Treatment of metabolic acidosis in patients with stage 3 chronic kidney disease with fruits and vegetables or oral bicarbonate reduces urine angiotensinogen and preserves glomerular filtration rate

Abstract

Alkali therapy of metabolic acidosis in patients with chronic kidney disease (CKD) with plasma total CO2 (TCO2) below 22 mmol/l per KDOQI guidelines appears to preserve estimated glomerular filtration rate (eGFR). Since angiotensin II mediates GFR decline in partial nephrectomy models of CKD and even mild metabolic acidosis increases kidney angiotensin II in animals, alkali treatment of CKD-related metabolic acidosis in patients with plasma TCO2 over 22 mmol/l might preserve GFR through reduced kidney angiotensin II. To test this, we randomized 108 patients with stage 3 CKD and plasma TCO2 22-24 mmol/l to Usual Care or interventions designed to reduce dietary acid by 50% using sodium bicarbonate or base-producing fruits and vegetables. All were treated to achieve a systolic blood pressure below 130 mm Hg with regimens including angiotensin converting enzyme inhibition and followed for 3 years. Plasma TCO2 decreased in Usual Care but increased with bicarbonate or fruits and vegetables. By contrast, urine excretion of angiotensinogen, an index of kidney angiotensin II, increased in Usual Care but decreased with bicarbonate or fruits and vegetables. Creatinine-calculated and cystatin C-calculated eGFR decreased in all groups, but loss was less at 3 years with bicarbonate or fruits and vegetables than Usual Care. Thus, dietary alkali treatment of metabolic acidosis in CKD that is less severe than that for which KDOQI recommends therapy reduces kidney angiotensin II activity and preserves eGFR.

Dietary Protein as Kidney Protection: Quality or Quantity?

“…8 In addition, kidney protection provided by plantsourced protein in patients with CKD is associated with reduced urine excretion of angiotensinogen, 7 a marker of kidney AngII levels. 14 These data suggest that the benefits of vegetarian diets on nephropathy progression are mediated at least in part through AngII receptors and support the contention of Garneata et al 13 and other investigators [5][6][7] that vegetarian and possibly ketoanaloguesupplemented diets are kidney-protective interventions adjunctive to ACEIs. These data help guide further study on how these diets provide kidney protection.…”

“…Small-scale studies support that addition of plantsourced protein, such as fruits and vegetables, improves metabolic acidosis, reduces kidney injury, and slows nephropathy progression. [5][6][7] The mechanisms by which changes in the quality of ingested protein might slow nephropathy progression are incompletely understood. Substituting non-nitrogen ketoanalogues might allow patients to realize the benefit of dietary protein while avoiding possible untoward effects of nitrogenous wastes.…”

“…8 On the other hand, substituting plant-based for animal-based dietary protein promotes gut flora, which produce metabolites considered less nephrotoxic than flora promoted by animalsourced protein, 9 improves bone mineral parameters, 10,11 and reduces BP and body weight. [5][6][7]12 In this issue of the Journal of the American Society of Nephrology, Garneata et al 13 explored the potential contributions of ketoanalogues and plant-based diets to nephropathy progression by comparing effects of a very-low-vegetarian protein diet (0.3 g/kg per day) supplemented with ketoanalogues (VKD) with a usual mixed-source low-protein diet (0.6 g/kg per day) (LPD) on CKD progression to the end points of need for RRT or a 50% decline in baseline kidney function, measured as eGFR. This 18-month, prospective, randomized controlled trial of 207 patients involved a 3-month run-in to include only those who met compliance criteria.…”

“…Although Garneata et al 13 emphasize the benefit of ketoanalogues as yielding these benefits, the data do not exclude a concomitant, or possibly even a proportionately greater contribution of the vegetarian protein component of VKD. Plant-based protein without ketoanalogues is kidney protective, [5][6][7] improves metabolic acidosis, 6,7 and increases serum calcium and reduces serum phosphate in patients with CKD. 10,11 The calcium component of ketoanalogues can act as a phosphate binder to increase serum calcium and reduce serum phosphate, and ketoanalogues themselves can reduce serum urea.…”

Inflammation: A Key Contributor to the Genesis and Progression of Chronic Kidney Disease

“…A subsequent study of non-diabetic patients with CKD stage 3 ( n = 108) and with minimal metabolic acidosis (total plasma CO 2 : 22-24 mEq/L) [67] also showed consistent beneficial effects of alkali therapy or dietary acid reduction with fruits and vegetables on reducing inflammation and kidney injury. Notably, urine angio-tensinogen excretion was significantly reduced, and decline of estimated glomerular filtration rate significantly slowed with both interventions.…”