G. M. Dolson

Endothelin-1 increases rat distal tubule acidification in vivo

Because endothelin receptor inhibition blunts increased distal tubule acidification induced by dietary acid, we examined whether endothelin-1 (ET-1) increases acidification of in vivo perfused distal tubules of anesthetized rats. ET-1 was infused intra-aortically (1.4 pmol ⋅ kg-1 ⋅ min-1) into control animals and into those with increased distal tubule HCO3 secretion induced by drinking 80 mM NaHCO3 solution for 7-10 days. ET-1 increased distal tubule acidification in both control and NaHCO3 animals. Increased acidification in control animals was mediated by increased distal tubule H+ secretion (23.7 ± 2.2 vs. 18.7 ± 1.7 pmol ⋅ mm-1 ⋅ min-1, P < 0.05) with no changes in HCO3 secretion. By contrast, ET-1 increased distal tubule acidification in NaHCO3 animals predominantly by decreasing HCO3 secretion (-9.5 ± 1.0 vs. -18.7 ± 1.8 pmol ⋅ mm-1 ⋅ min-1, P < 0.001) with less influence on H+ secretion. When indomethacin was infused (83 μg ⋅ kg-1 ⋅ min-1) to inhibit synthesis of prostacyclin, an agent previously shown to increase HCO3 secretion in the distal tubule, ET-1 increased distal tubule H+ secretion in both control (24.3 ± 2.2 vs. 15.7 ± 1.6 pmol ⋅ mm-1 ⋅ min-1, P < 0.02) and NaHCO3 (20.0 ± 2.0 vs. 13.6 ± 1.4 pmol ⋅ mm-1 ⋅ min-1, P < 0.05) without affecting HCO3 secretion. The data show that ET-1 increases distal tubule acidification in vivo and can do so by increasing H+ secretion and by decreasing HCO3 secretion when the latter is augmented by dietary NaHCO3.Because endothelin receptor inhibition blunts increased distal tubule acidification induced by dietary acid, we examined whether endothelin-1 (ET-1) increases acidification of in vivo perfused distal tubules of anesthetized rats. ET-1 was infused intraaortically (1.4 pmol x kg(-1) x min[-1]) into control animals and into those with increased distal tubule HCO3 secretion induced by drinking 80 mM NaHCO3 solution for 7-10 days. ET-1 increased distal tubule acidification in both control and NaHCO3 animals. Increased acidification in control animals was mediated by increased distal tubule H+ secretion (23.7+/-2.2 vs. 18.7 +/- 1.7 pmol x mm(-1) x min(-1), P < 0.05) with no changes in HCO3 secretion. By contrast, ET-1 increased distal tubule acidification in NaHCO3 animals predominantly by decreasing HCO3 secretion (-9.5 +/- 1.0 vs. -18.7 +/-1.8 pmol x mm(-1) x min(-1), P < 0.001) with less influence on H+ secretion. When indomethacin was infused (83 microg x kg(-1) x min[-1]) to inhibit synthesis of prostacyclin, an agent previously shown to increase HCO3 secretion in the distal tubule, ET-1 increased distal tubule H+ secretion in both control (24.3 +/-2.2 vs. 15.7 +/- 1.6 pmol x mm(-1) x min(-1), P < 0.02) and NaHCO3 (20.0 +/- 2.0 vs. 13.6 +/- 1.4 pmol x mm(-1) x min(-1), P < 0.05) without affecting HCO3 secretion. The data show that ET-1 increases distal tubule acidification in vivo and can do so by increasing H+ secretion and by decreasing HCO3 secretion when the latter is augmented by dietary NaHCO3.

Novel H1N1‐associated rhabdomyolysis leading to acute renal failure

The WHO recently declared that the novel influenza H1N1 virus was responsible for the 2009 flu pandemic. As the virus continues to spread globally and affect more individuals, more complications of infection with this virus are being recognized. To our knowledge, we report the first case of H1N1-induced rhabdomyolysis leading to acute renal failure in an adult. This case highlights the importance of recognizing a significant extrapulmonary complication of H1N1 infection.

Vascular relaxation probably mediates the antihypertensive effect of a high-potassium diet : a role for enhanced vascular Na,K-ATPase activity

Objective to evaluate the effect of dietary potassium on blood pressure and vascular contractility in adult rats of two strains, spontaneously hypertensive rats (SHR) and normotensive Wistar–Kyoto (WKY) rats. Design ‘Potassium-induced relaxation’ was evaluated in aortic rings as a functional measure of Na,K-ATPase activity in the vascular wall. The rats were fed one of three diets: regular (American Institute of Nutrition-76 rat chow); high-sodium (7% sodium chloride) or high-sodium plus potassium (7% sodium chloride and 13.4% potassium citrate) for 12 ± 1 weeks. Results SHR fed the high-sodium diet had a mean blood pressure of 157 ± 8 mmHg, as compared with 130 ± 9 mmHg for those on a regular diet (P < 0.01). SHR fed the potassium-supplemented diet had a blood pressure of 122 ± 9 mmHg (P < 0.01 versus the high-sodium diet group). The mean blood pressure of WKY rats was 78 ± 3 mmHg and did not differ among the dietary groups. The ‘potassium-induced relaxation’ response of aortic rings from SHR and WKY rats fed a potassium-supplemented diet was significantly higher (P < 0.05) than that in animals in the corresponding high-sodium dietary group. This observation in potassium-supplemented rats is interpreted as indicative of increased Na,K-ATPase activity in the vascular wall. Conclusions: A potassium-rich diet in SHR receiving a high sodium intake was associated with lower blood pressure and higher vascular Na,K-ATPase activity. A similar effect of this diet on vascular Na,K-ATPase was observed in WKY. We propose that the antihypertensive effect of a potassium-rich diet is mediated, at least in part, by stimulation of vascular Na,K-ATPase activity.

