Home / Deep Research / Renal Tubular Acidosis Distal 4 with Hemolytic Anemia

Renal Tubular Acidosis Distal 4 with Hemolytic Anemia

1. Disease Information

2026-05-11
Falcon MONDO:0012700 Model: Edison Scientific Literature 41 citations

1. Disease Information

Disease overview

Renal tubular acidosis (RTA) comprises disorders of renal acid handling that cause chronic, normal-anion-gap (hyperchloremic) metabolic acidosis. Distal RTA (dRTA; type 1) is defined by the failure to acidify urine below pH ~5.5 despite systemic acidosis and is primarily a disorder of type A (α-) intercalated cells in the collecting duct. In the subset “dRTA with hemolytic anemia,” the renal phenotype co-occurs with hereditary hemolytic anemia and red-cell morphological abnormalities, most often due to biallelic SLC4A1 (AE1/band 3) variants, linking kidney and erythrocyte pathology. (batlle2012geneticcausesand pages 1-2, a2023thepathophysiologyof pages 1-5, alexander2025hereditarydistalrenal pages 5-7)

Key identifiers

Other requested identifiers (Orphanet, MONDO, MeSH, ICD-10/ICD-11): not retrievable from the available full-text evidence in this run; would require direct database lookup.

Synonyms / alternative names (used in literature)

Evidence source type

Evidence for this entity is largely derived from aggregated disease-level resources and reviews (e.g., Nature Reviews Nephrology 2023; systematic review Frontiers in Pediatrics 2023) plus primary case reports/series and functional studies (Thailand pediatric cohort; HEK293T trafficking work; mouse models). (a2023thepathophysiologyof pages 1-5, yang2023mutationsandclinical pages 1-2, khositseth2007distalrenaltubular pages 1-2, deejai2022impairedtraffickingand pages 6-9, stehberger2007distalrenaltubular pages 1-3)

2. Etiology

Primary causal factors (genetic)

The core causal factor for “distal RTA with hemolytic anemia” is pathogenic variation in SLC4A1, encoding the anion exchanger 1 (AE1) (band 3), with the combined renal+hematologic phenotype most often arising from autosomal recessive (biallelic) loss-of-function / inactivating or compound alleles. (alexander2025hereditarydistalrenal pages 5-7, deejai2022impairedtraffickingand pages 1-2)

Broader hereditary dRTA can also be caused by ATP6V1B1 and ATP6V0A4 (V-ATPase subunits), among other genes, but these are typically associated with renal phenotype (and often hearing loss) rather than hemolytic anemia. (batlle2012geneticcausesand pages 1-2, watanabe2018improvingoutcomesfor pages 1-2)

Risk factors

Protective factors / gene–environment interaction

No specific protective variants or clear gene–environment interaction data for this specific Mendelian entity were found in the available evidence. Clinically, adequate alkali therapy is repeatedly associated with improved systemic acid-base status and can reduce hemolytic manifestations, effectively acting as a protective clinical modifier. (alexander2025hereditarydistalrenald pages 5-7, khositseth2007distalrenaltubular pages 1-2)

3. Phenotypes

Core phenotype set (renal + hematologic)

Distal RTA phenotype (renal acidification failure) - Hyperchloremic metabolic acidosis with normal anion gap; inappropriately alkaline urine (urine pH >5.5) in the presence of systemic acidosis (watanabe2018improvingoutcomesfor pages 1-2, batlle2012geneticcausesand pages 1-2, khositseth2007distalrenaltubular pages 1-2) - Hypokalemia is common (watanabe2018improvingoutcomesfor pages 1-2, yang2023mutationsandclinical pages 3-4) - Nephrocalcinosis and/or nephrolithiasis, often with hypercalciuria and hypocitraturia (watanabe2018improvingoutcomesfor pages 1-2, stehberger2007distalrenaltubular pages 1-3) - Growth delay/failure to thrive; rickets/osteomalacia (watanabe2018improvingoutcomesfor pages 1-2, yang2023mutationsandclinical pages 1-2)

Hematologic phenotype - Hemolytic anemia with RBC morphological abnormalities (e.g., hereditary spherocytosis, SAO/ovalocytosis; acanthocytosis in some reports) (watanabe2018improvingoutcomesfor pages 1-2, alexander2025hereditarydistalrenal pages 5-7, yang2023mutationsandclinical pages 3-4)

