Kidney Transplantation in Monoclonal Immunoglobulin Deposition Disease: A Report of 6 Cases.

Monoclonal immunoglobulin deposition disease (MIDD) usually leads to kidney failure. Treatment of patients with a bortezomib-based regimen followed by autologous stem cell transplantation (SCT) has been increasingly used, with improvements in the response rates and allograft outcomes in kidney transplant recipients. The objective of this report was to analyze the outcomes of 6 patients who underwent kidney transplantation in our institution after treatment of MIDD between 2010 and 2019. Monoclonal immunoglobulin deposition disease was initially treated with bortezomib-based therapy followed by high-dose melphalan and autologous SCT with complete hematologic response, although all patients remained on dialysis. During a median follow-up of 20.5 months from kidney transplant (54 months from SCT), 1 patient experienced hematologic relapse and 2 had hematologic progression (one of them with MIDD relapse in the allograft) requiring treatment. The patient with organ relapse received daratumumab monotherapy, achieving complete hematologic response but with graft failure. The other 5 patients had functional grafts with median serum creatinine 1.68 mg/dL. These results support that, in patients with MIDD and sustained complete hematologic response, a kidney transplant can be considered. The optimal approach to treatment of hematologic relapse or recurrence of MIDD after kidney transplant remains to be determined.

SARS-CoV-2 Infection in a Spanish Cohort of CKD-5D Patients: Prevalence, Clinical Presentation, Outcomes, and De-Isolation Results.

INTRODUCTION: COVID-19 is a highly contagious disease that has easily spread worldwide. Outpatient maintenance hemodialysis seems to entail an increased risk of contagion, and previous reports inform of increased mortality among this population. METHODS: We retrospectively analyzed clinical and laboratory parameters, outcomes, and management once discharged of CKD-5D patients infected with SARS-CoV-2 from our health area. RESULTS: Out of the 429 CKD-5D population, 36 were diagnosed with SARS-CoV-2 infection (8%): 34 on in-center hemodialysis and 2 on peritoneal dialysis. Five were asymptomatic. The most common symptom was fever (70%), followed by dyspnea and cough. History of cardiovascular disease and elevation of LDH and C-reactive protein during admission were associated with higher mortality. Thirteen patients died (36%), 8 patients were admitted to an ICU, and survival was low (38%) among the latter. The mean time to death was 12 days. Most discharged patients got negative rRT-PCR in nasopharyngeal swabs within 26 days of diagnosis. However, there is a portion of cured patients that continue to have positive results even more than 2 months after the initial presentation. CONCLUSIONS: Patients on dialysis have an increased mortality risk if infected with SARS-CoV-2. Preventive measures have proven useful. Thus, proper ones, such as universal screening of the population and isolation when required, need to be generalized. Better de-isolation criteria are necessary to ensure an appropriate use of public health resources.

Rapid re-transplantation safety following early kidney graft loss.

INTRODUCTION: Early graft loss is a devastating kidney transplant complication associated with high mortality and an increased risk of sensitization to antigens from the failed graft. Moreover, if rapid re-transplantation were to occur, given that the human leukocyte antigen antibodies identification may not be reliable until several weeks after transplantation, the recipient's immunological status would be uncertain. Hence, there could be an increased immunological risk. To date, there is no information on whether a rapid re-transplantation after early graft loss, without a new reliable anti-HLA determination, is safe. METHODS: We retrospectively analysed the number of rejections and the graft survival of re-transplanted patients with early graft loss (defined as graft failure before 30 days from transplant) from our centre between June 2003 and November 2019. The studied population was divided into rapid re-transplantation (performed within 30 days of early graft loss) and late re-transplantation (performed beyond those 30 days). RESULTS: Forty-seven patients were re-transplanted after early graft loss. There were nine rapid re-transplantation cases with an 89% five-year graft survival and one antibody-mediated rejection episode. Furthermore, we identified 38 cases of late re-transplantation with a 69% five-year graft survival, 4 T cell-mediated, and 11 antibody-mediated rejections. CONCLUSIONS: Rapid re-transplantation appears to be safe and does not entail increased rejection risk, nor does it impact long-term graft survival when compared to late re-transplantation.

Factor B Inhibition with Iptacopan in Recurrent C3 Glomerulopathy Following Kidney Transplant: A Report of Two Cases.

C3 glomerulopathy is a rare disease caused by fluid phase dysregulation of the alternative complement pathway. Currently, treatment depends on clinical and histological severity and includes nephroprotection, unspecific immunosuppression, and terminal complement blockers (C5), without having an etiological treatment approved. C3 glomerulopathy has high recurrence rates after kidney transplantation with a high risk of graft loss. Fortunately, new molecules are being developed that specifically target the proximal alternative complement pathway, such as iptacopan, a factor B inhibitor that showed promising results in native kidneys and cases of transplant recurrence in a phase 2 clinical trial. We present 2 "real-world" cases of C3 glomerulopathy recurrence in kidney allografts treated with iptacopan, with initial excellent clinical response and safety profile, especially with early introduction. We also present follow-up biopsies that showed no C3 deposition during factor B inhibition. Our cases suggest that proximal blockade of the alternative complement pathway can be effective and safe in the treatment of C3 glomerulopathy recurrence in kidney transplantation, bringing other questions such as dual blockade (eg, in C3 and C5), the optimal patient profile to benefit from factor B inhibition or treatment duration and its potential use in other forms of membranoproliferative glomerulonephritis (eg, immune complex-mediated).

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.

Humoral Response after Three Doses of mRNA-1273 or BNT162b2 SARS-CoV-2 Vaccines in Hemodialysis Patients.

