Normal Anion Gap Metabolic Acidosis Research Articles

Unusual presentation of Sjogren’s syndrome during pregnancy: a case report

BackgroundPregnancy imposes significant physiological changes, including alterations in electrolyte balance and renal function. This is especially important because certain disorders might worsen and make people more susceptible to electrolyte abnormalities. One such condition is Sjogren's syndrome (SS), an autoimmune disease that can cause distal renal tubular acidosis (dRTA). This case report offers a unique perspective on the intricate physiological interplay during pregnancy, emphasizing the critical importance of recognizing and managing electrolyte abnormalities, particularly in the context of autoimmune disorders such as Sjogren’s syndrome.Case presentationWe report a case of a 31-year-old pregnant Indian woman at 24 weeks gestation presenting with fever, gastrointestinal symptoms, and progressive quadriparesis followed by altered sensorium. Severe hypokalaemia and respiratory acidosis necessitated immediate intubation and ventilatory support. Investigations revealed hypokalaemia, normal anion gap metabolic acidosis, and positive autoimmune markers for SS. Concurrently, she tested positive for IgM Leptospira. Management involved aggressive correction of electrolyte imbalances and addressing the underlying SS and leptospirosis.ConclusionThis case underscores that prompt recognition and management are paramount to prevent life-threatening complications in pregnant patients with autoimmune disease. This report sheds light on the unique challenge of managing hypokalaemic quadriparesis in the context of Sjogren’s syndrome during pregnancy.

Hypokalaemic paralysis due to underlying distal renal tubular acidosis as the first presentation of primary Sjogren’s syndrome: a case report

Sjögren syndrome is a systemic autoimmune disease that primarily affects the exocrine glands. A 36-year-old woman presented with sudden onset of bilateral lower limb weakness. She was noted to have hypokalaemia with a normal anion gap metabolic acidosis. Subsequent investigations revealed high ESR, positive ANA, absent dsDNA, normal C3, C4, positive anti-Ro and negative anti-La. Labial biopsy revealed a lymphocytic infiltrate and renal biopsy revealed tubulointerstitial nephritis. Sjogren’s syndrome rarely (less than 5%) presents for the first time as renal manifestations such as hypokalaemia related paralysis as a result of type I – distal renal tubular acidosis due to the underlying tubulointerstitial nephritis.

Neonatal Onset Distal Renal Tubular Acidosis: Description of Two Novel Variants on the ATP6V0A4 Gene and Review of the Literature on Associated Extrarenal Manifestations

AbstractDistal renal tubular acidosis (dRTA) is an extremely rare disease that affects the distal tubule's ability to excrete proton cations, acidify urine, and maintain the acid–base balance. The clinical presentation of dRTA typically includes normal anion gap metabolic acidosis with decreased serum bicarbonate levels, hypokalemia, hypercalcemia, nephrocalcinosis, and alkaline urine. Hereditary causes of dRTA include pathogenic variants in ATP6V1B1, ATP6V0A4, SLC4A1, FOXI1, and WDR72 genes, which encode different transmembrane proteins on the apical surface of type A intercalated cells in the distal tubule. Variants in these genes lead to various defects in the function of the encoded proteins and can also account for extrarenal manifestations of dRTA due to the expression of these proteins in other organs, such as the stria vascularis of the inner ear. However, the literature on extrarenal manifestations, associated renal complications of hereditary dRTA, and appropriate investigations, and follow-up for patients with dRTA is scarce. In this article, we present a challenging case of neonatal-onset dRTA and contribute two novel variants of the ATP6V0A4 gene and a novel phenotype associated with a pathogenic variant on ATP6V0A4 to the scientific community. We also review the existing literature on hereditary causes of dRTA, with emphasis on associated renal and extrarenal complications.

The elevation of the anion gap in steady state chronic kidney disease may be less prominent than generally accepted.

A presumed cause of metabolic acidosis in chronic kidney disease (CKD) is accumulation of unmeasured anions, leading to a high anion gap (AG). In patients with CKD with a high AG, only minor increases are expected. The aim of this study is to evaluate the magnitude of the AG in documented steady state CKD to examine the effect of CKD on a high-AG metabolic acidosis (HAGMA). In this cross-sectional study the AG, bicarbonate, and chloride were evaluated in 1045 blood and urine samples of 501 patients with steady state CKD in the outpatient clinic. The influence of phosphate, albumin and potassium on the AG were evaluated. The mean AG increased from 8.8mEq/l (±1.57) in CKD stage 1 to 11.2mEq/l (±2.22) in CKD stage 5 (P<0.001). Correction for albumin or phosphate did not influence the magnitude of the AG. Correction for potassium did alter the prevalence of HAGMA, but not the severity. [HCO3-] decreased between CKD stages 1 and 5 by 5.1mEq/l. The [Cl-] increased by 2.6mEq/l between CKD stages 1 and 5. The elevation of the AG in patients with steady state CKD is limited and less pronounced than the decrease in [HCO3-]. Normal AG metabolic acidosis seems to be more important in CKD than HAGMA. The CKD stage and the magnitude of the AG should be taken into account when evaluating a patient with HAGMA. This study suggests that an AG >15mEq/l is rarely due to renal failure alone.