Quantitative phenotype frequencies (recent systematic review)

A 2023 systematic review of published SLC4A1-dRTA cases (169 patients; 53 articles) reported: - Nephrocalcinosis or kidney stones: 72.27% - Developmental disorders: 61.16% - Hematological abnormalities: 33.88% - Impaired renal function: 14.29% - Muscle weakness: 13.45% (yang2023mutationsandclinical pages 1-2)

More granular counts from extracted datasets in the same work include: - Nephrocalcinosis: 65/121 (53.72%); kidney stones 23/121 (19.01%) - Renal impairment: 17/121 (14.29%) - Hematologic abnormalities: 41/121 (33.88%) - Alkaline urine pH >6.5: 64/79 (81.01%) - Hypokalemia: 72/109 (66.06%) - Hyperchloremia: 50/53 (94.34%) (yang2023mutationsandclinical pages 3-4)

AR enrichment of hematologic findings: hematologic abnormalities were particularly common among AR patients (30/61; 49.18%) in this synthesis. (yang2023mutationsandclinical pages 3-4)

Onset/severity/progression

AR SLC4A1-dRTA cases tend to have earlier onset and more severe biochemical phenotype than AD SLC4A1-dRTA, with earlier age at onset, higher urine pH, and lower serum potassium in AR cases. (yang2023mutationsandclinical pages 1-2)

Suggested HPO terms (non-exhaustive)

(Notes: HPO IDs are suggested for ontology mapping; the evidence supports the phenotypes, not the specific IDs.)

4. Genetic / Molecular Information

Causal gene(s)

Inheritance patterns

Pathogenic variants (examples; not exhaustive)

A 2023 synthesis of published cases identified 41 distinct SLC4A1 mutations with both AD and AR forms. (yang2023mutationsandclinical pages 1-2)

Variant examples explicitly appearing in compiled evidence include: - p.Ala858Asp (A858D) (recurrent; associated with dRTA and hemolytic anemia in some biallelic contexts) (alexander2025hereditarydistalrenalc pages 5-7, yang2023mutationsandclinical pages 3-4) - p.Gly701Asp (G701D) (frequent in AR Southeast Asian cases; reported with hemolytic anemia in some genotypes) (deejai2022impairedtraffickingand pages 1-2, yang2023mutationsandclinical pages 3-4) - SAO deletion p.Ala400_Ala408del (c.1199_1225del) (deejai2022impairedtraffickingand pages 1-2) - p.Thr444Asn (T444N) in compound genotype with SAO deletion (deejai2022impairedtraffickingand pages 1-2) - p.Ser477* (truncating) listed in case compilations (yang2023mutationsandclinical pages 3-4) - p.Ser725Arg described as abolishing transport and producing anemia + RTA (as cited within broader AE1/dRTA mechanistic discussions) (batlle2012geneticcausesand pages 3-4)

Compound heterozygous patterns repeatedly associated with dRTA plus hematologic abnormalities include SAO/G701D, SAO/Q759H, SAO/A858D, G701D/A858D, and others. (deejai2022impairedtraffickingand pages 1-2)

Functional consequence classes

Mechanisms described across reviews and functional studies include: - Trafficking defects / intracellular retention (ER/Golgi), reduced stability/shorter half-life of mutant kAE1 (deejai2022impairedtraffickingand pages 6-9, fry2007inheritedrenalacidoses. pages 3-4) - Mistargeting (e.g., apical mislocalization in polarized epithelia) (batlle2012geneticcausesand pages 3-4) - Transport loss-of-function for some variants (batlle2012geneticcausesand pages 3-4)

Population frequency

No gnomAD or population allele-frequency values were available in the retrieved evidence.

Modifier genes / epigenetics

No validated modifier genes or epigenetic mechanisms specific to this disease were identified in the retrieved evidence.

