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Current Opinion in Nephrology and... Mar 2023The present review summarizes findings of recent studies examining the epidemiology, pathophysiology, and treatment of type 4 renal tubular acidosis (RTA) and uric acid... (Review)
Review
PURPOSE OF REVIEW
The present review summarizes findings of recent studies examining the epidemiology, pathophysiology, and treatment of type 4 renal tubular acidosis (RTA) and uric acid nephrolithiasis, two conditions characterized by an abnormally acidic urine.
RECENT FINDINGS
Both type 4 RTA and uric acid nephrolithiasis disproportionately occur in patients with type 2 diabetes and/or chronic kidney disease. Biochemically, both conditions are associated with reduced renal ammonium excretion resulting in impaired urinary buffering and low urine pH. Reduced ammoniagenesis is postulated to result from hyperkalemia in type 4 RTA and from insulin resistance and fat accumulation in the renal proximal tubule in uric acid nephrolithiasis. The typical biochemical findings of hyperkalemia and systemic acidosis of type 4 RTA are rarely reported in uric acid stone formers. Additional clinical differences between the two conditions include findings of higher urinary uric acid excretion and consequent urinary uric acid supersaturation in uric acid stone formers but not in type 4 RTA.
SUMMARY
Type 4 RTA and uric acid nephrolithiasis share several epidemiological, clinical, and biochemical features. Although both conditions may be manifestations of diabetes mellitus and thus have a large at-risk population, the means to the shared biochemical finding of overly acidic urine are different. This difference in pathophysiology may explain the dissimilarity in the prevalence of kidney stone formation.
Topics: Humans; Uric Acid; Diabetes Mellitus, Type 2; Acidosis, Renal Tubular; Hyperkalemia; Hydrogen-Ion Concentration; Kidney Calculi; Nephrolithiasis
PubMed: 36683539
DOI: 10.1097/MNH.0000000000000859 -
Archivos Espanoles de Urologia Jan 2021Urolithiasis is a multifactorial and recurrent disease whose incidence is increasing, especially in women but also in the paediatric population. Differences can be found...
Urolithiasis is a multifactorial and recurrent disease whose incidence is increasing, especially in women but also in the paediatric population. Differences can be found between different regions and between different ethnicities, often due to dietary and environmental factors, without forgetting the genetic influence on different types of stones. There are disease sthat require a high index of suspicion in order to reach a diagnosis, such as renal tubular acidosis (RTA), not only for the benefit of the patient but also for their family members in the case a genetic mutation. Calcium-based stones continue to be the most frequent, but with a progressive increase in uric stones...
Topics: Acidosis, Renal Tubular; Calculi; Child; Female; Humans; Incidence; Urolithiasis
PubMed: 33459616
DOI: No ID Found -
Nefrologia 2021Distal renal tubular acidosis (DRTA) is a rare disease resulting from a failure in the normal urine acidification process at the distal tubule and collecting duct level.... (Review)
Review
Distal renal tubular acidosis (DRTA) is a rare disease resulting from a failure in the normal urine acidification process at the distal tubule and collecting duct level. It is characterised by persistent hyperchloremic metabolic acidosis, with a normal anion gap in plasma, in the presence of high urinary pH and low urinary excretion of ammonium. To date, 5 genes whose mutations give rise to primary DRTA have been described. Alterations in the ATP6V1B1 and ATP6V0A4 genes are inherited recessively and are associated with forms of early onset and, in many cases, with neurosensorial deafness. Pathogenic variants in the SLC4A1 gene are habitually inherited dominantly and give rise to milder symptoms, with a later diagnosis and milder electrolytic alterations. Nonetheless, evolution to nephrocalcinosis and lithiasis, and the development of chronic kidney disease in the medium to long term has been described in a similar manner in all 3 groups. Lastly, recessive forms of DTRA associated to mutations in the FOXI1 and WDR72 genes have also been described. The clinical management of DTRA is based on bicarbonate or citrate salts, which do not succeed in correcting all cases of the metabolic alterations described and, thus, the consequences associated with them. Recently, a new treatment based on slow-release bicarbonate and citrate salts has received the designation of orphan drug in Europe for the treatment of DTRA.
