Metabolic Acidosis In Patients Research Articles

Perioperative urinary ketosis and metabolic acidosis in patients fasted for undergoing gynecologic surgery.

Our bodies have adaptive mechanisms to fasting, in which glycogen stored in the liver and muscle protein are broken down, but also lipid mobilisation is triggered. As a result, glycerol and fatty acids are released into the bloodstream, increasing the production of ketone bodies in liver. However, there are limited studies on the incidence of perioperative urinary ketosis, the intraoperative blood glucose changes and metabolic acidosis after fasting for surgery in non-diabetic adult patients. We conducted a retrospective cohort study involving 1831 patients undergoing gynecologic surgery under general anesthesia from January to December 2022. Ketosis was assessed using a postoperative urine test, while blood glucose levels and acid-base status were collected from intraoperative arterial blood gas analyses. Of 1535 patients who underwent postoperative urinalysis, 912 (59.4%) patients had ketonuria. Patients with ketonuria were younger, had lower body mass index, and had fewer comorbidities than those without ketonuria. After adjustments, younger age, higher body mass index and surgery starting late afternoon were significant risk factors for postoperative ketonuria. Of the 929 patients assessed with intraoperative arterial blood gas analyses, 29.0% showed metabolic acidosis. Multivariable logistic regression revealed that perioperative ketonuria and prolonged surgery significantly increased the risk for moderate-to-severe metabolic acidosis. Perioperative urinary ketosis and intraoperative metabolic acidosis are common in patients undergoing gynecologic surgery, even with short-term preoperative fasting. The risks are notably higher in younger patients with lower body mass index. Optimization of preoperative fasting strategies including implementation of oral carbohydrate loading should be considered for reducing perioperative metabolic derangement due to ketosis.

Long Suffering Type 1 Diabetes Mellitus During Metabolic Acidosis on Positiveness of Ketones in Urine Patients

Examination of ketones in the patient's urine and measuring the patient's blood sugar level will determine whether there will be metabolic acidosis in patients with type 1 diabetes mellitus, which is a metabolic disorder that can be caused by various etiologies, such as chronic hyperglycemia due to impaired insulin secretion or impaired insulin action. alone. Diabetes Mellitus type 1 itself is more caused by reduced insulin secretion due to damage to pancreatic -cells. This study was conducted to examine ketones in urine on the duration of suffering from type 1 diabetes mellitus when metabolic acidosis occurs Data collection in this study was carried out by accidental sampling method by researchers to collect secondary and primary data on urine ketones in patients with metabolic acidosis. Based on research that has been done, data obtained from 34 patients with type 1 diabetes mellitus at the Sigerongan Health Center, as many as 8 patients with positive results of urine ketones with a prevalence of +2 totaling 3 people and +3 totaling 5 people. Judging from the high level of glucose (hyperglycemia) that is > 200 mg/dl and the positivity of ketone bodies in the patient's urine as a sign of metabolic acidosis. With a long-susceptibility to suffer from diabetes mellitus 1-5 years and above. The results of measuring ketone levels in the patient's urine show that there is no relationship with the duration of suffering from diabetes mellitus in the urine but blood sugar levels.

Hypokalemic Paralysis Due to Distal Renal Tubular Acidosis, Case Report

Distal renal tubular acidosis (dRTA) is a metabolic disease characterized by hypokalemia, hyperchloremic metabolic acidosis and urine pH above 5.5. These findings may be accompanied by hypercalciuria, nephrocalcinosis, nephrolithiasis, jaundice, osteomalacia or rickets in children. Although hypokalemia is frequently seen as a laboratory finding in dRTA, weakness, which is the clinical finding of this deficiency, is rare. A 33-year-old female patient was brought to the emergency department (ED) with complaints of weakness, loss of strength in the extremities, and difficulty in breathing. Laboratory analyzes of the patient revealed metabolic acidosis and hypokalemia. Urea and creatinine values were normal. The patient was admitted to the internal medicine department with a preliminary diagnosis of dRTA and hypokalemic paralysis. Initially, parenteral infusion of KCl and NaHCO3 was administered in the treatment. In the follow-up of the patient, it was observed that hypokalemia and metabolic acidosis improved from the 3rd day and clinical findings improved within 36 hours following the replacement therapy. dRTA, which is rare in adults, is among the secondary causes of hypokalemic paralysis. dRTA should be considered among the differential diagnoses in the presence of hypokalemia and metabolic acidosis in patients presenting with bilateral weakness.

