Antonio Quintanilla

Pharmacokinetics of furosemide in advanced renal failure

The pharmacokinetics of furosemide were studied in 12 patients with advanced renal failure. The elimination half‐life of furosemide averaged 9.7 hours. Renal furosemide clearance was reduced, but furosemide elimination by non renal mechanisms was unimpaired in uremic patients without liver disease and accounted for 86% to 98% of total elimination. Nonrenal furosemide clearance also was reduced in 3 uremic patients with liver cirrhosis, and elimination half‐life was prolonged to 20 hours in 1 of these patients. The diuretic response to intravenous furosemide appeared to be adversely affected by poor renal function and dehydration. Diuretic response was always less after oral than after intravenous furosemide, and the slow, intravenous infusion of this drug is recommended for maximal efficacy in uremic patients.

Acute hemolysis due to profound hypo-osmolality. A complication of hemodialysis.

Acute hemolysis in maintenance hemodialysis patients is not a rare occurrence. Significant hemolysis is life-threatening and may be unrecognized because of nonspecific symptomatology. This paper reports observation of a severe hemolytic episode in a hemodialysis patient. The hemolysis was associated with a sudden drop in serum osmolality and profound hyponatremia, resulting from accidental dialysis against deionized water. Recognizing the condition and treating it promptly by dialysis with physiological dialysate are essential for patient survival.

Electrophysiological studies on uremic patients-comparison of peritoneal dialysis and hemodialysis.

Introduction Electrophysiological studies on uremic patients, whose symptoms typically reflect brain dysfunction, have shown abnormalities in the EEG (1-7), visual evoked responses (810) and photic driving responses(11). Most of these studies have emphasized changes of only one of these physiological indices. By contrast, in the present study all three types of measures were investigated in each patient. Furthermore, since controversy still exists regarding the relative benefits of different types of dialysis, our patients were paired according to the two kinds of dialytic therapy used, i.e., peritoneal dialysis and hemodialysis. Therefore, the goal of this project was to compare the quantified and computerized (1) EEG, (2) visual evoked and (3) photic driving responses of these paired patients, especially to investigate the possibility that different neurophysiological effects may be produced by these two kinds of dialysis.

Effect of acute changes in serum digoxin concentration on renal digoxin clearance

The effect of acute alterations of serum digoxin concentration (SDIG) on the renal clearance of digoxin (CDIG) was studied in six normal subjects undergoing water diuresis. Digoxin in a 5% dextrose and water solution was infused at a rate of 0.01 µg/kg/min (low dose). One hour after the infusion began, three 20‐min urine samples for clearance determination were taken. The digoxin infusion rate was then increased to 0.05 µg/kg/min (high dose) and three additional urine samples were taken an hour later. With low doses of digoxin, the SDIG was (X̄ ± SD) 0.63 ± 0.08 ng/ml, CDIG was 252.3 ± 65.1 ml/min, inulin clearance (CIN) was 96.8 ± 15.7 ml/min, the ratio CDIG/CIN was 2.59 ± 0.38, and renal blood flow (CPAH) was 516 ± 90 ml/min. With the high‐dose infusion, SDIG rose to 3.23 ± 0.44 ng/ml; CIN, CDIG, CDIG/CIN, and CPAH remained stable. CDIG correlated strongly with both CINand CPAH. We conclude that in normal subjects undergoing water diuresis, CDIG/CIN is not altered by acutely increasing SDIG, digoxin is extensively secreted by the nephron, and CDIG is linearly related to renal plasma flow.

