Urine Anion Research Articles

Revisiting the Urinary Anion Gap: A Sound Concept during Hyperchloremic Metabolic Acidosis

Revisiting the Urinary Anion Gap: A Sound Concept during Hyperchloremic Metabolic Acidosis

#1294 The impact of plant-based diet on renal function and metabolic profile in kidney transplant recipients

Abstract Background and Aims Controlling and reducing protein intake is the most used approach to preserve renal function in CKD patients. Compared to protein restriction alone, plant-based diets have received particular attention. However, data on the potential risks and benefits of a plant-based diet in kidney transplant patients remains sparse, and evidence in this population is indirect. The primary purpose of this study was to evaluate if a plant-based diet affects proteinuria and eGFR in renal transplant patients. Establishing whether it influences acid load, glycolipid profile, nutritional status, and performance status were secondary objectives. Method 26 renal transplant recipients with eGFR >20 ml/min/1.73 m², urinary protein excretion >0.5 g/day, and transplant age >1 year were considered eligible for the study. Enrolled subjects underwent dietary assessment and biochemical tests at baseline, three and six months after starting the plant-based diet. All subjects underwent performance tests: sit-to-stand and handgrip tests. Results Only 18 patients were included in the statistical analysis. After six months, no significant changes in levels of proteinuria, urinary anion gap, triglycerides, and grip strength were detected. However, there was a statistically significant reduction in total cholesterol (p=0.03), LDL (p=0.04), and fasting blood sugar levels (p=0.001). A statistically significant reduction in eGFR (p=0.033) was observed, likely the regression of the previous hyperfiltration caused by the animal protein diet. A significant improvement was found in sit-to-stand test performance (p=0.037). Finally, a direct relationship between azoturia and urinary anion gap was observed. Conclusions The work carried out has highlighted how some of the potential benefits of the plant-based diet may also be relevant among kidney transplant patients. The plant-based diet is also associated with improved performance tests.

Beyond the Urine Anion Gap: In Support of the Direct Measurement of Urinary Ammonium

Ammonium is a major urinary buffer that is necessary for the normal excretion of the daily acid load. Its urinary rate of excretion (UNH4) may be increased several fold in the presence of extrarenal metabolic acidosis. Therefore, measurement of UNH4 can provide important clues about causes of metabolic acidosis. Because UNH4 is not commonly measured in clinical laboratories, the urinary anion gap (UAG) was proposed as its surrogate about 4 decades ago, and it is still frequently used for that purpose. Several published studies strongly suggest that UAG is not a good index of UNH4 and support the concept that direct measurement of UNH4 is an important parameter to define in clinical nephrology. Low UNH4 levels have recently been found to be associated with a higher risk of metabolic acidosis, loss of kidney function, and death in persons with chronic kidney disease, while surrogates like the UAG do not recapitulate this risk. In order to advance the field it is necessary for the medical community to become more familiar with UNH4 levels in a variety of clinical settings. Herein, we review the literature, searching for available data on UNH4 under normal and various pathological conditions, in an attempt to establish reference values to interpret UNH4 results if and when UNH4 measurements become available as a routine clinical test. In addition, we present original data in 2 large populations that provide further evidence that the UAG is not a good predictor of UNH4. Measurement of urine NH4 holds promise to aid clinicians in the care of patients, and we encourage further research to determine its best diagnostic usage.

DISTAL RENAL TUBULAR ACIDOSIS WITH SEVERE HYPOKALEMIA – A CASE REPORT

Background: Renal tubular acidosis is a group of transport defects secondary to either reduced distal secretion of hydrogen ion or decreased proximal tubular reabsorption of bicarbonate or both, resulting in impaired acidication of urine with persistent hyperchloremic metabolic acidosis. Our case is that of a 5-year-old female child presenting with failure to thrive and weakness.Clinical description and Investigations: Physical examination revealed skeletal deformities with enamel defects. Subsequent blood tests and arterial blood gas analysis revealed hyperchloremic metabolic acidosis with hypokalemia. Urine analysis revealed a positive urinary anion gap with hypercalciuria and hypocitraturia. Imaging studies revealed skeletal changes secondary to rickets and USG whole abdomen showed bilateral kidney nephrocalcinosis. Oral ammonium chloride loading was given and blood and urine pH were monitored every hour for the next 6 hours but the urine pH failed to fall below 5.3 which led us to a diagnosis of distal renal tubular acidosis. Bicarbonate and potassium citrate supplementation was given alongTreatment: with vitamin D and calcium to this child. Timely diagnosis and initiation of appropriate supplementation can help in improving theConclusion: quality of life of these patients.