5. Environmental Information

This is primarily a genetic disease. Environmental contributions are mainly relevant as clinical modifiers (e.g., acid–base status affecting hemolysis risk), rather than primary causes. (alexander2025hereditarydistalrenal pages 5-7)

6. Mechanism / Pathophysiology

Current understanding (renal)

In kidney type A (α-) intercalated cells, apical H+-ATPase secretes protons into the tubular lumen; this process is functionally coupled to basolateral bicarbonate extrusion via AE1 (SLC4A1), a Cl−/HCO3− exchanger. Cytosolic carbonic anhydrase provides intracellular H+ and HCO3− substrates. Therefore, AE1 dysfunction disrupts the basolateral bicarbonate exit step needed for sustained proton secretion, producing distal acidification failure. (batlle2012geneticcausesand pages 1-2, batlle2012geneticcausesand pages 2-3, batlle2012geneticcausesand pages 3-4)

Current understanding (hematologic)

In erythrocytes, AE1/band 3 contributes both to anion exchange and to membrane skeleton anchoring; mutations can cause red-cell morphological disorders (HS, SAO/ovalocytosis) and hemolysis. In the combined phenotype, RBCs can be especially susceptible to hemolysis during systemic acidosis. (parker2018mousemodelsof pages 2-3, alexander2025hereditarydistalrenal pages 5-7)

Trafficking/processing mechanism (key expert consensus)

Several authoritative discussions emphasize that many AE1 mutations have near-normal anion exchange in heterologous systems, and that trafficking and targeting defects are a major disease mechanism (intracellular retention in nonpolarized cells; apical mistargeting/retention in polarized renal epithelia). (fry2007inheritedrenalacidoses. pages 3-4, batlle2012geneticcausesand pages 3-4)

A 2022 mechanistic study of AR dRTA with mild hemolytic anemia identified compound heterozygous SAO deletion + T444N and demonstrated: - WT and T444N kAE1 localized at the cell surface, whereas SAO and SAO/T444N were intracellularly retained - Mutant kAE1 proteins had shorter half-lives than WT, supporting impaired trafficking and instability as pathogenic mechanisms. (deejai2022impairedtraffickingand pages 1-2, deejai2022impairedtraffickingand pages 6-9)

Visual evidence supporting this mechanism: immunofluorescence localization of WT vs mutant kAE1 (cell-surface vs intracellular retention) and structural modeling were retrieved from Deejai et al. (deejai2022impairedtraffickingand media 9d60dc11, deejai2022impairedtraffickingand media 94347afb)

Model organism evidence

Slc4a1-null mice recapitulate core dRTA features: spontaneous hyperchloremic metabolic acidosis with inappropriate urine alkalinity, nephrocalcinosis and related urinary abnormalities, supporting AE1’s causal role in distal acidification. (stehberger2007distalrenaltubular pages 1-3)

Pathway/ontology mappings (suggested)

Key cell types (CL): - α-intercalated cell (collecting duct): CL:0000653 (suggested) - Erythrocyte: CL:0000232 (suggested)

Key anatomical structures (UBERON): - Kidney collecting duct: UBERON:0001230 (suggested) - Renal cortical collecting duct / distal nephron segments (suggested; evidence supports collecting duct localization) (batlle2012geneticcausesand pages 3-4)

Key GO Biological Process terms (suggested): - Renal acid secretion / urinary acidification (supported conceptually by coupling described) (batlle2012geneticcausesand pages 1-2) - Bicarbonate transport; chloride transport; anion exchange (batlle2012geneticcausesand pages 3-4) - Protein targeting to membrane; intracellular protein transport; ER retention/quality control (fry2007inheritedrenalacidoses. pages 3-4, deejai2022impairedtraffickingand pages 6-9)

(Notes: ontology IDs are suggested; supporting mechanistic statements are cited.)

7. Anatomical Structures Affected

Primary organs

Secondary involvement/complications

8. Temporal Development

9. Inheritance and Population

Inheritance

Epidemiology and prevalence

Disease-specific prevalence for the hemolytic anemia subset was not found in the retrieved evidence.

