Salt-sensitive hypertension in chronic kidney disease: distal tubular mechanisms

AJP Renal Physiology, Journal Year: 2020, Volume and Issue: 319(5), P. F729 - F745

Published: Sept. 28, 2020

Chronic kidney disease (CKD) causes salt-sensitive hypertension that is often resistant to treatment and contributes the progression of injury cardiovascular disease. A better understanding mechanisms contributing in CKD essential improve these outcomes. This review critically explores by focusing on how affects distal nephron Na+ reabsorption. glomerulotubular imbalance with reduced proximal reabsorption increased delivery Aldosterone secretion further not only mediated renin K+ but also metabolic acidosis, endothelin-1, vasopressin. activates intrarenal renin-angiotensin system, generating intratubular angiotensin II promote High dietary intake retention aldosterone-independent activation mineralocorticoid receptor through Rac1. produces an inflammatory response T helper 17 cells cytokines increasing transport. accompanied proteinuria, which contains plasmin capable activating epithelial channel. Thus, both local systemic changes together hypertension. Future studies should address remaining knowledge gaps, including relative contribution each mechanism, influence sex, differences between stages etiologies CKD, clinical relevance experimentally identified mechanisms. Several pathways offer opportunities for intervention, reduction, diuretics, system inhibitors, antagonists, or H+ binders.

Language: Английский

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Metabolic Acidosis in Chronic Kidney Disease: Pathogenesis, Clinical Consequences, and Treatment

Electrolytes & Blood Pressure, Journal Year: 2021, Volume and Issue: 19(2), P. 29 - 29

Published: Jan. 1, 2021

The kidneys play an important role in regulating the acid-base balance. Metabolic acidosis is common chronic kidney disease (CKD) patients and can lead to poor outcomes, such as bone demineralization, muscle mass loss, worsening of renal function. usually approached with evaluating serum bicarbonate levels but should be assessed by counting blood pH. Current guidelines recommend oral supplementation maintain within normal range. However, a slow decline glomerular filtration rate might occur, even though were Because decrease when metabolic advances, other biomarkers are necessary indicate acid retention for early diagnosis acidosis. For this, urine citrate ammonium excretion may used follow course CKD patients. treated increased fruit vegetable intake alkali supplementation. Previous studies have suggested that administration sodium preserve function without significant increases pressure body weight. Veverimer, non-absorbed, counterion-free, polymeric drug, emerging treat acidosis, further researches awaited. Further also needed clarify target therapeutic range drugs

Language: Английский

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Metabolic Acidosis in CKD: A Review of Recent Findings

