Evidence for abnormal linkage between urine oxalate and citrate excretion in human kidney stone formers

Abstract Background Animal models have demonstrated an interactive relationship between the epithelial anion exchanger SLC26A6 and transporter NaDC‐1 that regulates citrate and oxalate homeostasis. This relationship is a potential mechanism to protect against kidney stones as higher urine oxalate is accompanied by higher urine citrate but it has not been explored in humans. Methods We examined 24‐h urine data on 13,155 kidney stone forming patients (SF) from separate datasets at the University of Chicago and Litholink, a national laboratory, and 143 non‐kidney stone forming participants (NSF) to examine this relationship in humans. We used multivariate linear regression models to examine the association between oxalate and citrate in all study participants and separately in SF and NSF. Results Higher urinary oxalate was associated with higher urinary citrate in both SF and NSF. In NSF, the multivariate adjusted urine citrate excretion was 3.0 (1.5–4.6) (mmol)/creatinine (mmol) per oxalate (mmol)/creatinine (mmol). In SF, the multivariate adjusted urine citrate excretion was 0.3 (0.2–0.4) (mmol)/creatinine (mmol) per oxalate (mmol)/creatinine (mmol). Conclusions Higher urinary oxalate excretion was associated with higher urinary citrate excretion and this effect was larger in non‐kidney stone forming participants compared with those who form kidney stones.

Introduction: Kidneys are one of the more commonly affected non-exocrine glands by Sjögren's syndrome.Renal involvement includes glomerulonephritis, interstitial nephritis, or both.Chronic TIN is the most common renal manifestation in Sjögren's syndrome.Clinical manifestations of TIN present as abnormalities of tubular function such as Fanconi syndrome, Distal RTA and Nephrogenic DI.
Case Description: 26 y/o Hispanic female with no known past medical history present with nausea and vomiting at 21 weeks gestation of her second pregnancy.Workup was significant for elevated creatinine with proteinuria and pyuria, normal anion gap metabolic acidosis, hypokalemia, and hyphosphatemia.Urine studies revealed an inappropriately alkaline urine with impaired renal reclamation of potassium and phosphorous.Serological workup was significant for positive ANA, SSA, and SSB antibodies.Kidney biopsy revealed acute tubulointerstitial nephritis.The patient was started on an IV steroid course with oral taper and hydroxychloroquine with improvement in Cr from 2.2 to 1.2 mg/dL.with a potassium, phosphate and sodium bicarbonate supplementation regimen.
Discussion: Sjögren's syndrome is typically associated with lymphocytic infiltration of exocrine glands.However, this can also affect the kidneys causing tubulointerstitial nephritis and defects in tubular function initiating a cascade of electrolyte abnormalities.Understanding the renal physiology behind the observed electrolyte abnormalities is important to optimize our treatment regimen.While the management of a distal RTA that has been well described in Sjögrens syndrome typically involves judicious potassium and alkali supplementation, this case highlights the worsening potassium wasting and phosphorous wasting which also needs to be addressed with a concomitant proximal tubulopathy.We propose that this set of features can best be explained by dysfunctional carbonic anhydrase, a cause of the extremely rare type III RTA.We use this case presentation to highlight the spectrum of renal manifestations of Sjogren's syndrome and their treatment principles.

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Mineral Homeostasis and Acid-Base Disorders: Clinical Background: Bone is the largest body buffer and body mass index (BMI) is directly related to bone mass.We explored the relationship between BMI and incident metabolic acidosis in patients with CKD.
Methods: Optum's de-identified Integrated Claims-Clinical dataset of US patients (2007-2019) was queried to identify patients with non-dialysis CKD stages 3-5 with 2 consecutive serum bicarbonate values in the normal range (22 to <30 mEq/L), 28-365 days apart, with data ≥12 months pre-index during which covariates were assessed.The first qualifying serum bicarbonate test established the index date.The primary exposure variable was BMI category (World Health Organization classification).Other exposures included hypertension diagnosis, triglycerides ≥1.7 mmol/L, HDL cholesterol ≤1 mmol/L in women or ≤0.9 mmol/L in men.Adjusted Cox Proportional Hazards models were performed to evaluate the time to development of new-onset metabolic acidosis (serum bicarbonate 12 to <22 mEq/L) over a follow-up period of ≤11.5 years.Other covariates included age, sex, race, education and income status, diabetes or heart failure, eGFR, log albumin-to-creatinine ratio, angiotensin converting enzyme inhibitors or angiotensin receptor blockers prescription, and diuretic prescription.
Conclusions: In this large cohort of patients with CKD, an incremental increase in BMI was inversely associated with the development metabolic acidosis.The mechanism of this association merits further study.

