Hyperchloremic Acidosis Research Articles

Physico-chemical stability of Plasma-Lyte 148® and Plasma-Lyte 148®+5% Glucose with eight common intravenous medications.

Plasma-Lyte 148® is a balanced, crystalloid intravenous (IV) fluid which is both calcium-free and isotonic. It prevents the hyperchloremic metabolic acidosis and iatrogenic hyponatremia seen with use of 0.9% sodium chloride and hypotonic solutions, respectively. However, data on compatibility with commonly used drugs are lacking. To investigate the stability of Plasma-Lyte 148® and Plasma-Lyte 148®+5% Glucose with eight commonly used therapeutic agents when compared with 5% glucose and 0.9% sodium chloride as diluents. We aimed to provide vital data which may facilitate the introduction of what appears to be a safer and more economic fluid. Plasma-Lyte 148® and Plasma-Lyte 148®+5% Glucose were mixed with morphine, midazolam, fentanyl, ketamine, clonidine, aminophylline, salbutamol, and furosemide at set concentrations. Comparisons were made to 0.9% sodium chloride and 5% glucose fluid controls. Six repeats of each IV fluid and drug admixture were analyzed through high-performance liquid chromatography at three time points: 0, 2, and 24hours. A concentration change of <5% was defined as chemically stable. Physical stability was assessed by observation of precipitate formation or color change. pH changes were measured using a Fisherbrand Hydrus 300 pH meter. Relative to starting concentration, all drugs except midazolam were stable to ±3%. All examined therapeutic agents were chemically stable at 2 and 24hours relative to control solutions. No precipitate formed in any of the samples. All Plasma-Lyte 148® and Plasma-Lyte 148®+5% Glucose drug admixtures remained in a safe, peripheral administration pH range of 5-9 and were closer to the pH of blood than standard fluid-drug admixtures. Morphine, fentanyl, ketamine, salbutamol, aminophylline, and clonidine are stable for 24hours when mixed with Plasma-Lyte 148® and Plasma-Lyte 148®+5% Glucose for administration at concentrations equivalent to those found at a typical Y-site with maintenance fluid. Furosemide is stable at lower concentrations than those seen at a Y-site, but midazolam displayed instability.

Balanced crystalloids in the acutely ill patient.

Administration of intravenous fluids is the most common therapy given to patients admitted to a hospital. Evidence suggests that the use of normal saline (NS) in large quantities is not without adverse effects. Balanced salt solutions (BSS) contain bicarbonate or one of its precursors that act as a buffer, and the electrolyte composition resembles that of plasma. We reviewed studies across different setups such as intensive care units (ICUs), major surgeries, renal transplants and emergency departments to identify the effect(s) of NS and to find evidence favouring the use of BSS over NS. The use of NS is strongly associated with hyperchloraemic acidosis in almost all the studies. In the largest and latest trial in ICUs, it was found that higher chloride levels were associated with renal injury. No significant difference was found in mortality in any of the trials. In surgical patients, studies found only transient hyperchloraemia and increase in the base deficit in patients receiving NS. Systematic reviews and meta-analyses did not find any significant differences in adverse outcomes such as the need for renal replacement therapy or mortality with the use of saline; however, blood chloride levels were consistently higher with saline compared to BSS. There is a need for larger trials with better methodology to determine if the physiological benefits of BSS translate into better clinical outcomes.

Epidemiological profiles of diabetic ketoacidosis in the Emergency Department

IntroductionL'acidocétose diabétique (ACD) est une complication métabolique grave du diabète. Son incidence est en augmentation ces dernières années, cependant sa mortalité reste faible. L'objectif de cette étude a été de décrire les caractéristiques épidémiologiques, cliniques, thérapeutiques et pronostiques des patients admis aux urgences pour ACD sévère ou modérée.MéthodesIl s'agissait d'une étude prospective, descriptive qui a inclus les ACD modérées ou sévères. Standardisation du protocole de prise en charge thérapeutique. Nous avons étudié les caractéristiques épidémiologiques, cliniques, thérapeutiques et pronostiques chez ces patients.RésultatsNous avons inclus 185 patients avec ACD sévère ou modérée. L'âge moyen a été de 38 +/- 18 ans; le sexe ratio=0,94. Diabète connue= 159 patients (85%) dont 116 étaient des diabétiques type 1. Les facteurs de décompensation les plus fréquents étaient l'arrêt du traitement chez 42% et l'infection chez 32%. La glycémie moyenne a été de 32,7+/-12mmol/L, pH =7,14+/-0,13, HCO3- =7,2+/-3,56 mmol /L. La durée moyenne de l'insuline intraveineuse était de 17,3 +/- 16 heures. L'hypoglycémie a été observée chez 26 patients (14%), l'hypokaliémie chez 80 (43%). La mortalité au cours de l'hospitalisation a été de 2,1%.ConclusionL'acidocétose diabétique survient chez les sujets jeunes traités par insulinothérapie. Le traitement est à base d'insuline par voie intraveineuse en plus de la correction du déficit hydrique. Les complications sont essentiellement l'hypokaliémie et l'hypoglycémie; et la mortalité reste faible.

