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K S Kamel

Publications and source records attributed to K S Kamel.

At least 37 records · Page 2Linked to original sources
PubMed1993

Treatment of hyponatremia: a quantitative analysis.

The bulk of clinical and experimental evidence seems to support the view that a catastrophic outcome can accompany rapid correction of chronic hyponatremia. However, the dilemma that faces the clinicians is controlling the rate at which the serum sodium concentration is increased during the treatment of hyponatremia. We present a case of severe hyponatremia and hypokalemia to illustrate, in a quantitative fashion, that the increase in serum sodium concentration will be determined not only by the tonicity of infused fluids, but also, and to a major degree, by the rate of excretion of free water by the kidney. A rapid increase in serum sodium concentration would occur if antidiuretic hormone (ADH) release is inhibited and water diuresis ensues. We suggest that the administration of potassium chloride (orally or via a central line) would have been the appropriate therapy for this patient.

Diuresis↗
PubMed1992

Might distal renal tubular acidosis be a proximal tubular cell disorder?

Incomplete renal tubular acidosis (RTA) and overt distal RTA may be different stages of the same underlying pathophysiology in certain individuals. The rationale that draws these conditions together is the relatively alkaline pH of the urine, hypocitraturia, and a possible familial association. The rate of excretion of ammonium (NH4+), on the other hand, suggests that these conditions stem from fundamentally different lesions. To explain this difference, we suggest that two possible disorders may result in the evolution from incomplete RTA to overt distal RTA. One subgroup could have gradient-limited distal RTA, while the other subgroup may have a lower pH of the intracellular fluid of the proximal convoluted tubular epithelium. Indices of proximal intracellular pH (rates of excretion of NH4+, NH3, and citrate) were culled from the literature spanning the years 1959 to 1991 on patients with incomplete RTA and overt distal RTA. Three points emerge: (1) the rate of excretion of NH4+ was lower in patients with overt distal RTA than in normals following an acute acid load (23 +/- 1 v 49 +/- 3 mumol/min); (2) the concentration of NH3 in the urine was almost 25-fold higher in incomplete RTA than in normals (69 +/- 14 v 3 +/- 0.4 nmol/min); and (3) in incomplete RTA, the pH of the urine fell to very low values (4.9 +/- 0.1) when high urine flows were induced with furosemide. The low pH of the urine would therefore suggest that many of these patients do not gradient-limited distal RTA, but more likely have proximal renal epithelial cell acidosis. We hypothesize that this high rate of excretion of NH4+ and low rate of excretion of citrate in the absence of acidosis or hypokalemia is consistent with proximal cell acidosis. To explain a transition from incomplete RTA to overt distal RTA, we speculate that toxicity of high concentrations of NH3 in the medullary interstitium as well as nephrolithiasis and nephrocalcinosis due to low urinary citrate and possibly an alkaline medullary interstitium may lead to damage of structures in this region.

Acid-Base Equilibrium↗
PubMed1992

Is accelerated oxidation of lactate required for dichloroacetate to lower the level of lactate in blood?

We examined mechanisms by which dichloroacetate (DCA), an activator of pyruvate dehydrogenase (PDH), led to a decrease in the concentration of lactate in blood in a unique "metabolic setting," where the concentration of lactate in blood was 5.4 +/- 0.5 mmol/L. Elevated levels of lactate were induced in anaesthetized rabbits by the administration of a large dose of insulin. The rate of consumption of oxygen was 1.2 +/- 0.1 mmol/min, the respiratory quotient was close to unity, and close to half of the PDH was in its active form; therefore, virtually all ATP synthesis should require flux through PDH. Hence, we predicted that DCA should not cause a significant decrease in the concentration of lactate in blood in this model. In contrast, if DCA was effective, new insights could be obtained into its mechanisms of action, at least in this setting. During steady-state hyperlactatemia, DCA was given as its sodium salt, 2 mmol/kg (n = 10); a control group (n = 5) received equimolar NaCl. Forty minutes later, the level of lactate in blood in the DCA group was 1.3 +/- 0.2 mmol/L, significantly lower than in the NaCl group (4.2 +/- 0.6 mmol/L). To determine the organ(s) responsible for removing lactate, arteriovenous differences were measured in organs drained by the jugular, femoral, and hepatic veins. There was no net uptake of lactate in these drainage beds after DCA was administered. From a quantitative analysis of the rate of removal of lactate and the rate of consumption of oxygen, it seems unlikely that the majority of the decrease in lactate could be directly attributed to an increase in its oxidation.

