Plasma Bicarbonate Research Articles

8226 A Diagnostic Challenge: Factitious Hypobicarbonatemia in Severe Hypertriglyceridemia

Abstract Disclosure: U. Rafat: None. S. Azmat: None. M. Siddiqui: None. R. Alshantti: None. D. Kircheva: None. V. Trendafilova: None. Background: Serum CO2 levels measured by a chemistry analyzer usually correlate with calculated bicarbonate levels on an ABG. There are some instances however, when this is not the case. Severe hypertriglyceridemia can cause serum bicarbonate levels to appear falsely low on metabolic panel. Clinical Case: A 48-year-old man was referred to Endocrinology Clinic for evaluation of hypogonadism and severe hypertriglyceridemia. Routine labs revealed a plasma CO2 of 11 mmol/L (20-31). Na was 133 mmol/L (136-145), K was 4.4 mmol/L (3.5-4.7), Chloride was 101 mmol/L (98-109) and anion gap was 25 (8-20) measured using a Siemens Vista enzymatic chemistry analyzer. His triglycerides were > 1100 mg/dL (0-150), above upper detection limits of the analyzer. The patient reported fatigue and mild abdominal pain. He was admitted to the hospital for further evaluation. His lipase was 41 U/L (12-73), lactic acid 1.2 mmol/L (0.50-2.20). ABG showed pH of 7.41, HCO3 of 26.6 mmol/L (22-29), and anion gap of 7 (10-20). The patient was well-appearing with normal vital signs and normal physical exam. He was made NPO and started on pravastatin, fenofibrate and fish oil. Once his triglycerides were < 1000 mg/dL, he was started on a very low-fat, low-carbohydrate diet. The CO2 level on BMP normalized on day 3 of hospitalization, when triglycerides measured 1010 mg/dL. No other treatment was given for the low CO2 levels. It does not appear that other lab indices were significantly affected by the hypertriglyceridemia. Review of Literature: A BMP measures serum total carbon dioxide using a chemistry analyzer using either an enzymatic/spectro-photometric method, or an electrode-based method; an ABG sample calculates plasma bicarbonate with the Henderson-Hasselbach equation, using the pH and partial pressure of pCO2 in the sample. Enzymatic analyzers measure CO2 using spectrophotometry and decrease in light absorbance is proportional to the sample’s CO2 levels. It is postulated that severely high triglycerides can interfere with this reaction and cause spuriously low CO2 levels, a phenomenon called pseudohypobicarbonatemia. One proposed mechanism for interference with the enzymatic assay method is turbidity causing a falsely low measured CO2 level. Verghese et al found that the severity of the CO2 measurement error positively correlates with the severity of triglyceride elevation. Conclusion: Awareness of the phenomenon of hypertriglyceridemia-induced pseudohypobicarbonatemia can prevent misdiagnosis or delays in diagnosis, as well as unwarranted testing and treatment. Presentation: 6/3/2024

The physiological significance of plasma-accessible carbonic anhydrase in the respiratory systems of fishes.

Carbonic anhydrase (CA) activity is ubiquitously found in all vertebrate species, tissues and cellular compartments. Most species have plasma-accessible CA (paCA) isoforms at the respiratory surfaces, where the enzyme catalyzes the conversion of plasma bicarbonate to carbon dioxide (CO2) that can be excreted by diffusion. A notable exception are the teleost fishes that appear to lack paCA at their gills. The present review: (i) recapitulates the significance of CA activity and distribution in vertebrates; (ii) summarizes the current evidence for the presence or absence of paCA at the gills of fishes, from the basal cyclostomes to the derived teleosts and extremophiles such as the Antarctic icefishes; (iii) explores the contribution of paCA to organismal CO2 excretion in fishes; and (iv) the functional significance of its absence at the gills, for the specialized system of O2 transport in most teleosts; (v) outlines the multiplicity and isoform distribution of membrane-associated CAs in fishes and methodologies to determine their plasma-accessible orientation; and (vi) sketches a tentative time line for the evolutionary dynamics of branchial paCA distribution in the major groups of fishes. Finally, this review highlights current gaps in the knowledge on branchial paCA function and provides recommendations for future work.

Diabetic ketoacidosis resolution: From the traditional way to guideline-based management in the MICU at University Medical Center, Lubbock, Texas

Diabetes is a chronic, metabolic disease characterized by hyperglycemia which eventually can cause serious organ damage. The prevalence of diabetes has steadily increased over the past few decades, and approximately 1.4 million Americans are diagnosed with diabetes every year. Diabetes was the seventh leading cause of death in the United States in 2019. Diabetic ketoacidosis (DKA) is a serious complication of diabetes that can be life-threatening. It occurs more frequently in the patients with type 1 diabetes but can also develop in people with type 2 diabetes. It was determined that the average cost per DKA episode was $6,444, and that the annual cost of medical treatment in a diabetic patient with a prior episode of DKA was 2.67 times higher than a diabetic patient with no history of DKA. The criteria for DKA resolution at University Medical Center (UMC) in Lubbock, Texas, are different from current American Diabetes Association (ADA) guidelines. At UMC, a plasma bicarbonate ≥18 mEq/L, a venous pH > 7.3, and anion gap ≤12 mEq/L must be recorded twice (4 hours apart) before bridging to subcutaneous long-acting insulin administration. This time requirement could contribute to a longer time for DKA resolution and longer intensive care unit and hospital stays.Keywords: Diabetic ketoacidosis, DKA resolution

Primary Distal Renal Tubular Acidosis: Toward an Optimal Correction of Metabolic Acidosis.

