Search

Rationale & Objective: Recent studies suggest that metabolic acidosis is associated with mortality and graft failure in kidney transplant recipients. However, it is unknown whether serum bicarbonate (measured as total carbon dioxide [tCO 2 ] in serum) levels predict cardiovascular events (CVEs) following kidney transplantation., Study Design: Observational cohort study., Settings & Participants: Single-center study of 2,128 kidney transplant recipients free of CVEs during the first 13.5 months following transplantation., Predictor: tCO 2 level at 1 year posttransplantation., Outcomes: Ischemic, arrhythmic, and heart failure CVEs and death from any cause., Analytical Approach: Independent associations were assessed using multivariable proportional hazards regression models. Restricted cubic spline Poisson models were used to explore nonlinear associations. Linear spline proportional hazards models were used to assess associations at different tCO 2 levels., Results: The prevalence of metabolic acidosis defined as tCO 2 level < 24 mEq/L was 38.8% (n=826). There were 384 recipients with a CVE and 610 deaths during a median follow-up of 4.0 years. CVEs included 241 ischemic, 137 arrhythmic, and 150 heart failure events. tCO 2  level < 20 mEq/L was associated with increased risk for CVEs (adjusted HR [aHR], 2.00; 95% CI, 1.29-3.10) compared to the reference category of tCO 2 level of 24.0 to 25.9 mEq/L. This association was primarily due to ischemic CVEs (aHR, 2.28; 95% CI, 1.34-3.90). For every 1 mEq/L lower tCO 2 level for those with tCO 2 < 24 mEq/L, risks for all CVEs and ischemic events were 17% and 15% higher, respectively (aHR for all CVEs of 0.83 [95% CI, 0.74-0.94] and aHR for ischemic CVEs of 0.85 [95% CI, 0.74-0.99]). Notably, tCO 2 level < 20 mEq/L, compared to tCO 2 level of 24.0 to 25.9 mEq/L, was independently associated with all-cause mortality (aHR, 1.43; 95% CI, 1.02-2.02). For every 1-mEq/L lower tCO 2 level for those with tCO 2 < 24 mEq/L, there was 17% higher risk for death (aHR, 0.83; 95% CI, 0.75-0.92)., Limitations: Single-center observational study., Conclusions: Metabolic acidosis is an independent risk factor for ischemic CVEs after kidney transplantation. It is unknown whether correction of acidosis improves outcomes in these patients., (Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

High anion gap (AG) metabolic acidosis, a common laboratory abnormality encountered in clinical practice, frequently is due to accumulation of organic acids such as lactic acid, keto acids, alcohol metabolites, and reduced kidney function. The cause of high AG metabolic acidosis often is established easily using historical and simple laboratory data. Despite this, several challenges in the diagnosis and management of high AG metabolic acidosis remain, including quantifying the increase in AG, understanding the relationship between changes in AG and serum bicarbonate level, and identifying the cause of high AG metabolic acidosis when common causes are ruled out. The present case was selected to highlight the importance of the correction of AG for serum albumin level, the use of actual baseline AG rather than mean normal AG, the relationship between changes in serum bicarbonate level and AG, and a systematic diagnostic approach to uncommon causes of high AG metabolic acidosis, such as 5-oxoproline acidosis (pyroglutamic acidosis)., (Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Metabolic acidosis is a common complication of chronic kidney disease and is believed to contribute to a number of sequelae, including bone disease, altered protein metabolism, skeletal muscle wasting, and progressive glomerular filtration rate loss. Small trials in animal models and humans suggest a role for alkali therapy to lessen these complications. Recent studies support this notion, although more definitive evidence is needed on the long-term benefits of alkali therapy and the optimal serum bicarbonate level. The role of dietary modification also should be given greater consideration. In addition, potential adverse effects of alkali treatment must be taken into consideration, including sodium retention and the theoretical concern of promoting vascular calcification. This teaching case summarizes the rationale for and benefits and complications of base therapy in patients with chronic kidney disease., (Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Topiramate is a novel neuromodulatory agent commonly prescribed for the treatment of seizure disorders and for migraine headache prophylaxis. Calcium phosphate kidney stones have been observed with topiramate treatment, but a comprehensive elucidation of stone-risk profile was not reported previously. This study explores the relationship between topiramate treatment and propensity for kidney stone formation., Methods: Thirty-two topiramate-treated subjects and 50 healthy volunteers participated in a cross-sectional study in which serum chemistry test and 24-hour urine collection results were evaluated for stone risk. Furthermore, a short-term longitudinal study was conducted in 7 patients to assess stone risk before and 3 months after topiramate treatment., Results: Serum bicarbonate levels were lower with topiramate treatment. Urinary pH, urinary bicarbonate excretion, and fractional excretion of bicarbonate increased, whereas urinary citrate excretion was significantly lower (737 +/- 329 versus 278 +/- 226 mg/d; P < 0.001). Net acid excretion did not change. The relative saturation ratio for brushite increased with topiramate treatment (3.14 +/- 1.69 versus 1.27 +/- 1.26; P < 0.001) because of urinary alkalinization and decreased urinary citrate levels. Urinary saturation of undissociated uric acid decreased (41 +/- 52 versus 76 +/- 60 mg/d; P < 0.001)., Conclusion: Treatment with topiramate causes systemic metabolic acidosis, markedly lower urinary citrate excretion, and increased urinary pH. These changes increase the propensity to form calcium phosphate stones.

