Skip to main content

Advertisement

SpringerLink
Log in

Understanding and preventing contrast-induced acute kidney injury

  • Review Article
  • Published:

From Nature Reviews Nephrology

View current issue Sign up to alerts

Key Points

  • The incidence of contrast-induced acute kidney injury (CIAKI) is disputed, but clinically relevant CIAKI is less frequent than previously assumed

  • Individual patient risk factors determine the mechanisms by which contrast media will induce damage to the kidney

  • Pre-existing reduced renal tissue perfusion enhances the cytotoxic effects of contrast agents, which aggravate renal hypoxia; the rheological properties of contrast media have deleterious effects particularly in dehydrated patients

  • Contrast medium induces apoptosis by damaging cell membranes, which increases intracellular Ca2+ levels, activates the pro-apoptotic unfolded protein response, decreases ATP levels and subsequently inhibits the PI3K/AKT/mTOR axis

  • Volume expansion is effective in preventing CIAKI; oral hydration provides rapid short-term renal protection, whereas intravenous administration of isotonic saline offers long-lasting protection, but must be started hours before exposure to contrast agents

  • Diuretics combined with servo-controlled volume infusion might provide optimum renal protection against CIAKI; urine excretion or central venous pressure can be used as set points in this context

Abstract

Contrast-induced acute kidney injury (CIAKI) occurs in up to 30% of patients who receive iodinated contrast media and is generally considered to be the third most common cause of hospital-acquired AKI. Accurate assessment of the incidence of CIAKI is obscured, however, by the use of various definitions for diagnosis, the different populations studied and the prophylactic measures put in place. A deeper understanding of the mechanisms that underlie CIAKI is required to enable reliable risk assessment for individual patients, as their medical histories will determine the specific pathways by which contrast media administration might lead to kidney damage. Here, we highlight common triggers that prompt the development of CIAKI and the subsequent mechanisms that ultimately cause kidney damage. We also discuss effective protective measures, such as rapidly acting oral hydration schemes and loop diuretics, in the context of CIAKI pathophysiology. Understanding of how CIAKI arises in different patient groups could enable a marked reduction in incidence and improved outcomes. The ultimate goal is to shape CIAKI prevention strategies for individual patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1: Biomarkers dynamics in contrast-induced acute kidney injury (CIAKI).
Figure 2: Determinants of renal contrast medium enrichment.
Figure 3: Pathophysiological events and preventive strategies in contrast-induced acute kidney injury (CIAKI).
Figure 4: Differential protective effects of hydration and volume expansion according to administration route and fluid use.

Similar content being viewed by others

References

  1. Berlyne, N. & Berlyne, G. M. Acute renal failure following intravenous pyelography with hypaque. Acta Med. Scand. 171, 39–41 (1962).

    Article  CAS  PubMed  Google Scholar 

  2. Nash, K., Hafeez, A. & Hou, S. Hospital-acquired renal insufficiency. Am. J. Kidney Dis. 39, 930–936 (2002).

    Article  PubMed  Google Scholar 

  3. Mozaffarian, D. et al. Executive summary: heart disease and stroke statistics — 2016 update: a report from the American Heart Association. Circulation 133, 447–454 (2016).

    Article  PubMed  Google Scholar 

  4. Solomon, R. Contrast media: are there differences in nephrotoxicity among contrast media? Biomed. Res. Int. 2014, 934947 (2014).

    PubMed  PubMed Central  Google Scholar 

  5. Weisbord, S. D. & Palevsky, P. M. Contrast-induced acute kidney injury: short- and long-term implications. Semin. Nephrol. 31, 300–309 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Tong, J. et al. Neutrophil gelatinase-associated lipocalin in the prediction of contrast-induced nephropathy: a systemic review and meta-analysis. J. Cardiovasc. Pharmacol. 66, 239–245 (2015).

    Article  CAS  PubMed  Google Scholar 

  7. Lenhard, D. C. et al. The osmolality of nonionic, iodinated contrast agents as an important factor for renal safety. Invest. Radiol. 47, 503–510 (2012).