RESPIRATORY FAILURE ASSOCIATED WITH DISTAL RENAL TUBULAR ACIDOSIS IN AN OLDER ADULT WITH SOUTHEAST ASIAN OVALOCYTOSIS AND CONCOMITANT THYROTOXIC ATRIAL FIBRILLATION

Distal renal tubular acidosis (dRTA) is characterized by hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis and metabolic bone disease. It has been associated with Southeast Asian Ovalocytosis (SAO), particularly in malaria endemic region. We present a case of an older adult with dRTA who presented with respiratory failure as a result of hyperchloremic normal anion gap metabolic acidosis, in association with nephrocalcinosis and SAO, however, without hypokalaemia due to concurrent acute kidney injury. Oxygen therapy was able to be weaned off after treatment with alkali supplementation. Distal RTA may be associated with SAO, and early recognition and treatment of dRTA is paramount in preventing complications such as chronic kidney disease, metabolic bone disease and life-threatening respiratory arrest.

Metabolic Acidosis in Children: A Literature Review

Metabolic acidosis is characterised by a primary decrease in the serum bicarbonate concentration, a secondary decrease in the arterial partial pressure of CO­2, and a reduction in blood pH. Metabolic acidosis, acute or chronic, may have deleterious effects on cellular function and cause increased morbidity and mortality. A systematic review of the available literature was performed to identify data on the prevalence, manifestations, cause, outcomes, and treatment of metabolic acidosis in children. Online databases (Ovid Medline, Embase, and PubMed), commercial search engines (including Google), and chapters on metabolic acidosis in the standard textbooks of paediatrics and medicine were reviewed. Systematic approach to acute metabolic acidosis starts with proper history taking and examination. This is followed by assessment of acid-base parameters, including pH, partial pressure of CO2, and bicarbonate concentration in arterial blood. Blood gas is needed to differentiate primary metabolic acidosis from compensated respiratory alkalosis. Once the diagnosis of a metabolic acidosis has been confirmed, serum electrolyte values are used to determine the serum anion gap. The various causes of increased and normal anion gap metabolic acidosis have been discussed in the article. The main aim of treatment in metabolic acidosis is to reverse the primary pathophysiology. In acute metabolic acidosis, sodium bicarbonate therapy is not beneficial due to potential complications and is reserved for specific situations. Base therapy is used in chronic metabolic acidosis where it ameliorates many of its untoward effects. Other modalities of treatment of metabolic acidosis include peritoneal or haemodialysis and tris-hydroxymethyl aminomethane.

Nephrolithiasis and/or nephrocalcinosis is significantly related to renal dysfunction in patients with primary Sjögren's syndrome.

The present study compared the clinical features of patients with primary Sjögren's syndrome (pSS) with and without nephrolithiasis and/or nephrocalcinosis to determine factors related to renal dysfunction. The clinical features of 68 patients with anti-Sjogren's syndrome antigen A (SSA)/Ro-antibody-positive pSS with and without nephrolithiasis and/or nephrocalcinosis who underwent abdominal computed tomography and/or ultrasonography were retrospectively analysed. Of the 68 patients with anti-SSA-antibody-positive pSS, 23 (33%) had renal nephrolithiasis and/or nephrocalcinosis, whereas 45 (67%) did not. Fourteen (20%) patients had renal dysfunction at diagnostic imaging. Among five patients who underwent renal biopsy, four patients with renal nephrolithiasis and/or nephrocalcinosis were diagnosed with tubulointerstitial nephritis, and one without nephrolithiasis and/or nephrocalcinosis was diagnosed with minimal change nephrotic syndrome. Estimated glomerular filtration rate at diagnostic imaging was significantly lower in patients with than without nephrolithiasis and/or nephrocalcinosis group (P = 0.010). In addition to nephrolithiasis and/or nephrocalcinosis (odds ratio [OR], 3.467; P = 0.045), the gap between serum sodium and chloride concentrations (OR, 10.400; P = 0.012) and increased urinary β2-microglobulin (OR, 5.444; P = 0.033) were associated with renal dysfunction at the time of diagnostic imaging. Nephrolithiasis and/or nephrocalcinosis, normal anion gap metabolic acidosis, and tubulointerstitial damage are associated with renal dysfunction in patients with pSS.

