Hypoglycemia is the usual feature of commonly occurring organic acidemias. Organic acidemias manifesting as hyperglycemia or diabetic ketoacidosis are rare and only a few cases have been reported. We report a 13-month-old boy who presented with vomiting, dehydration, coma, hyperglycemia, high anion gap metabolic acidosis and ketosis, mimicking diabetic ketoacidosis (DKA). Treatment with parenteral fluid, electrolytes, and insulin infusion resulted in an improvement in hyperglycemia, but persistence of metabolic acidosis and lack of improvement of neurologic status led us to suspect an organic acidemia. Urinary organic acid analysis revealed increased methylmalonic acid levels. In addition, hyperhomocysteinemia and homocystinuria were also noted in presence of normal vitamin B12 levels. This confirmed the diagnosis of cobalamin metabolism defect leading to combined methylmalonic aciduria and homocystinuria. There was some improvement in neurologic status and metabolic parameters after treatment with low-protein diet, vitamin B12, folic acid, and L-carnitine, but he ultimately succumbed to polymicrobial nosocomial sepsis. The entire MMACHC gene of the patient was sequenced and no mutations were identified. This is probably the first case report of cobalamin intracellular metabolism defect (CblC/CblD/CblF/CblJ or ABCD4) presenting as diabetic ketoacidosis.

Descriptions of acid-base disturbances in atypical myopathy (AM) are limited.Describe and compare traditional and quantitative acid-base abnormalities and cardiovascular shock status in horses with AM at admission.34 horses with AM, 15 healthy controls.Retrospective case-control study. Records were searched for shock variables (packed cell volume [PCV], blood urea nitrogen [BUN], heart and respiratory rate) and acid-base variables (venous blood gas analysis, electrolytes, total protein, lactate) on admission. Base excess (BE) of free water (BEfw), chloride (BEcl), total protein (BEtp), and unidentified anions (BEua), anion gap (AG), measured strong ion difference (SIDm), and concentration of total nonvolatile weak acids ([Atot]) were calculated. Acid-base classifications, using simplified strong ion model and traditional approach, and shock grades were assigned. A 2-sample Wilcoxon rank-sum test and Bonferroni correction compared variables in AM cases versus control horses. Significance was P < .05/16 for acid-base and P < .05/5 for shock variables.Tachycardia, tachypnea, and normal to increased PCV and BUN were common in AM cases. Respiratory, metabolic acid-base alterations, or both were mainly caused by respiratory alkalosis, lactic acidosis, and SIDm alkalosis, alone or in combination. Evaluated variables (except pH, potassium concentration, total protein, and related calculations) were significantly different (P < .001) between AM cases and control horses. The strong ion model provided a more accurate assessment than the traditional approach and identified mixed derangements.Acid-base derangements should be evaluated in horses with AM and this preferably with the strong ion model.

Oral rehydration solutions (ORS) are a simple and cheap method to treat diarrheal dehydration and acidosis. To maintain the energy supply of diarrheic calves, it is necessary to continue milk feeding. Suckling of milk or milk-based or hypertonic water-based ORS produces a slower rate of abomasal emptying than suckling isotonic water-based ORS. The faster abomasal passage of isotonic water-based ORS implies that efficacious electrolytes reach the gut more quickly, possibly providing a faster rate of rehydration. The aim of the study was to verify when and to what extent milk and water- and milk-based ORS increase plasma volume and affect plasma osmolality and acid-base status in healthy suckling calves. Eleven calves were fed with milk and with an ORS that was prepared in water or milk. Moreover, for one experiment, the calves remained fasting without suckling milk or ORS. During the experimental phase, the calves were deprived of water, hay, and concentrates. Blood samples were taken before and at various time points after feeding. Total plasma protein, osmolality, [Na(+)], [K(+)], [Cl(-)], and albumin were determined. In 6 of 11 experiments, blood gas analysis was also performed. The calculated change in plasma volume after feeding was assessed from the plasma protein concentration before feeding (P(t=0)) and the plasma protein concentration after feeding (P(t=x)): (P(t=0)- P(t=x)) × 100/P(t=x). Water- and milk-based ORS produced equal rates of plasma expansion in healthy calves. After milk feeding, the change in plasma volume was decelerated. Because of water influx, we did not observe a significant effect of feeding regimen on plasma osmolality. Acid-base status was little affected by feeding regimen. Feeding of milk-based ORS increased plasma strong ion difference, an alkaline response, which could potentially also reduce acidosis in calves suffering from diarrhea.

Metabolic acidosis is a common complication associated with progressive loss of kidney function. The diminishing ability of the kidneys to maintain acid-base homeostasis results in acid accumulation, leading to various complications such as impairment in nutritional status, worsened uremic bone disease and an association with increased mortality. In addition to these adverse effects which are related to acid retention, metabolic acidosis may also cause kidney damage, possibly through the stimulation of adaptive mechanisms aimed at maintaining acid-base homeostasis in the face of decreasing kidney function. Recent clinical trials have suggested that correction or prevention of metabolic acidosis by alkali administration is able to attenuate kidney damage and to slow progression of chronic kidney disease (CKD), and may hence offer an effective, safe and affordable renoprotective strategy. We review the physiology and pathophysiology of acid-base homeostasis in CKD, the mechanisms whereby metabolic acidosis may be deleterious to kidney function, and the results of clinical trials suggesting a benefit of alkali therapy, with special attention to details related to the practical implementation of the results of these trials.

