Serum potassium changes during hypothermia and rewarming: a case series and hypothesis on the mechanism.

Introduction: Hypokalemia is known to occur in association with therapeutically induced hypothermia and is usually managed by the administration of potassium (K+). Methods: We reviewed data from 74 patients who underwent a therapeutic hypothermia protocol at our medical institution. Results: In four patients in whom data on serum K+ and temperature were available, a strong positive correlation between serum K+ and body temperature was found. Based on the close positive relationship between serum K+ and total body temperature, we hypothesize that serum K+ decreases during hypothermia owing to decreased activity of temperature-dependent K+ exit channels that under normal conditions are sufficiently active to match cellular K+ intake via sodium/K+/adenosine triphosphatase. Upon rewarming, reactivation of these channels results in a rapid increase in serum K+ as a result of K+ exit down its concentration gradient. Conclusion: Administration of K+ during hypothermia should be done cautiously and avoided during rewarming to avoid potentially life-threatening hyperkalemia. K+ exit via temperature-dependent K+ channels provides a logical explanation for the rebound hyperkalemia. K+ exit channels may play a bigger role than previously appreciated in the regulation of serum K+ during normal and pathophysiological conditions.

Urinary Ammonium in Clinical Medicine: Direct Measurement and the Urine Anion Gap as a Surrogate Marker During Metabolic Acidosis.

Ammonium is the most important component of urinary acid excretion, normally accounting for about two-third of net acid excretion. In this article, we discuss urine ammonium not only in the evaluation of metabolic acidosis but also in other clinical conditions such as chronic kidney disease. Different methods to measure urine NH4+ that have been employed over the years are discussed. The enzymatic method used by clinical laboratories in the United States to measure plasma ammonia via the glutamate dehydrogenase can be used for urine ammonium. The urine anion gap calculation can be used as a rough marker of urine ammonium in the initial bedside evaluation of metabolic acidosis such as in distal renal tubular acidosis. Urine ammonium measurements, however, should be made more available in clinical medicine for a precise evaluation of this important component of urinary acid excretion.

Hypokalemia associated with acute colonic pseudo-obstruction in an ESRD patient.

Ogilvie's syndrome, or acute colonic pseudo-obstruction, is characterized by massive dilation of the colon without mechanical obstruction. Water and electrolytes often can be sequestered in the dilated intestinal loops resulting in profuse and watery diarrhea as well as hypokalemia. We report an anuric, end-stage renal disease (ESRD) patient undergoing peritoneal dialysis (PD) who developed acute colonic pseudo-obstruction causing a prolonged hospitalization. He also developed severe hypokalemia with a serum potassium (K+) as low as 2.4 mEq/L and required 180 - 240 mEq of potassium chloride per day for more than a month to correct it. While PD K+ losses often contribute to hypokalemia, the PD K+ loss was estimated to be only 39 mEq/day. Therefore, PD could only contribute modestly to the recalcitrant hypokalemia observed during the episode of pseudo-obstruction. It has been shown, however, that patients with colonic pseudo-obstruction have enhanced colonic K+ secretion. In addition, experimental studies in patients with chronic kidney disease (CKD) have demonstrated that colonic K+ excretion can be up to 3 times greater than in individuals with normal renal function. This increase may involve an upregulation of the large conductance K+ channel (maxi-K), also known as the BK channel, in the apical border of the colonocytes. We suggest that ESRD may have placed our patient at a greater risk of developing hypokalemia as his colon may have already adapted to secrete more K+. Clinicians should be aware of this extrarenal K+ wasting etiology in patients with colonic pseudo-obstruction, particularly in those with CKD where such a severe K+ deficit is not anticipated and, therefore, may inhibit more rigorous K+ replacement.

Physician Prevention of Acute Kidney Injury.

