Consensus Report from Oncology Advisory Board Meeting

12 • Strategies for Prevention and Management of CI-AKI and the Role of Contrast in Oncology CT Settings Renal Functional Reserve The difference between baseline GFR and increased GFR (as in pregnancy, diabetes mellitus or increased protein intake and other conditions) is called as renal functional reserve. Even if there is a loss of 50% of the nephrons functionally (as in case of damage to one out of two kidneys), the patient will have normal GFR, but, the renal functional reserve is lost completely. After an insult to kidney, complete recovery occurs when baseline GFR as well as renal function reserves recover Many subclinical insults or events happen to kidney which affect the renal functional reserve but do not affect the baseline GFR. But, when insults to kidney occur in future, the baseline GFR also starts getting affected and patient progresses on the slippery path of chronic kidney disease (CKD). completely. But, a partial recovery is said to happen when baseline GFR recovers but renal function reserve does not. The kidney which recovers partially is highly susceptible to kidney disease; any future insult to such a kidney results in increase in Cr but not GFR.This condition leads to chronic renal hypoperfusion, apoptosis, sclerosis, and progression to CKD. In patients presenting for diagnosis of cancer or for treatment with chemotherapeutic drugs, the presence of renal function reserve will ensure that kidney functions are not affected even if a strong chemotherapeutic drug or a CM is used. However, in patients with damage to renal function reserve, even a minor insult by a chemotherapeutic drug or CM will lead to AKI. So, the development of AKI is always dependent on a balance between exposure to nephrotoxic agents and susceptibility of the kidney to damage. Patients who develop AKI have almost 10 times more chances of developing CKD. The risk is influenced by decreasing renal functions and increasing comorbidities (especially the increasing rate of diabetes globally), as well as CM use due to the growing number of procedures. The risk of AKI in patients receiving CM for diagnostic imaging appears to be lower than in patients having interventional procedures; however, the risk is not zero and must not be ignored. Overall, recognition of full spetrum of AKI will improve its detection and management. Figure 4 depicts full spectrum of AKI. It would be worthwhile to mention that prophylactic renal replacement therapy with hemodialysis or hemofiltration does not appear to prevent the development of CI-AKI. In a meta- analysis of studies involving hemodialysis/hemofiltration in patients scheduled for radiocontrast media administration, Nature Reviews | Nephrology 0 Low High 1 2 3 4 5 6 7 Time after contrast-media exposure (days) Biomarker level GFR (ml/min/1.73m 2 ) NGAL CyC Creatinine GFR that contrary to previous belief that use of intra-arterial and intravenous administration of contrast medium could reduce the risk of CIAKI, both delivery modes might be associated with similar incidences of CIAKI 48 . more accurately is now widely recognized. Fundamental problems exist in shaping appropri- ate controls for patients receiving contrast media. The main reason for performing a non-enhanced CT scan, thereby potentially forfeiting imaging quality, lies in higher risk of CIAKI. Thus, the control group can be expected to have more renal risk factors than those receiving contrast-enhanced CTs. Such selection bias can b corrected for statistically. Once the inherent differences b twee the control gr up and the group that received contrast medium were co sidered in the anal sis, only patients with estim ted GFR <30 ml/ min/1.73 m 2 (REF. 50) were at risk of developing CIAKI. Subsequent similar studies failed to identify intravenous contrast medium exposure as an independent risk factor for AKI 51,52 . However, mimicking an appropriate control group statistically with propensity score models 48,51,52 requires having measured serum creatinine levels in the control group before the intervention 53 . Several patients whose serum creatinine levels are measured, and then do not receive contrast medium, will be at high-risk of developing AKI. In addition, contrast-enhanced imag- ing is performed for different indications than non- enhanc d imaging, thus, making the two g oup very different. The same imaging examination in the pres- ence or absence of contrast agents can only be compared directly in a few instances 54 . Reassessing CIAKI incidence The swing from considering CIAKI as a major threat to the kidney to suggesting that exposure to contrast agents does not inflict any damage to the kidney has Figure 1 | Biomarkers dynamics in contrast-induced acute kidney injury (CIAKI). Modelling serumcreatinine time courses 120 revealed a specific pattern during CIAKI, which is characterized by a sharp decline in glomerular filtration rate (GFR) followed by slowGFR recovery. Typically, serumcreatinine levels peak 2–3 days after contrast mediumexposure 16 . The tubular specific biomarker neutrophil gelatinase-associated lipocalin (NGAL) is particularly sensitive for the early diagnosis of acute kidney injury (AKI), including CIAKI 121 , showing an increase as early as 6h post-procedure 122 . Levels of cystatin C (CyC), an indicator of GFR, increase within 24h after administration of contrast medium, thus constituting a further putative indicator of early stages of CIAKI 29 . S | NEPHROLOGY VOLUME 13 | MARCH 2017 | 171 ©2017 Mac mill an Publishers Li mited, part of Spri nger Nature. All ri ghts reserved. Fig. 3. Biomarkers dynamics in contrast-induced acute kidney injury (CI-AKI). Modelling serum creatinine time courses revealed a specific pattern d ring CI-AKI, which is characterized by a sharp decline in glomerular filtration rate (GFR) followed by slow GFR recovery. Typically, serum creatinine levels peak 2–3 days after contrast medium exposure. The tubular specific biomarker neutrophil gelatinase-associated lipocalin (NGAL) is particularly sensitive for the early diagnosis of acute kidney injury (AKI), including CI-AKI, showing an increase as early as 6 h post- procedu e. Lev ls of cystatin C (CyC), an indicator of GFR, increase within 24 h after administration of contrast medium, thus constituting a further putative indicator of early stages of CI-AKI. Fig. 4. Recognition of the full spectrum of AKI will improve detection and management. Source: Ronco C, et al. Eur Radiol. 2013;23:319–323. • RIFLE/AKIN negative • Biomarker positive • RIFLE/AKIN negative • Biomarker negative • RIFLE/AKIN positive • Biomarker positive • RIFLE/ AKIN positive • Biomarker negative AKI: Acute Kidney Injury AKIN: Acute Kidney Injury Network RIFLE: Risk, Injury, Failure, Loss, End-stage renal disease AKI with structural damage AKI with structural damage and functional loss No AKI AKI with functional loss