Rationale & Objective: Outcomes of kidney transplantation for patients with renal AA amyloidosis are uncertain, with reports of poor survival and high rates of disease recurrence. However, the data are inconclusive and mostly based on studies from the early 2000s and earlier. Study Design: Retrospective multicenter cohort study. Setting & Participants: We searched the French national transplant database to identify all patients with renal AA amyloidosis who underwent kidney transplantation between 2008 and 2018. Exposures: Age, cause of amyloidosis, use of biotherapies, and C-reactive protein levels. Outcomes: Outcomes were all-cause mortality and allograft loss. We also reported amyloidosis allograft recurrence, occurrence of acute rejection episodes, as well as infectious, cardiovascular, and neoplastic disease events. Analytical Approach: Kaplan-Meier estimator for mortality and cumulative incidence function method for allograft loss. Factors associated with patient and allograft survival were investigated using a Cox proportional hazards model and a cause-specific hazards model, respectively. Results: 86 patients who received kidney transplants for AA amyloidosis at 26 French centers were included. The median age was 49.4 years (IQR, 39.7-61.1). The main cause of amyloidosis was familial Mediterranean fever (37 cases; 43%). 16 (18.6%) patients received biotherapy after transplantation. Patient survival rates were 94.0% (95% CI, 89.1-9 9.2) at 1 year and 85.5% (77.8-9 4.0) at 5 years after transplantation. Cumulative incidences of allograft loss were 10.5% (4.0-17.0) at 1 year and 13.0% (5.8-20.1) at 5 years after transplantation. Histologically proven AA amyloidosis recurrence occurred in 5 transplants (5.8%). An infection requiring hospit alization developed in 55.8% of cases, and there was a 27.9% incidence of acute allograft rejection. Multivariable analysis showed that C-reactive protein concentration at the time of transplant ation was associated with patient survival (HR, 1.01; 95% CI, 1.00-1.02; P = 0.01) and allograft survival (HR, 1.68; 95% CI, 1.10-2.57; P = 0.02). Limitations: The study lacked a control group, and the effect of biotherapies on transplantation outcomes could not be explored. Conclusions: This relatively contemporary cohort of patients who received a kidney transplant for AA amyloidosis experienced favorable rates of survival and lower recurrence rates than previously reported. These data support the practice of treating these patients with kidney transplant ation for end -stage kidney disease.

Abstract Background and Aims Outcomes of kidney transplantation for patients with renal AA amyloidosis are uncertain, with reports of poor survival and high allograft recurrence. However, recent advances in biotherapies, especially anti-IL-1 treatments, may have improved patients’ outcome in the transplantation setting. Method We conducted a retrospective multicenter matched cohort study in 26 French centers reporting all patients with AA amyloidosis who received a kidney transplant between 2008 and 2018, and compared them to matched control patients (ratio 1:2 controls) who received a kidney transplant for other causes Results Eighty-six AA amyloidosis transplants and 157 control transplants were included. Median age was 49.4 years (interquartile range 39.7-61.1), and the main cause of amyloidosis was Familial Mediterranean Fever (37 cases, 43%). Sixteen (18.6%) patients received a biotherapy after transplantation. At 5 years, patient survival was 85.5% (95% confidence interval 77.8-94.0) and 86.2% (80.5-92.2) for cases and controls, respectively (p = 0.5). Death censored graft survival was 78.2% (78.2-93.5) and 91.7% (87.0-96.6), respectively (p = 0.05). Histologically proven AA amyloidosis recurrence was found in 5 patients (5.8%). 55.8% of amyloid patients had at least one infection requiring hospitalization and 27.9% an episode of acute graft rejection. In this group, multivariable analysis showed that CRP concentration at time of transplantation was associated with patient survival (HR 1.01, p = 0.01). Conclusion In this recent cohort, patient survival was comparable to controls and recurrence rates were lower than previously reported. Provided the underlying inflammatory disease is well controlled, patients with AA amyloidosis may be transplanted with similar patient and graft outcomes than that of matched controls.

