Cardio-renal benefits of sacubitril/valsartan in patients with advanced chronic kidney disease: experience in daily clinical practice.

BACKGROUND: The association between cardiac complications, such as heart failure (HF), and chronic kidney disease (CKD) is well known. In this study, we examined the effectiveness and safety of treatment with neprilysin inhibition in patients with advanced chronic kidney disease (stage 3b-4). METHODS: This single-centre, longitudinal, retrospective study of 31 months duration involved consecutive patients with CKD and HF with a reduced ejection fraction (HFrEF) who started treatment with sacubitril/valsartan. Glomerular filtration rate (GFR), cardiovascular risk factors, proteinuria, potassium, echocardiographic parameters and admissions for heart failure were analysed. RESULTS: The study comprised 25 patients with a median age of 73.2 ± 5.9 years. The most frequent aetiology of heart failure was ischemic heart disease. The median GFR was 29.4 ± 8.3 ml/min/1.73 m2 and the left ventricular ejection fraction (LVEF) 36.4 ± 8.9%. The GFR improved after initiating the treatment (F = 3.396, p = 0.019), as did the LVEF at one year of follow-up (p = 0.018). The number of visits to the emergency department for heart failure was also reduced. No patients needed to start renal replacement therapy. CONCLUSIONS: This study shows that sacubitril/valsartan may play a beneficial role in patients who have advanced CKD and HFrEF, with a satisfactory safety profile.

Treatment of early borderline lesions in low immunological risk kidney transplant patients: a Spanish multicenter, randomized, controlled parallel-group study protocol: the TRAINING study.

BACKGROUND: Subclinical inflammation, including borderline lesions (BL), is very common (30-40%) after kidney transplantation (KT), even in low immunological risk patients, and can lead to interstitial fibrosis/tubular atrophy (IFTA) and worsening of renal function with graft loss. Few controlled studies have analyzed the therapeutic benefit of treating these BL on renal function and graft histology. Furthermore, these studies have only used bolus steroids, which may be insufficient to slow the progression of these lesions. Klotho, a transmembrane protein produced mainly in the kidney with antifibrotic properties, plays a crucial role in the senescence-inflammation binomial of kidney tissue. Systemic and local inflammation decrease renal tissue expression and soluble levels of α-klotho. It is therefore important to determine whether treatment of BL prevents a decrease in α-klotho levels, progression of IFTA, and loss of kidney function. METHODS: The TRAINING study will randomize 80 patients with low immunological risk who will receive their first KT. The aim of the study is to determine whether the treatment of early BL (3rd month post-KT) with polyclonal rabbit antithymocyte globulin (Grafalon®) (6 mg/kg/day) prevents or decreases the progression of IFTA and the worsening of graft function compared to conventional therapy after two years post-KT, as well as to analyze whether treatment of BL with Grafalon® can modify the expression and levels of klotho, as well as the pro-inflammatory cytokines that regulate its expression. DISCUSSION: This phase IV investigator-driven, randomized, placebo-controlled clinical trial will examine the efficacy and safety of Grafalon® treatment in low-immunological-risk KT patients with early BL. TRIAL REGISTRATION: clinicaltrials.gov : NCT04936282. Registered June 23, 2021, https://clinicaltrials.gov/ct2/show/NCT04936282?term=NCT04936282&draw=2&rank=1 . Protocol Version 2 of 21 January 2022. SPONSOR: Canary Isles Institute for Health Research Foundation, Canary Isles (FIISC). mgomez@fciisc.org .

Waiting List and Kidney Transplant Vascular Risk: An Ongoing Unmet Concern.

BACKGROUND: Chronic kidney disease (CKD) is an important independent risk factor for adverse cardiovascular events in patients waitlisted for kidney transplantation (KT). Although KT reduces cardiovascular risk, these patients still have a higher all-cause and cardiovascular mortality than the general population. This concerning situation is due to a high burden of traditional and nontraditional risk factors as well as uremia-related factors and transplant-specific factors, leading to 2 differentiated processes under the framework of CKD, atherosclerosis and arteriosclerosis. These can be initiated by insults to the vascular endothelial endothelium, leading to vascular calcification (VC) of the tunica media or the tunica intima, which may coexist. Several pathogenic mechanisms such as inflammation-related endothelial dysfunction, mineral metabolism disorders, activation of the renin-angiotensin system, reduction of nitric oxide, lipid disorders, and the fibroblast growth factor 23-klotho axis are involved in the pathogenesis of atherosclerosis and arteriosclerosis, including VC. SUMMARY: This review focuses on the current understanding of atherosclerosis and arteriosclerosis, both in patients on the waiting list as well as in kidney transplant recipients, emphasizing the cardiovascular risk factors in both populations and the inflammation-related pathogenic mechanisms. Key Message: The importance of cardiovascular risk factors and the pathogenic mechanisms related to inflammation in patients waitlisted for KT and kidney transplant recipients.