Antihypertensive and Hemodynamic Effects of Ticrynafen Compared with Hydrochlorothiazide

A double-blind study was performed in 33 ambulatory men, 27 black and 6 white, with mild to moderate essential hypertension to evaluate antihypertensive effects of ticrynafen (Ty) versus hydrochloroth

Renal Handling of Enalaprilat

Most converting enzyme inhibitors share a predominantly renal dual elimination pathway consisting of glomerular filtration and tubular secretion. Since enalaprilat has two functional acidic groups, it is likely that it may be secreted via the proximal tubule organic acid system and, thus, its clearances would exceed that of glomerular filtration rate markers. We therefore examined the renal clearance of enalaprilat in normal volunteers and compared it with simultaneously measured inulin and creatinine clearances to explore the contribution of tubular secretion to the renal elimination of the drug. Twelve healthy male subjects with an age range of 24 to 58 years (mean +/- SE, 33.1 +/- 2.8) were studied. They had representative height (178.6 +/- 1.99 cm) and weight (73.3 +/- 2.1 kg) and had normal renal function as judged by blood urea nitrogen (BUN) (6 +/- 0.3 mmol/L [17 +/- 0.8 mg/dL]), plasma creatinine (88 +/- 3 mumol/L [1.0 +/- 0.03 mg/dL]), and creatinine clearance determined by a prestudy 24-hour urine collection (123.2 +/- 6.2 mL/min). Results are as follows: mean creatinine clearance, 2.12 mL/s (127 mL/min); mean inulin clearance, 119.1 ml/min mean creatinine clearance/inulin clearance, 1.07 mean enalaprilat protein binding, 37.9% unbound enalaprilat clearance, 222.4 ml/min; and the mean fractional enalaprilat clearances were: enalaprilat clearance/creatinine clearance, 1.72 (P less than 0.05, difference from 1.0); enalaprilat clearance/inulin clearance, 1.85, (P less than 0.05, difference from 1.0). Our results demonstrate that the clearance of free enalaprilat exceeds that of inulin and creatinine, suggesting that elimination of the drug proceeds through two complementary pathways, namely glomerular filtration and tubular secretion.

Metabolic Alkalosis in the Patient With Uremia

A 55-year-old man was admitted with the chief complaints of nausea, vomiting, abdominal pain, and weakness. He experienced intermittent nausea and vomiting that became progressively more severe for several weeks. During the last week he could not retain food in his stomach, and developed moderately severe epigastric pain. He became progessively weaker, which the patient attributed to lack of food. He also admitted moderate to heavy alcohol intake. He had a past history of peptic ulcer disease, gout, and 15 years of hypertension for which he took medications sporadically. About a year prior to the current admission, a physician told him that the high blood pressure had caused kidney damage. He had had nocturia (once or twice) for many years, which became more pronounced (two or three times per night) during the last 6 months. During the last week he noticed a reduced volume of urine, with a sharp decline over the last 24 hours. Physical examination showed a well-developed, thin, anxious, pale, and somewhat confused white man. Vital signs included pulse rate, 96/min and regular; respirations, 18/min; blood pressure, 156/110 mm Hg supine and 140/100 mm Hg sitting; and a normal temperature. The skin was pale, with poor turgor in the upper part of the body, although mild pitting edema was present in his legs. Conjunctivae and oral mucosae were pale. A systolic ejection murmur was heard at the base of his heart. Scattered inspiratory rales were present at both pulmonary bases. The abdomen was soft, without distention, and moderately tender to palpation in the epigastric and umbilical areas. The prostate was slightly enlarged, but the bladder was not distended. No occult blood was present in the stool. The chest x-ray showed an enlarged heart and possibly a small amount of fluid in the costophrenic pleural space. The electrocardiogram changed consistently with left ventricular hypertrophy. Laboratory tests disclosed anemia, advanced renal in sufficiency, electrolyte disturbances, and a mixed acidbase disturbance (metabolic acidosis and metabolic alkalosis) (Table 1). An increased anion gap, common in severe renal failure and not uncommon in alkalemia, was also observed. The 8 mmollL increment in the anion gap approximately reflects the 8 mmol/L of retained acid that, in turn, consumed 8 mmollL of bicarbonate. Thus, had the renal failure acidosis not been present, the serum bicarbonate concentration would have increased from 38 mmol/L to perhaps as high as 46 mmollL. The clinical picture was initially interpreted as a vicious circle of uremia, vomiting, and worsening of the uremic syndrome by volume contraction. Persistent hypertension despite volume contraction was almost certainly related to his long history of essential hypertension and perhaps to an exaggerated release of renin that was triggered by the hypovolemia. Administration of 0.9% NaCl solution corrected the dehydration but failed to increase the urine output. The patient was dialyzed (standard acetate bath) through a subclavian catheter, with marked improvement of his blood chemical profile. However, attempts to remove the nasogastric tube were unsuccessful because of the recurrrence and persistence of vomiting. On the third day after admission, following endoscopy and x-ray examination of the stomach, a diagnosis of pyloric stenosis secondary to chronic peptic ulcer disease was determined. Treatment began with intravenous ranitidine and fluid replacement with 0.9% NaCl solution, later changed to 5% dextrose in 0.3% NaCl and 20 mmoles KCI. The dialysis bath had the standard acetate concentration and 4.0 mmollL KCI. Packed red-cell transfusions were given before surgical correction of the pyloric stenosis.

