Table 2.
Preclinical and clinical evidence of GBCM nephrotoxicity.
| Report | Study Design | Aim | Number of Subjects | GFR (mL/min) | GBCM | Dose of Gd (mmol/kg) | Results |
|---|---|---|---|---|---|---|---|
| Preclinical studies | |||||||
| Leader et al. [29] | Experimental animal model | Evaluation of nephrotoxicity in a rabbit model | 31 | Not reported | Gadopentetate (L, I) | Not reported | Brushborder enzyme (LAP, ALP, and GGT) and lysosomal enzyme of tubular cell increase after GBCM intravenous administration. |
| Chien et al. [30] | Experimental animal model | Evaluation con 0.9% saline hydration to prevent kidney failure in a rat model | 12 | Cr-Cl 2.5 | Gadodiamide (L, non-I) | 5 | High doses of GBCM impact kidney function (reduction in Cr-Cl 40%) and lead to vacuolization of proximal tubules. Hydration limits the nephrotoxicity. |
| Brillet et al. [31] | Experimental animal model | Comparison changing in kidney function between GBMC (M and I) and GBCM (L and I) | GBMC (M, I): 10 GBCM (L, I): 10 |
Cr-Cl 1.6 | Gadoterate (M, I) Gadopentetate (L, I) |
Not reported | There is no change in S-Cr with GBCM (M and L); conversely, there is a significant change in S-Cr with GBCM (L and I). |
| Barbosa Pereira et al. [32] | Experimental animal model | Evaluation of nephrotoxicity in a rat model and acetylcysteine nephron protection | 31 | 16 normal kidney function and 13 with kidney impairment |
Gadoterate meglumine (M, I) | Not applicable | In kidney impairment rats, GBCM shows a reduction of GFR. Acetylcysteine seems to reduce nephrotoxicity. |
| Elmstahl et al. [33] | Experimental animal model | Comparison between GBCM and I-CM group versus control group, intraarterial route | Case group 40 Control group 24 |
Decutered by nephrectomy | Gadopentetate, (L, I) gadodiamide (L, nonI) | Not applicable | GBCMs are more nephrotoxic than I-CM. |
| Elmstahl et al. [34] | Experimental animal model | Comparison between GBCM and I-CM, intraarterial route | 64 | Kidney impaired (Partial nephrectomy) | Gadopentetate (L, I) Gadodiamide (L, non-I) |
3 mL/kg | GBCMs induce more kidney damage than I-CM. |
| Elmstahl et al. [20] | Experimental animal model | Kidney biopsy description | 152 | Gadopentetate (L, I), Gadobutrol (M, non-I) Gadodiamide (L, non-I) |
Necrosis of proximal tubules and glomerulus Hemorrhage and congestion of the cortex, medulla, and glomerulus Vacuolation of proximal tubules Protein-filled tubules in the cortex and medulla |
||
| Kwak et al. [35] | Experimental animal model | Comparison of apoptosis in medulla and cortex between the control, GBCM group, and I-CM. | Control:3 GBCM: 9 I-CM: 9 |
Not reported | Gadopentetate (L, I) | Not reported | No difference in S-Cr between GBCM and I-CM and increase in apoptosis between the control and GBCM |
| Clinical studies | |||||||
| Safi et al. [36] | Retrospective series | Comparison in the AKI rate between GBCM and I-CM in cirrhotic patients | GBCM: 68 I-CM:84 |
S-Cr 0.88 |
Gadobytrol (M, non-I) | Not reported | The rate of AKI (defined as an increase of S-Cr of 0.5 mg/dL) is 17.9% in I-CM and 5.9% in GBCM. |
| Sambol et al. [17] | Retrospettive series | Comparison between the GBCM group and GBCM + I-CM group | 153 GBCM group 59 |
43.3 | Gadodiamide (L, non-I) |
Non reported | Rate of AKI (defined as an increase of S-Cr >0.5 mg/dL within 48 h) is 25% in the GBCM group. |
| Takahashi et al. [16] | Retrospective series | Incidence of AKI after endovascular intervention with GBCM | 68 | With AKI 18.2 No Aki 25 |
