Highlights
- •NP cause diuresis and natriuresis, enhances GFR and are anti-inflammatory.
- •Despite mixed results in several trials, NP decrease postoperative AKI.
- •AKI is a complex interplay between renal injury, renal hemodynamics and inflammation.
- •Natriuretic peptides modulate only some of these pathways.
- •Endpoints of dialysis/death in trials were overambitious nullifying the true effects of NP.
Abstract
Objective
The focus of this review was to elicit the mechanistic logic of the experimental and
clinical study designs of natriuretic peptides (NP) in acute kidney injury (AKI) and
to understand their respective outcomes.
Methods
Online search of PubMed and manual review of articles. Randomized trials, observational
and physiologic studies of NPs and AKI were extracted. Rationale, design and study
outcomes were analyzed.
Results
In experimental models of AKI, infusion of NP prevented post-ischemic fall in renal
blood flow (RBF) or improvement in RBF, GFR, diuresis and natriuresis and demonstrated
anti-inflammatory properties. NPs were most effective in the early stages of AKI,
also in established phase of AKI but their effectiveness were limited to the time
of infusion. Hypotension was a major side-effect. Based on these observations, preliminary
clinical studies were performed which demonstrated improved urine output, RBF and
GFR and reduced need for dialysis. However, randomized, controlled trials failed to
demonstrate improvement in dialysis-free survival in different cohorts and study designs.
Although NPs reduced the incidence of AKI in the postoperative period in cardiac surgery,
it was not associated with improved long-term survival. In contrast to randomized
trials, meta-analysis reported favorable results.
Conclusions
Reasons for the divergence of experimental and clinical outcomes of NPs in AKI are
discussed in this review article.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to European Journal of Internal MedicineAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats.Life Sci. 1981; 28: 89-94
- Emerging pathways of communication between the heart and non-cardiac organs.J Biomed Res. 2018 Jul 2; https://doi.org/10.7555/JBR.32.20170137
- Particulate guanylyl cyclase a/cGMP signaling pathway in the kidney: physiologic and therapeutic indications.Int J Mol Sci. 2018; 19 (Pii): E1006
- Atrial natriuretic peptide and dopamine in established acute renal failure in the rat.Kidney Int. 1991; 40: 21-28
- Amelioration with vessel dilator of acute tubular necrosis and renal failure established for 2 days.Am J Physiol Heart Circ Physiol. 2000; 278: H1555-H1564
- Urodilantin, not nitroprusside, combined with dopamine reverses acute renal failure.Kidney Int. 1992; 42: 1153-1159
- Beneficial effects of atrial natriuretic factor on cisplatin-induced acute renal failure in the rat.Am J Nephrol. 1987; 7: 228-234
- Effects of atrial natriuretic peptide in clinical acute renal failure.Kidney Int. 1994; 45: 1178-1731
- Effects of atrial natriuretic peptide on acute renal impairment in patients with heart failure after cardiac surgery.Intensive Care Med. 1996; 22: 230-236
- Anaritide in acute tubular necrosis. Auriculin anaritide acute renal failure study group.N Engl J Med. 1997; 336: 828-834
- Atrial natriuretic factor in oliguric acute renal failure. Anaritide acute renal failure study group.Am J Kidney Dis. 2000; 36: 767-774
- Human atrial natriuretic peptide for acute kidney injury in adult critically ill patients: a multicenter prospective observational study.J Crit Care. 2019; 51: 229-235
- In vitro and in vivo protective effect of atriopeptin iii on ischemic acute renal failure.J Clin Invest. 1987; 80: 698-705
- Atrial natriuretic factor infusion following acute renal ischemia in anesthetized dogs.Ren Physiol Biochem. 1992; 15: 73-82
- Effects of atrial natriuretic peptide on glycerol induced acute renal failure in the rat.Jpn Heart J. 1992; 33: 383-393
- Atrial natriuretic peptide protects against acute ischemic renal failure in the rat.J Clin Invest. 1987; 80: 1232-1237
- Effects of prolonged infusion of the natriuretic peptides Escherichia coli enterotoxin and atrial natriuretic peptide on the outcome of acute ischemic renal failure in the rat.Ren Fail. 2000; 22: 45-53
- Brain natriuretic peptide is not Reno-protective during renal ischemia-reperfusion injury in the rat.J Surg Res. 2010; 164: e13-e19
- Long-term infusion of atrial natriuretic peptide (ANP) improves renal blood flow and glomerular filtration rate in clinical acute renal failure.Acta Anaesthesiol Scand. 2001; 45: 536-542
- Recombinant human atrial natriuretic peptide in ischemic acute renal failure: a randomized placebo-controlled trial.Crit Care Med. 2004; 32: 1310-1315
- Effectiveness of nesiritide on dialysis or all-cause mortality in patients undergoing cardiothoracic surgery.Clin Cardiol. 2006; 29: 18-24
- Prophylactic nesiritide does not prevent dialysis or all-cause mortality in patients undergoing high-risk cardiac surgery.J Thorac Cardiovasc Surg. 2009; 138: 959-964
- NAPA investigators. effects of perioperative nesiritide in patients with left ventricular dysfunction undergoing cardiac surgery: the NAPA trial.J Am Coll Cardiol. 2007; 49: 716-726
- Multicenter trial of carperitide in patients with renal dysfunction undergoing cardiovascular surgery.Gen Thorac Cardiovasc Surg. 2012; 60: 21-30
