Acidosis: progression of chronic kidney disease and quality of life

Ashurst, Ione; O’Lone, Emma; Kaushik, Tarun; McCafferty, Kieran; Yaqoob, Muhammad

doi:10.1007/s00467-014-2873-9

Cited by 18 publications

(8 citation statements)

References 32 publications

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“…It is known that metabolic acidosis in people with chronic renal failure can lead to muscle wasting and correction of the acidosis can mitigate the muscle loss [20]. This effect of acidosis on muscle may contribute to the diminished weight gain observed in people on KD.…”

Section: Acidosis-related Adverse Effects Of Ketogenic Dietmentioning

confidence: 99%

An acidosis-sparing ketogenic (ASK) diet to improve efficacy and reduce adverse effects in the treatment of refractory epilepsy

Yuen

Walcutt

Sander

2017

Epilepsy & Behavior

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Diets that increase production of ketone bodies to provide alternative fuel for the brain are evolving from the classic ketogenic diet for epilepsy devised nearly a century ago. The classic ketogenic diet and its more recent variants all appear to have similar efficacy with approximately 50% of users showing a greater than 50% seizure reduction. They all require significant medical and dietetic support, and there are tolerability issues. A review suggests that low-grade chronic metabolic acidosis associated with ketosis is likely to be an important contributor to the short term and long term adverse effects of ketogenic diets. Recent studies, particularly with the characterization of the acid sensing ion channels, suggest that chronic metabolic acidosis may increase the propensity for seizures. It is also known that low-grade chronic metabolic acidosis has a broad range of negative health effects and an increased risk of early mortality in the general population. The modified ketogenic dietary treatment we propose is formulated to limit acidosis by measures that include monitoring protein intake and maximizing consumption of alkaline mineral-rich, low carbohydrate green vegetables. We hypothesize that this acidosis-sparing ketogenic diet is expected to be associated with less adverse effects and improved efficacy. A case history of life-long intractable epilepsy shows this diet to be a successful long-term strategy but, clearly, clinical studies are needed.

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Section: Acidosis-related Adverse Effects Of Ketogenic Dietmentioning

confidence: 99%

An acidosis-sparing ketogenic (ASK) diet to improve efficacy and reduce adverse effects in the treatment of refractory epilepsy

Yuen

Walcutt

Sander

2017

Epilepsy & Behavior

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“…Our research question will be linked to the recent evidence that alkali therapy also slows the progression of CKD [32,33]. To this end, the clinical trial will include 3 arms, namely, placebo, potassium chloride, and potassium citrate.…”

Section: Introductionmentioning

confidence: 99%

Rationale and Design of a Randomized Placebo-Controlled Clinical Trial Assessing the Renoprotective Effects of Potassium Supplementation in Chronic Kidney Disease

Gritter

Vogt

Yeung

et al. 2018

Nephron

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Background/Aims: Dietary potassium (K⁺) has beneficial effects on blood pressure and cardiovascular (CV) outcomes. Recently, several epidemiological studies have revealed an association between urinary K⁺ excretion (as proxy for dietary intake) and better renal outcomes in subjects with chronic kidney disease (CKD). To address causality, we designed the “K⁺ in CKD” study. Methods: The K⁺ in CKD study is a multicenter, randomized, double blind, placebo-controlled clinical trial aiming to include 399 patients with hypertension, CKD stage 3b or 4 (estimated glomerular filtration rate [eGFR] 15–44 mL/min/1.73 m²), and an average eGFR decline > 2 mL/min/1.73 m²/year. As safety measure, all included subjects will start with a 2-week open-label phase of 40 mmol potassium chloride daily. Patients who do not subsequently develop hyperkalemia (defined as serum K⁺ >5.5 mmol/L) will be randomized to receive potassium chloride, potassium citrate (both K⁺ 40 mmol/day), or placebo for 2 years. The primary end point is the difference in eGFR after 2 years of treatment. Secondary end points include other renal outcomes (> 30% decrease in eGFR, doubling of serum creatinine, end-stage renal disease, albuminuria), ambulatory blood pressure, CV events, all-cause mortality, and incidence of hyperkalemia. Several measurements will be performed to analyze the effects of potassium supplementation, including body composition monitoring, pulse wave velocity, plasma renin and aldosterone concentrations, urinary ammonium, and intracellular K⁺ concentrations. Conclusion: The K⁺ in CKD study will demonstrate if K⁺ supplementation has a renoprotective effect in progressive CKD, and whether alkali therapy has additional beneficial effects.

