Acid retention with reduced glomerular filtration rate increases urine biomarkers of kidney and bone injury

Abstract

Diets high in acid of developed societies that do not cause metabolic acidosis in patients with chronic kidney disease nevertheless appear to cause acid retention with associated morbidity, particularly in those with reduced glomerular filtration rate. Here we used a rat 2/3 nephrectomy model of chronic kidney disease to study induction and maintenance of acid retention and its consequences on indicators of kidney and bone injury. Dietary acid was increased in animals eating base-producing soy protein with acid-producing casein and in casein-eating animals with added ammonium chloride. Using microdialysis to measure the kidney cortical acid content, we found that nephrectomized animals had greater acid retention than sham-operated animals when both ate the soy diet. Each increment in dietary acid further increased acid retention more in nephrectomized than in sham rats. Nephrectomized and sham animals achieved similar steady-state daily urine net acid excretion in response to increments in dietary acid but nephrectomized animals took longer to do so, contributing to greater acid retention that was maintained until the increased dietary acid was stopped. Acid retention was associated with increased urine excretion of both N-acetyl-β-D-glucosaminidase and deoxypyridinoline, greater in nephrectomized than control rats, consistent with kidney tubulointerstitial and bone matrix injury, respectively. Greater acid retention in nephrectomized than control animals was induced by a slower increase in urinary net acid excretion rate in response to the increment in dietary acid and also maintained until the dietary acid increment was stopped. Thus, acid retention increased biomarkers of kidney and bone injury in the urine, supporting untoward consequences to these two tissues.

Randomized, Controlled Trial of TRC101 to Increase Serum Bicarbonate in Patients with CKD

“…| TRC101 significantly increased mean serum bicarbonate (SBC) throughout the 2-week treatment period, with serum bicarbonate returning to baseline after treatment discontinuation. Mean SBC response with treatment over the 14-day intervention period (days [1][2][3][4][5][6][7][8][9][10][11][12][13][14] and during the 7-to 14-day off-treatment follow-up period (days 15-28) by dose group. Treatment with TRC101 caused a steady increase in mean SBC in all TRC101 dose groups during the on-treatment period.…”

“…Metabolic acidosis associated with CKD is characterized by an imbalance in acid production relative to excretion, resulting in the depletion of the extracellular buffer, bicarbonate, as well as buffers mobilized from bone and muscle (1)(2)(3)(4)(5)(6). Chronic metabolic acidosis is common in advanced stages of CKD, and it is associated with adverse consequences, including increased mortality, acceleration of kidney disease progression, increased muscle breakdown and insulin resistance, and the development or exacerbation of bone disease (5,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16).…”

Urine Ammonium and Preclinical Acidosis in CKD

“…Interestingly, Wesson et al 13 reported recently that incremental increases in dietary acid loads in rats after 2/3 nephrectomy (model of progressive CKD) displayed evidence of cortical interstitial acid retention (compared with sham-operated controls). The renal cortical acid milieu in these animals was associated with higher excretion rates of N-acetyl-b-Dglucosaminidase, consistent with the development of tubulointerstitial disease.…”

Eating Like a Rainbow: The Development of a Visual Aid for Nutritional Treatment of CKD Patients. A South African Project

“…Correction of acidosis, as well as maintenance of regular physical activity and correction of obesity are two further fundamental issues; a plant-based approach may be of help, in particular for acidosis correction [44,45,46,47,48]. All these issues merge into the need for higher food-awareness, a comprehensive concept that needs to be adapted to the different clinical and cultural contexts [49].…”