Application of delta gap equation for the assessment of metabolic acidosis in renal failure patients

Introduction: Metabolic acidosis is commonly encountered in chronic kidney disease (CKD) which contributes to its progression. The metabolic acidosis in chronic kidney disease is presumed to be due to accumulation of unmeasured anions leading to a high anion gap (AG). The aim of the study was to assess the metabolic acidosis in renal failure patients using the calculation of delta gap. Methods: 100 renal failure cases were included. Their abnormal urea and creatinine values were utilized to calculate the BUN/creatinine ratio for all the cases. Based on the dipstick urine testing grading, proteinuric renal diseases were identified. The urine and serum osmolality were calculated in these renal failure patients. Serum osmolality was calculated using the values of serum sodium and urea. Urinary density which is also called urine specific gravity was used for indirect calculation of urine osmolality. Modified delta gap equation was applied for quick evaluation of mixed metabolic acid-base disorders. Results: Out of the 100 cases, 41 were proteinuric renal disease cases and 59 were non-proteinuric renal disease cases. High anion gap metabolic acidosis were seen in 65% of the total 100 cases. In 33% of the total cases, non-anion gap metabolic acidosis was also seen in addition to the high anion gap metabolic acidosis as it is evidenced by the delta gap value of less than -6 mmol/L. Conclusions: Earlier identification of the type and causative mechanism of metabolic acidosis in these patients may help to decrease the morbidity and mortality of these patients. The delta gap that can be easily calculated using this quick and short equation at the bedside may serve as a marker in the management of metabolic acidosis in renal failure patients. Keywords: delta gap; modified quick equation; metabolic acidosis; renal failure

B-012 Validation of a Urine Ammonium Assay on Roche Cobas c502 Chemistry Analyzer

Abstract Background Urine ammonium (uNH4+) excretion is critical for the maintenance of acid-base balance and reduced uNH4+ excretion can cause retention of hydrogen ions resulting in metabolic acidosis in patients with chronic kidney disease (CKD). In addition, study found that declined urine ammonium excretion is an independent factor for predicting the worsening of kidney function. However, urine ammonium assay is not readily available on automated chemistry analyzers. We developed a protocol for the determination of urine ammonium levels using an ammonia assay for plasma samples on an automated chemistry analyzer. In this report, we present the urine ammonium protocol used in our laboratory and the validation of the urine ammonium assay. Methods All urine samples were diluted 100 times with deionized water and ammonium in the diluted samples was measured using the NH2L2 ammonia II assay on Roche cobas c502 chemistry analyzer. When a urine sample containing ammonium level less than 1.06 mmol/L, a 50-fold dilution was performed. Recovery was determined in six urine samples when 9 parts of the urine were mixed with one part of a standard 200 mmol/L ammonium solution (made with Ammonium Chloride from Thermo Scientific). Linearity was determined by serial dilutions of a sample containing 187 mmol/L ammonium. Limit of quantitation was determined using a 50-fold dilution protocol. The reference interval of 3–65 mmol/L was verified using 64 urine samples from volunteer donors and patient without CKD and metabolic acidosis. The stability was determined by testing two samples kept at room temperature for 0, 8, and 24 hour, respectively. The within-run precisions were determined by testing three urine samples 20 times in a run, and the between-run precisions were determined by testing three samples 2 times a day for 10 days, respectively. Results Recovery was 95.8% to 102.2% in six urine samples contained varying amount of ammonium ranged between 6.0 mmol/L to 22.2 mmol/L. Linearity was 0.5–99 mmol/L. Limit of quantification was 0.5 mmol/L. The reference interval of 3–65 mmol/L was verified. Urine ammonium was stable up to 24 h at room temperature. For within-run precision, the coefficient of variation (CV) was 1.51%, 0.49%, and 0.54% for samples containing 6.0 mmol/L, 27.7 mmol/L, and 75.7 mmol/L ammonium, respectively. For between-run precision, the CV was 2.54%, 5.98%, and 6.13% for samples containing 4.4 mmol/L, 27.9 mmol/L, and 55.1 mmol/L ammonium, respectively. Conclusion Urine ammonium levels can be determined using the NH2L2 ammonia II assay on Roche cobas c502 chemistry analyzer after manual dilution of urine samples 100 times with deionized water. The limit of quantitation is extended to 0.5 mmol/L when urine samples are diluted 50 times with deionized water.

Effects of correcting metabolic acidosis on muscle mass and functionality in chronic kidney disease: a systematic review and meta-analysis.

