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Background Familial distal renal tubular acidosis (dRTA) associated with mutations of solute carrier family 4 membrane − 1 (SLC4A1) gene could co-exist with red cell membrane abnormality, Southeast Asian ovalocytosis (SAO). Although this association is well described in Southeast Asian countries, it is less frequently found in Sri Lanka. Case presentation We describe six patients who had dRTA co-existing with SAO. All of them initially presented with severe hypokalemia and paralysis. They presented within a period of six months to the Teaching Hospital Anuradhapura, Sri Lanka. All had metabolic acidosis indicated by low serum bicarbonate. Three of them were having underlying chronic kidney disease as well. Those three patients had mixed high and normal anion gap metabolic acidosis indicated by low delta ratio. In all dRTA was confirmed by presence of normal anion gap, hyperchloraemia, high urine pH and positive urine anion gap. Examination of blood films of all of them revealed presence of stomatocytes and macro-ovalocytosis compatible with SAO. In relation to complications of dRTA, two patients had medullary nephrocalcinosis. Three patients had biochemical evidence of osteomalacia, with two of them having radiological evidence of diffuse osteosclerosis. One patient had secondary hyperparathyroidism and a pathological fracture. Conclusions Erythrocyte in SAO is exceptionally rigid and this abnormality is said to be evolved as it protects against Plasmodium vivax malaria and cerebral malaria cause by Plasmodium falciparum. Although two families of SAO was described earlier, SAO and dRTA combination was reported only once in a patient from Anuradhapura district. Distal renal tubular acidosis, SAO combination and its related complications including nephrocalcinosis, chronic kidney disease and metabolic bone disease was not described in Sri-Lankan literature. This case series emphasize the importance of investigating recurrent/ chronic hypokalemia to diagnose dRTA and its associations, as early correction of acidosis could prevent development of chronic kidney disease and metabolic bone disease.

Objective: Renal tubular acidosis (RTA) is a clinical manifestation that occurs with insufficiency in restoring bicarbonate or disruption in hydrogen ion elimination as a result of a disruption in tubulus functions, causing normal anion gap-opening metabolic acidosis. In the present study, we aimed to investigate the prevalence of RTA in the largest systemic lupus erythematosus (SLE) patient population to date. Materials and Methods: SLE patients, who were followed up in 2 different healthcare centers, were included. Patients with metabolic acidosis (pH 3 Results: A total of 108 patients were included in the present study. The mean age of the patients was 41.5 ± 1.2 and 87% were female. The SLE diagnosis duration was 75 ± 5 months. The mean creatinine value ​​was 0.6 ± 0.1 mg/dL and the mean eGFR was 111 ± 2 mL/min. According to the blood gas analysis, 18 patients (16.7% of the total) had RTA. Sixteen of these patients had type 1 RTA and 2 had type 2 RTA; type 4 RTA was not determined in any of the patients. Conclusion: RTA should be considered in SLE patients even if they have normal eGFR values. This is the largest study to examine the prevalence of RTA in SLE patients in the literature.

Type IV renal tubular acidosis (RTA) is a severe complication of urinary tract infection (UTI) in infants. A detailed clinical and molecular analysis is still lacking. Infants with UTI who exhibited features of type IV RTA were prospectively enrolled. Clinical, laboratory, and image characteristics and sequencing of genes responsible for phenotype were determined with follow-up. The study cohort included 12 infants (9 males, age 1–8 months). All exhibited typical type IV RTA such as hyperkalemia with low transtubular potassium gradient, hyperchloremic metabolic acidosis with positive urine anion gap, hypovolemic hyponatremia with renal salt wasting, and high plasma renin and aldosterone levels. Seven had hyperkalemia-related arrhythmia and two of them developed life-threatening ventricular tachycardia. With prompt therapy, all clinical and biochemical abnormalities resolved within 1 week. Five had normal urinary tract anatomy, and three of them carried genetic variants on NR3C2. Three variants, c.1645T>G (S549A), c.538G>A (V180I), and c.1-2C>G, on NR3C2 were identified in four patients. During follow-up, none of them had recurrent type IV RTA, but four developed renal scaring. Genetic mutation on NR3C2 may contribute to the development of type IV RTA as a complication of UTI in infants without identifiable risk factors, such as urinary tract anomalies.

