Reduced Urinary Excretion of Dopamine and Metabolites in Chronic Renal Parenchymal Disease

Abstract

Background: Chronic renal parenchymal diseases are accompanied by a progressive 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 that under in vitro conditions, dopamine newly synthesised in tubular epithelial cells undergoes extensive deamination to 3,4-dihydroxyphenylacetic acid (DOPAC) by monoamine oxidase (MAO); a small amount of the amine is converted to homovanillic acid by both MAO and catechol-O-methyltransferase (COMT) and a minor amount is methylated to 3-methoxytyramine. Aims: The present study aimed at examining the relationship between renal function and daily urinary levels of L-DOPA, free dopamine and its main metabolites, DOPAC and homovanillic acid (HVA) in patients (n = 28) with chronic renal parenchymal disease, in conditions of controlled sodium, potassium and phosphate intake. The levels of 5-hydroxyindolacetic acid (5-HIAA) were also evaluated in the same cohort of patients. Results: The patients were divided in two groups according to creatinine clearance (group 1, 39±6 ml/min/1.73 m², n = 14; group 2, 139±6 ml/min/1.73 m², n = 14). In patients of group 1, the urinary levels of L-DOPA, dopamine and DOPAC (in nmol/24 h) were significantly lower (60% reduction) than in patients of group 2 (L-DOPA, 134±36 vs. 308±51; dopamine, 759± 175 vs. 1,936± 117; DOPAC 2,595±340 vs. 7,938±833). Also, the urinary excretion of HVA in patients group 1 was significantly lower (40% reduction) than in patients of group 2 (17,434±2,455 vs. 27,179±2,271 nmol/24 h). By contrast, no significant difference was observed in daily urinary excretion of 5-HIAA between 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 urinary excretion 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), but not with that of 5-HIAA (r = 0.14; ns). The U_{dopamine/L-DOPA} and U_{DOPAC/dopamine} ratios were found to be similar in both groups of patients, whereas the U_HVA/DOPAC ratios in patients of group 1 were found greater than in group 2 (p < 0.05). Conclusion: Patients suffering from chronic parenchymal disease with a compromised renal function present with a reduced activity of their renal dopaminergic system which correlates well with the degree of deterioration of renal function. The reduced urinary dopamine output in renal insufficiency is not attributable to enhanced metabolism of renal dopamine. We suggest that the urinary levels of DOPAC may represent a useful parameter for the assessment of renal dopamine synthesis.

Renal Dopamine and Salt Sensitivity of Blood Pressure in IgA Nephropathy

“…The apparent absence of change in L-DOPA uptake/decarboxylation in proximal tubules suggests that the lower excretion rate of dopamine in SS IgA-N patients may simply denote the decreased luminal supply of L-DOPA to a reduced number of tubular units endowed with the ability to synthesize dopamine especially because a good relationship of creatinine clearance and urinary excretion of dopamine was found. This interpretation is almost consistent with a previous observation that decline of renal function in patients with chronic renal insufficiency is accompanied with a decrease in the renal production of dopamine with no changes in U dopamine/L-DOPA ratios between patients with compromised and preserved renal function [16]. The good relationship observed in the present study between creatinine clearance and urinary excretion of dopamine suggests that a reduced renal dopamine output may well come to be a useful parameter to predict the extent of tubulointerstitial involvement in IgA-N patients with Pestana/Santos/Santos/Coroas/Correia/ Serrão/Valbuena/Soares-da-Silva near normal renal function.…”

“…In fact, the urinary excretion of free dopamine and metabolites was found much lower in chronic renal insufficiency including that resulting from IgA-N than in control subjects [15,16]. In addition, the abnormal retention of sodium in these conditions was suggested to be accompanied by failure to mobilize dopamine in kidney [17].…”

Psychomotor functions at various weeks of chronic renal failure in rats

“…Many neuromediators and hormones as well as multiple regions in the brain appear to be involved in the regulation of grooming behaviour (Bolivar et al 1996;Bressers et al 1998;Cromwell et al 1998;Van Erp et al 1995).The sequential coordination of grooming depends on dopamine neurotransmission in basal ganglia circuits, as the pattern is disrupted by dopaminergic nigrostriatal lesions (Berridge 1989), and the pattern is made more rigid by the transgenic elevation of neostriatal extracellular dopamine (Berridge et al 2005). The dopamine level in renal failure was reported to be low and therefore, the mechanism of grooming appears to be much more complex in these animals (Pestana et al 1988). Future studies focussing on the role of dopamine on grooming could throw more light on this mechanism.…”

Role of Chronic Inhibition of Dopamine-Metabolizing Enzymes in the Regulation of Renal Sodium and Phosphate Excretion in the Rat Remnant Kidney

“…Patients suffering from chronic renal insuffi ciency have a reduction in the urinary excretion of dopamine and metabolites, the extent of which is related to the decrease in renal function [5,6] . However, the residual nephrons in patients with chronic renal insuffi ciency maintain an intact ability to take up and decarboxylate L-DOPA to dopamine and deaminate the newly-formed amine to DOPAC [5,7,8] .…”

“…However, the residual nephrons in patients with chronic renal insuffi ciency maintain an intact ability to take up and decarboxylate L-DOPA to dopamine and deaminate the newly-formed amine to DOPAC [5,7,8] . The physiological role of the renal dopamine system in chronic renal insuffi ciency was addressed further in studies performed with animal models of reduced renal mass.…”