Kidney Medicine, Journal Year: 2021, Volume and Issue: 3(2), P. 267 - 277

Published: Feb. 10, 2021

Metabolic acidosis is fairly common in patients with chronic kidney disease (CKD). The prevalence of metabolic increases worsening function and observed ∼40% those stage 4 CKD. For the past 2 decades, clinical practice guidelines have suggested treatment to counterbalance adverse effects on bone muscle. Studies animal models CKD also demonstrated that causes fibrosis. During decade, results from observational studies identified associations between outcomes, interventional support hypothesis treating sodium bicarbonate preserves function. However, convincing data large-scale, double-blinded, placebo-controlled, randomized trials been lacking. This review discusses findings recent alkali therapy new linking cardiovascular adults progression children. Finally, a novel agent treats by binding hydrochloric acid gastrointestinal tract discussed. Kidney regulation systemic pH principally involves excretion protons as ammonium dihydrogen phosphate. Proton elimination facilitates reclamation generation restore ions consumed buffer endogenously produced acid. characterized proton accumulation resulting insufficient relative nonvolatile burden. In (CKD), diagnosis typically made when serum level decreases <22 mEq/L. present before decreases, state referred eubicarbonatemic acidosis, normobicarbonatemic or subclinical (Fig 11Raphael K.L. Kraut J.A. Assessing acid-base status CKD: does measurement blood matter?.Am J Dis. 2021; 77: 9-11Abstract Full Text PDF PubMed Scopus (3) Google Scholar). Continued impaired production eventually lead low levels, but not always accompanied CKD.2Kajimoto S. Sakaguchi Y. Asahina Kaimori J.Y. Isaka Modulation association hypobicarbonatemia incident failure replacement venous pH: cohort study.Am 35-43Abstract (5) Scholar Hence, there spectrum extending an acidemia 1). There theoretical direct severity risk for poor outcomes.1Raphael Studying this relationship challenging because identifying straightforward routinely measured research protocols. Consequently, most define mEq/L individuals CKD, which how term used here. A number excellent articles discussed pathogenesis factors mechanisms acid-mediated organ injury, evidence function, role diet strategy treat CKD.3Scialla J.J. Anderson C.A. Dietary load: nutritional target disease?.Adv Chronic 2013; 20: 141-149Abstract (111) Scholar, 4Wesson D.E. Buysse J.M. Bushinsky D.A. Mechanisms acidosis-induced injury disease.J Am Soc Nephrol. 2020; 31: 469-482Crossref (30) 5Dobre M. Rahman Hostetter T.H. Current CKD.J 2015; 26: 515-523Crossref (72) 6Raphael 2018; 29: 376-382Crossref (24) 7Kraut Madias N.E. Adverse disease.Adv 2017; 24: 289-297Abstract (45) field, including children events (CVEs) adults. pharmacologic agent, veverimer, tract, brief discussion end-stage (ESKD) considerations regarding initiate concentration are presented. First, article reviews several recently published (Table 18Di Iorio B.R. Bellasi A. Raphael et al.Treatment delays disease: UBI Study.J 2019; 32: 989-1001Crossref (35) 9BiCARB Study GroupClinical cost-effectiveness oral older low-grade (BiCARB): pragmatic randomised, double-blind, placebo-controlled trial.BMC Med. 18: 91Crossref (2) 10Melamed M.L. Horwitz E.J. Dobre M.A. al.Effects stages 3 4: randomized, multicenter trial.Am 75: 225-234Abstract (15) Greene T. Wei G. al.Sodium supplementation urinary TGF-beta1 nonacidotic diabetic controlled trial.Clin 15: 200-208Crossref (4) 12Raphael Isakova Ix J.H. al.A trial comparing safety, adherence, pharmacodynamics profiles two doses BASE Pilot Trial.J 161-174Crossref (14) 13Wesson Mathur V. Tangri N. al.Long-term safety efficacy veverimer multicentre, blinded, 40-week extension.Lancet. 394: 396-406Abstract (23) Scholar), largest conducted date.Table 1Summary Recent Interventional TrialsTrialPopulationSerum Bicarbonate, mEq/LTotal Sample SizeDurationInterventionMajor FindingsUBI8Di ScholarCKD 3, 4, 5>18 <2479536 moNaHCO3 24-28 mEq/L•Lower creatinine doubling, RRT, deathBiCARB9BiCARB ScholarAge > 60 y, eGFR < 30 mL/min/1.73 m2<2230024 up 3,000 mg/d•No significant effect Short Physical Performance Battery after 12 mo•Shorter 6-min walk distance reduction hand-grip strength group•More treatmentAlkali Therapy CKD10Melamed 420-2614924 moNaHCO3, 0.4 mEq/kg body weight/d•No mineral density, sit-to-stand time, other physical assessments, eGFRVA BiCARB11Raphael ScholarDiabetesCKD 2, 4ACR mg/g22-28746 mo0.5 lean statistically markers injuryBASE Trial12Raphael 3b 3a ACR ≥ 50 mg/g20-2819228 wk0.5 0.8 pressure weight•Dose-dependent increase bicarbonate•Dose-dependent ACRVeverimer (40-wk extension study)13Wesson ScholareGFR 20-40 m212-2019652 wkVeverimer 6 g/d then titrated 22-29 mEq/L•3% vs 10% placebo discontinued treatment•Treatment improved function•Fewer treated died progressed ESKDAbbreviations: ACR, albumin-creatinine ratio; BASE, Bicarbonate Administration Stabilize eGFR; disease; eGFR, estimated glomerular filtration rate; ESKD, renal therapy; UBI, Use Open table tab Abbreviations: muscle were some first complications CKD.14Bushinsky Chabala Gavrilov Levi-Setti R. Effects vivo midcortical ion composition.Am Physiol. 1999; 277: F813-F819PubMed 15Krieger N.S. Sessler Acidosis inhibits osteoblastic stimulates osteoclastic activity vitro.Am 1992; 262: F442-F448PubMed 16Bailey J.L. Wang X. England B.K. Price S.R. Ding Mitch W.E. activates proteolysis rats augmenting transcription genes encoding proteins ATP-dependent ubiquitin-proteasome pathway.J Clin Invest. 