Animals↗
PubMed1992

Studies to determine the basis for hyperkalemia in recipients of a renal transplant who are treated with cyclosporine.

Hyperkalemia is commonly encountered in patients who receive a renal transplant and the immunosuppressive drug, cyclosporine. There is also a high incidence of hypertension (which is thought to be due to expansion of the extracellular fluid volume) and hyperchloremic metabolic acidosis in this group of patients. This constellation of findings led to the suspicion of the possibility that their basis might be type II hypoaldosteronism. To test this hypothesis, 12 patients with hyperkalemia (plasma K+, 5.1 +/- 0.2 mmol/L at the time of study) while receiving cyclosporine were studied. Patients who had diabetes mellitus, those receiving drugs known to cause hyperkalemia (e.g., beta blockers, angiotensin-converting enzyme inhibitors, K(+)-sparing diuretics), or those with a serum creatinine greater than 200 mumol/L were excluded. The renal response to hyperkalemia was inappropriate because the transtubular K+ concentration gradient (TTKG) was only 4.3 +/- 0.4 compared with a TTKG of 13 +/- 1, 2 h after 50 mmol of KCl was given to normal subjects. The TTKG, after administration of 200 micrograms of fludrocortisone, was still very low (5.6 +/- 0.6) in the patients compared with that of controls (12 +/- 1). After administration of 250 to 500 mg of acetazolamide to increase the delivery of bicarbonate to the distal nephron, the TTKG rose significantly to 11 +/- 1 in patients on cyclosporine, compared with 17 +/- 1 in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetazolamide↗
PubMed1992

Persistent hyperkalemia in a patient with diabetes mellitus: a reversible defect in kaliuresis during bicarbonaturia.

The purpose of this report is to apply recent advances in the understanding of the physiology of the excretion of potassium to a patient who had hyperkalemia due to a low rate of excretion of potassium. The defect was first suspected during therapy for diabetic ketoacidosis, when the concentration of potassium in plasma was unusually high (7.3 mmol/l) on admission and the deficit of potassium, as judged from the quantity of potassium infused to maintain normokalemia (40 mmol/24 h), was much less than expected. After recovery from diabetic ketoacidosis, hyperkalemia persisted despite near-normal values for creatinine and glucose in plasma. Excretion of potassium was low, considering the stimulus of hyperkalemia, and did not rise appreciably after the acute or chronic administration of a mineralocorticoid. The transtubular potassium concentration gradient (TTKG) did not exceed 6 after a large dose of fludrocortisone (200 micrograms) was administered. Notwithstanding, the TTKG rose to 14.4 following the intake of acetazolamide. We speculate that the basis for the hyperkalemia was type II hypoaldosteronism.

Bicarbonates↗
PubMed1992

Lactic acidosis, ketoacidosis, and energy turnover: "figure" you made the correct diagnosis only when you have "counted" on it--quantitative analysis based on principles of metabolism.

Three cases are presented to illustrate that quantitative analysis based on physiologic principles can help resolve certain controversies in clinical medicine. For example, in case 1, a patient with severe hypoxia, the rate of production of lactic acid is so high that only restoration of delivery of oxygen is rational therapy. If the degree of hypoxia exceeds 5.6% of demand, dichloroacetate will not lessen the degree of acidosis. Further, even when delivery of oxygen is returned to normal, the rate of fall in lactate and rise in bicarbonate in plasma will be relatively slow. In case 2, a patient with diabetic ketoacidosis, our discussion stresses that the rate of production of ketoacids is not that rapid and that the degree of ketoacidosis is influenced to a major degree by decreasing the rate of oxidation of ketoacids in brain and kidneys. Case 3, a patient with severe hyperglycemia, illustrates that insulin will only promote the oxidation of glucose at a rapid rate once the levels of fatty acids and ketoacids decline to low levels. Accelerated transport of glucose by insulin is only a permissive action for the oxidation of glucose.

