HYPOURICAEMIA AS A MARKER OF A GENERALIZED PROXIMAL TUBULAR DAMAGE IN ALCOHOLIC PATIENTS

Evagelos Liberopoulos, George Miltiadous and Moses Elisaf*

Department of Internal Medicine, Medical School, University of Ioannina, 451 10 Ioannina, Greece

Received 26 October 2001; in revised form 14 March 2002; accepted 22 March 2002

ABSTRACT

Aims and Methods: Hypouricaemia is not frequently encountered in alcoholic patients. Described herein is the case of a 69-year-old alcoholic patient. Results: The patient presented with severe hypouricaemia (serum uric acid 95.2 µmol/l) due to renal urate wasting associated with a cluster of other metabolic abnormalities in the context of a reversible generalized dysfunction of the proximal tubules that mimicked Fanconi syndrome. Conclusions: The underlying mechanisms of this rare presentation are discussed.

INTRODUCTION

Increased serum uric acid levels are frequently encountered in alcoholic patients. However, hypouricaemia associated with uricosuria has been reported in patients with hepatic cirrhosis including patients with alcoholic liver disease (Michelis et al., 1974Go; Decaux et al., 1982Go). In such cases, a loss of hepatic xanthine oxidase activity due to severe hepatocellular injury may contribute to the pathogenesis of decreased serum uric acid levels (Michelis et al., 1974Go). Furthermore, in a carefully conducted study, De Marchi et al. (1993) showed that serum uric acid levels were slightly decreased in alcoholic patients compared with the control population (297.5 ± 71.4 vs 321.3 ± 107.1 µmol/l). Upon alcohol withdrawal, serum uric acid levels significantly increased to 321.3 ± 71.4 µmol/l (P < 0.05). On admission, seven patients (11% of the study population) exhibited hypouricaemia (serum uric acid concentration <190.4 µmol/l). Six of these patients had increased fractional excretion of uric acid (>15%). However, to the best of our knowledge, severe hypouricaemia (serum uric acid levels < 119 µmol/l) has not been reported in alcoholic patients. Here, we describe an alcoholic patient who developed severe hypouricaemia due to renal urate wasting associated with a cluster of other metabolic abnormalities in the context of a reversible generalized dysfunction of the proximal tubules that mimicked Fanconi syndrome.

CASE REPORT

A 69-year-old man was admitted to our clinic because of transient ischaemic attack (TIA). He was a heavy alcohol misuser (consuming ~200 g of alcohol per day for many years) and did not receive any drugs. On admission, the patient had severe hypouricaemia (serum uric acid 95.2 µmol/l), hypokalaemia, hypophosphataemia and hypomagnesaemia (Table 1Go). These metabolic abnormalities were accompanied by a profound renal urate, potassium, phosphate and magnesium wasting (see Table 1Go), as well as renal glucosuria (Bairaktari et al., 2001Go). Twenty-four-hour urine protein was 150 mg. There was no evidence of renal bicarbonate wasting; the arterial pH was 7.48, the serum bicarbonate concentration 21 mmol/l and the partial pressure of carbon dioxide was 30 mmHg. Renal and liver function tests (levels of serum creatinine, serum urea, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin and prothrombin time) as well as serum sodium, chloride and calcium concentrations were all within the normal ranges. Oral supplements of potassium chloride and magnesium sulphate were given to the patient. Five days after alcohol withdrawal, a significant improvement in these metabolic parameters was noticed accompanied by a marked reduction in their tubular excretion (Table 1Go).


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Table 1. Laboratory parameters on admission and after alcohol withdrawal
 
Our patient reduced his alcohol consumption during a follow-up period of 6 months and did not present with the same cluster of metabolic disorders again.

DISCUSSION

The observed reversible non-acidotic proximal tubular damage could be due to the toxic effects of alcohol on renal tubules. In fact, it is known that alcohol misuse may result in a generalized reduction in the reabsorptive ability of the proximal tubular cells (De Marchi et al., 1993Go). This hypothesis is supported by studies indicating that ethanol interferes with the carrier function of these cells by decreasing the Na+-K+-ATPase activity (Parenti et al., 1991Go; Rodrigo et al., 1991Go; Rothman et al., 1992Go). Furthermore, it is possible that the acetaldehyde, produced after oxidation of ethanol by alcohol dehydrogenase, may inhibit the activity of several enzymes in renal tubules (Gonzalez-Calvin et al., 1983Go; Rothman et al., 1992Go). Finally, the oxidation of acetaldehyde by aldehyde dehydrogenase generates free radicals of oxygen reactive species that are capable of damaging cell membranes (Lieber, 1988Go).

Even though alcohol-induced increased electrolyte excretion could be the main underlying mechanism for the observed electrolyte abnormalities, other mechanisms may play a fundamental role in their pathogenesis. In fact, the coexistent respiratory alkalosis, the elevated adrenalin concentrations and increased insulin levels, commonly found in this population, can promote the movement of ions (potassium, magnesium and phosphate) into cells (Elisaf et al., 1994Go, 1998Go). Moreover, multifactorial origin electrolyte depletion, commonly encountered in this population, can interfere with a variety of renal functions, including renal urate and electrolyte excretion (Elisaf et al., 1994Go, 1998Go; Elisaf and Siamopoulos, 1997Go; Liamis et al., 2000Go).

We conclude that hypouricaemia in alcoholic patients should be considered either as a marker of liver cirrhosis or, in the absence of severe liver disease, as a marker of alcohol-induced reversible proximal tubular damage. This abnormality may be overlooked in everyday clinical practice, since serum uric acid measurements are infrequently carried out, and this may explain why this phenomenon has not been reported before.

FOOTNOTES

* Author to whom correspondence should be addressed. Back

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