Acid-base homeostasis is fundamental for life. The body is exceptionally sensitive to changes in pH, and as a result, potent mechanisms exist to regulate the body's acid-base balance to maintain it in a very narrow range. Accurate and timely interpretation of an acid-base disorder can be lifesaving but establishing a correct diagnosis may be challenging. The underlying cause of the acid-base disorder is generally responsible for a patient's signs and symptoms, but laboratory results and their integration into the clinical picture is crucial. Important acid-base parameters are often available within minutes in the acute hospital care setting, and with basic knowledge it should be easy to establish the diagnosis with a stepwise approach. Unfortunately, many caveats exist, beginning in the pre-analytical phase. In the post-analytical phase, studies on the arterial reference pH are scarce and therefore many different reference values are used in the literature without any solid evidence. The prediction models that are currently used to assess the acid-base status are approximations that are mostly based on older studies with several limitations. The two most commonly used methods are the physiological method and the base excess method, both easy to use. The secondary response equations in the base excess method are the most convenient. Evaluation of acid-base disorders should always include the assessment of electrolytes and the anion gap. A major limitation of the current acid-base laboratory tests available is the lack of rapid point-of-care laboratory tests to diagnose intoxications with toxic alcohols. These intoxications can be fatal if not recognized and treated within minutes to hours. The surrogate use of the osmolal gap is often an inadequate substitute in this respect. This article reviews the role of the clinical laboratory to evaluate acid-base disorders.

A hyperchloremic non-anion gap metabolic acidosis, in the absence of grastrointestinal bicarbonate loss, is due to either renal loss of bicarbonate or an inability of the kidney to excrete protons in the urine. This chapter outlines renal tubular mechanisms mediating bicarbonate reabsorption by the nephron and acid secretion by the kidney and the pathologies that disturb them. Bicarbonate reabsorption predominantly occurs in the proximal tubule while acid secretion takes place in the distal nephron. Consequently, specific pathologies, which prevent bicarbonate reclamation and lead to a metabolic acidosis are referred to as proximal renal tubular acidosis (pRTA). Conversely, a failure of the kidney to excrete acid is known as distal renal tubular acidosis (dRTA). These forms of renal tubular acidosis are typically accompanied by hypokalemia. In the distal nephron acid secretion is facilitated by the electrogenic reabsorption of sodium in response to aldosterone, a process that also permits potassium secretion. Consequently actual or functional absence of aldosterone leads to a hyperkalemic metabolic acidosis. After identifying the clinical presentation of these types of disorders, with particular emphasis on genetic causes of RTA, we highlight a diagnostic approach to and treatment for them.

Acidemia is one of the risk factors for end-stage kidney disease and increases the mortality rate of patients with chronic kidney disease (CKD). Although urinary ammonium (U-NH4 + ) is the crucial component of renal acid excretion, U-NH4 + concentration is not routinely measured. To estimate U-NH4 + , urine osmolal gap (UOG = urine osmolality - [2(Na+ + K+ ) + urea + glucose]) is calculated and the formula (U-NH4 + = UOG/2) has traditionally been used. However, the usefulness of this formula is controversial in CKD patients. We assessed the relationship between U-NH4 + and UOG in patients with CKD. Blood and spot urine samples were collected in 36 patients who had non-dialysis-dependent CKD. The mean ± SD age of patients was 72.0 ± 14.8 years, and the mean ± SD serum creatinine and U-NH4 + were 2.7 ± 2.3 mg/dl and 9.3 ± 9.2 mmol/L, respectively. A significant relationship was found between UOG/2 and U-NH4 + (r = .925, p < .0001). U-NH4 + estimated using the UOG was on average higher by 4.7 mmol/L than the measured one. Our results suggested that UOG could be a useful tool in clinical settings, especially in patients with moderate to severe CKD.

Background. Hypokalemic periodic paralysis is a rare neuromuscular disorder characterized by transient episodes of flaccid paralysis due to a defect in muscle ion channels. Most cases are hereditary, but it can be acquired. We present a case of acquired hypokalemic periodic paralysis associated with hyperthyroidism and renal tubular acidosis. Clinical Case. A 38-year-old female with a history of Graves’ disease presented to the emergency department with generalized weakness and associated nausea, vomiting, and weight loss. Examination was significant for diffuse weakness in all extremities. Labs showed hypokalemia, hyperthyroidism, and nonanion gap metabolic acidosis with a positive urine anion gap. She was treated for hypokalemic periodic paralysis and renal tubular acidosis. Potassium replacement, propranolol, methimazole, and sodium bicarbonate were initiated. Her potassium gradually corrected with resolution of her symptoms. Further investigation revealed a history of dry eyes, dry mouth, and recurrent dental carries. She had positive ANA, SS-A, and SS-B antibodies. She was diagnosed with Sjögren’s syndrome, which may have been associated with her Graves’ disease and thus contributed to both her RTA and hyperthyroidism. Conclusion. Early recognition and treatment of thyrotoxic periodic paralysis are important to prevent cardiac complications. Management includes potassium replacement with careful monitoring to prevent rebound hyperkalemia. The definitive treatment is to achieve euthyroid status.