Acidosis, Lactic↗
PubMed1991

Modulation of the secretion of potassium by accompanying anions in humans.

In animals, secretion of potassium (K) in the cortical collecting duct (CCD) is modulated by the properties of the accompanying anion. In humans, results are inconclusive as previous studies have not differentiated between a kaliuresis due to a rise in the concentration of K from one due to an increase in the volume of urine. Our purpose was to study the effects of chloride (Cl) and bicarbonate on the secretion of K in the CCD in humans using the transtubular K concentration gradient (TTKG), a semi-quantitative index of secretion of K in the terminal CCD. After control blood and urine samples were obtained, all subjects ingested 0.2 mg fludrocortisone to ensure that mineralocorticoids were not limiting the secretion of K. The anionic composition of the urine was varied using three protocols: Normal subjects (N = 11) ingested cystine and methionine to induce sulfaturia; nine subjects with a contracted ECF volume (to lower the concentration of Cl in the urine) were also studied during sulfaturia following the ingestion of cystine and methionine; 13 normovolemic subjects were studied during bicarbonaturia following the ingestion of acetazolamide. When the concentration of Cl in the urine was greater than 15 mmol/liter, sulfate had no effect on the TTKG. With lower concentrations of Cl in the urine, the TTKG rose 1.5-fold. The TTKG rose 1.8-fold in the presence of bicarbonaturia despite concentrations of Cl in the urine that were greater than 15 mmol/liter, suggesting that bicarbonate has additional effects on this K secretory process. At comparable concentrations of sulfate and bicarbonate in the urine, the TTKG was increased only with bicarbonaturia.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetazolamide↗
PubMed1991

Glue-sniffing and distal renal tubular acidosis: sticking to the facts.

An index case is presented to introduce the subject of the acid-base and electrolyte abnormalities resulting from toluene abuse. These include metabolic acidosis associated with a normal anion gap and excessive loss of sodium and potassium in the urine. The major question addressed is, what is the basis for the metabolic acidosis? Overproduction of hippuric acid resulting from the metabolism of toluene plays a more important role in the genesis of the metabolic acidosis than was previously believed. This conclusion is supported by the observation that the rate of excretion of ammonium was not low during metabolic acidosis in six of eight patients, suggesting that distal renal tubular acidosis was not an important acid-base abnormality in most cases where ammonium was measured. The excretion of hippurate in the urine unmatched by ammonium also mandates an enhanced rate of excretion of the cations, sodium and potassium. The loss of sodium causes extracellular fluid volume contraction and a fall in the glomerular filtration rate, which may transform the normal anion gap type of metabolic acidosis into one with a high anion gap (accumulation of hippurate and other anions). Continuing loss of potassium in the urine leads to hypokalemia. An understanding of the metabolism of toluene provides the basis for the unusual biochemical abnormalities seen with abuse of this solvent.

Acid-Base Equilibrium↗
PubMed1991

Interpretation of the urine osmolality: the role of ethanol and the rate of excretion of osmoles.

One purpose of this report is to illustrate that calculating the rate of excretion of osmoles in the urine can be of value in the differential diagnosis of hypernatremia and polyuria. A second purpose is to illustrate a clinical example where the osmolality of the urine did not reflect the lack of action of ADH. A patient with ethanol intoxication seemed to have central diabetes insipidus on clinical grounds. However, the osmolality of the urine was 287 mosm/kg H2O, a value which made this diagnosis unlikely. Since the concentration of ethanol in plasma was 119 mmol/L, we suspected that the urine contained an appreciable quantity of alcohol; this might obscure the lack of action of ADH. A study was performed to document the quantitative relationship between the concentrations of ethanol in plasma and urine. The concentration of ethanol in the urine was approximately 1.4-fold greater than in plasma. Using this correction factor, the osmolality of the urine adjusted for ethanol in the patient was only 120 mosm/kg H2O, a value more consistent with the diagnosis of central diabetes insipidus.