Mortality in Elderly Waiting-List Patients Versus Age-Matched Kidney Transplant Recipients: Where is the Risk?

The number of elderly patients on the waiting list (WL) for kidney transplantation (KT) has risen significantly in recent years. Because KT offers a better survival than dialysis therapy, even in the elderly, candidates for KT should be selected carefully, particularly in older waitlisted patients. Identification of risk factors for death in WL patients and prediction of both perioperative risk and long-term post-transplant mortality are crucial for the proper allocation of organs and the clinical management of these patients in order to decrease mortality, both while on the WL and after KT. In this review, we examine the clinical results in studies concerning: a) risk factors for mortality in WL patients and KT recipients; 2) the benefits and risks of performing KT in the elderly, comparing survival between patients on the WL and KT recipients; and 3) clinical tools that should be used to assess the perioperative risk of mortality and predict long-term post-transplant survival. The acknowledgment of these concerns could contribute to better management of high-risk patients and prophylactic interventions to prolong survival in this particular population, provided a higher mortality is assumed.

C3 glomerulonephritis associated with monoclonal gammopathy of renal significance: case report.

BACKGROUND: Morbidity associated with monoclonal gammopathy of renal significance is high due to the severe renal lesions and the associated systemic alterations. Accordingly, early diagnosis is fundamental, as is stopping the clonal production of immunoglobulins using specific chemotherapy. CASE PRESENTATION: A 75-year-old man with chronic renal disease of unknown origin since 2010 experienced rapid worsening of renal function over a period of 6 mos. Bone marrow biopsy showed monoclonal gammopathy of undetermined significance. Kidney biopsy showed the presence of C3 glomerulonephritis, with exclusive deposits of C3 visible on immunofluorescence and a membranoproliferative pattern on light microscopy. Skin biopsy showed endothelial deposition of complement. Given both the renal and cutaneous involvement the patient was considered to have monoclonal gammopathy of renal significance. We considered an underlying pathogenic mechanism for the renal alteration secondary to activation of the alternative complement pathway by the anomalous immunoglobulin. Despite treatment with plasmapheresis, bortezomib and steroids, advanced chronic kidney disease developed. CONCLUSIONS: The possible underlying cause of the monoclonal gammopathy of renal significance suggests that monoclonal gammopathy should be considered in adult patients with membranoproliferative glomerulonephritis.

Regression of cardiac growth in kidney transplant recipients using anti-m-TOR drugs plus RAS blockers: a controlled longitudinal study.

BACKGROUND: Left ventricular hypertrophy (LVH) is common in kidney transplant (KT) recipients. LVH is associated with a worse outcome, though m-TOR therapy may help to revert this complication. We therefore conducted a longitudinal study to assess morphological and functional echocardiographic changes after conversion from CNI to m-TOR inhibitor drugs in nondiabetic KT patients who had previously received RAS blockers during the follow-up. METHODS: We undertook a 1-year nonrandomized controlled study in 30 non-diabetic KT patients who were converted from calcineurin inhibitor (CNI) to m-TOR therapy. A control group received immunosuppressive therapy based on CNIs. Two echocardiograms were done during the follow-up. RESULTS: Nineteen patients were switched to SRL and 11 to EVL. The m-TOR group showed a significant reduction in LVMi after 1 year (from 62 ± 22 to 55 ± 20 g/m2.7; P=0.003, paired t-test). A higher proportion of patients showing LVMi reduction was observed in the m-TOR group (53.3 versus 29.3%, P=0.048) at the study end. In addition, only 56% of the m-TOR patients had LVH at the study end compared to 77% of the control group (P=0.047). A significant change from baseline in deceleration time in early diastole was observed in the m-TOR group compared with the control group (P=0.019). CONCLUSIONS: Switching from CNI to m-TOR therapy in non-diabetic KT patients may regress LVH, independently of blood pressure changes and follow-up time. This suggests a direct non-hemodynamic effect of m-TOR drugs on cardiac mass.

