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K A Kirchner

Publications and source records attributed to K A Kirchner.

At least 37 records · Page 2Linked to original sources
PubMed1992

Verapamil prevents insulin antinatriuresis in euglycemic rats.

To determine whether calcium entry is necessary for insulin antinatriuresis, urinary sodium excretion was determined before and during euglycemic insulin administration in rats receiving verapamil (10 micrograms.kg-1.min-1) or vehicle. In vehicle rats, insulin reduced sodium excretion from 2.7 +/- 0.5 to 0.98 +/- 0.2 mu eq/min (P less than 0.05) without altering arterial pressure or inulin clearance. Insulin did not reduce sodium excretion in rats receiving verapamil. Baseline mean arterial pressure was lower in verapamil rats than in vehicle rats. To exclude the possibility that lower baseline arterial pressures prevented insulin antinatriuresis, insulin's effect on sodium excretion was determined in rats receiving captopril at a dose that reduced arterial pressure to the level observed in verapamil rats, and in verapamil rats with angiotensin II levels fixed to maintain arterial pressure equivalent to vehicle rats. In captopril rats, insulin reduced (P less than 0.05) sodium excretion from 1.07 +/- 0.3 to 0.3 +/- 0.01 mu eq/min, even though arterial pressure was not different from that in verapamil rats. Insulin failed to reduce sodium excretion in verapamil rats receiving angiotensin II. Thus verapamil prevents insulin antinatriuresis by renal mechanisms related to inhibition of calcium entry. Additionally, insulin antinatriuresis is independent of angiotensin II.

Animals↗
PubMed1992

Effects of insulin on renal sodium excretion.

The ability of insulin to decrease urinary sodium excretion has been recognized for more than 30 years. While most investigators agree that this occurs predominantly through increased tubular sodium reabsorption, the nephron segments at which insulin exerts this effect in vivo remain controversial. Additionally, little information is available in mammalian systems on the mechanism of the insulin response or its relation to other hormonal systems important in the regulation of tubular sodium transport. Data from amphibian transporting epithelia suggest a potential for interactions between insulin and several other peptide hormones in the regulation of sodium transport. The following discussion attempts to review our knowledge of the effects of insulin on renal sodium reabsorption and describes new data suggesting that insulin's antinatriuretic response is dependent on antidiuretic hormone but independent of the angiotensin and prostaglandin systems.

Animals↗
PubMed1992

Tubular resistance to furosemide contributes to the attenuated diuretic response in nephrotic rats.

A blunted response to loop diuretics frequently occurs in nephrotic syndrome (NS). Observations that nephrotic humans have reduced sodium excretion at normal rates of diuretic excretion have suggested that tubular resistance to the drug may contribute to diuretic resistance. To determine if tubular resistance to furosemide exists in NS, late proximal and early distal tubular micropuncture was performed in rats with puromycin aminonucleoside-induced NS and in control rats after an i.v. bolus dose of furosemide of 1 mg/kg body wt. Absolute and fractional urinary sodium excretions were less (P less than 0.05) in NS rats than in control rats after furosemide. Inulin clearance and total urinary furosemide excretion, however, were not different between groups. Thus, similar to reports in humans, the urinary sodium-to-furosemide excretion ratio was less (P less than 0.05) in NS than in control rats. Single-nephron GFR and chloride delivery to late proximal sites were not different between groups after furosemide. In contrast, absolute and fractional chloride deliveries to early distal sites were less (P less than 0.05) in NS rats after furosemide. Calculated loop chloride reabsorption after furosemide was greater (P less than 0.05) in NS than in control rats when expressed either as percentage of filtered load (39.4 +/- 3.1 versus 28.2 +/- 2.0%) or delivered load (67.9 +/- 4.7 versus 48.3 +/- 3.0%). Loop fluid reabsorption was not different between groups. Thus, loop chloride reabsorption is inhibited to a lesser extent by i.v. furosemide in NS than in normal rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Postpartum preeclampsia-induced shock and death: a report of three cases.

Three patients with preeclampsia died as a result of prolonged postpartum hypotension that was unrelated to blood loss. Autopsy failed to reveal a cause of death. The sudden onset of hypotensive shock within 24 hours of delivery occurred in all patients, with coexistent hyponatremia present in the two patients in whom it was evaluated. These three maternal deaths appear to have occurred as a result of the previously described entity of postpartum preeclamptic shock.

Adolescent↗
PubMed1991

Binding inhibitors restore furosemide potency in tubule fluid containing albumin.