For dRTA overall, a 2023 Nature Reviews Nephrology synthesis reported prevalence estimates from administrative datasets: - UK database: ~0.46 recorded and 1.60 suspected/recorded per 10,000 - US insurance data: ~0.38 primary and 3.88 acquired dRTA per 100,000 (a2023thepathophysiologyof pages 1-5)

Geographic distribution

AR SLC4A1-dRTA is disproportionately reported in Asian populations in systematic synthesis, and many dRTA/hemolysis cases are reported from Southeast Asia and India. (yang2023mutationsandclinical pages 1-2, alexander2025hereditarydistalrenal pages 5-7)

10. Diagnostics

Clinical/laboratory diagnosis

Key diagnostic pattern for dRTA includes: - Normal anion gap (hyperchloremic) metabolic acidosis - Inappropriately high urine pH (>5.5) during systemic acidosis - Frequent hypokalemia - Evidence of hypercalciuria/hypocitraturia and imaging evidence of nephrocalcinosis/nephrolithiasis (watanabe2018improvingoutcomesfor pages 1-2, khositseth2007distalrenaltubular pages 1-2)

Genetic testing

For suspected hereditary dRTA with or without hemolysis, reviews recommend genetic testing of known genes including SLC4A1 (and ATP6V1B1, ATP6V0A4, FOXI1, WDR72 in broader dRTA). (yang2023mutationsandclinical pages 1-2, alexander2025hereditarydistalrenal pages 1-3)

Differential diagnosis

Differential diagnosis includes other genetic and acquired causes of dRTA (autoimmune disease, drug-induced) as well as other causes of hemolytic anemia; the specific co-occurrence suggests SLC4A1 involvement. (a2023thepathophysiologyof pages 1-5, watanabe2018improvingoutcomesfor pages 1-2)

11. Outcome / Prognosis

With appropriate alkali therapy, prognosis is often described as generally good, but long-term follow-up studies indicate risk of chronic kidney disease (CKD) in dRTA cohorts, and nephrocalcinosis can persist despite therapy. (watanabe2018improvingoutcomesfor pages 1-2, a2023thepathophysiologyof pages 1-5, bertholetthomas20256yeartreatmentfollowup pages 7-10)

12. Treatment

Standard of care

Oral alkali therapy (bicarbonate and/or citrate) is central; early and sufficient dosing is emphasized to support growth, bone health, and reduce kidney complications. (watanabe2018improvingoutcomesfor pages 1-2)

Clinical principles summarized in expert guidance include: - Maintain bicarbonate and potassium to reduce acute symptoms and long-term complications - Avoid sodium salts when possible because sodium can worsen hypercalciuria - Citrate provides bicarbonate equivalents in vivo and can reduce required dosing. (alexander2025hereditarydistalrenald pages 10-12, alexander2025hereditarydistalrenalc pages 10-12)

For hemolytic anemia: supportive transfusion and iron therapy as needed; correction of systemic acidosis may improve anemia/reticulocytosis in SLC4A1-related hemolysis. (alexander2025hereditarydistalrenald pages 5-7)

Recent therapeutic development / real-world implementation: ADV7103 (Sibnayal®)

ADV7103 is a prolonged-release, twice-daily combination of potassium bicarbonate and potassium citrate.

Real-world pediatric implementation (2024): At a UK center after Oct 2022 availability, 20 children with RTA were prescribed Sibnayal; 14/20 (70%) preferred and tolerated it; 6/20 (30%) reverted due to refusal or texture issues, especially in younger/developmentally affected children. Efficacy was comparable to standard therapy with maintenance of normal plasma bicarbonate; dosing was similar between standard vs Sibnayal. (tan2024treatmentofpaediatric pages 1-5)

Long-term outcomes (peer-reviewed 2025): In a 6-year open-label follow-up (B22CS; n=30; mean age 10.6 years), plasma bicarbonate control was sustained (22.0→22.6 mmol/L), growth improved (height Z −0.6→−0.3), eGFR remained stable (105→104 mL/min/1.73m²) with no progression to CKD stage 3–5, and lumbar spine BMD Z-score improved (−1.1→−0.8). Nephrocalcinosis remained common (86% at baseline; 92% at end), illustrating prevention/stabilization rather than reversal. (bertholetthomas20256yeartreatmentfollowup pages 7-10, bertholetthomas20256yeartreatmentfollowup pages 1-2)

Preprint (Dec 2024): A preprint describing the same long-term B22CS dataset reports similar outcomes and describes the formulation as prolonged-release, tasteless granules providing ~12-hour effect with twice-daily dosing. (bertholetthomas2024longtermclinicaloutcomes pages 1-5)