    Article  CAS  PubMed  Google Scholar 

  8. Molitoris, B. A. Urinary biomarkers: alone are they enough? J. Am. Soc. Nephrol. 26, 1485–1488 (2015).

    Article  PubMed  Google Scholar 

  9. Niendorf, T. et al. How bold is blood oxygenation level-dependent (BOLD) magnetic resonance imaging of the kidney? Opportunities, challenges and future directions. Acta Physiol. (Oxf.) 213, 19–38 (2015).

    Article  CAS  Google Scholar 

  10. Seeliger, E. et al. Viscosity of contrast media perturbs renal hemodynamics. J. Am. Soc. Nephrol. 18, 2912–2920 (2007).

    Article  CAS  PubMed  Google Scholar 

  11. Haase, M. et al. The outcome of neutrophil gelatinase-associated lipocalin-positive subclinical acute kidney injury: a multicenter pooled analysis of prospective studies. J. Am. Coll. Cardiol. 57, 1752–1761 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ronco, C., Stacul, F. & McCullough, P. A. Subclinical acute kidney injury (AKI) due to iodine-based contrast media. Eur. Radiol. 23, 319–323 (2013).

    Article  PubMed  Google Scholar 

  13. Solomon, R. & Dauerman, H. L. Contrast-induced acute kidney injury. Circulation 122, 2451–2455 (2010).

    Article  PubMed  Google Scholar 

  14. Solomon, R. & Segal, A. Defining acute kidney injury: what is the most appropriate metric? Nat. Clin. Pract. Nephrol. 4, 208–215 (2008).

    Article  PubMed  Google Scholar 

  15. Katzberg, R. W. & Newhouse, J. H. Intravenous contrast medium-induced nephrotoxicity: is the medical risk really as great as we have come to believe? Radiology 256, 21–28 (2010).

    Article  PubMed  Google Scholar 

  16. European Society of Urogenital Radiology. Non-renal adverse reactions. ESUR http://www.esur.org/guidelines/ (2016).

  17. American College of Radiology. Manual on contrast media v10.2. ACR https://www.acr.org/quality-safety/resources/contrast-manual (2016).

  18. Levy, E. M., Viscoli, C. M. & Horwitz, R. I. The effect of acute renal failure on mortality. A cohort analysis. JAMA 275, 1489–1494 (1996).

    Article  CAS  PubMed  Google Scholar 

  19. Chawla, L. S. & Kimmel, P. L. Acute kidney injury and chronic kidney disease: an integrated clinical syndrome. Kidney Int. 82, 516–524 (2012).

    Article  PubMed  Google Scholar 

  20. Singh, P., Ricksten, S. E., Bragadottir, G., Redfors, B. & Nordquist, L. Renal oxygenation and haemodynamics in acute kidney injury and chronic kidney disease. Clin. Exp. Pharmacol. Physiol. 40, 138–147 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Bellomo, R. et al. Acute renal failure — definition, outcome measures, animal models, fluid therapy and information technology needs: the second international consensus conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit. Care 8, R204–R212 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  22. KDIGO. KDIGO clinical practice guideline for acute kidney injury. Kidney Int. Suppl. 2, 1 (2012).

  23. Goussot, S. et al. N-Terminal fragment of pro B-type natriuretic peptide as a marker of contrast-induced nephropathy after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Am. J. Cardiol. 116, 865–871 (2015).

    Article  CAS  PubMed  Google Scholar 

  24. Jurado-Roman, A. et al. Role of hydration in contrast-induced nephropathy in patients who underwent primary percutaneous coronary intervention. Am. J. Cardiol. 115, 1174–1178 (2015).

    Article  PubMed  Google Scholar 

  25. Mitchell, A. M., Molitoris, B. A. & Teague, S. D. Contrast material-induced nephropathy: causation quandaries. Radiology 275, 928–929 (2015).

    Article  PubMed  Google Scholar 

  26. Pickering, J. W. & Endre, Z. H. Bench to bedside: the next steps for biomarkers in acute kidney injury. Am. J. Physiol. Renal Physiol. 311, F717–F721 (2016).

    Article  CAS  PubMed  Google Scholar 

  27. Lacquaniti, A. et al. Can neutrophil gelatinase-associated lipocalin help depict early contrast material-induced nephropathy? Radiology 267, 86–93 (2013).