Patients with a moderately reduced glomerular filtration rate (GFR) typically have no metabolic acidosis and a urine net acid excretion comparable to those with normal GFR, supporting greater per nephron acidification with moderately reduced GFR. We modeled such patients using rats with a surgical reduction of 2/3 kidney mass, yielding animals with reduced GFR without metabolic acidosis. We then tested the hypothesis that reduction of nephron mass augments distal nephron acidification in remnant nephrons mediated by increased angiotensin II activity, and that the latter is induced by underlying acid retention. Nephron mass reduction yielded lower GFR than controls (sham operation), higher acid retention (measured by microdialysis of kidney cortex), higher distal nephron acidification, and higher plasma and kidney levels of angiotensin II, but plasma total CO(2) and urine net acid excretion were not different. Angiotensin II receptor antagonism reduced distal nephron acidification to levels similar to control. Dietary alkali that lowered acid retention to that of control also reduced plasma and kidney levels of angiotensin II and reduced distal nephron acidification to control. Angiotensin II receptor antagonism with dietary alkali had no significant added effect on distal nephron acidification. Thus, nephron reduction that moderately reduced GFR with no metabolic acidosis is characterized by increased angiotensin II activity. This mediates increased distal nephron acidification and is induced by acid retention.

Acidosis and transplantation are associated with increased risk of bone disturbances. This study aimed to assess bone morphology and metabolism in acidotic patients with a renal graft, and to ameliorate bone characteristics by restoration of acid/base homeostasis with potassium citrate.This was a 12-month controlled, randomized, interventional trial that included 30 renal transplant patients with metabolic acidosis (S-[HCO(3)(-)] <24 mmol/L) undergoing treatment with either potassium citrate to maintain S-[HCO(3)(-)] >24 mmol/L, or potassium chloride (control group). Iliac crest bone biopsies and dual-energy X-ray absorptiometry were performed at baseline and after 12 months of treatment. Bone biopsies were analyzed by in vitro micro-computed tomography and histomorphometry, including tetracycline double labeling. Serum biomarkers of bone turnover were measured at baseline and study end. Twenty-three healthy participants with normal kidney function comprised the reference group.Administration of potassium citrate resulted in persisting normalization of S-[HCO(3)(-)] versus potassium chloride. At 12 months, bone surface, connectivity density, cortical thickness, and cortical porosity were better preserved with potassium citrate than with potassium chloride, respectively. Serological biomarkers and bone tetracycline labeling indicate higher bone turnover with potassium citrate versus potassium chloride. In contrast, no relevant changes in bone mineral density were detected by dual-energy X-ray absorptiometry.Treatment with potassium citrate in renal transplant patients is efficient and well tolerated for correction of metabolic acidosis and may be associated with improvement in bone quality. This study is limited by the heterogeneity of the investigated population with regard to age, sex, and transplant vintage.

To asses the prevalence of post-transplant renal tubular acidosis (RTA) and its associated risk factors.A cross-sectional study was conducted on 100 live related renal transplant recipients, with a transplant duration of more than one year and an estimated GFR > 40 ml/min/1.73m2. Patients with acute graft rejection within last 6 months, unstable graft function, acute urinary tract infection and diarrhoea were excluded. Renal Tubular Acidosis (RTA) was diagnosed on the basis of plasma bicarbonate, venous pH, urine and serum anion gap measurements.Out of 100 patients (74 male, 26 female) RTA was observed in 40 (29 male, 11 female). Patients with RTA had a lower GFR (65.87 +/- 12.35 versus 74.23 +/- 14.8 ml/min/1.73m2, P = 0.004) and higher number of previous acute rejections. Lower bicarbonate was associated with higher serum chloride (108.2 +/- 3.19 versus 105.72 +/- 3.9 mEq/L, P = 0.001) and higher potassium concentration (3.95 +/- 0.53 vs 3.61 +/- 0.46 mg/dl, P = 0.001). Higher phosphorous level (3.46 +/- 0.71 in RTA vs 3.19 +/- 0.59 mg/dl in non-RTA, P = 0.045) but lower total serum calcium concentrations were found in patients with RTA. Intake of angiotensin converting enzyme inhibitors (ACE 1) was associated with the development of RTA. Calcineurin inhibitor (CNI) therapy was not associated with an increased likelihood of RTA. While no difference was noted in sex, age, pre-transplant dialysis duration, post transplant period, body mass index and serum albumin levels.There is a high prevalence of RTA in renal transplant recipients. In most of the patients, this is subclinical and does not require treatment.