Cardiovascular health and target end-organ damage and comorbidities in hypertensive patients from a Spanish primary care urban population.

We hypothesized that a poorer cardiovascular health status is related to a higher risk of hypertension-mediated organ-damage (HMOD) or hypertension-related comorbidities (HRC). We assessed the relationship between cardiovascular health metrics (CVHM) and HMOD-HRC in 243 hypertensive patients from primary care center followed for two years. We recorded the baseline CVHM score (Life's Simple 7) plus clinical data, including prevalent and incident HMOD-HRC, hospitalization and mortality. The prevalence of ideal CVHM scores was very low in both men and women. The patients with healthier CVHM scores were younger, and had a lower prevalence of diabetes, cardiovascular disease and chronic kidney disease. We recorded 264 cases of HMOD-HRC (225 at baseline and 39 during follow-up). Nine patients died and 64 had any-cause hospitalization during follow-up. A lower prevalence of HMOD-HRC and unfavorable outcomes was observed as the number of ideal CVHM increased (P<0.05). Multivariate logistic regression adjusted for confounders showed a lower CVHM score (0-1) was associated with increased odds of HMOD-HRC (4.04, 95% CI 1.26-12.94; P=0.019) and composite endpoint (HMOD-HRC, death or all-cause hospitalization) (3.43, 95% CI 1.19-9.92; P=0.023). Individual components were less predictive than the cumulative CVHM score. Few hypertensive patients in this urban population had ideal CVHM scores. An inverse relationship between scores and outcomes (HMOD-HRC, death or hospitalizations) was observed. Interventions to increase this score may improve prognosis among community-based hypertensive patients.

The Effect of Pulmonary Rehabilitation on Cardiovascular Risk, Oxidative Stress and Systemic Inflammation in Patients with COPD.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is a leading cause of death, and cardiovascular (CV) comorbidities play a role. Evidence of the pulmonary rehabilitation (PR) effect in reducing the CV risk (CVR) in COPD patients is limited. In this study, we aimed to determine the impact of an 8-week PR program (PRP) on the CVR of the overall population and to compare the impact on the exacerbator versus non-exacerbator patients. PATIENTS AND METHODS: This was a prospective study that included adults who had post-bronchodilator forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) (FEV1/FVC) ratio <70% and FEV1 <80% predicted, had quit smoking for at least 1 year and had a history of tobacco consumption greater than 10 packs/year, and were clinically stable in the last 8 weeks. Pre- and post-PRP assessments included respiratory function evaluation, laboratory tests, and exercise capacity assessment (6-minute walking test [6MWT]). CVR was assessed using different risk prediction models. RESULTS: A total of 50 patients (28 exacerbators and 22 non-exacerbators) completed the PRP (median age: 64.5 years, men: 72%; arterial hypertension: 70%, dyslipidemia: 30%, diabetes: 20%; CV disease (CVD): 24%. After the PRP, exacerbator patients showed a significant decrease in the CVR calculated by the COPDCoRi model (p<0.001); patients with ≥30-meter increase on the 6MWT showed statistically significant lower levels of glucose (p=0.004), HbA1c (p=0.004) and BODE index score (p=0.026) compared to patients with <30-meter increase. CONCLUSIONS: PR reduced certain modifiable CVR factors and CVD risk, especially in exacerbator patients.

Differences in cardiovascular risk and health-related quality of life in COPD patients according to clinical phenotype.

