A 55-year-old woman with a history of insulin-dependent diabetes mellitus was admitted for glucose optimization prior to bilateral salpingo-oophorectomy for ovarian masses. Nephrology was consulted after routine morning laboratory measurements revealed a bicarbonate of 12 mEq/L and an anion gap of 22 mEq/L (Table 1). Inpatient medications included insulin, and acetaminophen as needed. She revealed that a few weeks prior, she was started on a sodium/glucose cotransporter 2 (SGLT2) inhibitor but that she had not taken it in more than 1 week. Her serum glucose was 232 mg/dL and serum creatinine was 1.03 mg/dL (corresponding to an estimated glomerular filtration rate of 61 mL/min/1.73 m2). Her examination was unremarkable and she was asymptomatic.•What could be the cause of the high anion gap?•What could be the cause of the low bicarbonate concentration?•What additional testing is warranted in this clinical scenario?Table 1Laboratory Values From Venous Blood Sample at 8 AMParameterValueReference RangeGlucose, mg/dL23270-139SUN, mg/dL206-24Creatinine, mg/dL1.030.57-1.30Sodium, mEq/L140135-145Potassium, mEq/L4.13.6-5.1Chloride, mEq/L10698-110Bicarbonate, mEq/L1220-30Calculated anion gap, mEq/L22Triglycerides, mg/dL485240-250Total cholesterol, mg/dL649110-199HDL cholesterol, mg/dL1235-75LDL cholesterol, mg/dL310-129 Open table in a new tab Presence of an elevated anion gap is most often indicative of an increase in unmeasured anions in the form of organic acids or, less commonly, in the setting of hyperalbuminemia or presence of anionic paraprotein.1Kraut J.A. Madias N.E. Serum anion gap: its uses and limitations in clinical medicine.Clin J Am Soc Nephrol. 2007; 2: 162-174https://doi.org/10.2215/CJN.03020906Crossref PubMed Scopus (240) Google Scholar Use of the mnemonic “GOLDMARK” (glycols, oxoproline, L-lactate, D-lactate, methanol, aspirin, renal failure, and ketoacidosis) can assist in finding the etiology of the high anion gap.2Mehta A.N. Emmett J.B. Emmett M. GOLD MARK: an anion gap mnemonic for the 21st century.Lancet. 2008; 372: 892https://doi.org/10.1016/S0140-6736(08)61398-7Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar There was no history of toxic alcohol, aspirin, or long-term acetaminophen ingestion. Serum osmolar gap was 6 mOsm/kg and toxicology studies did not show presence of ethanol, salicylates, or acetaminophen. Serum lactate was normal and there was no clinical concern for d-lactic acidosis. Serum beta-hydroxybutyrate was not elevated and her urinalysis did not show any ketones (euglycemic ketoacidosis from SGLT2 inhibitors would result in elevated beta-hydroxybutyrate levels). Serum bicarbonate can be measured using different techniques. Analysis of blood chemistries can be performed either by enzymatic reactions to generate products that are quantified by spectrophotometry or by ion-specific electrode (ISE) techniques that use either indirect or direct measurement. Venous samples are typically analyzed by spectrophotometry or indirect ISE methods, while arterial blood gas samples use the direct ISE method. Turbidity in the blood sample can scatter light and produce inaccurate spectrophotometric results. In addition, dilution of the blood samples, as is needed for enzymatic and indirect ISE techniques, can cause further inaccuracies owing to incorrect assumptions about the distribution of water and solids in the sample (“space-occupying effect”). This space-occupying effect is classically taught as causing pseudo-hyponatremia in the setting of either hyperlipidemia or hyperproteinemia (Fig 1). Hyperlipidemia can affect a broad number of chemistries, most notably sodium, potassium, and chloride.3Dimeski G. Mollee P. Carter A. Effects of hyperlipidemia on plasma sodium, potassium, and chloride measurements by an indirect ion-selective electrode measuring system.Clin Chem. 2006; 52: 155-156https://doi.org/10.1373/clinchem.2005.054981Crossref PubMed Scopus (46) Google Scholar Importantly, use of ISE techniques can overcome the light-scattering effect and use of direct ISE can overcome the space-occupying effect. Most commonly, serum bicarbonate is measured using the enzymatic technique, which assumes a normal distribution of water and solids in the sample. In the absence of a clinical reason or other laboratory evidence for an acidosis other than a low serum bicarbonate, measurement error should be considered. On further discussion with our laboratory colleagues, it was noted that the blood sample from the patient was lipemic and that testing had revealed a triglyceride level of 4852 mg/dL and a total cholesterol level of 649 mg/dL. In the setting of lipemia, the chemistry analyzers had been programmed to not report sodium, potassium, and chloride concentrations and to prompt the technicians to reanalyze those electrolytes using a blood gas analyzer (using direct ISE). However, there was no such prompt to reanalyze bicarbonate. Use of direct ISE was warranted in this scenario, since this provides a calculated serum bicarbonate concentration using the Henderson-Hasselbalch equation after directly measuring pH and pCO2 and avoids errors due to any space-occupying effect. An arterial blood gas was obtained 5 hours after the patient’s morning laboratory testing and revealed a pH of 7.43, bicarbonate of 23 mEq/L, and a pCO2 of 36 mm Hg. The arterial blood sample revealed a normal anion gap of 9 mEq/L. This arterial blood bicarbonate measurement of 23 meq/L was confirmed by reanalyzing the patient’s initial venous blood sample using a blood gas analyzer (direct ISE), which resulted in a calculated bicarbonate of 24 mEq/L. Thus, the patient’s venous measured bicarbonate level of 12 mEq/L was inaccurate owing to the light scattering and/or a space-occupying effect of high triglyceride levels.4Rifkin S. Shaub B. Factitious hypobicarbonatemia associated with profound hyperlipidemia.Ren Fail. 2014; 36: 1155-1157https://doi.org/10.3109/0886022X.2014.917945Crossref PubMed Scopus (11) Google Scholar,5Carag C. Baxi P.V. Behara V. Gashti C. Rodby R. Pseudo-anion gap metabolic acidosis from severe hypertriglyceridemia corrected by plasma exchange.Clin Nephrol. 