Fluid Choice: Balanced Crystalloid Instead of Saline

The choice of crystalloid fluid for volume resuscitation is debated often. With rising concern about the effect of hyperchloremic metabolic acidosis

Порівняння ефективності рідинної ресусцитації хворих із септичним шоком розчинами рінгер-малат та ізотонічним розчином натрію хлориду

One of the key elements of therapy for sepsis and septic shock is the fluid replacement. Current guidelines suggests an insfusion of at least 30 ml / kg of crystalloid in the first three hours, and if necessary, more. Preference is given to balanced crystalloid solutions, but the choice of a particular solution remains unclear. A randomized, controlled study of the “Ringer-Malat” balanced crystalloid solution was performed, compared with isotonic saline for primary resuscitation of septic shock patients. The study involved 48 patients randomized to ringer malate (experimental) and 0.9% sodium chloride (control) group. The 30-day mortality rate was not significantly different between the groups (20.0% and 21.4% respectively, p = 0.521), but the trend was noted for less time on vasopressor support (58.2 versus 74.3 hours, respectively, p = 0.072), higher delivery of oxygen (1064.26 vs. 612.38 ml / min, p <0.001), greater clearance of lactate (22.14% vs. 16.28% p <0.001). In the Ringer Malate group, no cases of hyperchloremic acidosis were noted, and in the control group there were 3 cases (13.04%). Thus, the use of balanced crystalloids (in particular, Ringer Malat) allows for better results in the treatment of septic shock compared with isotonic sodium chloride solution, although additional studies on a larger scale are needed to determine the effect on mortality.

Novel compound heterozygous ATP6V1B1 mutations in a Chinese child patient with primary distal renal tubular acidosis: a case report

BackgroundDistal renal tubular acidosis (dRTA) is a heterogeneous disorder characterized by normal anion gap metabolic acidosis. Autosomal recessive dRTA is usually caused by mutations occurring in ATP6V1B1 and ATP6V0A4 genes,encoding subunits B1 and a4 of apical H+-ATPase, respectively. The heterogeneous clinical manifestations of dRTA have been described in different ethnic groups harboring distinct mutations. Most of the reported cases are from Europe and Africa. At present, the prevalence of primary dRTA is still poorly elucidated in Chinese population.Case presentationA 2-year and six-month-old female patient was hospitalized because of recurrent hypokalemia, hyperchloremic metabolic acidosis and growth retardation. Laboratory investigations presented a normal anion gap hyperchloremic metabolic acidosis, hypokalemia, and inappropriate alkaline urine. Renal ultrasound indicated bilateral nephrocalcinosis. Bilateral sensorineural hearing loss (SNHL) was confirmed with moderately severe (45 dB) on the left ear and severe (80 dB) on the right ear, which was accompanied with enlarged vestibular aqueduct (EVA) on both sides. According to these findings, a diagnosis of dRTA was made. To identify the pathogenic gene mutation, all coding regions of ATP6V1B1 and ATP6V0A4 gene, including intron-exon boundaries, were analyzed using PCR followed by direct sequence analysis. The splicing variants were verified in peripheral blood leucocytes of the patient by RT-PCR. As a result, two novel heterozygous mutations in ATP6V1B1 were identified in the child. One mutation was a successive 2-nucleotide deletion in exon 2(c.133-134delTG), which caused a marked nonsense mediated mRNA decay. The other was a guanine to adenine substitution of the first nucleotide of intron 8(c.785 + 1 G > A), which led to the exclusion of exon 8. After treatment with sodium citrate, potassium citrateand citric acid, metabolic acidosis and hypokalemia were corrected, but her hearing decreased gradually during the 2 years and had to accept the use of bilateral hearing aids.ConclusionsWe described two novel dRTA associated mutations in ATP6V1B1 identified in a Chinese child patient accompanying with SNHL and EVA. Our study will help to expand the understanding of this rare disease in Chinese population.

