S. Kamel

Acid–Base Problems in Diabetic Ketoacidosis

This review focuses on the safe removal of excess hydrogen ions, the administration of sodium bicarbonate, and the possible contribution of intracellular acidosis to the development of cerebral edema in patients with diabetic ketoacidosis.

Mechanisms to concentrate the urine: an opinion.

Purpose of reviewOur goal is to suggest how the renal concentrating mechanism is regulated in vivo. Recent findingsThe majority of descending thin limbs of the loop of Henle lack aquaporin-1 water channels, and loops of Henle in the inner medulla lack urea transporters. SummaryLack of water permeability in the descending thin limbs of the loop of Henle offers several advantages. First, since much less water is added to the outer medullary interstitial compartment, inhibitory control mechanisms on sodium and chloride reabsorption from the medullary thick ascending of loop of Henle initiated by water addition from the medullary collecting duct can be effective. Second, recycling of urea is efficient, as little urea will be washed out of the medulla. Third, delivery of a larger volume of filtrate to the medullary thick ascending limb of the loop of Henle permits both an appreciable reabsorption of sodium along with only a small fall in the luminal concentration of sodium in each of these liters. Hence there need be only a small lumen positive voltage in the medullary thick ascending limb of the loop of Henle. The absence of urea transporters in the loop of Henle in the inner medulla is required for a passive mechanism of sodium and chloride reabsorption in the inner medulla. Control of urea reabsorption from the medullary collecting duct is needed to prevent excessive oliguria in electrolyte-poor urine.

Properties Permitting the Renal Cortex to Be the Oxygen Sensor for the Release of Erythropoietin: Clinical Implications

The PO2 at this site where erythropoietin release is regulated should vary only when the hemoglobin concentration changes in capillary blood. The kidney cortex is an ideal location for this O2 sensor for four reasons. First, it extracts a small proportion of the oxygen that is delivered in each liter of blood; this makes the PO2 signal easier to recognize. Second, there is a constant ratio of the work performed (consumption of O2) to the renal blood flow rate (delivery of O2). Third, the high renal blood flow rate improves diffusion of O2 from capillaries to this O2 receptor. Fourth, a high renal cortical PCO2 prevents an additional shift of the O2:hemoglobin dissociation curve by other factors from being a confounding variable. This suggests that the GFR and the renal blood flow rate should be examined in patients with unexplained anemia or erythrocytosis.

Control of potassium excretion: a Paleolithic perspective.

Purpose of reviewRegulation of potassium (K+) excretion was examined in an experimental setting that reflects the dietary conditions for humans in Paleolithic times (high, episodic intake of K+ with organic anions; low intake of NaCl), because this is when major control mechanisms were likely to have developed. Recent findingsThe major control of K+ secretion in this setting is to regulate the number of luminal K+ channels in the cortical collecting duct. Following a KCl load, the K+ concentration in the medullary interstitial compartment rose; the likely source of this medullary K+ was its absorption by the H+/K+-ATPase in the inner medullary collecting duct. As a result of the higher medullary K+ concentration, the absorption of Na+ and Cl− was inhibited in the loop of Henle, and this led to an increased distal delivery of a sufficient quantity of Na+ to raise K+ excretion markedly, while avoiding a large natriuresis. In addition, because K+ in the diet was accompanied by ‘future’ bicarbonate, a role for bicarbonate in the control of K+ secretion via ‘selecting’ whether aldosterone would be a NaCl-conserving or a kaliuretic hormone is discussed. SummaryThis way of examining the control of K+ excretion provides new insights into clinical disorders with an abnormal plasma K+ concentration secondary to altered K+ excretion, and also into the pathophysiology of calcium-containing kidney stones.

Intrarenal urea recycling leads to a higher rate of renal excretion of potassium: an hypothesis with clinical implications.

Purpose of reviewThis review aims to illustrate why urea recycling may play an important role in potassium (K+) excretion and to emphasize its potential clinical implications. Recent findingsA quantitative analysis of the process of intrarenal urea recycling reveals that the amount of urea delivered to the distal convoluted tubule is about two-fold larger than the quantity of urea excreted in the urine. As the number of osmoles delivered to the late cortical distal nephron (CCD) determines its flow rate when aquaporin 2 water channels have been inserted in the luminal membrane of principal cells, urea recycling may play an important role in regulating the rate of excretion of K+ when the distal delivery of electrolytes is not very high. SummaryUrea recycling aids the excretion of K+; this is especially important in patients with disorders or those who are taking drugs that lead to a less lumen-negative voltage in the CCD. As a large quantity of urea is reabsorbed daily in the inner medullary collecting duct, the assumption made in the calculation of the transtubular K concentration gradient that there is no appreciable reabsorption of osmoles downstream CCD is not valid.