Metabolic acidosis unfavourably influences the nutritional status of patients with non-dialysis dependent chronic kidney disease (CKD) including the loss of muscle mass and functionality, but the benefits of correction are uncertain. We investigated the effects of correcting metabolic acidosis on nutritional status in patients with CKD in a systematic review and meta-analysis. A search was conducted in MEDLINE and the Cochrane Library from inception to June 2023. Study selection, bias assessment, and data extraction were independently performed by two reviewers. The Cochrane risk of bias tool was used to assess the quality of individual studies. We applied random effects meta-analysis to obtain pooled standardized mean difference (SMD) and 95% confidence intervals (CIs). We retrieved data from 12 intervention studies including 1995 patients, with a mean age of 63.7±11.7years, a mean estimated glomerular filtration rate of 29.8±8.8mL/min per 1.73m2 , and 58% were male. Eleven studies performed an intervention with oral sodium bicarbonate compared with either placebo or with standard care and one study compared veverimer, an oral HCl-binding polymer, with placebo. The mean change in serum bicarbonate was +3.6mEq/L in the intervention group and +0.4mEq/L in the control group. Correcting metabolic acidosis significantly improved muscle mass assessed by mid-arm muscle circumference (SMD 0.35 [95% CI 0.16 to 0.54], P<0.001) and functionality assessed with the sit-to-stand test (SMD -0.31 [95% CI -0.52 to 0.11], P=0.003). We found no statistically significant effects on dietary protein intake, handgrip strength, serum albumin and prealbumin concentrations, and blood urea nitrogen. Correcting metabolic acidosis in patients with CKD improves muscle mass and physical function. Correction of metabolic acidosis should be considered as part of the nutritional care for patients with CKD.

Association of body mass index with the development of metabolic acidosis in patients with chronic kidney disease

AbstractAimsHigher body mass index (BMI) is associated with higher bone mass and bone serves as a buffer during the development of metabolic acidosis. The authors sought to examine the relationship between BMI and metabolic acidosis in patients with chronic kidney disease (CKD).Materials and MethodsThe study utilized a large US longitudinal data repository including over 103 million patients from healthcare provider organizations to evaluate the relationship between the exposure variable (BMI) and the prevalence and incidence of metabolic acidosis among patients with estimated glomerular filtration rate &lt;60 ml/min/1.73 m2. Incident metabolic acidosis was identified at the first of two consecutive post‐index serum bicarbonate values, 10–365 days apart, between 12 and &lt;22 mEq/L in patients with normal index serum bicarbonate. Cox proportional hazard models were adjusted for multiple variables including demographics, comorbidities, income, education, and kidney function.Results103,766 patients qualified for this study; 6472 (6.2%) had metabolic acidosis at index. An inverse association between BMI category and metabolic acidosis was observed for both baseline (prevalence) and new‐onset (incidence) metabolic acidosis. Compared to BMI category of 18.5 to &lt;25 kg/m2, each category of incrementally higher BMI was associated with a decreasing risk of incident metabolic acidosis; the adjusted hazard ratios (95% confidence interval) were 0.866 (0.824–0.911), 0.770 (0.729–0.813), 0.664 (0.622–0.709), and 0.612 (0.571–0.655) for BMI 25 to &lt;30, 30 to &lt;35, 35 to &lt;40, and 40+ kg/m2, respectively.ConclusionsAmong patients with CKD, an incremental increase in BMI was inversely associated with both the prevalence and incidence of metabolic acidosis. These associations suggest that increased body weight may protect against the development of metabolic acidosis, a risk factor for progressive loss of kidney function.