Clinical Impact of Saline Volume Infused Through Irrigated-Tip Ablation Catheter in Low Acuity Paroxysmal Atrial Fibrillation Ablation Patients.

Radio-Frequency ablation (RFA) to achieve pulmonary vein isolation (PVI) remains mainstay therapy for symptomatic paroxysmal atrial fibrillation (PAF). The clinical consequences of large saline infusions during AF ablation have not been systematically studied. We utilized the differential flow-rates of the two commercially available ablation catheters (AC): 'ThermoCool' (TCAC) and 'Surround Flow' (SFAC) from Biosense-Webster to evaluate the clinical impact of the saline infused in the immediate post-ablation period. Consecutive charts of PAF patients between 18 and 81 years who underwent RFA procedure at a tertiary care hospital were reviewed. Forty-seven patients were included in the study (33Males, 65±11years, LVEF 58±7% and left atrial diameter 44±7.5mm, 23TCAC-use). The saline volume infused through the AC was significantly higher with TCAC vs SFAC use (1277±316vs697±299 ml; p<0.001), with no difference in volume infused from other sources, total procedure or RFA times (p>0.05). This led to significant increase in post-ablation weight gain (96±23 vs 97.5±24kg; p=0.002), furosemide usage (39% vs 0%; p=0.0006), urine production (120±79 vs 63±31ml/hr; p=0.003) and post-RFA potassium reduction (4.4±0.42 vs 4±0.32mmol/l; p<0.001) with TCAC use. Significant post-RFA reduction in magnesium, calcium and creatinine, associated hyperchloremic metabolic acidosis and a modest QTc prolongation were also observed with use of both ACs albeit only moderate to weakly correlated with saline volume infused through the AC. No clinical adverse outcomes were encountered. Higher saline-volume infusing AC use in PAF ablation causes significant post-ablation weight gain despite higher furosemide use, larger urine production and associated post-RFA potassium reduction without increasing morbidity in lower acuity patients. Furthermore, an array of post-ablation electrolyte disturbances causes a modest and clinically insignificant QTc prolongation.

Fluid administration: Which direction?

Introduction: Although fluid administration for intravenous hydration is a common practice in pediatric age, it is not devoid of risks. Methods: This was a retrospective cohort study including all children admitted to surgical recovery and receiving intravenous hydration at a Pediatric Intensive Care Unit between January and December 2015. Sodium, chloride, and base excess values were registered on two occasions: after surgery and during Unit’s hospitalization. Results: Two hundred and seven children were included in the study, 66% of which, male, with a median age of 6.7 years. Fluids used consisted of 0.9% saline solution, 0.45% saline solution, and polyelectrolyte solution. The most frequently used fluids were polyelectrolyte (62%) and 0.9% saline solution (48%) at the operating room, and 0.9% saline (63%) and 0.45% saline (44%) solutions at the Pediatric Intensive Care Unit. At the operating room, 0.9% saline solution led to higher chloride median values and more negative base excess (metabolic acidosis) values compared with polyelectrolyte solution. At the Pediatric Intensive Care Unit, 0.9% saline solution administration resulted in hyperchloremia (p=0.002) and more metabolic acidosis (p=0.019) compared with 0.45% saline solution. There was no statistically significant association between type of solution used and sodium values. Discussion: This study shows that the use of 0.9% saline solution is associated with development of hyperchloremic acidosis. This suggests that replacement of 0.9% saline solution with a plasma-like electrolyte solution may improve patient outcomes.

Shock Etiologies and Fluid Management in Liver Failure.

Liver failure can occur in patients with or without underlying chronic liver disease (mainly cirrhosis) and is, respectively, termed acute on chronic liver failure or acute liver failure (ALF). In both cases, it is associated with marked systemic inflammation and profound hemodynamic disturbances, that is, increased cardiac output, peripheral vasodilation, and decreased systemic vascular resistance, on top of several superimposed etiologies of shock. In patients with cirrhosis, sepsis is the main cause of intensive care unit admission but portal hypertension-related gastrointestinal hemorrhage is also common. Septic shock is also particularly frequent in patients with ALF and can complicate the initial hypovolemic shock related to poor oral intake, vomiting, and encephalopathy prior to admission. Given the susceptibility of the liver to hypoxia and also the potential deleterious effects of fluid on liver function, the assessment of hemodynamic status and volume responsiveness is especially important in these patients. However, one should keep in mind that the hyperdynamic state and low systemic vascular resistance in liver failure may bias the accuracy of some hemodynamic monitoring devices. Fluid therapy should use crystalloids, and balanced salt solutions may limit the risk of hyperchloremic acidosis and subsequent adverse kidney events. Nevertheless, the beneficial effects of albumin resuscitation have been demonstrated in patients with cirrhosis and may reflect more than mere volume expansion.