1996; 97: 1447-1453Crossref (342) Evidence caused loss architecture catabolism prompted National Foundation suggest early 2000s.17National FoundationK/DOQI nutrition failure.Am 2000; 35: S1-S140PubMed Scholar,18National evaluation, classification, stratification.Am 2002; 39: S1-S266PubMed and/or health was death uncovered, corroborating studies.19Kovesdy C.P. J.E. Kalantar-Zadeh K. Association levels mortality non-dialysis-dependent CKD.Nephrol Dial Transplant. 2009; 1232-1237Crossref (170) 20Nath K.A. M.K. Pathophysiology tubulo-interstitial rats. Interactions dietary load, ammonia, complement component C3.J 1985; 76: 667-675Crossref (377) 21Navaneethan S.D. Schold J.D. Arrigain al.Serum disease.Clin 2011; 6: 2395-2402Crossref (105) 22Raphael Baird B. Beddhu Higher within normal range associated better survival outcomes African Americans.Kidney Int. 79: 356-362Abstract (136) 23Raphael Zhang Cheung A.K. Serum NHANES III.Nephrol 28: 1207-1213Crossref (50) 24Shah S.N. Abramowitz Melamed 54: 270-277Abstract (176) 25Wesson Jo C.H. Simoni J. Angiotensin II-mediated GFR decline subtotal nephrectomy due retention reduced GFR.Nephrol 30: 762-770Crossref (37) 26Wesson Acid during induces endothelin aldosterone progressive decline, situation ameliorated diet.Kidney 2010; 78: 1128-1135Abstract (129) Results early-phase either function.27de Brito-Ashurst I. Varagunam Raftery M.J. Yaqoob M.M. slows improves status.J 2075-2084Crossref (549) 28Phisitkul Khanna al.Amelioration preserved GFR.Kidney 617-623Abstract (210) 29Goraya C. Wesson fruits vegetables attenuates moderately rate hypertensive nephropathy.Kidney 2012; 81: 86-93Abstract (202) 30Goraya comparison bicarbonate.Clin 8: 371-381Crossref (205) 31Goraya Treatment reduces urine angiotensinogen rate.Kidney 2014; 86: 1031-1038Abstract (179) 32Mahajan Sheather S.J. Broglio K.R. Rajab M.H. Daily slowing its 303-309Abstract (254) 2009, de al27de reported unblinded, non–placebo-controlled testing whether 134 They found clearance (5.9 1.9 m2), lowered ESKD 87%, parameters, midarm circumference.27de Shortly thereafter, Phisitkul al28Phisitkul citrate (n = 30) had improvement marker (such endothelin-1 N-acetyl-β-d-glucosaminidase) over years than similar who 29). Based totality these findings, has guidelines.17National Scholar,33Kidney Disease: Improving Global Outcomes (KDIGO) Work GroupKDIGO 2012 guideline evaluation management disease.Kidney Int Suppl. 3: 1-150Abstract (1064) Findings challenged notion should be reserved acidosis. Mahajan al32Mahajan 2010 40), irrespective baseline concentration, (eGFR) 40) equimolar chloride 5 years. Goraya al31Goraya later 36) similarly compared control group 22 24 These raised possibility might benefit mitigating compensatory responses facilitate excretion, detrimentally promote damage, maintain levels. Although single center limited sample size, only enrolled attributed hypertension. Nevertheless, led design execution parameters broad concentrations. (UBI) Study, at 10 sites Italy, randomly assigned 795 3-5 >18 <24 receive usual care 36 months. experimental group, dose adjusted 28 Key exclusion criteria New York Heart class III IV heart symptoms 150/90 mm Hg. follow-up period, ∼26 active versus group. 17% experienced doubling (primary end point) 6% (P 0.0001; Fig 28Di Further, 50% lower hazard initiating therapy, hospitalization rate, (6.8% 3.1%; P 0.016), providing humans may improve survival. no appreciable weight.8Di study open label controlled, date, patient While primary outcome level, BiCARB Trial tested function.9BiCARB strong adversely affects health, unclear. Several links poorer function.34Abramowitz Lower higher anion gap cardiorespiratory fitness young adults.Kidney 1033-1042Abstract (41) 35Abramowitz gait speed quadriceps adults.Am 58: 29-38Abstract 36Yenchek Rifkin al.Association functional limitation adults.Clin 9: 2111-2116Crossref (19) As far evidence, circumference27de sit-stand-sit although latter single-arm study.37Abramowitz Bauer Raff A.C. CKD.Clin 714-720Crossref (78) multicenter, double controlled.9BiCARB entry m2, age years, Participants However change (SPPB) score month 12. Importantly, starting 1.5 increased 3.0 if Dose allowed even remained Recruitment stopped 300 enrolled, instead 380 planned. general, unfavorable. At 1 year, did assessed SPPB score. Those arm slightly, significantly, scores (−0.4 point; 95% CI, −0.9 0.1), indicating worse Along lines, 6-minute (mean, 33 m) grip kg) significantly arm. No various observed. more analysis, authors concluded unfavorable, potentially harmful, cost-effective. concerning, major weaknesses. recruitment challenging, partly lack equipoise. smaller size anticipated. 87% power detect 1-point difference participants. (SPPB 12) available 274 participants 187 missing considerable. second insufficiently trial. 1.1 course study; however, mean 20.6 mEq/L, substantial proportion still study. overall conclusion harmful interpreted limitations mind. Like Trial, Alkali related. Instead, coprimary density femoral neck time.10Melamed One hundred forty-nine 20 26 United States medical centers bicarbonate, ideal weight per day matching placebo. Mean 26.4 (SD, 2.2) months 23.6 2.5) 0.001). separation groups sustained. Bone time decreased both 2-year differences sig

