Diagnostic and Prognostic Potential of Multiparametric Renal MRI in Kidney Transplant Patients.

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, ∆ $$ \Delta $$ D, D*, flowing fraction f), T1 and ∆ $$ \Delta $$ T1 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, ∆T1 , and ∆D. 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.

The coexistence of diabetic retinopathy and diabetic nephropathy is associated with worse kidney outcomes.

Background: Up to 50-60% of patients with diabetes have non-diabetic kidney disease (NDKD) on kidney biopsy. Diabetic retinopathy (DR) is a microvascular complication of diabetes frequently associated with diabetic nephropathy (DN). The objective of the current study was to investigate the kidney outcomes and survival in patients with biopsy diagnoses of DN and NDKD according to the presence of DR. Methods: We conducted an observational, multicentre and retrospective study of the pathological findings of renal biopsies from 832 consecutive patients with diabetes from 2002 to 2014 from 18 nephrology departments. The association of DR with kidney replacement therapy (KRT) or survival was assessed by Kaplan-Meier and Cox regression analyses. Results: Of 832 patients with diabetes and renal biopsy, 768 had a retinal examination and 221/768 (22.6%) had DR. During a follow-up of 10 years, 288/760 (37.9%) patients with follow-up data needed KRT and 157/760 (20.7%) died. The incidence of KRT was higher among patients with DN (alone or with NDKD) and DR [103/175 (58.9%)] than among patients without DR [88/216 (40.7%), P < .0001]. The incidence of KRT was also higher among patients with only NDKD and DR than among those without DR [18/46 (39.1%) versus 79/331 (23.9%), P < .0001]. In multivariate analysis, DR or DN were independent risk factors for KRT {hazard ratio [HR] 2.48 [confidence interval (CI) 1.85-3.31], P < .001}. DN (with or without DR) was also identified as an independent risk factor for mortality [HR 1.81 (CI 1.26-2.62), P = .001]. Conclusions: DR is associated with a higher risk of progression to kidney failure in patients with histological DN and in patients with NDKD.

A deep learning image analysis method for renal perfusion estimation in pseudo-continuous arterial spin labelling MRI.

Accurate segmentation of renal tissues is an essential step for renal perfusion estimation and postoperative assessment of the allograft. Images are usually manually labeled, which is tedious and prone to human error. We present an image analysis method for the automatic estimation of renal perfusion based on perfusion magnetic resonance imaging. Specifically, non-contrasted pseudo-continuous arterial spin labeling (PCASL) images are used for kidney transplant evaluation and perfusion estimation, as a biomarker of the status of the allograft. The proposed method uses machine/deep learning tools for the segmentation and classification of renal cortical and medullary tissues and automates the estimation of perfusion values. Data from 16 transplant patients has been used for the experiments. The automatic analysis of differentiated tissues within the kidney, such as cortex and medulla, is performed by employing the time-intensity-curves of non-contrasted T1-weighted MRI series. Specifically, using the Dice similarity coefficient as a figure of merit, results above 93%, 92% and 82% are obtained for whole kidney, cortex, and medulla, respectively. Besides, estimated cortical and medullary perfusion values are considered to be within the acceptable ranges within clinical practice.

Food Insecurity and Chronic Kidney Disease: Considerations for Practitioners.

The coronavirus disease 2019 pandemic has exacerbated existing health disparities related to food security status. Emerging literature suggests individuals with Chronic Kidney Disease (CKD) who are also food insecure have a greater likelihood of disease progression compared to food secure individuals. However, the complex relationship between CKD and food insecurity (FI) is understudied relative to other chronic conditions. The purpose of this practical application article is to summarize the recent literature on the social-economic, nutritional, to care through which FI may negatively impact health outcomes in individuals with CKD. While several studies have reported on the cross-sectional prevalence of FI among persons with CKD, literature is lacking about the severity and duration of exposure to FI on CKD outcomes. Future research is needed to better understand how FI impairs CKD care, nutritional and structural barriers that impact disease prevention and disease progression, and effective strategies to support patients.

In Vivo Effectiveness of Several Antimicrobial Locks To Eradicate Intravascular Catheter Coagulase-Negative Staphylococci Biofilms.