Simultaneous analysis of six inorganic anions in urine by double-suppress ion-exchange chromatography.

This study is aimed to establish a simple, rapid, and accurate ion chromatography approach for the simultaneous detection of six inorganic anions in urine. Various performance parameters affecting the determination of anions were optimized, including the selection of sample protein precipitation agent, eluent, and flow rate. The final eluent was 3.6mmol/L sodium carbonate and 12% isopropanol with a flow rate of 0.6mL/min. Acetonitrile was used for pretreatment to precipitate proteins, and the volume ratio of urine to acetonitrile was 1:4. The correlation coefficient of the target anion calibration curve ranged from 0.9973 to 0.9999. The limit of detection ranged from 1.50 to 12.0 μg/L, and the method detection limit ranged from 15.0 to 120 μg/L. The standard recovery rate for low, medium, and high concentrations ranged from 90 to 110%. The inter-day and intra-day relative standard deviations were<5%. The method has high accuracy and good reproducibility and is suitable for the separation and determination of anions in urine.

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.

POS-090 CYSTINOSIS: A RARE BUT TREATABLE CAUSE OF PROXIMAL RENAL TUBULAR ACIDOSIS

Cystinosis is a rare lysosomal storage disorder which is characterized by defective cystine transporter and accumulation of cystine in lysosomes of cells of various body organs. Most common and severe presentation is in infancy as Fanconi syndrome (infantile nephropathic cystinosis). Incidence of cystinosis is 1 in 1 to 2 lakh newborns; with high incidence in Europe and UK. In India total 19 cases are registered with Cystinosis Society of India. The most common reported Indian mutation is p. Ser141Phe in contrast to 57Kb deletion affecting first 10 exons of CTNS which is commonly reported in Europe. We report a 23 months old male child of Indian origin, born out of non-consanguineous marriage, who presented with acute gastroenteritis and seizure. On examination, child had severe dehydration, pallor, signs of rickets, failure to thrive and polyuria even in the state of dehydration. Initial evaluation revealed a S. creatinine 2.62mg/dl. After fluid resuscitation renal functions improved (nadir S. creatinine 0.82mg/dl). As per mother the child had increased frequency of urination since age of 7 months with history of hospitalization twice for dehydration and dyselectrolytemia at the age of 8 months and 10 months. During follow up period, child had persistent hyperchloremic metabolic acidosis and low serum phosphate.Urine analysis revealed- proteinuria (2+, 100mg/dl), glycosuria (sugar 1+ , 100mg/dl) and phosphaturia. Urinary anion gap was positive; Urine chromatography was suggestive of generalized aminoaciduria. Ultrasound abdomen was normal. On the basis of above findings, the diagnosis of proximal renal tubular acidosis was made. Eye evaluation was suggestive of fine crystals deposition in cornea. In view of possibility of cystinosis, Genetic analysis by next generation sequencing was done which confirmed novel mutation in cystinosine gene (NM_001031681.2: c.771_793delGGGACCACGTGGCTGCAGT;p.Gly258SerfsTer30). Child was started treatment with cysteamine capsules and eyedrops along with bicarbonate, vitamin D, calcium and phosphorus supplements. On treatment child started gaining height and weight, urine output decreased and S. creatinine continued to be at nadir value of 0.8 mg/dl. Renal tubular acidosis may be just a clinical presentation of an underlying systemic disorder, therefore relevant clinical examination with need based molecular testing should be done. As early diagnosis forms the key to specific therapy for long term favorable outcome.