Language: Английский

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Nutritional Approaches for the Management of Metabolic Acidosis in Chronic Kidney Disease

Nutrients, Journal Year: 2021, Volume and Issue: 13(8), P. 2534 - 2534

Published: July 24, 2021

Metabolic acidosis is a severe complication of chronic kidney disease (CKD) which associated with nefarious impairments such as bone demineralization, muscle wasting, and hormonal alterations, for example, insulin resistance. Whilst it possible to control this condition alkali treatment, consisting in the oral administration sodium citrate or bicarbonate, type intervention not free from side effects. On contrary, opting implementation targeted dietetic-nutritional treatment CKD metabolic also comes range additional benefits lipid profile control, increased vitamins, antioxidants intake. In our review, we evaluated main dietary-nutritional regimens useful counteract acidosis, Mediterranean diet, alkaline low-protein vegan analyzing potentialities limits every treatment. Literature data suggest that diets represent valid nutritional approach prevention correction early stages, while diet are more effective advanced stages. conclusion, propose tailored approaches should therapeutic alternative acidosis.

Language: Английский

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Artificial Kidney Engineering: The Development of Dialysis Membranes for Blood Purification

Membranes, Journal Year: 2022, Volume and Issue: 12(2), P. 177 - 177

Published: Feb. 2, 2022

The artificial kidney, one of the greatest medical inventions in 20th century, has saved innumerable lives with end stage renal disease. Designs kidney evolved dramatically decades development. A hollow-fibered membrane well controlled blood and dialysate flow became major design modern kidney. Although they have been established to prolong patients' lives, purification system is still imperfect. Patient's quality life, complications, lack metabolic functions are shortcomings current treatment. direction future kidneys toward miniaturization, better biocompatibility, providing functions. Studies trials silicon nanopore membranes, tissue engineering for cell bioreactors, regeneration all under development overcome kidneys. With these advancements, wearable or implantable will be achievable.

Language: Английский

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