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Polyomavirus BK (BKV) nephropathy, an emerging cause of renal-allograft failure, may be linked to immunosuppressive regimens containing tacrolimus or mycophenolate mofetil. This prospective, single-center study examined urine for cells with viral inclusions, measured BKV DNA in plasma, and evaluated renal-biopsy specimens for evidence of nephropathy in 78 renal-transplant recipients who were being treated with such regimens. Four of five patients in whom BKV nephropathy developed were among the 77 percent of patients who had BKV antibodies before transplantation. The probability of BKV nephropathy was 8 percent (95 percent confidence interval, 1 to 15 percent). Since it was first reported in 1995, nephropathy associated with the polyomavirus type BK (BKV) has emerged as an important cause of allograft failure in renal-transplant recipients. 1 – 3 BKV is closely related to another human polyomavirus, JC virus (JCV), which causes progressive multifocal leukoencephalopathy in immunocompromised patients. 4 Infection with either polyomavirus is widespread, as indicated by seroprevalence rates of up to 90 percent worldwide. 5 The risk factors for BKV nephropathy in renal-transplant recipients are not known, but most patients with BKV nephropathy have received newer immunosuppressive drugs such as tacrolimus or mycophenolate mofetil. 6 – 13 Because BKV persists in the kidney, . . .

The interplay of recipient age and graft loss causes is underexplored, despite its relevance for patient management and endpoint definition in clinical trials. This study aimed to investigate the impact of recipient age on graft loss causes. In this retrospective single-center cohort study with 1743 kidney transplantations between 1995 and 2022, graft losses were assigned to either death with graft function (DwGF) or graft failure (GF). Additionally, causes of death and GF were determined by reviewing all available clinical/histological information. Data were analyzed across recipient age groups (≤40, 41–60 and >60 years) and across three time periods (1995–2004, 2005–2014, 2015–2022). Among 816 graft losses, 56% were attributed to DwGF and 44% to GF. The proportion of DwGF increased stepwise with age (21% in young vs. 52% in middle-aged vs. 76% in elderly patients; p < 0.0001), with similar proportions across the three time periods. Rejection alone or in combination with other events caused GF in 76% of young, 51% of middle-aged, and 34% of elderly patients (p < 0.0001). Main death-causes were cardiovascular events (23%), infections (23%) and malignancies (23%). Graft loss causes are strongly age-related. This might have significant implications for clinical study design and patient management.

Background/objectives Shock and accompanying acute kidney injury (AKI) as a frequent complication is a well-known cause of morbidity and mortality worldwide. The current standard parameters to guide fluid resuscitation therapy (i.e., cardiac output, heart rate, blood pressure, central venous pressure) to avoid AKI and renal replacement therapy remain imprecise, and fluid overload with consequent organ oedema and high intestinal pressures result in further complications. The VoluKid study investigated additional non-invasive fluid volume parameters including assessment of total body water (TBW), renal vascular resistance [renal resistive index (RRI)], intra-abdominal pressure (IAP) and microcirculatory blood flow (MBF) to predict AKI during the first 72 h of intensive care therapy. Methods, design and analysis This mono-centre observational cohort study included patients with shock who presented to the intensive care unit (ICU). Routine volume resuscitation parameters (i.e., cardiac output, heart rate, blood pressure, central venous pressure) were used to guide fluid therapy. In addition, four parameters, including MBF using sublingual incident dark-field microscopy, IAP, RRI assessed by duplex-sonography, and TBW using bioimpedance analysis (BIA), were measured daily and evaluated for predicting the primary outcome of acute kidney injury (AKI) and need for renal replacement therapy within the first 72 h of admission. Baseline and post-ICU admission values of these parameters were compared between patients with and without AKI. Results A total of 45 patients were enrolled in this study. Of those 45 patients, 37 could be followed for the entire study period of 72 h and 14 patients developed AKI (31.1%). Twelve patients (26.7%) had pre-existing renal impairment, one of whom died during the observation period. Nineteen patients (42.2%) had no renal impairment. RRI and IAP did not differ between patients with AKI and without AKI and did not predict AKI. TBW measured by BIA predicted AKI ( p  = 0.029). After adjustment for covariates (age, body mass index,and gender) this prediction was not significant [adjusted odds rato (OR) 0.99, p  = 0.258, 95% confidence interval (CI) [0.97,1.01]]. MBF could not be estimated due a high number of missing values. Conclusions Based on our limited data, none of the non-invasive parameters (TBA, IAP, RRI,) serve as predictors for AKI when assessed during the first 72 h after ICU admission, either when analysed separately or in combination. Registration ClinicalTrials.gov Identifier: NCT02666404, registered 28/01/2016; URL: https://classic.clinicaltrials.gov/ct2/show/NCT02666404 .

