duct fraction from normal animals, the data are consistent with the view that the natriuretic factor may be biologically important in the regulation of sodium balance via it's regulatory role in active sodium transport in the collecting tubule.

Animals↗
PubMed1976

A study of the intrarenal recycling of urea in the rat with chronic experimental pyelonephritis.

The concentrating ability of the kidney was studied by clearance and micropuncture techniques and tissue slice analyses in normal rats with two intact kidneys (intact controls), normal rats with a solitary kidney (uninephrectomized controls), and uremic rats with a single pyelonephritic kidney. Urinary osmolality after water deprivation for 24 h and administration of antidiuretic hormone was 2,501+/-217 and 2,874+/-392 mosmol/kg H2O in intact and uninephrectomized control rats, respectively, and 929+/-130 mosmol/kg H2O in pyelonephritic rats (P less than 0.001 compared to each control group). Fractional water reabsorption and concentrating ability were significantly decreased in the pyelonephritic group, and, to achieve an equivalent fractional excretion of urea, a greater fractional excretion of water was required in the pyelonephritic rats than in the control rats. Whole animal glomerular filtration rate was 1.57+/-0.19 ml/min and 1.39+/-0.18 ml/min in intact and in uninephrectomized controls, respectively, and 0.30+/-0.07 ml/min in pyelonephritic rats (P less than 0.001 compared to each control group). Single nephron glomerular filtration rate was 35.6+/-3.8 nl/min in intact control rats and was significantly increased (P less than 0.05) in both uninephrectomized (88.0+/-10.8 nl/min) and pyelonephritic rats (71.5+/-14.4 nl/min). In all groups fractional water delivery and fractional sodium delivery were closely comparable at the end of the proximal convoluted tubule and at the beginning of the distal convoluted tubule. In contrast, fractional urea delivery out of the proximal tubule was greater in the intact control group (73+/-8%) than in either the uninephrectomized (52+/-2%) or the pyelonephritic group (53+/-3%) (P less than 0.005). Fractional urea delivery at the early part of the distal tubule increased significantly to 137+/-11% and 93+/-6% of the filtered load in intact control and uninephrectomized control rats, respectively (P less than 0.001 compared to the late proximal values of each group), but failed to increase significantly in pyelonephritic rats (65+/-13%), indicating interruption of the normal recycling of urea in the latter group. Analysis of tissue slices demonstrated a rising corticopapillary gradient for total tissue water solute concentration as well as for tissue water urea concentration in both groups of control rats. In contrast, the pyelonephritic animals exhibited no similar gradients from cortex to papilla. These data indicate that the pyelonephritic kidney fails to recycle urea and accumulate interstitial solute. The latter must inevitably lead to a concentrating defect.

Animals↗
PubMed1975

Effect of sodium intake on single nephron glomerular filtration rate and sodium reabsorption in experimental uremia.

Sodium balance, clearance and micropuncture studies were performed on three groups of uremic rats in which renal mass was reduced experimentally by approximately 85%. All animals received a sodium-free synthetic diet to which a measured amount of NaCl was added. Sodium intake was 3 mEq/day in one group, 1 mEq/day in a second group and 0.13 mEq/day in the third. In the latter, the Na intake was reduced (from an initial level of 1 mEq/day) as renal mass was reduced in proportion to the estimated reduction in renal mass in an effort to obviate the requirement for an increased natriuresis/nephron. Clearance and micropuncture studies also were performed in a group of normal rats maintained on 1 mEq/day of Na. All three groups of uremic rats on the standard diet maintained external Na balance. Single nephron glomerular filtration rate (SNGFR) in superficial nephrons was increased in all three groups of uremic rats and seemed to be independent of the Na intake; fractional fluid reabsorption was decreased in the proximal tubules in all three groups of uremic rats. Furthermore, absolute proximal Na reabsorption was markedly increased; and calculated values for distal reabsorption were markedly increased in all groups of uremic rats. The data suggest that the increase in SNGFR and the decrease in tubular fluid to plasma (TF/P) inulin ratios in superficial proximal tubules correlate poorly with the dictates for an increase in sodium excretion rate per residual nephron. These data also have implications regarding the operation of the control system in the regulation of external Na balance in uremia.

Animals↗
PubMed1975

An inhibitor of sodium transport in the urine of dogs with normal renal function.

The urine and serum of chronically uremic patients and dogs contain an inhibitor of sodium transport that reduces short-circuit current (SCC) in the toad bladder and produces natriuresis in the rat. The present studies represent an effort to determine whether the same inhibitor is detectable in urine of normal dogs maintained on a dosium intake varying from 3 to 258 meq/day. Observations were made with and without fludrocortisone. The same Sephadex G-25 gel filtration fraction previously shown to contain the "uremic" inhibitor was tested in both the isolated toad bladder and rat bioassay systems. The fraction from dogs maintained on 258 meq qodium plus 0.2 mg fludrocortisone/day consistently inhibited SCC in the toad bladder and induced a natriuresis in the rat (P less than 0.001). The fraction from dogs on the same sodium intake without fludrocortisone was also natriuretic (P less than 0.01) but did not inhibit SCC significantly. In contrast, the fraction from dogs fed 3 meq sodium with fludrocortisone or 91 meq sodium without fludrocortisone had no significant effect in either assay system. Thus, an inhibitor of sodium transport has been found in the urine of nonuremic dogs. Both the degree of natriuresis in the rat and the degree of inhibition of SCC in the toad bladder correlated with the state of sodium balance which ensued in the dog.

