Altered fractional excretion of uric acid during total parenteral nutrition

The presence of crystal proven podagra coincident with a 52% decrease in plasma urate after a 3-day course of total parenteral nutrition (TPN) prompted a study of urate excretion in 9 patients with Crohn's disease. By Day 9 in those receiving TPN, plasma urate decreased 58% (p less than 0.001), while fractional urate excretion increased 94% (p less than 0.005). Twenty-four hour urate excretion and serum creatinine were not significantly altered. These findings persisted for the duration of TPN. In 2 patients with ileocolitis, the addition or deletion of either lipid emulsion or multivitamin infusions during TPN had no effect on urate values. Rather, the amino acid load or a specific constituent appears to be the causal factor. These data suggest that hypouricemia due to extensive net urate excretion is common during TPN therapy. Finally, patients with established gout may be at risk for acute gouty attacks during TPN therapy.     

肾脏调节尿酸排泄的分子机制

痛风是长期嘌呤代谢紊乱所导致的一种炎症性关节炎,高尿酸血症是其发病的重要生物化学基础.全基因组关联研究及Meta分析等研究发现了许多导致高尿酸血症的基因,其中研究较为充分的包括SLC2A9、ABCG2以及SLC22A12.SLC2A9基因编码葡萄糖转运体9(GLUT-9),GLUT-9参与调节肾小管转运尿酸,在近端小管尿酸盐的重吸收中起重要作用.ABCG2编码ABCG2蛋白,在尿酸盐的顶端分泌中发挥作用.SLC22A12基因编码尿酸重吸收转运子1(URAT1),负责尿酸盐的重吸收.本文通过阐述这三个基因及其他一些基因与高尿酸血症的关系来探究肾脏调节尿酸排泄的分子机制.     

Control of renal uric acid excretion and gout

PURPOSE OF REVIEW: Impaired renal uric acid excretion is the major mechanism of hyperuricemia in patients with primary gout. This review highlights recent advances in the knowledge of normal mechanisms of renal uric acid handling and derangement of these mechanisms in uric acid underexcretion. RECENT FINDINGS: The discovery of URAT1 has facilitated identification of other molecules potentially involved in uric acid transport in the renal tubules. Some of these molecules show gender differential expression in animal experiments. Sodium-dependent monocarboxylate cotransporters have been shown to transport lactate and butyrate, and may have roles in hyperuricemia associated with diabetic ketoacidosis and alcohol ingestion. Certain polymorphisms in SLC22A12 may be associated with the development of hyperuricemia or gout, although confirmation is needed. Mechanisms of hyperuricemia associated with uric acid underexcretion in patients with familial juvenile hyperuricemic nephropathy also remain to be clarified. Distal tubular salt wasting and compensatory upregulation of the resorption of sodium and uric acid in the proximal tubule may explain the hyperuricemia associated with this disorder. SUMMARY: Much progress has been made in understanding the mechanisms of renal uric acid handling. Elucidation of the mechanisms of hyperuricemia in patients with familial juvenile hyperuricemic nephropathy will shed light on the function of uromodulin, functional impairment of which eventually results in diminished uric acid excretion.     

Relation between creatinine and uric acid excretion.

The relation between creatinine and uric acid metabolism was analysed in 77 male patients with primary gout and 62 healthy male subjects. Significant positive correlations between 24 hour urinary creatinine and uric acid excretion were shown in both groups. The mean urinary creatinine and uric acid excretions in the patients with gout were significantly increased as compared with those of normal male controls. These results suggest that there is a close correlation between creatinine and uric acid synthesis. In addition, it seems that accelerated uric acid synthesis seen in some patients with gout is due to increased creatinine synthesis.     

Renal excretion of uric acid during prolonged fasting.