Adult↗
PubMed1990

The excretion of ammonium ions and acid base balance.

The role of the kidney in acid base balance is to generate "new" bicarbonate ions, largely as a result of the excretion of ammonium ions. Three points will be covered in this review. First, we challenge the traditional view that the proximal nephron reclaims filtered bicarbonate ions, whereas, the distal nephron generates "new" bicarbonate ions. Virtually all "new" bicarbonate ions are generated in the proximal convoluted tubule during glutamine metabolism; very little is formed at distal sites. Second, the excretion of ammonium ions plays an important role in acid base balance only during chronic ketoacidosis, in response to diarrhea, in chronic renal insufficiency, and in distal renal tubular acidosis. Third, although the excretion of ammonium ions is said to signal the addition of bicarbonate ions to the extracellular fluid, the anion excreted with the ammonium cation is also important for acid base balance.

Acid-Base Equilibrium↗
PubMed1990

The transtubular potassium concentration in patients with hypokalemia and hyperkalemia.

It is advantageous to make an independent assessment of the potassium (K) secretory process and the luminal flow rate in the renal cortex to evaluate K handling by the kidney during hypokalemia or hyperkalemia. The transtubular potassium concentration gradient (TTKG) is a semiquantitative index of the activity of the K secretory process. The purpose of this study was to define expected values for the TTKG in normal subjects with hypokalemia or following an acute K load. During hypokalemia of non-renal origin, the TTKG was 0.9 +/- 0.2; in contrast, the TTKG was significantly higher during the hypokalemia of hyperaldosteronism, 6.7 +/- 1.3. The TTKG was 11.8 +/- 3.6, 2 hours after normokalemic subjects received 0.2 mg 9 alpha-fludrocortisone (9 alpha-F). To obtain expected values during hyperkalemia, normal subjects ingested 50 mmol potassium chloride; 2 hours later, the TTKG was 13.1 +/- 3.8. Therefore, the expected value for the TTKG must be interpreted relative to the concentration of K in the plasma. Circumstances were also defined where the TTKG is low despite hyperaldosteronism, namely, during a water diuresis and pre-existing hypokalemia.

Desoxycorticosterone↗
PubMed1990

Removal of an inorganic acid load in subjects with ketoacidosis of chronic fasting.

When a large inorganic acid load is ingested by normals, the proton load is eliminated because the rate of excretion of ammonium can rise to 200 to 300 mmol/day. In subjects with ketoacidosis of chronic fasting, such a large increase in the rate of excretion of ammonium might not be possible because of ATP balance considerations in proximal cells. Subjects with ketoacidosis of chronic fasting excreted less net acid as defined in the conventional way when they consumed a large inorganic acid load (136 +/- 6 vs. 176 +/- 26 mmol/day in control fasted subjects). Nevertheless, the vast majority of this inorganic acid load was eliminated because they were in steady state and had only a slightly lower concentration of bicarbonate (13 +/- 0.6 vs. 15 +/- 0.5 mmol/liter) and ketoacid anions (3.3 +/- 0.2 vs. 5.5 +/- 0.2 mmol/liter) in their blood. Using a definition of net acid excretion where the component of bicarbonate loss was expanded to include "potential bicarbonate" (ketoacid anions) in the urine, the rate of excretion of net acid was higher in subjects who ingested the inorganic acid load, owing to a much lower rate of excretion of ketoacid anions (9 +/- 2 vs. 120 +/- 7 mmol/day). This lower rate of excretion was not only due to a lower filtered load, but also to a higher fractional reabsorption of ketoacid anions during acidosis (97 +/- 0.1 vs. 77 +/- 0.2%). This higher fractional reabsorption could not be explained by a lower filtered load of ketoacid anions or to a restricted intake of sodium.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗
PubMed1990

Urine electrolytes and osmolality: when and how to use them.