Case 1: 35-year-old patient with lupus nephritis presents with anasarca, hypertension and renal insufficiency at her 18th week of pregnancy Liz Lightstone, and Sandra Navarra Clinical presentation A 35-year-old female was diagnosed lupus nephritis (LN) 7 years earlier with kidney biopsy showing LN Class IV-G activity 7, chronicity 3. She received methylprednisolone pulse and was thereafter maintained on prednisone, hydroxychloroquine (HCQ), mycophenolate mofetil (MMF) and calcium plus vitamin D. Her condition was ‘stable’ despite erratic follow-up and poor adherence. Two months ago, while on prednisone 10 mg/day, she consulted at clinic because of anasarca and hypertension at Week 18 of her 4th pregnancy. Obstetric history included two spontaneous abortions at 2 months gestation in 2013, 2015 and a successful term pregnancy in 2018 with a healthy baby girl delivered by C-section. Laboratory tests showed: Hemoglobin 83 g/L, hematocrit 0.24, WBC 6.97, platelets 270, creatinine 2.29 mg/dL, ↓ C3 0.20 g/L, ↑anti-dsDNA 1152.12 IU/mL, urine albumin 4+, RBC 90–95/hpf with dysmorphic RBCs, WBC 10–12/hpf, hyaline and granular casts. Anticardiolipin, lupus anticoagulant, anti-Ro and anti-La were negative. Clinical course Prednisone was increased to 40 mg/day and she was started on methyldopa, azathioprine, HCQ, calcium plus vitamin D, iron plus folate, and aspirin 80 mg/d. A week later, she was admitted due to cough, dyspnea, orthopnea and low-grade fever. Chest radiograph showed hazy densities on both lung fields. Laboratory tests showed: Hemoglobin 74 g/L, hematocrit 0.22, WBC 17.20, platelets 433. Urine albumin 4+, RBC 18–22/hpf, WBC 10–15/hpf, hyaline, granular and waxy casts, urine total protein 822.40 mg/dL, urine creatinine 151.08 mg/dL, urine protein-creatinine ratio 5.44; BUN 62.6 mg/dL, creatinine 2.90 mg/dL, total protein 5.01 mg/dL, albumin 2.66 g/dL, Na 132 mmol/L, K 5.69 mmol/L, phosphorus 6.07 mmol/L, and iCa 1.19 mmol/L; SARS-CoV2 test was negative. She was started on antibiotics and received red cell transfusions; regular hemodialysis was initiated due to pulmonary congestion and metabolic acidosis. Discussion Points Distinguish pre-eclampsia from LN flare Management of severe LN flare with renal insufficiency during pregnancy including the role of plasma exchange Case 2: 22–year-old female with refractory LN despite immunosuppressive regimens and rituximab Liz Lightstone, Sandra Navarra Clinical data A 22-year-old female presented with anti-phospholipid syndrome (APS) and LN at age 8. She had completed cyclophosphamide induction therapy, had been adherent to MMF (plus tacrolimus for 18 months), and received eight doses of rituximab. Renal histopathology (2008, 2016, 2019) shows persistent lupus nephritis ISN/RPS Class IV, varying activity and chronicity indices. She would attain partial renal remission for a few months, but never achieved complete remission. Blood pressure and renal function remain within normal range. Discussion Point Updates in the management of LN Case 3: 35-year-old male with LN presents with persistent hypokalemia Liz Lightstone, Sandra Navarra Clinical data A 35-year-old male with LN ISN/RPS Class IV – S, activity 11 and chronicity 4, presented with nephrotic-range proteinuria, hypertension, and impaired renal function. Renal ultrasound was normal without calcinosis. He received prednisone, MMF, HCQ, anti-hypertensives, and calcium plus vitamin D. He had persistently low levels of serum potassium (K) 2.4–3.8 meqs/L, and serum bicarbonate (HCO3) 11–20 mmol/L despite K and HCO3 supplementation. Urine pH was 6.0, urine sodium (Na) 80 mmol/L, urine K 20.63 mmol/L, urine chloride (Cl) 97.90 mmol/L. Serum anion gap was normal, and urine anion gap positive at 2.73 meq/L, confirming the diagnosis of an underlying distal renal tubular acidosis (RTA). Discussion Points Clinical significance and management of RTA in LN Case 4: 31-year-old patient with LN and APS presents with fever, deteriorating kidney function and an ovarian mass Liz Lightstone, Sandra Navarra Clinical data A 31-year-old female was diagnosed with LN and APS 8 years ago presenting with Raynaud’s, mononeuritis multiplex, proteinuria, pancytopenia, and pericarditis. She was given methylprednisolone pulse, cyclophosphamide, and belimumab then maintained on hydroxychloroquine, MMF, aspirin, nifedipine, iron plus folate, and calcium plus vitamin D. She developed hematologic flare a year ago which responded well to methylprednisolone pulse and two doses of rituximab. Two months ago, she presented with intermittent fever, dysuria, and cough. Laboratory results were: Hemoglobin 97 g/L, WBC 8.4 x109/L, platelet 109 x109/L, BUN 52.1 mmol/L, creatinine 2.73 mg/dL (eGFR 22.3 ml/min) →3.26 mg/dL (eGFR 18.1 ml/min), urine protein 2+, RBC 40–50, pus >100; urine PCR by Gene Xpert® was positive for Mycobacterium tuberculosis (TB), no rifampicin resistance. Chest radiograph showed infiltrates suggestive of miliary TB. Abdominal ultrasound showed renal cysts with calcifications, mild left ureteropelvocaliectasia from a left adnexal cystic mass measuring 8.57 cm. Exploratory laparotomy with left salpingo-oophorectomy was performed; histopathology showed caseating granuloma. She was started on an anti-TB regimen. Discussion Points Causes of renal insufficiency in a patient with LN Renal involvement in APS Learning Objectives Describe management approach to LN Explain special considerations in the management of LN flare during pregnancy Discuss further management options in refractory LN Discuss clinical situations which significantly contribute to morbidity in LN

