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Nephrology, Dialysis, Transplantation :... May 2022
Topics: Acidosis; Acidosis, Renal Tubular; Humans; Kidney Diseases
PubMed: 33313681
DOI: 10.1093/ndt/gfaa309 -
American Journal of Physiology. Renal... Jan 2011Renal ammonia excretion is the predominant component of renal net acid excretion. The majority of ammonia excretion is produced in the kidney and then undergoes... (Review)
Review
Renal ammonia excretion is the predominant component of renal net acid excretion. The majority of ammonia excretion is produced in the kidney and then undergoes regulated transport in a number of renal epithelial segments. Recent findings have substantially altered our understanding of renal ammonia transport. In particular, the classic model of passive, diffusive NH3 movement coupled with NH4+ "trapping" is being replaced by a model in which specific proteins mediate regulated transport of NH3 and NH4+ across plasma membranes. In the proximal tubule, the apical Na+/H+ exchanger, NHE-3, is a major mechanism of preferential NH4+ secretion. In the thick ascending limb of Henle's loop, the apical Na+-K+-2Cl- cotransporter, NKCC2, is a major contributor to ammonia reabsorption and the basolateral Na+/H+ exchanger, NHE-4, appears to be important for basolateral NH4+ exit. The collecting duct is a major site for renal ammonia secretion, involving parallel H+ secretion and NH3 secretion. The Rhesus glycoproteins, Rh B Glycoprotein (Rhbg) and Rh C Glycoprotein (Rhcg), are recently recognized ammonia transporters in the distal tubule and collecting duct. Rhcg is present in both the apical and basolateral plasma membrane, is expressed in parallel with renal ammonia excretion, and mediates a critical role in renal ammonia excretion and collecting duct ammonia transport. Rhbg is expressed specifically in the basolateral plasma membrane, and its role in renal acid-base homeostasis is controversial. In the inner medullary collecting duct (IMCD), basolateral Na+-K+-ATPase enables active basolateral NH4+ uptake. In addition to these proteins, several other proteins also contribute to renal NH3/NH4+ transport. The role and mechanisms of these proteins are discussed in depth in this review.
Topics: Acid-Base Equilibrium; Acidosis, Renal Tubular; Ammonia; Animals; Blood Proteins; Cation Transport Proteins; Glycoproteins; Humans; Kidney; Kidney Tubules, Collecting; Loop of Henle; Membrane Glycoproteins; Membrane Transport Proteins; Protein Structure, Tertiary; Quaternary Ammonium Compounds; Sodium-Hydrogen Exchanger 3; Sodium-Hydrogen Exchangers; Sodium-Potassium-Exchanging ATPase
PubMed: 21048022
DOI: 10.1152/ajprenal.00554.2010 -
Journal of Medical Case Reports Apr 2019Distal renal tubular acidosis is a relatively infrequent condition with complex pathophysiology that can present with life-threatening electrolyte abnormalities. (Review)
Review
BACKGROUND
Distal renal tubular acidosis is a relatively infrequent condition with complex pathophysiology that can present with life-threatening electrolyte abnormalities.
CASE PRESENTATION
We 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 m. The literature on this topic was reviewed.
CONCLUSIONS
Cases 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.
Topics: Acid-Base Equilibrium; Acidosis, Renal Tubular; Disease Progression; Female; Glomerular Filtration Rate; Humans; Hypokalemia; Immunomodulation; Middle Aged; Potassium; Sjogren's Syndrome; Sodium Bicarbonate; Trace Elements; Treatment Outcome
PubMed: 31023369
DOI: 10.1186/s13256-019-2056-1 -
Pediatric Nephrology (Berlin, Germany) Jun 2017Distal renal tubular acidosis (dRTA) is characterized by hyperchloraemic metabolic acidosis, hypokalaemia, hypercalciuria and nephrocalcinosis. It is due to reduced...
BACKGROUND
Distal renal tubular acidosis (dRTA) is characterized by hyperchloraemic metabolic acidosis, hypokalaemia, hypercalciuria and nephrocalcinosis. It is due to reduced urinary acidification by the α-intercalated cells in the collecting duct and can be caused by mutations in genes that encode subunits of the vacuolar H-ATPase (ATP6V1B1, ATP6V0A4) or the anion exchanger 1 (SLC4A1). Treatment with alkali is the mainstay of therapy.
METHODS
This study is an analysis of clinical data from a long-term follow-up of 24 children with dRTA in a single centre, including a genetic analysis.
