[Evaluation of hemostasis disorders using the thrombodynamic test in patients with chronic glomerulonephritis with nephrotic syndrome].

BACKGROUND: Nephrotic syndrome (NS) is accompanied by a risk of thrombotic complications due to hypercoagulability. Routine laboratory tests are not sensitive enough to detect these disorders, and therefore the use of integral coagulation tests, including a new thrombodynamic test (TT) in patients with NS, is of high relevance. AIM: Using a TT to determine hemostasis disorders in patients with chronic glomerulonephritis (CGN) with NS. MATERIALS AND METHODS: The study included 49 patients with CGN, mean age 37 years, of which 25 (51%) women and 24 (49%) men. Of all the examined patients, 20 (40.8%) of people had NS, 29 (59.2%) had no NS. The process of clot formation was assessed by TT. RESULTS: According to TT, 30% (6/20) of patients with NS and 13.7% (4/29) of patients without NS have hypercoagulation with changes in parameters that go beyond the reference values. In patients with NS, an increase in clot density (D), clot formation rate (V) and clot size (CS) was found, especially when albumin decreased below 25 g/l. Negative correlations were found between the levels of albumin, creatinine and clot density (D), which reflects the level of hyperfibrinogenemia, the rate of clot formation (V) and the integral index of coagulation (CS). The results indicate mainly the activation of the plasma hemostasis due to the internal coagulation pathway. However, the correlation of Tlag (delay time for the onset of clot formation after contact of blood plasma with the insert-activator) with serum cholesterol levels may also indicate activation of the extrinsic coagulation pathway. CONCLUSION: In CGN patients with NS, activation of the plasma hemostasis is noted, as evidenced by an increase in the rate of formation (V) and size of the clot (CS) after 30 minutes, as well as the density of the formed clot (D).

Mechanism of effect of hypoxia on renal water excretion.

The effect of lowering the pressure of oxygen from 80 to 34 mm Hg was examined in anesthetized dogs that were undergoing a water diuresis. This degree of hypoxia was associated with an antidiuresis as urine osmolality (Uosm) increased from 107 to 316 mosmol/kg H(2)O (P < 0.001) and plasma arginine vasopressin increased from 0.06 to 7.5 muU/ml, (P < 0.05). However, hypoxia was not associated with significant changes in cardiac output (CO, from 4.2 to 4.7 liters/ min), mean arterial pressure (MAP, from 143 to 149 mm Hg), glomerular filtration rate (GFR, from 46 to 42 ml/min), solute excretion rate (SV, from 302 to 297 mosmol/min), or filtration fraction (from 0.26 to 0.27, NS). Hypoxia was associated with an increase in renal vascular resistance (from 0.49 to 0.58 mm Hg/ml per min, P < 0.01). The magnitude of hypoxia-induced antidiuresis was the same in innervated kidneys and denervated kidneys. To further examine the role of vasopressin in this antidiuresis, hypoxia was induced in hypophysectomized animals. The effect of hypoxia on CO, MAP, GFR, SV, and renal blood flow in hypophysectomized animals was the same as in intact animals. In contrast to intact animals, however, hypoxia did not induce a significant antidiuresis in hypophysectomized animals (Uosm from 72 to 82 mosmol/kg H(2)O). To delineate the afferent pathway for hypoxia-stimulated vasopressin release, hypoxia was induced in dogs with either chemo- or baroreceptor denervation. The effect of hypoxia on CO, MAP, GFR, SV, and renal blood flow in the denervated animals was the same as in nondenervated animals. Hypoxia resulted in an antidiuresis in chemoreceptor (Uosm from 113 to 357 mosmol/kg H(2)O, P < 0.001) but not in baroreceptor (Uosm from 116 to 138 mosmol/kg H(2)O, NS) denervated animals. To determine if hypoxia alters renal response to vasopressin, exogenous vasopressin was administered to normoxic and hypoxic groups of dogs. The antidiuretic effect of vasopressin was no different in these two groups. These results demonstrate that hypoxia induces an antidiuresis which is independent of alterations in CO, MAP, SV, filtration fraction, renal nerves, or renal response to vasopressin and occurs through baroreceptor-mediated vasopressin release. The nature of the baroreceptor stimulation remains to be elucidated.