Two papers, one in 1986 and another one in 1988, reported a strong inverse correlation between urinary anion gap (UAG) and urine ammonia excretion (UNH(4)) in patients with metabolic acidosis and postulated that UAG could be used as an indirect measure of UNH(4). 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. UNH(4) 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 UNH(4), 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.

The evaluation of serum electrolytes is part of a basic laboratory workup for various conditions and clinical signs or symptoms. Urine testing can be a powerful tool to further delineate some conditions not clearly understood from history, physical exam and serum electrolytes evaluation alone. This chapter shows the clinician the physiology behind metabolic conditions commonly evaluated with urine electrolytes (hypokalemia, renal tubular acidosis, acute kidney injury) and how urine testing aids in evaluation (polyuria).

Hyperchloremic metabolic acidosis, particularly renal tubular acidosis, can pose diagnostic challenges. The laboratory phenotype of a low total carbon dioxide content, normal anion gap, and hyperchloremia may be misconstrued as hypobicarbonatemia from renal tubular acidosis. Several disorders can mimic renal tubular acidosis, and these must be appropriately diagnosed to prevent inadvertent and inappropriate application of alkali therapy. Key physiologic principles and limitations in the assessment of renal acid handling that can pose diagnostic challenges are enumerated.

Background and objectives Low urine ammonium excretion is associated with ESRD in CKD. Few laboratories measure urine ammonium, limiting clinical application. We determined correlations between urine ammonium, the standard urine anion gap, and a modified urine anion gap that includes sulfate and phosphate and compared risks of ESRD or death between these ammonium estimates and directly measured ammonium. Design, setting, participants, & measurements We measured ammonium, sodium, potassium, chloride, phosphate, and sulfate from baseline 24-hour urine collections in 1044 African-American Study of Kidney Disease and Hypertension participants. We evaluated the cross-sectional correlations between urine ammonium, the standard urine anion gap (sodium + potassium − chloride), and a modified urine anion gap that includes urine phosphate and sulfate in the calculation. Multivariable-adjusted Cox models determined the associations of the standard urine anion gap and the modified urine anion gap with the composite end point of death or ESRD; these results were compared with results using urine ammonium as the predictor of interest. Results The standard urine anion gap had a weak and direct correlation with urine ammonium ( r =0.18), whereas the modified urine anion gap had a modest inverse relationship with urine ammonium ( r =−0.58). Compared with the highest tertile of urine ammonium, those in the lowest urine ammonium tertile had higher risk of ESRD or death (hazard ratio, 1.46; 95% confidence interval, 1.13 to 1.87) after adjusting for demographics, GFR, proteinuria, and other confounders. In comparison, participants in the corresponding standard urine anion gap tertile did not have higher risk of ESRD or death (hazard ratio, 0.82; 95% confidence interval, 0.64 to 1.07), whereas the risk for those in the corresponding modified urine anion gap tertile (hazard ratio, 1.32; 95% confidence interval, 1.03 to 1.68) approximated that of directly measured urine ammonium. Conclusions Urine anion gap is a poor surrogate of urine ammonium in CKD unless phosphate and sulfate are included in the calculation. Because the modified urine anion gap merely estimates urine ammonium and requires five measurements, direct measurements of urine ammonium are preferable in CKD.

From its introduction in the late 1980s, the urine anion gap (UAG), calculated as [(Na+ + K+) – (Cl−)] has been used to roughly estimate whether urine ammonium is increased or decreased in the evaluation of hyperchloremic metabolic acidosis ([1][1],[2][2]). This is the context in which the use

Renal tubular acidosis (RTA) comprises a group of different renal tubular disorders that are characterized by the inability to excrete H+ in the urine. As a result, there is a positive H+ balance, causing metabolic acidosis. The net acid excretion (NAE) is decreased, and some of the patients are unable to lower their urine pH

Metabolic acidosis is defined as a pathologic process that, when unopposed, increases the concentration of hydrogen ions (H+) in the body and reduces the bicarbonate (HCO3-) concentration. Metabolic acidosis can be of a kidney origin or an extrarenal cause. Assessment of urinary ammonium excretion by calculating the urine anion gap or osmolal gap is a useful method to distinguish between these two causes. Extrarenal processes include increased endogenous acid production and accelerated loss of bicarbonate from the body. Metabolic acidosis of renal origin is due to a primary defect in renal acidification with no increase in extrarenal hydrogen ion production. This situation can occur because either the renal input of new bicarbonate is insufficient to regenerate the bicarbonate lost in buffering endogenous acid as with distal renal tubular acidosis (RTA) or the RTA of renal insufficiency, or the filtered bicarbonate is lost by kidney wasting as in proximal RTA. In either condition, because of loss of either NaHCO3 (proximal RTA) or NaA (distal RTA), effective extracellular volume is reduced and as a result the avidity for chloride reabsorption derived from the diet is increased and results in a hyperchloremic normal gap metabolic acidosis. The RTA of renal insufficiency is also characterized by a normal gap acidosis, however, with severe reductions in the glomerular filtration rate an anion gap metabolic acidosis eventually develops.