Animals↗
PubMed1974

The presence of a natriuretic factor in urine of patients with chronic uremia. The absence of the factor in nephrotic uremic patients.

A gel filtration fraction of serum from chronically uremic patients has been shown previously to produce natriuresis in the rat. In the present studies, the same fraction from urine of uremic patients and normal subjects was studied for its natriuretic activity. Urine samples were obtained from 17 chronically uremic patients (mean glomerular filtration rate [GFR], 8.7 ml/min; mean fractional sodium excretion [FE(Na)], 5.7%), and 14 normal subjects. The fraction from the uremic patients produced a significant increase in absolute sodium excretion (U(Na)V) and FE(Na); the fraction from normal subjects had no statistically significant effect on either U(Na)V or FE(Na); and the difference between the response to the uremic vs. normal fractions was highly significant for both parameters of sodium excretion. When a more concentrated urine fraction from uremic patients was administered, a striking natriuresis was observed with values for FE(Na) rising to levels as high as 12%. Studies also were performed on eight patients with far advanced chronic renal insufficiency and the nephrotic syndrome. The serum fraction was studied in each of these patients and the urine fraction in three. For the group, U(Na)V in the assay rats decreased by 0.87 mueq/min and FE(Na) decreased by 1.35% after infusion of the serum fraction. These results differ significantly from those of patients with chronic uremia without the nephrotic syndrome. The data are consistent with the view that the increased activity of the natriuretic factor in the serum of chronically uremic patients is not due to failure of excretion; rather it relates either to an increased rate of production and/or a decreased rate of degradation. The data also show that the inhibitor is detectable when FE(Na) is increased, but not when uremia is associated with a sodium-retaining state.

Animals↗
PubMed1974

The effects of the natriuretic factor from uremic urine on sodium transport, water and electrolyte content, and pyruvate oxidation by the isolated toad bladder.

The urine of patients with chronic uremia contains a gel filtration fraction that is natriuretic in the rat. The effects of this fraction on the isolated urinary bladder of the toad were examined in the present studies. When added to the serosal surface of the bladder, a significant and substantial fall in short-circuit current and potential difference was observed. The changes began after a lag period of at least 10 min and continued over a period of 60 min. The decrease in short-circuit current at the end of 1 h averaged 44%. The same fraction from the urine of normal subjects produced no significant change in either short-circuit current or potential difference. When the isolated epithelial cells from the toad bladder were incubated in the presence of the inhibitor, intracellular sodium content increased significantly. There was no change in intracellular water content; hence the intracellular concentration of sodium increased by a mean of 7 meq/liter. The changes in intracellular potassium content and concentration were not satistically significant. When the isolated epithelia were incubated with the uremic factor, there was also a significant decrease in pyruvate utilization in relation to cells from paired hemibladders incubated in the absence of the fraction. The fraction from normal subjects produced no change in either intracellular sodium content or pyruvate oxidation. The results suggest that the inhibitor acts from the serosal surface, inhibits sodium transport across the serosal barrier, and produces a decrease in substrate utilization in association with the change in transepithelial sodium transport.

Ammonium Chloride↗
PubMed1974

On the adaptation in sodium excretion in chronic uremia. The effects of "proportional reduction" of sodium intake.

Renal mass and glomerular filtration rate (GFR) were reduced from normal to approximately 15% of normal in two groups of dogs. One group received a constant salt intake (CSI) throughout the study. The second group was subjected to "proportional reduction" of sodium intake (PRS), a dietary regimen which involved the reduction of sodium intake in exact proportion to the decrement in GFR. In the CSI group, absolute sodium excretion rate (U(Na)V) remained essentially unchanged as GFR fell, while fractional sodium excretion (FE(Na)) increased progressively from a mean control value of 0.3% to a final value of 4.4%. In the PRS group, U(Na)V decreased with each reduction in GFR and salt intake, and FE(Na) remained constant throughout. In a second study, the fraction of serum that previously has been shown to possess natriuretic activity in studies of uremic patients was obtained from a group of uremic dogs on the CSI and from another group on the PRS regimen, and the effects of the fraction was measured on sodium excretion in rats. The serum fractions from the dogs on the CSI regimen produced a significant increase in both U(Na)V and FE(Na) in the assay rats. The same serum fraction from the dogs on the PRS regimen failed to produce a significant increase in either U(Na)V or FE(Na). The data are consistent with the view that (a) The increase in FE(Na) in chronically uremic dogs is dictated by the requirements for external sodium balance and may be prevented by prospective manipulation of salt intake: (b) a natriuretic factor, previously shown to exist in the serum of patients with chronic uremia, is also demonstrable in the serum of uremic dogs; and (c) with the present bioassay system, the factor is not detectable in the serum fraction of uremic dogs in which the requirements for an increased natriuresis per nephron have been obviated.

Adaptation, Physiological↗