We have previously suggested that albumin in tubule fluid at concentrations found in the nephrotic syndrome (NS) binds furosemide, thereby diminishing diuretic effect. This mechanism may contribute to diuretic resistance in NS. If this hypothesis is correct, displacement of albumin from furosemide should restore diuretic response in tubule fluid containing albumin. To test this supposition, in vivo loop microperfusion was performed in rats using perfusates containing 6 microM furosemide in the presence or absence of 3.8 microM albumin, or furosemide and albumin to which 12 microM warfarin or 5.4 mM sulfisoxazole had been added. These drugs are inhibitors of albumin-furosemide binding in plasma. Albumin in the perfusate impaired furosemide effect on loop chloride reabsorption (1248 +/- 59 vs. 886 +/- 65 pEq/min; P less than 0.05). Addition of warfarin or sulfisoxazole to perfusate containing albumin normalized furosemide's effect. Neither drug affected furosemide response in the absence of albumin. Dansylsarcosine, a probe that binds albumin at a different site than furosemide, failed to normalize furosemide response in albumin perfusates. These data suggest that albumin in tubule fluid reduces diuretic response through a diminution in the free furosemide concentration. In as much as this mechanism contributes to diuretic resistance observed clinically in NS, displacement of furosemide from albumin binding sites may be a therapeutic strategy warranting study.

Albumins↗
PubMed1991

Effects of alpha-thalassemia and sickle polymerization tendency on the urine-concentrating defect of individuals with sickle cell trait.

A defect in urine concentrating ability occurs in individuals with sickle cell trait (HbAS). This may result from intracellular polymerization of sickle hemoglobin (HbS) in erythrocytes, leading to microvascular occlusion, in the vasa recta of the renal medulla. To test the hypothesis that the severity of the concentrating defect is related to the percentage of sickle hemoglobin present in erythrocytes, urinary concentrating ability was examined after overnight water deprivation, and intranasal desmopressin acetate (dDAVP) in 27 individuals with HbAS. The HbAS individuals were separated into those who had a normal alpha-globin genotype (alpha alpha/alpha alpha), and those who were either heterozygous (-alpha/alpha alpha) or homozygous (-alpha/-alpha) for gene-deletion alpha-thalassemia, because alpha-thalassemia modulates the HbS concentration in HbAS. The urinary concentrating ability was less in the alpha alpha/alpha alpha genotype than in the -alpha/alpha alpha or -alpha/-alpha genotypes (P less than 0.05). After dDAVP, the urine osmolality was greater in patients with the -alpha/-alpha genotype than with the -alpha/alpha alpha genotype (882 +/- 37 vs. 672 +/- 38 mOsm/kg H2O) (P less than 0.05); patients with the -alpha/alpha alpha genotype had greater concentrating ability than individuals with a normal alpha-globin gene arrangement. There was an inverse linear correlation between urinary osmolality after dDAVP and the percentage HbS in all patients studied (r = -0.654; P less than 0.05). A linear correlation also existed for urine concentrating ability and the calculated polymerization tendencies for an oxygen saturation of 0.4 and O (r = -0.62 and 0.69, respectively). We conclude that the severity of hyposthenuria in HbAS is heterogeneous. It is determined by the amount of HbS polymer, that in turn is dependent upon the percentage HbS, which is itself related to the alpha-globin genotype.

Adult↗
PubMed1990

Greater loop chloride uptake contributes to blunted pressure natriuresis in Dahl salt sensitive rats.

A blunted pressure natriuretic response is present in Dahl salt sensitive rats. To determine whether this results from tubular or glomerular mechanisms, late proximal, early distal, and late distal micropuncture were performed in salt resistant (R), salt sensitive (S), or salt sensitive rats with renal perfusion reduced to that of R rats (S-AC). Differences in neuro-endocrine background between groups were eliminated by renal denervation and by fixing plasma aldosterone, norepinephrine, and vasopressin levels by infusion. Renal perfusion pressure was greater (P less than 0.05) and inulin clearance less (P less than 0.05) in S than R rats. Urinary sodium excretion, however, was not different. S-AC had renal perfusion pressures that were similar to R rats and inulin clearance similar to S rats. Urinary NaCl excretion was less (P less than 0.05) than either group. Single nephron inulin clearance, fluid, and chloride delivery to late proximal sites were not different between groups. Absolute and fractional chloride delivery to early distal sites was less (P less than 0.05) in S-AC than R or S but not different between R and S. Late distal chloride delivery was not different between any group. Calculated loop chloride reabsorption was greater in S-AC than R or S. Thus, the lower urinary NaCl excretion in S-AC rats is in part due to increased loop chloride reabsorption. This effect is probably intrinsic to the S kidney as it occurs despite renal denervation when plasma levels of vasopressin, norepinephrine, and aldosterone are fixed. The increased loop chloride uptake is abolished when perfusion pressure increases.