#6212 SEVERE HYPERCHLOREMIC METABOLIC ACIDOSIS WITH SGLT-2 INHIBITORS IN PATIENTS WITH URINARY DIVERSION

Abstract Background and Aims Urinary diversion after cystectomy using autologous intestinal segments has been the gold standard treatment of benign and malignant diseases of urinary tract. The most frequent metabolic abnormalities is hyperchloremic metabolic acidosis, due to ammonium absorption alongside chloride gain and bicarbonate excretion in the bowel conduit. Sodium-glucose co-transporter-2 (SGLT2) inhibitors are a class of antihyperglycemic agents that recently revolutionized the paradigm of chronic kidney disease. It exerts its effect by preventing the reabsorption of filtered glucose from the tubular lumen, acting on the SGLT2 proteins in the renal proximal convoluted tubules, and thus promoting a greater urinary glucose excretion. The authors described 2 patients with bowel conduit and mild hyperchloremic metabolic acidosis, presented with severe metabolic acidosis short after starting SGLT2 inhibitors. Method Consultation of medical records. Results Case 1: 62-year-old male with an orthotopic neobladder since 2005, type 2 diabetes and nonspecific interstitial pneumonia. In 2018 arterial blood gas (ABG) was: pH 7.45, pO2 81, pCO2 28, HCO3- 19.3, Cl 107, AG 7.7 (normal albumin), K+ 3.25. In February 2022 he was sent to the emergency department (ER) from a Pneumology appointment, after an ABG showed an aggravated hyperchloremic metabolic acidosis: pH 7.25, pCO2 27.5, HCO3- 12, Cl 122, Na+ 143, K+ 3.74, AG 9, lactate 0.69, glucose 261, ketone bodies negative); blood workup added acute kidney injury (AKI), urea 81, creatinine 1.6. The patient medical history revealed: administration of 5 cycles of cyclophosphamide (7 months before) and the introduction of empagliflozin 10mg id, 10 months prior to this event, as an addition to Metformin 1000mg id. A progressive metabolic normalization was observed after the SGLT2 inhibitor was withdrawn and intravenous hydration. Case 2: A 63-year-old male with an ileal conduit since 2018 and type 2 diabetes. He had chronic renal disease since 2021 with serum creatinine 1.5-2. He presented with a 3-day history of lethargy and anorexia. He had started dapagliflozina 10mg id 10 months prior to this event. At admission the patient had normal vital signs, glasgow coma scale 15 and no major signs at observation. ABG showed severe hyperchloremic metabolic acidemia (pH 6.98, pCO2 20.5, pO2 124.4, HCO3- 4.7, Na 129, Cl 120, AG 4.3, K+ 3.54, glucose 200, lactate 0.5) alongside AKI, urea 209 and creatinine 2.8 and spot urine without ketone bodies. He was admitted for a short period to the intensive care unit, for intravenous sodium bicarbonate and hydration, on top of SGLT2 inhibitor suspension, with progressive clinical and metabolic resolution. Conclusion Chronic hyperchloremic metabolic acidosis is a frequent and known complication of urinary diversion, due to the reabsorption of solutes by the intestinal mucosa because of the presence of urine (ammonium and chloride absorption and bicarbonate excretion) and diarrhea and volume depletion due to reduced sodium absorption in the gout. Euglycemic Ketoacidosis is a well-known complication of SGLT2 Inhibitor therapy and was not this case as both patients had normal anion gap. Hyperchloremic acidosis as been rarely described but not so severe as we presented. Although both patients had AKI, was not severe. We hypothesize that SGLT2 inhibitors, could exacerbate the chronic hyperchloremic metabolic acidosis by increasing urinary sodium and glucose excretion, that could exacerbate volume depletion, diarrhea and hyperglycemia (and subsequent volume depletion). This are the first 2 cases reported of severe hyperchloremic metabolic acidosis in patients with orthotopic neobladder and SGLT2 inhibitors treatment. The physiopathology of this presentation needs to be studied.

Risks of Topical Carbonic Anhydrase Inhibitors in Glaucoma Patients With Chronic Kidney Disease: A Nationwide Population-Based Study

To investigate the risks of metabolic acidosis and renal outcomes after topical carbonic anhydrase inhibitor (CAI) use in patients with both primary open-angle glaucoma (POAG) and advanced chronic kidney disease (CKD). Nationwide, population-based cohort study. This study was conducted with population data from Taiwan's National Health Insurance (NHI) Research Database between January 2000 and June 2009. Patients with advanced CKD who were diagnosed with glaucoma (International Classification of Diseases, Ninth Revision [ICD-9] code 365) and had been receiving eye drops for glaucoma (including carbonic anhydrase inhibitors selected by NHI drug code) were enrolled. Using Kaplan-Meier methods, we compared the cumulative incidence of mortality, long-term dialysis, and cumulative incidence of metabolic acidosis over time between CAI users and CAI non-users. Primary outcomes comprised mortality, renal outcome (progression to hemodialysis), and metabolic acidosis. In this cohort, topical CAI users had a higher incidence of long-term dialysis than non-users (incidence=1,216.85 vs 764.17 events per 100 patient-years; adjusted hazard ratio=1.17, 95% CI=1.01-1.37). Hospital admissions due to metabolic acidosis were higher in CAI users compared with non-users (incidence=21.54 vs 11.87 events per 100 patient-years; adjusted hazard ratio=1.89, 95% CI=1.07-3.36). Topical CAIs may be associated with higher risks of long-term dialysis and metabolic acidosis in patients with POAG and pre-dialysis advanced CKD. Therefore, topical CAIs should be used with caution in advanced CKD patients.