Rhabdomyolysis and Acute Renal Failure During High-Dose Haloperidol Therapy

Severe adverse reactions to neuroleptic medications are not uncommon and include the neuroleptic malignant syndrome, rhabdomyolysis, and acute renal failure. The neuroleptic malignant syndrome consists of hyperthermia, diaphoresis, tachycardia, tachypnea, abnormal blood pressure, alteration of consciousness, and extrapyramidal rigidity. Rhabdomyolysis--which might be due to hyperthermia, muscle rigidity, and/or metabolic changes in skeletal muscle function--results in acute renal failure. We report a patient with rhabdomyolysis and acute renal failure that developed after large doses of haloperidol were given, but without muscle rigidity or hyperthermia. This patients presentation illustrates that high-dose haloperidol therapy might cause rhabdomyolysis and acute renal failure without significant rigidity or hyperthermia.

Do potassium deficient diets and K+ removal by dialysis contribute to the cardiovascular morbidity and mortality of patients with end stage renal disease?

As a group, the general health of patients with end stage renal disease (ESRD) remains poor, even after more than 30 years of experience in providing treatment for them. In the United States the expected remaining life expectancy for middle aged adults starting dialysis is only 23% of the overall population; and more than 25% of patients with ESRD die during the first year of treatment (1). Cardiac and other vascular disease account for 48% of deaths. Intermittent hypokalemia associated with dialysis treatments and excessive dietary potassium restrictions could possibly contribute to the high incidence of cardiovascular disease in the ESRD population (2). Although various nutritional factors have been associated with mortality in dialysis patients, the relation between potassium balance and cardiovascular health has not been extensively investigated (3, 4). Individuals with normal renal function, however, show cardiovascular benefits from consuming a potassium-rich diet. Potassium, the major intracellular cation, has an important role in the function of mammalian cells. Epidemiological studies have shown that potassium consumption correlates inversely with the incidence of hypertension; and the use of large doses of potassium wasting diuretics to control blood pressure might increase the incidence of fatal arrhythmias (5). Accordingly, restriction of dietary potassium and acute loses during hemodialysis could contribute to the cardiovascular mortality of ESRD patients. Hemodialysis patients are prescribed low potassium diets. In persons with normal kidney function, a potassium deficient diet is associated with higher blood pressures and an increased risk for myocardial infarction, heart failure, and stroke (6-8). Data taken from the Health and Nutrition Examination Survey (HANES I) show an inverse relationship between potassium consumption and hypertension (9). The incidence of vascular complications usually attributed to hypertension, particularly cerebral vascular accidents, are reduced in populations known to have an increased potassium intake. An effect of dietary potassium on the architecture of the vascular system independent of blood pressure has been demonstrated. Clinical studies revealed that Japanese farmers consuming a higher than average amount of potassium had fewer strokes than their

Diabetic Ketoacidosis: A Practical Approach

Insulin deficiency along with significant electrolyte depletion are the hallmarks of DKA. Precision in therapeutic dosing is required for complete recovery.

Incidence and consequences of total body potassium depletion in chronic hemodialysis patients.

OBJECTIVE This study determined relationship between total body potassium (TBK) and morbidity and mortality of patients with end stage renal disease (ESRD). DESIGN, PATIENTS, SETTING: Long term observational study of 15 ESRD patients receiving chronic hemodialysis in an academically affiliated Veterans Affairs Medical Center Hospital. METHODOLOGY AND OUTCOME MEASURE: TBK by whole-body counting of 40K, dialysis potassium losses, and patient demographic characteristics were determined. Survival was evaluated retrospectively after seven years of follow-up. RESULTS Six of 15 patients (40%) had TBK depletion. All patients who were TBK depleted, expired by study end. In contrast, only 4 of 9 patients with normal K+ stores had died during the same time period (P<0.02). Median survival time of subjects with normal TBK was 100 vs 55 months for the depleted group (chi2=4.6, P<0.05). Patients with normal TBK were younger (41.9 vs 62.5 years, P<0.02) and predominantly black (78%). The ESRD group with normal TBK received more hours of hemodialysis (HD) per week (11.2 hours vs 9.7, P<0.02) and had greater K+ removal than the depleted patients (70.5 mmol/treatment vs 43.8). Urea reduction ratio was not statistically different between groups. Serum albumin, interdialytic increases in BUN and weight, and body mass index were not different between normal and TBK depleted groups. CONCLUSIONS TBK depletion occurs in a significant proportion of HD patients and is associated with increased mortality. It is prudent to customize HD and dietary prescriptions to maintain normal levels of TBK in ESRD patients.