Abstract Introduction: Nowadays, there is insufficient evidence for the recommendation of management patients with a primary membranoproliferative glomerulonephritis (MPGN). A better understanding of the pathogenesis has led to the reclassification of primary MPGN and distinction into the two main entities of either primary immune complex-MPGN or C3 glomerulopathy. Both entities share overlapping pathophysiological features with complement alternative pathway (AP) dysregulation. Iptacopan is an oral inhibitor of the complement factor B that effectively blocks the complement AP. Case Presentation: We report the first successful treatment of a 47-year-old man suffering from a primary immune complex-MPGN with iptacopan. So far established immunosuppressive therapies with prednisone and mycophenolate mofetil failed to control the current flare of the disease, mainly presenting with impaired kidney function and proteinuria within the nephrotic range. However, 3 months after starting the treatment with iptacopan urine protein-creatinine ratio decreased impressively to a level of 100–150 mg/mmol. Thereafter, low-level proteinuria and kidney function remained stable during follow-up. Do date, the treatment with iptacopan is continued as a monotherapy and is well tolerated. Conclusion: To the best of our knowledge, this is the first case report which suggests that iptacopan may be an interesting treatment option for primary immune complex-MPGN.

Acute antibody-mediated rejection (AMR) remains a challenge after kidney transplantation (KT). As there is no clear-cut treatment recommendation, accurate information on current therapeutic strategies in real-life practice is needed. KT recipients from the multicenter Swiss Transplant Cohort Study treated for acute AMR during the first post-transplant year were included retrospectively. We aimed at describing the anti-rejection protocols used routinely, as well as patient and graft outcomes, with focus on infectious complications. Overall, 65/1669 (3.9%) KT recipients were treated for 75 episodes of acute AMR. In addition to corticosteroid boluses, most common therapies included plasmapheresis (56.0%), intravenous immunoglobulins (IVIg) (38.7%), rituximab (25.3%), and antithymocyte globulin (22.7%). At least one infectious complication occurred within 6 months from AMR treatment in 63.6% of patients. Plasmapheresis increased the risk of overall (hazard ratio [HR]: 2.89; P -value = 0.002) and opportunistic infection (HR: 5.32; P -value = 0.033). IVIg exerted a protective effect for bacterial infection (HR: 0.29; P -value = 0.053). The recovery of renal function was complete at 3 months after AMR treatment in 67% of episodes. One-year death-censored graft survival was 90.9%. Four patients (6.2%) died during the first year (two due to severe infection). In this nationwide cohort we found significant heterogeneity in therapeutic approaches for acute AMR. Infectious complications were common, particularly among KT recipients receiving plasmapheresis.

Background Since the implementation of universal antiretroviral therapy, kidney transplantation (K-Tx) has become a valuable option for treatment of end-stage kidney disease for people with HIV (PWH) with similar patient and graft survival as compared to HIV-uninfected patients. Little is known about the hazards and manifestations of infectious disease (ID) events occurring in kidney transplant recipients with HIV. Methods Using linked information collected in the Swiss HIV Cohort Study (SHCS) and the Swiss Transplant Cohort Study (STCS), we described in-depth demographical and clinical characteristics of PWH who received a K-Tx since 2008. Further, we performed recurrent time to event analyses to understand whether HIV was an independent risk factor for ID events. Results Overall, 24 PWH with 57 ID events were included in this study (100% match of SHCS to STCS). Of these, 17 (70.8%) patients had at least one ID event: 22 (38.6%) viral (HIV not counted), 18 (31.6%) bacterial, one (1.8%) fungal and 16 (28.1%) probable infections. Most ID events affected the respiratory tract (25, 37.3%) or the urinary tract (13, 19.4%). Pathogen types and infection sites were similar in PWH and a matched control group of HIV-uninfected patients. HIV was not an independent risk factor for ID events (adjusted hazard ratio 0.94, p  = 0.9). Conclusion By linking data from two large national Swiss cohorts, we provided in-depth information on ID events in PWH receiving a K-Tx in Switzerland. HIV infection was not associated with an increased hazard for ID events after K-Tx. Summary In a matched analysis based on longitudinal data from the Swiss HIV and Transplant Cohort Studies including all people with HIV who received a kidney transplantation, HIV was not an independent risk factor for infectious disease events post-transplant.