Hypokalemic Periodic Paralysis and Renal Tubular Acidosis in Patient withHypothyroidism

Hypokalemiaperiodic paralysis (HPP) is a rare disorder characterized by acute muscle paralysis. Basedon its etiology, HPP can be classified as primary and secondary types. One of the most common causes ofsecondary HPP is renal tubular acidosis (RTA) which may be also present in thyroid disease. We observed acase of a 48-year-old female, with complaints of weakness in both lower extremities for two days. Difficultiesin walking and weakness in both arms were also present. Patient also experienced nausea, vomiting, anddiarrhea 4 days before coming to the hospital. She had a history of thyroidectomy in 2009 and in 2019 wasadmitted for similar symptoms. Medication consumed by the patient were Euthyrox 100 mg one time dailyand KSR 600 mg three times daily. In the last week, Euthyrox was discontinued by the patient due to herdiarrhea. The patient’s general condition was weak and vital signs were BP 120/80 mmHg, pulse 84 bpm, RR18 times per minute and temperature was 36.6°C. Motoric strength was 4/4 in both arms and 3/3 in both legs.No pathological neurological reflexes were found during examination. Inverted T wave and prominent Uwave were seen on electrocardiogram (ECG) results.Laboratory results showed hypokalemia (2.0 mmol/L),Blood Gas Analysis: Metabolic Acidosis (pH 7.42, pCO2 32 mmHg, HCO3 20.8 mmol/L, BE -3.7 mmol/L)with anion gap of 14.2 meq/L. Urinalysis results were pH 8, urinary anion gap 18.29 mmol/h. Decreasedthyroid function was also shown in the endocrine laboratory panel FT4 0.57 ng/dl and TSH 32.097 IU/mL.HPP is a disorder characterized by muscle weakness and may be present in distal type RTA. Clinicalsymptoms of distal type RTA are hypokalemia, hyperchloremic metabolic acidosis, urinary pH &lt;5.5. Distaltype RTA can be caused by endocrine disorder i.e., hypothyroidism. Observation of patient condition andlaboratory results lead to the conclusion that the patient is diagnosed with hypokalemic periodic paralysisand renal tubular acidosis based on hypokalemia, metabolic acidosis with normal anion gap, and alkalineurine with positive urinary anion gap.

The Urine Anion Gap: Common Misconceptions.

Two papers, one in 1986 and another one in 1988, reported a strong inverse correlation between urinary anion gap (UAG) and urine ammonia excretion (UNH4) in patients with metabolic acidosis and postulated that UAG could be used as an indirect measure of UNH4 This postulation has persisted until now and is widely accepted. In this review, we discuss factors regulating UAG and examine published evidence to uncover errors in the postulate and the design of the original studies. The essential fact is that, in the steady state, UAG reflects intake of Na, K, and Cl. Discrepancy between intake and urinary output of these electrolytes (i.e, UAG) indicates selective extrarenal loss of these electrolytes or nonsteady state. UNH4 excretion, which depends, in the absence of renal dysfunction, mainly on the daily acid load, has no consistent relationship to UAG either theoretically or in reality. Any correlation between UAG and UNH4, when observed, was a fortuitous correlation and cannot be extrapolated to other situations. Furthermore, the normal value of UAG has greatly increased over the past few decades, mainly due to increases in dietary intake of potassium and widespread use of sodium salts with anions other than chloride as food additives. The higher normal values of UAG must be taken into consideration in interpreting UAG.

A colorimetric indicator-displacement assay based on stable Cu2+ selective carbon dots for fluorescence turn-on detection of pyrophosphate anions in urine

Determination of PPi levels in urine represents a measurable factor for diagnostic, treatment, and monitoring of urolithiasis. Owing to the quenching ability of Cu2+ on fluorescent carbon dots (CDs) and strong binding affinity between Cu2+ and PPi, we develop a new off–on assay for PPi detection using newly BPHA CDs (BPHA: N,N-bis(pyridin-2-ylmethyl)hexan-1-amine). The fluorescence intensity of BPHA CDs was significantly quenched by Cu2+ (“off”) through forming BPHA CDs/Cu2+ complexes and the fluorescence intensity of BPHA CDs /Cu2+ system was completely resumed by PPi (“on”) owing to the release of free Cu2+. The fluorescence turn-off/on approach showed a highly selective response to PPi over the large family of other anions. The detection limits were 0.094 μM for Cu2+ and 0.025 μM for PPi, respectively. A wide linear range for PPi was up to 4400 μM. The indicator displacement assay (IDAs) using pyrocatechol violet (PV) as a colorimetric indicator was carried out to detect PPi with the naked eyes. The “off–on” fluorescent sensor based on BPHA CDs shows many merits, including convenient operation, cost-saving, high sensitivity, selectivity, stability and wide detecting range, which is applied to PPi detection in human urine sample.