BACKGROUND: The frequency of acute kidney injury has become substantially greater over the recent past. Acute kidney injury, moreover, is associated with increased mortality and morbidity over both the short and long term. Despite these facts, its therapy has not changed significantly for many decades. Currently, therefore, prevention is the only action that can reduce the frequency and consequences of acute kidney injury. METHODS: Charts of 492 patients were reviewed retrospectively for the presence of acute kidney injury based on creatinine elevation. One hundred seventy patients were found to have acute kidney injury defined as a sustained elevation of serum creatinine ≥ 0.3 mg/dL for 48 hours or more. An agent or event was determined to be responsible for renal injury if there was the defined increase in serum creatinine within 48 hours of exposure. Charts were reviewed to determine if the renal injury was preventable. RESULTS: Fifty-one cases were considered to be preventable. Of these, 16 had not received saline prophylaxis for intravenous contrast when appropriate, 15 were not treated appropriately for hemodynamic instability or for hypertension, 9 had inappropriate use of medications, and 11 received multiple nephrotoxic agents. CONCLUSIONS: In a retrospective analysis of 170 hospitalized patients who developed acute kidney injury during admission, 30% of episodes could have been avoided if physicians had taken appropriate preventive actions.

Gastrointestinal and renal excretion of potassium in African-Americans and White Americans.

OBJECTIVE: Several studies have confirmed the remarkable observation that cumulative urinary potassium (K(+)) excretion is less in African-Americans than White Americans even when identical amounts of potassium are provided in the diet. This study was designed to examine whether this decrease in urinary potassium could be compensatory to an increase in gastrointestinal excretion of potassium in African-Americans. METHODS: Twenty-three young, healthy, normotensive participants of both sexes and races were placed on a fixed diet of 100 mEq per day of K(+) and 180 mEq per day of sodium (Na(+)) for 9 days. All urine and stool were collected daily and analyzed for electrolytes. Blood was obtained for determination of electrolytes, blood urea nitrogen (BUN), creatinine, glucose, insulin, renin, and aldosterone at the beginning and at the end of the study period. RESULTS: Cumulative urinary excretion of K(+) was significantly less in African-Americans (609 ± 31 mEq) compared with White Americans (713 ± 22 mEq, P = 0.015). There was no significant racial difference, however, in the cumulative gastrointestinal excretion of K (105 ± 11 versus 95 ± 9 mEq, P = 0.28) in African-Americans versus White Americans, respectively. CONCLUSION: The racial difference in urinary K(+) handling manifested by decreased excretion of K(+) in African-Americans cannot be attributed to an increase in net gastrointestinal excretion of this cation.

Potential benefits of alkali therapy to prevent GFR loss: time for a palatable 'solution' for the management of CKD.

There is increasing evidence that alkali therapy can retard progression of chronic kidney disease (CKD). We summarize recent studies and discuss a mechanism whereby alkali therapy may neutralize acid production associated with typical Western diets, which generate acid. We emphasize the rationale for using alkali therapy early in the course of CKD, even in the absence of overt metabolic acidosis, and we urge the pharmaceutical industry to develop palatable alkali-containing solutions.

Resolution of SLE-related soft-tissue calcification following haematopoietic stem cell transplantation.

BACKGROUND: Calciphylaxis and calcinosis can both cause severe morbidity and mortality in patients with systemic lupus erythematosus (SLE). Haematopoietic stem cell transplantation (HSCT) has been successfully used to treat patients with refractory SLE. It was hypothesized that in calciphylaxis and calcinosis, ongoing inflammatory activity contributes to the calcium deposition in the media of small arteries, as well as perivascular and periarticular tissues. We report three patients whose soft-tissue calcification syndromes dramatically resolved after undergoing HSCT. METHODS: Three patients referred for refractory SLE underwent HSCT at a tertiary care medical center. SLE serologies and clinical features before and after HSCT were recorded. RESULTS: Despite receiving >6 months of intravenous cyclophosphamide (CYC), three SLE patients showed signs of persistent lupus activity, including severe soft-tissue calcification. The first patient was on haemodialysis and developed severe calciphylaxis with large ulcers and tissue necrosis. The second patient had calcinosis, with palpable crystals extruding from ulcers. The third patient had calcinosis characterized by subcutaneous nodules and plaques. Because prior conventional therapies had failed, the three were treated with high-dose CYC, anti-thymocyte globulin and HSCT. They have been followed post-HSCT for 26-38 months, with excellent clinical responses, including sustained resolution of skin abnormalities. CONCLUSIONS: The successful treatment of advanced calcium deposition by aggressive immune ablation underscores the contribution of SLE-mediated inflammation to soft-tissue calcification syndromes.