2019; 92: 258-262https://doi.org/10.5414/CN109627Crossref PubMed Scopus (4) Google Scholar Pseudo–anion gap elevation due to pseudo-hypobicarbonatemia in the setting of previously undiagnosed hypertriglyceridemia. Fellowship Program HighlightNote from editors: To recognize fellowship programs’ educational mission, AJKD is using its popular Quiz feature to highlight Nephrology Fellowship programs when an author is a Nephrology Fellow. To participate, Fellowship Program Directors mentor fellows in submitting prospective Quizzes; those that are selected for publication include a brief description of the fellowship program from the Director. For “Low Serum Bicarbonate in a Patient With Diabetes Mellitus” the corresponding author is Vladimir Mushailov, who was a Nephrology Fellow at Tufts Medical Center at the time the Quiz was submitted.Program: Tufts Medical Center Nephrology Fellowship Training Program (https://www.tuftsmedicalcenter.org/patient-care-services/departments-and-services/nephrology/training-education)Program Director: Scott Gilbert, MDProgram Description: The Nephrology Fellowship Training Program at Tufts Medical Center is designed to provide trainees with the opportunity to achieve the fundamental knowledge, procedural expertise, practical experience, and professional and ethical skills necessary for the subspecialty of Nephrology. Fellows care for patients with the full spectrum of kidney disorders at all stages of the disease process. Efforts are made at every point to emphasize the integration of medical knowledge, compassionate care, and social, psychological, and economic issues. The program offers 2 distinct fellowship tracks: a 2-year Clinical Track and a 3-year Clinical-Research Track. In the first year of the Clinical Track, fellows participate in 12 months of clinical rotations along with twice-weekly half-day continuity clinics and a monthly home dialysis continuity clinic. The second year comprises advanced clinical rotations, a series of focused study blocks to develop expertise in a specific domain, a weekly half-day continuity clinic, management of an outpatient hemodialysis shift, and a monthly home dialysis continuity clinic. The Clinical-Research Track devotes 2 years to research training and 1 year to clinical training (which is identical to the first year of the Clinical Track). In the first year of research training, fellows are enrolled in the master’s program in Clinical and Translational Sciences at the Sackler School of Graduate Biomedical Sciences of Tufts University. They participate in mentored research, attend a weekly half-day continuity clinic, and manage a hemodialysis shift. The second year involves completion of the master’s thesis and the master’s degree, and a weekly half-day continuity clinic. Note from editors: To recognize fellowship programs’ educational mission, AJKD is using its popular Quiz feature to highlight Nephrology Fellowship programs when an author is a Nephrology Fellow. To participate, Fellowship Program Directors mentor fellows in submitting prospective Quizzes; those that are selected for publication include a brief description of the fellowship program from the Director. For “Low Serum Bicarbonate in a Patient With Diabetes Mellitus” the corresponding author is Vladimir Mushailov, who was a Nephrology Fellow at Tufts Medical Center at the time the Quiz was submitted. Program: Tufts Medical Center Nephrology Fellowship Training Program (https://www.tuftsmedicalcenter.org/patient-care-services/departments-and-services/nephrology/training-education) Program Director: Scott Gilbert, MD Program Description: The Nephrology Fellowship Training Program at Tufts Medical Center is designed to provide trainees with the opportunity to achieve the fundamental knowledge, procedural expertise, practical experience, and professional and ethical skills necessary for the subspecialty of Nephrology. Fellows care for patients with the full spectrum of kidney disorders at all stages of the disease process. Efforts are made at every point to emphasize the integration of medical knowledge, compassionate care, and social, psychological, and economic issues. The program offers 2 distinct fellowship tracks: a 2-year Clinical Track and a 3-year Clinical-Research Track. In the first year of the Clinical Track, fellows participate in 12 months of clinical rotations along with twice-weekly half-day continuity clinics and a monthly home dialysis continuity clinic. The second year comprises advanced clinical rotations, a series of focused study blocks to develop expertise in a specific domain, a weekly half-day continuity clinic, management of an outpatient hemodialysis shift, and a monthly home dialysis continuity clinic. The Clinical-Research Track devotes 2 years to research training and 1 year to clinical training (which is identical to the first year of the Clinical Track). In the first year of research training, fellows are enrolled in the master’s program in Clinical and Translational Sciences at the Sackler School of Graduate Biomedical Sciences of Tufts University. They participate in mentored research, attend a weekly half-day continuity clinic, and manage a hemodialysis shift. The second year involves completion of the master’s thesis and the master’s degree, and a weekly half-day continuity clinic. Vladimir Mushailov, MD, Gary Horowitz, MD, and Taimur Dad, MD, MS. None. The authors declare that they have no relevant financial interests. The authors declare that they have obtained written consent from the patient reported in this article for publication of the information about her that appears within this Quiz. Received April 29, 2022. Direct editorial input from the Engagement Editor. Accepted in revised form August 12, 2022.