Chronic obstructive pulmonary disease (COPD) has a high prevalence and a major impact on health-related quality of life (HRQL). COPD exacerbations are an important cause of morbidity and mortality, affecting cardiovascular risk, and are associated with poorer health status. The aim of this study was to assess the association between cardiovascular risk (CVR) and HRQL, according to exacerbator or non-exacerbator phenotype. We undertook a cross-sectional, observational, descriptive study of 107 patients with COPD. Patients with two or more moderate exacerbations or one severe exacerbation in the previous year were considered as exacerbators. The CVR was calculated with the Framingham scale and SCORE (Systematic Coronary Risk Evaluation) and the HRQL was assessed with the generic questionnaire Short Form-36 Health Survey (SF-36), the St George Respiratory Questionnaire (SGRQ) and the COPD Assessment Test (CAT). Statistical analysis was done with SPSS version 26.0 for Windows. The SF-36 and the SGRQ showed lower values for the exacerbator phenotype, indicating a poorer quality of life. The CAT questionnaire showed values above 10 for the exacerbator phenotype, and lower values in the non-exacerbator group. After categorizing the sample according to their median age (65 years), we found a greater deterioration in HRQL in patients under 65 years of age according to the SF-36, the SGRQ and the CAT. We also detected differences in HRQL between non-exacerbator patients with a high CVR according to the Framingham (≥ 20%) and SCORE (≥ 5%) scales compared to those without this risk. A tendency towards worse HRQL was observed in non-exacerbator patients with a high CVR, which was statistically significant for the SGRQ impact domain on the SCORE scale. The CAT also showed a worse quality of life in non-exacerbator patients with a high CVR, which was significant in the Framingham model (Framingham high risk 8.41 vs non-high risk 6.05, p < 0.01). These differences were not observed in exacerbator patients. Our findings confirm that a high CVR influences HRQL in patients with COPD, especially in non-exacerbator patients with a high CVR, measured according to the SGRQ and the CAT.

Association of HbA1c and cardiovascular and renal disease in an adult Mediterranean population.

BACKGROUND: Increasing evidence suggests a mechanistic link between the glycemic environment and renal and cardiovascular events, even below the threshold for diabetes. We aimed to assess the association between HbA1c and chronic kidney disease (CKD) and cardiovascular disease (CVD). METHODS: A cross-sectional study involving a random representative sample of 2270 adults from southern Spain (Malaga) was undertaken. We measured HbA1c, serum creatinine and albuminuria in fasting blood and urine samples. RESULTS: Individuals without diabetes in the upper HbA1c tertile had an unfavorable cardiovascular and renal profile and shared certain clinical characteristics with the patients with diabetes. Overall, a higher HbA1c concentration was strongly associated with CKD or CVD after adjustment for traditional risk factors. The patients with known diabetes had a 2-fold higher odds of CKD or CVD. However, when both parameters were introduced in the same model, the HbA1c concentration was only significantly associated with clinical endpoints (OR: 1.4, 95% CI, 1.1-1.6, P = 0.002). An increase in HbA1c of one percentage point was associated with a 30% to 40% increase in the rate of CKD or CVD. This relationship was apparent in persons with and without known diabetes. ROC curves illustrated that a HbA1c of 37 mmol/mol (5.5%) was the optimal value in terms of sensitivity and specificity for predicting endpoints in this population. CONCLUSION: HbA1c levels were associated with a higher prevalence of CKD and CVD cross-sectionally, regardless of diabetes status. These data support the value of HbA1c as a marker of cardiovascular and renal disease in the general population.

Association between Cardiovascular Health, C-Reactive Protein, and Comorbidities in Spanish Urban-Dwelling Overweight/Obese Hypertensive Patients.

The relationship between poorer cardiovascular health metrics (CVHM) plus low-grade inflammation (LGI) and hypertension-mediated organ damage (HMOD) and hypertension-related comorbidities (HRC) in hypertensive populations with an overweight/obese (Ow/Ob) hypertension-related phenotype is understudied. We examined the relationship between the CVHM score and the presence of LGI and Ow/Ob hypertension-associated phenotype morbidities and mortality in 243 hypertensive patients from an urban primary care center. We recorded the baseline CVHM score plus clinical data, including hs-C-reactive protein (CRP) and prevalent and incident HMOD-HRC and death. A total of 26 (10.7%) had a body mass index (BMI) < 25 kg/m2, 95 (31.1%) were overweight (BMI 25-29.9 kg/m2), and 122 (50.2%) were obese (BMI ≥ 30 kg/m2). There were 264 cases of HMOD-HRC and 9 deaths. Higher hs-CRP levels were observed as BMI increased. Linear regression analysis showed a significant correlation between BMI and hs-CRP, adjusted for confounders. Additionally, individuals with a higher hs-CRP tertile had a significant increase in BMI. Significantly lower log hs-CRP levels were found as the number of ideal CVHM scores rose. Multivariate binary logistic regression found the risk of HMOD-HRC increased significantly as the ideal CVHM scores decreased, and hs-CRP levels also correlated with HMOD-HRC in the whole cohort and in the Ow and Ob subpopulations. These findings highlight the need for early intervention targeting ideal CVHMs among hypertensive individuals with an Ow/Ob phenotype in order to attenuate the inflammatory state and prevent cardiovascular disease.