Compared effectiveness of sodium zirconium cyclosilicate and calcium polystyrene sulfonate on hyperkalemia in patients with chronic kidney disease.

Hyperkalemia is a well-recognized electrolyte abnormality in patients with chronic kidney disease (CKD). Potassium binders are often used to prevent and treat hyperkalemia. However, few studies have evaluated the difference in serum potassium (K+) level-lowering effect during the post-acute phase between the novel potassium binder, sodium zirconium cyclosilicate (ZSC), and conventional agents. This retrospective study included patients who received potassium binders (either ZSC or calcium polystyrene sulfonate [CPS]) in our hospital between May 2020 and July 2022. The patients were divided into the ZSC and CPS groups. After propensity score matching, we compared changes from baseline to the first follow-up point, at least 4 weeks after initiating potassium binders, in electrolytes including K+ level between the two groups. Of the 132 patients, ZSC and CPS were administered in 48 and 84 patients, respectively. After matching, 38 patients were allocated to each group. The ZSC group showed greater reduction in K+ levels than did the CPS group (P < 0.05). Moreover, a significant increase in serum sodium minus chloride levels, a surrogate marker for metabolic acidosis, was observed in the ZSC group (P < 0.05). Our results demonstrated that ZSC could potentially improve hyperkalemia and metabolic acidosis in patients with CKD.

Hidden Acid Retention with Normal Serum Bicarbonate Level in Chronic Kidney Disease.

Management of metabolic acidosis is crucial for preserving bone, muscle, and renal health, as evidenced by the results of several interventional studies conducted on patients with chronic kidney disease (CKD). Considering the continuity of CKD progression over time, it is reasonable to deduce that a subclinical form of metabolic acidosis may exist prior to the manifestation of overt metabolic acidosis. Covert H+ retention with normal serum bicarbonate level in patients with CKD may result in maladaptive responses that contribute to kidney function deterioration, even in the early stages of the disease. The loss of adaptive compensatory mechanisms of urinary acid excretion may be a key factor in this process. Early modulation of these responses could be an important therapeutic strategy in preventing CKD progression. However, to date, the optimal approach for alkali therapy in subclinical metabolic acidosis in CKD remains uncertain. There is a lack of established guidelines on when to initiate alkali therapy, potential side effects of alkali agents, and the optimal blood bicarbonate levels based on evidence-based practices. Therefore, further research is necessary to address these concerns and establish more robust guidelines for the use of alkali therapy in patients with CKD. Herein, we provide an overview of recent developments on this subject and examine the potential therapeutic approaches that interventional treatments may present for patients with hidden H+ retention, exhibiting normal serum bicarbonate levels - commonly described as subclinical or eubicarbonatemic metabolic acidosis in patients with CKD.

Uremic Encephalopathy.