The term classic, type 1 renal tubular acidosis or primary distal renal tubular acidosis is used to designate patients with impaired ability to excrete acid normally in the urine as a result of tubular transport defects involving type A intercalated cells in the collecting duct. The clinical phenotype is largely characterized by the complications of chronic metabolic acidosis (MA): stunted growth, bone abnormalities, and nephrocalcinosis and nephrolithiasis that develop as the consequence of hypercalciuria and hypocitraturia. All these manifestations are preventable with early and sustained correction of MA with alkali therapy. The optimal target for plasma bicarbonate should be as close as possible to the range considered normal by current standards (between 23 and 28 mEq/L.). Most of the benefits of alkali therapy are tangible early in the course of the disease in childhood, but life-long treatment is required to prevent the vast array of complications attributable to chronic MA.

Serial paired arterial and jugular venous point-of-care values in dogs undergoing manual basic life support.

To evaluate differences in point-of-care (POC) variables obtained from arterial and jugular venous blood in dogs undergoing manual basic life support (BLS) and report changes over time. Experimental study. Small animal research facility. Twenty-four purpose-bred research dogs. Dogs were anesthetized, and arterial catheters were placed before euthanasia. One minute after cardiopulmonary arrest, BLS consisting of manual chest compressions and ventilation delivered via endotracheal intubation, face mask, mouth-to-nose, or no ventilation was initiated. Paired arterial and jugular venous blood samples were obtained for POC testing before euthanasia (T0), at 3minutes (T3), and at 6minutes (T6) into BLS. The association of POC variables with arterial or venous sample type while controlling for type of ventilation and sampling timepoint was determined using a generalized linear mixed model. Variables obtained from arterial and venous blood samples were compared over time using repeated measures ANOVA or Friedman test. Pao2, anion gap, potassium, chloride, glucose concentration, and PCV were significantly higher in arterial blood samples compared with venous samples (P<0.03). By T6, arterial glucose concentration, arterial and venous base excess, venous pH, and plasma lactate, potassium, creatinine, bicarbonate, and sodium concentrations were significantly increased, and arterial and venous Po2, ionized calcium concentration, PCV, and total plasma protein concentration were significantly decreased from T0 (P<0.05). Although statistically significant, arteriovenous differences and changes in POC blood variables during BLS were small and not clinically relevant over time. Given the challenges of arterial blood sampling, it may be reasonable to pursue venous blood sampling during CPR. Further studies in dogs undergoing BLS and advanced life support are needed to better understand the potential clinical role of POC testing during CPR.

#2725 Chronic kidney disease is a risk factor for hyperchloremic metabolic acidosis after plasma exchange

Abstract Background and Aims Observational studies have demonstrated that metabolic acidosis due to hyperchloremia is an often encountered metabolic disorder following plasma exchange (PE) with an albumin-saline solution. Because of the reduced capacity for acid and chloride excretion, we hypothesized that patients with chronic kidney disease have the highest risk for hyperchloremic metabolic acidosis, in particular when multiple PE sessions are performed in a limited period. Method We prospectively collected data from all patients who received PE at Amsterdam UMC, between February 2023, and January 2024. We collected data on demographics, exchanged plasma volume, replacement fluids, and collected blood for analysis of sodium, chloride and bicarbonate before and after plasma exchange. We selected patients who received ≥5 plasma exchanges in an intensive cycle (≥4.2 sessions/week). We excluded patients who received Omniplasma, intravenous sodium bicarbonate or dialysis during the PE period. We assessed the effect of PE and kidney function on plasma bicarbonate and chloride concentration throughout the PE period with repeated measures mixed ANOVA, corrected for baseline plasma bicarbonate concentration, volume of exchanged plasma and PE intensity. Results Data from 26 patients, corresponding to 130 plasma exchanges, were included in the analysis. The mean age was 56 ± 14 years and 46% was female. Mean eGFR was 45 ± 14 ml/min/1.73 m2. Patients with an eGFR ≤59 ml/min/1.73 m2 (n = 17) had a significantly lower baseline plasma bicarbonate concentration (19.0 ± 2.8 versus 24.0 ± 1.9 mmol/L; p &amp;lt; 0.001) and used oral bicarbonate supplements (29% versus 0%; p = 0.02) more often than patients with an eGFR ≥60 ml/min/1.73 m2 (n = 9). Despite the lower baseline plasma bicarbonate and more frequent use of oral bicarbonate supplements, the plasma bicarbonate levels decreased the most in subjects with an eGFR ≤59 ml/min/1.73 m2 (mean difference −4.2; 95% CI −7.1 to −1.3; p = 0.006; Fig. 1A) during a cycle of 5 PE sessions. Baseline plasma chloride concentration was similar in both groups (103 ± 7 vs 103 ± 4 mmol/L) and increased the most in patients with an eGFR ≤59 ml/min/1.73 m2 (mean difference −1.4; 95% CI −2.2 to 5.0; p = 0.426; Fig. 1B). Conclusion Repeated plasma exchange with albumin-saline as a replacement fluid is associated with a significant decrease in plasma bicarbonate concentration in patients with impaired kidney function. Future studies should determine whether this hyperchloremic metabolic acidosis has impact on the patients’ symptoms or long-term outcome.