Time-Dependent Changes of Klotho and FGF-23 Levels after Kidney Transplantation: Role of Cold Ischemia Time, Renal Function and Graft Inflammation.

We investigated the evolution of serum klotho (s-Kl) and FGF-23 during the first two years post-kidney transplantation (KT), considering the cold ischemia time (CIT), glomerular filtration rate (GFR) and graft subclinical inflammation (SCI). We undertook a prospective, cohort, multicenter study of consecutive patients between April 2018 and January 2021 (with follow-up at 24 months). Subgroups were analyzed according to the median CIT (<14 vs. ≥14 h), the median GFR (≤40 vs. >40 mL/min/1.73 m2) and the presence of SCI at month 3. A total of 147 patients were included. s-Kl and fibroblast growth factor-23 (FGF-23) levels were measured at baseline and at months 3, 12 and 24. Graft biopsies (n = 96) were performed at month 3. All patients had low s-Kl levels at month 3. Patients with CIT < 14 h exhibited a significant increase in s-Kl at month 24. In patients with CIT ≥ 14 h, s-Kl at month 3 fell and lower s-Kl levels were seen at month 24. Patients with a GFR > 40 had a lesser decrease in s-Kl at month 3. FGF-23 fell significantly at months 3 and 12 in both GFR groups, a reduction maintained during follow-up. There were significant inter-group differences in s-Kl from months 3 to 24. CIT, GFR at 3 months and SCI were significantly associated with s-KI at month 3. A reduction in s-Kl at month 3 post-KT could be explained by longer CIT and delayed graft function as well as by impaired graft function. Early SCI may regulate s-Kl increase post-KT.

Abnormal ankle-brachial index, cardiovascular risk factors and healthy lifestyle factors in hypertensive patients: prospective cohort study from a primary care urban population.

BACKGROUND: Peripheral arterial disease (PAD) and arterial stiffness (AS) may be hypertension-mediated vascular lesions. Both are determined by an abnormal ankle-brachial index (ABI) and are predictors of cardiovascular disease (CVD) and mortality. We assessed the relationship in urban hypertensive patients between an abnormal ABI and an ideal cardiovascular health (CVH) score, plus other healthy factors, with unfavourable outcomes. METHODS: We studied 243 hypertensive patients from a primary care urban population, followed for two years. Clinical data, comorbid conditions, including hypertension-mediated organ damage (HMOD) and hypertension-related comorbidities (HRC), hospitalizations and mortality were also recorded. RESULTS: A low prevalence of ideal CVH was observed in urban hypertensive patients. The ABI ≤ 0.9 group (n = 16) showed a higher proportion of prior CVD other than PAD, mortality and hospitalizations than the ABI > 1.4 group (n = 41), and a poorer lipid, metabolic and renal profile. An inverse relationship between CVH score and ABI ≤ 0.9 and unfavourable outcomes (HMOD, HRC, death or hospitalization) was observed. Chronic kidney disease (CKD) and diabetes were independently associated with an ABI ≤ 0.9. Age, sex, diabetes, CKD, ABI ≤ 0.9 and ideal cholesterol were also associated with outcomes, but not other CVH metrics. CONCLUSIONS: Besides a low prevalence of ideal CVH, an inverse relationship between CVH score and ABI ≤ 0.9 and unfavourable outcomes was observed in hypertensive patients from an urban population. Stronger efforts to promote ideal CVH may improve outcomes in this particular population.

Monoclonal gammopathy of renal significance: Early diagnosis is key.