Hyperparathyroidism (HPT) in patients with chronic kidney disease (CKD) includes secondary (sHPT) and tertiary hyperparathyroidism (tHPT). Considering that the role of preoperative imaging in the clinical setting is controversial, in the present study we have retrospectively compared pre-surgical diagnostic performances of 18F-Fluorocholine (18F-FCH) PET/CT, cervical ultrasonography (US), parathyroid scintigraphy, and 4D-CT in a group of 30 patients with CKD and HPT (18/12 sHPT/tHPT), 21 CKD G5 including 18 in dialysis, and 9 kidney transplant recipients. All patients underwent 18F-FCH, and 22 had cervical US, 12 had parathyroid scintigraphy, and 11 had 4D-CT. Histopathology was the gold standard. Seventy-four parathyroids were removed: 65 hyperplasia, 6 adenomas, and 3 normal glands. In the whole population, in a per gland analysis, 18F-FCH PET/CT was significantly more sensitive and accurate (72%, 71%) than neck US (25%, 43%), parathyroid scintigraphy (35%, 47%), and 4D-CT (40%, 47%). The specificity of 18F-FCH PET/CT (69%) was lower than that of neck US (95%) and parathyroid scintigraphy (90%), without, however, achieving significance. 18F-FCH PET/CT was more accurate than all other diagnostic techniques when sHPT and tHPT patients were considered separately. 18F-FCH PET/CT sensitivity was significantly higher in tHPT (88%) than in sHPT (66%). Three ectopic hyperfunctioning glands (in three different patients) were all detected by 18F-FCH PET/CT, two by parathyroid scintigraphy, and none by cervical US and 4D-CT. Our study confirms that 18F-FCH PET/CT is an effective preoperative imaging option in patients with CKD and HPT. These findings may be of greater importance in patients with tHPT (who could benefit from minimally invasive parathyroidectomy) than in patients with sHPT, who often undergo bilateral cervicotomy. In these cases, preoperative 18F-FCH PET/CT may be helpful in locating ectopic glands and may guide the surgical choice for gland preservation.

Introduction: Kidney transplant recipients (KTRs) are at an increased risk of fractures. Total urinary hydroxyproline excretion served as marker for bone resorption (BR) but was replaced by β‐CrossLaps (CTX), a C‐terminal collagen α‐1(I) chain (COL1A1) telopeptide. We investigated the low‐molecular‐weight urinary proteome for peptides associated with changes in bone metabolism after kidney transplantation. Methods: Clinical and laboratory data including serum levels of CTX in 96 KTR from two nephrology centers were correlated with signal intensities of urinary peptides identified by capillary electrophoresis mass spectrometry. Results: Eighty‐two urinary peptides were significantly correlated with serum CTX levels. COL1A1 was the predominant peptide source. Oral bisphosphonates were administered for decreased bone density in an independent group of 11 KTR and their effect was evaluated on the aforementioned peptides. Study of the peptides cleavage sites revealed a signature of Cathepsin K and MMP9. Seventeen of these peptides were significantly associated with bisphosphonate treatment, all showing a marked reduction in their excretion levels compared to baseline. Discussion: This study provides strong evidence for the presence of collagen peptides in the urine of KTR that are associated with BR and that are sensitive to bisphosphonate treatment. Their assessment might become a valuable tool to monitor bone status in KTR.

Kidney transplant recipients (KTR) are at increased risk of fractures. Total urinary hydroxyproline excretion used to be a marker for bone resorption (BR) but faded into the background when more specific markers like Beta-CrossLaps (CTX) became available. Proteomic studies identified numerous hydroxyproline-containing urinary collagen peptides but their origin remains unknown. We followed the hypothesis that some of the urinary collagen peptides are associated with BR and are markers for pathophysiological changes in bone metabolism of KTR. Clinical and laboratory data including serum levels of CTX in 96 KTR from two French centers (Strasbourg, n=38; Paris-Necker, n=58) were correlated with the signal intensity of urinary peptides identified by capillary electrophoresis (CE) coupled to mass spectrometry (MS) and tandem-MS. The effect of oral bisphosphonates on urinary peptides was studied in an independent group of 11 KTR. Eighty-two urinary peptides were identified to be significantly correlated with serum CTX levels in both cohorts. Statistical association with parameters other than BR markers were not significant. Collagen alpha-1(I) chain (COL1A1) was the most frequently identified peptide source. COL1A1 peptides associated with BR were significantly more hydroxylated than those showing no association (55.9% versus 45,2%, p<0.0003 by a chi2-test). From the 82 urinary peptides correlated to CTX, 17 were significantly associated with bisphosphonate treatment. All of these 17 peptides showed a marked reduction in their excretion levels after 410 +- 344 days of bisphosphonate treatment compared to baseline levels. We studied the cleavage sites of these COL1A1 peptides and observed a signature of Cathepsin K and Matrix Metallopeptidase 9. This study provides strong evidence for the occurrence of collagen peptides in the urine of KTR that are associated with BR and that are sensitive to bisphosphonate treatment. Their assessment might become a valuable tool to monitor bone status in KTR.