#1001 Model-based profiling of bicarbonate supplementation during a hemodialysis cycle

Abstract Background and Aims Bicarbonate is delivered to hemodialysis (HD) patients via diffusion following a concentration gradient across the dialyzer membrane. However, the concentration of bicarbonate in the dialysis fluid ([HCO3]d) is usually not individualized for the specific patient's conditions, as no clear guidelines are provided, which leads to suboptimal pre- and post-dialytic plasma bicarbonate concentrations ([HCO3]p) during each treatment cycle. We used a mathematical model to predict the outcomes of a week-long HD cycle with time-dependent [HCO3]d in 24 patients, tuning the [HCO3]d prescription to keep the simulated pre-dialytic [HCO3]p in the range 22-24 mEq/L throughout the week. The [HCO3]d profiles thus developed were then tested, and [HCO3]p during HD compared with those using a constant [HCO3]d in the same patients. Method The compartmental model (Pietribiasi et al PLOS ONE 2023) describes the transport of total CO2, O2, and total buffer base in arterial and mixed-venous blood (plasma and red blood cells), tissues (interstitial and intracellular fluid), and lung capillaries and alveoli, calculating derivate quantities such as bicarbonate concentration, pH, partial pressure of CO2. The patients underwent one week of standard HD with constant [HCO3}d (Week 1, [HCO3]d = 33.6 ± 1.8 mEq/L) consisting of 3 sessions (HD1, HD2, HD3) to estimate the baseline model parameters and, successively, an intervention week (Week 2), during which the model-derived [HCO3]d profiles were implemented. Each profile consisted of a single step increase after 2 hours of HD, the two values of [HCO3]d chosen for each session and patient according to the model's simulations. Blood samples for the blood gas analyzer were taken before and after each session, and each hour during HD2. Results [HCO3]p profiles in Week 2 showed a more linear increase compared those of Week 1 (Fig. 1). The efficacy of the response to the model-based treatment was different depending on whether the intervention aimed to decrease or increase pre-dialytic [HCO3]p during Week 2 (Fig. 2). In the group of patients attempting to decrease pre-dialytic [HCO3]p (Decrease group, n = 10, average [HCO3]d = 31.3 ± 1.5 mEq/L), a significant fraction of sessions achieved the target (60% across the whole week). In contrast, among the patients attempting to increase pre-dialytic [HCO3]p (Increase group, n = 6, average [HCO3]d = 35.3 ± 2.0 mEq/L), the model-based prescription was effective only in increasing post-dialytic concentration (20% of sessions achieved pre-dialytic targets). By comparison, during Week 1 only 30% and 10% of sessions were in the target range for Decrease and Increase groups, respectively. Patients for which we didn't want to alter pre-dialytic [HCO3]p were termed the Neutral group (n = 8, average [HCO3]d = 33.3 ± 2.1 mEq/L, 40% and 50% of sessions in the target [HCO3]p range in Week 1 and 2, respectively). Conclusion The model-based profiling intervention was only partially successful in achieving the targets for pre-dialytic [HCO3]p in Week 2. The reasons why pre-dialytic [HCO3]p were resistant to the model-based [HCO3]d in the Increase group are not clear, but it could be that the increase in the average [HCO3]d was too small (6-7% higher than Week 1). However, in the Decrease group a similar difference was sufficient to produce a more marked decrease in pre-dialytic [HCO3]p. The profiling of [HCO3]d was shown to be effective in reducing the time the patients spend at higher [HCO3]p. Nevertheless, our study demonstrated that, upon refinement, mathematical modeling can be used to develop individualized treatments to pilot the markers of the acid-base response to HD towards desired values.