Monoclonal gammopathy of renal significance is a clinical-pathological entity grouping renal disorders secondary to the secretion of a monoclonal immunoglobulin synthesized by a B-cell-derived clone and/or plasma cells in a patient with no diagnostic criteria for multiple myeloma. This term applies to a concept recently introduced owing to the need to differentiate this entity from monoclonal gammopathy of undetermined significance, given the negative prognostic impact of its high morbidity and mortality resulting from both renal and systemic involvement, occasionally even progressing to advanced chronic kidney disease. The renal damage occurs via both direct pathogenic mechanisms, with the deposition of the monoclonal protein in different renal structures, as well as indirect mechanisms, acting as an autoantibody provoking dysregulation of the alternative complement pathway. The detection of this monoclonal protein and an early hematologic study are essential, as is the need for a kidney biopsy to establish the associated nephropathological diagnosis. Consequently, this then leads to the start of specific hematologic treatment to detain the production of the monoclonal protein and minimize renal and systemic injury.

Risk Factors for Mortality in Stable Kidney Transplant Patients Infected by SARS-CoV-2 in the South of Spain.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has especially affected kidney transplant (KT) recipients, who are more vulnerable than the general population because of their immunosuppressive status and added comorbidities. The purpose of this study was to determine risk factors related to infection and mortality from COVID-19 in KT recipients. METHODS: The study included 113 stable KT recipients who had polymerase chain reaction-confirmed COVID-19 infection between March 2020 and February 2021, from a total of 2150 KT recipients. Outcomes related to patient survival were analyzed. RESULTS: The mean (standard deviation) age of the patients was 56 (14) years; 62% (n = 70) were men. The median time between KT and infection was 88 months (interquartile range, 39-155 months); 90% (n = 102) were on tacrolimus therapy and 81% (n = 92) on mycophenolate mofetil. The clinical presentation was pneumonia (n = 57; 51%), fever (n = 61; 54%), cough (n = 62; 55%), dyspnea (n = 43; 38%), lymphopenia (n = 57; 50%), and gastrointestinal symptoms (n = 28; 25%). A total of 21% (n = 24) required intubation and intensive care unit admission, and 27 patients (25%) were asymptomatic. A total of 9% (n = 10) received hydroxychloroquine therapy plus azithromycin, 11% (n = 12) tocilizumab, 3.7% (n = 4) lopinavir/ritonavir, 49% (n = 55) steroids, 0.9% (n = 1) remdesivir, and 9.3% (n = 11) convalescent plasma. Immunosuppression was reduced in all symptomatic patients. Nineteen patients (17%) died. Cox univariate analysis showed that the factors significantly associated with death were patient age, presence of pneumonia or lymphopenia, and elevated C-reactive protein on admission. CONCLUSIONS: Mortality in KT recipients with COVID-19 is very high, more than for the general population. Risk factors are patient age, presence of pneumonia or lymphopenia, and a higher C-reactive protein level at the time of diagnosis.

Decrease in CD14++CD16+ Monocytes in Low-Immunological-Risk Kidney Transplant Patients with Subclinical Borderline Inflammation.

We determined the association between CD14++CD16+ monocytes and subclinical infiltrates that do not reach the histological threshold for rejection (≥Banff IA). We studied low-immunological-risk kidney-transplant recipients in a clinical trial (NCT02284464; EudraCT 2012-003298-24) whose protocol biopsy in the third month showed no significant changes or borderline lesions (BL). Flow cytometry was used to analyze the percentage of CD14++CD16+ monocytes in peripheral blood (PB) and blood from a fine-needle-aspiration biopsy (FNAB). A protocol biopsy was performed in 81 low-immunological-risk patients, of whom 15 were excluded (BK polyomavirus and rejection). The 28 (42.4%) with borderline lesions had significantly low levels of CD14++CD16+ in PB compared to patients with normal biopsies (7.9 ± 5.4 vs. 13.0 ± 12.8; p = 0.047). Patients without significant changes had similar percentages of CD14++CD16+ monocytes in the graft blood (GB) and FNAB blood. The percentage of these monocytes in the patients with an interstitial infiltrate, however, increased significantly in the FNAB blood compared to the GB: 16.9 ± 16.6 vs. 7.9 ± 5.4; p = 0.006. A difference of 50% in CD14++CD16+ in the GB versus the PB was a significant risk factor (p = 0.002) for BL, increasing the risk seven times. A decrease in CD14++CD16+ in the PB could be associated with the recruitment of these cells to the graft tissue in cases of subclinical BL inflammatory infiltrates below the threshold for rejection.