While loss-of-function variants in the WAS gene are associated with Wiskott-Aldrich syndrome and lead to microthrombocytopenia, gain-of-function variants of WAS are associated with X-linked neutropenia (XLN) and the absence of microthrombocytopenia. Only a few XLN families have been reported so far, and their platelet phenotype was not described in detail. To date, no renal involvement was described in XLN. In the present study, we report exome sequencing of individuals from 3 generations of a family with a dominant disease combining neutropenia, macrothrombocytopenia, and renal failure. We identified a heterozygous missense gain-of-function variant in the WAS gene (c.881T.C, p.I294T) that segregates with the disease and is already known to cause XLN. There was no pathogenic variant in MYH9, TUBB1, or ACTN1. This is the first report of a WAS gain-of-function variant associated with both the hematological phenotype of XLN (neutropenia, macrothrombocytopenia) and renal disease (proteinuria, renal failure) with glomerular tip lesion hyalinosis and actin condensations in effaced podocytes foot processes.

Cryptococcosis is the third most common cause of invasive fungal infection in solid organ transplant recipients and cryptococcal meningitis (CM) its main clinical presentation. CM outcomes, as well as its clinical features and radiological characteristics, have not yet been considered on a large scale in the context of kidney transplantation (KT). We performed a nationwide retrospective study of adult patients diagnosed with cryptococcosis after KT between 2002 and 2020 across 30 clinical centers in France. We sought to describe overall and graft survival based on whether KT patients with cryptococcosis developed CM or not. Clinical indicators of CNS involvement and brain radiological characteristics were assessed. Eighty-eight cases of cryptococcosis were diagnosed during the study period, with 61 (69.3%) cases of CM. Mortality was high (32.8%) at 12 months (M12) but not significantly different whether or not patients presented with CM. Baseline hyponatremia and at least one neurological symptom were independently associated with CM (p < 0.001). Positive serum cryptococcal antigen at diagnosis was also significantly associated with CM (p < 0.001). On magnetic resonance imaging (MRI), three patterns of brain injury were identified: parenchymal, meningeal, and vascular lesions. Although CM does not affect graft function directly, it entails a grim prognosis.

Background. Data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence in kidney transplant recipients (KTRs) remain rare. We sought to shed further light on this issue by conducting a single-center study in a kidney transplant center located in one of the France’s highest risk zone (Grand Est) for coronavirus disease 2019 (Covid-19) during the initial disease outbreak. Methods. To this aim, we used a survey approach coupled with systematic investigation of SARS-CoV-2 serology in a cohort of 1390 KTRs. Results. SARS-CoV-2 serologies were available for 780 survey respondents, among whom 48 had anti-SARS-CoV-2 antibodies (total seroprevalence: 6.2%). Thirty-five of the 48 seropositive KTRs had previously received a diagnosis of Covid-19, whereas the remaining 13 patients were not known to be infected (8 asymptomatic cases). Specifically, 18.7% of seropositive KTRs and 1.1% of the entire cohort were asymptomatic. Household exposure was found to markedly increase the risk of SARS-CoV-2 transmission. Conclusions. Our findings demonstrate that the overall SARS-CoV-2 seroprevalence in KTRs living in one of the France’s highest risk zone for Covid-19 during the first French lockdown was as low as 6.3%. Rapid and strict implementation of protective measures could have significantly mitigated virus spread even in an area of high virus circulation.