Animals↗
PubMed1990

Effect of diuretic and antidiuretic agents on lithium clearance as a marker for proximal delivery.

Diuretic drugs have marked effects on lithium clearance. The magnitude and mechanism of the effect depend not only on the site of action of the diuretic but also on the sodium intake of the subject as well. In sodium restricted rats all diuretics except the thiazides increase FeLi and abolish distal lithium uptake. The increase in FeLi produced by proximal and loop diuretics are associated with changes in proximal delivery. Amiloride, on the other hand, increases FeLi solely through inhibition of distal lithium uptake. Therefore, this agent is useful to detect lithium reabsorption beyond the proximal tubule. Additionally the values for FeLi obtained after amiloride administration may provide the best quantitative estimate for proximal delivery in conditions where distal lithium uptake is a consideration. Antidiuretic agents, especially those which potentiate ADH activity, may also have marked effects on lithium clearance. NSAID's and dDAVP are able to significantly reduce FeLi even in sodium loaded animals. As this occurs without a change in proximal delivery, these agents increase lithium reabsorption in distal nephron segments preferentially. Thus, estimates of proximal delivery determined by lithium clearance are not valid in the presence of these agents. Experimental conditions which produce high levels of endogenous ADH or potentiate the action of endogenous ADH may also adversely effect FeLi as a quantitative marker for proximal delivery. Whether there are other drugs which disrupt the ability of lithium clearance to function as a marker for proximal delivery requires further study.

Animals↗
PubMed1990

Intratubular albumin blunts the response to furosemide-A mechanism for diuretic resistance in the nephrotic syndrome.

An attenuated response to loop diuretics is a frequent observation in the nephrotic syndrome. To determine if the presence of albumin in renal tubular fluid attenuates diuretic response in normal rats, in vivo loop segment microperfusion was performed in normal rats at 20 nl/min with perfusates containing 6.0 microM furosemide in the presence and absence of 3.8 microM albumin. Compared to loop segments perfused without diuretic (control), furosemide reduced (P less than .001) fractional chloride uptake from 56 +/- 2 to 34 +/- 2%. After addition of albumin to furosemide perfusate, fractional loop chloride reabsorption was 45 +/- 1%; a value greater (P less than .01) than that observed in furosemide perfused loop segments, but less (P less than .05) than that observed in control loop segments. Albumin added to perfusate in the absence of furosemide had no effect on fractional loop segment chloride uptake. Addition of 1.7 microM immunoglobulin G to furosemide perfusate failed to attenuate furosemide response. Absolute loop segment chloride reabsorption demonstrated a similar pattern. Tubule fluid perfusion rates determined in vivo and loop segment fluid reabsorption were equivalent in all groups. Thus, albumin in renal tubule fluid attenuates the effect of furosemide on loop segment chloride reabsorption in the rat. This blunted response presumably occurs because of a reduction in the amount of pharmacologically active drug due to albumin-furosemide binding. Consequently, albumin-furosemide binding in the renal tubule may contribute to the diuretic resistance in nephrotic syndrome.

Absorption↗
PubMed1990

Renal transplantation in Mississippi.

The present article reviews the results of cadaveric renal transplantation and organ donation in Mississippi during the years 1984-88. Patient and graft survival in cadaveric renal transplantation have continued to improve since the introduction of cyclosporine as an immunosuppressive agent. In the Mississippi Transplant Program recipients of primary cadaveric renal transplants currently demonstrate 93% patient and 82.3% graft survival rates. Despite this improvement in outcome slightly more than 1% of ESRD patients in the state undergo transplantation annually compared to 7.5% nationally.

Adolescent↗
PubMed1989

Attenuation of ischemic renal injury with fructose 1,6-diphosphate.

Fructose 1,6-diphosphate (FDP) has been shown to attenuate tissue injury associated with ischemia and shock by enhancing the anaerobic carbohydrate utilization and by inhibiting oxygen-free-radical generation by the neutrophils. Previously, we have reported that FDP prevents ischemic renal failure if administered prior to the ischemic insult. The present study was designed to determine whether this agent could prevent renal damage when administered during the postischemic reperfusion period. Rats were subjected to 30 min of bilateral renal artery occlusion and infused with FDP (350 mg/kg body wt) beginning 10 min after release of the renal artery clamps. Control rats received an equal volume of glucose/saline solution. A third group of rats were sham operated. Twenty-four hours after injury, BUN, creatinine, and fractional sodium excretion values were less in FDP-treated rats than in control rats (P less than 0.001, P less than 0.005, and P less than 0.001, respectively) and not different from values observed in sham-operated rats. Inulin clearance was greater (P less than 0.001) in FDP-treated rats than in control rats (665 +/- 38 microliters/min/g kidney wt). Renal histology was also better preserved in the FDP-treated group. These data suggest that FDP infused after the initiation of an acute ischemic insult provides significant, but not complete, functional and histologic protection from renal damage.