Utility of urinary organic anion transporter 5 as an early biomarker of obstructive nephropathy.

Ureteral obstruction is a relevant cause of kidney damage. The traditional parameters used in clinical practice for the detection of renal injury are insensitive and non-specific for the diagnosis of obstructive renal disease. The organic anion transporter 5 (Oat5) is a carrier expressed exclusively in the kidney. In this study, the Oat5 urinary excretion (Oat5u ) was evaluated as a potential biomarker of obstructive nephropathy, comparing it with traditional markers of renal function and with neutrophil gelatinase-associated lipocalin in urine (NGALu ), a more recent biomarker of renal pathology. Bilateral ureteral obstruction (BUO) was induced in male Wistar rats, by complete ligation of ureters for 1hour (BUO1), 2hours (BUO2), 5hours (BUO5), or 24hours (BUO24). After 24hours of ureteral releasing, urea and creatinine plasma concentrations, creatinine clearance, urinary total proteins, urinary glucose, and alkaline phosphatase activities in urine were evaluated. Oat5 and NGAL levels were assessed in urine samples by immunoblotting. All parameters of renal function were altered in the BUO24 and some also in BUO5, while the Oat5u increased in all of the experimental groups analyzed. After a long time of ureteral obstruction (BUO24), the urinary excretion of Oat5 markedly increased, in parallel with the alteration in the other parameters evaluated. Nevertheless, in BUO1 and BUO2, Oat5u appeared as the only parameter modified. Therefore, Oat5u could be proposed as a novel early biomarker of ureteral obstruction, with the additional potential to inform about the severity of the obstructive injury suffered by the kidney.

SUN-060 LATE PRESENTATION OF NEPHROTOXICITY DUE TO OXALIPLATIN

Oxaliplatin is a third-generation platinum derivative and considered less nephrotoxic than Cisplatin. It is frequently used as part of chemotherapy to treat various gastrointestinal tumors. Although hypokalemia, ATN and acute nephrotoxicity in the form of renal tubular acidosis due to Oxaliplatin has been reported; long term nephrotoxic effects of Oxaliplatin are not known. We report a novel case of 57- year old male who presented with muscle aches and electrolyte disturbances, several months after receiving oxaliplatin based chemotherapy. Patient had a premorbid history of diabetes mellitus, hypertension and he was diagnosed to have intrahepatic cholangiocarcinoma with neuroendocrine differentiation in September 2018. His creatinine was normal 74 umol/L at baseline. He received five cycles of chemotherapy with FOLFIRINOX (Folinic acid, Flourouracil, Irinotecan and Oxaliplatin). After five cycles he developed Oxaliplatin related ileus and nephropathy causing ATN and required few sessions of hemodialysis. Subsequently his kidney function improved partially with a new elevated baseline creatinine which was stable at 133 umol/L in February 2019. He presented on 28th September 2019 with severe muscle aches to emergency department (ED). His investigations done in ED revealed severe hypokalemia K 1.9 mmol/L, worsening of renal function, baseline creatinine had risen from 133 umol/L to 205 umol/L, he had severe metabolic acidosis with tCO 2 10, with normal anion gap 15 (range 7-16) and hyperchloremia 111 mmol/L, pH was 7.15. His serum phosphorus was low (0.63 mmol/L). Magnesium was normal. Urinary TTKG was calculated and was suggestive of urinary potassium loss. His Urinary Anion Gap was negative. He had glycosuria 4 + even though his blood sugars were well controlled. His urine pH was 5.5. Patient was treated with very high doses of potassium tricitrate and phosphorus supplements. He was discharged home after normalization of electrolytes and acid base status. Proximal renal tubular acidosis (type 2, pRTA) / Fanconi’s syndrome is characterized by bicarbonate wasting and low serum bicarbonate, proximal tubular dysfunction also leads to poor absorption of other substances, like glucose and phosphate. Further investigations were carried out to rule out other causes of Fanconi’s syndrome / Type 2 renal tubular acidosis in this patient. ANA, dsDNA, SPEP, IFE and serum Free light chain assay were all unremarkable. His Lactate was normal. A diagnosis of Fanconi’s syndrome and renal tubular acidosis type 2 (Proximal) due to remote exposure with Oxaliplatin was made. Fanconi’s syndrome due to platinum based drugs like Cisplatin and Oxaliplatin has been reported in Literature. Persistence of subtle partial renal tubular defects is well noted even after many months to years of exposure of Cisplatin but not with Oxaliplatin. We believe this is the first report of Type 2 pRTA and Fanconi’s syndrome presenting several months after exposure to Oxaliplatin. Physicians should be aware of unexpected late nephrotoxicity with Oxaliplatin use.

