Extracorporeal Photopheresis Improves Graft Survival in a Full-Mismatch Rat Model of Kidney Transplantation.

Extracorporeal photopheresis (ECP) is an immunomodulatory therapy based on the infusion of autologous cellular products exposed to ultraviolet light (UV) in the presence of a photosensitizer. The study evaluates the ECP efficacy as induction therapy in a full-mismatch kidney transplant rat model. Dark Agouti to Lewis (DA-L) kidney transplant model has been established. ECP product was obtained from Lewis rat recipients after DA kidney graft transplantation (LewDA). Leukocytes of those LewDA rats were exposed to 8-methoxy psoralen, and illuminated with UV-A. The ECP doses assessed were 10 × 106 and 100 × 106 cells/time point. Lewis recipients received seven ECP infusions. DA-L model was characterized by the appearance of donor-specific antibodies (DSA) and kidney function deterioration from day three after kidney transplant. The dysfunction progressed rapidly until graft loss (6.1 ± 0.5 days). Tacrolimus at 0.25 mg/kg prolonged rat survival until 11.4 ± 0.7 days (p = 0.0004). In this context, the application of leukocytes from LewDA sensitized rats accelerated the rejection (8.7 ± 0.45, p = 0.0012), whereas ECP product at high dose extended kidney graft survival until 26.3 ± 7.3 days, reducing class I and II DSA in surviving rats. ECP treatment increases kidney graft survival in full-mismatch rat model of acute rejection and is a suitable immunomodulatory therapy to be explored in kidney transplantation.

Immune Profiling of Peripheral Blood Mononuclear Cells at Pancreas Acute Rejection Episodes in Kidney-Pancreas Transplant Recipients.

Profiling of circulating immune cells provides valuable insight to the pathophysiology of acute rejection in organ transplantation. Herein we characterized the peripheral blood mononuclear cells in simultaneous kidney-pancreas transplant recipients. We conducted a retrospective analysis in a biopsy-matched cohort (n = 67) and compared patients with biopsy proven acute rejection (BPAR; 41%) to those without rejection (No-AR). We observed that CD3+ T cells, both CD8+ and CD4+, as well as CD19+ B cells were increased in patients with BPAR, particularly in biopsies performed in the early post-transplant period (<3 months). During this period immune subsets presented a good discriminative ability (CD4+ AUC 0.79; CD8+ AUC 0.80; B cells AUC 0.86; p < 0.05) and outperformed lipase (AUC 0.62; p = 0.12) for the diagnosis of acute rejection. We further evaluated whether this could be explained by differences in frequencies prior to transplantation. Patients presenting with early post-transplant rejection (<3 months) had a significant increase in T-cell frequencies pre-transplant, both CD4+ T cells and CD8+ T cells (p < 0.01), which were associated with a significant inferior rejection-free graft survival. T cell frequencies in peripheral blood correlated with pancreas acute rejection episodes, and variations prior to transplantation were associated with pancreas early acute rejection.

Immunogenic and immunotolerogenic effects of extracorporeal photopheresis in high immunological risk kidney recipients. A single center case series.

The immunomodulatory effects of extracorporeal photopheresis (ECP) have been used for the treatment of T-cell mediated disorders, such as rejection in organ transplantation. Currently, it is an established therapy for heart and lung rejection, but not for kidney transplantation (KT), where experience is limited. In addition, some data suggest that ECP could generate an immune response against infections, thus being an alternative for the treatment of rejection in case of active or high-risk of infection. In the present study, we analyze four cases of use of ECP as concomitant therapy in patients with KT and high risk of opportunistic infections due to the high burden of immunosuppression throughout their renal diseases. Two patients had concomitant viral infection (cytomegalovirus and BK virus, respectively) and three patients were on treatment for graft rejection. In the two patients with active viral infection, the infection was successfully controlled during ECP treatment. In all cases, ECP has been shown to be a safe procedure, without complications.

Advantages of plasmatic CXCL-10 as a prognostic and diagnostic biomarker for the risk of rejection and subclinical rejection in kidney transplantation.

This study evaluate the potential of plasmatic CXCL-10 (pCXCL-10) as a pre&post transplantation prognostic and diagnostic biomarker of T-cell-mediated rejection (TCMR), antibody-mediated rejection (ABMR) and subclinical rejection (SCR) risk in adult kidney recipients considering BKV and CMV infections as possible clinical confounder factors. Twenty-eight of 100 patients included experienced rejection (TCMR:14; ABMR:14); 8 SCR; 13 and 16 were diagnosed with BKV and CMV infection, respectively. Pre-transplantation pCXCL-10 was significantly increased in TCMR and ABMR and post-transplantation in TCMR, ABMR and SCR compared with nonrejectors. All CMV+ patients showed pCXCL-10 levels above the cutoff values established for rejection whereas the 80% of BKV+ patients showed pCXCL-10 concentration < 100 pg/mL. pCXCL-10 could improve pre-transplantation patient stratification and immunosuppressive treatment selection according to rejection risk; and after kidney transplantation could be a potential early prognostic biomarker for rejection. Clinical confounding factor in BKV+ and particularly in CMV+ patients must be discarded.