    Article  PubMed  Google Scholar 

  28. Kafkas, N. et al. Neutrophil gelatinase-associated lipocalin as an early marker of contrast-induced nephropathy after elective invasive cardiac procedures. Clin. Cardiol. 39, 464–470 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  29. Briguori, C. et al. Cystatin C and contrast-induced acute kidney injury. Circulation 121, 2117–2122 (2010).

    Article  CAS  PubMed  Google Scholar 

  30. Sjostrom, P., Tidman, M. & Jones, I. Determination of the production rate and non-renal clearance of cystatin C and estimation of the glomerular filtration rate from the serum concentration of cystatin C in humans. Scand. J. Clin. Lab. Invest. 65, 111–124 (2005).

    Article  CAS  PubMed  Google Scholar 

  31. Schloerb, P. R. Total body water distribution of creatinine and urea in nephrectomized dogs. Am. J. Physiol. 199, 661–665 (1960).

    Article  CAS  PubMed  Google Scholar 

  32. Tenstad, O., Roald, A. B., Grubb, A. & Aukland, K. Renal handling of radiolabelled human cystatin C in the rat. Scand. J. Clin. Lab. Invest. 56, 409–414 (1996).

    Article  CAS  PubMed  Google Scholar 

  33. Li, L. P. et al. Efficacy of preventive interventions for iodinated contrast-induced acute kidney injury evaluated by intrarenal oxygenation as an early marker. Invest. Radiol. 49, 647–652 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Lim, A. I., Tang, S. C., Lai, K. N. & Leung, J. C. Kidney injury molecule-1: more than just an injury marker of tubular epithelial cells? J. Cell. Physiol. 228, 917–924 (2013).

    Article  CAS  PubMed  Google Scholar 

  35. Singer, E. et al. Neutrophil gelatinase-associated lipocalin: pathophysiology and clinical applications. Acta Physiol. (Oxf.) 207, 663–672 (2013).

    Article  CAS  Google Scholar 

  36. Calvin, A. D., Misra, S. & Pflueger, A. Contrast-induced acute kidney injury and diabetic nephropathy. Nat. Rev. Nephrol. 6, 679–688 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  37. Zuk, A. & Bonventre, J. V. Acute kidney injury. Annu. Rev. Med. 67, 293–307 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Zafrani, L. & Ince, C. Microcirculation in acute and chronic kidney diseases. Am. J. Kidney Dis. 66, 1083–1094 (2015).

    Article  PubMed  Google Scholar 

  39. Heyman, S. N., Rosen, S., Khamaisi, M., Idee, J. M. & Rosenberger, C. Reactive oxygen species and the pathogenesis of radiocontrast-induced nephropathy. Invest. Radiol. 45, 188–195 (2010).

    Article  PubMed  Google Scholar 

  40. Li, L. P. et al. Evaluation of intrarenal oxygenation in iodinated contrast-induced acute kidney injury-susceptible rats by blood oxygen level-dependent magnetic resonance imaging. Invest. Radiol. 49, 403–410 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Arakelyan, K. et al. Early effects of an x-ray contrast medium on renal T2*/T2 MRI as compared to short-term hyperoxia, hypoxia and aortic occlusion in rats. Acta Physiol. (Oxf.) 208, 202–213 (2013).

    Article  CAS  Google Scholar 

  42. Rihal, C. S. et al. Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention. Circulation 105, 2259–2264 (2002).

    Article  PubMed  Google Scholar 

  43. Rabbani, A. B. & Nallamothu, B. K. Contrast-induced nephropathy risk assessment in real world practice. Am. J. Med. 124, 1127–1128 (2011).

    Article  PubMed  Google Scholar 

  44. Banda, J. et al. Risk factors and outcomes of contrast-induced nephropathy in hospitalised South Africans. S. Afr. Med. J. 106, 699–703 (2016).

    Article  PubMed  Google Scholar 

  45. Bhatt, S., Rajpal, N., Rathi, V. & Avasthi, R. Contrast induced nephropathy with intravenous iodinated contrast media in routine diagnostic imaging: an initial experience in a tertiary care hospital. Radiol. Res. Pract. 2016, 8792984 (2016).

