Successful transplantation of four kidney grafts from two small pediatric donors with anuric acute renal failure into adult recipients

Background Kidneys from infants with anuric acute kidney injury (AKI) only rarely get accepted for transplantation despite encouraging data that such kidneys can have very good long-term outcome. Methods We report the transplantation of four kidney grafts from two pediatric donors (3 and 4 years) with anuric acute kidney injury as single kidneys into four adult recipients. Results All grafts gained function within 14 days posttransplantation, only one recipient needed dialysis after transplantation. None of the recipients suffered from surgical complications. One month after transplantation, all recipients were free of dialysis. Estimated glomerular filtration rates (eGFR) 3 months after transplantation were 37, 40, 50, and 83 mL/min/1.73 m2. eGFR increased further through month 6, reaching 45, 50, 58, and 89 mL/min/1.73 m2. Conclusion These cases highlight the feasibility of successful transplantation of single pediatric kidney grafts into adult recipients despite anuric AKI of the donor

Plasma exchange for treatment of a therapy-related thrombotic microangiopathy in a patient with advanced hepatocellular carcinoma : case report

Key Clinical Message: Thrombotic microangiopathies are a side effect of anti-VEGF therapies, which are often limited to the kidneys but can also occur systemically and be life-threatening. Screening for increasing proteinuria is essential. We present the case of a 65-year-old male patient with a multifocal HCC, Barcelona clinic liver cancer (BCLC) classification B at the time of diagnosis. The HCC was treated with nine sessions of transarterial chemoembolization (TACE), and after a progress, the therapy was switched to a combination of atezolizumab and bevacizumab. Five months after therapy change, he presented with an acute kidney injury. The histopathology of the renal biopsy showed findings of a thrombotic microangiopathy (TMA), which we treated with 12 sessions of therapeutic plasma exchange in combination with steroids, resulting in a decreased TMA activity and later in a remission of the TMA. This case suggests the importance of monitoring the kidney function and proteinuria in patients under anti-vascular endothelial growth factor (VEGF) therapy and shows a rare differential diagnosis for a worsening of kidney function in these patients. Furthermore, it shows that therapeutic plasma exchange might be a valuable therapeutic option for patients with TMA due to anti-VEGF therapy

Validating quantitative PCR assays for cfDNA detection without DNA extraction in exercising SLE patients

Circulating cell-free DNA (cfDNA) has been investigated as a screening tool for many diseases. To avoid expensive and time-consuming DNA isolation, direct quantification PCR assays can be established. However, rigorous validation is required to provide reliable data in the clinical and non-clinical context. Considering the International Organization for Standardization, as well as bioanalytical method validation guidelines, we provide a comprehensive procedure to validate assays for cfDNA quantification from blood plasma without DNA isolation. A 90 and 222 bp assay was validated to study the kinetics of cfDNA after exercise in patients with systemic lupus erythematosus (SLE). The assays showed ultra-low limit of quantification (LOQ) with 0.47 and 0.69 ng/ml, repeatability ≤ 11.6% (95% CI 8.1–20.3), and intermediate precision ≤ 12.1% (95% CI 9.2–17.7). Incurred sample reanalysis confirmed the precision of the procedure. The additional consideration of pre-analytical factors shows that centrifugation speed and temperature do not change cfDNA concentrations. In SLE patients cfDNA increases ~ twofold after a walking exercise, normalizing after 60 min of rest. The established assays allow reliable and cost-efficient quantification of cfDNA in minute amounts of plasma in the clinical setting. Additionally, the assay can be used as a tool to determine the impact of pre-analytical factors and validate cfDNA quantity and quality of isolated samples

Immunoadsorption and plasma exchange : efficient treatment options for neurological autoimmune diseases

Background Therapeutic plasma exchange (TPE) and immunoadsorption (IA) are first or second line treatment options in patients with neurological autoimmune diseases, including multiple sclerosis, neuromyelitis optica spectrum disorders (NMSOD), chronic inflammatory demyelinating polyneuropathy, acute inflammatory demyelinating polyradiculoneuropathy (Guillain-Barré syndrome), and autoimmune encephalitis. Methods In this prospective randomized controlled monocentric study, we assessed safety and efficacy of therapy with IA or TPE in patients with neurological autoimmune diseases. Treatment response was assessed using various neurological scores as well by measuring immunoglobulin and cytokine concentrations. Clinical outcome was evaluated by application of specific scores for the underlying diseases. Results A total of 32 patients were analyzed. Among these, 19 patients were treated with TPE and 13 patients with IA. IA and TPE therapy showed a comparable significant treatment response. In patients with MS and NMOSD, mean EDSS before and after treatment showed a significant reduction after treatment with IA. We observed a significant reduction of the pro-inflammatory cytokines IL-12, lL-17, IL-6, INF-γ, and tumor necrosis factor alpha during IA treatment, whereas this reduction was not seen in patients treated with TPE. Conclusions In summary, both IA and TPE were effective and safe procedures for treating neurological autoimmune diseases. However, there was a trend towards longer therapy response in patients treated with IA compared to TPE, possibly related to a reduction in plasma levels of pro-inflammatory cytokines seen only in the IA-treated group

Sex-specific differences in SLE – Significance in the experimental setting of inflammation and kidney damage in MRL-Faslpr mice

