ArticleJournal of the American Society of Nephrology : JASN2011
Luminal alkalinization attenuates proteinuria-induced oxidative damage in proximal tubular cells.
Article in Journal of the American Society of Nephrology : JASN, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- Impact of adding urine alkalization therapy to xanthine oxidase inhibitor in gout management: a prospective cohort study.Rheumatology (Oxford, England) · 2025Trial
- Oral alkalinizing supplementation suppressed intrarenal reactive oxidative stress in mild-stage chronic kidney disease: a randomized cohort study.Clinical and experimental nephrology · 2024Trial
- The efficacy and safety of citrate mixture vs sodium bicarbonate on urine alkalization in Chinese primary gout patients with benzbromarone: a prospective, randomized controlled study.Rheumatology (Oxford, England) · 2021Trial
- The effects of urine alkalinization on kidney function in critically ill patients with COVID-19: a proof-of-concept randomized clinical trial.Intensive care medicine experimental · 2025Article
- Clinical efficacy of beraprost sodium in treating chronic kidney disease: A six-month prospective study.Heliyon · 2024Article
- Increased risk of chronic kidney disease in uric acid stone formers with high neutrophil-to-lymphocyte ratio.Scientific reports · 2023Article
- Association of acidic urine pH with impaired renal function in primary gout patients: a Chinese population-based cross-sectional study.Arthritis research & therapy · 2022Article
- Oxidative Stress Markers in Chronic Kidney Disease with Emphasis on Diabetic Nephropathy.Antioxidants (Basel, Switzerland) · 2020Review
- Reno-protective effects of oral alkalizing agents in chronic kidney disease with aciduria: protocol for a randomized cohort study.BMC nephrology · 2020Article
- Oxidative Stress in the Pathogenesis and Evolution of Chronic Kidney Disease: Untangling Ariadne's Thread.International journal of molecular sciences · 2019Review
- High glucose level and angiotensin II type 1 receptor stimulation synergistically amplify oxidative stress in renal mesangial cells.Scientific reports · 2019Article
- Sphingolipids and Redox Signaling in Renal Regulation and Chronic Kidney Diseases.Antioxidants & redox signaling · 2018Article
- The relationship between the renal reabsorption of cysteine and the lowered urinary pH in diabetics.Clinical and experimental nephrology · 2017Article
- Plasma levels of oxidative stress-responsive apoptosis inducing protein (ORAIP) in rats subjected to physicochemical oxidative stresses.Bioscience reports · 2016Article
- Chelation of dietary iron prevents iron accumulation and macrophage infiltration in the type I diabetic kidney.European journal of pharmacology · 2015Article
- Lower urinary pH is useful for predicting renovascular disorder onset in patients with diabetes.BMJ open diabetes research & care · 2015Article
- Remnant nephron physiology and the progression of chronic kidney disease.Pediatric nephrology (Berlin, Germany) · 2014Review
- Proximal tubules forget "self-eating" when they meet Western meals.Journal of the American Society of Nephrology : JASN · 2013Article
- Relationship between estimated glomerular filtration rate, albuminuria, and oxidant status in the Japanese population.BMC nephrology · 2013Article
- Alkalizer administration improves renal function in hyperuricemia associated with obesity.Japanese clinical medicine · 2013Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A highly acidic environment surrounds proximal tubular cells as a result of their reabsorption of HCO(3)(-). It is unclear whether this luminal acidity affects proteinuria-induced progression of tubular cell damage. Here, we investigated the contribution of luminal acidity to superoxide (O(2)(·-)) production induced by oleic acid-bound albumin (OA-Alb) in proximal tubular cells. Acidic media significantly enhanced OA-Alb-induced O(2)(·-) production in the HK-2 proximal tubular cell line. Simultaneous treatment with both OA-Alb and acidic media led to phosphorylation of the intracellular pH sensor Pyk2. Highly phosphorylated Pyk2 associated with activation of Rac1, an essential subcomponent of NAD(P)H oxidase. Furthermore, knockdown of Pyk2 with siRNA attenuated the O(2)(·-) production induced by cotreatment with OA-Alb and acid. To assess whether luminal alkalinization abrogates proteinuria-induced tubular damage, we studied a mouse model of protein-overload nephropathy. NaHCO(3) feeding selectively alkalinized the urine and dramatically attenuated the accumulation of O(2)(·-)-induced DNA damage and proximal tubular injury. Overall, these observations suggest that luminal acidity aggravates proteinuria-induced tubular damage and that modulation of this acidic environment may hold potential as a therapeutic target for proteinuric kidney disease.
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