The role of renal nerves and prostaglandins in control of renal hemodynamics and plasma renin activity during hypotensive hemorrhage in the dog.

The effects of hypotensive hemorrhage (HH) on renal hemodynamics and plasma renin activity (PRA) during prostaglandin (PG) synthesis inhibition were examined in three groups of dogs. In each group of animals arterial blood pressure was lowered by a 30% decrement. In the first group of eight control animals, HH was not associated with a significant change in glomerular filtration rate (GFR, 42-36 ml/min, NS); renal blood flow (RBF) declined significantly, from 234 to 171 ml/min, P < 0.05. In the second group of eight animals, pretreated with RO 20-5720 (RO, 2 mg/kg), a competitive inhibitor of PG synthesis, HH was associated with a significant fall in GFR (43-17 ml/min, P < 0.001) and RBF (195-89 ml/min, P < 0.001). In the third group of eight animals, pretreatment with indomethacin (IN, 10 mg/kg), a chemically dissimilar PG inhibitor, HH was also associated with a significant fall in GFR (38-8 ml/min, P < 0.001) and RBF (150-30 ml/min, P < 0.001). Renal denervation attenuated this renal ischemic effect of HH in the presence of PG inhibition. In the RO group, GFR (34 vs. 17 ml/min, P < 0.005) and RBF (145 vs. 89 ml/min, P < 0.025) were significantly greater in denervated vs. innervated kidneys during HH. Similarly, in animals treated with IN, a significantly higher GFR (28 vs. 8 ml/min, P < 0.005) and RBF (101 vs. 30 ml/min, P < 0.005) occurred in denervated as compared to innervated kidneys during HH. With HH, the increase in PRA in the control group (3.34-11.68 ng/ml per h, P < 0.005) was no different than that observed in the RO group (4.96-18.9 ng/ml per h, P < 0.001) or IN group (4.71-17.8 ng/ml per h, P < 0.001). In summary, the present results indicate that renal PG significantly attenuate the effect of HH to decrease GFR and RBF. Furthermore, renal denervation exerts a protective effect against the enhanced renal ischemic effects which occur in the presence of PG inhibition during HH. Finally, PG inhibition does not alter the effect of HH to cause an increase in PRA.

Prescribing medication in long-term dialysis units.

Little information is available regarding the current patterns of medication use in long-term dialysis centers. Therefore, we surveyed the medication records of 1,023 patients undergoing long-term dialysis therapy in 27 dialysis centers. The mean number of medications prescribed per patient was 7.7 +/- 0.54, increasing patient age, increasing duration of dialysis, in-center dialysis, and the presence of underlying diabetic and hypertensive nephropathy were associated with increased frequency of medication use. The use of multiple pharmacologic agents was associated with a high frequency of drug duplication (12%), potential dosage error (9%), potential significant drug interaction (15%), and use of contraindicated drugs (2.5%). A lack of individualization of the use of several pharmacologic agents was apparent. An extreme degree of center variability in drug use was also apparent. Periodic review of medication use should be undertaken in the long-term dialysis setting.

Isotonic hyponatremia following transurethral prostate resection.

The proper treatment of hyponatremia during transurethral resection of the prostate continues to be controversial. Two cases of isotonic hyponatremia are reported here, and the literature regarding the incidence and treatment of hyponatremia during transurethral resection of the prostate is reviewed. In each case, the patient developed neurologic changes during complicated transurethral prostate resection. Despite the rapid decrease in the serum sodium concentration, serum osmolality remained normal due to the resorption of the bladder irrigant glycine. Therefore, etiologies other than cerebral edema are postulated as the cause of the neurologic manifestations. Also, the role of the osmolar gap in directing appropriate therapy is emphasized in an effort to avoid unnecessary use of hypertonic saline. Finally, an appropriate differential diagnosis of the neurologic changes seen during the transurethral resection of the prostate syndrome is discussed.

Hypokalaemic, hypophosphatemic thyrotoxic periodic paralysis.