Tunneled central venous catheter (TCVC) related infection remains a challenge in the care of hemodialysis patients. We aimed to determine the best antimicrobial lock therapy (ALT) to eradicate coagulase-negative staphylococci (CoNS) biofilms. We studied the colonization status of the catheter every 30 days by quantitative blood cultures (QBC) drawn through all catheter lumens. Those patients with a significant culture (i.e.,100 to 1,000 CFU/mL) of a CoNS were classified as patients with a high risk of developing catheter-related bloodstream infections (CRBSI). They were assigned to receive daptomycin, vancomycin, teicoplanin lock solution, or the standard of care (SoC) (i.e., heparin lock). The primary endpoint was to compare eradication ability (i.e., negative QBC for 30 days after ending ALT) rates between different locks and the SoC. A second objective was to analyze the correlation between ALT exposure and isolation of CoNS with antimicrobial resistance. Daptomycin lock was associated with a significant higher eradication success than with the SoC: 85% versus 30% (relative risk [RR] = 14, 95% confidence interval [CI] = 2.4 - 82.7); followed by teicoplanin locks with a 83.3% success (RR = 11.7; 95% CI = 2 - 70.2). We observed CoNs isolates with a higher teicoplanin MIC in patients with repeated teicoplanin locks exposure (coefficient = 0.3; 95% CI = 0.11 - 0.47). However, teicoplanin MICs decreased in patients treated with vancomycin locks (coefficient = -0.56; 95% CI = -0.85 - -0.02). Methicillin-resistance decreased with accumulative ALT (RR = 0.82; 95% CI = 0.69 - 0.98). In this study, daptomycin locks achieve the highest eradication rate of CoNS from hemodialysis catheters in vivo.

Multiparametric renal magnetic resonance imaging: A reproducibility study in renal allografts with stable function.

Monitoring renal allograft function after transplantation is key for the early detection of allograft impairment, which in turn can contribute to preventing the loss of the allograft. Multiparametric renal MRI (mpMRI) is a promising noninvasive technique to assess and characterize renal physiopathology; however, few studies have employed mpMRI in renal allografts with stable function (maintained function over a long time period). The purposes of the current study were to evaluate the reproducibility of mpMRI in transplant patients and to characterize normal values of the measured parameters, and to estimate the labeling efficiency of Pseudo-Continuous Arterial Spin Labeling (PCASL) in the infrarenal aorta using numerical simulations considering experimental measurements of aortic blood flow profiles. The subjects were 20 transplant patients with stable kidney function, maintained over 1 year. The MRI protocol consisted of PCASL, intravoxel incoherent motion, and T1 inversion recovery. Phase contrast was used to measure aortic blood flow. Renal blood flow (RBF), diffusion coefficient (D), pseudo-diffusion coefficient (D*), flowing fraction ( f ), and T1 maps were calculated and mean values were measured in the cortex and medulla. The labeling efficiency of PCASL was estimated from simulation of Bloch equations. Reproducibility was assessed with the within-subject coefficient of variation, intraclass correlation coefficient, and Bland-Altman analysis. Correlations were evaluated using the Pearson correlation coefficient. The significance level was p less than 0.05. Cortical reproducibility was very good for T1, D, and RBF, moderate for f , and low for D*, while medullary reproducibility was good for T1 and D. Significant correlations in the cortex between RBF and f (r = 0.66), RBF and eGFR (r = 0.64), and D* and eGFR (r = -0.57) were found. Normal values of the measured parameters employing the mpMRI protocol in kidney transplant patients with stable function were characterized and the results showed good reproducibility of the techniques.

Pre-Emptive Antimicrobial Locks Decrease Long-Term Catheter-Related Bloodstream Infections in Hemodialysis Patients.

This study aimed to prove that pre-emptive antimicrobial locks in patients at risk of bacteremia decrease infection. We performed a non-randomized prospective pilot study of hemodialysis patients with tunneled central venous catheters. We drew quantitative blood cultures monthly to detect colonization. Patients with a critical catheter colonization by coagulase-negative staphylococci (defined as counts of 100−999 CFU/mL) were at high risk of developing a catheter-related bloodstream infection. We recommended antimicrobial lock for this set of patients. The nephrologist in charge of the patient decided whether to follow the recommendation or not (i.e., standard of care). We compared bloodstream infection rates between patients treated with antimicrobial lock therapy versus patients treated with the standard of care (i.e., heparin). We enrolled 149 patients and diagnosed 86 episodes of critical catheter colonization by coagulase-negative staphylococci. Patients treated with antimicrobial lock had a relative risk of bloodstream infection of 0.19 when compared with heparin lock (CI 95%, 0.11−0.33, p < 0.001) within three months of treatment. We avoided one catheter-related bloodstream infection for every ten catheter-critical colonizations treated with antimicrobial lock [number needed to treat 10, 95% CI, 5.26−100, p = 0.046]. In conclusion, pre-emptive antimicrobial locks decrease bloodstream infection rates in hemodialysis patients with critical catheter colonization.