    PubMed  PubMed Central  Google Scholar 

  46. Cantais, A. et al. Incidence of contrast-induced acute kidney injury in a pediatric setting: a cohort study. Pediatr. Nephrol. 31, 1355–1362 (2016).

    Article  PubMed  Google Scholar 

  47. Eng, J. et al. Comparative effect of contrast media type on the incidence of contrast-induced nephropathy: a systematic review and meta-analysis. Ann. Intern. Med. 164, 417–424 (2016).

    Article  PubMed  Google Scholar 

  48. McDonald, J. S. et al. Acute kidney injury after intravenous versus intra-arterial contrast material administration in a paired cohort. Invest. Radiol. 51, 804–809 (2016).

    Article  CAS  PubMed  Google Scholar 

  49. Newhouse, J. H., Kho, D., Rao, Q. A. & Starren, J. Frequency of serum creatinine changes in the absence of iodinated contrast material: implications for studies of contrast nephrotoxicity. AJR Am. J. Roentgenol. 191, 376–382 (2008).

    Article  PubMed  Google Scholar 

  50. Davenport, M. S. et al. Contrast material-induced nephrotoxicity and intravenous low-osmolality iodinated contrast material: risk stratification by using estimated glomerular filtration rate. Radiology 268, 719–728 (2013).

    Article  PubMed  Google Scholar 

  51. McDonald, R. J. et al. Intravenous contrast material exposure is not an independent risk factor for dialysis or mortality. Radiology 273, 714–725 (2014).

    Article  PubMed  Google Scholar 

  52. McDonald, J. S. et al. Risk of intravenous contrast material-mediated acute kidney injury: a propensity score-matched study stratified by baseline-estimated glomerular filtration rate. Radiology 271, 65–73 (2014).

    Article  PubMed  Google Scholar 

  53. Gramberg, M. C. & Penne, E. L. No association between intravenous contrast material exposure and adverse clinical outcome: are prevention protocols effective? Radiology 277, 306 (2015).

    Article  PubMed  Google Scholar 

  54. McDonald, J. S. et al. Response. Radiology 275, 929 (2015).

    Article  PubMed  Google Scholar 

  55. Mirrakhimov, A. E. & Mirrakhimov, E. M. Intravenous contrast material and acute kidney injury: a need for caution. Radiology 275, 931 (2015).

    Article  PubMed  Google Scholar 

  56. Liss, P., Persson, P. B., Hansell, P. & Lagerqvist, B. Renal failure in 57 925 patients undergoing coronary procedures using iso-osmolar or low-osmolar contrast media. Kidney Int. 70, 1811–1817 (2006).

    Article  CAS  PubMed  Google Scholar 

  57. Jost, G. et al. Viscosity of iodinated contrast agents during renal excretion. Eur. J. Radiol. 80, 373–377 (2011).

    Article  PubMed  Google Scholar 

  58. Rabelink, T. J. & de Zeeuw, D. The glycocalyx — linking albuminuria with renal and cardiovascular disease. Nat. Rev. Nephrol. 11, 667–676 (2015).

    Article  CAS  PubMed  Google Scholar 

  59. Sendeski, M. M. et al. Iodinated contrast media cause endothelial damage leading to vasoconstriction of human and rat vasa recta. Am. J. Physiol. Renal Physiol. 303, F1592–F1598 (2012).

    Article  CAS  PubMed  Google Scholar 

  60. Li, L. P. et al. Effect of iodinated contrast medium in diabetic rat kidneys as evaluated by blood-oxygenation-level-dependent magnetic resonance imaging and urinary neutrophil gelatinase-associated lipocalin. Invest. Radiol. 50, 392–396 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Heyman, S. N. et al. Radiocontrast agents induce endothelin release in vivo and in vitro. J. Am. Soc. Nephrol. 3, 58–65 (1992).

    CAS  PubMed  Google Scholar 

  62. Kennedy-Lydon, T. M., Crawford, C., Wildman, S. S. & Peppiatt-Wildman, C. M. Renal pericytes: regulators of medullary blood flow. Acta Physiol. (Oxf.) 207, 212–225 (2013).