Topics: Acidosis, Renal Tubular; Ammonium Compounds; Bicarbonates; Citrates; Forkhead Transcription Factors; Humans; Vacuolar Proton-Translocating ATPases
PubMed: 36165107
DOI: 10.1016/j.nefroe.2021.09.004 -
Kidney360 Oct 2021
Topics: Acidosis, Renal Tubular; Humans; Hypokalemia; Lupus Nephritis
PubMed: 35372981
DOI: 10.34067/KID.0005302021 -
Journal of Nephrology Aug 2018Distal renal tubular acidosis (dRTA) is a tubular disorder with a primary defect of urinary acidification and acid excretion in the collecting duct system. Consequently,... (Review)
Review
Distal renal tubular acidosis (dRTA) is a tubular disorder with a primary defect of urinary acidification and acid excretion in the collecting duct system. Consequently, patients develop hyperchloremic metabolic acidosis with an inappropriately alkaline urine. Inherited forms of dRTA are due to mutations in at least three distinct genes: SLC4A1, ATP6V1B1, ATP6V0A4. Mutations in SLC4A1-(AE1) are inherited either in an autosomal dominant manner or in a recessive one. ATP6V1B and ATP6V0A4 mutations affect two different subunits of the vacuolar H-ATPase proton-pump, the B1 and a4 subunits, and are inherited in an autosomal recessive manner. Clinical manifestations of inherited forms of dRTA usually occur during infancy or childhood. However, heterozygous carriers of ATP6V1B1 and ATP6V0A4 mutations may have a higher risk of developing nephrolithiasis and nephrocalcinosis in adulthood, respectively. In full forms of dRTA, patients may present with mild clinical symptoms, such as mild metabolic acidosis and incidental detection of kidney stones, as well as with more severe manifestations such as failure to thrive, severe metabolic acidosis, and nephrocalcinosis. Progressive sensorineural hearing loss develops in the majority of patients with recessive dRTA (ATP6V1B1 and ATP6V0A4 mutations). Some patients with recessive dRTA may also develop abnormal widening of the vestibular aqueduct. This review will discuss our current understanding of the pathophysiology of inherited forms of dRTA, diagnosis and prognosis of patients, and therapy.
Topics: Acidosis, Renal Tubular; Adult; Anion Exchange Protein 1, Erythrocyte; Disease Progression; Hearing Loss, Sensorineural; Humans; Hypokalemia; Kidney Tubules, Distal; Male; Nephrocalcinosis; Prognosis; Renal Insufficiency, Chronic; Vacuolar Proton-Translocating ATPases
PubMed: 28994037
DOI: 10.1007/s40620-017-0447-1 -
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 -
Physiology (Bethesda, Md.) Jun 2007Inherited acidosis may result from a primary renal defect in acid-base handling, emphasizing the central role of the kidney in control of body pH; as a secondary... (Review)
Review
Inherited acidosis may result from a primary renal defect in acid-base handling, emphasizing the central role of the kidney in control of body pH; as a secondary phenomenon resulting from abnormal renal electrolyte handling; or from excess production of acid elsewhere in the body. Here, we review our current understanding of the inherited renal acidoses at a genetic and molecular level.
Topics: Acid-Base Imbalance; Acidosis, Renal Tubular; Animals; Humans; Kidney Tubules
PubMed: 17557941
DOI: 10.1152/physiol.00044.2006 -
Nephrology, Dialysis, Transplantation :... May 2022
Topics: Acidosis; Acidosis, Renal Tubular; Humans; Kidney Diseases
PubMed: 33313681
DOI: 10.1093/ndt/gfaa309 -
Physiology (Bethesda, Md.) Sep 2013Specialized cells in the body express high levels of V-ATPase in their plasma membrane and respond to hormonal and nonhormonal cues to regulate extracellular... (Review)
Review
Specialized cells in the body express high levels of V-ATPase in their plasma membrane and respond to hormonal and nonhormonal cues to regulate extracellular acidification. Mutations in or loss of some V-ATPase subunits cause several disorders, including renal distal tubular acidosis and male infertility. This review focuses on the regulation of V-ATPase-dependent luminal acidification in renal intercalated cells and epididymal clear cells, which are key players in these physiological processes.
Topics: Acidosis, Renal Tubular; Animals; Cell Membrane; Epididymis; Genetic Predisposition to Disease; Homeostasis; Humans; Hydrogen-Ion Concentration; Infertility, Male; Kidney; Male; Mutation; Phenotype; Vacuolar Proton-Translocating ATPases
PubMed: 23997191
DOI: 10.1152/physiol.00007.2013 -
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