REDUCED URINARY-EXCRETION OF DOPAMINE AND METABOLITES IN CHRONIC RENAL PARENCHYMAL DISEASE

Background: Chronic renal parenchymal diseases are accompanied by a pr ogressive loss of tubular units endowed with the ability to synthesise dopamine from L-3,4-dihydroxyphenylalanine (L-DOPA), and preliminary evidence has suggested that the urinary excretion of free dopamine may be reduced in these disorders. However, it is well recognised now tha t under in vitro conditions, dopamine newly synthesised in tubular epi thelial cells undergoes extensive deamination to 3,4-dihydroxyphenylac etic acid (DOPAC) by monoamine oxidase (MAO); a small amount of the am ine is converted to homovanillic acid by both MAO and catechol-O-methy ltransferase (COMT) and a minor amount is methylated to 3-methoxytyram ine. Aims: The present study aimed at examining the relationship betwe en renal function and daily urinary levels of L-DOPA, free dopamine an d its main metabolites, DOPAC and homovanillic acid (HVA) in patients (n = 28) with chronic renal parenchymal disease, in conditions of cont rolled sodium, potassium and phosphate intake. The levels of 5-hydroxy indolacetic acid (5-HIAA) were also evaluated in the same cohort of pa tients. Results: The patients were divided in two groups according to creatinine clearance (group 1, 39+/-6 ml/min/1.73 m(2), n=14; group 2, 139+/-6 ml/min/1.73 m(2), n=14). In patients of group 1, the urinary levels of L-DOPA, dopamine and DOPAC (in nmo1/24 h) were significantly lower (60% I:eduction) than in patients of group 2 (L-DOPA, 134+/-36 vs. 308+/-51; dopamine, 759+/-75 vs. 1,936+/-117; DOPAC 2,595+/-340 vs . 7,938+/-833). Also, the urinary excretion of HVA in patients group I was significantly lower (40% reduction) than in patients of group 2 ( 17,434+/-2,455 vs. 27,179+/-2,271 nmo1/24 h). By contrast, no signific ant difference was observed in daily urinary excretion of 5-HIAA betwe en the two groups of patients (group 1, 27,280+/-3,721 nmol/day; group 2, 28,851+/-2,854 nmol/day). A positive linear relationship was found in these 28 patients between the creatinine clearance and the daily u rinary exertion of L-DOPA (r = 0.64, p< 0.001), free dopamine (r= 0.83 ; p<0.0001), DOPAC (r = 0.86; p<0.0001) and HVA (r = 0.65; p < 0.002), jut not with that of 5-HIAA (r = 0.14; ns). The Udopamine/L-DOPA and U-DOPAC/dopamine ratios were found to be similar in both groups of pat ients, whereas the U-HVA/DOPAC ratios in patients of group 1 were foun d greater than in group 2 (p<0.05). Conclusion: Patients suffering fro m chronic parenchymal disease with a compromised renal function presen t with a reduced activity of their renal dopaminergic system which cor relates well with the degree of deterioration of renal function. The r educed urinary dopamine output in renal insufficiency is not attributa ble to enhanced metabolism of renal dopamine. We suggest that the urin ary levels of DOPAC may represent a useful parameter for the assessmen t of renal dopamine synthesis.