    Article  CAS  Google Scholar 

  63. Sendeski, M. et al. Iodixanol, constriction of medullary descending vasa recta, and risk for contrast medium-induced nephropathy. Radiology 251, 697–704 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  64. Sendeski, M., Patzak, A. & Persson, P. B. Constriction of the vasa recta, the vessels supplying the area at risk for acute kidney injury, by four different iodinated contrast media, evaluating ionic, nonionic, monomeric and dimeric agents. Invest. Radiol. 45, 453–457 (2010).

    Article  PubMed  Google Scholar 

  65. Liu, Z. Z. et al. Iodinated contrast media cause direct tubular cell damage, leading to oxidative stress, low nitric oxide, and impairment of tubuloglomerular feedback. Am. J. Physiol. Renal Physiol. 306, F864–F872 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Liu, Z. Z. et al. Iodinated contrast media differentially affect afferent and efferent arteriolar tone and reactivity in mice: a possible explanation for reduced glomerular filtration rate. Radiology 265, 762–771 (2012).

    Article  PubMed  Google Scholar 

  67. Patzak, A. et al. Diadenosine pentaphosphate modulates glomerular arteriolar tone and glomerular filtration rate. Acta Physiol. (Oxf.) 213, 285–293 (2015).

    Article  CAS  Google Scholar 

  68. Ueda, J., Nygren, A., Hansell, P. & Ulfendahl, H. R. Effect of intravenous contrast media on proximal and distal tubular hydrostatic pressure in the rat kidney. Acta Radiol. 34, 83–87 (1993).

    Article  CAS  PubMed  Google Scholar 

  69. Leyssac, P. P., Holstein-Rathlou, N. H. & Skott, O. Renal blood flow, early distal sodium, and plasma renin concentrations during osmotic diuresis. Am. J. Physiol. Regul. Integr. Comp. Physiol. 279, R1268–R1276 (2000).

    Article  CAS  PubMed  Google Scholar 

  70. Michael, A. et al. Molecular mechanisms of renal cellular nephrotoxicity due to radiocontrast media. Biomed. Res. Int. 2014, 249810 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Andersen, K. J., Christensen, E. I. & Vik, H. Effects of iodinated x-ray contrast media on renal epithelial cells in culture. Invest. Radiol. 29, 955–962 (1994).

    Article  CAS  PubMed  Google Scholar 

  72. Zager, R. A., Johnson, A. C. & Hanson, S. Y. Radiographic contrast media-induced tubular injury: evaluation of oxidant stress and plasma membrane integrity. Kidney Int. 64, 128–139 (2003).

    Article  CAS  PubMed  Google Scholar 

  73. Lenhard, D. C., Frisk, A. L., Lengsfeld, P., Pietsch, H. & Jost, G. The effect of iodinated contrast agent properties on renal kinetics and oxygenation. Invest. Radiol. 48, 175–182 (2013).

    Article  CAS  PubMed  Google Scholar 

  74. Heyman, S. N. et al. Acute renal failure with selective medullary injury in the rat. J. Clin. Invest. 82, 401–412 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Yano, T., Itoh, Y., Kubota, T., Sendo, T. & Oishi, R. A prostacyclin analog beraprost sodium attenuates radiocontrast media-induced LLC-PK1 cells injury. Kidney Int. 65, 1654–1663 (2004).

    Article  CAS  PubMed  Google Scholar 

  76. Romano, G. et al. Contrast agents and renal cell apoptosis. Eur. Heart J. 29, 2569–2576 (2008).

    Article  CAS  PubMed  Google Scholar 

  77. Sumimura, T. et al. Calcium-dependent injury of human microvascular endothelial cells induced by a variety of iodinated radiographic contrast media. Invest. Radiol. 38, 366–374 (2003).

    CAS  PubMed  Google Scholar 

  78. Inagi, R., Ishimoto, Y. & Nangaku, M. Proteostasis in endoplasmic reticulum — new mechanisms in kidney disease. Nat. Rev. Nephrol. 10, 369–378 (2014).

    Article  CAS  PubMed  Google Scholar 

  79. Wu, C. T. et al. The role of endoplasmic reticulum stress-related unfolded protein response in the radiocontrast medium-induced renal tubular cell injury. Toxicol. Sci. 114, 295–301 (2010).

    Article  CAS  PubMed  Google Scholar 

  80. Peng, P. et al. Preconditioning with tauroursodeoxycholic acid protects against contrast-induced HK-2 cell apoptosis by inhibiting endoplasmic reticulum stress. Angiology 66, 941–949 (2015).