Serum and urine uric acid were evaluated during prolonged therapeutic fasting in 15 obese patients. With increasing ketonemia the serum uric acid rose from a control value of 5.9 +/- 0.4 to 12.5 +/- 1.0 mg/100 ml at 7 days and then decreased progressively to 7.7 +/- 1.3 mg/100 ml by 28 days despite sustained ketonemia. The uric acid clearance were 5.5 +/- 0.9, 1.8 +/- 0.2, and 4.4 +/- 1.5 ml/min at days 0, 7, and 25 of fasting. At the same times the creatinine clearances were 114 +/- 11, 80 +/- 6, and 64 +/- 6.3 ml/min. There was no evidence of a renal tubular abnormality as assessed by glycosuria, bicarbonaturia, or increased phosphaturia. Urate binding to plasma proteins remained unchanged. Acute studies of the renal handling of uric acid revealed a uricosuric response to the administration of sodium lactate or sodium bicarbonate by intravenous infusion and low-dose acetylsalicylic acid orally. This renal tubular response departs significantly from that observed during the overnight fasted state and could not be accounted for by extracellular fluid volume expansion or the induced acid-base changes.     

Spot urine uric acid to creatinine ratio used in the estimation of uric acid excretion in primary gout.

OBJECTIVE: Uric acid overexcretion in patients with gout is frequently assessed by the measurement of 24 hour urinary uric acid excretion, which is cumbersome with ambulatory patients, and requires accurate timing and complete collection of the specimen. We assessed whether uric acid to creatinine ratio (Uua/Ucr) in spot urine is useful for the estimation of uric acid overexcretion in patients with gout. METHODS: One hundred thirty male patients with gout and 33 non-gout male control subjects were studied. Early morning urine and/or a portion of 24 h collected urine (24 h urine) were used as spot urine samples. Uric acid overexcreters were defined as those with a 24 h urinary uric acid excretion > or = 1000 mg/day, while uric acid underexcreters were defined as those with uric acid clearance < 6 ml/min. RESULTS: There was a significant relationship between 24 h urinary uric acid excretion and early morning urine Uua/Ucr in patients with gout, while no such relationship was observed in controls. No significant difference in Uua/Ucr was observed between patients with gout and controls, or in Uua/Ucr between gout uric acid overexcreters and underexcreters in early morning urine. A significant difference in this value was observed between the 2 groups in the 24 h urine specimens. Although the diagnostic accuracy of gout uric acid overexcretion was 87.2% using early morning urine and 89.6% using 24 h urine, the sensitivity of gout uric acid overexcretion was only 25.0% when using early morning urine and 25.0% when using 24 h urine, when the cutoff value of Uua/Ucr was 0.63 and 0.64, respectively. CONCLUSION: Uua/Ucr using spot urine, especially early morning urine, is not an accurate indicator of uric acid overexcretion in patients with gout.     

Relationship between serum uric acid levels and urinary albumin excretion in patients with heart failure

OBJECTIVES: Hyperuricaemia is a constant finding in patients with heart failure (HF). Upregulated xanthine-oxidase activity seems to contribute to progression of the disease through the production of oxidative stress and the development of vascular and endothelial dysfunction. On this basis we speculated that in HF serum uric acid levels correlated with a reliable marker of endothelial dysfunction as urinary albumin excretion. METHODS: Fifty-three patients with HF underwent assessment of serum uric acid, N-terminal probrain natriuretic peptide (NT-proBNP), glomerular filtration rate (GFR), other metabolic parameters and determination of urinary albumin concentration (UAC) in a morning urine sample. RESULTS: In univariate analysis there is a direct correlation between serum uric acid levels and log UAC (r = 0.43, P < 0.01); uric acid correlates also positively with log NT-proBNP (r = 0.31, P < 0.05) and negatively with log-GFR (r = -0.38, P < 0.01). In stepwise regression analysis serum uric acid emerged as the only predictor of increased UAC (standardized coefficient = 0.42, P = 0.001) independent of other clinical determinants and metabolic factors. CONCLUSION: Serum uric acid represents the strongest predictor of elevated UAC in HF. Regression of albuminuria may be a simple target to verify the efficacy of xanthine-oxidase inhibition in these patients.     

Effect of nonsteroidal anti-inflammatory drugs on the renal excretion of uric acid

The effect of 9 nonsteroidal anti-inflammatory drugs on the renal excretion of uric acid was studied in patients with normal renal function. Diflunisal, Azapropazone and Indomethacin caused an increase and Piroxicam a decrease in the uric acid excretion. Other drugs studied had no significant influence.