Quantitative contrast-enhanced ultrasound of renal perfusion: a technology for the assessment of early diabetic nephropathy in cynomolgus macaques with type 2 diabetes mellitus
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The aim of this study was to investigate the effectiveness of contrast-enhanced ultrasound (CEUS) in predicting early nephropathy in cynomolgus macaques with spontaneous type 2 diabetes mellitus (T2DM).
Six cynomolgus macaques with spontaneous T2DM and six normal cynomolgus macaques (Group 1) were included in this study. The time–intensity curve was used to obtain parameters such as peak values, red blood volume (RBV), red blood flow (RBF), time to peak (TTP), and mean transit time (MTT). Biopsy renal tissue samples were assessed histopathologically. Six cynomolgus macaques with spontaneous T2DM were subgrouped into T2DM without nephropathy group (Group 2) and T2DM with nephropathy group (Group 3) based on histopathological findings.
Peak value had the largest area under the curve comparing with RBF, RBV, TTP, MTT. The sensitivity and specificity of peak value with cut-off value of 38.65 dB for the diagnosis of DN were 98.3% and 83%, respectively. Peak value, RBV, and RBF in Group 3 was significantly decreased compared with Group 1 and Group 2 (P = 0.000, x2 = 23.99; P = 0.003, x2 = 9.14; P = 0.02, x2 = 5.14).
The perfusion parameter of peak value in CEUS might be useful in predicting early diabetic nephropathy in spontaneous T2DM cynomolgus macaques.
KeywordsDiabetes Nephropathy Cut-off value Histopathology Glomerular filtration rate
Dr. Pintong Huang is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
PH designed this study. JL, JC, YS, KX, and FH acquired the data. JL, JC, and YS interpreted the data. JL wrote the main manuscript text. HZ edited the manuscript. All authors reviewed the manuscript. All authors have approved of the final version of the manuscript.
This study was funded by the National Natural Science Foundation of China (Grant Nos. 81420108018, 81527803) of China.
Compliance with ethical standards
Conflict of interest
The authors declare that there is no duality of interest associated with this manuscript.
- 2.Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, Shaw W, Law G, Desai M, Matthews DR, Group CPC (2017) Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med 377 (7):644-657. https://doi.org/10.1056/NEJMoa1611925
- 3.Hanssen NMJ, Scheijen J, Jorsal A, Parving HH, Tarnow L, Rossing P, Stehouwer CDA, Schalkwijk CG (2017) Higher Plasma Methylglyoxal Levels Are Associated With Incident Cardiovascular Disease in Individuals With Type 1 Diabetes: A 12-Year Follow-up Study. Diabetes 66 (8):2278-2283. https://doi.org/10.2337/db16-1578 CrossRefGoogle Scholar
- 6.Zhong C, Chen Z, Luo X, Wang C, Jiang H, Shao J, Guan M, Huang L, Huang X, Wang J (2018) Corrigendum to "Barhl1 is required for the differentiation of inner ear hair cell-like cells from mouse embryonic stem cells" [Int. J. Biochem. Cell Biol. 96 (2018) 79-89]. Int J Biochem Cell Biol 97:128-129. https://doi.org/10.1016/j.biocel.2018.02.009 CrossRefGoogle Scholar
- 7.Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators (2000). Lancet 355 (9200):253-259Google Scholar
- 8.Bodzek P, Olejek A, Adamusiak-Kutrowska I, Zamlynski J, Wolnicka B (2002) [Evaluation of the health care of diabetic pregnant women and their newborns in 1992-2001 in the Obstetrics and Gynaecology Department in Bytom]. Wiad Lek 55 Suppl 1:43-49Google Scholar
- 9.Moriya T, Tanaka S, Sone H, Ishibashi S, Matsunaga S, Ohashi Y, Akanuma Y, Haneda M, Katayama S (2017) Patients with type 2 diabetes having higher glomerular filtration rate showed rapid renal function decline followed by impaired glomerular filtration rate: Japan Diabetes Complications Study. J Diabetes Complications 31 (2):473-478. https://doi.org/10.1016/j.jdiacomp.2016.06.020 CrossRefGoogle Scholar
- 10.Derlin T, Gueler F, Brasen JH, Schmitz J, Hartung D, Herrmann TR, Ross TL, Wacker F, Wester HJ, Hiss M, Haller H, Bengel FM, Hueper K (2017) Integrating MRI and Chemokine Receptor CXCR4-Targeted PET for Detection of Leukocyte Infiltration in Complicated Urinary Tract Infections After Kidney Transplantation. J Nucl Med 58 (11):1831-1837. https://doi.org/10.2967/jnumed.117.193037 CrossRefGoogle Scholar
- 12.Panduru NM, Forsblom C, Saraheimo M, Thorn LM, Gordin D, Elonen N, Harjusalo V, Bierhaus A, Humpert PM, Groop PH, FinnDiane Study G (2017) Urinary liver-type fatty acid binding protein is an independent predictor of stroke and mortality in individuals with type 1 diabetes. Diabetologia 60 (9):1782-1790. https://doi.org/10.1007/s00125-017-4328-x