Background: Podocalyxin (PODXL) is a highly sialylated adhesion glycoprotein that plays an important role in podocyte's physiology. Recently, missense and nonsense dominant variants in the PODXL gene have been associated with focal segmental glomerulosclerosis (FSGS), a leading cause of nephrotic syndrome and kidney failure. Their histologic description, however, was superficial or absent. Methods: We performed exome sequencing on a three-generation family affected by an atypical glomerular nephropathy and characterized the disease by light and electron microscopy. Results: The disease was characterized by FSGS features and glomerular basement membrane duplication. Six family members displayed chronic proteinuria, ranging from mild manifestations without renal failure, to severe forms with end-stage renal disease. Exome sequencing of affected twin sisters, their affected mother, healthy father, and healthy maternal uncle revealed a new nonsense variant cosegregating with the disease (c.1453C>T, NM_001018111) in the PODXL gene, which is known to be expressed in the kidney and to cause nephropathy when mutated. The variant is predicted to lead to a premature stop codon (p.Q485*) that results in the loss of the intracytoplasmic tail of the protein. Conclusion: This is the first description of a peculiar association combining a PODXL stop-gain variant and both FSGS and membranoproliferative glomerulonephritis features, described by light and electron microscopy.

Abstract Background and Aims BK virus-associated nephropathy (BKvN) is an important complication occurring after kidney transplantation. Its treatment mainly relies on lowering immune suppression. BKvN’s histological aspect can mimic T cell-mediated rejection (TCMR) and other inflammatory conditions featuring tubulitis and interstitial infiltrate. At present, the screening strategy consists of measuring urinary and blood viral loads of BKv. Upon rising BK viremia, BKvN diagnosis is established by a graft biopsy. Biopsies are invasive and are not suitable for repeated screening. Therefore, the aim of this case-control study was to establish a urinary proteome-based test for BKvN diagnosis. Method Urine was obtained from 700 allograft recipients prior to either protocol or „for cause“ biopsies during the first year of post-transplantation surveillance. Aside from normal biopsy findings (N=294), the histological diagnoses included BKvN (N=50), IFTA II-III (N=145), glomerulonephritis (N=17) and T cell-mediated, antibody-mediated, mixed or borderline rejection episodes (N=194). From all patients, relevant clinical and demographic data including Banff classification scores, HLA mismatches and the presence of donor-specific antibodies was collected at the date of sample collection and in further clinical follow-up. BKvN cases were defined as having SV40-positive immunostaining on allograft biopsy. BKvN patients were considered as cases and all other recipients were considered as controls. Patient’s urinary peptide profiles were generated using capillary electrophoresis coupled to mass spectrometry consisting of 9430 different peptides in the mass range of 0.8 to 20 kDa. Results The CE-MS peptide profiles of randomly selected 30 BKvN cases and 307 kidney allograft controls (one sample per patient) were statistically analyzed to identify the most discriminative peptide markers for BKvN. In total, there were 117 peptides detected to have significantly different urinary excretion rates between both patient groups after false discovery rate adjustment for multiple testing. Thirty-two of these peptides were selected by cross-validated variable selection to establish a Support Vector Machine-based multi-marker model. Applying the 32-peptide marker model to an independent validation cohort consisting of 20 BKvN cases and 343 controls resulted in an area under the receiver operating characteristic curve of 0.86 and a 95% confidence interval from 0.82 to 0.89 with the p-value below 0.0001 and sensitivities and specificities for BKvN diagnosis of 85 and 76 %, respectively. Most notably, distribution of the classification values (figure 1) in the different patient groups of the validation set indicated specificities of the peptide marker model for TCMR/borderline of 85% (17 of 20 true negative classifications) and for viruria/viremia of 73% (8 of 11 true negative classifications) Conclusion In conclusion, the established urinary peptide marker model might serve as a non-invasive diagnostic test for BKvN and its differentiation from TCMR and states of isolated viruria or viremia.

The urinary chemokines CXCL9 and CXCL10 are promising noninvasive diagnostic markers of acute rejection (AR) in kidney recipients, but their levels might be confounded by urinary tract infection (UTI) and BK virus (BKV) reactivation. Multiparametric model development and validation addressed these confounding factors in a training set of 391 samples, optimizing the diagnostic performance of urinary chemokines. CXCL9/creatinine increased in UTI and BKV viremia with or without nephropathy (BKVN) (no UTI/leukocyturia/UTI: -0.10/1.61/2.09,P = .0001 and no BKV/viremia/BKVN: -0.10/1.90/2.29,P < .001) as well as CXCL10/creatinine (1.17/2.09/1.98,P < .0001 and 1.13/2.21/2.51,P < .001, respectively). An optimized 8-parameter model (recipient age, sex, estimated glomerular filtration rate, donor specific antibodies, UTI, BKV blood viral load, CXCL9, and CXCL10) diagnosed AR with high accuracy (area under the curve [AUC]: 0.85, 95% confidence interval [CI]: 0.80-0.89) and remained highly accurate at the time of screening (AUC: 0.81, 95% CI: 0.48-1) or indication biopsies (AUC: 0.85, 95% CI: 0.81-0.90) and within the first year (AUC: 0.86, 95% CI: 0.80-0.91) or later (AUC: 0.90, 95% CI: 0.84-0.96), achieving AR diagnosis with an AUC of 0.85 and 0.92 (P < .0001) in 2 external validation cohorts. Decision curve analyses demonstrated the clinical utility of the model. Considering confounding factors rather than excluding them, we optimized a noninvasive multiparametric diagnostic model for AR of kidney allografts with unprecedented accuracy.