Acidosis tubular renal como presentación clínica de Síndrome de Sjögren: reporte de caso

We present the clinical case of a woman in the fifth decade of life, argentina, who went to the Internal Medicine emergency room of a third level hospital for symptoms of myalgia and paresis in all four extremities, acute onset, progressive, with difficulty for the mobilization of members superior, standing and walking. Severe hypokalemia, metabolic acidosis, alkaline urinary pH, positive urinary anion GAP (ammonium excretion), hypocitraturia and hypercalciuria were diagnosed. Renal Tubular Acidosis (RTA) type I was diagnosed; acute renal failure was also noted, which corrected with the treatment and elevated creatine kinase (CK). In the anamnesis, the patient reported dry syndrome associated with arthralgias of years of evolution, so that complementary studies were carried out that supported the diagnosis of Sjögren’s Syndrome (SS).

Distal renal tubular acidosis and severe hypokalemia: a case report and review of the literature

BackgroundDistal renal tubular acidosis is a relatively infrequent condition with complex pathophysiology that can present with life-threatening electrolyte abnormalities.Case presentationWe describe a case of a 57-year-old Caucasian woman with previous episodes of hypokalemia, severe muscle weakness, and fatigue. Upon further questioning, symptoms of dry eye and dry mouth became evident. Initial evaluation revealed hyperchloremic metabolic acidosis, severe hypokalemia, persistent alkaline urine, and a positive urinary anion gap, suggestive of distal renal tubular acidosis. Additional laboratory workup and renal biopsy led to the diagnosis of primary Sjögren’s syndrome with associated acute tubulointerstitial nephritis. After potassium and bicarbonate supplementation, immunomodulatory therapy with hydroxychloroquine, azathioprine, and prednisone was started. Nonetheless, her renal function failed to improve and remained steady with an estimated glomerular filtration rate of 42 ml/min/1.73 m2. The literature on this topic was reviewed.ConclusionsCases of renal tubular acidosis should be carefully evaluated to prevent adverse complications, uncover a potentially treatable condition, and prevent the progression to chronic kidney disease. Repeated episodes of unexplained hypokalemia could be an important clue for diagnosis.

Renal aspects of metabolic acid-base disorders in neonates.

Acid-base homeostasis is one of the most tightly regulated systems in the body. Maintaining the acid-base balance is particularly challenging for preterm infants and growing neonates. The kidney, which represents the crucial ultimate line of defense against disturbances of acid-base balance, undergoes a complex maturation process during the transition from a fetal to an extra-uterine environment. This review article summarizes the physiology of acid-base regulation by the immature human kidney and discusses disorders of acid-base balance, such as metabolic acidosis, respiratory acidosis, metabolic alkalosis, and respiratory alkalosis. In conditions of metabolic acidosis, the serum anion gap and the urinary anion gap can be useful tools to define the nature of the acidosis. Metabolic acidosis can reflect a decrease in glomerular filtration rate, or be the consequence of selective disorders of proximal or distal tubular function. Most tubulopathies associated with metabolic acidosis observed in neonates are primary, hereditary, isolated tubulopathies. Proximal renal tubular acidosis is characterized by bicarbonate wasting, while the distal types of renal tubular acidosis are secondary to distal acidification defects. All tubulopathies are associated with hypokalemia, with the exception of type 4 hyperkalemic distal renal tubular acidosis. The transporter defects in the various acid-base tubulopathies are now well defined. Treatment of the acidosis varies according to the site and mechanism of the defect. Chronic renal tubular acidosis or alkalosis severely impair growth and calcium metabolism. Early rational therapeutic intervention can prevent some of the consequences of the disorders and improves the prognosis.