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“…A recent retrospective study has evidenced that MA is also associated with increased risk of graft loss and patient mortality in kidney transplant recipients [ 19 ]. Although several studies have demonstrated a beneficial role for alkali therapy on the progression of CKD [ 5 , 7 , 11 – 15 ], no data is available if alkali treatment may also allow to better preserve renal allograft function in kidney transplant recipients with metabolic acidosis.…”

Section: Discussionmentioning

confidence: 99%

“…These data could be confirmed by other authors [ 9 ] and similar to CKD patients creatinine clearance was markedly lower in the group of transplant patients with MA compared to the non-acidotic patients. Over the past few years several studies have shown that MA plays an important role in the progression of CKD and that low serum bicarbonate levels are associated with a higher risk of progressing to end-stage renal disease [ 5 , 7 , 11 – 15 ]. Amelioration of MA in CKD patients with alkalinizing therapies delayed progression of GFR loss [ 16 – 18 ].…”

Section: Introductionmentioning

confidence: 99%

Preservation of kidney function in kidney transplant recipients by alkali therapy (Preserve-Transplant Study): rationale and study protocol

Wiegand

Ritter

Graf³

et al. 2018

BMC Nephrol

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BackgroundGraft survival after kidney transplantation has significantly improved within the last decades but there is a substantial number of patients with declining transplant function and graft loss. Over the past years several studies have shown that metabolic acidosis plays an important role in the progression of Chronic Kidney Disease (CKD) and that alkalinizing therapies significantly delayed progression of CKD. Importantly, metabolic acidosis is highly prevalent in renal transplant patients and a recent retrospective study has shown that metabolic acidosis is associated with increased risk of graft loss and patient death in kidney transplant recipients. However, no prospective trial has been initiated yet to test the role of alkali treatment on renal allograft function.MethodsThe Preserve-Transplant Study is an investigator-initiated, prospective, patient-blinded, multi-center, randomized, controlled phase-IV trial with two parallel-groups comparing sodium bicarbonate to placebo. The primary objective is to test if alkali treatment will preserve kidney graft function and diminish the progression of CKD in renal transplant patients by assesing the change in eGFR over 2 years from baseline. Additionally we want to investigate the underlying pathomechanisms of nephrotoxicity of metabolic acidosis.DiscussionThis study has the potential to provide evidence that alkali treatment may slow or reduce the progression towards graft failure and significantly decrease the rate of end stage renal disease (ESRD), thus prolonging long-term graft survival. The implementation of alkali therapy into the drug regimen of kidney transplant recipients would have a favorable risk-benefit ratio since alkali supplements are routinely used in CKD patients and represent a well-tolerated, safe and cost-effective treatment.Trial registrationClinicalTrials.gov NCT03102996. Trial registration was completed on April 6, 2017.

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Acidosis: progression of chronic kidney disease and quality of life

Cited by 18 publications

References 32 publications

An acidosis-sparing ketogenic (ASK) diet to improve efficacy and reduce adverse effects in the treatment of refractory epilepsy

An acidosis-sparing ketogenic (ASK) diet to improve efficacy and reduce adverse effects in the treatment of refractory epilepsy

Rationale and Design of a Randomized Placebo-Controlled Clinical Trial Assessing the Renoprotective Effects of Potassium Supplementation in Chronic Kidney Disease

Preservation of kidney function in kidney transplant recipients by alkali therapy (Preserve-Transplant Study): rationale and study protocol

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