Clinical trials

  • NCT03644706 (ClinicalTrials.gov): phase 3 randomized withdrawal study of ADV7103 in primary dRTA; record notes TERMINATED, enrollment 3, completion 2023-12-20; primary endpoint focused on preventing metabolic acidosis during withdrawal. (NCT03644706 chunk 1)

Suggested MAXO terms (examples; suggested)

  • Alkali therapy / bicarbonate supplementation
  • Potassium citrate supplementation
  • Blood transfusion
  • Iron supplementation

(Notes: MAXO IDs not retrieved in evidence; terms suggested for mapping.)

13. Prevention

Primary prevention is not applicable for most Mendelian cases beyond genetic counseling and reproductive options. Clinically, tertiary prevention focuses on preventing nephrocalcinosis progression and growth/bone complications through sustained alkali therapy and adherence. (watanabe2018improvingoutcomesfor pages 1-2, alexander2025hereditarydistalrenalc pages 10-12)

14. Other Species / Natural Disease

No natural disease in other species specific to SLC4A1-related dRTA with hemolytic anemia was retrieved in the available evidence.

15. Model Organisms

  • Mouse (Slc4a1-null): exhibits a robust dRTA phenotype with hyperchloremic metabolic acidosis and nephrocalcinosis, supporting causal biology and enabling mechanistic investigation. (stehberger2007distalrenaltubular pages 1-3)
  • Additional Slc4 model discussion contextualizes AE1 isoforms and how mutations can cause both kidney and RBC phenotypes. (parker2018mousemodelsof pages 2-3)

Expert synthesis / key takeaways

  1. The disorder is best conceptualized as a shared-molecule syndrome: a single gene (SLC4A1/AE1) expressed in kidney α-intercalated cells and erythrocytes produces combined defects in urinary acidification and RBC integrity. (batlle2012geneticcausesand pages 3-4, guo2023geneticdiagnosisand pages 1-3)
  2. The most typical “dRTA + hemolytic anemia” cases are autosomal recessive, often involving compound alleles including SAO or other inactivating variants; systematic synthesis shows hematologic abnormalities are common in AR SLC4A1-dRTA. (yang2023mutationsandclinical pages 1-2, deejai2022impairedtraffickingand pages 1-2)
  3. A major mechanistic theme is protein mistrafficking/instability (not just loss of exchanger activity), supported by cellular studies and kidney epithelial targeting biology. (deejai2022impairedtraffickingand pages 6-9, fry2007inheritedrenalacidoses. pages 3-4)
  4. 2023–2024 literature emphasizes improved characterization (systematic review statistics) and improved real-world treatment options (prolonged-release alkali therapy) supporting adherence and long-term outcomes. (yang2023mutationsandclinical pages 1-2, tan2024treatmentofpaediatric pages 1-5)

Evidence table (summary)

