Treatment and long-term outcome in primary distal renal tubular acidosis

Lopez-Garcia, Sergio Camilo; Emma, Francesco; Walsh, Stephen B.; Fila, Marc; Hooman, Nakysa; Zaniew, Marcin; Bertholet‐Thomas, Aurélia; Colussi, Giacomo; Burgmaier, Kathrin; Levtchenko, Elena; Sharma, Jyoti; Singhal, Jyoti; Soliman, Neveen A.; Ariceta, Gema; Basu, Biswanath; Murer, Luisa; Tasić, Velibor; Tsygin, A.N.; Decramer, Stéphane; Gil‐Peña, Helena; Koster-Kamphuis, Linda; Scola, Claudio La; Gellermann, Jutta; Konrad, Martin; Lilien, Marc R.; Francisco, Telma; Tramma, Despoina; Trnka, Peter; Yüksel, Selçuk; Caruso, Maria Rosa; Chromek, Milan; Ekinci, Zelal; Gambaro, Giovanni; Kari, Jameela A.; König, Jens; Taroni, Francesca; Thumfart, Julia; Trepiccione, Francesco; Winding, Louise; Wühl, Elke; Ağbaş, Ayşe; Белькевич, А. Г.; Vargas‐Poussou, Rosa; Blanchard, Anne; Conti, Giovanni; Boyer, Olivia; Dursun, İsmail; Pınarbaşı, Ayşe Seda; Melek, Engin; Miglinas, Marius; Novo, Robert; Mallett, Andrew; Milošević, Danko; Szczepańska, Maria; Wente, Sarah; Cheong, Hae Il; Sinha, Rajiv; Gucev, Zoran; Dufek, Stephanie; Iancu, Daniela; Kleta, Robert; Schaefer, Franz; Böckenhauer, Detlef

doi:10.1093/ndt/gfy409

Cited by 85 publications

(81 citation statements)

References 32 publications

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“…Consequently, disturbances of acid-base balance are potentially catastrophic and can include dysrhythmias, apnea, coma, and death (46). And even relatively mild forms of distal RTA reveal that acidosis is associated not only with rickets and nephrocalcinosis/urolithiasis, but also with more general symptoms, such as impaired growth (47).…”

Section: Acid-base Homeostasismentioning

confidence: 99%

Inherited Tubulopathies of the Kidney

Downie

Lopez-Garcia

Kleta

et al. 2020

CJASN

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The kidney tubules provide homeostasis by maintaining the external milieu that is critical for proper cellular function. Without homeostasis, there would be no heartbeat, no muscle movement, no thought, sensation, or emotion. The task is achieved by an orchestra of proteins, directly or indirectly involved in the tubular transport of water and solutes. Inherited tubulopathies are characterized by impaired function of one or more of these specific transport molecules. The clinical consequences can range from isolated alterations in the concentration of specific solutes in blood or urine to serious and life-threatening disorders of homeostasis. In this review, we will focus on genetic aspects of the tubulopathies and how genetic investigations and kidney physiology have crossfertilized each other and facilitated the identification of these disorders and their molecular basis. In turn, clinical investigations of genetically defined patients have shaped our understanding of kidney physiology.

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Section: Acid-base Homeostasismentioning

confidence: 99%

Inherited Tubulopathies of the Kidney

Downie

Lopez-Garcia

Kleta

et al. 2020

CJASN

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“…Here, we report data on the transport activity of band 3 in RBCs and on the membrane/ cytoskeleton relationship, as well as of RBC shape and hemoglobin concentration. Other reports have also shown that SLC4A1 gene mutations are the main observed anomalies in dRTA, not only in Europe, 18 but also in south Asia. 36 Obvious hematological anomalies appear to be present only if patients carry the specific SAO anomaly, 23 which is consistent with our findings.…”

Section: Clinical Researchmentioning

confidence: 82%

“…Nonetheless, this is the first report of in-depth assessment of RBC membrane disorders in patients with AE1-related dRTA. Very recently, an international cohort of dRTA patients was reported with many data on both the phenotypic diagnosis and evolution, 18 but the authors did not collect any hematological data. Previous studies that focused on the correlation between hematological and renal involvements of AE1 mutations were performed in patients carrying recessive mutations (mostly p.G701D) and the specific SAO deletion.…”