Clinical Relevance of Corticosteroid Withdrawal on Graft Histological Lesions in Low-Immunological-Risk Kidney Transplant Patients.

The impact of corticosteroid withdrawal on medium-term graft histological changes in kidney transplant (KT) recipients under standard immunosuppression is uncertain. As part of an open-label, multicenter, prospective, phase IV, 24-month clinical trial (ClinicalTrials.gov, NCT02284464) in low-immunological-risk KT recipients, 105 patients were randomized, after a protocol-biopsy at 3 months, to corticosteroid continuation (CSC, n = 52) or corticosteroid withdrawal (CSW, n = 53). Both groups received tacrolimus and MMF and had another protocol-biopsy at 24 months. The acute rejection rate, including subclinical inflammation (SCI), was comparable between groups (21.2 vs. 24.5%). No patients developed dnDSA. Inflammatory and chronicity scores increased from 3 to 24 months in patients with, at baseline, no inflammation (NI) or SCI, regardless of treatment. CSW patients with SCI at 3 months had a significantly increased chronicity score at 24 months. HbA1c levels were lower in CSW patients (6.4 ± 1.2 vs. 5.7 ± 0.6%; p = 0.013) at 24 months, as was systolic blood pressure (134.2 ± 14.9 vs. 125.7 ± 15.3 mmHg; p = 0.016). Allograft function was comparable between groups and no patients died or lost their graft. An increase in chronicity scores at 2-years post-transplantation was observed in low-immunological-risk KT recipients with initial NI or SCI, but CSW may accelerate chronicity changes, especially in patients with early SCI. This strategy did, however, improve the cardiovascular profiles of patients.

Impact of HLA Mismatching on Early Subclinical Inflammation in Low-Immunological-Risk Kidney Transplant Recipients.

The impact of human leukocyte antigen (HLA)-mismatching on the early appearance of subclinical inflammation (SCI) in low-immunological-risk kidney transplant (KT) recipients is undetermined. We aimed to assess whether HLA-mismatching (A-B-C-DR-DQ) is a risk factor for early SCI. As part of a clinical trial (Clinicaltrials.gov, number NCT02284464), a total of 105 low-immunological-risk KT patients underwent a protocol biopsy on the third month post-KT. As a result, 54 presented SCI, showing a greater number of total HLA-mismatches (p = 0.008) and worse allograft function compared with the no inflammation group (48.5 ± 13.6 vs. 60 ± 23.4 mL/min; p = 0.003). Multiple logistic regression showed that the only risk factor associated with SCI was the total HLA-mismatch score (OR 1.32, 95%CI 1.06-1.64, p = 0.013) or class II HLA mismatching (OR 1.51; 95%CI 1.04-2.19, p = 0.032) after adjusting for confounder variables (recipient age, delayed graft function, transfusion prior KT, and tacrolimus levels). The ROC curve illustrated that the HLA mismatching of six antigens was the optimal value in terms of sensitivity and specificity for predicting the SCI. Finally, a significantly higher proportion of SCI was seen in patients with >6 vs. ≤6 HLA-mismatches (62.3 vs. 37.7%; p = 0.008). HLA compatibility is an independent risk factor associated with early SCI. Thus, transplant physicians should perhaps be more aware of HLA mismatching to reduce these early harmful lesions.

Cardiovascular health and target end-organ damage and comorbidities in hypertensive patients from a Spanish primary care urban population / Salud cardiovascular y daño a órganos diana y comorbilidades en pacientes hipertensos procedentes de una población urbana de atención primaria en España

We hypothesized that a poorer cardiovascular health status is related to a higher risk of hypertension-mediated organ-damage (HMOD) or hypertension-related comorbidities (HRC). We assessed the relationship between cardiovascular health metrics (CVHM) and HMOD-HRC in 243 hypertensive patients from primary care center followed for two years. We recorded the baseline CVHM score (Life's Simple 7) plus clinical data, including prevalent and incident HMOD-HRC, hospitalization and mortality. The prevalence of ideal CVHM scores was very low in both men and women. The patients with healthier CVHM scores were younger, and had a lower prevalence of diabetes, cardiovascular disease and chronic kidney disease. We recorded 264 cases of HMOD-HRC (225 at baseline and 39 during follow-up). Nine patients died and 64 had any-cause hospitalization during follow-up. A lower prevalence of HMOD-HRC and unfavorable outcomes was observed as the number of ideal CVHM increased (P<0.05). Multivariate logistic regression adjusted for confounders showed a lower CVHM score (0–1) was associated with increased odds of HMOD-HRC (4.04, 95% CI 1.26–12.94; P=0.019) and composite endpoint (HMOD-HRC, death or all-cause hospitalization) (3.43, 95% CI 1.19–9.92; P=0.023). Individual components were less predictive than the cumulative CVHM score. Few hypertensive patients in this urban population had ideal CVHM scores. An inverse relationship between scores and outcomes (HMOD-HRC, death or hospitalizations) was observed. Interventions to increase this score may improve prognosis among community-based hypertensive patients (AU)