Racial differences in potassium disposal.

BACKGROUND: African Americans appear relatively potassium (K(+))-deficient compared with Caucasian Americans whether on unregulated diets or on diets controlled for K(+) content. METHODS: To determine whether extrarenal K(+) disposal was affected by race, KCl (0.5 mEq/kg in 0.9% saline) was infused over 48 minutes to 12 African American and 12 Caucasian American normotensive, healthy subjects. Identical infusions were administered before and after 10 days of fixed electrolyte intake. In addition to serum K(+), glucose, insulin, renin, and aldosterone were measured in blood, and K(+) and sodium (Na(+)) in urine voided spontaneously during the infusions. Data were analyzed using a two-factor analysis of variance (ANOVA) with repeated measures. RESULTS: Basal serum K(+) did not differ between races (African American 3.97 +/- 0.06 mEq/L and Caucasian American 3.98 +/- 0.05, P= NS). The rise in serum K(+) during the infusion and the area under the curve of serum K(+) over the 3.5 hours of observation were both greater in African American (African American +0.82 +/- 0.07 mEq/L and Caucasian American +0.61 +/- 0.06, P= 0.001; and African American 6.9 +/- 0.5 units and Caucasian American 5.1 +/- 0.6, P= 0.0012). The 10-day period of controlled intake did not abolish these differences. Aldosterone at baseline was lower and insulin was higher in African Americans at the end of the infusion. Urinary K(+), plasma glucose, and renin levels did not differ between African Americans and Caucasian Americans. CONCLUSION: Disposal of an intravenous (iv) K(+) load is decreased in African Americans compared with Caucasian Americans, which may reflect decreased Na(+),K(+)-ATPase activity in African Americans in vivo.

Hematopoietic stem cell transplantation for severe and refractory lupus. Analysis after five years and fifteen patients.

OBJECTIVE: To determine the safety and long-term efficacy of immune ablation and autologous hematopoietic stem cell transplantation (HSCT) in severe systemic lupus erythematosus (SLE). METHODS: Fifteen patients with persistently active SLE after intravenous (IV) cyclophosphamide (CYC) therapy underwent HSCT. Stem cells were mobilized with CYC (2.0 gm/m(2)) and granulocyte colony-stimulating factor (5 microg/kg/day). Lymphocytes were depleted from the graft by selection of CD34-positive cells. The conditioning regimen used was CYC (200 mg/kg), antithymocyte globulin (90 mg/kg), and methylprednisolone (3 mg/kg). Outcome was evaluated by the SLE Disease Activity Index (SLEDAI), serum complement levels, serologic features, function of diseased organs, and immunosuppressive medication requirements. RESULTS: Fifteen patients with persistent, severe SLE, 7 of whom were critically ill, were treated. No deaths occurred following treatment. The median followup after HSCT has been 36 months (range 12-66 months). All patients demonstrated a gradual, but marked, improvement. The SLEDAI score has declined to 1 year after HSCT, 10 have discontinued immunosuppressive medications, and the prednisone dosage has been tapered to 15 mg/day in 1. Only 2 patients have demonstrated clinical evidence of recurrence of active lupus. One of these patients currently requires no immunosuppressive medication and has a normal performance status. The other patient is currently receiving IV CYC. CONCLUSION: In patients experiencing the persistence of organ-threatening lupus following standard, aggressive therapy, HSCT may be performed safely, with marked improvement and sustained withdrawal of all immunosuppressive medication for most patients. A phase III randomized trial is warranted to determine the relative efficacy and durability of remission of HSCT compared with standard therapies.