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Mineral Homeostasis and Acid-Base Disorders: Clinical

Effects of Pseudohyponatremia on the Diagnosis of Severe Metabolic Acidosis
Hafiz Muhammad Ali Raza, 1 Barry M. Wall.Introduction: Pseudohyponatremia is defined as falsely low sodium levels in plasma caused by severe hyperlipidemia or hyperproteinemia.We discuss a case of pseudohyponatremia due to hypertriglyceridemia in a patient admitted with severe metabolic acidosis and acetaminophen induced liver toxicity.
Case Description: 43-year-old male with hyperlipidemia, diabetes mellitus, and obesity presented with 4 day-history of abdominal pain, nausea, vomiting, and polydipsia.He had decreased intake and was not taking his insulin for 4 days.Medications include glargine insulin, dulaglutide, empagliflozin, glimepiride, rosuvastatin, fenofibrate and losartan.BP:141/59 mmHg, HR:125 bpm, respirations 28/min, Temperature: 98.7, SpO2.95% on room air.He appeared clinically volume depleted.Laboratory testing revealed severely lipemic serum, elevated acetaminophen level 44.1 ug/ml, severely elevated transaminases, arterial pH: 7.03, pCO2 11 mmHg, HCO3 <5 mEq/l.Plasma sodium:109 mEq/L and chloride 81 mEq/l using indirect potentiometry and 131 and 111 mEq/l using direct potentiometry.Serum triglycerides 2951 mg/dl, blood glucose 204 mg/dl, plasma lactate 7.5 mmol/l, and creatinine 0.6 mg/dl.Plasma anion gap was 11 mEq/l using direct potentiometry and could not be calculated using indirect potentiometry, as bicarbonate concentration could not be determined due to lipemia.Based on severe metabolic acidosis, elevated lactate, and positive urinary ketones, a diagnosis of lactic acidosis and suspected euglycemic DKA was made.Patient was treated with DKA-protocol with insulin and fluid resuscitation, and N-acetylcysteine for acetaminophen induced liver toxicity.Metabolic acidosis markedly improved over the next 72 hours.Hypertriglyceridemia, transaminase elevations, and metabolic acidosis fully resolved during 6 week follow up visit.
Discussion: Severe hyperlipidemia reduces water content of plasma such that autoanalyzers utilizing indirect potentiometry requiring sample dilution, result in pseudohyponatremia.Direct potentiometry does not require sample dilution and measures true sodium concentration, however, plasma anion gap is reduced due to higher measured chloride concentrations with direct potentiometry.Therefore, physicians must be familiar with the laboratory methods to correctly interpret the plasma anion gap in mangagement of metabolic acidosis when using direct potentiomery measurements.

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Mineral Homeostasis and Acid-Base Disorders: Clinical

The Association of Body Mass Index with the Development of Metabolic Acidosis in Patients with CKD
1,2 1 The University of Tennessee Health Science Center College of Medicine, Memphis, TN; 2 VA Memphis Medical Center, Memphis, TN.

Anion Gap Metabolic Acidosis on Continuous Renal Replacement Therapy: Are You Missing Something?
Mustafa Dawood, Vandana D. Niyyar.Emory University School of Medicine, Atlanta, GA.Anion gap metabolic acidosis is a common metabolic abnormality seen in the clinical practice.Causes includes Lactic acidosis, Ketoacidosis, Renal failure, volatile acid toxicity and salicylate poisoing.Ketoacidosis is due to decreased glucose and insulin availability leading to starvation ketosis and diabetic ketoacidosis respectively.Ketoacidosis is uncommonly seen in patients on prolonged continuous renal replacement therapy.We present 2 cases at Grady Hospital admitted with Acute hypoxic Respiratory Failure due to COVID 19 pneumonia, developed euglycemic ketoacidosis on Continuous Renal Replacement Therapy Case Description: case 1: 73 male with the history of HTN, DM, CKD III admitted for acute hypoxic respiratory failure due to COVID 19 pneumonia.He was intubated on admission day 9. Course got complicated by hypotension during intubation leading to Acute Renal Failure on day 11.Patient was started on Renal Replacement Therapy on day 12 due to volume overload and acidosis.Day 19, Anion gap worsened and betahydroxybutyrate was elevated.Patient was started on insulin drip with resolution of acidosis on day 20.Case 2: 48 yo male with the history of HTN, DM II, CKD stage III admitted for Altered mental status, hypertensive emergency and cough.He was diagnosed with COVID 19 Pneumonia.Patient had non oliguric acute kidney injury on admission.Hospital day 11, patient was oliguric, volume overloaded and hyperkalemia prompted Renal replacement therapy initiation.Day 14, Anion gap worsened and betahydroxybutyrate was elevated.Tube feed were initiated and Dialysate prescription was reduced leading to resolution of anion gap on day 12. Discussion: Diabetic ketoacidosis is a medical emergency commonly in patients with Type I DM but also in Type II DM patients as well.It occurs due to decrease insulin concentration or increase insulin resistance with or without decreased glucose availability leading to release of counterregulatory hormone and fatty acid metabolism producing ketoacids.Diagnostic criteria include pH <7.3, Serum HCO3 <18, Serum glucose >250 mg/dl and positive serum +/-Urine ketones.Euglycemic DKA is a subtype of DKA with serum glucose of <200 mg/dl.Incidence of Euglycemic DKA varies from 2.6-3.2%.Continuous renal replacement therapy is an under-recognized cause of Euglycemic DKA in patients with Diabetes Mellitus. Introduction: