Mora-Gutiérrez, J.M. (José María)
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- MMP-10 is Increased in Early Stage Diabetic Kidney Disease and can be Reduced by Renin-Angiotensin System Blockade(2020) Paramo, J.A. (José Antonio); Escalada, F.J. (Francisco Javier); Riera, M. (Marta); Orbe, J. (Josune); Rodriguez, J.A. (José Antonio); Fernández-Seara, M.A. (María A.); Mora-Gutiérrez, J.M. (José María); Garcia-Fernandez, N. (Nuria); Slon-Roblero, M.F. (María Fernanda); Soler, M.J. (María José)Matrix metalloproteinases have been implicated in diabetic microvascular complications. However, little is known about the pathophysiological links between MMP-10 and the renin-angiotensin system (RAS) in diabetic kidney disease (DKD). We tested the hypothesis that MMP-10 may be up-regulated in early stage DKD, and could be down-regulated by angiotensin II receptor blockade (telmisartan). Serum MMP-10 and TIMP-1 levels were measured in 268 type 2 diabetic subjects and 111 controls. Furthermore, histological and molecular analyses were performed to evaluate the renal expression of Mmp10 and Timp1 in a murine model of early type 2 DKD (db/db) after telmisartan treatment. MMP-10 (473±274pg/ml vs. 332±151; p=0.02) and TIMP-1 (573±296ng/ml vs. 375±317; p<0.001) levels were signifcantly increased in diabetic patients as compared to controls. An early increase in MMP-10 and TIMP-1 was observed and a further progressive elevation was found as DKD progressed to endstage renal disease. Diabetic mice had 4-fold greater glomerular Mmp10 expression and signifcant albuminuria compared to wild-type, which was prevented by telmisartan. MMP-10 and TIMP-1 are increased from the early stages of type 2 diabetes. Prevention of MMP-10 upregulation observed in diabetic mice could be another protective mechanism of RAS blockade in DKD.
- Perspectives on the role of magnetic resonance imaging (Mri) for noninvasive evaluation of diabetic kidney disease(2021) Echeverría-Chasco, R. (Rebeca); Fernández-Seara, M.A. (María A.); Mora-Gutiérrez, J.M. (José María); Garcia-Fernandez, N. (Nuria)Renal magnetic resonance imaging (MRI) techniques are currently in vogue, as they provide in vivo information on renal volume, function, metabolism, perfusion, oxygenation, and microstructural alterations, without the need for exogenous contrast media. New imaging biomarkers can be identified using these tools, which represent a major advance in the understanding and study of the different pathologies affecting the kidney. Diabetic kidney disease (DKD) is one of the most important diseases worldwide due to its high prevalence and impact on public health. However, its multifactorial etiology poses a challenge for both basic and clinical research. Therefore, the use of novel renal MRI techniques is an attractive step forward in the comprehension of DKD, both in its pathogenesis and in its detection and surveillance in the clinical practice. This review article outlines the most promising MRI techniques in the study of DKD, with the purpose of stimulating their clinical translation as possible tools for the diagnosis, follow-up, and monitoring of the clinical impacts of new DKD treatments.
- Glomerular diseases in diabetic patients: implications for diagnosis and management(MDPI, 2021) Bomback, A.S. (Andrew S.); Mora-Gutiérrez, J.M. (José María); Oliva-Damaso, N. (Nestor)The prevalence of diabetes continues to rise worldwide. In addition to rising rates of diabetic kidney disease, we are also seeing a parallel rise in nondiabetic kidney disease among patients with diabetes. These nondiabetic lesions include focal segmental glomerulosclerosis, IgA nephropathy, membranous nephropathy, and other glomerular diseases. The management of diabetic kidney disease is rapidly evolving to include, beyond glycemic control and renin angiotensin inhibition, the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors and mineralocorticoid receptor antagonists. These and other new treatment strategies should be applicable to managing glomerular disease in diabetic patients to reduce toxicities associated with immunosuppression and, in particular, corticosteroids. The prevalence of glomerular disease in diabetic patients is underappreciated. Diagnosis and appropriately treating these diseases remain an important avenue to modify kidney outcomes in diabetic patients.
- Matrix metalloproteinases in diabetic kidney disease(MDPI, 2020) Jacobs-Cachá, C. (Conxita); Orbe, J. (Josune); Vergara, A. (Ander); Mora-Gutiérrez, J.M. (José María); Garcia-Fernandez, N. (Nuria); Soler, M.J. (María José)Around the world diabetic kidney disease (DKD) is the main cause of chronic kidney disease (CKD), which is characterized by mesangial expansion, glomerulosclerosis, tubular atrophy, and interstitial fibrosis. The hallmark of the pathogenesis of DKD is an increased extracellular matrix (ECM) accumulation causing thickening of the glomerular and tubular basement membranes, mesangial expansion, sclerosis, and tubulointerstitial fibrosis. The matrix metalloproteases (MMPs) family are composed of zinc-dependent enzymes involved in the degradation and hydrolysis of ECM components. Several MMPs are expressed in the kidney; nephron compartments, vasculature and connective tissue. Given their important role in DKD, several studies have been performed in patients with DKD proposing that the measurement of their activity in serum or in urine may become in the future markers of early DKD. Studies from diabetic nephropathy experimental models suggest that a balance between MMPs levels and their inhibitors is needed to maintain renal homeostasis. This review focuses in the importance of the MMPs within the kidney and their modifications at the circulation, kidney and urine in patients with DKD. We also cover the most important studies performed in experimental models of diabetes in terms of MMPs levels, renal expression and its down-regulation effect
- Diagnostic and prognostic potential of multiparametric renal MRI in kidney transplant patients.(Wiley, 2023) Martín-Moreno, P.L. (Paloma L.); Echeverría-Chasco, R. (Rebeca); Bastarrika, G. (Gorka); Garcia-Ruiz, L. (Leyre); Aramendía-Vidaurreta, V. (Verónica); Cano, D. (David); Vidorreta, M. (Marta); Fernández-Seara, M.A. (María A.); Mora-Gutiérrez, J.M. (José María); Garcia-Fernandez, N. (Nuria); Villanueva, A. (Arantxa)Background: Multiparametric MRI provides assessment of functional and structural parameters in kidney allografts. It offers a non-invasive alternative to the current reference standard of kidney biopsy. Purpose: To evaluate the diagnostic and prognostic utility of MRI parameters in the assessment of allograft function in the first 3-months post-transplantation. Study Type: Prospective. Subjects: 32 transplant recipients (54 17 years, 20 females), divided into two groups according to estimated glomerular filtration rate (eGFR) at 3-months post-transplantation: inferior graft function (IGF; eGFR<45 mL/min/1.73 m2 , n = 10) and superior graft function (SGF; eGFR ≥ 45 mL/min/1.73 m2 , n = 22). Further categorization was based on the need for hemodialysis (C1) and decrease in s-creatinine (C2) at 1-week post-transplantation: delayed-graft-function (DGF: n = 4 C1, n = 10 C2) and early graft-function (EGF: n = 28 C1, n = 22 C2). Field Strength/Sequence: 3-T, pseudo-continuous arterial spin labeling, T1-mapping, and diffusion-weighted imaging. Assessment: Multiparametric MRI was evaluated at 1-week in all patients and 3-months after transplantation in 28 patients. Renal blood flow (RBF), diffusion coefficients (ADC, ΔADC, D, ΔD, D*, flowing fraction f), T1 and ΔT1 were calculated in cortex and medulla. The diagnostic and prognostic value of these parameters, obtained at 3-months and 1-week post-transplantation, respectively, was evaluated in the cortex to discriminate between DGF and EGF, and between SGF and IGF. Statistical Tests: Logistic regression, receiver-operating-characteristics, area-under-the-curve (AUC), confidence intervals (CIs), analysis-of-variance, t-test, Wilcoxon-Mann–Whitney test, Fisher’s exact test, Pearson’s correlation. P-value<0.05 was considered significant. Results: DGF patients exhibited significantly lower cortical RBF and f and higher D*. The diagnostic value of MRI for detecting DGF was excellent (AUC = 100%). Significant differences between patients with IGF and SGF were found in RBF, ΔT1, and ΔD. Multiparametric MRI showed higher diagnostic (AUC = 95.32%; CI: 88%–100%) and prognostic (AUC = 97.47%, CI: 92%–100%) values for detecting IGF than eGFR (AUC = 89.50%, CI: 79%–100%). Data Conclusion: Multiparametric MRI may show high diagnostic and prognostic value in transplanted patients, yielding better results compared to eGFR measurements. Level of Evidence: 2 Technical Efficacy: Stage 1
- Association between Circulating Levels of 25-Hydroxyvitamin D3 and Matrix Metalloproteinase-10 (MMP-10) in Patients with Type 2 Diabetes(MDPI AG, 2022) Escalada, F.J. (Francisco Javier); Orbe, J. (Josune); Fernández-Seara, M.A. (María A.); Mora-Gutiérrez, J.M. (José María); Garcia-Fernandez, N. (Nuria); Dolcet-Negre, M.M. (Marta M.); Abasheva, D. (Daria)Background: Matrix metalloproteinase-10 (MMP-10) levels increase progressively starting from early diabetic kidney disease (DKD) stages. Vitamin D3 (vitD3 ) deficit is associated with a higher risk of diabetic microangiopathy. Reduced MMP-10 expression has been observed after exposure to vitD3 . Aim: to assess how vitD3 status is related to MMP-10 levels in patients with Type 2 diabetes (T2D). Methods: 256 patients with T2D were included in this cross-sectional study. Demographic, clinical and serum MMP-10 and 25-hydroxyvitamin D3 (25(OH)D3 ) levels were collected from each patient. The association between MMP-10 and (25(OH)D3 ) levels was assessed using a correlation analysis and fitting a multivariate linear regression model. Results: Serum MMP-10 levels were inversely correlated with circulating 25(OH)D3 (rho = −0.25; p < 0.001). In the subgroup analysis this correlation was significant in patients with DKD (rho = −0.28; p = 0.001) and in subjects with vitD3 deficit (rho = −0.24; p = 0.005). In the regression model adjusted for kidney function, body adiposity, smoking and vitD supplementation MMP-10 levels were 68.7 pg/mL lower in patients with 25(OH)D3 > 20 ng/mL, with respect to ≤20 ng/mL (p = 0.006). Conclusions: vitD3 repletion status is an independent predictor of MMP-10 levels in T2D patients. Perhaps, high 25(OH)D3 values should be targeted in these patients in order to prevent vascular complications.