Validation of a Capillary Electrophoresis Assay for Monitoring Iodine Nutrition in Populations for Prevention of Iodine Deficiency: An Interlaboratory Method Comparison.

A capillary electrophoresis (CE) assay was recently introduced as a new method for monitoring iodine nutrition in large-scale epidemiological studies. However, further tests revealed unanticipated matrix-dependent interferences when analyzing submicromolar levels of iodide in human urine as the predominate ionic form of dietary iodine. Herein, we describe a rigorous validation study that was used to identify sources of bias and establish modifications to the original CE method to improve method accuracy. An interlaboratory method comparison using CE with UV detection and inductively coupled plasma-mass spectrometry (ICP-MS) was performed to quantify urinary iodide concentrations (n = 71) independently at McMaster University and Hamilton General Hospital, as well as the CDC as part of their quality assurance program. A positive bias in the original CE method was indicated, and buffer conditions were subsequently optimized to overcome matrix interferences for reliable iodine status determination. Positive bias in CE was attributed to variable concentrations of sulfate, a major urinary anion interference with similar mobility to iodide under the conditions originally reported. By increasing the concentration of α-cyclodextrin in the background electrolyte, the CE method was able to tolerate urinary sulfate over its normal physiological range without loss in signal response for iodide. The optimized CE assay generated results that were consistent with ICP-MS using 2 different internal standards (187Re and 130Te) with a median bias under 10%. CE offers a simple, selective, and cost-effective separation platform for surveillance of the iodine status of a population requiring only small volumes (<10 μL) of biobanked urine specimens, which is comparable to previously validated screening methods currently used in global health initiatives for prevention of iodine deficiency disorders.

Application of the highly basic nano-sized anionite for the capillary electrophoresis separation and on-line concentration of inorganic anions

In this study, the possibilities of using the highly basic nano-sized anionite based on the anionite AB-17 as a modifier of the background electrolyte (BGE) in the capillary electrophoresis (CE) for the separation of inorganic anions was investigated. The influence of the concentration of nano-sized anionite in BGE on the velocity and direction of EOF as well as on the efficiency ( N , t.p./m) and peaks resolution (R) of inorganic anions was determined. It was established that the addition of the highly basic nano-sized anionite to the BGE (with the concentration of functional groups of nano-sized anionite more than 0.1 mM) leads to the reversal of the EOF. This indicates the dynamic modification of the silica capillary walls by the particles of nano-sized anionites and leads to the better efficiency (up to 1 200* 10 3 t.p./m) and increased resolution of inorganic anions compared to BGE containing conventional cationic surfactant – CTAB. Various on-line concentration technics were applied to decrease the LOD of analytes. The LOD of inorganic anions with UV detection and nano-sized anionite as a modifier of BGE were 8-30 ng/ml in case of field amplified sample stacking and 1pg/ml – 7μg/ml for the electro stacking respectively. Thus, the new method of simultaneous electrophoretic determination of 8 inorganic anions was developed and realized for the quantitative analysis of inorganic anions in urine. Key words : capillary electrophoresis, inorganic anions, strong basic nano-sized anionite, on-line concentration (Russian) DOI: http://dx.doi.org/10.15826/analitika.2017.21.1.004 Dzema D.V., Kartsova L.A., Polikarpova D.A. Saint-Petersburg State University, Institute of Chemistry 7/9 Universitetskaya nab., St. Petersburg, 199034, Russian Federatin

Real-time urinary electrolyte monitoring after furosemide administration in surgical ICU patients with normal renal function.