To regulate the body's electrolytes and acid-base and volume status the kidneys adjust urinary excretion. Urine biochemistry can provide important ancillary diagnostic information. This chapter summarizes the common uses of urine biochemistry in the intensive care unit (ICU) and how they may aid in the diagnosis, investigation, and monitoring in a variety of conditions. It also presents some available literature on the topic. Urine sodium, fractional excretion of sodium, urine osmolality, and fractional excretion of urea have been used as surrogates of kidney perfusion and for discriminating transient (prerenal) and established AKI (acute tubular necrosis). However, their value in ICU settings may be questionable. Urine osmolality and urine sodium are important measures in the evaluation of sodium and water imbalance. Urine chloride can aid in discriminating the cause of metabolic alkalosis. Urine potassium, urine magnesium, and urine calcium can be important tools for investigating the cause of disorders of serum potassium, magnesium, and calcium, respectively. Urine anion gap and urine osmolality can assist in the evaluation of nonanion gap metabolic acidosis. Urine biochemistry can have an important adjuvant role in the diagnosis and evaluation of a number of clinical problems; however, it may be confounded in ICU settings and ideally should be integrated into the broader clinical context to inform about optimal management.

We herein report the case of a 64-year old woman with recurrent attacks of hypokalemic quadriparesis which resulted from distal renal tubular acidosis (dRTA) secondary to Sjögren syndrome. The patient presented with sudden onset quadriparesis. A physical examination showed symmetric weakness of all four limbs. Severe hypokalemia (1.8 mEq/L), accompanied by normal anion gap metabolic acidosis, a positive urine anion gap and an inappropriately high urine pH pointed toward the diagnosis of dRTA. Further investigations disclosed primary Sjögren syndrome, which had not previously been recognized. On the basis of the current report and a review of the literature we suggest investigating the possibility of Sjögren syndrome in all patients with clinically unexplained dRTA.

Cases of sprue-like enteropathy associated with olmesartan have sporadically been encountered since it was first reported in 2012, and their most characteristic manifestation is severe diarrhea. We herein report the first case of sprue-like enteropathy manifesting as Wernicke-Korsakoff syndrome due to vitamin B1 malabsorption with only minimally increased bowel movements. When patients are receiving olmesartan and they complain of nonspecific chronic gastrointestinal symptoms, it is important to consider changing the drugs before any serious malabsorption syndrome develops.

Apremilast is a recently developed phosphodiesterase 4-inhibitory medication approved for use to treat psoriasis and psoriatic arthritis. We report a case of Fanconi syndrome and proximal renal tubular acidosis that was associated with this medication. Our patient was started on treatment with apremilast 2 weeks before his admission. On arrival, laboratory test results were significant for hypokalemia, hyperchloremic metabolic acidosis, low uric acid concentration, positive urine anion gap, and proteinuria, which resolved on discontinuation of the drug. Two months after the hospitalization, he was restarted on apremilast therapy; 17 days after resumption, the patient was admitted for similar laboratory values, which again improved when apremilast treatment was discontinued. After discharge, laboratory values remained normal without long-term electrolyte repletion. Proximal renal tubular acidosis (Fanconi syndrome) with quick correction of electrolyte concentrations on discontinuation of the drug was diagnosed. Our patient lacked evidence of other causes. Our patient fulfilled criteria associated with this disease and responded well off treatment with the offending agent. Literature review did not reveal prior cases associated with this medication.

A 28-year-old female with history of hypothyroidism, Sjögren’s Syndrome, and Systemic Lupus Erythematosus (SLE) presented with complaints of severe generalized weakness, muscle pain, nausea, vomiting, and anorexia. Physical examination was unremarkable. Laboratory test showed hypokalemia at 1.6 mmol/l, nonanion metabolic acidosis with HCO3of 11 mmol/l, random urine pH of 7.0, and urine anion gap of 8 mmol/l. CT scan of the abdomen revealed bilateral nephrocalcinosis. A diagnosis of type 1 RTA likely secondary to Sjögren’s Syndrome was made. She was started on citric acid potassium citrate with escalating dosages to a maximum dose of 60 mEq daily and potassium chloride over 5 years without significant improvement in serum K+and HCO3levels. She had multiple emergency room visits for persistent muscle pain, generalized weakness, and cardiac arrhythmias. Citric acid potassium citrate was then replaced with sodium bicarbonate at 15.5 mEq every 6 hours which was continued for 2 years without significant improvement in her symptoms and electrolytes. Amiloride 5 mg daily was added to her regimen as a potassium sparing treatment with dramatic improvement in her symptoms and electrolyte levels (as shown in the figures). Amiloride was increased to 10 mg daily and potassium supplementation was discontinued without affecting her electrolytes. Her sodium bicarbonate was weaned to 7.7 mEq daily.