The impact of functional delayed graft function in the modern era of kidney transplantation - A retrospective study.

The dialysis-based definition of Delayed Graft Function (dDGF) is not necessarily objective as it depends on the individual physician's decision. The functional definition of DGF (fDGF, the failure of serum creatinine to decrease by at least 10% daily on 3 consecutive days during the first week post-transplant), may be more sensitive to reflect recovery after the ischemia-reperfusion injury. We retrospectively analyzed both definitions in 253 deceased donor kidney transplant recipients for predicting death-censored graft failure as primary outcome, using eGFR < 25 ml/min/1.73 m2 as a surrogate end-point for graft failure. Secondary outcome was a composite outcome that included graft failure as above and also patient's death. Median follow-up was 3.22 [2.38-4.21] years. Seventy-nine patients developed dDGF (31.2%) and 127 developed fDGF (50.2%). Sixty-three patients fulfilled criteria for both definitions (24.9%). At multivariable analysis, the two definitions were significantly associated with the primary [HR (95%CI) 2.07 (1.09-3.94), P = 0.026 for fDGF and HR (95%CI) 2.41 (1.33-4.37), P = 0.004 for dDGF] and the secondary composite outcome [HR (95%CI) 1.58 (1.01-2.51), P = 0.047 for fDGF and HR (95%CI) 1.67 (1.05-2.66), P = 0.028 for dDGF]. Patients who met criteria for both definitions had the worst prognosis, with a three-year estimates (95%CI) of survival from the primary and secondary outcomes of 2.31 (2.02-2.59) and 2.20 (1.91-2.49) years for fDGF+/dDGF+, in comparison with the other groups (P < 0.01 for trend). fDGF provides supplementary information about graft outcomes on top of the dDGF definition in a modern series of kidney transplantation.

Case report of COVID-19 in a kidney transplant recipient: Does immunosuppression alter the clinical presentation?

COVID-19 is novel infectious disease with an evolving understanding of its epidemiology and clinical manifestations. Immunocompromised patients often present atypical presentations of viral diseases. Herein we report a case of a COVID-19 infection in a solid organ transplant recipient, in which the first clinical symptoms were of gastrointestinal viral disease and fever, which further progressed to respiratory symptoms in 48 hours. In these high risk populations, protocols for screening for SARS-Cov2 may be needed to be re-evaluated.

Kidney Graft Outcomes in High Immunological Risk Simultaneous Liver-Kidney Transplants.

Recipients of simultaneous liver-kidney transplantations (SLKTs) have a lower risk of rejection compared with recipients of kidney transplants alone. However, there is disagreement about the impact of pretransplant anti-human leukocyte antigen sensitization on patient and kidney graft survival in the long term. The aim of the study was to evaluate the impact of the recipient immunological risk and comorbidities in renal graft outcomes on SLKT. We reviewed the SLKTs performed in our center from May 1993 until September 2017. Patient and graft survival were analyzed according to the immunological risk, comorbidities, liver and kidney rejection episodes, immunosuppression, and infections. A total of 20 recipients of SLKT were considered in the high immunological risk (HIR) group, and 68 recipients were included in the low immunological risk (LIR) control group. The prevalence of hepatitis C virus infection, second renal transplant, and time on dialysis prior to transplantation were significantly higher in the HIR group. The incidence of acute kidney rejection was higher in the HIR group (P<0.01). However, death-censored kidney graft survival as well as the estimated glomerular filtration rate at follow-up were not different between the 2 groups. Comorbidities, but not the immunological risk, impact negatively on patient survival. Despite the higher incidence of rejection in the HIR SLKT group, longterm renal function and graft survival were similar to the LIR group.

Successful use of nonantigen-specific immunoadsorption with antihuman Ig-columns in kidney graft antibody-mediated rejection.