Background. Data on coronavirus disease 2019 (COVID-19) in immunocompromised kidney transplant recipients (KTR) remain scanty. Although markers of inflammation, cardiac injury, and coagulopathy have been previously associated with mortality in the general population of patients with COVID-19, their prognostic impact amongst KTR with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has not been specifically investigated. Methods. We conducted a cohort study of 49 KTR who presented with COVID-19. Clinical and laboratory risk factors for severe disease and mortality were prospectively collected and analyzed with respect to outcomes. The study participants were divided into 3 groups: (1) mild disease manageable in an outpatient setting (n = 8), (2) nonsevere disease requiring hospitalization (n = 21), and (3) severe disease (n = 20). Results. Gastrointestinal manifestations were common at diagnosis. The 30-day mortality rate in hospitalized patients was 19.5%. Early elevations of C-reactive protein (>100 mg/L) and interleukin-6 (>65 ng/L) followed by increases in high-sensitivity troponin I (>30 ng/L) and D-dimer (>960 ng/mL) were significantly associated with severe disease and mortality. Viral load did not have prognostic significance in our sample, suggesting that outcomes were chiefly driven by a cytokine release syndrome (CRS). Conclusions. Regular monitoring of CRS biomarkers in KTR with COVID-19 is paramount to improve clinical outcomes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread widely, causing coronavirus disease 2019 (COVID-19) and significant mortality. However, data on viral loads and antibody kinetics in immunocompromised populations are lacking. We aimed to determine nasopharyngeal and plasma viral loads via reverse transcription-polymerase chain reaction and SARS-CoV-2 serology via enzyme-linked immunosorbent assay and study their association with severe forms of COVID-19 and death in kidney transplant recipients. In this study, we examined hospitalized kidney transplant recipients with nonsevere (n = 21) and severe (n = 19) COVID-19. SARS-CoV-2 nasopharyngeal and plasma viral load and serological response were evaluated based on outcomes and disease severity. Ten recipients (25%) displayed persistent viral shedding 30 days after symptom onset. The SARS-CoV-2 viral load of the upper respiratory tract was not associated with severe COVID-19, whereas the plasma viral load was associated with COVID-19 severity (P = .010) and mortality (P = .010). All patients harbored antibodies during the second week after symptom onset that persisted for 2 months. We conclude that plasma viral load is associated with COVID-19 morbidity and mortality, whereas nasopharyngeal viral load is not. SARS-CoV-2 shedding is prolonged in kidney transplant recipients and the humoral response to SARS-CoV-2 does not show significant impairment in this series of transplant recipients.

BK virus (BKV) replication occurs frequently in kidney transplant recipients (KTR), potentially leading to BKV-associated nephropathy (BKVAN) and graft loss. Patients with high titers of BKV-neutralizing antibodies (NAbs) are protected against BKV replication, and intravenous immunoglobulin (IVIg) infusion can increase NAb titers. We investigated whether early IVIg administration prevents BKV replication in patients with low NAb titers (<4 log10 against the BKV-specific genotype). Based on NAb titers on the day of transplantation, KTR followed in the Strasbourg University Hospital (n = 174) were retrospectively divided into the following 3 risk categories for BKV replication: (1) patients with low NAb titers ("high-risk") who received IVIg for the first 3 posttransplant months (n = 44), (2) patients with low NAb titers ("high-risk") who did not undergo IVIg treatment (n = 41), and (3) patients with high NAb titers ("low-risk") who did not receive IVIg (n = 89). At 12 posttransplant months, the incidence of BKV viremia in the high-risk group treated with IVIg (6.8%) was similar to that observed in the low-risk group (10.1%) and markedly lower than that of the untreated high-risk group (36.6%; P < .001). Similar results were observed with regard to BKVAN. We conclude that IVIg may be a valuable strategy for preventing BKV replication.