Renal tubular acidosis: mechanisms and management.

Renal tubular acidosis is not one entity but several. Even though all its forms are characterized by the kidneys inability to excrete an appropriately acid urine, the mechanism of the defect, its laboratory and clinical manifestations, and its management vary considerably. One type can cause disabling complications in various organ systems, while another is generally asymptomatic. Differential diagnosis is straightforward, and treatment effective.

Renal hemodynamics and water excretion in Addison's disease☆

Patients with Addisons disease have impaired ability to excrete free water. The mechanism of this defect is still not clear. These experiments were designed to help clarify the role of altered renal hemodynamics in the genesis of the defect. Six patients with Addisons disease were studied. Enough salt and water was administered to maintain adequate hydration throughout the study but no hormonal replacement was instituted. After a water load, the urine output (V), free water clearance (CH2O), sodium excretion (UNaV), total solute clearance (COsm), inulin clearance (CIn), and para-aminohippurate clearance (CPAH) were measured by standard clearance techniques. In the control studies V and CH2O were abnormally low. The studies were repeated after administration of DOCA, 2.5 mg daily, for a week. This medication decreased UNaV and improved the plasma electrolyte profile but did not cause a significant change in V, CH2O, GFR, or RPF. The same studies were repeated once more after administration of prednisone, 5 mg daily in divided doses, for a week. This drug induced a marked water diuresis while GFR and RPF remained unchanged. It is concluded that hypovolemia and altered renal hemodynamics are not the only mechanisms of the impaired water excretion in Addisons disease. A severe defect remains after normalization of hypovolemia and this is corrected by prednisone but not by DOCA, through mechanisms which do not involve changes in GFR or RPF.

Unilateral renal papillectomy via laser or incisional techniques: Chronic functional effects in the dog

OBJECTIVE To determine if selective renal papillectomy would impair urinary concentrating ability, thereby decreasing urinary calcium concentration. METHODS Left papillectomy was performed in dogs using either incisional (n = 6) or Neodymium:yttrium-aluminum-garnet (Nd:YAG) laser (n = 5) techniques. Split renal function studies were then performed four months postoperatively to determine the effect on multiple parameters including inulin and para-aminohippurate (PAH) clearance, free water reabsorption, and calcium concentrations. Partially infarcted kidneys (n = 6) were evaluated in a similar fashion to determine the role of impaired glomerular filtration rate (GFR) in the observed concentrating defect occurring after papillectomy. RESULTS Papillectomized kidneys demonstrated impaired free water reabsorption, resulting in a decreased urinary osmolality and an increased fractional excretion of water. Osmolar clearance [Na+] and Na+ excretion were unaffected by papillectomy, whereas [Ca++] was significantly reduced. While a slight defect in free water reabsorption existed following partial infarction, urinary osmolality was only minimally decreased, fractional excretion of water was unchanged, and Na+ excretion was decreased. CONCLUSIONS The concentrating defect induced by papillectomy via either sharp excision or laser ablation is due to loss of medullary tissue and is greater than the defect resulting from impaired GFR, which is presumably due to decreased medullary solute delivery and increased flow of water in remaining nephrons. Since the physiologic consequences of papillectomy (formation of less concentrated urine with decreased [Ca++]) have potential clinical applicability, further study of this concept is warranted.