NEW PARAMAGNETIC NANOPARTICLES AS CONTRAST FOR MAGNETIC RESONANCE IMAGING IN ACUTE AND CHRONIC KIDNEY DISEASES. A NEPHROTOXICITY STUDY IN RATS

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https://storage.unitedwebnetwork.com/files/1099/68dbd8c2f3e356f36c0f109a34ae85a7.pdf

Abstract Title *

NEW PARAMAGNETIC NANOPARTICLES AS CONTRAST FOR MAGNETIC RESONANCE IMAGING IN ACUTE AND CHRONIC KIDNEY DISEASES. A NEPHROTOXICITY STUDY IN RATS

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Co-author 1

Mayara Klimuk Uchiyama mayklimuk@gmail.com School of Medicine of University of Sao Paulo Internal Medicine Sao Paulo Brazil -

Co-author 2

Katia Rodrigues Neves katza@uol.com.br School of Medicine of University of Sao Paulo Internal Medicine Sao Paulo Brazil -

Co-author 3

Robson Raphael Guimaraes robsonguimares_1@hotmail.com Istitute of Chemistry of University of Sao Paulo Fundamental Chemistry Department Sao Paulo Brazil -

Co-author 4

Claudia Ramos de Sena c.sena@hc.fm.usp.br School of Medicine of University of Sao Paulo Internal Medicine Sao Paulo Brazil -

Co-author 5

Maria Heloisa Massola Shimizu hmshimizu@gmail.com School of Medicine of University of Sao Paulo Internal Medicine Sao Paulo Brazil -

Co-author 6

Victor Alves Santana victor.asantana@fm.usp.br School of Medicine of University of Sao Paulo Internal Medicine Sao Paulo Brazil -

Co-author 7

Khallil Taverna Chaim khallil.chaim@hc.fm.usp.br School of Medicine of University of Sao Paulo Radiology Department Sao Paulo Brazil -

Co-author 8

Luzia Naoko Shinohara Furukawa luzia@usp.br School of Medicine of University of Sao Paulo Internal Medicine Sao Paulo Brazil *

Co-author 9

Co-author 10

Co-author 11

Co-author 12

Co-author 13

Co-author 14

Co-author 15

Introduction

The prevalence of both chronic and acute kidney disease has risen worldwide, increasing the need for imaging procedures. However, their use is often restricted by contraindications to contrast agents, mainly due to the risks linked to gadolinium (Gd) in magnetic resonance image (MRI). Therefore, developing new biocompatible contrast agents is essential to reduce adverse effects and allow more patients to undergo these exams. In this context, new paramagnetic nanoparticles (PNPs) could be ideal for such applications. This study aimed to evaluate the nephrotoxicity of PNPs in experimental models of acute (ischemia and reperfusion-I/R) and chronic (5/6 nephrectomy – Nx5/6) kidney failure in both male and female animals.

Methods

10-week-old male and female Wistar rats underwent bilateral renal artery ischemia for either 45 minutes (males) or 30 minutes (females), followed by reperfusion (I/R) and 5/6 nephrectomy (Nx 5/6). After the recovery period, saline solution (control), Gd (0.100 mmol/kg), or PNPs (0.175 mmol/kg) were infused via the tail vein under isoflurane anesthesia. Renal function and hemodynamic parameters were assessed 24 hours later. Additionally, an MRI was performed with PNPs infusion on I/R animals using a 7 Tesla system.

Results

Figure1. Anatomical coronal T2-weighted MRI images of a Wistar rat before (pre-contrast) and 15, 20, 25, 40, 45, and 50 minutes, and also 24 hours after intravenous injection by infusion of PNPs. The series of images in the upper and lower rows shows the arrival and accumulation of the contrast agent, respectively, in the renal calyx (yellow arrow) and in the bladder (blue arrow).

PNPs image showed positive contrast in the renal calyx and bladder after 15 min of injetion in the I/R model. After 24 hours, it was no longer possible to visualize the positive contrast.

MBP (mean blood pressure), Clcreat (clearance of creatinine), *p<0,05 vs control male, **P<0.05 vs control female

		Male I/R (n=10)			Female IR (n=10)
	Control	Gd	PNPs	Control	Gd	PnPs
MBP (mmHg)	117.67±5.18	115.86±4.08	122,29±2.36	131.6±3.0	124.56±8.4	129.7±2.61
Serum creatinine (mg/dL)	0.76±0.09	0.69±0.06	0.44±0.06	0.62±0.02	0.70±0.04	0.77±0.05
Cl creatinine (mL/min/100g body weight)	0.38±0.04	0.45±0.03	0.78±0.08	0.46±0.02	0.36±0.03	0.39±0.03
Urinary protein (mg/24h)	8.94±1.4	5.53±0.75*	5.11±1.26*	2.75±0.87	1.92±0.30	3.30±0.57
Urinary albumin (mg/24h)	0.71±0.13	0.66±0.05	0.83±0.11	0.75±0.14	0.44±0.05	0.70±0.13

		Male Nx (n=9)			Female Nx (n=8)
	Control	Gd	PNPs	Control	Gd	PNPs
MBP (mmHg)	155.7±13.4	104.7±9.7*	129.8±15.6	143.3±11.3	128.9±10.3	136.4.0±14.2
Serum creatinine (mg/dL)	1.46±0.29	1.11±0.21	0.76±0.03	1.01±0.08	0.95±0.14	1.27±0.17
Cl creatinine (mL/min/100g body weight)	0.28±0.52	0.33±0.04	0.43±0.03	0.29±0.06	0.36±0.04	0.29±0.06
Urinary protein (mg/24h)	67.61±12.7	49.06±22.8	19.9±7.7*	51.05±20.8	18.86±5.9**	41.87±22.7
Urinary albumin (mg/24h)	106.02±31.7	41.75±26.3*	20.38±8.21*	56.92±25.4	23.57±8.68	2.1±1.65

Conclusion

The results indicate a promising use of PNPs in patients with renal disease. Further studies are needed to evaluate their effective excretion via the kidneys and fecal route.

Kewords