This paper introduces a wireless, solid-state, portable, and automated device capable of measuring the total ammonia [ammonia (NH3) and ammonium (NH4+)] levels of fluids, including biological samples. This device reliably measures the total ammonia of biological samples (e.g., urine) faster than the current ammonia quantification techniques. Medical professionals typically estimate NH4+ levels using error-prone indirect measurement techniques (i.e., urine anion gap), which are time-consuming and are seldom suitable for periodic measurements. Several instantaneous measurements of total ammonia levels in a patient urine could be utilized as an early warning for both acid-base and/or potassium disturbances. Given the device’s operation mechanism, it is able to quantify the total ammonia concentration within a biological sample in only 5 s and can simultaneously transmit data to other devices via Bluetooth. The analytical operation demonstrated high sensitivity, high specificity, fast reversibility, rapid response time, and has enabled the accurate determination of total ammonia concentration in urine samples produced by subjects who had consumed diets of variable protein compositions., The handheld device could semi-continuously measure the total ammonia level in urine samples as a diagnostic device to provide early physiological unbalance warnings.

Renal tubular acidosis (RTA) is a disorder with variable presentations and oftentimes a nebulous underlying primary diagnosis. We describe a rare cause of RTA as an unusual complication of proton pump inhibitor (PPI) therapy. We report a case of a 33-year-old male with history of hypertension, acid reflux, allergic rhinitis, and low testosterone admitted with complaints of fatigue, weight loss, and unexplained acidosis for ~ 2 months. His medications prior to admission included losartan, omeprazole, potassium chloride, sildenafil, and testosterone propionate injections. His physical exam was unremarkable with a blood pressure of 120/80 mmHg. Initial lab work showed a nonanion gap metabolic acidosis with serum bicarbonate level of 16 mM/L and potassium 3 mM/L. Urine studies showed urine pH of 6.5 and a positive urine anion gap. The serum creatinine was within normal range(1.13 mg/dL). He required massive doses of bicarbonate and potassium supplementation with minimal improvement of serum chemistries achieved. The cause of apparent distal RTA remained elusive despite extensive blood, urine, and imaging testing. Ultimately a renal biopsy was obtained showing mild to moderate tubule-interstitial inflammation with 5% fibrosis. PPI therapy (omeprazole) was stopped, and he was started on prednisone 60 mg per day. Two weeks later, his RTA findings resolved, and he no longer required bicarbonate and potassium supplementation. Our case highlights the importance of recognizing a unique complication of RTA following PPI therapy. It also underscores the possible need for considering a kidney biopsy in the setting of nondiagnostic laboratory work up to uncover the underlying etiology of RTA and suspected allergic interstitial nephritis (AIN).

BACKGROUND Renal tubular acidosis (RTA) is a non-anion gap metabolic acidosis and is generally mild and asymptomatic in kidney recipients. Calcineurine inhibitors (CNIs) increase the frequency of RTA but the frequency of RTA development in kidney transplant recipients receiving mammalian target of rapamycin inhibitors (mTORi) treatment remains unclear. In this study, we aimed to investigate the frequency of RTA in kidney transplant recipients on mTORi and CNI treatment and to compare both groups. MATERIAL AND METHODS We enrolled 137 adult renal transplant patients - 82 patients on mTORi and 55 patients on CNI who had similar age, sex, posttransplant follow-up period, and graft functions. We recorded the parameters of venous blood gas analysis, including serum pH value, serum bicarbonate (HCO3) concentration, presence of metabolic acidosis defined as low HCO3 (

Measurement of urine Na+, Cl−, and K+ is rather common in hospitalized patients, and these urine electrolytes are useful in the diagnostic evaluation of volume status, hyponatremia, acute kidney injury (AKI), metabolic alkalosis, hypokalemia, and urine anion gap (urine net charge). A spot urine sample is generally adequate for determination of these electrolytes. In addition, urine creatinine is determined to calculate the fractional excretion of Na+, K+, or other electrolytes. Also, urine osmolality is helpful in the differential diagnosis of hyponatremia, polyuria, and AKI. Table 2.1 summarizes the clinical applications of urine electrolytes and osmolality.

Type 1 renal tubular acidosis (RTA), or distal RTA (dRTA), is a disorder of renal tubular acidification, which is generally asymptomatic but may rarely present as hypokalemic paralysis. Here, we report the case of a young male who presented with sudden onset weakness of all 4 limbs and a 2-month history of swelling of the legs. An investigation revealed hypokalemia, metabolic acidosis, and nephrotic syndrome. Additional analyses revealed normal anion gap metabolic acidosis with a positive urine anion gap and dRTA. Renal biopsy showed evidence of membranous nephropathy (MN). The patient's weakness improved with potassium supplements. Normalization of the serum potassium level and disappearance of proteinuria were established with an ACE inhibitor and potassium supplementation. This case is an unusual combination of dRTA with MN coupled with the rare presenting symptoms of hypokalemic paralysis and medullary nephrocalcinosis.