Diagnostic Evaluation of Renal Tubular Acidosis: A Clinical Biochemistry Perspective

Tight regulation of plasma pH is critical for cellular homeostasis. Physiological pH is maintained through a complex synergy of buffering, pulmonary modulation of carbon dioxide concentration, and regulation of systemic bicarbonate by the renal system. Renal tubular acidosis (RTA) describes a group of disorders in which the tubular excretion of acid is reduced despite relatively normal glomerular filtration. Several subtypes of RTA are known, all of which classically present with normal anion gap metabolic acidosis in addition to a variety of associated biochemical abnormalities. RTA can pose a diagnostic challenge to the clinician as it can be triggered by a substantial number of different aetiologies and clinical presentations can be highly variable. This review addresses the normal renal handling of acid-base, the renal response to high acid load, and the RTA pathologies where these acid-base homeostatic mechanisms are impaired. A particular focus of this review is the challenges faced by the biochemical laboratory regarding the development, validation and interpretation of suitable plasma and urine tests for accurate RTA diagnosis.

Normal Anion-Gap Metabolic Acidosis in an Extremely Preterm Neonate.

Extremely preterm neonates (< 28 wk) are at risk of metabolic complications like hypocalcemia, hypophosphatemia, hyponatremia, and metabolic acidosis. Many of these complications are often the result of prematurity per se, while some of them may be the result of prolonged parenteral nutrition. Most of the complications occur in the initial few weeks of hospital stay, but hyponatremia, hypocalcemia, and hypophosphatemia may persist for longer periods of time. Optimizing enteral nutrition along with fortification helps in promoting optimal growth and overcoming the aforementioned problems. The authors report one such extremely preterm neonate with hyperchloremic metabolic acidosis, the cause of which is uncommon and not reported previously in the literature.

ODP043 Hypokalemia in Autoimmune Polyglandular Syndrome: A Case of Newfound Type I (Distal) Renal Tubular Acidosis

Abstract Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy Type 1 (APECED) is a rare autosomal recessive disorder predisposing to early development of chronic mucosal candidiasis and progressive development of various endocrinopathies, such as Addison's disease, Primary Hypoparathyroidism, and Type 1 Diabetes (T1D). Few cases described in literature regarding renal involvement in this disorder, with most common manifestation being tubulo-interstitial nephritis, however, there is limited evidence regarding presentation of APECED with hypokalemia due to concomitant Type I Renal Tubular Acidosis (RTA). Case of a 47-year-old female with past medical history of APECED Type 1 (consisting of hypoparathyroidism, adrenal insufficiency, and chronic mucocutaneos candidiasis), T1DM on honeymoon, hypothyroidism, and nephrolithiasis presenting to the emergency department complaining of bilateral upper and lower extremity weakness of one week in evolution, but worsening on day of admission. Denies associated constitutional symptoms. Strong positive first-degree relative history for autoimmune diseases. Physical examination: 2/5 strength in all four extremities, deep tendon reflexes grossly intact, no gross sensory or motor deficits. Patient on oral steroid therapy for her Addison's, calcitriol supplementation for hypoparathyroidism, and potassium chloride supplementation since a prior hypokalemic episode 17 years ago. Laboratory workup results remarkable for sodium: 140 mmol/L (N: 135-144 mmol/L), chloride: 110 mmol/L (N: 95-105 mmol/L), potassium: 2. 0 mmol/L (N: 3.4-4.5 mmol/L), central bicarbonate: 18mmol/L (N: 23-31 mmol / L), anion gap: 12 (N: 10-12), glycosylated hemoglobin: 5.2% (N: 4.7-6.2%) and anti-glutamic acid decarboxylase antibodies &amp;gt;25,000 U/mL (N: &amp;lt;5 U/mL). Adrenal insufficiency was ruled out by laboratory findings, but she had normal anion gap metabolic acidosis (NAGMA) and hypokalemia. Urinalysis was negative for urinary tract infection but with pH: 7. 0 (N: 4.5-8. 0). Urine spots, measured to find the cause of her NAGMA, showed urine sodium: 92 mmol/L, urine potassium: 10 mmol/L, urine chloride: 90 mmol/L, and urine anion gap of 12 mEq/L, which is positive and suggests low urinary NH4+, consistent with Type I (Distal) RTA as the main etiology. Patient started on IV potassium replacement, which increased potassium to 3.8 mmol/L, and improved acidotic state, with central bicarbonate of 29mmol/L, and overall symptoms. Patient was discharged home with alkali therapy (Sodium citrate) for Type I (Distal) RTA. RTA is an underrecognized condition that may be inherited or acquired. Diagnosis is difficult but can be verified with a thoughtful workup. RTA should be considered for any patient with otherwise unexplained hyperchloremic metabolic acidosis and may be the presenting manifestation of autoimmune diseases. Regular renal monitoring for any APECED patient should be performed. We present this case as evidence for the coexistence of several different immune-mediated diseases in the clinical context of APECED with an unusual concomitant Type I (Distal) RTA, where there is few documented evidence of association with this disorder. Presentation: No date and time listed

Renal Tubular Acidosis in Pregnant Critically Ill COVID-19 Patients: A Secondary Analysis of a Prospective Cohort.