Control of excretion of potassium: lessons from studies during prolonged total fasting in human subjects.

A deficit of K+ of close to 300 mmol develops in the first 2 wk of fasting, but little further excretion of K+ occurs, despite high levels of aldosterone and the delivery of ketoacid anions that are not reabsorbed in the distal nephron. Our purpose was to evaluate how aldosterone could have primarily NaCl-retaining, rather than kaliuretic, properties in this setting. To evaluate the role of distal delivery of Na+, four fasted subjects recieved an acute infusion of NaCl to induce a natriuresis. To assess the role of distal delivery of [Formula: see text], five fasted subjects were given an infusion containing NaHCO3. The natriuresis induced by an infusion of NaCl caused only a small rise in the rate of excretion of K+ (0.8 ± 0.1 to 1.9 ± 0.3 mmol/h); in contrast, when [Formula: see text]replaced Cl- in the infusate, K+ excretion rose to 8.3 ± 2.2 mmol/h, despite little excretion of[Formula: see text] (urine, pH 5.8) and similar rates of excretion of Na+. The transtubular K+ concentration gradient was 19 ± 3 with [Formula: see text] and 6 ± 2 with NaCl. We conclude that the infusion of NaHCO3 led to an increase in K+ excretion, likely reflecting an increased rate of distal K+secretion. With a low distal delivery of[Formula: see text], aldosterone acts as a NaCl-retaining, rather than a kaliuretic, hormone.A deficit of K+ of close to 300 mmol develops in the first 2 wk of fasting, but little further excretion of K+ occurs, despite high levels of aldosterone and the delivery of ketoacid anions that are not reabsorbed in the distal nephron. Our purpose was to evaluate how aldosterone could have primarily NaCl-retaining, rather than kaliuretic, properties in this setting. To evaluate the role of distal delivery of Na+, four fasted subjects received an acute infusion of NaCl to induce a natriuresis. To assess the role of distal delivery of HCO3-, five fasted subjects were given an infusion containing NaHCO3. The natriuresis induced by an infusion of NaCl caused only a small rise in the rate of excretion of K+ (0.8 +/- 0.1 to 1.9 +/- 0.3 mmol/h); in contrast, when HCO3- replaced Cl- in the infusate, K+ excretion rose to 8.3 +/- 2.2 mmol/h, despite little excretion of HCO3- (urine, pH 5.8) and similar rates of excretion of Na+. The transtubular K+ concentration gradient was 19 +/- 3 with HCO3- and 6 +/- 2 with NaCl. We conclude that the infusion of NaHCO3 led to an increase in K+ excretion, likely reflecting an increased rate of distal K+ secretion. With a low distal delivery of HCO3-, aldosterone acts as a NaCl-retaining, rather than a kaliuretic, hormone.

Some Observations on the Clinical Approach to Metabolic Acidosis

The first step in the clinical approach to patients with metabolic acidosis is to deal with emergencies and to anticipate and prevent dangers associated with therapy. The traditional clinicalanalysisforthepresenceofmetabolicacidosissuffersfrom a number of limitations that at times hinders one’s ability to reach a proper diagnosis. Our aim here is to raise awareness of some of the nuanced difficulties and illustrate why other considerations add value. In patients with metabolic acidosis, analyses based on the anion gap in plasma (Panion gap) 1 or the strong ion difference 2 have major deficiencies. For example, the diagnosis of metabolic acidosis may be missed if one relies solely on pH and the concentration of bicarbonate (HCO3 ) in plasma (PHCO3) without considering changes in the content of HCO3 in the extracellular fluid (ECF) compartment. In addition, the rules of respiratory compensation, which are based solely on the arterial PCO2 rather than the more valuable PCO2 in capillary blood-draining skeletal muscle (as reflected by the venous PCO2), fail to assess the effectiveness of the bulk of the bicarbonate buffer system to remove Hand, hence, whether more H will bind to intracellular proteins in vital organs, such as the brain or the heart. 3

Managing Overly Rapid Correction of Chronic Hyponatremia: An Ounce of Prevention or a Pound of Cure?

Rapid correction of chronic hyponatremia may lead to osmotic demyelination syndrome (ODS) and devastating neurologic sequelae.[1][1] The rate of rise in plasma sodium concentration (PNa) in patients with chronic hyponatremia should be <8 mmol/L per d[2][2] and even lower in patients at higher risk

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.