Animals↗
PubMed1989

Nocardial infections in renal transplant recipients.

Upon review of the English literature and the patients at our hospital, we identified 94 renal transplant recipients with nocardiosis. These patients were further evaluated and compared to nonrenal transplant patients with nocardiosis. We found that these patients were similar in presentation, course, and therapeutic outcome to non-transplant patients. Survival was related to underlying disease, site of infection, rapidity with which the diagnosis was made and, especially, the inclusion of a sulfa compound in the antimicrobial regimen. Transplant centers with high rates of Nocardia infection should consider trimethoprim/sulfamethoxazole prophylaxis for at least the first year after transplantation.

Adult↗
PubMed1989

Effect of antidiuretic hormone on lithium as a marker for proximal tubule delivery.

To determine whether acute changes in antidiuretic hormone (ADH) alter the ability of lithium to quantitatively reflect proximal delivery, fractional lithium excretion (CLi/CIn) and late proximal (TF/P)In determined by micropuncture were measured in sodium-loaded rats following administration of desamino-8-D-arginine vasopressin (dDAVP) at rates equivalent to approximately half-maximal (20 pg/min) and maximal (40 pg/min) plasma levels of endogenous hormone. dDAVP dissociated the linear correlation between CLi/CIn and 1/(TF/P)In (r = 0.05) usually observed in sodium-loaded rats. Proximal delivery determined by lithium clearance underestimated (P less than 0.001) values obtained by micropuncture. Amiloride restored the linear correlation between CLi/CIn and 1/(TF/P)In in sodium-loaded dDAVP-treated rats (r = 0.70) and quantitative estimates of proximal delivery by each technique became equivalent. Indomethacin also reduced (P less than 0.001) estimates of proximal delivery obtained by lithium techniques in sodium-loaded rats. Water loading in hydropenic rats restored concordance between estimates of proximal delivery obtained by lithium clearance and micropuncture methods. Thus changes in ADH markedly alter the ability of lithium to function as a quantitative marker for proximal delivery. Furthermore, ADH may increase lithium uptake at distal nephron sites by an amiloride-sensitive pathway.

Amiloride↗
PubMed1989

Role of medullary plasma flow in the attenuated furosemide response in indomethacin-treated rats.

To determine the role of medullary hemodynamics in the attenuated furosemide response observed during prostaglandin synthesis inhibition, medullary plasma flow was measured by the albumin accumulation technique in nondiuretic rats and during furosemide administration (4 mg/kg b.wt./hr) in indomethacin- or indomethacin vehicle-treated rats. As in previous studies indomethacin attenuated furosemide chloruresis (FeCl: 11.4 +/- 1.1 vs. 5.0 +/- 0.9%, P less than .001) without altering mean arterial pressure, inulin clearance or total renal blood flow. Medullary plasma flow was not different between nondiuretic rats and furosemide-treated rats (41.4 +/- 4.3 vs. 41.3 +/- 3.4 ml/min/100 g of tissue). Medullary plasma flow was reduced (P less than .05) during indomethacin antagonism of furosemide chloruresis (41.3 +/- 3.4 vs. 29.1 +/- 2.8 ml/min/100 g of tissue). Angiotensin II blockade with saralasin (2 micrograms/kg/min) prevented the fall in medullary plasma flow in indomethacin-treated rats during furosemide infusion but did not alter mean arterial pressure, inulin clearance or total renal blood flow. However, furosemide's chloruretic response in rats treated with both indomethacin and saralasin remained lower (P less than .001) than that in vehicle-treated rats (FeCl 4.7 +/- .94 vs. 11.4 +/- 1.1%) and was not different from that in indomethacin-treated rats. These data demonstrate that although medullary plasma flow is reduced during indomethacin antagonism of furosemide response this change does not contribute to the attenuated chloruresis. Additionally, the dissociation of the antichloruretic and hemodynamic effects of indomethacin observed during saralasin administration suggest that hemodynamic mechanisms are not involved in the attenuated response to furosemide observed during prostaglandin synthesis inhibition.

Animals↗
PubMed1988

Insulin increases loop segment chloride reabsorption in the euglycemic rat.