Section: Clinical Researchmentioning

confidence: 99%

Red Blood Cell AE1/Band 3 Transports in Dominant Distal Renal Tubular Acidosis Patients

Bertocchio

Genetet

Costa

et al. 2020

Kidney International Reports

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Introduction: Anion exchanger 1 (AE1) (SLC4A1 gene product) is a membrane protein expressed in both kidney and red blood cells (RBCs): it exchanges extracellular bicarbonate (HCO 3-) for intracellular chloride (Cl-) and participates in acidÀbase homeostasis. AE1 mutations in kidney a-intercalated cells can lead to distal renal tubular acidosis (dRTA). In RBC, AE1 (known as band 3) is also implicated in membrane stability: deletions can cause South Asian ovalocytosis (SAO). Methods: We retrospectively collected clinical and biological data from patients harboring dRTA due to a SLC4A1 mutation and analyzed HCO 3 and Cltransports (by stopped-flow spectrophotometry) and expression (by flow cytometry, fluorescence activated cell sorting, and Coomassie blue staining) in RBCs, as well as RBC membrane stability (ektacytometry). Results: Fifteen patients were included. All experience nephrolithiasis and/or nephrocalcinosis, 2 had SAO and dRTA (dRTA SAOþ), 13 dominant dRTA (dRTA SAOÀ). The latter did not exert specific RBC membrane anomalies. Both HCO 3 and Cltransports were lower in patients with dRTA SAOþ than in those with dRTA SAOÀ or controls. Using 3 different extracellular probes, we report a decreased expression (by 52%, P < 0.05) in dRTA SAOþ patients by fluorescence activated cell sorting, whereas total amount of protein was not affected. Conclusion: Band 3 transport function and expression in RBCs from dRTA SAOÀ patients is normal. However, in SAO RBCs, impaired conformation of AE1/band 3 corresponds to an impaired function. Thus, the driver of acidÀbase defect during dominant dRTA is probably an impaired membrane expression.

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“…ATP6V1B1 and ATP6V0A4 encode the B1 and A4 subunits of the apical H + -ATPase pump, that is, the proton pump, in α-intercalated cells, respectively, and mutations in these genes cause autosomal recessive (AR) forms of dRTA with or without sensorineural hearing loss 6,7) . In a recent large multicenter study by the European dRTA Consortium, the prevalence of hearing loss was 88% in patients with ATP6V1B1 mutations and 36% in patients with ATP6V0A4 mutations 8) . SLC4A1 encodes the basolateral anion (Cl − /HCO 3 − ) exchanger 1 (AE1) 9) .…”

Section: Discussionmentioning

confidence: 98%

A Pediatric Case of Long-term Untreated Distal Renal Tubular Acidosis

et al. 2020

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Distal renal tubular acidosis (dRTA) is a rare renal tubular disorder characterized by normal anion gap metabolic acidosis, hypokalemia, and high urine pH. It can be inherited or acquired. In untreated pediatric patients with dRTA, rickets and growth retardation are common. We report the case of a 12-year-old Lao girl who presented with typical clinical features of dRTA with severe bone deformities that developed after a bedridden state due to a bicycle accident at the age of 8 years. Initial laboratory tests revealed metabolic acidosis with a normal anion gap, hypokalemia, and alkali urine. Renal ultrasonography revealed bilateral medullary nephrocalcinosis. Whole exome sequencing revealed no pathogenic mutations. After treatment with oral alkali, potassium, and vitamin D, she could walk and run. Later, she underwent corrective orthopedic surgeries for bony deformities. Thus, in pediatric dRTA patients, despite severe symptoms remaining untreated, accurate diagnosis and proper management can improve quality of life.

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Treatment and long-term outcome in primary distal renal tubular acidosis

Cited by 85 publications

References 32 publications

Inherited Tubulopathies of the Kidney

Inherited Tubulopathies of the Kidney

Red Blood Cell AE1/Band 3 Transports in Dominant Distal Renal Tubular Acidosis Patients

A Pediatric Case of Long-term Untreated Distal Renal Tubular Acidosis

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