Acid-base disturbances have been usually evaluated with the traditional Henderson-Hasselbach method and Stewart's physiochemical approach by quantifying anions of tissue acids (TA). It is hypothesized that an increase in tissue acids during metabolic acidosis would cause a compensatory decrease in the plasma chloride (Cl) relative to sodium (Cl-Na ratio) in order to preserve electroneutral balance. Therefore, we aimed to investigate the use of Cl-Na ratio as a bedside tool to evaluate the identifying raised TA in neonates as an alternative to complex calculations of Stewart's physiochemical approach. This retrospective study was conducted between January 2008 and December 2009. Infants were included in the study when blood gas analysis reveals a metabolic acidosis; pH <7.25 and sHCO(3) concentration was <22 mEq/L. The Cl-Na ratio, sodium-chloride difference (Diff(NaCl)), anion gap (AG), albumin-corrected AG (AG(corr)), strong ion difference (SID), unmeasured anions (UMA), and TA were calculated at each episode of metabolic acidosis. A total of 105 metabolic acidosis episodes occurred in 59 infants during follow-up. Hypochloremic metabolic acidosis occurred in 17 (16%) of samples, and all had increased TA. The dominant component of TA was UMA rather than lactate. There was a negative correlation between the Cl-Na ratio and SID, AG(corr), UMA, and TA. Also, there was a positive correlation between Diff(NaCl) and SID, AG(corr), UMA, and TA. Base deficit and actual bicarbonate performed poorly in identifying the TA. In conclusion, our study suggested that Diff(NaCl) and Cl-Na ratio are simple and fast, and may be an alternative method to complex Stewart's physiochemical approach in identifying raised UMA and TA in critically ill neonates.

The aim of the present study was to test the hypothesis that balanced crystalloid resuscitation would be better for the kidney than unbalanced crystalloid resuscitation in a rat hemorrhagic shock model.Male Wistar rats were randomly assigned to four groups (n=6/group): (1) time control; (2) hemorrhagic shock control; (3) hemorrhagic shock followed by unbalanced crystalloid resuscitation (0.9% NaCl); and (4) hemorrhagic shock followed by acetate and gluconate-balanced crystalloid resuscitation (Plasma Lyte). We tested the solutions for their effects on renal hemodynamics and microvascular oxygenation, strong-ion difference, systemic and renal markers of inflammation and oxidative stress including glycocalyx degradation as well as their effects on renal function.The main findings of our study were that: (1) both the balanced and unbalanced crystalloid solutions successfully restored the blood pressure, but renal blood flow was only recovered by the balanced solution although this did not lead to improved renal microvascular oxygenation; (2) while unbalanced crystalloid resuscitation induced hyperchloremia and worsened metabolic acidosis in hemorrhaged rats, balanced crystalloid resuscitation prevented hyperchloremia, restored the acid-base balance, and preserved the anion gap and strong ion difference in these animals; (3) in addition balanced crystalloid resuscitation significantly improved renal oxygen consumption (increased VO(2), decreased [Formula: see text] ); and (4) however neither balanced nor unbalanced crystalloid resuscitation could normalize systemic inflammation or oxidative stress. Functional immunohistochemistry biomarkers showed improvement in L-FABP in favor of balanced solutions in comparison to the hemorrhagic group although no such benefit was seen for renal tubular injury (measured by NGAL) by giving either unbalanced or balanced solutions.Although balanced crystalloid resuscitation seems superior to balanced crystalloid resuscitation in protecting the kidney after hemorrhagic shock and is certainly better than not applying fluid resuscitation, these solutions were not able to correct systemic inflammation or oxidative stress associated with hemorrhagic shock.

This prospective clinical observational study was conducted to investigate the effects of contrast medium on acid-base balance, electrolyte concentrations, and osmolality in children. Background: For pediatric cardiac catheterization, high doses of nonionic hyperosmolar contrast medium are widely used.Forty pediatric patients (age 0-16 years) undergoing cardiac angiography with more than 3 ml·kg(-1) of nonionic hyperosmolar contrast medium (Iomeprol) were enrolled, and the total amount of the contrast agent given was documented. Before and after contrast medium administration, a blood sample was collected to analyze electrolytes, acid-base parameters, osmolality, hemoglobin, and hematocrit.After cardiac catheterization, pH, hemoglobin, hematocrit, bicarbonate, base excess, sodium, chloride, calcium, anion gap and strong ion difference decreased, whereas osmolality increased significantly (base excess -1.8 ± 1.8 vs -3.4 ± 2.3, sodium 138 ± 2.9 vs 132 ± 4.1 mm, osmolality 284 ± 5.7 vs 294 ± 7.6 mosmol·kg(-1), P < 0.01). Seventy-eight percent of the children developed hyponatremia (sodium <135 mm). No changes were seen in pCO(2) , lactate, and potassium levels.Regarding the differential diagnosis of metabolic disturbances after pediatric cardiac catheterization, low-anion gap metabolic acidosis and hyponatremia should be considered as a possible side effect of the administered contrast medium.