To elucidate the nephron segment(s) responsible for insulin's antinatriuretic effect in the mammalian kidney, late proximal, early distal, and late distal tubule micropuncture was performed during base-line and intravenous insulin infusion in glucose-clamped, volume-expanded rats. During insulin infusion, urinary sodium chloride excretion fell. Blood glucose, arterial pressure, whole kidney and single-nephron inulin clearance, fluid, and chloride delivery out of the proximal convoluted tubule remained unchanged. Early distal chloride delivery decreased (P less than 0.001) during insulin administration. Insulin infusion increased calculated loop chloride reabsorption compared with both base-line values and values for time-control rats. Distal convoluted tubule chloride reabsorption was unchanged during insulin administration. We conclude that 1) euglycemic insulin administration reduces urinary chloride excretion in volume-expanded rats by tubular mechanisms; 2) in superficial nephrons, insulin has no effect on proximal tubule fluid or chloride reabsorption but markedly stimulates chloride reabsorption in the loop; and 3) chloride reabsorption in the distal convoluted tubule was unaltered by insulin administration.

Animals↗
PubMed1988

Role of antidiuretic hormone in the attenuated furosemide response observed during indomethacin administration.

Recently we demonstrated that increased chloride reabsorption in Henle's loop is a major contributor to the blunted furosemide response observed during prostaglandin synthesis inhibition. Because antidiuretic hormone (ADH) modulates chloride reabsorption in the loop and because prostaglandin synthesis inhibition potentiates ADH-mediated water reabsorption, ADH may be necessary for the attenuated furosemide response observed during prostaglandin synthesis inhibition. If such were the case, then prostaglandin synthesis inhibition should have no effect on furosemide's chloruretic response in the absence of ADH. To test this hypothesis, the effect of indomethacin on furosemide chloruresis was determined in homozygous (ADH-deficient) Brattleboro rats and in homozygous Brattleboro rats receiving ADH (2.4 mU/hr) over a short period of time. Furosemide-induced chloruresis was not different (P was not significant) between indomethacin-treated homozygous Brattleboro rats and homozygous Brattleboro rats receiving the indomethacin vehicle (fractional excretion of chloride: 6.28% +/- 1.08% vs. 6.24% +/- 0.98%). However, in ADH-infused Brattleboro rats, furosemide chloruresis was lower in indomethacin-treated rat groups than in vehicle-treated rat groups (fractional excretion of chloride: 3.09% +/- 0.62% vs. 6.61% +/- 0.88%; P less than 0.02) and lower than in indomethacin-treated ADH-deficient Brattleboro rats as well (P less than 0.05). Mean arterial pressure, inulin clearance, and renal blood flow were not different between any groups. Urinary prostaglandin excretion rates were not different between ADH-deficient Brattleboro rats and ADH-treated Brattleboro rats during furosemide administration and were markedly reduced by indomethacin in both circumstances. Thus, ADH is necessary for the blunted furosemide response observed during prostaglandin synthesis inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Mechanism of attenuated hydrochlorothiazide response during indomethacin administration.

Indomethacin antagonizes the natriuretic and chloruretic response to hydrochlorothiazide in most studies. Neither the mechanism nor nephron site of this antagonism has been determined. To identify sites and potential mechanisms, cortical micropuncture was performed during hydrochlorothiazide treatment in control and indomethacin rats. Indomethacin reduced (P less than 0.005) FeCl from 5.20 +/- 0.49% to 2.26 +/- 0.49% (mean +/- SE). MAP, CIn, and plasma volume were not different between groups. SNGFR and fractional proximal fluid and chloride delivery were not different between groups. Fractional chloride delivery to early distal tubules was 10.8 +/- 0.4% in control but 6.2 +/- 0.3% in indomethacin rats (P less than 0.001). Calculated loop chloride reabsorption was greater in indomethacin than control rats during hydrochlorothiazide administration (41.0 +/- 1.6% vs. 34.3 +/- 2.3%; P less than 0.05). Fractional chloride delivery to late distal tubules was 7.8 +/- 0.7% in control and 4.6 +/- 0.3% in indomethacin rats (P less than 0.005), but distal tubule chloride reabsorption was not different between groups. Papillary tissue chloride was less in control than indomethacin rats during hydrochlorothiazide (P less than 0.05). Urinary PGE2 excretion was reduced (P less than 0.001) by indomethacin during hydrochlorothiazide. Thus indomethacin induced reductions in hydrochlorothiazide response result in part from increased chloride reabsorption in the loop segment. This suggests indomethacin antagonizes hydrochlorothiazide by reducing chloride delivery to hydrochlorothiazide's site of action in the distal tubule rather than by effects of indomethacin on hydrochlorothiazide pharmacokinetics.

Animals↗