Association between Circulating Levels of 25-Hydroxyvitamin D3 and Matrix Metalloproteinase-10 (MMP-10) in Patients with Type 2 Diabetes.

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.

Anti-Spike antibodies 3 months after SARS-CoV-2 mRNA vaccine booster dose in patients on hemodialysis: the prospective SENCOVAC study.

Background: Patients on hemodialysis are at high-risk for complications derived from coronavirus disease 2019 (COVID-19). The present analysis evaluated the impact of a booster vaccine dose and breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on humoral immunity 3 months after the booster dose. Methods: This is a multicentric and prospective study assessing immunoglobulin G anti-Spike antibodies 6 and 9 months after initial SARS-CoV-2 vaccination in patients on hemodialysis that had also received a booster dose before the 6-month assessment (early booster) or between the 6- and 9-month assessments (late booster). The impact of breakthrough infections, type of vaccine, time from the booster and clinical variables were assessed. Results: A total of 711 patients [67% male, median age (range) 67 (20-89) years] were included. Of these, 545 (77%) received an early booster and the rest a late booster. At 6 months, 64 (9%) patients had negative anti-Spike antibody titers (3% of early booster and 29% of late booster patients, P = .001). At 9 months, 91% of patients with 6-month negative response had seroconverted and there were no differences in residual prevalence of negative humoral response between early and late booster patients (0.9% vs 0.6%, P = .693). During follow-up, 35 patients (5%) developed breakthrough SARS-CoV-2 infection. Antibody titers at 9 months were independently associated with mRNA-1273 booster (P = .001), lower time from booster (P = .043) and past breakthrough SARS-CoV-2 infection (P < .001). Conclusions: In hemodialysis patients, higher titers of anti-Spike antibodies at 9 months were associated with mRNA-1273 booster, lower time from booster and past breakthrough SARS-CoV-2 infection.

Safety and effectiveness of sucroferric oxyhydroxide in Spanish patients on dialysis: sub-analysis of the VERIFIE study.

BACKGROUND AND AIMS: In this study, we show the results of the subset of Spanish patients of the VERIFIE study, the first post-marketing study assessing the long-term safety and effectiveness of sucroferric oxyhydroxide (SFOH) in patients with hyperphosphatemia undergoing dialysis during clinical practice. PATIENTS AND METHODS: Patients undergoing hemodialysis and peritoneal dialysis with indication of SFOH treatment were included. Follow-up duration was 12-36 months after SFOH initiation. Primary safety variables were the incidence of adverse drug reactions (ADRs), medical events of special interest (MESIs), and variations in iron-related parameters. SFOH effectiveness was evaluated by the change in serum phosphorus levels. RESULTS: A total of 286 patients were recruited and data from 282 were analyzed. Among those 282 patients, 161 (57.1%) withdrew the study prematurely and 52.5% received concomitant treatment with other phosphate binders. ADRs were observed in 35.1% of patients, the most common of which were gastrointestinal disorders (77.1%) and mild/moderate in severity (83.7%). MESIs were reported in 14.2% of patients, and 93.7% were mild/moderate. An increase in ferritin (386.66ng/mL vs 447.55ng/mL; p=0.0013) and transferrin saturation (28.07% vs 30.34%; p=0.043) was observed from baseline to the last visit (p=0.0013). Serum phosphorus levels progressively decreased from 5.69mg/dL at baseline to 4.84mg/dL at the last visit (p<0.0001), increasing by 32.2% the proportion of patients who achieved serum phosphorus levels ≤5.5mg/dL, with a mean daily SFOH dose of 1.98 pills/day. CONCLUSIONS: SFOH showed a favorable effectiveness profile, a similar safety profile to that observed in the international study with most adverse events of mild/moderate severity, and a low daily pill burden in Spanish patients in dialysis.

Perspectives on the Role of Magnetic Resonance Imaging (MRI) for Noninvasive Evaluation of Diabetic Kidney Disease.

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.