Animal models are an important tool in the research of chronic autoimmune diseases, like systemic lupus erythematosus (SLE). MRL-Faslpr mice are one of different lupus models that develop spontaneously an SLE-like disease with autoantibodies and immune complex deposition that leads into damage of different organs. In contrast to human SLE, both sexes of MRL-Faslpr mice develop a similar autoimmune disease. Due to the sex bias in human and the delayed disease progression in male MRL-Faslpr mice, the majority of studies have been performed in female mice. To determine the suitability of male MRL-Faslpr mice for SLE research, especially with regard to the 3 R-principle and animal welfare, analyses of phenotype, inflammation and damage with focus on kidney and spleen were performed in mice of both sexes. Female mice developed lymphadenopathy and skin lesions earlier as males. At an age of 3.5 month, more immune cells infiltrated kidney and spleen in females compared to males. At the age of 5 months, however, substantially less sex-specific differences were detected. Since other studies have shown differences between both sexes on other manifestations like autoimmune pancreatitis and Sjögren syndrome in MRL-Faslpr mice, the use of male mice as part of 3 R-principle and animal welfare must be carefully considered

COVID-19—Importance for Patients on the Waiting List and after Kidney Transplantation—A Single Center Evaluation in 2020–2021

(1) Background: Dialysis patients and recipients of a kidney allograft are at high risk for infection with SARS-CoV-2. It has been shown that the development of potent neutralizing humoral immunity against SARS CoV-2 leads to an increased probability of survival. However, the question of whether immunocompromised patients develop antibodies has not yet been sufficiently investigated; (2) Methods: SARS-CoV-2 antibodies were examined in hemodialysis patients on the waiting list for kidney transplantation as well as patients after kidney transplantation. Patients were interviewed about symptoms and comorbidities, BMI, and smoking history; (3) Results: SARS-CoV-2 antibodies were found in 16 out of 259 patients (6%). The trend of infections here reflects the general course of infection in Germany with a peak in November/December of 2020. Remarkably, patients on the waiting list experienced only mild disease. In contrast, transplanted patients had to be hospitalized but recovered rapidly from COVID-19. Most interesting is that all immunosuppressed patients developed antibodies against SARS-CoV-2 after infection; (4) Conclusions: Even with extensive hygiene concepts, an above-average number of patients were infected with SARS-CoV-2 during the second wave of infections in Germany. Because SARS-CoV-2 infection triggered the formation of antibodies even in these immunocompromised patients, we expect vaccination to be effective in this group of patients. Thus, dialysis patients and patients after kidney transplantation should be given high priority in vaccination programs

Six-Month Follow-Up after Vaccination with BNT162b2: SARS-CoV-2 Antigen-Specific Cellular and Humoral Immune Responses in Hemodialysis Patients and Kidney Transplant Recipients

Hemodialysis patients (HDP) and kidney transplant recipients (KTR) have a high risk of infection with SARS-CoV-2 with poor clinical outcomes. Because of this, vaccination of these groups of patients against SARS-CoV-2 is particularly important. However, immune responses may be impaired in immunosuppressed and chronically ill patients. Here, our aim was to compare the efficacy of an mRNA-based vaccine in HDP, KTR, and healthy subjects. Design: In this prospective observational cohort study, the humoral and cellular response of prevalent 192 HDP, 50 KTR, and 28 healthy controls (HC) was assessed 1, 2, and 6 months after the first immunization with the BNT162b2 mRNA vaccine. Results: After 6 months, 97.5% of HDP, 37.9% of KTR, and 100% of HC had an antibody response. Median antibody levels were 1539.7 (±3355.8), 178.5 (±369.5), and 2657.8 (±2965.8) AU/mL in HDP, KTR, and HC, respectively (p ≤ 0.05). A SARS-CoV-2 antigen-specific cell response to vaccination was found in 68.8% of HDP, 64.5% of KTR, and 90% of HC. Conclusion: The humoral response rates to mRNA-based vaccination of HDPs are comparable to HCs, but antibody titers are lower. Furthermore, HDPs have weaker T-cell response to vaccination than HCs. KTRs have very low humoral and antigen-specific cellular response rates and antibody titers, which requires other vaccination strategies in addition to booster vaccination.</jats:p

COVID-19—Importance for Patients on the Waiting List and after Kidney Transplantation—A Single Center Evaluation in 2020–2021

(1) Background: Dialysis patients and recipients of a kidney allograft are at high risk for infection with SARS-CoV-2. It has been shown that the development of potent neutralizing humoral immunity against SARS CoV-2 leads to an increased probability of survival. However, the question of whether immunocompromised patients develop antibodies has not yet been sufficiently investigated; (2) Methods: SARS-CoV-2 antibodies were examined in hemodialysis patients on the waiting list for kidney transplantation as well as patients after kidney transplantation. Patients were interviewed about symptoms and comorbidities, BMI, and smoking history; (3) Results: SARS-CoV-2 antibodies were found in 16 out of 259 patients (6%). The trend of infections here reflects the general course of infection in Germany with a peak in November/December of 2020. Remarkably, patients on the waiting list experienced only mild disease. In contrast, transplanted patients had to be hospitalized but recovered rapidly from COVID-19. Most interesting is that all immunosuppressed patients developed antibodies against SARS-CoV-2 after infection; (4) Conclusions: Even with extensive hygiene concepts, an above-average number of patients were infected with SARS-CoV-2 during the second wave of infections in Germany. Because SARS-CoV-2 infection triggered the formation of antibodies even in these immunocompromised patients, we expect vaccination to be effective in this group of patients. Thus, dialysis patients and patients after kidney transplantation should be given high priority in vaccination programs.</jats:p