Background: Renal tubular acidosis (RTA) is an extremely rare cause of metabolic acidosis (10 in 100,000). RTA has been linked neither to pregnancy nor to severe coronavirus disease 2019 (COVID-19). The purpose of this study was to analyze the prevalence and clinical course of normal anion gap metabolic acidosis in critically ill pregnant COVID-19 patients and to compare them to an age-matched nonpregnant female patient cohort. Methods: Secondary analysis was conducted on a prospective observational cohort of critically ill patients suffering from COVID-19 consecutively admitted to a tertiary intensive care unit (ICU) between February 2020 and April 2021. Results: A total of 321 COVID-19 patients required admission to the ICU; 95 (30%) were female, and 18 (19%) were of childbearing age. Seven of eight (88%) pregnant women (all in the last trimester) required advanced respiratory support due to COVID-19. The estimated glomerular filtration rate was 135 (123–158) mL/min/m2 body surface area, and six pregnant women (86%) were diagnosed with a normal, respiratory compensated, anion gap metabolic acidosis (pHmin 7.3 (7.18–7.31), HCO3−min 14.8 (12.8–18.6) mmol/L, and paCO2 3.4 (3.3–4.5) kPa). Three (43%) acidotic pregnant women fulfilled diagnostic criteria for RTA. All women recovered spontaneously within less 7 days. Conclusions: Metabolic acidosis seems to be very common (85%) in pregnant critically ill COVID-19 patients, and the prevalence of RTA might be higher than normal. It remains to be demonstrated if this observation is an indirect epiphenomenon or due to a direct viral effect on the tubular epithelium.

Tenofovir-induced distal renal tubular acidosis: A rare cause of recurrent hypokalaemic paralysis

Tenofovir disoproxil fumarate was the first nucleotide analogue reverse transcriptase inhibitor to be approved for treatment of human immunodeficiency virus infection. It is a relatively safe drug but can present with nephrotoxicity. We report a case of 36-year-old male who presented with acute onset flaccid paraparesis. He was a diagnosed case of acquired immunodeficiency syndrome for 9 years ago and was on tenofovir-based antiretroviral therapy for last 6 months. As the patient had normal anion gap metabolic acidosis, hypokalaemia and urine pH > 5.5, distal renal tubular acidosis (RTA) was suspected. He improved dramatically within 24 h of hospitalisation after potassium correction to regain normal power. Tenofovir-induced distal RTA presenting as hypokalaemic paralysis is a very rare complication of tenofovir; hence, we are reporting this case. In addition, we suggest regular follow-up of patients taking tenofovir with urine analysis and serum potassium to detect this complication earlier as it is reversible.

Distal renal tubular acidosis and nephrocalcinosis as initial manifestation of primary sjögren's syndrome.

There is a well-established association between primary Sjögren's syndrome and distal renal tubular acidosis (dRTA). dRTA is a relatively infrequent manifestation of primary Sjögren's syndrome which can present with life-threatening electrolyte abnormalities while, in some patients, it could be the first manifestation of the syndrome. We report the case of a 35-year-old woman who presented with unexplained episodes of generalized weakness, severe hypokalemia, nephrocalcinosis, and normal anion gap metabolic acidosis. Subsequent evaluation revealed primary Sjögren's syndrome as her underlying condition. The patient responded well to potassium supplementation, sodium bicarbonate, and oral prednisolone. After four years of follow-up, there were no other extraglandular manifestations, the renal function remained stable and the acidosis was partially improved without the need for oral bicarbonate. This case demonstrates that dRTA could be the initial manifestation of primary Sjögren's syndrome and highlights the necessity for increased vigilance for patients presenting with persistent hypokalemia or nephrocalcinosis so that an early diagnosis can be made allowing for better control and prevention of disease progression.