Diabetic Kidney Disease, Cardiovascular Disease and Non-Alcoholic Fatty Liver Disease: A New Triumvirate?

Non-alcoholic fatty liver disease is a highly prevalent disease worldwide with a renowned relation to cardiovascular disease and chronic kidney disease. These diseases share a common pathophysiology including insulin resistance, oxidative stress, chronic inflammation, dysbiosis and genetic susceptibilities. Non-alcoholic fatty liver disease is especially prevalent and more severe in type 2 diabetes. Patients with non-alcoholic fatty liver disease should have liver fibrosis assessment in order to identify those at the highest risk of adverse outcomes so that appropriate management strategies can be implemented. Early diagnosis and treatment of non-alcoholic fatty liver disease could ameliorate the burden of cardiovascular disease and chronic kidney disease.

Effect of exopolysaccharides produced by dairy starter cultures on biofilms formed on reverse osmosis membranes.

Two different cheese starter cultures producing exopolysaccharides (EPS+: Streptococcus thermophilus strain ST3534 and Lactococcus lactis ssp. cremoris strain JFR+) and their isogenic EPS-negative (EPS-: S. thermophilus strain ST5842 and L. lactis ssp. cremoris strain JFR-) variants were used to study the attachment of bacterial cells in the absence of growth (at 4°C) and the resultant biofilm formation on reverse osmosis membranes (at 30 or 35°C). We used M17 broth and a 10% solution of whey protein concentrate (with 35% protein) as growth media for biofilm development under static conditions. As expected, ST3534 (EPS+) showed significantly greater cell counts within biofilms than ST5842 (EPS-). In the absence of growth, however, cells of these 2 isogenic Streptococcus strains attached to the membrane in similar numbers. In contrast, JFR+ counts were significantly lower than those of JFR- under all conditions. These findings indicate that the EPS produced by S. thermophilus may play a greater role in building up the 3-dimensional structure of the biofilm, rather than only assisting during initial attachment of the cells to the membrane, whereas the EPS produced by L. lactis ssp. cremoris hampered both initial attachment to the membrane and biofilm formation. Although no differences were observed in the surface charge of the cells between the 2 EPS-producing cultures, surface hydrophobicity was associated with the different adhesive properties of these microorganisms. In conclusion, our results exclude the hypothesis that all EPS-producing starter cultures have an advantage in regard to their ability to form biofilm on membrane separation surfaces. In contrast, variations between different EPS, with hydrophobicity being an important influencing feature, modify adhesive behavior to reverse osmosis membranes.

Optimization of pseudo-continuous arterial spin labeling for renal perfusion imaging.

PURPOSE: To evaluate labeling efficiency of pseudo-continuous arterial spin labeling (PCASL) and to find the gradient parameters that increase PCASL robustness for renal perfusion measurements. METHODS: Aortic blood flow was characterized in 3 groups: young healthy volunteers (YHV1), chronic kidney disease (CKD) patients (CKDP), and healthy controls (HCO). PCASL inversion efficiency was evaluated through numeric simulations considering the measured pulsatile flow velocity profiles and off-resonance effects for a wide range of gradient parameters, and the results were assessed in vivo. The most robust PCASL implementation was used to measure renal blood flow (RBF) in CKDP and HCO. RESULTS: Aortic blood velocities reached peak values of 120 cm/s in YHV1, whereas for elderly subjects values were lower by approximately a factor of 2. Simulations and experiments showed that by reducing the gradient average (Gave ) and the selective to average gradient ratio (Gmax /Gave ), labeling efficiency was maximized and PCASL robustness to off-resonance was improved. The study in CKDP and HCO showed significant differences in RBF between groups. CONCLUSION: An efficient and robust PCASL scheme for renal applications requires a Gmax /Gave ratio of 6-7 and a Gave value that depends on the aortic blood flow velocities (0.5 mT/m being appropriate for CKDP and HCO).

Population Genomic Analysis of Mycoplasma bovis Elucidates Geographical Variations and Genes associated with Host-Types.