Assessment of Blood Gas Pattern amongst Artisanal Refinery Operators in Rivers State, Nigeria

Some identified setbacks of the legitimate and illegitimate explorations/exploitations of crude oil and its derivatives in the Niger Delta are degraded environment, weak economy, and deteriorating health of the populace. Therefore, the current study evaluated the effect of artisanal refinery operation on respiratory blood gases and renal functions of its workers in Rivers State. As a cross-sectional investigation with sparse population, the multistage sampling technique (including purposive and snowball tools) was adopted to recruit 203 (including 120 operators of artisanal refinery―OAR-actively exposed and 83 non-OAR- actively exposed) willing and apparently healthy male and female adult subjects. Following receipt of ethical approval and consent, five milliliter of blood was taken from each subject from their antecubital vein after sterilizing the portion of the cubital fossa. The sample was then put into plain sample bottle and centrifuged to recover serum. Thereafter, the automated blood gas analyzer was used to measure the arterial blood gases of the subjects. The result showed marked (P&lt;0.05) reductions in the partial pressure of oxygen (PO2) and oxygen saturation (SO2) levels in artisanal refinery operators (actively exposed) when compared to that of the passively-exposed subjects. Again, there were marked (P&lt;0.05) elevations in the plasma pH and bicarbonate ions (HCO-3) levels in the actively exposed subjects compared to their passively-exposed counterparts. In conclusion, there could be adverse impact on respiratory blood gases and incidences of metabolic alkalosis over chronic exposures to the OAR activities.

Clinical, genetic profile and therapy evaluation of 11 Chinese pediatric patients with Fanconi-Bickel syndrome

BackgroundFanconi-Bickel syndrome (FBS) is a rare autosomal recessive disorder characterized by impaired glucose and galactose utilization as well as proximal renal tubular dysfunction.MethodsClinical, biochemical, genetic, treatment, and follow-up data for 11 pediatric patients with FBS were retrospectively analysed.ResultsHepatomegaly (10/11), short stature (10/11) and hypophosphataemic rickets (7/11) were the most common initial symptoms. At diagnosis, all patients had decreased fasting blood glucose (FBG), plasma bicarbonate (HCO3−) and serum phosphorus, as well as elevated liver transaminases, alkaline phosphatase (AKP) and proximal renal tubular dysfunction. Two infant patients were misdiagnosed with transient neonatal diabetes mellitus. After therapy with uncooked cornstarch and conventional rickets treatment, remission of hepatomegaly was observed in all patients, with significant improvements in pre-prandial blood glucose, liver transaminases, triglyceride, plasma HCO3− and AKP (p < 0.05). At the last follow-up, 5/7 patients with elevated AKP had nephrocalcinosis. The mean height standard deviation score (Ht SDS) of eight patients with regular treatment increased from − 4.1 to -3.5 (p = 0.02). Recombinant human growth hormone (rhGH) was administered to 4/9 patients, but their Ht SDS did not improve significantly (p = 0.13). Fourteen variants of the SLC2A2 gene were identified, with six being novel, among which one was recurrent: c.1217T > G (p.L406R) (allele frequency: 4/22, 18%). Patients with biallelic missense variants showed milder metabolic acidosis than those with null variants. Two of five patients from nonconsanguineous families with rare homozygous variations showed 5.3 Mb and 36.6 Mb of homozygosity surrounding the variants, respectively; a region of homozygosity (ROH) involving the entire chromosome 3 covering the SLC2A2 gene, suggesting uniparental disomy 3, was detected in one patient.ConclusionsEarly diagnosis of FBS is difficult due to the heterogeneity of initial symptoms. Although short stature is a major issue of treatment for FBS, rhGH is not recommended in FBS patients who have normal GH stimulation tests. Patients with biallelic null variants may require alkali supplementation since urine bicarbonate loss is genetically related. ROH is a mechanism for rare homozygous variants of FBS in nonconsanguineous families.

Evaluation of the Acid-Base Status in Patients Admitted to the ICU Due to Severe COVID-19: Physicochemical versus Traditional Approaches.

Stewart's approach is known to have better diagnostic accuracy for the identification of metabolic acid-base disturbances compared to traditional methods based either on plasma bicarbonate concentration ([HCO3-]) and anion gap (AG) or on base excess/deficit (BE). This study aimed to identify metabolic acid-base disorders using either Stewart's or traditional approaches in critically ill COVID-19 patients admitted to the ICU, to recognize potential hidden acid-base metabolic abnormalities and to assess the prognostic value of these abnormalities for patient outcome. This was a single-center retrospective study, in which we collected data from patients with severe COVID-19 admitted to the ICU. Electronical files were used to retrieve data for arterial blood gases, serum electrolytes, and proteins and to derive [HCO3-], BE, anion gap (AG), AG adjusted for albumin (AGadj), strong ion difference, strong ion gap (SIG), and SIG corrected for water excess/deficit (SIGcorr). The acid-base status was evaluated in each patient using the BE, [HCO3-], and physicochemical approaches. We included 185 patients. The physicochemical approach detected more individuals with metabolic acid-base abnormalities than the BE and [HCO3-] approaches (p < 0.001), and at least one acid-base disorder was recognized in most patients. According to the physicochemical method, 170/185 patients (91.4%) had at least one disorder, as opposed to the number of patients identified using the BE 90/186 (48%) and HCO3 62/186 (33%) methods. Regarding the derived acid-base status variables, non-survivors had greater AGadj, (p = 0.013) and SIGcorr (p = 0.035) compared to survivors. The identification of hidden acid-base disturbances may provide a detailed understanding of the underlying conditions in patients and of the possible pathophysiological mechanisms implicated. The association of these acid-base abnormalities with mortality provides the opportunity to recognize patients at increased risk of death and support them accordingly.