Table (click to expand)
Topic Key evidence Citation
Causal gene The combined phenotype is chiefly linked to SLC4A1 (encoding AE1/band 3), expressed in both erythrocytes and type A intercalated cells of the distal nephron, providing the molecular basis for coexisting renal acidification failure and red-cell disease. (guo2023geneticdiagnosisand pages 1-3, a2023thepathophysiologyof pages 1-5)
Disease mechanism In kidney, mutant kAE1 impairs basolateral Cl-/HCO3- exchange, disrupting distal acid secretion and causing distal renal tubular acidosis; in red cells, AE1 defects alter membrane/cytoskeletal anchoring and can increase erythrocyte fragility, especially during acidosis, producing hemolytic anemia or RBC morphologic abnormalities. (alexander2025hereditarydistalrenala pages 5-7, a2023thepathophysiologyof pages 1-5)
Inheritance and hemolytic-anemia association Autosomal recessive (AR) SLC4A1 disease is the form most strongly associated with hemolytic anemia / hereditary spherocytosis / ovalocytosis; autosomal dominant (AD) SLC4A1 dRTA more often causes isolated renal disease, though rare AD families with hematologic involvement exist. (batlle2012geneticcausesand pages 3-4, watanabe2018improvingoutcomesfor pages 1-2)
AR vs AD distribution in published cases 2023 systematic review of 169 patients identified 41 SLC4A1 mutations: 15 mutations / 100 patients AD and 21 mutations / 61 patients AR; AR patients had younger onset, higher urine pH, and lower serum K+ than AD patients. (yang2023mutationsandclinical pages 1-2)
Key reported variants linked to dRTA ± hemolysis Reported pathogenic/likely pathogenic SLC4A1 variants associated with this spectrum include p.Ala858Asp (A858D), p.Gly701Asp (G701D), SAO deletion p.Ala400_Ala408del, p.Thr444Asn, p.Ser477*, p.Ser725Arg, plus combinations such as SAO/G701D, SAO/R602H, SAO/Q759H, SAO/A858D, and G701D/A858D. (yang2023mutationsandclinical pages 3-4, deejai2022impairedtraffickingand pages 1-2)
A858D-specific evidence Biallelic p.Ala858Asp (A858D) is a recurrent variant in Indian families with the combined phenotype; reported with hemolytic anemia/acanthocytosis plus dRTA, and heterozygous parents may show only mild erythrocyte changes. (alexander2025hereditarydistalrenalc pages 5-7, alexander2025hereditarydistalrenalb pages 5-7)
SAO/T444N evidence A 2022 case identified compound heterozygous SAO deletion (p.Ala400_Ala408del) + p.Thr444Asn, causing AR dRTA with mild hemolytic anemia; functional work showed intracellular retention of SAO-containing kAE1 and reduced protein stability. (deejai2022impairedtraffickingand pages 1-2)
Truncating / severe variants The 2023 review includes p.Ser477* among reported SLC4A1 dRTA alleles, and severe truncating disease has been described with marked hemolysis and complete dRTA; these support loss-of-function/trafficking-defect mechanisms. (yang2023mutationsandclinical pages 3-4)
Transport-null missense variant p.Ser725Arg was reported to abolish AE1 transport function and cause anemia plus renal tubular acidosis, illustrating that some variants directly impair exchanger activity in addition to trafficking defects. (batlle2012geneticcausesand pages 3-4)
Core clinical/laboratory phenotype Typical findings are hyperchloremic normal-anion-gap metabolic acidosis, inability to acidify urine (urine pH >5.5 despite acidosis), hypokalemia, nephrocalcinosis/nephrolithiasis, growth failure, rickets/osteomalacia, and hemolysis / RBC morphology abnormalities. (watanabe2018improvingoutcomesfor pages 1-2, batlle2012geneticcausesand pages 1-2)
Quantitative phenotype statistics (2023 systematic review) Across published SLC4A1-dRTA patients, nephrocalcinosis or kidney stones 72.27%, developmental disorders 61.16%, hematological abnormalities 33.88%, renal impairment 14.29%, muscle weakness 13.45%. (yang2023mutationsandclinical pages 1-2)
More detailed phenotype frequencies In the subset with data: nephrocalcinosis 65/121 (53.72%), kidney stones 23/121 (19.01%), renal impairment 17/121 (14.29%), hematologic abnormalities 41/121 (33.88%); alkaline urine pH >6.5 in 64/79 (81.01%), hypokalemia 72/109 (66.06%), hyperchloremia 50/53 (94.34%). (yang2023mutationsandclinical pages 3-4)
AR hematologic burden Hematologic abnormalities were particularly enriched in AR disease: 30/61 (49.18%) in AR cases in the 2023 review; AR inheritance was also more common in Asian patients. (yang2023mutationsandclinical pages 3-4, yang2023mutationsandclinical pages 1-2)
Prevalence estimates (recent authoritative review) 2023 Nature Reviews Nephrology reported dRTA prevalence estimates of about 0.46 recorded and 1.60 suspected/recorded per 10,000 in a UK database, and about 0.38 primary and 3.88 acquired dRTA per 100,000 in US insurance data; these are for dRTA overall, not specifically the hemolytic-anemia subset. (a2023thepathophysiologyof pages 1-5)
Diagnostic clues Suspect SLC4A1-related disease in a child with metabolic acidosis + high urine pH + hypokalemia + hyperchloremia + nephrocalcinosis/growth delay, especially if there is hemolytic anemia or abnormal RBC morphology; genetic testing is recommended. (yang2023mutationsandclinical pages 1-2, khositseth2007distalrenaltubular pages 1-2)
Treatment and outcomes Alkali therapy is the core treatment; studies/reviews report that adequate alkalinization improves acidosis, growth, bone disease, and may reduce or correct reticulocytosis/anemia in SLC4A1-related hemolytic cases. (alexander2025hereditarydistalrenald pages 5-7, khositseth2007distalrenaltubular pages 1-2)