COMPARISON OF TWO DIFFERENT MODALITIES OF BICARBONATE FOR DETERMINATION OF ANION GAP IN CRITICALLY ILL PATIENTS

OBJECTIVE: To compare anion gap estimated through measured and calculated bicarbonate modalities to be used interchangeably in critically ill metabolic acidosis patients. METHODS: This cross-sectional study was conducted at Rehman Medical Institute, Peshawar, Pakistan from September 2019 to March 2020.  Out of 390 critically ill patients, 200 cases of metabolic acidosis were selected by non-probability consecutive sampling technique. Measured and calculated bicarbonate values were obtained through Cobas-c 501© (Roche) using enzymatic method and Cobas-b 221© (Roche) blood gas analyzer respectively. Statistical analysis was done by using SPSS-23. RESULTS: Normal anion gap metabolic acidosis (NAG-MA) and high anion gap metabolic acidosis (HAG-MA) based on calculated bicarbonate levels was observed in 57 (28.5%) and 143 (71.5%) cases as compared to 55 (27.5%) and 145 (72.5%) cases based on measured bicarbonate levels respectively (p&gt;0.45). A significant correlation (r=0.888 and 0.656, r2=0.788 and 0.431) (p&lt;.001) was found between mean values of NAG-MA and HAG-MA respectively, when each was calculated through both modalities of bicarbonate. On applying Bland Altman plot, bias was 1.45±2.89 and -2.14±3.87mmol/L, Upper limit of agreement (LOA) was 7.13 and 5.46 for NAG-MA and HAG-MA, while lower LOA was -4.23 and -9.74 for NAG-MA and HAG-MA respectively. According to the model Bland Altman plot and Story &amp; Postuie criteria, bias and the levels of agreement were not appropriate to conclude that both entities of anion gap could be used interchangeably.  CONCLUSION: Normal and high anion gap metabolic acidosis estimated by measured and calculated bicarbonate cannot be used interchangeably in critically ill patients.

Abstract 13: Isolated bicarbonaturia: A rare case of proximal renal tubular acidosis

Case Report: A 9 years old girl presented to us with progressive bowing of legs since 2 years of age and failure to gain height since 5 years of age. She had previously received calcium and Vitamin D supplements multiple times since the age of 2 years. Her parents noticed knock knees since 5 years of age. She had undergone corrective surgery for deformity before admission. On examination, Bone age <Height age< Chronological age. Height was less than 3rd percentile and weight was 50th percentile. On evaluation, she had hyperchloremic normal anion gap metabolic acidosis and positive urinary anion gap, no evidence of nephrocalcinosis. She was having bicarbonaturia but no glucosuria, aminoaciduria, phosphaturia. So possibly a case of isolated bicarbonaturia. For this, a more common candidate gene SLC4A4 mutation was tested but was negative. Since there can be many other candidate genes involved, testing each and every potential gene couldn’t be done. Meanwhile patient was started on sodium bicarbonate, calcitriol, calcium and vitamin D supplementation.Conclusion: As an isolated defect for bicarbonate transport, proximal RTA is rare and is more often associated with Fanconi syndrome. Many candidate genes could be involved in the etiology yet to be discovered.

Transient Type 3 Renal Tubular Acidosis during Cyclic Vomiting Syndrome

Type 3 renal tubular acidosis is a pathological condition characterized by the simultaneous occurrence of distal renal tubular acidosis, which causes urinary acidification disorders, and proximal renal tubular acidosis, which causes impaired reabsorption of bicarbonate ions. Type 3 renal tubular acidosis is considered rare. A 5-year-old boy was admitted to our hospital because of frequent vomiting, poor vitality, and fever. He was diagnosed with cyclic vomiting syndrome. Type 3 renal tubular acidosis was also diagnosed because of severe mixed metabolic acidosis with impaired urinary acidification, a low tubular phosphorus reabsorption rate with hypophosphatemia, low-molecular-weight proteinuria, pan-aminoaciduria, and glucosuria. Fluid infusion was performed. On the second day of hospitalization, the vomiting disappeared and the patient was able to eat and drink. He was discharged on the eighth day of hospitalization. The laboratory test abnormalities associated with the renal tubular acidosis gradually improved, and testing at discharge on the eighth day of admission showed no metabolic acidosis, hypophosphatemia, low-molecular-weight proteinuria, or glucosuria. These findings suggested that the type 3 renal tubular acidosis was transient. Severe metabolic acidosis was observed in this patient because of both normal anion gap metabolic acidosis due to type 3 renal tubular acidosis and anion gap metabolic acidosis due to cyclic vomiting syndrome. Although type 3 tubular acidosis is rare, the resultant metabolic acidosis worsens when combined with a disease that causes metabolic acidosis. Type 3 tubular acidosis should be ruled out when severe metabolic acidosis is present.

High-Anion-Gap Metabolic Acidosis During a Prolonged Hospitalization Following Perforated Diverticulitis: An Educational Case Report.