We report the effectiveness of daratumumab, a human IgGκ monoclonal antibody targeting CD38 on plasma cells, for therapy-refractory antibody-mediated rejection (AMR) due to blood group antibodies in a 59-year-old man who received a living ABO-incompatible kidney transplantation. Standard treatment options for AMR due to blood group antibodies including immunoadsorption, lymphocyte depletion with anti-human T-lymphocyte globulins, intravenous methylprednisolone pulses and eculizumab limited tissue injury, however failed to sufficiently suppress blood group antibody production. After administration of daratumumab as a rescue therapy, blood group antibody titers decreased and remained at low levels without further immunoadsorption and allowed kidney graft function to recover.

Background Late 2019, a new highly contagious coronavirus SARS-CoV-2 has emerged in Wuhan, China, causing within 2 months a pandemic with the highest disease burden in elderly and people with pre-existing medical conditions. The pandemic has highlighted that new and more flexible clinical trial approaches, such as trial platforms, are needed to assess the efficacy and safety of interventions in a timely manner. The two existing Swiss cohorts of immunocompromised patients (i.e., Swiss HIV Cohort Study (SHCS) and Swiss Transplant Cohort Study (STCS)) are an ideal foundation to set-up a trial platform in Switzerland leveraging routinely collected data. Within a newly founded trial platform, we plan to assess the efficacy of the first two mRNA SARS-CoV-2 vaccines that reached market authorization in Switzerland in the frame of a pilot randomized controlled trial (RCT) while at the same time assessing the functionality of the trial platform. Methods We will conduct a multicenter randomized controlled, open-label, 2-arm sub-study pilot trial of a platform trial nested into two Swiss cohorts. Patients included in the SHCS or the STCS will be eligible for randomization to either receiving the mRNA vaccine Comirnaty® (Pfizer/BioNTech) or the COVID-19 mRNA Vaccine Moderna®. The primary clinical outcome will be change in pan-lg antibody response (pan-Ig anti-S1-RBD; baseline vs. 3 months after first vaccination; binary outcome, considering ≥ 0.8 units/ml as a positive antibody response). The pilot study will also enable us to assess endpoints related to trial conduct feasibility (i.e., duration of RCT set-up; time of patient recruitment; patient consent rate; proportion of missing data). Assuming vaccine reactivity of 90% in both vaccine groups, we power our trial, using a non-inferiority margin such that a 95% two-sided confidence interval excludes a difference in favor of the reference group of more than 10%. A sample size of 380 (190 in each treatment arm) is required for a statistical power of 90% and a type I error of 0.025. The study is funded by the Swiss National Science Foundation (National Research Program NRP 78, “COVID-19”). Discussion This study will provide crucial information about the efficacy and safety of the mRNA SARS-CoV-2 vaccines in HIV patients and organ transplant recipients. Furthermore, this project has the potential to pave the way for further platform trials in Switzerland. Trial registration ClinicalTrials.gov NCT04805125 . Registered on March 18, 2021

Background We report a case of sudden, lethal metabolic acidosis in a 70-year-old man on long-term nucleoside reverse transcriptase inhibitor (NRTI) -based antiretroviral therapy (ART) who had developed atypical necrotizing fasciitis 1 month after kidney transplantation. Case presentation The HIV infection of the patient was treated for the last four months with an integrase strand inhibitor (dolutegravir 50 mg/d) plus a NRTI backbone including lamivudine (150 mg/d) and abacavir (600 mg/d). In this renal transplant patient we hypothesize that the co-existence of sepsis, renal failure and an accumulation of lamivudine led to the development of fatal metabolic acidosis and hyperlactatemia. Although lamivudine is only rarely associated with hyperlactatemia, there is evidence that overdose may be a risk factor for developing it. In our patient the lamivudine concentration two days after stopping and during hemodiafiltration was more than 50 times higher than therapeutic target trough concentrations. Likely reasons for this were renal impairment and concurrent treatment with trimethoprim, known to inhibit the renal elimination of lamivudine. Conclusions NRTIs could trigger the development of hyperlactatemia in septic patients. The use of NRTI sparing regimens might be considered in the presence of this critical condition.