The COVID-19 pandemic continues to be a worldwide health issue. Among hemodialysis (HD) patients, two-dose immunization schemes with mRNA vaccines have contributed to preventing severe COVID-19 cases; however, some have not produced a sufficient humoral response, and most have developed a rapid decline in antibody levels over the months following vaccination. This observational, prospective, multi-center study evaluated the humoral response in terms of presence and levels of IgG antibodies to the receptor-binding domain of the S1 spike antigen of SARS-CoV-2 (anti-S1-RBD IgG) to the third dose of SARS-CoV-2 mRNA vaccines, either the mRNA-1273 (Moderna) or BNT162b2 (Pfizer), in 153 patients from three dialysis units affiliated to Hospital Clínic of Barcelona (Spain). Most hemodialysis patients responded intensely to this third vaccine dose, achieving the seroconversion in three out of four non- or weak responders to two doses. Moreover, 96.1% maintained the upper limit or generated higher titers than after the second. BNT162b2 vaccine, active cancer, and immunosuppressive treatment were related to a worse humoral response. Every hemodialysis patient should be administered a third vaccine dose six months after receiving the second one. Despite the lack of data, immunosuppressed patients and those with active cancer may benefit from more frequent vaccine boosters.

Tailoring the dialysate bicarbonate eliminates pre-dialysis acidosis and post-dialysis alkalosis.

Background: Both metabolic acidosis and alkalosis increase hospitalizations, haemodynamic instability and mortality in haemodialysis patients. Unfortunately, current practices opt for a one-size-fits-all approach, leaving many patients either acidotic before or alkalotic after dialysis sessions. Therefore an individualized adjustment of these patients' dialysate bicarbonate prescriptions could reduce these acid-base imbalances. Methods: This is a prospective single-cohort study of patients on a chronic haemodiafiltration programme. The dialysate bicarbonate prescription was modified according to the pre- and post-dialysis total carbon dioxide (TCO2) values of 19-25 mEq/L and ≤29 mEq/L, respectively, with an adjustment formula calculated with the data obtained from previously published work by our group. In addition, we analysed this adjustment's effect on plasma sodium, potassium, phosphorus, parathyroid hormone (PTH) and calcium. Results: At baseline, only 67.9% of patients were within the desired pre- and post-dialysis TCO2 target range. As of the first month, every followed patient met the TCO2 target range objective in pre-dialysis measurements and ˃95% met the post-dialysis TCO2 target. At the end of the study, 75% of the patients were on dialysate bicarbonate of 32-34 mEq/L. There were no clinically significant changes in calcium, phosphate, PTH, sodium or potassium levels. Also, we did not notice any increase in intradialytic adverse events. Conclusions: We suggest an individualized adjustment of the dialysate bicarbonate concentration according to the pre- and post-dialysis TCO2 values. With it, nearly every patient in our cohort reached the established range, potentially reducing their mortality risk.

Post-Intensive Care COVID Survivorship Clinic: A Single-Center Experience.

Patients discharged from the ICU post-COVID-19 pneumonitis may experience long-term morbidity related to their critical illness, the treatment for this and the ICU environment. The aim of this study was to characterize the cognitive, psychologic, and physical consequences of COVID-19 in patients admitted to the ICU and discharged alive. DESIGN: Prospective cohort study. SETTING: Post-intensive care syndrome (PICS) follow-up clinic at Tallaght University Hospital, a tertiary referral center with a 16-bed mixed medical-surgical ICU, including critical care physicians, a psychologist, a physiotherapist, and a research nurse. PATIENTS: Patients who had been admitted to the ICU in our tertiary referral center with COVID-19 pneumonitis 6 months earlier. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 22 patients attended the 6-month PICS follow-up clinic following admission to ICU with COVID-19 pneumonitis. Mean grip strength was low at the 6-month follow-up at 24.1 pounds (sd 9.8) with a minimally active median metabolic equivalent (MET) of 970 METs/wk (interquartile range, 0-7,794 METs/wk). Only 59% of patients were independent with regard to their activities of daily living. Eight of 14 patients (57%) had returned to work by 6 months post-ICU discharge. Their mean Intensive Care Psychological Assessment Tool (IPAT) score was 6.6 (sd 4.6) with a Post-Traumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders-5th Edition (PCL-5) score of 21.1 (sd 17.5) and a mean Montreal Cognitive Assessment (MoCA) score of 24 (sd 8.4); suggestive of mild cognitive impairment. In a multivariable regression model, only Acute Physiology and Chronic Health Evaluation II score was significantly independently associated with MoCA score as a cognitive PICS outcome (beta-coefficient, -1.6; se, 0.6; p = 0.04). None of the predictor variables were significantly independently associated with IPAT and PCL-5 as psychologic outcomes, nor with International Physical Activity Questionnaire-Short Form as a physical PICS outcome. CONCLUSIONS: In this single-center prospective cohort study, we found that patients have a high burden of physical and psychologic impairment at 6 months following ICU discharge post-COVID-19 pneumonitis; in many cases requiring specialist referrals for long-term input. We advocate for increased resources for this much needed follow-up multidisciplinary intervention for an ever-growing population of patients.

A case of recurrent anemia due to chronic parvovirus B19 infection in a kidney transplant recipient. Can everolimus make a difference?

Parvovirus B19 (PB19) is a common infection among solid transplant recipients. Usually, it is asymptomatic, but sometimes it can become a real therapeutic challenge. We report a case of a kidney transplant recipient with relapsing pure red cell aplasia due to PB19 infection. Our patient was initially managed with standard treatment consisting of intravenous immunoglobulins and minimization of immunosuppressive treatment. However, when this approach became ineffective, conversion from tacrolimus to everolimus was done, with favorable results. This paper explores infection by PB19 in kidney transplant recipients and the potential benefits of a calcineurin inhibitor-free immunosuppression and the antiviral properties of mTOR inhibitors.