A Case of Cardiac Arrhythmia from Absorption of Normal Saline during Hysteroscopic Myomectomy

We present a case of severe hypokalemia, metabolic acidosis, and arrhythmia after absorption of 2500 mL normal saline during a hysteroscopic myomectomy. The patient was a 36-year-old woman with abnormal uterine bleeding caused by a submucosal leiomyoma. She received a total of 3500 mL normal saline (2500 mL was absorbed via the uterus and 1000 mL given intravenously) during hysteroscopy. This resulted in hemodilution, electrolyte disturbances, and arrhythmia. She was treated with electrolyte replacement and closely monitored. Normal saline may result in severe metabolic derangements caused by hemodilution and hyperchloremic metabolic acidosis when used as a hysteroscopic distension medium even when adhering to the American Association of Gynecologic Laparoscopists guidelines.

Clinical and genetic analysis of distal renal tubular acidosis in three Chinese children

Objective: Primary distal renal tubular acidosis (dRTA) is a rare genetic disease characterized by distal tubular dysfunction leading to metabolic acidosis and alkaline urine. Growth retardation is a major concern in these children. The disease is caused by defects in at least three genes (SLC4A1, ATP6V0A4, and ATP6V1B1) involved in urinary distal acidification. Several series of dRTA patients from different ethnic backgrounds have been genetically studied, but genetic studies regarding Chinese population is rare. Our aim was to investigate the clinical features and genetic basis of primary dRTA in Chinese children. Methods: Three unrelated patients with dRTA participated in our study. Next-generation sequencing was performed, and the findings were validated using the Sanger sequencing method. Results: All patients exhibited hyperchloraemic metabolic acidosis, abnormally high urine pH, hypokalemia, and nephrocalcinosis. Growth retardation was observed in all patients. During the follow-up (range 1–4 years), alkali replacement therapy corrected the systemic metabolic acidosis, and two patients demonstrated normal growth. rhGH therapy was administered to patient-3 at the age of 6 years, and his growth rate was significantly improved (growth velocity 9.6 cm/yr). In total, 5 mutations were identified in our cohort of three patients, and four mutations were novel. Conclusions: We report the clinical and molecular characteristics of dRTA patients from China. The four novel mutations detected in our study extend the spectrum of gene mutations associated with primary dRTA. Furthermore, our study confirms the effect of early treatment in improving growth for dRTA patient and provides insight into the effects of rhGH on dRTA patients who were diagnosed late and exhibiting a persistent growth delay despite appropriate therapy.

Etiology and pathogenesis of hereditary renal tubular acidosis

Renal tubular acidosis(RTA) is a hyperchloremic metabolic acidosis characterized by a normal anion gap due to reduced urinary acidification.Multiple mechanisms act in the renal tubule to maintain balance in hydrogen ion secretions and bicarbonate absorption.In recent years, more and more proteins have been found to be associated with RTA, so hereditary RTA has attracted people′s attention.Mutations in the gene SLC4A1, encoding Cl-/HCO3- exchanger (kAE1); in the gene ATP6V1B1, encoding B1 subunit of H+ -ATP ase; in the gene ATP6V0A4, encoding a4 subunit of H+ -ATP ase; in the gene SLC4A4, encoding Na+ /HCO3-cotransporter(kNBCe1); in the gene CA2, encoding carbonic anhydrase Ⅱ are identified in the pathogenesis of hereditary RTA.The search for pathogenetic genes for clinically suspected hereditary RTA patients can help us to make accurate genetic diagnosis and provide targeted treatment interventions. Key words: Renal tubular acidosis; Hereditary; Pathogenetic gene

Acid base variables predict survival early in the course of treatment with continuous venovenous hemodiafiltration.

