Copyright ©The Author(s) 2015.
World J Nephrol. May 6, 2015; 4(2): 196-212
Published online May 6, 2015. doi: 10.5527/wjn.v4.i2.196
Table 1 Renal dopaminergic system impairment in experimental hypertension
Animal experimental modelRenal dopaminergic system impairmentPrincipal findingsRef.
Spontaneously hypertensive ratsD1-like receptor function impairment caused by a defective coupling of the receptor with ACIncreased sodium reabsorption as a mechanism of hypertensionOhbu et al[61]
Dahl salt-sensitive ratsD1-like receptor function impairment caused by a defective coupling of the receptor with ACPrehypertensive Dahl salt-sensitive rats exhibit a blunted natriuretic response to dopamine compared with Dahl salt-resistant ratsNishi et al[62]
DOCA salt-sensitive ratsDecreased renal dopamine productionRenal dopaminergic system is dominantly supressed in this model of hypertensionIimura et al[63]
Dopamine receptor knockout miceDefective D1-D2 like receptor/signal transductionImpaired D1 and D2-like receptor signal pathway associated with development of hypertensionBanday et al[64] Zeng et al[65] Albrecht et al[66]
C57BL/6 miceD1-like receptor function impairment associated with increased expression of GRK4 upon salt loadingImpaired ability to excrete a salt load with a resultant increase in blood pressure levelsEscano et al[67]
Mice with selective proximal tubule AADC deletionDeletion of the kidney’s ability to generate dopamine is associated with unbuffered response to angiotensin II that leads to hypertension and decreased longevity in miceIncreased expression of tubular sodium transporters, decreased natriuresis and diuresis in response to L-Dopa, decreased medullary COX-2 expression and urinary prostaglandin E2 excretion, increased renin and AT1 receptor expression, decreased AT2 and Mas receptor expression, and finally salt-sensitive hypertension.Zhang et al[42]
Old FBN ratsReduction of G-protein coupling in response to D1R activation associated with exaggerated AT1 receptor activityIncrease of oxidative stressChugh et al[68]
Renalase knockout miceAlteration of urinary dopamine concentration in luminal fluid and proximal tubular transportImpaired sodium excretion with increased blood pressureDesir[18]
3/4 nephrectomized (3/4nx) ratsDecrease in urinary levels of dopamine and in renal AADC activityA reduction in the natriuretic response to volume expansion with a time-dependent increase in both systolic and diastolic blood pressureMoreira-Rodrigues et al[69]
Obese Zucker ratsDecrease in D1-like dopamine receptor binding sites and diminished activation of G proteinsOverproduction of ROSHussain et al[70]
Table 2 Clinical studies providing evidence against/in support of clinical use of low dose dopamine
Study designResultsRef.
Against clinical use of low dose dopamineThe Australian and New Zealand Intensive Care Society (ANZICS): multicenter, randomized, double-blind, placebo-controlled324 patients with at least two criteria for the systemic inflammatory response syndrome and clinical evidence of early renal dysfunction: continuous intravenous infusion of low-dose dopamine (2 µg/kg per minute) did not attenuate the peak serum creatinine compared with placebo. There was no statistical difference in mortality between dopamine and placebo armsBellomo et al[119]
Meta-analysis study: 17 studies were randomized clinical trials (n = 854)Low dose dopamine administration did not prevent mortality or the onset of acute renal failure, or the need for haemodialysis in clinically ill patientsKellum and M Decker[120]
Meta-analysis study: 15 randomized controlled studiesDopamine administration did not present beneficial results in terms of serum creatinine changes and incidence of acute renal failure in clinically ill patientsMarik[121]
Sepsis Occurrence in Acutely Ill Patients (SOAP): Cohort, multiple-center, observational studyDopamine administration in shock patients, compared to patients who did not receive it, was associated with 20% increase in ICU and hospital mortality ratesSakr et al[122]
Renal Optimization Strategies Evaluation (ROSE) study: multicenter, double-blind, placebo-controlled randomized clinical trialLow dose dopamine (2 µg/kg per minute) did not enhance decongestion or improved renal function when added to diuretic therapy in 360 patients with acute heart failure and renal dysfunctionChen et al[123]
In support of clinical use of low dose dopamineDopamine in Acute Decompensated Heart Failure (DAD-HF) Trial: randomized clinical trialThe addition of low-dose dopamine (5 μg/kg per minute) to low-dose furosemide (5 mg/h) was associated with improvement in renal function profile and potassium homeostasis at 24 h and it was equally effective as high-dose furosemide (20 mg/h) alone on subjective perception of dyspnoea in 60 patients with acute decompensated heart failureGiamouzis et al[124]
Retrospective clinical studyContinuous infusion of furosemide in addition to low-dose dopamine compared to intermittent boluses of furosemide was less nephrotoxic and carried a lower readmission rate at 30 d in 116 patients with acute decompensated heart failureAziz et al[125]
A prospective single-center randomized double-blind placebo controlled trialThe treatment with high-dose fenoldopam at 1 μg/kg per minute (short-acting D1 agonist) during cardiopulmonary bypass in 80 pediatric patients undergoing cardiac surgery for congenital heart disease significantly decreased urinary biomarkers of acute kidney injury (urinary neutrophil gelatinase-associated lipocaline and cystatin C levels) and also reduced the incidence of acute kidney injury in the postoperative period and the use of diuretics and vasodilatorsRicci et al[126]
Clinical case findingLow doses of ANP (0.0125 μg/kg per minute) with low dose dopamine (1.0 μg/kg per minute) in acute decompensated heart failure increased urine output, decreased heart rate, improved congestion with a reduced brain natriuretic peptide level, reduced serum creatinine and the levels of urinary liver-type fatty acid binding protein -a novel reno-tubular stress marker- and 8-hydroxydeoxyguanosine -an oxidative stress markerKamiya[127]
Prospective randomized clinical studyLow dose dopamine infusion reduces renal tubular injury following cardiopulmonary bypass in 48 patients with normal or near normal baseline renal functionSumeray et al[128]