INTRODUCTION: Nonantigen-specific immunoadsorption (IA) has proven to be effective in acute antibody-mediated rejection (aAMR). However, there is a lack of solid studies evaluating the safety and efficacy of IA with antihuman Ig-columns in aAMR. For chronic-active AMR (cAMR), no studies have evaluated the efficacy of nonantingen-specific IA with antihuman Ig-columns. The purpose of this study was to evaluate the role of nonantigen-specific IA with antihuman Ig-columns in the treatment of both aAMR and cAMR in kidney transplantation. MATERIAL AND METHODS: In retrospective and observational study, kidney graft and recipient survival rates were assessed after treatment of aAMR and cAMR with nonantigen-specific IA with Ig-Flex columns (Therasorb) between January 2012 and May 2018. Protocols included nonantigen-specific IA, rituximab, intravenous immunoglobulin, and rescue plasma exchange, if necessary. RESULTS: The study included 14 patients with AMR (acute in 9, chronic active in 5). For aAMR, mean follow-up was 13 ± 6 months, and patient and graft survival were, respectively, of 100% and 83%, with a mean increase in estimated glomerular filtration rate (eGFR) of 7.98 ± 12.96, 10.18 ± 16.71, and 11.43 ± 13.85 mL/min/1.72 m2 (P > .05) at 3, 12 months after treatment, and at the end of follow-up, respectively. For cAMR, mean follow-up was 14 ± 8 months, and patient and graft survival were, respectively, of 100% and 60%, with an average increase in eGFR of 4.30 ± 7.86, 5.64 ± 10.47, and 14.5 ± 7.86 mL/min/m2 (P > .05) at 3, 12 months after IA treatment, and at the end of the follow-up, respectively, although 40% did not respond and required chronic hemodialysis. CONCLUSION: Nonantigen-specific IA with Ig-Flex columns was safe and effective for aAMR treatment in kidney transplantation. In cAMR, IA with Ig-Flex columns was associated with a satisfactory kidney graft survival, suggesting that IA could potentially offer some benefits supporting its indication in cAMR.

Rituximab, plasma exchange and immunoglobulins: an ineffective treatment for chronic active antibody-mediated rejection.

BACKGROUND: Chronic active antibody-mediated rejection (c-aABMR) is an important cause of allograft failure and graft loss in long-term kidney transplants. METHODS: To determine the efficacy and safety of combined therapy with rituximab, plasma exchange (PE) and intravenous immunoglobulins (IVIG), a cohort of patients with transplant glomerulopathy (TG) that met criteria of active cABMR, according to BANFF'17 classification, was identified. RESULTS: We identified 62 patients with active c-aABMR and TG (cg ≥ 1). Twenty-three patients were treated with the combination therapy and, 39 patients did not receive treatment and were considered the control group. There were no significant differences in the graft survival between the two groups. The number of graft losses at 12 and 24 months and the decline of eGFR were not different and independent of the treatment. A decrease of eGFR≥13 ml/min between 6 months before and c-aABMR diagnosis, was an independent risk factor for graft loss at 24 months (OR = 5; P = 0.01). Infections that required hospitalization during the first year after c-aABMR diagnosis were significantly more frequent in treated patients (OR = 4.22; P = 0.013), with a ratio infection/patient-year of 0.65 and 0.20 respectively. CONCLUSIONS: Treatment with rituximab, PE, and IVIG in kidney transplants with c-aABMR did not improve graft survival and was associated with a significant increase in severe infectious complications. TRIAL REGISTRATION: Agencia Española de Medicametos y Productos Sanitarios (AEMPS): 14566/RG 24161. Study code: UTR-INM-2017-01.

Repeated Renal Biopsy - A Predictive Tool to Assess the Probability of Renal Flare in Lupus Nephritis.

BACKGROUND: How one responds to treatment of lupus nephritis (LN) is based on clinical features, but the activity in renal biopsy (RB) is uncertain. We have described the therapeutic decisions after performing a repeated RB on the assessment of response to intravenous cyclophosphamide (IC) and the possible prognostic role of this repeated RB. METHODS: Clinical, laboratory and histological features at the initial RB and repeated RB were analyzed in 35 patients. RESULTS: Data in the initial versus the repeated RB were serum creatinine 1.23 ± 1.08 and 0.96 ± 0.45 mg/dl (p < 0.05), glomerular filtration rate <60 ml/min in 12 and 5% patients and proteinuria 4.1 ± 2.8 vs. 0.6 1.1 g/day (p < 0.05). Significant differences were detected in hematuria, nephrotic syndrome and serological immune features. Complete renal remission was reached in 60% (n = 21) at the time of the repeated RB, partial remission in 31.4% (n = 11), and no response IC in 8.6% (n = 3). Nine patients showed proliferative forms in the repeated RB, 3 of them had proteinuria <1 g/day. Just after the repeated RB, 34.3% increased or started a new immunosuppressive therapy, 17.1% remained with the same complementary IST, and 14.3% decreased or stopped it. In the follow-up post repeated RB, 34.5% without active lesions showed a renal flare versus 77.8% with active lesions (p = 0.04). The mean time was 120 and 45 months, respectively. CONCLUSION: A repeated biopsy in LN distinguishes patients in true remission from those in apparent remission. By doing this, we can identify patients who could benefit from intensified treatment and for whom unnecessary treatment methods can be modified or eliminated.