HomeRadiologyVol. 307, No. 1 PreviousNext Reviews and CommentaryFree AccessImages in RadiologyUremic EncephalopathyDavid A. Lizarazo , Jairo LizarazoDavid A. Lizarazo , Jairo LizarazoAuthor AffiliationsFrom the Department of Diagnostic Imaging, Fundación Santa Fe de Bogotá, Universidad El Bosque, Ave 116 No. 9-02, Bogotá 110246, Colombia (D.A.L.); and Department of Internal Medicine, Hospital Universitario Erasmo Meoz, Universidad de Pamplona, Cúcuta, Colombia (J.L.).Address correspondence to D.A.L. (email: [email protected]).David A. Lizarazo Jairo LizarazoPublished Online:Dec 20 2022https://doi.org/10.1148/radiol.221602MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In A 54-year-old man was admitted for a 3-day history of dysarthria, hand tremors, hypokinesia, and generalized muscle rigidity. His past medical history included diabetes mellitus and end-stage renal disease on hemodialysis. On admission, there were elevated blood urea nitrogen and creatinine levels with a metabolic acidosis. Axial CT scan of the brain showed symmetrical hypoattenuation of both basal ganglia (Figure). Noncontrast brain T2-weighted MRI demonstrated symmetrical high signal intensity in the basal ganglia surrounded by a more hyperintense rim delineating the lentiform nucleus (Figure). This is the lentiform fork sign, wherein the internal and external capsules and the medullary laminae become hyperintense with axial T2-weighted images (Figure). After correction of the metabolic acidosis with prompt dialysis and glycemic control, the neurologic examination returned to normal, and his symptoms completely resolved. A follow-up MRI examination was not performed.Images in a 54-year-old man who presented with a 3-day evolution of dysarthria, hand tremors, hypokinesia, and generalized muscle rigidity. He had diabetes mellitus and end-stage renal disease and was undergoing hemodialysis. Laboratory tests showed azotemia and metabolic acidosis. (A) Axial CT scan of brain shows symmetrical hypoattenuation in the bilateral basal ganglia. (B) Axial T2-weighted fluid-attenuated inversion recovery noncontrast brain MRI scan demonstrates bilateral symmetrical swollen lentiform nuclei with a hyperintense rim delineating the lentiform nucleus with a typical fork-like appearance representing the “lentiform fork sign.” (C) Schematic drawing shows the “lentiform fork sign.” At follow-up after correction of metabolic acidosis with prompt dialysis and glycaemic control, the neurologic examination was normal, and symptoms completely resolved. Follow-up scan was not performed. EC = external capsule, IC = internal capsule, LME = external medullary lamina, LMI = internal medullary lamina, TS = the stem.Download as PowerPointOpen in Image Viewer Uremic encephalopathy is a neurologic complication resulting from endogenous uremic toxins in patients with severe renal failure. The pathogenesis is complex and unclear (1). The lentiform fork sign (Figure) is attributed to metabolic acidosis in patients with diabetes and renal failure with a history of incomplete dialysis leading to reversible basal ganglia and adjacent white matter injury (2). The edematous external capsule represents the lateral arm of the fork, with both the external and internal capsule joining to build the stem of the fork. Edema of the medial lentiform margin forms the medial arm, which splits into two along the medullary laminae to envelop the globus pallidus (3). The lentiform fork sign is nonspecific for uremic encephalopathy. Differential diagnosis of pathologic conditions manifesting with this sign includes severe metabolic acidosis, ketoacidosis, dialysis disequilibrium syndrome, and intoxication (ie, methanol, ethylene glycol); this can also be drug induced (ie, metformin) (4).Disclosures of conflicts of interest: D.A.L. No relevant relationships. J.L. No relevant relationships.

Effect of Osteoblast-Specific Deletion of the Proton Receptor OGR1.

Metabolic acidosis (MET) stimulates bone resorption through inhibition of osteoblast (OB) bone formation and stimulation of osteoclast (OC) bone resorption. We found that OGR1, a G protein-coupled proton (H+)-sensing receptor, was critical for initial H+ signaling in the OB. In mice with a global deletion of OGR1, we demonstrated that loss of OGR1 impairs H+-induced bone resorption, leading to increased bone density through effects on both the OB and OC. Using an OC-specific deletion of OGR1, we found that MET directly activates OGR1 in the OC. To determine if the response of OGR1 to MET in the OB is independent of a response in OCs and to characterize direct activation of OGR1 in the OB, we studied female mice with an OB-specific deletion of OGR1 (OB-cKO) and differentiated osteoblasts derived from marrow of OB-cKO and wild-type (WT) mice. In OB-cKO mice, we found increased bone area in both tibial and femoral cortical bone. Specific loss of OB OGR1 increased in vitro mineralization, alkaline phosphatase activity, and expression of osteoblast-specific genes compared with WT with no alteration in OC activity. MET stimulation of OB cox2 and fgf23 gene expression was inhibited in OB-cKO OB. These results indicate that MET activation of OGR1 in the OB is independent of the response in the OC and that OGR1 in both cell types is required for a complete response to MET. Characterization of the role of OGR1 in MET-induced bone resorption will improve our understanding of bone loss associated with metabolic acidosis in patients with chronic kidney disease. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Hyperkalemia and Metabolic Acidosis Occur at a Higher eGFR in Sickle Cell Disease.