: Among more than twenty species belonging to the class Mollecutes, Mycoplasma bovis is the most common cause of bovine mycoplasmosis in North America and Europe. Bovine mycoplasmosis causes significant economic loss in the cattle industry. The number of M. bovis positive herds recently has increased in North America and Europe. Since antibiotic treatment is ineffective and no efficient vaccine is available, M. bovis induced mycoplasmosis is primarily controlled by herd management measures such as the restriction of moving infected animals out of the herds and culling of infected or shedders of M. bovis. To better understand the population structure and genomic factors that may contribute to its transmission, we sequenced 147 M. bovis strains isolated from four different countries viz. USA (n = 121), Canada (n = 22), Israel (n = 3) and Lithuania (n = 1). All except two of the isolates (KRB1 and KRB8) were isolated from two host types i.e., bovine (n = 75) and bison (n = 70). We performed a large-scale comparative analysis of M. bovis genomes by integrating 103 publicly available genomes and our dataset (250 total genomes). Whole genome single nucleotide polymorphism (SNP) based phylogeny using M. agalactiae as an outgroup revealed that M. bovis population structure is composed of five different clades. USA isolates showed a high degree of genomic divergence in comparison to the Australian isolates. Based on host of origin, all the isolates in clade IV was of bovine origin, whereas majority of the isolates in clades III and V was of bison origin. Our comparative genome analysis also revealed that M. bovis has an open pangenome with a large breadth of unexplored diversity of genes. The function based analysis of autogenous vaccine candidates (n = 10) included in this study revealed that their functional diversity does not span the genomic diversity observed in all five clades identified in this study. Our study also found that M. bovis genome harbors a large number of IS elements and their number increases significantly (p = 7.8x10-6) as the genome size increases. Collectively, the genome data and the whole genome-based population analysis in this study may help to develop better understanding of M. bovis induced mycoplasmosis in cattle.

Matrix Metalloproteinases in Diabetic Kidney Disease.

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.

Burden and challenges of heart failure in patients with chronic kidney disease. A call to action.

Patients with the dual burden of chronic kidney disease (CKD) and chronic congestive heart failure (HF) experience unacceptably high rates of symptom load, hospitalization, and mortality. Currently, concerted efforts to identify, prevent and treat HF in CKD patients are lacking at the institutional level, with emphasis still being placed on individual specialty views on this topic. The authors of this review paper endorse the need for a dedicated cardiorenal interdisciplinary team that includes nephrologists and renal nurses and jointly manages appropriate clinical interventions across the inpatient and outpatient settings. There is a critical need for guidelines and best clinical practice models from major cardiology and nephrology professional societies, as well as for research funding in both specialties to focus on the needs of future therapies for HF in CKD patients. The implementation of cross-specialty educational programs across all levels in cardiology and nephrology will help train future specialists and nurses who have the ability to diagnose, treat, and prevent HF in CKD patients in a precise, clinically effective, and cost-favorable manner.

MMP-10 is Increased in Early Stage Diabetic Kidney Disease and can be Reduced by Renin-Angiotensin System Blockade.

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 ± 274 pg/ml vs. 332 ± 151; p = 0.02) and TIMP-1 (573 ± 296 ng/ml vs. 375 ± 317; p < 0.001) levels were significantly 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 end-stage renal disease. Diabetic mice had 4-fold greater glomerular Mmp10 expression and significant 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.

Improvement of drug prescribing in acute kidney injury with a nephrotoxic drug alert system.

OBJECTIVE: Electronic alert systems have shown their capacity for improving the detection of acute kidney injury (AKI). The aim of this study was to design and implement a clinical decision support system (CDSS) for improving drug selection and reducing nephrotoxic drug use in patients with AKI. METHODS: The study was designed as an intervention study comparing a pre and post cohort of patients admitted during April 2014 and April 2015, respectively (phase I and phase II). The intervention was a CDSS which provided kidney function and nephrotoxic drug information. Furthermore, an interruptive alert was designed to detect patients suffering an AKI event while taking a nephrotoxic drug and to see if the dose was then reduced or the drug was discontinued by the physicians. RESULTS: One-third of the inpatients were included in the analysis because they met the inclusion criteria (1004 and 1002 patients in phases I and II, respectively). 735 and 761 of them received at least one nephrotoxic alert (73% vs 76%; p=0.763). 65 and 88 patients suffered AKI during admission (6.5% vs 8.8%; p=0.051). In phase I, patients received 384 nephrotoxic alerts (55%) with 78 (20%) of them provoking a change or discontinuation of the nephrotoxic drug. In phase II this value increased to 154 out of 526 (29%) after implementation of the CDSS (p<0.01). CONCLUSIONS: A CDSS with interruptive alerts that inform of the development of AKI in real time in patients with nephrotoxic drug prescription has a positive impact on the judicious use of these drugs.