Calcium carbide-ripened plantain induced alterations in plasma electrolytes concentration and kidney function in rats.

Artificial fruit ripening agents such as ethanol, ethylene, ethephon, and calcium carbide (CaC2) is usually employed in stimulating the fruit ripening process. Currently, there is a paucity of information regarding the effects of various artificial fruits ripening methods on the health status of consumers. In this study, the physiological effects and possible health hazards associated with the consumption of plantain ripened by CaC2 and other non-chemical methods on the kidneys were investigated. Artificially ripened plantain was mixed with rat feed and fed to Wistar albino rats for four weeks, and the levels of plasma electrolytes (Na+, HCO3-, K+, and Cl-), urea, creatinine, as well as histological changes in the kidneys were determined. Results indicated that rats fed with carbide-ripened plantain had a significantly high level of plasma bicarbonate (HCO3-) compared to control rats., but there was no difference in the level of plasma sodium (Na+). However, the levels of plasma potassium (K+) and chloride (Cl-) were significantly low in rats fed with CaC2-ripened plantain as compared to the control rats. Furthermore, the levels of urea and creatinine were significantly high in rats fed with CaC2-ripened plantain compared to the control animals. Histological analyses showed glomeruli atrophy and tubular necrosis in kidneys of rats fed with CaC2-ripened plantain, thereby further indicating toxicity to the kidneys. Histological evidence and alterations in the level of the plasma electrolytes, urea, and creatinine suggest that consumption of fruits ripened with calcium carbide may be harmful to the kidneys.

The dose of the normal saline pre-infusion and other risk factors for amphotericin B deoxycholate-associated acute kidney injury.

Conventional amphotericin B deoxycholate (AmBd) is the preferred amphotericin B formulation in countries with limited resources despite its nephrotoxicity. Normal saline pre-infusion is a recommended measure to reduce the risk of nephrotoxicity in patients receiving AmBd. To examine the effect of different normal saline solution (NSS) pre-infusion doses, and other potential risk factors, on the development of acute kidney injury (AKI) in patients with invasive fungal infection receiving AmBd. Adult patients with invasive fungal infections who received intravenous AmBd were included in this retrospective study. Doses of the normal saline pre-infusion were adjusted to the body weight (NSS/BW) and the daily dose of amphotericin B (NSS/AmBd). Kaplan-Meier survival analysis was used to estimate 14 d AKI-free survival rates, and the log-rank test was used to compare AKI-free survivals between groups. The present study included 60 patients; 31 patients developed AKI during the AmBd therapy. The overall 14 d AKI-free survival was 48.3%. NSS/AmBd, but not NSS/BW, was associated with AKI-free survival in patients receiving AmBd: the higher the NSS/AmBd, the higher the AKI-free survival. Gender, baseline blood urea nitrogen (BUN), and baseline plasma bicarbonate (Bicarb) also affected AKI-free survival. Female gender, higher BUN, and lower Bicarb were associated with higher AKI-free survival. The present study suggests that low NSS/AmBd, male gender, low BUN, and high Bicarb are risk factors for AmBd-associated AKI. Excluding gender, these risk factors are potentially modifiable and would guide tailoring appropriate preventive measures for AmBd-associated AKI.

Arterial Blood Gas, Electrolyte and Acid-Base Values as Diagnostic and Prognostic Indicators in Equine Colic.

The study aimed to investigate if arterial blood analysis in conscious horses presenting with signs of colic and breathing ambient air had diagnostic or prognostic value. Arterial blood samples from 352 horses presenting with colic at a university equine referral hospital were analysed for pH, partial pressure of carbon dioxide (PaCO2), partial pressure of oxygen (PaO2), concentrations of sodium (Na+), potassium (K+), ionised calcium (Ca2+) and chloride (Cl-), actual and standardised plasma bicarbonate concentration (HCO3- (P) and HCO3- (P, st)), blood and extracellular fluid base excess (Base (B) and Base (ecf)) and anion gap (AG). Results were compared to previously reported values for healthy horses, and comparisons were made between final diagnosis, treatment and survival to hospital discharge. Significant differences were found between colic cases and healthy reference values between some primary aetiologies. Overall, surgical and non-surgical colic cases differed in Ca2+ and Cl- concentrations and Ca2+ differed between cases that survived to discharge and those that did not. PaO2 differed between small intestinal surgical cases that survived and those that did not. From these results, we developed regression models that demonstrated excellent or good predictive value in identifying the likelihood of surgical versus medical management and survival to hospital discharge.