Contrast-induced encephalopathy in patients with advanced chronic kidney disease: What the nephrologist needs to know.

Contrast-induced encephalopathy is a neurological complication related to contrast used in endovascular procedures or computed tomography (CT). The main risk factors are arterial hypertension, diabetes mellitus, chronic kidney disease (CKD), hyperosmolar contrasts, the amount of infused contrast and its direct infusion in the posterior cerebral territory, or pathologies with blood-brain barrier damage. Symptomatology is non-specific and may present as altered level of consciousness, neurological focality or seizures. Diagnosis is done by exclusion after ischemic or hemorrhagic stroke has been ruled out; CT or MRI are useful for differentiation. Generally, it appears shortly after exposure and the symptoms lasts 48-72h with complete recovery, although cases with persistence of symptoms or longer duration have been described. Treatment consists of monitoring, supportive measures and kidney replacement therapy (KRT) with hemodialysis (HD) in patients in chronic KRT program. It is important for the nephrologist to be aware of this entity given the susceptibility of the patient on HD as well as its potential therapeutic role in these patients.

Acute hepatitis post arteriovenous graft thrombectomy of hemodialysis vascular access.

The following paper reports the case of a woman on in-center hemodialysis through an arteriovenous graft, who attended with an acute vascular access thrombosis. Post percutaneous thrombectomy, the patient presented a rare case of self-limited acute hepatitis secondary to the revascularization procedure. We explain the probable trigger for this complication, its pathophysiology, management, and evolution.

Impact of cardiac surgery associated acute kidney injury on 1-year major adverse kidney events.

Background: The incidence of acute kidney injury following cardiac surgery (CSA-AKI) is up to 30%, and the risk of chronic kidney disease (CKD) has been found to be higher in these patients compared to the AKI-free population. The aim of our study was to assess the risk of major adverse kidney events (MAKE) [25% or greater decline in estimated glomerular filtration rate (eGFR), new hemodialysis, and death] after cardiac surgery in a Spanish cohort and to evaluate the utility of the score developed by Legouis D et al. (CSA-CKD score) in predicting the occurrence of MAKE. Methods: This was a single-center retrospective study of patients who required cardiac surgery with cardiopulmonary bypass (CPB) during 2015, with a 1-year follow-up after the intervention. The inclusion criteria were patients over 18 years old who had undergone cardiac surgery [i.e., valve substitution (VS), coronary artery bypass graft (CABG), or a combination of both procedures]. Results: The number of patients with CKD (eGFR < 60 mL/min) increased from 74 (18.3%) to 97 (24%) within 1 year after surgery. The median eGFR declined from 85 to 82 mL/min in the non-CSA-AKI patient group and from 73 to 65 mL/min in those with CSA-AKI (p = 0.024). Fifty-eight patients (1.4%) presented with MAKE at the 1-year follow-up. Multivariate logistic regression analysis showed that the only variable associated with MAKE was CSA-AKI [odds ratio (OR) 2.386 (1.31-4.35), p = 0.004]. The median CSA-CKD score was higher in the MAKE cohort [3 (2-4) vs. 2 (1-3), p < 0.001], but discrimination was poor, with a receiver operating characteristic curve (AUC) value of 0.682 (0.611-0.754). Conclusion: Any-stage CSA-AKI is associated with a risk of MAKE after 1 year. Further research into new measures that identify at-risk patients is needed so that appropriate patient follow-up can be carried out.

Assessment of Individualized Mean Perfusion Pressure Targets for the Prevention of Cardiac Surgery-Associated Acute Kidney Injury-The PrevHemAKI Randomized Controlled Trial.