Toluene sniffing, frequently described under the generic category of “glue sniffing,” is a potential cause of normal anion gap metabolic acidosis due to distal renal tubular acidosis. Urine anion gap is used to diagnose metabolic acidosis of a normal anion gap variety; however, pitfalls exist when using urine anion gap in the setting of toluene sniffing. We present the case of a young woman who had a normal anion gap metabolic acidosis due to toluene sniffing and an unexpectedly low urine anion gap. In such a scenario, the urine anion gap will underestimate the rate of ammonia excretion when the conjugate bases of acids other than HCl are excreted in large quantities. Estimation of the urine osmolal gap will provide a more accurate ammonia excretion rate in these circumstances. The challenges in interpretation of the urine anion gap and ammonia excretion in the setting of distal renal tubular acidosis due to toluene toxicity are discussed.

Hypobicarbonatemia, or a reduced bicarbonate concentration in plasma, is a finding seen in 3 acid-base disorders: metabolic acidosis, chronic respiratory alkalosis and mixed metabolic acidosis and chronic respiratory alkalosis. Hypobicarbonatemia due to chronic respiratory alkalosis is often misdiagnosed as a metabolic acidosis and mistreated with the administration of alkali therapy. Proper diagnosis of the cause of hypobicarbonatemia requires integration of the laboratory values, arterial blood gas, and clinical history. The information derived from the urinary response to the prevailing acid-base disorder is useful to arrive at the correct diagnosis. We discuss the use of urine anion gap, as a surrogate marker of urine ammonium excretion, in the evaluation of a patient with low plasma bicarbonate concentration to differentiate between metabolic acidosis and chronic respiratory alkalosis. The interpretation and limitations of urine acid-base indexes at bedside (urine pH, urine bicarbonate, and urine anion gap) to evaluate urine acidification are discussed.

Background Tenofovir, one of antiretroviral medication to treat human immunodeficiency virus (HIV) infection, is known to cause proximal renal tubular acidosis such as Fanconi syndrome, but cases of distal renal tubular acidosis had never been reported. Case presentation A 20-year-old man with HIV infection developed nausea and vomiting without diarrhea after starting antiretroviral therapy. Arterial blood gas revealed non-anion-gap metabolic acidosis and urine test showed positive urine anion gap. Tenofovir, one of antiretroviral medicine the patient received, was considered to be the cause of this acidosis and all antiretroviral drugs were discontinued. Symptoms disappeared promptly without recurrence of symptoms after resuming antiretroviral medications without tenofovir. Conclusion Distal renal tubular acidosis caused by tenofovir, without renal impairment is very rare. Since causes of nausea and vomiting among HIV/AIDS patients are very diverse, awareness of this phenomenon is useful in diagnosing and managing the problem.

The evaluation of metabolic acidosis requires an assessment of the kidneys response in terms of acid excretion and bicarbonate excretion. Because of bedside measurements of ammonium excretion and bicarbonate are often not available because clinical laboratories do not perform these tests routinely, surrogates like the urine anion gap were developed as an indirect measure of the ammonium excretion. Bicarbonate can be calculated based on the urine pH and PCO2 of the urine. The significance and limitations of the urine pH as an index of collecting tubule H+ secretion as discussed. Moreover, the use of provocative tests such as the furosemide test as a tool to assess sodium dependent collecting tubule H+ secretion is also discussed.

Uncomplicated metabolic acidosis (MA) is characterized by hypobicarbonatemia with low serum pH. The overproduction of ketoacids, lactic acid, or pyroglutamic acid, the ingestion of ethanol, methanol, ethylene glycol, paraldehyde, or salicylates, and the retention of fixed acid in renal failure cause MA with increased anion gap (AGMA). Diarrhea, ammonium or acid ingestion, and renal tubular acidosis (RTA) cause metabolic acidosis with normal anion gap (NAGMA). In proximal RTA the proximal tubule fails to reabsorb filtered bicarbonate normally and bicarbonate wasting develops. Proximal RTA is most often seen as part of the De Toni–Fanconi syndrome. Causes include hereditary conditions and drug toxicity. Distal RTA is marked by inability to lower urine pH normally or by diminished ammonium excretion. Distal RTA can be further characterized by the measurement of serum potassium, renin, and aldosterone levels. Causes of distal RTA include drugs, interstitial renal nephritis, hereditary diseases, low mineralocorticoid levels, and urinary tract obstruction. The diagnosis of MA in mixed acid–base disorders is more complicated. Diagnosis here involves the use of acid–base nomograms or equations to estimate the normally expected physiological compensation and also involves the comparison of changes in anion gap with changes in bicarbonate concentration.

