SDF1 induction by acidosis from principal cells regulates intercalated cell subtype distribution

Schwartz, George J.; Gao, Xiao Bo; Tsuruoka, Shuichi; Purkerson, Jeffrey M.; Hu, Peng; D’Agati, Vivette D.; Picard, Nicolas; Eladari, Dominique; Al‐Awqati, Qais

doi:10.1172/jci80225

Cited by 22 publications

(27 citation statements)

References 45 publications

(47 reference statements)

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“…The link between acidosis and GFR decline is well established in experimental and human CKD and parallel non‐mutually exclusive mechanisms have been proposed. These mechanisms include local complement activation by renal ammonium, increased renal angiotensin 2 production, increased endothelin‐1 production by the kidney cortex, and increased CXCL12 production by tubular cells . Our results suggest that reduced bicarbonate levels rather than blood pH is the critical acid‐base parameter associated with adverse renal outcome in KTRs.…”

Section: Discussionmentioning

confidence: 74%

“…increased endothelin-1 production by the kidney cortex, 31,32 and increased CXCL12 production by tubular cells. 33 Our results suggest that reduced bicarbonate levels rather than blood pH is the critical acid-base parameter associated with adverse renal outcome in KTRs. This observation is in line with our current understanding of the mechanisms underlying acid-base status sensing by tubular cells.…”

Section: Ta B L Ementioning

confidence: 65%

“…Indeed, metabolic acidosis promotes complement activation, which in turn is an important factor in ischemia‐reperfusion injury and humoral rejection. In addition, metabolic acidosis increases the expression of the chemoattractant CXCL12, a chemokine promoting T cell recruitment, which has been associated with the occurrence of acute allograft rejection . Finally, a reduction in pH has been shown to promote dendritic cell maturation, which is a critical initiator of cellular rejection .…”

Section: Discussionmentioning

confidence: 99%

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Association of blood bicarbonate and pH with mineral metabolism disturbance and outcome after kidney transplantation

Brazier

Jouffroy

Martinez

et al. 2020

American Journal of Transplantation

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In kidney transplant recipients (KTRs), scarce evidence has associated low blood bicarbonate levels with mineral metabolic disturbance and reduced allograft survival. However, the contribution of the blood pH to these observations remains unassessed. Equally, little is known about the influence of the blood provenance (arteriovenous fistula vs peripheral vein) on bicarbonate values. We analyzed blood gas parameters in a single‐center cohort of 1260 stable KTRs, 3 months after transplantation. Inspection of pO2 distribution allowed the unambiguous identification of the arterial (N = 914) or venous (N = 346) origin of the samples. In patients with arterial blood samples, 435 (46%) had bicarbonate levels below 22 mmol/L. Among them, 196 (40%) were acidemic (blood pH <7.38). In multivariate analysis, low arterial blood pH was associated with increased blood ionized calcium and phosphate and reduced fibroblast growth factor 23 and calcitriol, but not with outcome. In contrast, low bicarbonate concentration predicted allograft loss independently of measured glomerular filtration rate and other potential confounders (hazard ratio [HR] 1.70; 95% confidence interval [CI] 1.04‐2.80). In KTRs, reduced arterial blood bicarbonate levels predict outcome while acidemia is associated with altered mineral metabolism.

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Section: Discussionmentioning

confidence: 74%

Section: Ta B L Ementioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

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Association of blood bicarbonate and pH with mineral metabolism disturbance and outcome after kidney transplantation

Brazier

Jouffroy

Martinez

et al. 2020

American Journal of Transplantation

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“…promoter region, or that mutations in additional genes may contribute to inherited dRTA. Candidate genes include the K + /Cl --cotransporter KCC4 (SLC12A7) 96 , the Cl -/HCO3 --exchanger SLC26A7 97 , the ammonia channels RhBG and RhCG (SLC42A2, SLC42A3) 30 , the hensin (DMBT1)-CXCL12 signal complex 98,99 , or other H + -ATPase subunits 100 .…”

Section: Further Genesmentioning

confidence: 99%

Molecular Pathophysiology of Acid-Base Disorders

Wagner

Silva

Bourgeois

2019

Seminars in Nephrology

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Acid-base balance is critical for normal life. Acute and chronic disturbances impact cellular energy metabolism, endocrine signaling, ion channel activity, neuronal activity, and cardiovascular functions such as cardiac contractility and vascular blood flow. Maintenance and adaptation of acid-base homeostasis are mostly controlled by respiration and kidney. The kidney contributes to acid-base balance by reabsorbing filtered bicarbonate, regenerating bicarbonate through ammoniagenesis and generation of protons, and by excreting acid. This review focuses on acid-base disorders caused by renal processes, both inherited and acquired. Distinct rare inherited monogenic diseases affecting acid-base handling in the proximal tubule and collecting duct have been identified. In the proximal tubule, mutations of solute carrier 4A4 (SLC4A4) (electrogenic Na/HCO-cotransporter Na/bicarbonate cotransporter e1 [NBCe1]) and other genes such as CLCN5 (Cl/H-antiporter), SLC2A2 (GLUT2 glucose transporter), or EHHADH (enoyl-CoA, hydratase/3-hydroxyacyl CoA dehydrogenase) causing more generalized proximal tubule dysfunction can cause proximal renal tubular acidosis resulting from bicarbonate wasting and reduced ammoniagenesis. Mutations in adenosine triphosphate ATP6V1 (B1 H-ATPase subunit), ATPV0A4 (a4 H-ATPase subunit), SLC4A1 (anion exchanger 1), and FOXI1 (forkhead transcription factor) cause distal renal tubular acidosis type I. Carbonic anhydrase II mutations affect several nephron segments and give rise to a mixed proximal and distal phenotype. Finally, mutations in genes affecting aldosterone synthesis, signaling, or downstream targets can lead to hyperkalemic variants of renal tubular acidosis (type IV). More common forms of renal acidosis are found in patients with advanced stages of chronic kidney disease and are owing, at least in part, to a reduced capacity for ammoniagenesis.

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“…The latter may be important for the control of NaCl homeostasis and blood pressure control [13][14][15][16][17][18]. [25], the Forkhead transcription factor Foxi1 [26], the Cl -/HCO 3 -exchanger SLC26A7 [27], the ammonia channel RhCG (SLC42A3) [8], the hensin (DMBT1)-CXCL12 signal complex [28][29], or other H + -ATPase subunits [30]. In Europe, mutations in ATP6V1B1 and ATP6V0A4 appear to be more prevalent whereas in other regions, the relative occurrence of mutations may be different.…”

Section: Renal Acid Excretionmentioning

confidence: 99%

Pathophysiology, diagnosis and treatment of inherited distal renal tubular acidosis

Mohebbi

Wagner

2017

J Nephrol

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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.

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SDF1 induction by acidosis from principal cells regulates intercalated cell subtype distribution

Cited by 22 publications

References 45 publications

Association of blood bicarbonate and pH with mineral metabolism disturbance and outcome after kidney transplantation

Association of blood bicarbonate and pH with mineral metabolism disturbance and outcome after kidney transplantation

Molecular Pathophysiology of Acid-Base Disorders

Pathophysiology, diagnosis and treatment of inherited distal renal tubular acidosis

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