Effect of oral alkali supplementation on progression of chronic kidney disease.

Metabolic acidosis is a frequent but asymptomatic complication in chronic kidney disease (CKD). In early stages of CKD acidosis is limited to the renal tissue and progresses to reduced serum bicarbonate levels. Reduced renal tissue pH and increased ammoniagenesis are the key mechanisms of the kidney to enhance acid excretion to the urine. The expressed protein patterns in the proximal tubular epithelial cells change remarkably, the proximal convoluted tubule develops hypertrophy, and an intra-renal enhanced renin-angiotensin-system leads to interstitial fibrosis. Since nephrons are numerically reduced in CKD each remaining functional unit has to progressively increase these mechanisms to keep up the equilibrium. The adverse effects of chronic metabolic acidosis include aside from acceleration of progression of kidney disease, the development or exacerbation of bone disease, increased degradation of muscle with muscle wasting, enhanced protein degradation and inflammation. Genome wide association studies demonstrated that tubular acid-base transporters are involved in the development of arterial hypertension. Several retrospective analyses have indicated that low serum bicarbonate predicts death in cohorts with CKD and cardiovascular disease. All studies confirmed a U-shaped association of mortality and serum bicarbonate, indicating that both, acidosis and alkalosis are associated with increased mortality. Randomized controlled trials showed that base substitution, either by modification of the diet or by simply adding alkalizing agents, might halt the decline of kidney function in subjects with CKD. In 2012 a meta-analysis concluded that alkali therapy might provide a long-term favorable effect on renal function in patients with CKD.

Carga ácida potencial renal de la dieta en niños de 2 a 6 años / Potential renal acid load in children from 2 to 6 years of age

El consumo proteico excesivo incrementa la producción endógena de ácido, lo que puede conducir a acidosis metabólica, pérdida de masa ósea, hipercalciuria, urolitiasis, retardo del crecimiento y sarcopenia, entre otros. Estimar y analizar la Carga Ácida Potencial Renal (CAPR) de la dieta en niños de 2 a 6 años. Estudio descriptivo y transversal, que incluyó 52 niños de la consulta de niños sanos del Instituto de Previsión y Asistencia Social del Ministerio del Poder Popular para la Educación, estado Miranda. Las principales variables estudiadas fueron: (1) consumo de macronutrientes, y patrón alimentario evaluado mediante recordatorio de 24 horas (R24h) y cuestionario de frecuencia de consumo (CFC). El R24H permitió determinar adecuación nutricional y el CFC la calidad de la dieta y factores de protección y riesgo dietético para una mayor carga ácida de la dieta. El consumo de nutrientes se comparó con recomendaciones nacionales e internacionales; (2) la CAPR según el método de Remer y Manz. Para el análisis estadístico se utilizó el programa SPSS, v17.0. El consumo de proteínas estuvo elevado en 46,15% de los niños. Los alimentos con mayor desbalance fueron: carnes y lácteos por consumo excesivo, frutas y hortalizas por consumo deficiente. La CAPR fue positiva en 96,2% de los niños y se correlacionó positivamente (p<0,05) con el consumo de energía, proteínas, grasas, carnes y lácteos. La dieta de los niños estudiados se caracterizó por su excesiva carga ácida con el consecuente riesgo para la generación de ácidosis sistémica y sus consecuencias metabólicas

High protein intake increases endogenous acid production, which may lead to metabolic acidosis, decrease in bone and muscle mass, hipercalciuria and urolithiasis, among other disorders. Estimate and analyze the Potential Renal Acid Load (PRAL) of the diet in children from two to six years of age. The study is descriptive, cross-sectional and correlational wich included fifty two children who assisted to an ambulatory well child clinic in Carrizales, Miranda State, Venezuela. The main variables studied were: (1) Macronutrient food intake and diet pattern which was assessed by a 24 hour recall (24hR) and a food frequency questionnaire (FFQ). The 24hR allowed to evaluate nutritional adequacy and the FFQ, the diet quality, as well as diet protection and risk factors. Nutrient intake was compared with national and international recommendations; (2) PRAL was determined according to Remer and Manz. Statistical analysis was performed by means of the SPSS, v17.0 software. Protein intake was high in 46,15% of the children. Food groups with the highest unbalance were meat and dairy products for excessive intake and fruits and vegetables for defective intake, both of which represent risk factors for acid production. PRAL was positive in 92% of the children and was positively correlated (p<0.05) with intake of energy, proteins, fat and with the food groups of meat and dairy. The diet of the studied children was characterized by an excessive acid load with the risk for the generation of systemic acidosis and its metabolic consequences

Modified cow's milk formula with reduced renal acid load preventing incipient late metabolic acidosis in premature infants.

BACKGROUND: Premature infants receiving alimentation with cow's milk formulas are at a considerably high risk of developing incipient late metabolic acidosis, an early stage in the development of manifest late metabolic acidosis. Is it possible to reduce this risk by modification of the composition of a standard formula? METHODS: The mineral composition of a cow's milk preterm formula A was modified (formula B) with the aim of reducing the alimentary load to that of human milk. 160 premature infants were fed either mother's milk (n = 50) or the modified formula B (enriched with sodium and potassium) (n = 110), and their urine pH was tested twice a week. Randomly collected subgroups of infants were studied in detail for nutrient balances. The results were compared with earlier observations of 282 premature infants fed either mother's milk (n = 28) or the standard formula A (n = 254). RESULTS: Incipient late metabolic acidosis was observed in nine of 78 premature infants receiving mother's milk, 53 of 254 premature infants receiving the standard formula A, and only one of 110 premature infants fed the modified formula B. Net acid excretion was 0.58 mmol/kg/day in 11 premature infants receiving alimentation with the modified formula B compared with 1.73 mmol/kg/day in 23 premature infants fed formula A. This reduction was mainly due to an increased alkali excess (sodium + potassium-chloride) in intake and urine. CONCLUSIONS: Reduction of renal acid load with the modified formula B had a preventive effect on the rate of development of incipient late metabolic acidosis in premature infants.