The metabolic acidoses are generally separated into 2 categories on the basis of an anion gap calculation: high-anion-gap and normal anion-gap metabolic acidosis. When a high-anion-gap metabolic acidosis (HAGMA) is not clearly explained by common etiologies and routine confirmatory testing, specialized testing can definitively establish rare diagnoses such as 5-oxoproline, d-lactate accumulation, or diethylene glycol toxicity. A 56-year-old woman had a prolonged hospital admission following perforated diverticulitis requiring sigmoid resection. Her hospitalization was complicated by feculent peritonitis and surgical wound dehiscence needing prolonged broad-spectrum antibiotics and wound debridements. She developed acute kidney injury and HAGMA in the hospital. Chart review showed that she received a large cumulative dose of acetaminophen during her hospital stay. Laboratory studies showed markedly increased serum 5-oxoproline causing HAGMA. Patient was admitted to the intensive care unit and treated with N-acetylcysteine and renal replacement therapy. After admission to the intensive care unit, the patient continued to require vasopressor and ventilatory support for septic shock and a ventilator-associated pneumonia. After an initial recovery and resolution of her HAGMA, she subsequently suffered recurrent aspirations which were fatal. 1. The acronym GOLD MARK is useful when assessing patients with HAGMA and most causes of HAGMA can be established with routine testing.2. When the etiology of HAGMA remains unclear, additional testing can be required to diagnose rare causes of HAGMA.3. Rare causes of HAGMA are diethylene glycol, 5-oxoproline, and d-lactate accumulation.4. Acidosis secondary to 5-oxoproline accumulation can occur even with "therapeutic" doses of acetaminophen in patients receiving it regularly for a prolonged period and who have depleted glutathione stores.5. Risk factors for glutathione depletion include malnutrition, older age, sepsis, pregnancy, multiple chronic illnesses, and chronic kidney disease.

Hyperchloremic Metabolic Acidosis in Diabetic Ketoacidosis – Boon or Bane in Paediatrics? Prospective Cohort Study

Introduction: Patients with DKA generally present with a high anion gap metabolic acidosis (AG &gt; 16) due to the presence of ketones but may also develop a narrow anion gap metabolic acidosis related to hyperchloremia. This study attempts to determine the incidence of hyperchloremic metabolic acidosis (before starting IV fluids) in children with DKA and to evaluate the impact of hyperchloremic metabolic acidosis on acute kidney injury and cerebral edema and inturn on mortality and duration of PICU stay.  Methods: This was a prospective study conducted in the Department of Paediatrics, VIMS, Bellary between May 2016 to December 2017 and a total of 32 patients with DKA were enrolled in the study. Along with routine investigations, ABG and serum chloride levels were measured at the time of admission for categorization into normochloremic (high anion-gap) metabolic acidosis and hyperchloremic (normal anion-gap) metabolic acidosis. Incidence of hyperchloremic metabolic acidosis and its impact on the development of acute kidney injury and cerebral edema was taken as the primary outcome of the study. Mortality rate and duration of PICU stay were taken as a secondary outcome.  Results: Hyperchloremic metabolic acidosis was observed in 18.8% of the study group. Acute kidney injury was seen in 38.4% of children who had normochloremic metabolic acidosis and in 83.3% of children with hyperchloremia. About 50% patients developed cerebral edema in the hyperchloremia group and only 3.8% developed cerebral edema in normochloremic group. These differences were statistically significant. Mortality rate in normochloremic and hyperchloremic metabolic acidosis was 3.8% and 50% respectively. Conclusions: Hyperchloremia at presentation in DKA is a risk factor for increased mortality. This fact should be born in mind while treating patients aggressively with chloride-containing fluids. Simple investigations like ABG and serum chloride levels can direct careful management of DKA and appropriate selection of IV fluids.