People with sickle cell disease (SCD) have an elevated estimated glomerular filtration rate (eGFR) compared with the general population, and this may alter the usual creatinine-based eGFR cutoffs for which physiologic evidence of kidney dysfunction is apparent. This study aimed to identify eGFR thresholds for hyperkalemia and metabolic acidosis in patients with SCD. This was a cross-sectional analysis of 733 patients with severe (hemoglobin SS or Sβ0-thalassemia) SCD genotype, 238 patients with moderate (hemoglobin SC or Sβ+-thalassemia) SCD genotype, and 1333 age- and sex-matched African Americans from the National Health and Nutrition Examination Survey (NHANES). The prevalence rates of hyperkalemia and metabolic acidosis were compared by eGFR category. Cutoffs for hyperkalemia and metabolic acidosis were determined using generalized additive models. Hyperkalemia and metabolic acidosis were more common in those with severe SCD genotype (13% and 21%, respectively) compared with the NHANES (0.3% and 5%, respectively); the prevalence rates in the moderate SCD genotype were intermediate for hyperkalemia (3%) and metabolic acidosis (11%). The proportion of patients with hyperkalemia and metabolic acidosis progressively increased with lower eGFR category in both SCD genotype groups. The eGFR thresholds for hyperkalemia and metabolic acidosis were higher in the severe (85 and 91 ml/min per 1.73 m2, respectively) and moderate (52 and 102 ml/min per 1.73 m2, respectively) SCD genotypes compared with the NHANES (34 and 46 ml/min per 1.73 m2). We demonstrate that hyperkalemia and metabolic acidosis are more common and occur at higher eGFR values in patients with SCD compared with age- and sex-matched African Americans, including in eGFR ranges considered to be normal. Future studies using redefined creatinine-based eGFR thresholds for abnormal kidney function may identify high-risk patients for earlier intervention strategies and referral for specialized renal care in SCD.

Diagnosing metabolic acidosis in chronic kidney disease: importance of blood pH and serum anion gap.

Metabolic acidosis is one of the most common complications of chronic kidney disease (CKD). It is associated with the progression of CKD, and many other functional impairments. Until recently, only serum bicarbonate levels have been used to evaluate acid-base changes in patients with reduced kidney function. However, recent emerging evidence suggests that nephrologists should reevaluate the clinical approach for diagnosing metabolic acidosis in patients with CKD based on two perspectives; pH and anion gap. Biochemistry and physiology textbooks clearly indicate that blood pH is the most important acid-base parameter for cellular function. Therefore, it is important to determine if the prognostic impact of hypobicarbonatemia varies according to pH level. A recent cohort study of CKD patients showed that venous pH modified the association between a low bicarbonate level and the progression of CKD. Furthermore, acidosis with a high anion gap has recently been recognized as an important prognostic factor, because veverimer, a nonabsorbable hydrochloride-binding polymer, has been shown to improve kidney function and decrease the anion gap. Acidosis with high anion gap frequently develops in later stages of CKD. Therefore, the anion gap is a time-varying factor and renal function (estimated glomerular filtration rate) is a time-dependent confounder for the anion gap and renal outcomes. Recent analyses using marginal structural models showed that acidosis with a high anion gap was associated with a high risk of CKD. Based on these observations, reconsideration of the clinical approach to diagnosing and treating metabolic acidosis in CKD may be warranted.

Sodium chloride or Plasmalyte-148 evaluation in severe diabetic ketoacidosis (SCOPE-DKA): a cluster, crossover, randomized, controlled trial.

To determine whether treatment with Plasmalyte-148 (PL) compared to sodium chloride 0.9% (SC) results in faster resolution of diabetic ketoacidosis (DKA) and whether the acetate in PL potentiates ketosis. We conducted a cluster, crossover, open-label, randomized, controlled Phase 2 trial at seven hospitals in adults admitted to intensive care unit (ICU) with severe DKA with hospital randomised to PL or SC as fluid therapy. The primary outcome, DKA resolution, was defined as a change in base excess to ≥ - 3mEq/L at 48h. Ninety-three patients were enrolled with 90 patients included in the modified-intention-to-treat population (PL n = 48, SC n = 42). At 48h, mean fluid administration was 6798 ± 4850ml vs 6574 ± 3123ml, median anion gap 6mEq/L (IQR 5-7) vs 7mEq/L (IQR 5-7) and median blood ketones 0.3mmol/L (IQR 0.1-0.5) vs 0.3 (IQR 0.1-0.5) in the PL and SC groups. DKA resolution at 48h occurred in 96% (PL) and 86% (SC) of patients; odds ratio 3.93 (95% CI 0.73-21.16, p = 0.111). At 24h, DKA resolution occurred in 69% (PL) and 36% (SC) of patients; odds ratio 4.24 (95% CI 1.68-10.72, p = 0.002). The median ICU and hospital lengths of stay were 49h (IQR 23-72) vs 55h (IQR 41-80) and 81h (IQR 58-137) vs 98h (IQR 65-195) in the PL and SC groups. Plasmalyte-148, compared to sodium chloride 0.9%, may lead to faster resolution of metabolic acidosis in patients with DKA without an increase in ketosis. These findings need confirmation in a large, Phase 3 trial.