BackgroundAlthough the loop-diuretic furosemide is widely employed in critically ill patients with known long-term effects on plasma electrolytes, accurate data describing its acute effects on renal electrolyte handling and the generation of plasma electrolyte alterations are lacking. We hypothesized that the long-term effects of furosemide on plasma electrolytes and acid–base depend on its immediate effects on electrolyte excretion rate and patient clinical baseline characteristics. By monitoring urinary electrolytes quasi-continuously, we aimed to verify this hypothesis in a cohort of surgical ICU patients with normal renal function.MethodsWe retrospectively enrolled 39 consecutive patients admitted to a postoperative ICU after major surgery, and receiving single low-dose intravenous administration of furosemide. Urinary output, pH, sodium [Na+], potassium [K+], chloride [Cl−] and ammonium [NH4+] concentrations were measured every 10 min for three to 8 h. Urinary anion gap (AG), electrolyte excretion rate, fractional excretion (Fe) and time constant of urinary [Na+] variation (τNa+) were calculated.ResultsTen minutes after furosemide administration (12 ± 5 mg), urinary [Na+] and [Cl−], and their excretion rates, increased to similar levels (P < 0.001). After the first hour, urinary [Cl−] decreased less rapidly than [Na+], leading to a reduction in urinary AG and pH and an increment in urinary [NH4+] (P < 0.001). Median urinary [Cl−] over the first 3-h period was higher than baseline urinary and plasmatic [Cl−] (P < 0.001). During the first 2 h, difference between FeCl− and FeNa+ increased (P < 0.05). Baseline higher values of central venous pressure and FeNa+ were associated with greater increases in FeNa+ after furosemide (P = 0.03 and P = 0.007), whereas higher values of mean arterial and central venous pressures were associated with a longer τNa+ (P < 0.05). In patients receiving multiple administrations (n = 11), arterial pH, base excess and strong ion difference increased, due to a decrease in plasmatic [Cl−].ConclusionsLow-dose furosemide administration immediately modifies urinary electrolyte excretion rates, likely in relation to the ongoing proximal tubular activity, unveiled by its inhibitory action on Henle’s loop. Such effects, when cumulative, found the bases for the long-term alterations observed. Real-time urinary electrolyte monitoring may help in tailoring patient diuretic and hemodynamic therapies.Electronic supplementary materialThe online version of this article (doi:10.1186/s13613-016-0168-y) contains supplementary material, which is available to authorized users.

Thyroid antagonists and thyroid indicators in U.S. pregnant women in the Vanguard Study of the National Children's Study

The sodium iodide-symporter (NIS) mediates uptake of iodide into thyroid follicular cells. This key step in thyroid hormone synthesis is inhibited by perchlorate, thiocyanate (SCN) and nitrate (NO3) anions. When these exposures occur during pregnancy the resulting decreases in thyroid hormones may adversely affect neurodevelopment of the human fetus. Our objectives were to describe and examine the relationship of these anions to the serum thyroid indicators, thyroid stimulating hormone (TSH) and free thyroxine (FT4), in third trimester women from the initial Vanguard Study of the National Children's Study (NCS); and to compare urine perchlorate results with those in pregnant women from the National Health and Nutritional Examination Survey (NHANES).Urinary perchlorate, SCN, NO3, and iodine, serum TSH, FT4, and cotinine were measured and a food frequency questionnaire (FFQ) was administered to pregnant women enrolled in the initial Vanguard Study. We used multiple regression models of FT4 and TSH that included perchlorate equivalent concentration (PEC, which estimates combined inhibitory effects of the anions perchlorate, SCN, and NO3 on the NIS). We used multiple regression to model predictors of each urinary anion, using FFQ results, drinking water source, season of year, smoking status, and demographic characteristics. Descriptive statistics were calculated for pregnant women in NHANES 2001–2012.The geometric mean (GM) for urinary perchlorate was 4.04µg/L, for TSH 1.46mIU/L, and the arithmetic mean for FT4 1.11ng/dL in 359 NCS women. In 330 women with completed FFQs, consumption of leafy greens, winter season, and Hispanic ethnicity were significant predictors of higher urinary perchlorate, which differed significantly by study site and primary drinking water source, and bottled water was associated with higher urinary perchlorate compared to filtered tap water. Leafy greens consumption was associated with higher urinary NO3 and higher urinary SCN. There was no association between urinary perchlorate or PEC and TSH or FT4, even for women with urinary iodine <100µg/L. GM urinary perchlorate concentrations in the full sample (n=494) of third trimester NCS women (4.03µg/L) were similar to pregnant women in NHANES (3.58µg/L).

A Rare Cause of Sudden Onset- Severe Metabolic Acidosis in Paediatric Surgical Patients- Organic Acidemia.