The purpose of this review is to provide an update on the use of the urine electrolyte and osmolality measurements in patients with disorders of fluid, electrolytes, and/or acid-base metabolism. It is critical to appreciate that there are no 'normal values' for these parameters, only 'expected values' relative to clinical situations. Pitfalls in the interpretation of each electrolyte in the urine are also provided. To detect a mild to moderate degree of reduction of the 'effective' intravascular volume, both urine sodium (Na) and chloride (Cl) concentrations should be measured. Pitfalls in this assessment are abnormal renal and adrenal function and the use of diuretics. Insights into the etiology of the low 'effective' intravascular volume can be deduced by comparing the urine Na, potassium (K), and Cl concentrations. The urine net charge (Cl vs. Na + K) is the most reliable way to estimate the urine ammonium concentration short of its direct measurement, an assay that is not provided by most laboratories. This measurement is important in the differential diagnosis of hyperchloremic metabolic acidosis. To examine the renal response to hypokalemia or hyperkalemia, the two components of K excretion (K secretion and urine flow rate) should be examined separately. The former is evaluated using the transtubular K, concentration gradient. The urine osmolality is used to assess antidiuretic hormone action and the osmolality of the renal medulla and to determine the etiology of polyuria and/or hypernatremia. The urine osmolality can also be used to assess the ammonium concentration, using the urine osmolal gap, and to detect unusual urine osmoles.

Acid-Base Imbalance↗
PubMed1990

Low dose ciclosporin from the early postoperative period yields potent immunosuppression after renal transplantation.

This study sought to determine if low doses of ciclosporin (CS) designed to give fasting serum levels of 50-100 ng/ml achieve effective immunosuppression when used from the early postoperative period after renal transplantation. Ninety-four primary renal transplant recipients were studied. Group 1 patients were treated with CS 100 ng/ml and prednisone (0.15 mg/kg/day). Group 2 patients received CS 50 ng/ml, prednisone (0.15 mg/kg/day) and azathioprine (1 mg/kg/day). These patients were compared to a control group of 26 patients (group 3) maintained on only prednisone and azathioprine. CS-treated patients suffered significantly fewer rejection episodes than control subjects (rejection episodes per patient in first year: group 1: 0.3 +/- SD 0.6; group 2: 0.7 +/- SD 0.7; group 3: 1.3 +/- SD 1.1, p less than 0.005). In addition, a greater number of CS-treated patients were completely free of rejection episodes during the first year posttransplant (group 1: 63%; group 2: 64%; group 3: 19%, p less than 0.005). Patient and graft survival were similar in all groups after 1 year (group 1: 92 and 92% respectively; group 2: 95 and 87% respectively; group 3: 96 and 85% respectively). These data suggest that the dose of CS required for effective immunosuppression in vivo is lower than has been previously thought.

Adult↗
PubMed1990

Ammonium metabolism: emphasis on energy considerations.

The metabolism of a typical North American diet yields a net acid load. Hydrogen ions are removed from the body after combining with bicarbonate to form CO2. This leaves the body with a deficit of bicarbonate. The role of the kidney is to add 'new' bicarbonate to the body. It does so primarily by synthesizing NH4+ plus bicarbonate while making NH4+ an end-product of metabolism (excreting it in the urine). Production of NH4+ occurs primarily in proximal convoluted tubule cells. Although several possible pathways can do this, the primary one stimulated by chronic metabolic acidosis is the glutaminase/glutamate dehydrogenase one. The upper limit on this pathway is set by energy turnover considerations. This, in effect, means control by renal work (sodium reabsorption) and fuel competitions (availability of fat-derived fuels).

Acidosis, Renal Tubular↗