RESULTS
Of the 24 children included in the study, genetic diagnosis was confirmed in 19 patients, with six children having mutations in ATP6V1B1, ten in ATP6V0A4 and three in SLC4A1; molecular diagnosis was not available for five children. Five novel mutations were detected (2 in ATP6V1B1 and 3 in ATP6V0A4). Two-thirds of patients presented with features of proximal tubular dysfunction leading to an erroneous diagnosis of renal Fanconi syndrome. The proximal tubulopathy disappeared after resolution of acidosis, indicating the importance of following proximal tubular function to establish the correct diagnosis. Growth retardation with a height below -2 standard deviation score was found in ten patients at presentation, but persisted in only three of these children once established on alkali treatment. Sensorineural hearing loss was found in five of the six patients with an ATP6V1B1 mutation. Only one patient with an ATP6V0A4 mutation had sensorineural hearing loss during childhood. Nine children developed medullary cysts, but without apparent clinical consequences. Cyst development in this cohort was not correlated with age at therapy onset, molecular diagnosis, growth parameters or renal function.
CONCLUSION
In general, the prognosis of dRTA is good in children treated with alkali.
Topics: Acidosis, Renal Tubular; Alkalies; Anion Exchange Protein 1, Erythrocyte; Child, Preschool; Cohort Studies; Comorbidity; Cysts; DNA Mutational Analysis; Female; Follow-Up Studies; Genetic Testing; Glomerular Filtration Rate; Growth Disorders; Hearing Loss, Sensorineural; Humans; Infant; Infant, Newborn; Kidney Medulla; Kidney Tubules, Collecting; Male; Mutation; Vacuolar Proton-Translocating ATPases
PubMed: 28188436
DOI: 10.1007/s00467-016-3573-4 -
Comprehensive Physiology Oct 2014The H(+) concentration in human blood is kept within very narrow limits, ~40 nmol/L, despite the fact that dietary metabolism generates acid and base loads that are... (Review)
Review
The H(+) concentration in human blood is kept within very narrow limits, ~40 nmol/L, despite the fact that dietary metabolism generates acid and base loads that are added to the systemic circulation throughout the life of mammals. One of the primary functions of the kidney is to maintain the constancy of systemic acid-base chemistry. The kidney has evolved the capacity to regulate blood acidity by performing three key functions: (i) reabsorb HCO3(-) that is filtered through the glomeruli to prevent its excretion in the urine; (ii) generate a sufficient quantity of new HCO3(-) to compensate for the loss of HCO3(-) resulting from dietary metabolic H(+) loads and loss of HCO3(-) in the urea cycle; and (iii) excrete HCO3(-) (or metabolizable organic anions) following a systemic base load. The ability of the kidney to perform these functions requires that various cell types throughout the nephron respond to changes in acid-base chemistry by modulating specific ion transport and/or metabolic processes in a coordinated fashion such that the urine and renal vein chemistry is altered appropriately. The purpose of the article is to provide the interested reader with a broad review of a field that began historically ~60 years ago with whole animal studies, and has evolved to where we are currently addressing questions related to kidney acid-base regulation at the single protein structure/function level.
Topics: Acidosis, Renal Tubular; Animals; Humans; Kidney Tubules; Potassium Channels; Sodium-Bicarbonate Symporters; Sodium-Hydrogen Exchangers; Water-Electrolyte Balance
PubMed: 25428859
DOI: 10.1002/cphy.c140021 -
Kidney International Sep 2018The sodium chloride cotransporter is regulated by the with-no-lysine kinases 1 and 4. Mutations in these genes are responsible for Mendelian hypertension, increased...
The sodium chloride cotransporter is regulated by the with-no-lysine kinases 1 and 4. Mutations in these genes are responsible for Mendelian hypertension, increased sodium chloride cotransporter activity, metabolic acidosis, and hyperkalemia. Explaining metabolic acidosis and hyperkalemia has been difficult. We now learn that the versatile bicarbonate-chloride exchanger, pendrin, is important in the process. As a result, we are confronted with still another mechanism causing renal tubular acidosis.
Topics: Acidosis, Renal Tubular; Animals; Hyperkalemia; Hypertension; Mice; Pseudohypoaldosteronism; Sodium Chloride Symporters
PubMed: 30143066
DOI: 10.1016/j.kint.2018.05.024 -
Kidney International Jul 2002Familial distal renal tubular acidosis (dRTA) and Southeast Asian ovalocytosis (SAO) may coexist in the same patient. Both can originate in mutations of the... (Review)
Review
Familial distal renal tubular acidosis (dRTA) and Southeast Asian ovalocytosis (SAO) may coexist in the same patient. Both can originate in mutations of the anion-exchanger 1 gene (AE1), which codes for band 3, the bicarbonate/chloride exchanger in both the red cell membrane and the basolateral membrane of the collecting tubule alpha-intercalated cell. Dominant dRTA is usually due to a mutation of the AE1 gene, which does not alter red cell morphology. SAO is caused by an AE1 mutation that leads to a nine amino acid deletion of red cell band 3, but by itself does not cause dRTA. Recent gene studies have shown that AE1 mutations are responsible for autosomal recessive dRTA in several countries in Southeast Asia; these patients may be homozygous for the mutation or be compound heterozygotes of two different AE1 mutations, one of which is usually the SAO mutation.