Metabolic Acidosis and Hyponatremia in a Patient With Metastatic Melanoma

A 72-year-old man with a history of metastatic melanoma and hypertension presented to the hospital with a 2-week duration of weakness and fatigue. He also reported poor appetite and decreased oral intake but no weight loss. He denied shortness of breath, lightheadedness, syncope, nausea, vomiting, or diarrhea. He also denied headache, confusion, polyuria, or polydipsia. Home medications included amlodipine 10 mg once a day, lisinopril 10 mg once a day, and pembrolizumab 200 mg intravenously every 3 weeks. The latter was started 3 months prior to admission and he had recently completed 3 cycles of therapy. On admission, he had blood pressure of 118/78 mm Hg and heart rate of 62 beats per minute. Initial work-up was notable for hyponatremia with serum sodium level of 120 mg/dL and metabolic acidosis with total CO2 of 16 mmol/L. Other laboratory results are shown in Table 1. A spot urinary protein-creatinine ratio was 0.12 mg/mg, and urine pH was 6.0. Urine analysis did not show any microscopic hematuria or pyuria. There was no glycosuria.Table 1Laboratory Findings on Admission and Work-upValueReference RangeSodium, mmol/L120136-145Potassium, mmol/L3.63.5-5.3Bicarbonate, mmol/L1621-32Chloride, mmol/L9098-107Creatinine, mg/dL0.60.5-1.3SUN, mg/dL86-23Phosphorus, mg/dL2.62.5-4.9Aldosterone, ng/dL5.00.0-30.0TSH, mIU/L1.040.44-3.98ACTH, pg/mL5.17.2-63.3Cortisol AM, μg/dL1.02.5-20.0Aldolase, U/L2.43.3-10.3LH, IU/L3.81.5-9.3 (adult male)FSH, IU/L8.22-10 (adult male)DHEA, μg/dL1228-290Urine sodium, mmol/L52Urine potassium, mmol/L19Urine chloride, mmol/L63Urine osmolality, mOsm/kg299200-1,200Abbreviations: ACTH, adrenocorticotropic hormone; DHEA, dehydroepiandrosterone; FSH, follicle-stimulating hormone; LH, luteinizing hormone; TSH, thyroid-stimulating hormone. Open table in a new tab Abbreviations: ACTH, adrenocorticotropic hormone; DHEA, dehydroepiandrosterone; FSH, follicle-stimulating hormone; LH, luteinizing hormone; TSH, thyroid-stimulating hormone. Computed tomography scan of the abdomen was normal. Other laboratory studies including titers of serum antinuclear antibody, anti-neutrophil cytoplasmic antibody, and anti-SSA/SSB; tests for hepatitis B and C virus; and levels of C3 and C4 were all unrevealing.•What is the general differential diagnosis for hyponatremia in a patient with cancer?•What is the most likely cause of this patient’s metabolic acidosis?•What is the cause of hyponatremia in this patient? Hyponatremia is frequently associated with cancers and it is commonly caused by inappropriate secretion of antidiuretic hormone, or the syndrome of inappropriate antidiuresis (SIAD). There are various causes of SIAD in a cancer patient: it may be a result of ectopic vasopressin production by tumor cells or a consequence of stimulation of vasopressin secretion or potentiation of vasopressin effects by anticancer drugs or palliative medications. There are many traditional chemotherapeutic treatments that can cause hyponatremia. Recently, immune checkpoint inhibitors have revolutionized the treatment of various solid tumors. There are adverse kidney effects associated with these drugs, including hyponatremia. New targeted therapies have also been associated with the development of hyponatremia and possibly SIAD. Diagnosis of the etiology of hyponatremia is necessary in order to provide appropriate treatment. Laboratory assessments, including measurements of plasma osmolality, urine osmolality, and urine sodium, and clinical assessment of extracellular volume status are critical to the differential diagnosis of hyponatremia. This patient had normal anion gap metabolic acidosis with positive urine anion gap and low positive urine osmolar gap (<150 mOsm/kg). This combination, in the absence of kidney failure, raises the possibility of a renal tubular acidosis (RTA). For this patient, the laboratory work-up is highly suggestive of a distal RTA (high urine pH and absence of features that are typically seen with a proximal RTA and Fanconi syndrome, such as hypophosphatemia and glucosuria). Although this condition is normally associated with hypokalemia, simultaneous adrenal insufficiency could have offset this finding. Distal or type I RTA is a tubulopathy characterized by dysfunction of distal urinary acidification, which subsequently can lead to a normal anion gap metabolic acidosis.1Mustaqeem R. Arif A. Renal Tubular Acidosis. [Updated 2020 Aug 16]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan.https://www.ncbi.nlm.nih.gov/books/NBK519044/Google Scholar Common causes include autoimmune diseases, drugs, genetic diseases, and tubulointerstitial diseases; however, in many cases a cause is not identified.1Mustaqeem R. Arif A. Renal Tubular Acidosis. [Updated 2020 Aug 16]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan.https://www.ncbi.nlm.nih.gov/books/NBK519044/Google Scholar In our patient, we suspected the distal RTA to be secondary to a renal immunotherapy-related adverse event (irAE). Distal RTA is an emerging irAE that has not been well recognized. There are only few case reports and case series thus far describing this phenomenon.2El Bitar S, Weerasinghe C, El-Charabaty E, Odaimi M. Renal tubular acidosis an adverse effect of PD-1 inhibitor immunotherapy. Case Rep Oncol Med. 2018 Jan 31;2018:8408015. doi:10.1155/2018/8408015Google Scholar, 3Herrmann S.M. Alexander M.P. Romero M.F. Zand L. Renal tubular acidosis and immune checkpoint inhibitor therapy: an immune-related adverse event of PD-1 inhibitor - a report of 3 cases.Kidney Med. 2020; 2: 657-662Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar, 4Charmetant X. Teuma C. Lake J. Dijoud F. Frochot V. Deeb A. A new expression of immune checkpoint inhibitors' renal toxicity: when distal tubular acidosis precedes creatinine elevation.Clin Kidney J. 2019; 13: 42-45Crossref PubMed Scopus (9) Google Scholar, 5Atiq S.O. Gokhale T. Atiq Z. Holmes R. Sparks M.A. A case of pembrolizumab induced distal renal tubular acidosis.Journal of Onco-Nephrology. 