Severe acidemia (blood pH < 7.1 to 7.2) suppresses myocardial contractility, predisposes to cardiac arrhythmias, causes venoconstriction, and can decrease total peripheral vascular resistance and blood pressure, reduce hepatic blood flow, and impair oxygen delivery. These alterations in organ function can contribute to increased morbidity and mortality. Although it seemed logical to administer sodium bicarbonate to attenuate acidemia and therefore lessen the impact on cardiac function, the routine use of bicarbonate in the treatment of the most common causes of severe acidemia, diabetic ketoacidosis, lactic acidosis, and cardiac arrest, has been an issue of great controversy. Studies of animals and patients with these disorders have reported conflicting data on the benefits of bicarbonate, showing both beneficial and detrimental effects. Alternative alkalinizing agents, tris-hydroxymethyl aminomethane and Carbicarb, have shown some promise in studies of animals and humans, and reevaluation of these buffers in the treatment of severe acidemic states seems warranted. The potential value of base therapy in the treatment of severe acidemia remains an important issue, and further studies are required to determine which patients should be administered base therapy and what base should be used.

Both hyponatremia and its rapid correction can cause neurological disorders. Slowly correcting hyponatremia (especially when asymptomatic) at a rate of 0.5 mEq/L/h is recommended; however, little information exists about treatment of hyponatremia in patients requiring dialysis. We report a case of successfully treated hyponatremia using continuous venovenous hemodialysis with a specially prepared dialysate containing a lower than usual sodium concentration.

Chronic metabolic acidosis is a process whereby an excess nonvolatile acid load is chronically placed on the body due to excess acid generation or diminished acid removal by normal homeostatic mechanisms. Two common, often-overlooked clinical conditions associated with chronic metabolic acidosis are aging and excessive meat ingestion. Because the body's homeostatic response to these pathologic processes is very efficient, the serum HCO3- and blood pH are frequently maintained within the "normal" range. Nevertheless, these homeostatic responses engender pathologic consequences, such as nephrolithiasis, bone demineralization, muscle protein breakdown, and renal growth. Based on this, the concept of eubicarbonatemic metabolic acidosis is introduced. Even in patients with a normal serum HCO3- and blood pH, it is important to treat the acid load and prevent pathologic homeostatic responses. These homeostatic responses, as well as the mechanisms responsible for their initiation, are reviewed.

