Alterations in urinary strong ion difference in critically ill patients with metabolic acidosis: a prospective observational study.

BACKGROUND AND OBJECTIVE: The correct renal response to metabolic acidosis should be a negative shift in the urinary strong ion difference ([SID](urinary) = [Na(+)](urinary) + [K(+)](urinary) - [Cl(-)](urinary)). Our hypothesis was that the failure to decrease the [SID](urinary) is frequently present and leads to a more severe metabolic acidosis. DESIGN, SETTING AND PARTICIPANTS: Prospective observational study conducted in the medical/surgical intensive care unit of a teaching hospital between 1 January 2006 and 30 April 2007. Participants were 98 patients with metabolic acidosis on ICU admission and 10 healthy volunteers. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Severity of metabolic acidosis; behaviour of acid-base variables according to positive or negative [SID](urinary). RESULTS: Twelve patients (12%) had negative [SID](urinary) and 86 (88%) had positive [SID](urinary). Compared with patients with positive [SID](urinary), those with negative [SID](urinary) had higher [HCO(3) (-)] (20 ±2 v 18 ±3 mmol/L), base excess ([BE]) (-5 ±2 v -7 ±2 mmol/L), anion gap ([AG]) (21 ±5 v 17 ±4 mmol/L), Δ[AG] - Δ[HCO(3)(-)] (1 ±5 v -3 ±3 mmol/L) and lower [Cl(-)] (105 ±5 v 111 ±3 mmol/L). CONCLUSIONS: Most of the critically ill patients with metabolic acidosis showed inappropriate renal compensation, as evidenced by positive [SID](urinary) and higher plasma [Cl(-)]. These patients had more severe metabolic acidosis. On the other hand, patients with adequate renal response and negative [SID](urinary) had positive Δ[AG] - Δ[HCO(3)(-)]. These findings, usually considered as a diagnosis of associated metabolic alkalosis, might be interpreted as the proper renal response to metabolic acidosis.

Chronic ethanol exposure does not impair urinary acidification even under stressful conditions.

BACKGROUND: Ethanol consumption is known to cause structural and functional renal damage in rat kidney. Acutely, ethanol impairs acid-base regulation, but a chronic effect on urine acidification has not been well elucidated. The aim of the present study was to assess urinary acidification in rats subjected to chronic ethanol consumption and renal function stressors, such as unilateral nephrectomy and/or metabolic acidosis. MATERIAL/METHODS: Ethanol-fed rats received aqueous ethanol 20% (v/v) as the sole drinking fluid for ten weeks. Then unilateral nephrectomy was performed and, five days later, metabolic acidosis was induced by administration of NH(4) Cl (1.5 mmol/kg body weight) twice a day for two days. The urinary acidification rate was assessed seven days after unilateral nephrectomy by determining urine pH, ammonium and titratable acid. RESULTS: Chronic ethanol consumption, with or without unilateral nephrectomy, did not change urine pH, titratable acid, or ammonium excretion. Although NH(4)Cl-induced metabolic acidosis resulted in a significant increase of the acidification rate, the changes were not significantly different between ethanol- fed and control groups. Renal (Na + K)-ATPase was enhanced by chronic ethanol consumption, as well as by unilateral nephrectomy, but not by NH(4)Cl-induced metabolic acidosis. CONCLUSIONS: Chronic ethanol consumption does not impair the urinary acidification function of the rat, even under stressful conditions, such as acid loading and/or unilateral nephrectomy. Although these data cannot be extrapolated to human settings, there is possible application when considering drinkers as potential kidney donors.

Aciduria glutárica tipo I: una encefalopatía metabólica extrapiramidal / Type I glutaric aciduria: an extrapyramidal metabolic encephalopathy

Se describen tres niños, uno varón, de 4, 6 y 2 años de edad, afectados de aciduria glutárica tipo I. Su desarrollo fue normal hasta la segunda mitad del primer año de vida, cuando sufrieron alteración de conciencia y convulsiones, seguidas de pérdida de las habilidades adquiridas, distonía y movimientos anormales. La tomografía axial y resonancia nuclear magnética de cerebro mostraron atrofia frontotemporal y de los núcleos caudados y putámenes. Habíagran cantidad de ácidos glutárico, 3-hidroxiglutárico y glutacónico en orina y actividad disminuida de la enzima glutaril CoA deshidrogenasa en cultivos de fibroblastos de los tres niños, confirmándose así el diagnóstico de esta afección metabólica

Effect of aluminium on urinary acidification in the rat: influence of parathyroid hormone.

1. The influence of thyroparathyroidectomy and/or acidosis on renal function and specifically on acid excretion was studied in rats treated with a cumulative dose of 2 mg of aluminium. 2. Aluminium-treated and non-treated thyroparathyroidectomized rats showed a significant decrease in glomerular filtration rate and in the urinary/plasma inulin ratio without alteration in net acid excretion. 3. Non-treated thyroparathyroidectomized acidotic rats showed a significant fall in the amount of ammonium excreted and in overall acid excretion, suggesting that parathyroid hormone participates in an important way in the defence against metabolic acidosis. 4. The effects of acidosis, thyroparathyroidectomy and aluminium treatment on renal function parameters were not additive, suggesting a common final mechanism. In normal or acidotic aluminium-treated rats, thyroparathyroidectomy had no effect on renal acid excretion, suggesting that aluminium even in low doses inhibited the action of PTH on the renal tubule. 5. After exposure to aluminium, the relative inhibition of PTH on the renal tubule may become an additional factor that could contribute to the worsening of clinical conditions in which an inappropriate retention of acid loads can occur.

Effects of parathyroid hormone on urinary acidification in the rat.

To evaluate the effects of parathyroid hormone (PTH) on urinary acidification parameters, thyroparathyroidectomy was performed in normal (TPTX) and in calcium-supplemented rats (TPTX + Ca2+). Both groups were supplemented with thyroxin. Glomerular filtration rate (GFR) fell from 7.79 +/- 0.33 in the control group (C) to 4.88 +/- 0.26 ml min-1 kg-1 in TPTX, while net acid excretion fell from 5.65 +/- 0.22 in C to 3.76 +/- 0.25 mumol min-1 kg-1 in TPTX. Kinetic data of urinary acidification obtained by microperfusion techniques in proximal tubules showed that the half-time of acidification (t/2) rose from 4.75 +/- 0.24 s in C to 8.97 +/- 0.64 s in TPTX and persisted elevated in TPTX + Ca2+ (7.40 +/- 0.43 s); in the latter group, stationary pH was not significantly different from that of the control group. Bicarbonate reabsorption (JHCO3) fell from 2.18 +/- 0.15 in C to 0.823 +/- 0.082 in TPTX and was 1.53 +/- 0.073 nmol s-1 cm-2 in TPTX + CA2+. These data suggest that normal pH gradients depend on normal calcium levels, but acidification half-times are dependent on PTH, which also contributes to keeping glomerular hemodynamics and acidification rates at normal levels.

Lipoamide dehydrogenase deficiency with primary lactic acidosis: favorable response to treatment with oral lipoic acid.

An 8-month-old boy with severe lactic acidosis was found to have lipoamide dehydrogenase deficiency. Treatment with thiamine, biotin, bicarbonate, protein restriction, and ketogenic diet failed to alleviate the lactic acidosis. Oral administration of lipoic acid 25 to 50 mg/kg produced dramatic improvement in lactic and pyruvic acidemia, which has continued for 2 years and which has been accompanied by clinical improvement.