Topics: Acidosis, Renal Tubular; Amino Acid Sequence; Anion Exchange Protein 1, Erythrocyte; Asia, Southeastern; Elliptocytosis, Hereditary; Humans; Kidney Tubules, Collecting; Molecular Sequence Data; Mutation
PubMed: 12081559
DOI: 10.1046/j.1523-1755.2002.00417.x -
Annals of Transplantation Feb 2015Renal tubular acidosis (RTA) is a non-anion gap metabolic acidosis and is generally mild and asymptomatic in kidney recipients. Calcineurine inhibitors (CNIs) increase...
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 (<22 mEq/L), and serum pH value (<7.35), as well as base excess and urine pH at last follow-up. RTA was defined to be metabolic acidosis with normal serum anion gap and positive urine anion gap.
RESULTS
The mean age of our study population was 41.2±11.3 years. RTA frequency was 35% in the mTORi group and 41% in the CNI group. mTORi and CNI groups did not differ significantly in terms of the development of metabolic and renal tubular acidosis. Type I RTA was common in both groups. RTA was affected by duration of time since transplantation and graft functions in both groups.
CONCLUSIONS
The rates of RTA development in patients on long-term CNI and mTORi treatment were similar.
Topics: Acidosis, Renal Tubular; Adult; Enzyme Inhibitors; Female; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; TOR Serine-Threonine Kinases; Treatment Outcome
PubMed: 25659354
DOI: 10.12659/AOT.892320 -
Nefrologia : Publicacion Oficial de La... 2013Distal renal tubular acidosis (dRTA) or RTA type I is characterised by reduced H+ hydrogen ions and ammonium urinary excretion. In children affected by dRTA there... (Review)
Review
Distal renal tubular acidosis (dRTA) or RTA type I is characterised by reduced H+ hydrogen ions and ammonium urinary excretion. In children affected by dRTA there is stunted growth, vomiting, constipation, loss of appetite, polydipsia and polyuria, nephrocalcinosis, weakness and muscle paralysis due to hypokalaemia. This work summarises progress made in dRTA genetic studies in populations studied so far. DRTA is heterogeneous and as such, transporters and ion channels are analysed which have been identified in alpha-intercalated cells of the collecting duct, which could explain cases of dRTA not associated with the hitherto studied genes. DRTA can be autosomal dominant or autosomal recessive. Autosomal recessive dRTA appears in the first months of life and progresses with nephrocalcinosis and early or late hearing loss. Autosomal dominant dRTA is less severe and appears during adolescence or adulthood and may or may not develop nephrocalcinosis. In alpha-intercalated cells of the collecting duct, the acid load is deposited into the urine as titratable acids (phosphates) and ammonium. Autosomal recessive dRTA is associated with mutations in genes ATP6V1B1, ATP6V0A4 and SLC4A1, which encode subunits a4 and B1 of V-ATPase and the AE1 bicarbonate/chloride exchanger respectively. By contrast, autosomal dominant dRTA is only related to mutations in AE1.
Topics: Acidosis, Renal Tubular; Humans
PubMed: 23640117
DOI: 10.3265/Nefrologia.pre2012.Oct.11592 -
Anaesthesia Apr 2008The correct identification of the cause, and ideally the individual acid, responsible for metabolic acidosis in the critically ill ensures rational management. In Part 2... (Review)
Review
The correct identification of the cause, and ideally the individual acid, responsible for metabolic acidosis in the critically ill ensures rational management. In Part 2 of this review, we examine the elevated (corrected) anion gap acidoses (lactic, ketones, uraemic and toxin ingestion) and contrast them with nonelevated conditions (bicarbonate wasting, renal tubular acidoses and iatrogenic hyperchloraemia) using readily available base excess and anion gap techniques. The potentially erroneous interpretation of elevated lactate signifying cell ischaemia is highlighted. We provide diagnostic and therapeutic guidance when faced with a high anion gap acidosis, for example pyroglutamate, in the common clinical scenario 'I can't identify the acid--but I know it's there'. The evidence that metabolic acidosis affects outcomes and thus warrants correction is considered and we provide management guidance including extracorporeal removal and fomepizole therapy.
Topics: Acid-Base Equilibrium; Acidosis; Acidosis, Lactic; Acidosis, Renal Tubular; Critical Illness; Humans; Prognosis
PubMed: 18336491
DOI: 10.1111/j.1365-2044.2007.05371.x