There are multiple causes of protein-energy malnutrition in maintenance dialysis patients. The requirements of protein in dialysis patients are higher than in healthy individuals, and the intake of protein and energy in relation to the requirements is frequently low. Anorexia may be caused by uremia and underdialysis. There is experimental evidence that dialyzable uremic toxins accumulate in renal failure and suppress the appetite. In addition there are several psychosocial and comorbidity factors that may hamper adequate nutrition. There are also several factors in dialysis patients that may enhance protein catabolism and increase protein requirements, such as low energy intake, metabolic acidosis, dialytic loss of glucose, protein and amino acids and other catabolic effects of the dialytic procedures, as well as effects of infections and other comorbidity factors. The relative importance of the various factors that cause anorexia and stimulate protein catabolism is still not well understood.

In both humans and animals, mineral acids predictably result in hyperkalemia, whereas plasma K+ remains normal or may even decrease during organic acidosis. The purpose of these studies was to define the mechanism for these effects in the opossum kidney cell, an established epithelial cell line derived from the renal cortex of the opossum. This cell was chosen because the acid/base transport pathways in this cell type are well defined and because it is one of the few cells known to express K/H antiport, the transport pathway that has been proposed to mediate the hyperkalemia of acidosis. Cell K+ at pH 7.4 averaged 988 +/- 48 nmol/mg protein. Relative to this value (100%), cell K+ increased when buffer pH was increased to pH 8.4 with NaOH (108% +/- 3%) and decreased when buffer pH was acidified with HCl to pH 6.4 (93% +/- 4%), producing a highly significant correlation of cell K+ with buffer pH: cell K+ (% of baseline at pH 7.4) = 6.9 (cell pH) + 49 (r = 0.5, P < 0.004). In contrast, acidification of the buffer to pH 6.4 with either butyric or lactic acid increased cell K+ (115% +/- 4% and 110% +/- 2%, respectively, both P < 0.05 v 7.4 or HCl value). Cell pH acidified in response to HCl at a rate of 0.0053 +/- 0.0007 pH U/s, a significantly slower rate than in response to lactic acid or butyric acid (0.0071 +/- 0.0007 and 0.0091 +/- 0.0007 pH U/s, respectively). Unidirectional ouabain-sensitive 42K+ influx was significantly inhibited by HCl acidosis and less so by the organic acids.(ABSTRACT TRUNCATED AT 250 WORDS)

The charts of 70 successive patients presenting for dialysis therapy for end-stage renal disease (ESRD) were evaluated for their serum electrolyte values. The "classical" pattern of low total CO2 (tCO2), elevated anion gap ("delta"), and normal chloride was found in a minority of patients (14 of 70, or 20%). Hyperchloremia was noted in 46%; in 21 patients (30%), this was associated with a normal delta and in 11 (16%), hyperchloremia was accompanied by an elevated delta. Fourteen patients (20%), most with diabetic nephropathy, had normal serum electrolytes. Patients with chronic glomerulonephritis had a hyperchloremic pattern as often as not, and two of four patients with interstitial nephritis demonstrated hyperchloremia without an elevated delta. We conclude that the previously held thesis that hyperchloremia is a rare or absent finding by the time renal failure progresses to ESRD is no longer tenable. Furthermore, a significant minority of ESRD patients may require the initiation of dialysis at a time when their serum electrolytes are still normal.

Methanol poisoning in humans is characterized by a latent period with subsequent development of anion gap metabolic acidosis and blindness. We describe a patient with potentially lethal methanol ingestion as evidenced by an admission serum methanol level of 403 mg/dL and sustained serum methanol levels greater than 50 mg/dL for more than 18 hours after ingestion, despite hemodialysis therapy. That anion gap metabolic acidosis or visual impairment did not develop in this patient was attributed to documented prior ethanol ingestion (admission serum ethanol level of 158 mg/dL) and continued ethanol administration during hospitalization (sustained serum ethanol levels greater than 100 mg/dL). This case demonstrates the ability of ethanol to inhibit the metabolism of methanol to formic acid in humans. This inhibition was achieved without induction of lactic acidosis. Thus this case documents the efficacy of ethanol therapy in patients with methanol poisoning.