- 13.Marso SP, McGuire DK, Zinman B, Poulter NR, Emerson SS, Pieber TR, Pratley RE, Haahr PM, Lange M, Brown-Frandsen K, Moses A, Skibsted S, Kvist K, Buse JB, Group DS (2017) Efficacy and Safety of Degludec versus Glargine in Type 2 Diabetes. N Engl J Med 377 (8):723-732. https://doi.org/10.1056/NEJMoa1615692
- 14.Malik S, Suchal K, Khan SI, Bhatia J, Kishore K, Dinda AK, Arya DS (2017) Apigenin ameliorates streptozotocin-induced diabetic nephropathy in rats via MAPK-NF-kappaB-TNF-alpha and TGF-beta1-MAPK-fibronectin pathways. Am J Physiol Renal Physiol 313 (2):F414-F422. https://doi.org/10.1152/ajprenal.00393.2016 CrossRefGoogle Scholar
- 18.Vanhove T, Hasan M, Annaert P, Oswald S, Kuypers DRJ (2017) Pretransplant 4beta-hydroxycholesterol does not predict tacrolimus exposure or dose requirements during the first days after kidney transplantation. Br J Clin Pharmacol 83 (11):2406-2415. https://doi.org/10.1111/bcp.13343 CrossRefGoogle Scholar
- 19.den Braver NR, de Vet E, Duijzer G, Ter Beek J, Jansen SC, Hiddink GJ, Feskens EJM, Haveman-Nies A (2017) Determinants of lifestyle behavior change to prevent type 2 diabetes in high-risk individuals. Int J Behav Nutr Phys Act 14 (1):78. https://doi.org/10.1186/s12966-017-0532-9 CrossRefGoogle Scholar
- 22.Budde K, Zeier M, Witzke O, Arns W, Lehner F, Guba M, Jacobi J, Kliem V, Reinke P, Hauser IA, Vogt B, Stahl R, Rath T, Duerr M, Paulus EM, May C, Porstner M, Sommerer C, Group HS (2017) Everolimus with cyclosporine withdrawal or low-exposure cyclosporine in kidney transplantation from Month 3: a multicentre, randomized trial. Nephrol Dial Transplant 32 (6):1060-1070. https://doi.org/10.1093/ndt/gfx075
- 24.Sabatino A, Regolisti G, Bozzoli L, Fani F, Antoniotti R, Maggiore U, Fiaccadori E (2017) Reliability of bedside ultrasound for measurement of quadriceps muscle thickness in critically ill patients with acute kidney injury. Clin Nutr 36 (6):1710-1715. https://doi.org/10.1016/j.clnu.2016.09.029 CrossRefGoogle Scholar
- 25.Nishimura M, Kato Y, Tanaka T, Taki H, Tone A, Yamada K, Suzuki S, Saito M, Ando Y, Hoshiyama Y (2017) Effect of Home Blood Pressure on Inducing Remission/Regression of Microalbuminuria in Patients With Type 2 Diabetes Mellitus. Am J Hypertens 30 (8):830-839. https://doi.org/10.1093/ajh/hpx050 CrossRefGoogle Scholar
- 26.Katahira M, Hanakita M, Ito T, Suzuki M (2013) The ratio of glycosylated albumin to glycosylated hemoglobin differs between type 2 diabetic patients with low normoalbuminuria and those with high normoalbuminuria or microalbuminuria. Diabetes Care 36 (12):e207-208. https://doi.org/10.2337/dc13-1243 CrossRefGoogle Scholar
- 27.Lindhardt M, Persson F, Zurbig P, Stalmach A, Mischak H, de Zeeuw D, Lambers Heerspink H, Klein R, Orchard T, Porta M, Fuller J, Bilous R, Chaturvedi N, Parving HH, Rossing P (2017) Urinary proteomics predict onset of microalbuminuria in normoalbuminuric type 2 diabetic patients, a sub-study of the DIRECT-Protect 2 study. Nephrol Dial Transplant 32 (11):1866-1873. https://doi.org/10.1093/ndt/gfw292 Google Scholar
- 29.Al-Rubeaan K, Siddiqui K, Al-Ghonaim MA, Youssef AM, Al-Sharqawi AH, AlNaqeb D (2017) Assessment of the diagnostic value of different biomarkers in relation to various stages of diabetic nephropathy in type 2 diabetic patients. Sci Rep 7 (1):2684. https://doi.org/10.1038/s41598-017-02421-9 CrossRefGoogle Scholar
- 32.Lee G, Jeon S, Lee SK, Cheon B, Moon S, Park JG, Cho KO, Choi J (2017) Quantitative evaluation of renal parenchymal perfusion using contrast-enhanced ultrasonography in renal ischemia-reperfusion injury in dogs. J Vet Sci 18 (4):507-514. https://doi.org/10.4142/jvs.2017.18.4.507 CrossRefGoogle Scholar
- 33.Dumont V, Tolvanen TA, Kuusela S, Wang H, Nyman TA, Lindfors S, Tienari J, Nisen H, Suetsugu S, Plomann M, Kawachi H, Lehtonen S (2017) PACSIN2 accelerates nephrin trafficking and is up-regulated in diabetic kidney disease. FASEB J 31 (9):3978-3990. https://doi.org/10.1096/fj.201601265R CrossRefGoogle Scholar
- 34.Dey A, Hao S, Wosiski-Kuhn M, Stranahan AM (2017) Glucocorticoid-mediated activation of GSK3beta promotes tau phosphorylation and impairs memory in type 2 diabetes. Neurobiol Aging 57:75-83. https://doi.org/10.1016/j.neurobiolaging.2017.05.010 CrossRefGoogle Scholar
- 35.Sidhu PS, Cantisani V, Deganello A, Dietrich CF, Duran C, Franke D, Harkanyi Z, Kosiak W, Miele V, Ntoulia A, Piskunowicz M, Sellars M, Gilja OH (2017) Authors' Reply to Letter: Role of Contrast-Enhanced Ultrasound (CEUS) in Paediatric Practice: An EFSUMB Position Statement. Ultraschall Med 38 (4):447-448. https://doi.org/10.1055/s-0043-106461 CrossRefGoogle Scholar