Metabolic acid–base disorders, especially metabolic acidosis, are common in critically ill patients who require renal replacement therapy. Continuous veno-venous hemodiafiltration (CVVHDF) achieves profound changes in acid–base status, but metabolic acidosis can remain unchanged or even deteriorate in some patients. The objective of this study is to understand the changes of acid–base variables in critically ill patients with septic associated acute kidney injury (SA-AKI) during CVVHDF and to determine how they relate to clinical outcome.Observational study of 200 subjects with SA-AKI treated with CVVHDF for at least 72 hours. Arterial blood gases and electrolytes and other relevant acid–base variables were analyzed using quantitative acid–base chemistry.Survivors and nonsurvivors had similar demographic characteristics and acid–base variables on day one of CVVHDF. However, during the next 48 hours, the resolution of acidosis was significantly different between the 2 groups, with an area under the ROC curve for standard base excess (SBE) and mortality of 0.62 (0.54–0.70), this was better than APACHE II score prediction power. Quantitative physicochemical analysis revealed that the majority of the change in SBE was due to changes in Cl and Na concentrations.Survivors of SA-AKI treated with CVVHDF recover hyperchloremic metabolic acidosis more rapidly than nonsurvivors. Further study is needed to determine if survival can be improved by measures to correct acidosis more rapidly.

Correlation of Hyperchloremic Metabolic Acidosis and Renal Function in Critically ill Patients of Emergency Department: an Observational Study.

Early detection is crucial for prompt management of acute kidney injury (AKI) patients in emergency department (ED). This study aimed to investigate the usefulness of hyperchloremic metabolic acidosis (HCMA) levels in this regard. In this retrospective observational study, > 18 years old critically ill patients presenting to ED of Marcianise Hospital, Italy, were divided into non-AKI and AKI group according to KDIGO guideline. The level of HCMA ((arterial pH x bicarbonate)/chloride) was compared between groups and correlation of HCMA with estimated glomerular filtration rate (e-GFR) in ARF patients was evaluated. 134 patients with the mean age of 76.5 ± 3.1 years were enrolled (64 non-AKI and 70 AKI; 64% female). Two groups were similar regarding mean age (p = 0.251), sex (p = 0.091), APACHII score (p = 0.215), Charlson Comorbidity Index (p= 0.187), and body mass index (p = 0.129). The mean HCMA level was 1.98 ± 0.09 in the non-AKI group and 1.56 ± 0.07 in the AKI group (p=0.039). There was a positive correlation between HCMA and e-GFR levels in AKI group (r: 0.467, p=0.0092). If confirmed and validated in a future study, ABG derived formula for HCMA may be a useful tool for early detection of AKI patients in emergency department.

FLUID trial: a protocol for a hospital-wide open-label cluster crossover pragmatic comparative effectiveness randomised pilot trial

Introduction0.9% saline and Ringer’s lactate are the two most common resuscitation crystalloid fluids. 0.9% saline may lead to hyperchloraemic metabolic acidosis and may be associated with impaired kidney function and...

Sjögren's, Renal Tubular Acidosis and Osteomalacia - An Asian Indian Series.

Objective: To study the profile of Renal Tubular Acidosis (RTA) in Asian Indian patients with Primary Sjogren's Syndrome (pSS). Methods: The Electronic medical records of patients with a diagnosis of pSS seen between 2003 and 2010 at our tertiary care teaching hospital were screened for RTA. Clinical features, immunological profile, acid-base balance and electrolyte status, 25-hydroxyvitamin D (25(OH) D3) levels, histopathological changes in minor salivary gland biopsy samples and radiological findings were retrieved. RTA was diagnosed in cases of hyperchloremic metabolic acidosis with urinary pH values higher than 5.5. Those with known features suggestive of RTA including hypokalemic paralysis, hyperchloremia and nephrocalcinosis without acidosis were defined as incomplete RTA. Results: Of the 380 patients with clinically suspected pSS, 25 had RTA. The median age was 32 (18-60) years. Nineteen patients had complete RTA. Six had incomplete RTA. Only 10 patients (40%) had symptoms related to RTA at presentation. Sixteen patients (64%) had present or past history of hypokalemic paralysis. Pseudofractures were seen in 7 patients and an additional 2 had subclinical radiological osteomalacia. Majority of the patients (61.2%) had a normal 25(OH) D3 level. Those with osteomalacia had significantly lower serum phosphate, blood ph and higher alkaline phosphatase. Serum calcium and 25(OH) D3 levels were not significantly different between patients with osteomalacia and those without. Conclusion: Most patients were asymptomatic for RTA inspite of clinically overt and elicitable features. Skeletal manifestation was a common finding in patients with Sjogren and RTA, despite normal levels of 25 (OH) D3 in a majority.