Nuestra hipótesis fue que un estado de peor salud cardiovascular está relacionado con un mayor riesgo de daño orgánico provocado por la hipertensión (DOP HTA) o de comorbilidades relacionadas con la hipertensión (CRHTA). Evaluamos la relación entre las métricas de la salud cardiovascular (MSCV) y el DOP HTA-CRHTA en 243 pacientes hipertensos procedentes de un centro de atención primaria, a quienes se realizó un seguimiento durante 2 años. Registramos la puntuación basal de MSCV (Life's Simple 7) y los datos clínicos, incluyendo DOP HTA-CRHTA prevalente e incidental, hospitalización y mortalidad. La prevalencia de puntuaciones MSCV ideales fue muy baja tanto en hombres como en mujeres. Los pacientes con puntuaciones MSCV más saludables fueron más jóvenes y tuvieron una menor prevalencia de diabetes, cardiopatías y enfermedad renal crónica. Registramos 264 casos de DOP HTA-CRHTA (225 al inicio y 39 durante el seguimiento). Nueve pacientes fallecieron y 64 fueron hospitalizados por cualquier causa durante el seguimiento. Se observó una menor prevalencia de DOP HTA-CRHTA y resultados no favorables a medida que aumentaba el MSCV ideal (p<0,05). La regresión logística multivariante ajustada a los factores de confusión reflejó una menor puntuación MSCV (0-1) asociada a un incremento de la odds ratio de DOP HTA-CRHTA (4,04, IC 95% 1,26-12,94; p=0,019) y un resultado compuesto (DOP HTA-CRHTA, muerte u hospitalización por cualquier causa) (3,43, IC 95% 1,19-9,92; p=0,023). Los componentes individuales fueron menos predictivos que la puntuación MSCV acumulada. Pocos pacientes hipertensos de esta población urbana tuvieron puntuaciones MSCV ideales. Se observó una relación inversa entre las puntuaciones y los resultados (DOP HTA-CRHTA, muerte u hospitalizaciones). Las intervenciones para incrementar esta puntuación pueden mejorar el pronóstico entre los pacientes hipertensos con base comunitaria (AU)

Survival in Southern European patients waitlisted for kidney transplant after graft failure: A competing risk analysis.

BACKGROUND: Whether patients waitlisted for a second transplant after failure of a previous kidney graft have higher mortality than transplant-näive waitlisted patients is uncertain. METHODS: We assessed the relationship between a failed transplant and mortality in 3851 adult KT candidates, listed between 1984-2012, using a competing risk analysis in the total population and in a propensity score-matched cohort. Mortality was also modeled by inverse probability weighting (IPTW) competing risk regression. RESULTS: At waitlist entry 225 (5.8%) patients had experienced transplant failure. All-cause mortality was higher in the post-graft failure group (16% vs. 11%; P = 0.033). Most deaths occurred within three years after listing. Cardiovascular disease was the leading cause of death (25.3%), followed by infections (19.3%). Multivariate competing risk regression showed that prior transplant failure was associated with a 1.5-fold increased risk of mortality (95% confidence interval [CI], 1.01-2.2). After propensity score matching (1:5), the competing risk regression model revealed a subhazard ratio (SHR) of 1.6 (95% CI, 1.01-2.5). A similar mortality risk was observed after the IPTW analysis (SHR, 1.7; 95% CI, 1.1-2.6). CONCLUSIONS: Previous transplant failure is associated with increased mortality among KT candidates after relisting. This information is important in daily clinical practice when assessing relisted patients for a retransplant.