#3827 BICARBONATE PROFILING IN HEMODIALYSIS: MATHEMATICAL MODELING OF DATA FROM A CLINICAL TRIAL

Abstract Background and Aims During hemodialysis (HD), bicarbonate and other bases are added to the dialysis fluid to correct chronic acidosis that may develop in kidney-impaired patients, increasing plasma bicarbonate concentration to physiological levels. Previous studies have shown that both exceedingly high and low post-dialysis bicarbonate concentrations are associated with adverse clinical outcomes; however, no clear guidelines for the prescription of bicarbonate concentration in the dialysis fluid are available. Data from a recent controlled clinical trial, carried out at the Department of Nephrology, Dialysis and Internal Medicine, Medical University of Warsaw (Poland), were used to identify transport parameters of a mathematical model of acid-base homeostasis in HD patients, as the first step in the implementation of a tool to optimize bicarbonate profiling during HD. Method The study was carried out in 20 chronic patients, undergoing thrice weekly 4-hr HD. The patients underwent three treatment regimens: A) constant dialysis fluid bicarbonate concentration (HCO3,D) equal to 35 mEq/L; B) HCO3,D decreasing from 35 to 30 mEq/L after 2 hrs; C) HCO3,D increasing from 30 to 35 mEq/L after 2 hrs. The patients were divided in two cohorts: for the first (n = 11) treatment schedule was: treatment A during the first and third week, B during the second week and C during the fourth week. For the second cohort (n = 9) treatment C was carried out during the second week and treatment B during the fourth. Data were collected only during the second and third sessions of the week, and acid-base composition was determined using a blood gas analyzer. The mathematical model describes the transport of bicarbonate and dissolved CO2 from dialysis fluid to the patient and can predict changes in the acid-base equilibrium of arterial and venous plasma and erythrocytes, interstitial fluid, and tissue cells, using mass transport equations. The dialysances for bicarbonate (KHCO3) and dissolved CO2 (KCO2) were estimated via least square minimization. Results No significant difference was found comparing patients in the two cohorts, or comparing sessions of the same week. Pre-dialysis plasma bicarbonate, pH, or CO2 partial pressure (PCO2) were significantly lower for treatment B compared to treatment A. Average plasma bicarbonate concentrations for the different treatments are shown in Figure 1 for data and model simulations. Table 1 reports the average values of the estimated parameters for week. No statistically significant difference was found between sessions, cohorts, or treatments. The model fitted bicarbonate data with an average error of 2.5 ± 1.4%, and PCO2 with an error of 4.5 ± 3.6%. Simulations of mixed-venous blood, interstitial fluid, and tissue cells concentrations showed a similar response to different treatments as in arterial blood. Conclusion The model accurately describes plasma bicarbonate data with high accuracy regardless of the treatment conditions. The parameters estimated showed considerable variability between treatments (less so between the sessions of the same week), but without statistical significance. The model can be used to simulate the effect of dialysate bicarbonate profiling on acid-base equilibrium in HD patients.

#6649 SIGNIFICANT CLINICAL IMPROVEMENT OF PAEDIATRIC AND ADULT PATIENTS WITH DISTAL RENAL TUBULAR ACIDOSIS AFTER 6 YEARS OF TREATMENT WITH SIBNAYAL®