Thyrotoxic periodic paralysis is an uncommon neuromuscular disorder frequently associated with severe hypokalemia. We describe a patient with hypophosphatemia occurring in the setting of hypokalemic thyrotoxic periodic paralysis, an association reported only once previously. A review of the literature indicates that this combined biochemical derangement may not be uncommon and that thyrotoxic periodic paralysis should be recognized as a potential cause of hypophosphatemia. The correction of both hypokalemia and hypophosphatemia may lead to a more rapid resolution of the associated acute neurologic syndrome.

Thermodynamics of carbohydrate-lipid interactions.

Thermodynamic analyses of carbohydrate-lipid interactions were performed by investigating the effects of a series of carbohydrates, including monosaccharides, disaccharides, and trisaccharides, on the phase-transition properties of aqueous dispersions of 1,2-dipalmitoyl phosphatidylcholine (DPPC). The temperature of the lipid's main phase transition from the gel to liquid-crystalline phase is essentially unchanged in the presence of carbohydrate. The change in the free energy (delta G) of the transition is zero when a carbohydrate is added to aqueous dispersions of DPPC, while the enthalpy (delta H) and the entropy of the melting of DPPC are decreased. The thermodynamic information was used to examine carbohydrate-lipid interactions. Such interactions were elucidated according to our knowledge of the specific properties of carbohydrates in aqueous solutions and the previously proposed hydrophobic interaction involving hydrocarbon tails of the lipid in aqueous dispersions.

Bromide intoxication secondary to pyridostigmine bromide therapy.

The diagnosis of bromide intoxication is often aided by the detection of a low or negative anion gap due to the laboratory detection of bromide as chloride. A 59-year-old woman with myasthenia gravis who received a large dose of pyridostigmine bromide developed postoperative psychosis and was diagnosed as having bromide intoxication. The diagnosis was suspected in the setting of a negative anion gap and only later confirmed by direct measurement of the serum bromide level. To our knowledge , this is the first reported case of bromide intoxication due to pyridostigmine bromide administration.

Controlled trial of the effects of 1,25-dihydroxycholecalciferol in patients treated with regular dialysis.

In a double-blind controlled study, 15 patients received 1,25-dihydroxycholecalciferol (1,25[OH]2D3) (0.5-1.5 microgram/day) and 16 patients received vitamin D3 (D3) (400-1,200 IU/day). The patients receiving 1,25(OH)2D3 had a rise in mean serum calcium concentration from 9.05 +/- 0.15 to 10.25 +/- 0.20 mg/dl (p less than .001) with a return to 9.37 +/- 0.16 (p less than .001) in the post-control period; however, hypercalcemia (greater than 11.5 mg/dl) occurred in 5 of 15 patients. Likewise, patients who received 1,25(OH)2D3 but not those given D3 had a reversible decrease in immunoreactive parathyroid levels. 9 of 12 patients given D3 had serial iliac crest bipsies showing histologic deterioration, while 6 of 7 patients who received 1,25(OH)2D3 were improved or unchanged (p less than 0.025). Bone mineral and calcium content decreased in patients on D3 (p less than .05) but not in those on 1,25(OH)2D3. We conclude that the administration of 1,25(OH)2D3 to dialysis patients: (1) has a calcemic effect. (2) decreases levels of immunoreactive parathyroid hormone, and (3) is associated with histologic improvement in bone disease.

Lactic acidosis from carboxyhemoglobinemia after smoke inhalation.

Tissue hypoxia as a result of a wide variety of clinical situations had frequently been implicated as a cause of systemic acidosis due to the accumulation of lactic acid. Four patients suffering from smoke inhalation had lactic acidosis in association with carboxyhemoglobinemia. There was no evidence of decreased tissue perfusion, hypotension, arterial hypoxemia, or anemia. The following were tested in all patients: arterial pH (7.25 to 7.40), Pco-2 (19 to 27 mm Hg), Po (63 to 116 mm Hg), HCO-2- (11 to 19 meq/litre), carboxyhemoglobin (13% to 37%), and lactic acid (5.1 to 9.3 meq/litre). After therapy with oxygen and intravenous corticosteroids, there was prompt return of lactic acid levels, carboxyhemoglobin values, and arterial pH to normal. It is concluded that the cause of lactic acidosis in the presence of carboxyhemoglobinemia during smoke inhalation is tissue hypoxia. This tissue hypoxia is due to the reduction of the oxygen-carrying capacity of the blood and the concomitant shift of the oxyhemoglobin dissociation curve to the left, both known to result from carboxyhemoglobinemia.