BACKGROUND: Retrospective studies support that mean perfusion pressure (MPP) deficit in cardiac surgery patients is associated with a higher incidence of acute kidney injury (CS-AKI). The aim of our study was to apply an algorithm based on MPP in the postoperative period to determine whether management with an individualized target reduces the incidence of CS-AKI. METHODS: Randomized controlled trial of patients undergoing cardiac surgery with extracorporeal circulation. Adult patients submitted to valve replacement and/or bypass surgery with a high risk of CS-AKI evaluated by a Leicester score >30 were randomized to follow a target MPP of >75% of the calculated baseline or a standard hemodynamic management during the first postoperative 24 h. RESULTS: Ninety-eight patients with an eGFR of 54 mL/min were included. There were no differences in MAP and MPP in the first 24 h between the randomized groups, although a higher use of noradrenaline was found in the intervention arm (38.78 vs. 63.27, p = 0.026). The percentage of time with MPP < 75% of measured baseline was similar in both groups (10 vs. 12.7%, p = 0.811). MAP during surgery was higher in the intervention group (73 vs. 77 mmHg, p = 0.008). The global incidence of CS-AKI was 36.7%, being 38.6% in the intervention group and 34.6% in the control group (p = 0.40). There were no differences in extrarenal complications between groups as well. CONCLUSION: An individualized hemodynamic management based on MPP compared to standard treatment in cardiac surgery patients was safe but did not reduce the incidence of CS-AKI in our study.

Creatine Kinase Elevation in Autosomal Dominant Polycystic Kidney Disease Patients on Tolvaptan Treatment.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary cause of end-stage kidney disease. Currently, tolvaptan is the only treatment that has proven to delay disease progression. The most notable side effect of this therapy is drug-induced liver injury; however, recently, there have been two reports of creatine kinase (CK) elevation in ADPKD patients on tolvaptan treatment. We set out to monitor and determine the actual incidence of CK elevation and evaluate its potential association with other clinical factors. METHODS: This is an observational retrospective multicenter study performed in rapidly progressive ADPKD patients on tolvaptan treatment from Barcelona, Spain. Laboratory tests, demographics, treatment dose, and reported symptoms were collected from October 2018 to March 2021. RESULTS: Ninety-five patients initiated tolvaptan treatment during follow-up. The medication had to be discontinued in 31 (32.6%) patients, primarily due to aquaretic effects (12.6%), elevated liver enzymes (8.4%), and symptomatic or persistently elevated CK levels (3.2%). Moreover, a total of 27 (28.4%) patients had elevated CK levels, with most of them being either transient (12.6%), mild and asymptomatic (4.2%), or resolved after dose reduction (3.2%) or temporary discontinuation (2.1%). CONCLUSION: We pre-sent the largest cohort that has monitored CK levels in a real-life setting, finding them elevated in 28.4% of patients. More research and monitoring will help us understand the clinical implications and the pathophysiological mechanism of CK elevation in this population.

Cross-sectional study of adherence to venous thromboembolism prophylaxis guidelines in hospitalized patients. The Trombo-Brit study.

BACKGROUND: DVT is the main cause of death in hospitalized patients and thromboprophylaxis is the only way to prevent these deaths. International recommendations suggested that active monitoring of DVT/PE prophylaxis can improve the efficacy in Hospitals. METHODS: We performed a cohort study in three consecutives periods to evaluate DVT prophylaxis in 388 adults hospitalized in a General Hospital. RESULTS: 85% of the population had high risk factors for DVT. Thromboprophylaxis was in accordance with local and International guidelines (ACCP 2008) in 72.7% and 86% of the patients respectively. No significant difference could be founded between clinical and surgical patients. One every 10 patients received higher prophylaxis than suggested by guidelines and two out of ten received deficient or no prophylaxis. The worst 2 groups of patients were those with moderate/low risk of DVT and the group with a contraindication to pharmacologic prophylaxis. We observed a progressive improvement of the DVT prophylaxis in the 3 periods of evaluation. CONCLUSIONS: Although the rate of recommended thromboprophylaxis is higher than many other reports in the region we still have some areas where we need to improve. Regular audits like these are very helpful to find out what specific areas of the hospital needs some careful attention in order to have a better quality of assistance.

Syndrome of inappropriate antidiuretic hormone secretion. / Síndrome de secreción inadecuada de hormona antidiurética.

Hyponatremia is the most frequent electrolytic disorder in hospitalized patients, and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), the most frequent cause of hiponatremia with clinically normal extracellular volume. It consists of a disorder of the regulation of body water that obeys to different causes, mainly cancer, pulmonary illnesses, disorders of the central nervous system and diverse drugs. As in any hiponatremia it a physiological knowledge of the regulation of body water and sodium is essential as well as the application of precise diagnostic criteria in order to manage the problem with an effective treatment. The available data until the moment show that the clinical diagnosis of SIADH made by professionals is mainly not supported on the established criteria drawn by experts and this lack of accuracy probably hits in the therapeutic result. The basis of the treatment of the SIADH is to correct its cause, water restriction, solutes (sodium chloride) and the use of vaptans in case of failure of the previous measures.