2021; 5: 23-26Crossref Google Scholar However, distal RTA being an immune-mediated phenomenon is not a novel concept, as there are a range of autoimmune diseases that have been associated with distal RTA. Distal RTA is also perhaps an underdiagnosed disease among patients receiving immune checkpoint inhibitors, as it is typically asymptomatic and associated with concurrent decreased kidney function. There has been extensive literature characterizing the various endocrinopathies associated with immune checkpoint inhibitors, including primary adrenal insufficiency, hypothyroidism, hyperthyroidism, and hypophysitis.6Barroso-Sousa R. Barry W.T. Garrido-Castro A.C. et al.Incidence of endocrine dysfunction following the use of different immune checkpoint inhibitor regimens: a systematic review and meta-analysis.JAMA Oncol. 2018; 4: 173-182Crossref PubMed Scopus (477) Google Scholar Although the risk of immune checkpoint inhibitor–associated adrenal insufficiency is less than 1%, it is still associated with significant morbidity and mortality.2El Bitar S, Weerasinghe C, El-Charabaty E, Odaimi M. Renal tubular acidosis an adverse effect of PD-1 inhibitor immunotherapy. Case Rep Oncol Med. 2018 Jan 31;2018:8408015. doi:10.1155/2018/8408015Google Scholar, 3Herrmann S.M. Alexander M.P. Romero M.F. Zand L. Renal tubular acidosis and immune checkpoint inhibitor therapy: an immune-related adverse event of PD-1 inhibitor - a report of 3 cases.Kidney Med. 2020; 2: 657-662Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar, 4Charmetant X. Teuma C. Lake J. Dijoud F. Frochot V. Deeb A. A new expression of immune checkpoint inhibitors' renal toxicity: when distal tubular acidosis precedes creatinine elevation.Clin Kidney J. 2019; 13: 42-45Crossref PubMed Scopus (9) Google Scholar, 5Atiq S.O. Gokhale T. Atiq Z. Holmes R. Sparks M.A. A case of pembrolizumab induced distal renal tubular acidosis.Journal of Onco-Nephrology. 2021; 5: 23-26Crossref Google Scholar, 6Barroso-Sousa R. Barry W.T. Garrido-Castro A.C. et al.Incidence of endocrine dysfunction following the use of different immune checkpoint inhibitor regimens: a systematic review and meta-analysis.JAMA Oncol. 2018; 4: 173-182Crossref PubMed Scopus (477) Google Scholar In our patient, we suspected that the patient had hypophysitis, which precipitated an adrenal insufficiency. This was supported by low levels of ACTH and cortisol. Hyponatremia is common in cancer patients receiving immune checkpoint inhibitors, and acute hyponatremia secondary to pembrolizumab has been reported.7Desikan S.P. Varghese R. Kamoga R. Desikan R. Acute hyponatremia from immune checkpoint inhibitor therapy for non-small cell lung cancer.Postgrad Med J. 2020; 96: 570-571Crossref PubMed Scopus (1) Google Scholar,8Seethapathy H. Rusibamayila N. Chute D.F. et al.Hyponatremia and other electrolyte abnormalities in patients receiving immune checkpoint inhibitors.Nephrol Dial Transplant. 2020; (gfaa272)https://doi.org/10.1093/ndt/gfaa272Crossref Scopus (11) Google Scholar However, endocrinopathies are an uncommon cause of severe hyponatremia in patients who receive an immune checkpoint inhibitor.8Seethapathy H. Rusibamayila N. Chute D.F. et al.Hyponatremia and other electrolyte abnormalities in patients receiving immune checkpoint inhibitors.Nephrol Dial Transplant. 2020; (gfaa272)https://doi.org/10.1093/ndt/gfaa272Crossref Scopus (11) Google Scholar The combination of hyponatremia, RTA, and adrenal insufficiency in this patient is highly suggestive that his hyponatremia was secondary to adrenal insufficiency, which in turn we considered as an irAE. The patient was started on hydrocortisone 40 mg daily. This was accompanied by improvement in serum sodium and bicarbonate levels. Two days later, the patient’s hyponatremia and metabolic acidosis had resolved. He was eventually discharged on a tapering dose of steroids. Rapid resolution of both conditions upon initiation of steroids suggests that they are both immune-mediated adverse effects associated with pembrolizumab. Immune-mediated central adrenal insufficiency causing hyponatremia and combined with distal RTA secondary to immune checkpoint inhibitor therapy. Dayyan Adoor, MD, Hafsa Tariq, MD, and Arash Rashidi, MD. None. The authors declare that they have no relevant financial interests. The authors declare that they have obtained consent from the patient reported in this article for publication of the information about him that appears within this Case Report. Received April 27, 2021. Direct editorial input from a Deputy Editor. Accepted in revised form May 21, 2021.

Latent Systemic Lupus Erythematosus Presenting as Acute Ascending Paralysis: A Case Report

Here I report a 29-year old woman who presented with acute ascending paralysis and required mechanical ventila­tion due to severe hypokalaemia. She was found to have normal anion gap metabolic acidosis due to distal renal tu­bular acidosis. She had American College of Rheumatology classification criteria compatible with diagnosis of latent Systemic Lupus Erythematosus (SLE). She was successfully treated with potassium citrate and sodium bicarbonate supplementation. The case is noteworthy as an atypical presentation of SLE.