    Article  CAS  PubMed  Google Scholar 

  81. Yang, Y., Yang, D., Yang, D., Jia, R. & Ding, G. Role of reactive oxygen species-mediated endoplasmic reticulum stress in contrast-induced renal tubular cell apoptosis. Nephron Exp. Nephrol. 128, 30–36 (2014).

    Article  CAS  PubMed  Google Scholar 

  82. Pannu, N., Wiebe, N., Tonelli, M. & Alberta Kidney Disease Network. Prophylaxis strategies for contrast-induced nephropathy. JAMA 295, 2765–2779 (2006).

    Article  CAS  PubMed  Google Scholar 

  83. Stratta, P., Quaglia, M., Airoldi, A. & Aime, S. Structure–function relationships of iodinated contrast media and risk of nephrotoxicity. Curr. Med. Chem. 19, 736–743 (2012).

    Article  CAS  PubMed  Google Scholar 

  84. Seeliger, E. et al. Up to 50-fold increase in urine viscosity with iso-osmolar contrast media in the rat. Radiology 256, 406–414 (2010).

    Article  PubMed  Google Scholar 

  85. Jost, G. et al. Changes of renal water diffusion coefficient after application of iodinated contrast agents: effect of viscosity. Invest. Radiol. 46, 796–800 (2011).

    Article  CAS  PubMed  Google Scholar 

  86. Wang, Y. C., Tang, A., Chang, D., Zhang, S. J. & Ju, S. Significant perturbation in renal functional magnetic resonance imaging parameters and contrast retention for iodixanol compared with iopromide: an experimental study using blood-oxygen-level-dependent/diffusion-weighted magnetic resonance imaging and computed tomography in rats. Invest. Radiol. 49, 699–706 (2014).

    Article  CAS  PubMed  Google Scholar 

  87. Wu, C. J. et al. Acute kidney damage induced by low- and iso-osmolar contrast media in rats: comparison study with physiologic MRI and histologic-gene examination. J. Magn. Reson. Imaging 45, 291–302 (2016).

    Article  PubMed  Google Scholar 

  88. Lancelot, E., Idee, J. M., Lacledere, C., Santus, R. & Corot, C. Effects of two dimeric iodinated contrast media on renal medullary blood perfusion and oxygenation in dogs. Invest. Radiol. 37, 368–375 (2002).

    Article  PubMed  Google Scholar 

  89. Ueda, J. et al. Iodine concentrations in the rat kidney measured by X-ray microanalysis. Comparison of concentrations and viscosities in the proximal tubules and renal pelvis after intravenous injections of contrast media. Acta Radiol. 39, 90–95 (1998).

    CAS  PubMed  Google Scholar 

  90. Ladwig, M., Cantow, K., Flemming, B., Persson, P. B. & Seeliger, E. Comparison of the effects of iodixanol and iopamidol on urine flow, urin viscosity and glomerular filtration in rats. J. Urol. Nephrol. 2, 7 (2015).

    Google Scholar 

  91. de Caestecker, M. et al. Bridging translation by improving preclinical study design in AKI. J. Am. Soc. Nephrol. 26, 2905–2916 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Subramaniam, R. M. et al. in Contrast-Induced Nephropathy: Comparative Effectiveness of Preventive Measures (Agency for Healthcare Research and Quality (US), 2016).

    Google Scholar 

  93. Parker, M. D. & Boron, W. F. The divergence, actions, roles, and relatives of sodium-coupled bicarbonate transporters. Physiol. Rev. 93, 803–959 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Boron, W. F. Acid-base transport by the renal proximal tubule. J. Am. Soc. Nephrol. 17, 2368–2382 (2006).

    Article  CAS  PubMed  Google Scholar 

  95. Solomon, R. et al. Randomized trial of bicarbonate or saline study for the prevention of contrast-induced nephropathy in patients with CKD. Clin. J. Am. Soc. Nephrol. 10, 1519–1524 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Seeliger, E. et al. Proof of principle: hydration by low-osmolar mannitol-glucose solution alleviates undesirable renal effects of an iso-osmolar contrast medium in rats. Invest. Radiol. 47, 240–246 (2012).