Sir, A one-year-old male, weighing 7 kg, suddenly developed recurrent vomiting, tachypnea and became lethargic 6 hours after cicumcision. Circumcision was done under sedation using intravenous midazolam and fentanyl. He was afebrile and blood sugar was normal at the time of presentation. On systemic examination, chest was clear, no murmur heard on auscultation of heart. Abdomen was soft, non tender with no organomegaly. On blood gas analysis, there was severe metabolic acidosis (pH <6.9) with increased anion gap [Table/Fig-1]. Intubation done and put on mechanical ventilation to decrease work of breathing. [Table/Fig-1]: ABG on 1st day. To rule out aetiologies of metabolic acidosis, blood was sent to measure levels of lactate, pyruvate, ammonia and chloride level along with complete blood count and serum procalcitonin level. After that, we started 0.45% DNS infusion as a maintenance fluid after giving some boluses. Inj. ceftriaxone 750 mg i.v. once a day started. Sodium bicarbonate infusion started as there was severe metabolic acidoses along with hypotension with nil urine output. After 1 hour, vitals became stable along with improvement in urine output. Urine was send to evaluate renal response of metabolic acidosis and to evaluate urinary organic acid profile. ABG repeated after 6 hours showing slight improvement in acidosis but still pH was<7.0. Complete blood count and serum procalcitonin was within normal limit. Urinary anion gap was negative while organic acids were found on analysis by Gas chromatography/mass spectrometry (GC/MS). With these investigation findings, we concluded that it could be a case of organic acidemia. We started tab thiamine 300 mg daily, tab biotin 10 mg 6th hourly, capsule carnisure (L-carnitine) 200 mg 8th hourly through Ryle’s tube and hydroxycobalamine (vitamine B12) 1 mg intramuscularly(IM) daily. There was significant improvement after 12 hours of treatment [Table/Fig-2]. [Table/Fig-2]: ABG on 2nd day after initiation of adjuvant therapy. Sodium bicarbonate infusion stopped after 24 hrs of infusion. He was off ventilator on 2nd day and discharged to ward after 3 days of ICU admission. He was discharged to home with continuation of oral cofactor therapy and regular follow-up to detect any developemental delays. From the literature, it has been found that Inborn Errors of Metabolism (IEM) are an important cause of acute illness in newborns and infants. IEM are disorders in which there is a block at some point in the normal metabolic pathway caused by a genetic defect of a specific enzyme [1]. While the diseases individually are rare, they collectively account for a significant proportion of neonatal and childhood morbidity and mortality. Diagnosis is important not only for treatment and prognostication but also for genetic counselling and antenatal diagnosis in subsequent pregnancies. Organic acidemias should be considered in the differential diagnosis of any sick child along with common acquired causes such as sepsis, hypoxic-ischemic encephalopathy, duct-dependant cardiac lesions, congenital adrenal hyperplasia and congenital infections. Children with an organic acidemia are susceptible to metabolic decompensation during episodes of increased catabolism, such as intercurrent illness, trauma, surgery, or prolonged episodes of fasting [2]. Metabolic investigations should be initiated as soon as the possibility is considered. The outcome of treatment of many IEM is directly related to the rapidity with which problems are detected and appropriate management instituted. Complete blood count, arterial blood gases and electrolytes, blood glucose, plasma ammonia, arterial blood lactate, liver function tests, urine ketones and CT/MRI are the first line investigations in suspected cases of IEM [3]. In most cases, treatment needs to be instituted empirically without a specific diagnosis. To reduce the formation of toxic metabolites, we can decrease availability of particular substrate for metabolism but we have to provide adequate calories parenterally as well. By means of haemodialysis, we can enhance the excretion of toxic metabolites. Co-factor therapy should be instituted for specific disease even if diagnosis is not established. Along with all these things supportive care is very important like treatment of seizures (avoid sodium valproate as it may increase ammonia levels), maintenance of euglycaemia and normothermia, fluid, electrolyte & acid-base balance, treatment of infection, mechanical ventilation if required. Appropriate immediate treatment not only improves survival but also reduces the chances of neurodevelopmental sequelae. Although IEM are rare findings but think of IEM in sick children in parallel with other common conditions such as sepsis so that it could be treated timely.