Gadodiamide (L, non-I) Gadoteridol (M, non-I) | Not reported | The rate of AKI within 48 h is 14.78%. Pre-hydration limits AKI incidence. |
| Ergun e al. [5] | Retrospective series | Evaluation of CIN after GBCM | 91 | 33 | Gadopentetate (L, I), Gadodiamide (L, non-I), or Gadoterate (M, I) |
0.2 | 12% of patients had S-Cr increase (≥0.5 mg/dL) |
| Briguori et al. [37] | Retrospective series | Comparison after coronary arterial procedure between GBCM and I-CM | GBCM:32 I-CM: 32 |
Cr-Cl GBCM 33 I-CM 30 |
Gadobutrol (M, non-I) or Gadodiamide (L-non-I) |
<0.4 | In the GBCM group, 28% of patients had S-Cr increase (≥0.5 mg/dL), while in the I-CM group, only 6.5% had S-Cr increase (≥0.5 mg/dL). |
| Sam et al. [38] | Retrospective series | Evaluation of CIN after GBCM | 195 | 38 | Gadopentetate (L, I) | 0.28 | 3.5% of patients had S-Cr increase (>1 mg/dL). |
| Rieger et al. [39] | Prospective series | Evaluation of CIN after GBCM | 29 | 23 | Gadopentetate (L, I) | 0.34 | 6.7% of patients had S-Cr increase (≥0.5 mg/dL). |
| Naito et al. [40] | Randomized trial | Comparison CIN between non-I and I GBCM | 102 | I: 94.1 Non-I: 90.5 |
Gadopentetate (L, I) Gadodiamide (L, non-I) |
Not reported | Significant S-Cystatin C increase in non-I GBCM |
| Spasojevic-Dimitrijeva et al. [41] | Prospective series | Comparison kidney damage between I-CM and GBCM | 123 | 133 | Gadopentetate (L, I) | 0.20 | Significant S-Cr and u-KIM1 increase after 24 h |
| Mawad et al. [42] | prospective series | Evaluation of urinary marker of kidney damage (IL-18, NAG, and NGAL) | 28 | >60 mL/min | Not reported | Not reported | Significant IL-18 and NAG increase, and no increase in NGAL |
| Erley et al. [43] | Randomized trial | Comparison of CIN between I-CM and GBCM | 21 | 31 | Gadobutrol | 0.57 | 50% of patients had over a 1.5-fold increase in basal S-Cr |
| Jurgensen et al. [44] | Case report | Description | 1 | 55 | Gadoteridol | Not reported | Cr-Cl descreased (<20 mL/min) within 10 days. |
| Giozzet et al. [45] | Case report | Description | 2 | 80 years: 40 84 years: 23 |
0.6 0.9 |
The need for dialysis, and partial recovery of kidney function |
|
| Thomsen et al. [46] | Case report | Description | 1 | 20 | Gadodiamide (L, non-I) | 0.14 | Need for dialysis |
| Schenker et al. [47] | Case report | Description | 1 | 15 | Gadodiamide (L, non-I) | Not reported | AKI |
| Gemery et al. [48] | Case report | Description | 1 | 13 | Gadoteridol (M, non-I) | 0.44 | S-Cr incresed to 9.3 mg/dL. |
| Akgun et al. [49] | Case report | Biopsy on human | 1 | 1 | Gadopentetate (L, I) + Gadodiamide |
0.1 + 0.19 |
S-Cr increased to 3.4 mg/dL. Tubular cell necrosis, tubular cell degeneration, and marked proliferation of tubular cells together with mild interstitial edema and interstitial inflammation |
| Fujisaki et al. [50] | Case report | Description | 1 | 20 | Gadopentetate (L, I) | 0.2 | Need for dialysis |
| Badero et al. [51] | Case report | Description | 1 | 38 | 2 times Gadobenate (L, I) in 24 ore | Not reported. Total volume of 98 cc | S-Cr increased to 7.4 mg/dL |
GBCM: Gadolinium-based contrast media, I-CM: iodinated contrast media, L: linear, M: macrocyclic, I: ionic, non-I: Non-ionic, Cr-Cl: Clearance of Creatine, S-Cr: S-Creatine, AKI: acute kidney injury, CIN: contrast-induced nephropathy, u-KIM1: kidney injury molecule-1, IL-18: Interleukin-18, NAG: N-acetyl-β-D-glucosaminidasem, NGAL: Neutrophil Gelatinase-Associated Lipocalin.