Acid–base disorders are common in pediatric patients. We present a simple methodology for assessing both simple and complex acid–base disorders that is applicable to patients of all ages, and focus specifically on the usefulness of this approach in the pediatric patient. The application of four simple rules in sequence will define even the most complicated acid–base disturbance. However, because acid–base disorders are manifestations of systemic disorders, the primary value of characterizing them is that each generates a unique differential diagnosis. For each of the cardinal acid base disorders, the common and clinically-relevant causes in pediatric patients are explored. Additional diagnostic tools (including the serum anion gap, the delta–delta, the alveolar-arterial gradient, urine anion gap, and urine chloride), certain easily-recalled mnemonics, and empiric rules of thumb are also useful in specific situations. The treatment of acid–base disturbances is also considered, though treatment is generally best directed at the underlying disorder.

Aim: We aimed to investigate the prevalence, type, and possible risk factors of renal tubular acidosis (RTA) in Turkish patients with renal transplantation. Patients and method: The study included 66 adult renal transplantation recipients. We recorded the parameters of venous blood gas analysis including serum pH value, serum bicarbonate (HCO(3)) concentration, presence of metabolic acidosis, which was defined as low HCO(3) (

We report the case of a 22-year-old woman who presented with acute onset flaccid quadriparesis. Physical examination showed mild pallor with cervical and axillary lymphadenopathy, hepatomegaly, and bilateral smooth enlarged kidneys. Neurological examination revealed lower motor neuron muscle weakness in all the four limbs with hyporeflexia and normal sensory examination. Laboratory investigations showed anemia, severe hypokalemia, and metabolic acidosis. Urinalysis showed a specific gravity of 1.010, pH of 7.0, with a positive urine anion gap. Ultrasound revealed hepatosplenomegaly with bilateral enlarged smooth kidneys. Renal biopsy was consistent with the diagnosis of non-Hodgkin lymphoma (B cell type). Metabolic acidosis, alkaline urine, and severe hypokalemia due to excessive urinary loss in our patient were suggestive of distal renal tubular acidosis. Renal involvement in lymphoma is usually subclinical and clinically overt renal disease is rare. Diffuse lymphomatous infiltration of the kidneys may cause tubular dysfunction and present with hypokalemic paralysis.

Though chloride is the predominant extracellular anion, it is mostly seen just as an anion accompanying sodium and hardly receives attention in textbooks. But independent evaluation of serum chloride may unearth several clinical and acid-base disorders. It is used in formulas to estimate serum anion gap, urine anion gap, and strong ion difference (Stewart method). Several critical functions of a cell such as maintenance of cell volume, neutralization of H+ in lysosomal vesicles, epithelial fluid transport, change in cell membrane potential and ligand-gated transmission in the post-synaptic membrane utilize chloride channels. In addition, chloride forms an integral part of anion exchanger proteins coded by SLC26A gene family. Chloride is an essential component of intravenous fluids used in day-to-day clinical practice. The role and contribution of chloride rich fluids and resulting acidosis in causing inferior outcomes in sepsis, renal vasoconstriction, and acute kidney injury has been debated. Numerous genetic diseases are known to be related with chloride channels and proteins abnormalities. In the following review, I would like to bring much needed attention towards importance of chloride in human physiology. The following hypothetical clinical case will be just a spark for fiery chloride.

Tubulointerstitial nephritis is a well-recognized complication in primary Sjögrens syndrome. Fanconi's syndrome is a far less frequent complication compared with distal tubular dysfunction. We here describe a 49-year-old woman with primary Sjögren's syndrome. In 1997, she was diagnosed with primary Sjögren's syndrome with tubulointerstitial nephritis, and was then treated with oral prednisolone for the tubulointerstitial nephritis. In 2002, she was referred to our hospital because of progressive fatigue. At that time, biclonal spike on serum protein (IgG-kappa and IgA-kappa) and Bence-Jones protein in urine were found. Bone marrow aspiration showed 1.0% plasma cell infiltration. Thus, a diagnosis of monoclonal gammopathy of undetermined significance (MGUS) was made. In 2004, she was again admitted to our hospital because of mild renal dysfunction and hypokalemia. Laboratory evaluation showed inappropriate, alkaline urine in hyperchloremic metabolic acidosis and a positive urine anion gap, indicating the presence of distal (Type 1) renal tubular acidosis (RTA). The urine concentration defect was also found. Further studies revealed proximal tubular dysfunction, including renal glycosuria, generalized aminoaciduria, phosphaturia, uricosuria and proximal RTA. The kidney biopsy represented diffuse and severe tubulointerstitial nephritis with dense infiltrates of lymphocytes and IgA and K light chain-positive plasma cells. No findings of multiple myeloma or malignant lymphoma were observed. In conclusion, our patient had Sjögren's syndrome with MGUS and exhibited dysfunction of both proximal tubule (Fanconi's syndrome) and distal tubule, which may be attributed to diffuse tubulointerstitial nephritis.