Table: This table condenses the main genetic, mechanistic, phenotypic, and epidemiologic evidence for renal tubular acidosis distal 4 with hemolytic anemia. It emphasizes how SLC4A1/AE1 variants connect distal acidification failure with erythrocyte pathology and highlights recent quantitative data.

Key references (URLs and publication dates where available)

Limitations of this run

  • Direct Orphanet/MONDO/MeSH/ICD identifiers were not found in the retrieved full-text evidence; OMIM identifiers (611590; SLC4A1 +109270) were supported by primary literature excerpts. (deejai2022impairedtraffickingand pages 1-2)
  • Not all variant-level details and PMIDs for every cited paper could be extracted from the current tool outputs; however, the cited sources provide DOIs and journal metadata, and include a 2023 systematic review covering 53 primary reports. (yang2023mutationsandclinical pages 1-2)

References

  1. (batlle2012geneticcausesand pages 1-2): D. Batlle and Syed K. Haque. Genetic causes and mechanisms of distal renal tubular acidosis. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 27 10:3691-704, Oct 2012. URL: https://doi.org/10.1093/ndt/gfs442, doi:10.1093/ndt/gfs442. This article has 257 citations.

  2. (a2023thepathophysiologyof pages 1-5): Carsten A Wagner, Robert Unwin, Sergio C Lopez-Garcia, Robert Kleta, Detlef Bockenhauer, and Stephen Walsh. The pathophysiology of distal renal tubular acidosis. Nature Reviews Nephrology, 19:384-400, Apr 2023. URL: https://doi.org/10.1038/s41581-023-00699-9, doi:10.1038/s41581-023-00699-9. This article has 78 citations and is from a domain leading peer-reviewed journal.

  3. (alexander2025hereditarydistalrenal pages 5-7): RT Alexander, H Gil-Peña, and LA Greenbaum. Hereditary distal renal tubular acidosis. Unknown journal, 2025.

  4. (deejai2022impairedtraffickingand pages 1-2): Nipaporn Deejai, Nunghathai Sawasdee, Choochai Nettuwakul, Wanchai Wanachiwanawin, Suchai Sritippayawan, Pa-thai Yenchitsomanus, and Nanyawan Rungroj. Impaired trafficking and instability of mutant kidney anion exchanger 1 proteins associated with autosomal recessive distal renal tubular acidosis. BMC Medical Genomics, Oct 2022. URL: https://doi.org/10.1186/s12920-022-01381-y, doi:10.1186/s12920-022-01381-y. This article has 3 citations and is from a peer-reviewed journal.

  5. (watanabe2018improvingoutcomesfor pages 1-2): Toru Watanabe. Improving outcomes for patients with distal renal tubular acidosis: recent advances and challenges ahead. Pediatric Health, Medicine and Therapeutics, 9:181-190, Dec 2018. URL: https://doi.org/10.2147/phmt.s174459, doi:10.2147/phmt.s174459. This article has 56 citations.

  6. (yang2023mutationsandclinical pages 1-2): Mengge Yang, Qiqi Sheng, Shenghui Ge, Xinxin Song, Jianjun Dong, Congcong Guo, and Lin Liao. Mutations and clinical characteristics of drta caused by slc4a1 mutations: analysis based on published patients. Frontiers in Pediatrics, Jan 2023. URL: https://doi.org/10.3389/fped.2023.1077120, doi:10.3389/fped.2023.1077120. This article has 11 citations.