A mouse model of pseudohypoaldosteronism type II reveals a novel mechanism of renal tubular acidosis

Pseudohypoaldosteronism type II (PHAII) is a genetic disease characterized by association of hyperkalemia, hyperchloremic metabolic acidosis, hypertension, low renin, and high sensitivity to thiazide diuretics. It is caused by mutations in the WNK1, WNK4, KLHL3 or CUL3 gene. There is strong evidence that excessive sodium chloride reabsorption by the sodium chloride cotransporter NCC in the distal convoluted tubule is involved. WNK4 is expressed not only in distal convoluted tubule cells but also in β-intercalated cells of the cortical collecting duct. These latter cells exchange intracellular bicarbonate for external chloride through pendrin, and therefore, account for renal base excretion. However, these cells can also mediate thiazide-sensitive sodium chloride absorption when the pendrin-dependent apical chloride influx is coupled to apical sodium influx by the sodium-driven chloride/bicarbonate exchanger. Here we determine whether this system is involved in the pathogenesis of PHAII. Renal pendrin activity was markedly increased in a mouse model carrying a WNK4 missense mutation (Q562E) previously identified in patients with PHAII. The upregulation of pendrin led to an increase in thiazide-sensitive sodium chloride absorption by the cortical collecting duct, and it caused metabolic acidosis. The function of apical potassium channels was altered in this model, and hyperkalemia was fully corrected by pendrin genetic ablation. Thus, we demonstrate an important contribution of pendrin in renal regulation of sodium chloride, potassium and acid-base homeostasis and in the pathophysiology of PHAII. Furthermore, we identify renal distal bicarbonate secretion as a novel mechanism of renal tubular acidosis.

Pseudo-Renal Tubular Acidosis: Conditions Mimicking Renal Tubular Acidosis.

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.

Clinical Approach to Proximal Renal Tubular Acidosis in Children.

Proximal renal tubular acidosis (pRTA) is an inherited or acquired clinical syndrome in which there is a decreased bicarbonate reclamation in the proximal tubule resulting in normal anion gap hyperchloremic metabolic acidosis. In children, pRTA may be isolated but is often associated with a general proximal tubular dysfunction known as Fanconi syndrome which frequently heralds an underlying systemic disorder from which it arises. When accompanied by Fanconi syndrome, pRTA is characterized by additional renal wasting of phosphate, glucose, uric acid, and amino acids. The most common cause of inherited Fanconi syndrome in the pediatric age group is cystinosis, a disease with therapeutic implications. In this article, we summarize the clinical presentation and differential diagnosis of pRTA and Fanconi syndrome and provide a practical approach to their evaluation in children.

Hyperkalemic Forms of Renal Tubular Acidosis: Clinical and Pathophysiological Aspects.

In contrast to distal type I or classic renal tubular acidosis (RTA) that is associated with hypokalemia, hyperkalemic forms of RTA also occur usually in the setting of mild-to-moderate CKD. Two pathogenic types of hyperkalemic metabolic acidosis are frequently encountered in adults with underlying CKD. One type, which corresponds to some extent to the animal model of selective aldosterone deficiency (SAD) created experimentally by adrenalectomy and glucocorticoid replacement, is manifested in humans by low plasma and urinary aldosterone levels, reduced ammonium excretion, and preserved ability to lower urine pH below 5.5. This type of hyperkalemic RTA is also referred to as type IV RTA. It should be noted that the mere deficiency of aldosterone when glomerular filtration rate is completely normal only causes a modest decline in plasma bicarbonate which emphasizes the importance of reduced glomerular filtration rate in the development of the hyperchloremic metabolic acidosis associated with SAD. Another type of hyperkalemic RTA distinctive from SAD in which plasma aldosterone is not reduced is referred to as hyperkalemic distal renal tubular acidosis because urine pH cannot be reduced despite acidemia or after provocative tests aimed at increasing sodium-dependent distal acidification such as the administration of sodium sulfate or loop diuretics with or without concurrent mineralocorticoid administration. This type of hyperkalemic RTA (also referred to as voltage-dependent distal renal tubular acidosis) has been best described in patients with obstructive uropathy and resembles the impairment in both hydrogen ion and potassium secretion that are induced experimentally by urinary tract obstruction and when sodium transport in the cortical collecting tubule is blocked by amiloride.