Abstract Background and Aims Distal renal tubular acidosis (dRTA) is a rare disease, inherited or acquired, characterized by hyperchloremic metabolic acidosis leading to negative effects on growth, bone and kidney, with growth retardation, rickets in children and osteomalacia in adults, nephrolithiasis and chronic kidney disease. No alkalizing treatment, necessary to control the metabolic acidosis and its consequences in growth, bone and kidney, has been shown, to date, to control the disease in the long term. The aim of this clinical study is to describe a cohort of adult and pediatric dRTA patients treated during 6 years by Sibnayal®, a new prolonged-release alkalizing formulation, in term of metabolic control, growth and long-term complications on bone mineralization and kidney function. Method Thirty patients with genetic dRTA taking Sibnayal®, previously treated with alkalizing standard of care and enrolled in the short-term B21CS study, were followed up for six years on average in a multicenter open-label extension trial (B22CS) to evaluate long-term impact of treatment on standard deviation score (SDS) of height, SDS weight, body mass index (BMI), Z-score spine bone mineral density (BMD), phosphocalcic metabolism (up to 4 years). glomerular filtration rate (GFR), nephrolithiasis, metabolic acidosis control, safety and compliance were also evaluated. Paired t-tests were done from baseline to end of study (EoS) when appropriate. The covariance ANCOVA test was performed to analyze spine BMD Z-score. Data are presented as mean ± standard error of mean. Results Clinical observations in this cohort, after an average of six years of treatment with Sibnayal®, confirmed the adequate control of metabolic acidosis (plasma bicarbonate from 22.0±0;6 mmol/L at baseline to 22.8±0.56 mmol/L at study end). The phosphocalcic metabolism analysis, from baseline to Month 48, demonstrated no significant change on Z-score for age of blood bone alkaline phosphatases, and a significant decrease of Z-score for age of blood phosphorus level (from to -0.5±0.7 to -1.3±1.0, p = 0.03). From baseline to EoS, SDS of height and weight increased significantly (-0.6±1.0 to -0.3±0.9 p = 0.04 and 0.2±1.5 to 0.7±1.4 p = 0.03, respectively), without significant difference in BMI. The spine BMD Z-score, relevant skeletal area for both pediatric and adult patients, underwent a continuous and significant increase of the change from baseline values over 6 years of treatment (difference [95% CI] = 0.404 [0.170; 0.639]). At EoS, spine BMD Z-score was improved in pre- and post-pubertal patients (mean 0.76±0.54 and 0.56±0.22 respectively), while it was stabilized in pubertal patients (mean -0.01±0.39). There was no significant variation of GFR between baseline and EoS. Nephrolithiasis increased slightly according to the increased age of the patient, without surgical intervention for stones removal. Safety and adherence to treatment remained good throughout the study. Conclusion Our data show the positive effect of the long-term treatment with Sibnayal® on growth and spine BMD, nicely improved, in the dRTA patients who participated to this long-term follow-up clinical study. The kidney function is also stabilized in these patients during the follow-up. This is the first report describing the prevention effect on the long-term complications of the distal Renal Tubular Acidosis patients under 6 years of Sibnayal® treatment.

#5807 FACTORS ASSOCIATED WITH KALEMIA IN RENAL DISEASE

Abstract Background and Aims International recommendations promote a strict potassium diet in order to avoid hyperkalemia in chronic kidney disease patients. However, efficiency of such a dietary counseling has never been demonstrated. The objectives of this study were to define the relationship between kalemia, dietary potassium intake estimated by kaliuresis and renal function and to define the factors associated with kalemia in patients using artificial intelligence. Method To this extent, data from patients followed in a nephrology unit, included in the UniverSel study and whose kalemia (measured on the day of urine collection; n = 367) were analyzed. The association between kalemia and thirty-four variables concerning the patients' characteristics, their biological work-up, their medications and their answers to the UniverSel dietary self-questionnaire on kalemia were assessed using a Bayesian network. Results The patients included had a wide range of estimated glomerular filtration rate, but few had stage 5 chronic kidney disease (CKD). Kalemia was negatively and linearly correlated to estimated glomerular filtration rate (p&amp;lt;0.001) but was not correlated to kaliuresis (p = 0.55). Kaliuresis was not correlated to estimated glomerular filtration rate (p = 0.08). Factors associated with kalemia were analyzed using a Bayesian network. The 5 variables most associated with kalemia were, in descending order, estimated glomerular filtration rate, original nephropathy, age, diabetes, and plasma bicarbonate level. RAS-blockers prescription was also associated to kalemia. Consumption of potassium rich food were poorly associated to kalemia. Conclusion Our results do not support a strict control of potassium intake in stage 1 to 4 CKD patients. Our results reinforce the interest of a multidimensional management including personalized therapy and strict correction of metabolic acidosis. Lightning dietary restrictions in potassium would improve the quality of life of patients with CKD who are often multi-pathological and already subject to multiple dietary constraints.

Metabolic Acidosis Results in Sexually Dimorphic Response in the Heart Tissue.

Metabolic acidosis (MA) is a highly prevalent disorder in a significant proportion of the population, resulting from imbalance in blood pH homeostasis. The heart, being an organ with very low regenerative capacity and high metabolic activity, is vulnerable to chronic, although low-grade, MA. To systematically characterize the effect of low-grade MA on the heart, we treated male and female mice with NH4Cl supplementation for 2 weeks and analyzed their blood chemistry and transcriptomic signature of the heart tissue. The reduction of pH and plasma bicarbonate levels without an associated change in anion gap indicated a physiological manifestation of low-grade MA with minimal respiratory compensation. On transcriptomic analysis, we observed changes in cardiac-specific genes with significant gender-based differences due to MA. We found many genes contributing to dilated cardiomyopathy to be altered in males, more than in females, while cardiac contractility and Na/K/ATPase-Src signaling were affected in the opposite way. Our model presents a systems-level understanding of how the cardiovascular tissue is affected by MA. As low-grade MA is a common ailment with many dietary and pharmaceutical interventions, our work presents avenues to limit chronic cardiac damage and disease manifestation, as well as highlighting the sex differences in MA-induced cardiovascular damage.

Comparison of Hemodynamic Effects of Dobutamine and Ephedrine Infusions in Isoflurane-Anesthetized Horses.