    Article  CAS  PubMed  Google Scholar 

  97. Weinstein, J. M., Heyman, S. & Brezis, M. Potential deleterious effect of furosemide in radiocontrast nephropathy. Nephron 62, 413–415 (1992).

    Article  CAS  PubMed  Google Scholar 

  98. Solomon, R., Werner, C., Mann, D., D'Elia, J. & Silva, P. Effects of saline, mannitol, and furosemide to prevent acute decreases in renal function induced by radiocontrast agents. N. Engl. J. Med. 331, 1416–1420 (1994).

    Article  CAS  PubMed  Google Scholar 

  99. Briguori, C. et al. RenalGuard system in high-risk patients for contrast-induced acute kidney injury. Am. Heart J. 173, 67–76 (2016).

    Article  PubMed  Google Scholar 

  100. Briguori, C. et al. Renal Insufficiency After Contrast Media Administration Trial II (REMEDIAL II): RenalGuard System in high-risk patients for contrast-induced acute kidney injury. Circulation 124, 1260–1269 (2011).

    Article  CAS  PubMed  Google Scholar 

  101. Huang, X., Dorhout Mees, E., Vos, P., Hamza, S. & Braam, B. Everything we always wanted to know about furosemide but were afraid to ask. Am. J. Physiol. Renal Physiol. 310, F958–F971 (2016).

    Article  CAS  PubMed  Google Scholar 

  102. Heyman, S. N., Brezis, M., Greenfeld, Z. & Rosen, S. Protective role of furosemide and saline in radiocontrast-induced acute renal failure in the rat. Am. J. Kidney Dis. 14, 377–385 (1989).

    Article  CAS  PubMed  Google Scholar 

  103. Solomon, R. Forced diuresis with the RenalGuard system: impact on contrast induced acute kidney injury. J. Cardiol. 63, 9–13 (2014).

    Article  PubMed  Google Scholar 

  104. Weisbord, S. D. et al. Prevention of contrast-induced AKI: a review of published trials and the design of the prevention of serious adverse events following angiography (PRESERVE) trial. Clin. J. Am. Soc. Nephrol. 8, 1618–1631 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  105. Liu, Y. et al. Excessively high hydration volume may not be associated with decreased risk of contrast-induced acute kidney injury after percutaneous coronary intervention in patients with renal insufficiency. J. Am. Heart Assoc. 5, e003171 (2016).

    PubMed  PubMed Central  Google Scholar 

  106. Qian, G., Fu, Z., Guo, J., Cao, F. & Chen, Y. Prevention of contrast-induced nephropathy by central venous pressure-guided fluid administration in chronic kidney disease and congestive heart failure patients. JACC Cardiovasc. Interv. 9, 89–96 (2016).

    Article  PubMed  Google Scholar 

  107. Brar, S. S. et al. Haemodynamic-guided fluid administration for the prevention of contrast-induced acute kidney injury: the POSEIDON randomised controlled trial. Lancet 383, 1814–1823 (2014).

    Article  PubMed  Google Scholar 

  108. Maioli, M. et al. Pre-procedural bioimpedance vectorial analysis of fluid status and prediction of contrast-induced acute kidney injury. J. Am. Coll. Cardiol. 63, 1387–1394 (2014).

    Article  PubMed  Google Scholar 

  109. Trivedi, H. S. et al. A randomized prospective trial to assess the role of saline hydration on the development of contrast nephrotoxicity. Nephron Clin. Pract. 93, C29–C34 (2003).

    Article  CAS  PubMed  Google Scholar 

  110. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02084771 (2016).

  111. Akyuz, S. et al. Efficacy of oral hydration in the prevention of contrast-induced acute kidney injury in patients undergoing coronary angiography or intervention. Nephron Clin. Pract. 128, 95–100 (2014).

    Article  CAS  PubMed  Google Scholar 

  112. Kong, D. G., Hou, Y. F., Ma, L. L., Yao, D. K. & Wang, L. X. Comparison of oral and intravenous hydration strategies for the prevention of contrast-induced nephropathy in patients undergoing coronary angiography or angioplasty: a randomized clinical trial. Acta Cardiol. 67, 565–569 (2012).