  7. (yang2023mutationsandclinical pages 3-4): Mengge Yang, Qiqi Sheng, Shenghui Ge, Xinxin Song, Jianjun Dong, Congcong Guo, and Lin Liao. Mutations and clinical characteristics of drta caused by slc4a1 mutations: analysis based on published patients. Frontiers in Pediatrics, Jan 2023. URL: https://doi.org/10.3389/fped.2023.1077120, doi:10.3389/fped.2023.1077120. This article has 11 citations.

  8. (khositseth2007distalrenaltubular pages 1-2): Sookkasem Khositseth, Apiwan Sirikanerat, Kulruedee Wongbenjarat, Sauwalak Opastirakul, Siri Khoprasert, Ratikorn Peuksungnern, Duangrurdee Wattanasirichaigoon, Wanna Thongnoppakhun, Vip Viprakasit, and Pa-thai Yenchitsomanus. Distal renal tubular acidosis associated with anion exchanger 1 mutations in children in thailand. American journal of kidney diseases : the official journal of the National Kidney Foundation, 49 6:841-850.e1, Jun 2007. URL: https://doi.org/10.1053/j.ajkd.2007.03.002, doi:10.1053/j.ajkd.2007.03.002. This article has 40 citations.

  9. (deejai2022impairedtraffickingand pages 6-9): Nipaporn Deejai, Nunghathai Sawasdee, Choochai Nettuwakul, Wanchai Wanachiwanawin, Suchai Sritippayawan, Pa-thai Yenchitsomanus, and Nanyawan Rungroj. Impaired trafficking and instability of mutant kidney anion exchanger 1 proteins associated with autosomal recessive distal renal tubular acidosis. BMC Medical Genomics, Oct 2022. URL: https://doi.org/10.1186/s12920-022-01381-y, doi:10.1186/s12920-022-01381-y. This article has 3 citations and is from a peer-reviewed journal.

  10. (stehberger2007distalrenaltubular pages 1-3): Paul A. Stehberger, Boris E. Shmukler, Alan K. Stuart-Tilley, Luanne L. Peters, Seth L. Alper, and Carsten A. Wagner. Distal renal tubular acidosis in mice lacking the ae1 (band3) cl−/hco3 − exchanger (slc4a1). Journal of the American Society of Nephrology, 18:1408-1418, May 2007. URL: https://doi.org/10.1681/asn.2006101072, doi:10.1681/asn.2006101072. This article has 161 citations and is from a highest quality peer-reviewed journal.

  11. (alexander2025hereditarydistalrenald pages 5-7): RT Alexander, H Gil-Peña, and LA Greenbaum. Hereditary distal renal tubular acidosis. Unknown journal, 2025.

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  16. (fry2007inheritedrenalacidoses. pages 3-4): Andrew C. Fry and Fiona E. Karet. Inherited renal acidoses. Physiology, 22:202-11, Jun 2007. URL: https://doi.org/10.1152/physiol.00044.2006, doi:10.1152/physiol.00044.2006. This article has 132 citations and is from a peer-reviewed journal.

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  24. (tan2024treatmentofpaediatric pages 1-5): Hai Liang Tan, Matko Marlais, Faidra Veligratli, Sarit Shah, Wesley Hayes, and Detlef Bockenhauer. Treatment of paediatric renal tubular acidosis with a prolonged-release alkali supplementation. Pediatric nephrology, 39:3373-3375, May 2024. URL: https://doi.org/10.1007/s00467-024-06411-8, doi:10.1007/s00467-024-06411-8. This article has 7 citations and is from a domain leading peer-reviewed journal.

  25. (bertholetthomas20256yeartreatmentfollowup pages 1-2): A. Bertholet-Thomas, Aurélie de Mul, J. Bernardor, G. Roussey-Kesler, Ludmila Podracká, R. Novo, F. Nobili, Bertrand Knebelmann, J. Harambat, Emilija Golubović, Olivia Boyer, Massimo Di Maio, M. Cailliez, V. Baudouin, Laure Chidler, Véronique Leblanc, and Justine Bacchetta. 6-year treatment follow-up with an extended-release alkaline formulation (sibnayal®) in primary distal renal tubular acidosis. Orphanet Journal of Rare Diseases, Aug 2025. URL: https://doi.org/10.1186/s13023-025-03953-4, doi:10.1186/s13023-025-03953-4. This article has 0 citations and is from a peer-reviewed journal.

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