The objective of this study was to compare the hemodynamic effects of dobutamine and ephedrine during the management of anesthesia-related hypotension in healthy horses. Thirteen horses underwent general anesthesia with isoflurane and were randomly divided into two different groups, one of which received a dobutamine constant rate infusion (CRI) (1 µg/kg bwt/min) and the other received an ephedrine CRI (20 µg/kg bwt/min) when hypotension (<60 mmHg) was identified, following up to 15 min after the blood pressure reached 70 mmHg. All horses were equipped with a pulmonary artery catheter and a peripheral artery catheter, and multiparameter monitoring commenced as soon as they were under mechanical ventilation. Hemodynamic parameters were recorded, while tissue perfusion markers (peripheral oxygen saturation, arterial oxygen partial pressure, arterial carbon dioxide partial pressure, arterial pH, arterial plasma bicarbonate concentration, arterial oxygen saturation, mixed venous oxygen saturation, mixed venous oxygen content, arterial oxygen content, arteriovenous oxygen difference, oxygen delivery index, oxygen consumption index, and oxygen extraction ratio), serum lactate concentration, and troponin I concentrations were analyzed before the start of infusions (T0), when the blood pressure reached 70 mmHg (T1), and 15 min after T1 (T2). The time to restore the arterial pressure was similar in both groups (p > 0.05); however, the heart rate was higher in the ephedrine group (p = 0.0098), and sinus bradyarrhythmia occurred in the dobutamine group. Furthermore, both experimental protocols increased cardiac output (p = 0.0012), cardiac index (p = 0.0013), systemic vascular resistance (p = 0.008), systemic vascular resistance index (p < 0.001), and ameliorated perfusion markers. In the dobutamine group, the pulmonary artery wedge pressure (p < 0.001) and systolic index (p = 0.003) were elevated, while the arteriovenous oxygen difference was reduced in the ephedrine group (p = 0.02). Troponin I was used as a myocardial injury indicator, and did not differ between moments or between groups (p > 0.05). We concluded that both drugs were effective and safe to treat anesthetic hypotension under the conditions of this study.

A Randomized Controlled Trial to Assess the Effects of Oral Alkali Therapy in Patients with Diabetic Kidney Disease

Background: To analyze the effects of oral alkali therapy on renal function, nutritional status and bone density in patients of diabetic kidney disease. Material &amp; Methods: A randomized controlled trial was conducted on 60 patients of age&gt;18 years with diabetic kidney disease who were not on dialysis and had plasma bicarbonate levels between 16 and 20 mmol/l. Patients were randomly divided into two groups: Test group (n=30) which received oral alkali therapy as sodium bicarbonate and control group (n=30) who did not receive oral alkali therapy. The patients were followed for 12 months to compare the improvement. Results: In comparison to controls, test group showed a significant improvement in the Hb (0.7 vs. 0.25, P =0.003), significantly less decrease in eGFR (-2.25 vs. -2.9, P=0.049), non-significant less increase in creatinine (-0.26 ± 0.4 vs. -0.43 ± 0.33, P=0.09), significant improvement in bicarbonate levels (7.5 vs. 1, p&lt;0.0001), significant restoration of albumin (0.32 vs. 0.05, P&lt;.0001), significant fall in iPTH levels (50 vs. 25, p=0.007) and ALP levels (32 vs. 12, p=0.015). Bone density (0.28 ± 0.17 vs. 0.01 ± 0.13, P&lt;.0001) and clinical well-being VAS scores improved significantly among the cases (9.83 ± 5.65 vs. -1.67 ± 7.11, P&lt;.0001). Conclusion: In conclusion, oral alkali therapy slows the rate of decline of renal function and the development of end stage renal disease in patients with advanced stages of CKD. This cheap and simple strategy, which is in line with current renal consensus documents, also improves the nutritional status of patients and bone density.

Factors associated with kalemia in renal disease.

International recommendations promote a strict potassium diet in order to avoid hyperkalemia in chronic kidney disease (CKD) patients. However, the efficiency of such a dietary recommendation has never been demonstrated. The objectives of this study were to define the relationship between kalemia, dietary potassium intake estimated by kaliuresis and renal function, and to define the factors associated with kalemia in patients using artificial intelligence. To this extent, data from patients followed in a nephrology unit, included in the UniverSel study and whose kalemia (measured on the day of urine collection; n=367) were analyzed. The patients included had a wide range of estimated glomerular filtration rate (eGFR), but few had stage 5 CKD. Kalemia was negatively and linearly correlated to eGFR (P<.001) but was not correlated to kaliuresis (P=.55). Kaliuresis was not correlated to eGFR (P=.08). Factors associated with kalemia were analyzed using a Bayesian network. The five variables most associated with kalemia were, in descending order, eGFR, original nephropathy, age, diabetes and plasma bicarbonate level. The results of this study do not support a strict dietary potassium control to regulate kalemia in stage 1-4 CKD patients.