    Article  PubMed  Google Scholar 

  113. Hiremath, S., Akbari, A., Shabana, W., Fergusson, D. A. & Knoll, G. A. Prevention of contrast-induced acute kidney injury: is simple oral hydration similar to intravenous? A systematic review of the evidence. PLoS ONE 8, e60009 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Moos, J. M. et al. Safety of carbon dioxide digital subtraction angiography. Arch. Surg. 146, 1428–1432 (2011).

    Article  PubMed  Google Scholar 

  115. Cho, K. J. Carbon dioxide angiography: scientific principles and practice. Vasc. Specialist Int. 31, 67–80 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  116. Stegemann, E. et al. Carbondioxide-aided angiography decreases contrast volume and preserves kidney function in peripheral vascular interventions. Angiology 67, 875–881 (2016).

    Article  CAS  PubMed  Google Scholar 

  117. Renton, M. et al. The use of carbon dioxide angiography for renal sympathetic denervation: a technical report. Br. J. Radiol. http://dx.doi.org/10.1259/bjr.20160311 (2016).

  118. Frenzel, T. et al. Characterization of a novel hafnium-based x-ray contrast agent. Invest. Radiol. 51, 776–785 (2016).

    Article  CAS  PubMed  Google Scholar 

  119. Roessler, A. C. et al. High atomic number contrast media offer potential for radiation dose reduction in contrast-enhanced computed tomography. Invest. Radiol. 51, 249–254 (2016).

    Article  CAS  PubMed  Google Scholar 

  120. Moran, S. M. & Myers, B. D. Course of acute renal failure studied by a model of creatinine kinetics. Kidney Int. 27, 928–937 (1985).

    Article  CAS  PubMed  Google Scholar 

  121. Haase, M. et al. Accuracy of neutrophil gelatinase-associated lipocalin (NGAL) in diagnosis and prognosis in acute kidney injury: a systematic review and meta-analysis. Am. J. Kidney Dis. 54, 1012–1024 (2009).

    Article  CAS  PubMed  Google Scholar 

  122. Filiopoulos, V., Biblaki, D. & Vlassopoulos, D. Neutrophil gelatinase-associated lipocalin (NGAL): a promising biomarker of contrast-induced nephropathy after computed tomography. Ren. Fail. 36, 979–986 (2014).

    Article  PubMed  Google Scholar 

  123. Danziger, J. & Zeidel, M. L. Osmotic homeostasis. Clin. J. Am. Soc. Nephrol. 10, 852–862 (2015).

    Article  CAS  PubMed  Google Scholar 

  124. Damkjaer, M. et al. Renal renin secretion as regulator of body fluid homeostasis. Pflugers Arch. 465, 153–165 (2013).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors' is supported by the German Research Foundation: FOR 1368 (M.F., E.S., A.P., P.B.P.) and the German Federal Ministry of Education and Research: programme VIP+ (E.S.).

Author information

Author notes

  1. Michael Fähling and Erdmann Seeliger: These authors contributed equally to this work.

Authors and Affiliations

  1. Charité - Universitätsmedizin Berlin, Institut für Vegetative Physiologie, Charitéplatz 1, Berlin, D-10117, Germany

    Michael Fähling, Erdmann Seeliger, Andreas Patzak & Pontus B. Persson

Authors
  1. Michael Fähling
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Erdmann Seeliger
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andreas Patzak
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pontus B. Persson
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors researched literature for the article, provided substantial discussion of the content and contributed to writing and editing of the manuscript.

Corresponding author

Correspondence to Pontus B. Persson.

Ethics declarations

Competing interests

P.B.P. is an advisor for Bayer on renal safety and has received funding from Bayer. The other authors declare no competing interests.

PowerPoint slides

Glossary

Loop diuretics

Diuretic agents that act on the thick ascending limb of the loop of Henle to inhibit sodium, chloride and potassium reabsorption.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fähling, M., Seeliger, E., Patzak, A. et al. Understanding and preventing contrast-induced acute kidney injury. Nat Rev Nephrol 13, 169–180 (2017). https://doi.org/10.1038/nrneph.2016.196

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrneph.2016.196

  • Springer Nature Limited

This article is cited by

Search

Navigation