- Reduction in the incidence of acute kidney injury after aortic arch surgery with low-dose atrial natriuretic peptide: a randomized controlled trial.Eur J Anaesthesiol. 2014; 31: 381-387
- JAPAN investigators. effects of low-dose atrial natriuretic peptide infusion on cardiac surgery-associated acute kidney injury: a multicenter randomized controlled trial.J Crit Care. 2017; 38: 253-258
- Results of low-dose carperitide infusion in high-risk patients undergoing coronary artery bypass grafting.Ann Thorac Surg. 2013; 96: 119-126
- The role of natriuretic peptide administration in cardiovascular surgery-associated renal dysfunction: a systematic review and meta-analysis of randomized controlled trials.J Cardiothorac Vasc Anesth. 2009; 23: 151-160
- Comparative efficacy of drugs for preventing acute kidney injury after cardiac surgery: a network meta-analysis.Am J Cardiovasc Drugs. 2018; 18: 49-58
- Endothelin and atrial natriuretic peptide levels following radiocontrast exposure in humans.Am J Kidney Dis. 1997; 30: 82-86
- Effects of atrial natriuretic peptide versus mannitol on renal blood flow during radiocontrast infusion in chronic renal failure.J Lab Clin Med. 1990; 116: 27-36
- Prospective study of atrial natriuretic peptide for the prevention of radiocontrast-induced nephropathy.AJKD. 1998; 31: 674-690
- Brain natriuretic peptide for prevention of contrast-induced nephropathy: a meta-analysis of randomized controlled trials.Eur J Clin Pharmacol. 2016; 72: 1311-1318
- Comparative effectiveness of 12 treatment strategies for preventing contrast-induced acute kidney injury: a systematic review and Bayesian network meta-analysis.Am J Kidney Dis. 2017; 69: 69-77
- Endotoxin-induced acute renal failure in the rat: effects of Urodilatin and Diltiazem on renal function.Clin Nephrol. 1996; 46: 117-124
- Beneficial effects of the atrial natriuretic factor analog A68828 in postischemic acute renal failure.J Pharmacol Exp Ther. 1990; 255: 1166-1169
- Short-term risk of death after treatment with nesiritide for decompensated heart failure: a pooled analysis of randomized controlled trials.JAMA. 2005; 293: 1900-1905
- Predictors of worsening renal function in adult patients with congestive heart failure receiving recombinant human B-type brain natriuretic peptide (nesiritide).Nephrol Dial Transp. 2006; 21: 3458-3465
- Impact of nesiritide on renal function in patients with acute decompensated heart failure and pre-existing renal dysfunction a randomized, double-blind, placebo-controlled clinical trial.J Am Coll Cardiol. 2007; 50: 1835-1840
- Role of medullary blood flow in the pathogenesis of renal ischemia-reperfusion injury.Curr Opin Nephrol Hypertens. 2012; 21: 33-38
- The effect of seventy-two-hour continuous infusion of long-acting natriuretic peptide on acute ischemic renal failure in the rat.Ren Fail. 2006; 28: 577-581
- Atrial natriuretic peptide has no direct effect on proximal tubule sodium and water reabsorption.Pflugers Arch. 1989; 415: 336-341
- Atrial natriuretic peptide protects against acute ischemic renal failure in the rat.J Clin Invest. 1987; 80: 1232-1237
- Differential effects of human atrial natriuretic peptide and furosemide on glomerular filtration rate and renal oxygen consumption in humans.Intensive Care Med. 2005; 31: 79-85
- C-type natriuretic peptide prevents kidney injury and attenuates oxidative and inflammatory responses in hemorrhagic shock.Amino Acids. 2017; 49: 347-354
- C-type natriuretic peptide ameliorates ischemia/reperfusion-induced acute kidney injury by inhibiting apoptosis and oxidative stress in rats.Life Sci. 2014; 117: 40-45
- Protective effect of lyophilized recombinant human brain natriuretic peptide on renal ischemia/reperfusion injury in mice.Genet Mol Res. 2015; 14: 13300-13311
- Protective effect of recombinant human brain natriuretic peptide on acute renal injury induced by endotoxin in canines.Cell Biochem Biophys. 2014; 70: 1317-1324
- Atrial natriuretic peptide attenuates ischemia/reperfusion-induced renal injury by reducing neutrophil activation in rats.Tohoku J Exp Med. 2008; 215: 257-266
- Atrial natriuretic peptide attenuation of renal ischemia-reperfusion injury after major surgery.J Surg Res. 2016; 201: 213-218
- Atrial natriuretic peptide protects against cisplatin-induced acute kidney injury.Cancer Chemother Pharmacol. 2015; 75: 123-129
- Atrial natriuretic peptide attenuates kidney-lung crosstalk in kidney injury.J Surg Res. 2014; 186: 217-225
- Atrial natriuretic peptide enhances recovery from ischemia/reperfusion-induced renal injury in rats.J Biosci Bioeng. 2010; 109: 526-530
- The protective effect of human atrial natriuretic peptide on renal damage during cardiac surgery.J Anesth. 2017; 31: 163-169
- Nesiritide modulates inflammatory response during cardiac surgery: a pilot study.Res Cardiovasc Med. 2018; 7: 137-143
- Targeting inflammation in so-called acute kidney injury.Semin Nephrol. 2016; 36: 17-30
- Immune mechanisms in the different phases of acute tubular necrosis.Kidney Res Clin Pract. 2018; 37: 185-196
- Long-term outcome of patients treated with prophylactic nesiritide for the prevention of acute kidney injury following cardiovascular surgery.Clin Cardiol. 2010; 33: 217-221
Article info
Publication history
Published online: December 04, 2019
Accepted:
November 30,
2019
Received in revised form:
November 15,
2019
Received:
August 8,
2019
Identification
Copyright
© 2019 Published by Elsevier B.V. on behalf of European Federation of Internal Medicine.