Physicochemical properties of brand and generic infusion fluid preparations (Part 3): Investigation of type 1 hypotonic infusion fluids.

In Japan, the increasing use of generic drugs has led to a reduction in drug prices, which affect the steady supply of drugs. A "basic drug" system was introduced to rescue these drugs by eliminating gaps in drug prices among preparations with the same constituents. "Type 1" hypotonic infusion fluids, which are potassium-free and commonly used to treat dehydration, meet the definition of a "basic drug" in Japan, and there are no drug price gaps. However, there is a lack of information on the physicochemical properties of "type 1" hypotonic infusion fluids, making it difficult to identify differences among them. Extracellular fluid-replacement solutions and "type 3" hypotonic infusion fluids have different pH and titratable acidity. Here, we measured the pH, titratable acidity, and osmolality of six different "type 1" hypotonic infusion fluids and compared the results with respect to risk avoidance considering metabolic acidosis, changes upon mixing, and vascular pain. There was a significant difference, or trend toward significance, in titratable acidity, which is a risk factor for metabolic acidosis in patients with impaired renal function, and pH, which is a risk factor for change upon mixing, among all combinations except one of the infusion fluids. Thus, the selection of "type 1" hypotonic infusion fluids for children with immature renal function, elderly patients with impaired renal function, and patients with unknown pathophysiology, considering titratable acidity and pH, is an effective strategy for risk avoidance.

Acidosis, cognitive dysfunction and motor impairments in patients with kidney disease

ABSTRACTMetabolic acidosis, defined as a plasma or serum bicarbonate concentration <22 mmol/L, is a frequent consequence of chronic kidney disease (CKD) and occurs in ~10–30% of patients with advanced stages of CKD. Likewise, in patients with a kidney transplant, prevalence rates of metabolic acidosis range from 20% to 50%. CKD has recently been associated with cognitive dysfunction, including mild cognitive impairment with memory and attention deficits, reduced executive functions and morphological damage detectable with imaging. Also, impaired motor functions and loss of muscle strength are often found in patients with advanced CKD, which in part may be attributed to altered central nervous system (CNS) functions. While the exact mechanisms of how CKD may cause cognitive dysfunction and reduced motor functions are still debated, recent data point towards the possibility that acidosis is one modifiable contributor to cognitive dysfunction. This review summarizes recent evidence for an association between acidosis and cognitive dysfunction in patients with CKD and discusses potential mechanisms by which acidosis may impact CNS functions. The review also identifies important open questions to be answered to improve prevention and therapy of cognitive dysfunction in the setting of metabolic acidosis in patients with CKD.

The Association of Body Mass Index with the Development of Metabolic Acidosis in Patients with CKD

The Association of Body Mass Index with the Development of Metabolic Acidosis in Patients with CKD

Ureteral reconstruction for complex strictures: a review of the current literature.

Frequently employed procedures for ureteral reconstruction include balloon dilation, pyeloplasty and ureteral re-implants. However, these procedures do not work for complex ureteral disease. The goal of this literature review is to report on techniques and success rates for the following techniques: buccal graft ureteroplasty, appendiceal interposition, transureteroureterostomy, ileal ureter and autotransplantation. A comprehensive literature search for English-language original and review articles was conducted using PubMed. The following terms were queried: "ureteral reconstruction", "buccal graft", "appendiceal interposition", "ileal ureter", "transureteroureterostomy", "autotransplantation". Procedures involving the buccal mucosa or appendix offer minimally invasive techniques and low morbidity with good short-term success. Drawbacks to appendiceal interposition include the availability and length of appendix, and 10-20% of patients may have insufficient appendix upon intra-operative assessment. Transureteroureterostomy is typically limited to extensive exonerations due to concerns of injury to the contralateral kidney, even with reported success rates > 90%. Ileal ureter may carry a risk of metabolic acidosis in patients with renal insufficiency along with bowel-related complications. Ileal ureter and autotransplantation are reserved for the most severe cases due to their high morbidity but do offer options for the complex patient. Ureteral stricture disease not amenable to pyeloplasty, ureteroureterostomy or ureteroneocystostomy offers a challenge to urologist. Careful patient selection with pre-operative assessment of renal and bladder is vital to a successful operation with minimal complications.