Urinary diagnostic indices in acute renal failure: a prospective study.

A prospective analysis of the value of urinary diagnostic indices in ascertaining the cause of acute renal failure was undertaken. Our results show that in the setting of acute oliguria a diagnosis of potentially reversible prerenal azotemia is likely with urine osmolality greater than 500 mosm/kg H2O, urine sodium concentration less than 20 meq/litre, urine/plasma urea nitrogen ratio greater than 8, and urine/plasma creatinine ratio greater than 40. Conversely, a urine osmolality less than 350 mosm/kg, urine sodium concentration greater than 40 meq/liter, urine/plasma urea nitrogen ratio less than 3, and urine/plasma creatinine ratio less than 20 suggest acute tubular necrosis. A significant number of oliguric patients will not have urinary indices that fall within these guidelines. In this setting, urine sodium concentration divided by the urine-to-plasma creatinine ratio (the renal failure index) and the fractional excretion of filtered sodium provide a reliable means of differentiating reversible prerenal azotemia from acute tubular necrosis.

1,25 dihydroxycholecalciferol effects in chronic dialysis. A double-blind controlled study.

1,25 dihydroxycholecalciferol [1,25(OH)2D3] was studied in a double-blind controlled fashion in patients on chronic dialysis. Serum calcium was unchanged in 16 patients on vitamin D3 (D3) (400 to 1200 IU/day). In 15 patients on 1,25(OH)2D3 (0.5 to 1.5 microgram/day), serum calcium increased from 9.05 +/- .15 to 10.25 +/- .20 mg/dl (p less than 0.001), returning to 9.37 +/- .16 mg/dl (p less than 0.001) in the post control period. Patients on D3 showed no reversible decrease in immunoreactive parathyroid hormone levels, but patients on 1,25(OH)2D3 did, from a control of 1077 +/- 258 to 595 +/- 213 microliter equivalents/ml (p less than 0.01), and returned to 1165 +/- 271 microliter equivalents/ml (p less than 0.005). Nine of 12 patients on D3 who underwent serial iliac-crest biopsies showed histologic deterioration, and six of seven who received 1,25(OH)2D3 were improved or unchanged (p less than 0.025). Bone mineral and calcium decreased in patients on D3 (p less than 0.05) but not in those on 1,25(OH)2D3. Hypercalcemia occurred in five of 15 patients. We conclude that 1,25(OH)2D3 has a calcemic effect in chronic dialysis patients, decreases levels of immunoreactive parathyroid hormone, and is associated with histologic improvement in bone disease. Thus, 1,25(OH)2D3 is a valuable adjunct to the management of renal osteodystrophy but requires monitoring of serum calcium to avoid hypercalcemia.

Nonoliguric acute renal failure.

To delineate the clinical spectrum of nonliguric renal failure, we studied prospectively 90 patients with acute renal failure 54 of whom were nonoliguric throughout their periods of azotemia. Although the causes of nonoliguric renal failure varied, nephrotoxic failure occurred more frequently in nonoliguric than in oliguric subjects (P is less than 0.01). As com pared to oliguric patients, those without oliguria had significantly lower urinary sodium concentrations (P is less than 0.05) and fractional excretions of sodium (P is less than 0.02), had shorter hospital stay (P is less than 0.01), had fewer septic episodes, neurologic abnormalities, gastrointestinal bleeding and acidemia, required dialysis less frequently (P is less than 0.001) and had lower mortality rate (26 per cent in nonoliguric vs. 50 per cent in oliguric patients -- P is less than 0.05). Nonoliguric renal failure occurs more often than is generally recognized and causes less morbidity and mortality than oliguric acute renal failure.