Self-limited neonatal familial hyperparathyroidism associated with hypercalciuria and renal tubular acidosis in three siblings.

Three siblings with neonatal familial hyperparathyroidism diagnosed at age 4 months, 2 months, and 5 days, respectively, were treated. Hypercalciuria, nephrocalcinosis, and renal tubular acidosis were present in each child. In all three, there were higher responses of serum parathyroid hormone to serum calcium and higher elevation of serum calcium with oral calcium loading. The metabolism of vitamin D and calcitonin seemed to be intact. Hypercalcemia associated with the abnormal response of parathyroid hormone secretion disappeared when the children passed the age of approximately 2 years, although renal tubular acidosis and nephrocalcinosis remained. An autosomal recessive inheritance seems likely.

Case report of two children with pseudohypoaldosteronism.

Two black male siblings with pseudohypoaldosteronism are reported. They became ill in infancy with failure to thrive, renal salt wasting, and marked elevation of plasma aldosterone. These two patients illustrate many features of this uncommon disorder, as well as a severe metabolic acidosis. To our knowledge, this is the first report of pseudohypoaldosteronism in a black family.

Amelioration of metabolic acidosis by dietary potassium restriction in hyperkalemic patients with chronic renal insufficiency.

Hyperkalemia has been implicated in the pathogenesis of metabolic acidosis in chronic renal insufficiency because acidosis is ameliorated after administration of medications that correct hyperkalemia: mineralocorticoids, diuretics, intestinal K+-binding agents. However, the acidosis-ameliorating effect of these medications may be a consequence not of their ability to correct hyperkalemia, but of their ability to directly stimulate renal or intestinal excretion of acid. To investigate the specific effect of correcting hyperkalemia, balance studies were performed wherein hyperkalemia was corrected solely by restriction of dietary K+ in three patients with moderate chronic renal insufficiency (Ccreat 36, 44, and 58 ml/min/1.73 m2, respectively). Reduction of K+ intake was effected by substitution of Na+ for K+ in the electrolyte supplement to a whole-food diet of low K+ content. This maneuver resulted in correction of hyperkalemia and sustained amelioration of metabolic acidosis in each patient. Net acid excretion increased only transiently, and not enough to fully account for the magnitude of the increment in plasma [HCO3-], suggesting that an extrarenal mechanism of HCO3- input to the systemic circulation was the major factor that ameliorated the systemic acidosis. Evidence of an extrarenal mechanism was obtained only during the phase of decreasing plasma [K+]. Subsequently, during sustained normokalemia, the increased plasma [HCO3-] was maintained as a consequence of a sustained increase in total renal H+ secretion, evidenced by complete reabsorption of the increased filtered load of HCO3- and no reduction in net acid excretion from control values. These results indicate that in some patients with moderate chronic renal insufficiency, metabolic acidosis is ameliorated when hyperkalemia is corrected by restriction of dietary K+ (Na+ substitution) without otherwise changing diet composition and without administration of medication. Amelioration of the acidosis is predominantly effected by extrarenal mechanisms, and is sustained by an increase in the set point at which plasma [HCO3-] is regulated by the kidney.

Severe hypertension, hyperkalemia, and renal tubular acidosis responding to dietary sodium restriction.

A 13-year-old girl with severe hypertension (240/140 mm Hg), short stature, marked hyperkalemia (8.6 mEq/liter), and renal tubular acidosis was studied. Renal parenchymal and renovascular diseases as well as endocrinologic causes of hypertension were ruled out by appropriate studies. The hypertension was associated with sodium retention, increased plasma volume, suppressed plasma renin activity, and decreased urinary excretion of aldosterone. Impaired renal excretion of potassium was demonstrated by sodium sulfate infusion when the patient was fed a high-sodium diet but a significant kaliuresis occurred when the test was performed on a low-sodium diet suggesting that renal sodium retention may play a role in the defect in potassium excretion. The renal tubular acidosis was associated with normal distal acidification but a low bicarbonate threshold (19 mmoles/liter) and marked suppression of urinary ammonium excretion. The hypertension, hyporeninemia, and hypoaldosteronism as well as the hyperkalemia and acid-base abnormalities were completely reversed by dietary sodium restriction or the administration of thiazides or furosemide. It is concluded that an unusual avidity for sodium chloride reabsorption by the renal tubules leading to extracellular volume expansion and renin-aldosterone suppression plays a significant pathogenic role in this syndrome and may explain the hypertension and biochemical abnormalities discussed.

Sodium chloride restriction and extracellular fluid volume contraction in hyperphosphatiuric vitamin D resistant rickets in the Lowe syndrome.

A patient with a Lowe syndrome was observed from birth. Progressive hyperchloraemic renal tubular acidosis, hypophosphataemia, hyperphosphaturia and generalized hyperaminoaciduria had developed in infancy. Supplementary vitamin D, alkali and a high intake of dietary phosphate were unsuccessful in controlling the severe phosphate diabetes and rickets. Contraction of the extracellular fluid volume by dietary sodium restriction resulted in correction of the acidosis, hypophosphataemia, hyperaminoaciduria, and hyperphosphaturia, and healing of the rickets.