To the Editor: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing public health emergency of international concern. Acute respiratory distress syndrome (ARDS) develops in 3%-30% of patients with COVID-19,1Guan W, Ni Z, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. [published online ahead of print March 11, 2020] N Engl J Med. https://doi.org/10.1056/NEJMoa2002032.Google Scholar,2Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. [published online ahead of print March 11, 2020] Lancet. https://linkinghub.elsevier.com/retrieve/pii/S0140673620305663.Google Scholar because of direct virus-induced cytopathic effects in the respiratory tract or cytokine storms triggered by the host's immune response. Comorbidities are known to increase the risk of ARDS in SARS-CoV-2-infected patients.1Guan W, Ni Z, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. [published online ahead of print March 11, 2020] N Engl J Med. https://doi.org/10.1056/NEJMoa2002032.Google Scholar Belatacept—a CTLA4-Ig molecule designed to block the costimulatory B7-CD28 signal needed for activation of effector T cells—is used in kidney transplant recipients (KTRs) to maintain effective long-term immunosuppression while minimizing calcineurin inhibitors (CNIs)-induced nephrotoxicity. However, a recent report has shown that the use of this drug may be associated with severe opportunistic infections.3Bertrand D Chavarot N Gatault P et al.Opportunistic infections after conversion to belatacept in kidney transplantation.Nephrol Dial Transplant. 2020; 35: 336-345Crossref PubMed Scopus (38) Google Scholar Here, we describe the first case of COVID-19 in a KTR treated with belatacept. The 58-year-old male patient—with a history of cured testicular cancer followed by renal vein thrombosis and coronary artery disease—had undergone kidney transplantation in January 2017. Because of nephrotoxicity, he was switched from a cyclosporine (CNI) to belatacept in June 2017. His maintenance immunosuppression consisted of belatacept (345 mg every 28 days), mycophenolate mofetil (MMF, 750 mg twice daily), and prednisone (5 mg/d). The last dose of belatacept was administered on February 18, 2020. The patient was referred to our center 3 weeks later (March 7, 2020) with fever (38°C), mild dyspnea, and cough 1 week after being in contact with a carrier of SARS-CoV-2 in Alsace, France. Figure 1 shows a timeline of immunosuppression management as well as the patient's clinical course and laboratory data. Belatacept and MMF were discontinued on the day of admission. SARS-CoV-2 infection was diagnosed by RT-PCR amplification of the RdRp viral gene from a nasopharyngeal swab specimen. On admission, blood oxygen saturation on room air was 96% and remained stable during the hospitalization period. Limited peripheral pulmonary ground-glass opacities were identified on chest CT (Figure 2). Serum IL-6 levels measured with a chemiluminescent enzyme assay were 29 ng/L, that is, markedly lower than those observed in COVID-19 patients requiring mechanical ventilation (consistently >100 ng/L; unpublished data, Dr Thomas Lavaux). The patient had a mild clinical course according to the World Health Organization interim guidance for COVID-194World Health Organization. Clinical management of severe acute respiratory infection (SARI) when Covid-19 disease is suspected. Interim guidance, 13 March 2020. https://www.who.int/publications-detail/clinical-management-of-severe-acute-respiratory-infection-when-novel-coronavirus-(ncov)-infection-is-suspected. Accessed April 20, 2020.Google Scholar with rapid recovery of respiratory symptoms after treatment of a possible bacterial superinfection. Low-dose cyclosporine (50 mg twice daily) was started on March 25. Five days after discharge, fever, cough, or breathing difficulties were absent. The results of laboratory tests were in line with those observed before SARS-CoV-2 infection (Figure 1). We are planning to withdraw cyclosporine and restart both belatacept and MMF on April 14, that is, on the date of the next scheduled belatacept infusion.FIGURE 2Lung CT scan performed 7 d after symptom onset. Evidence of minor, localized ground-glass opacitiesView Large Image Figure ViewerDownload Hi-res image Download (PPT) Altogether, severe manifestations of COVID-19 due to lymphopenia-associated immunosuppression could have been feared but did not occur in this patient. ARDS caused by coronaviruses (SARS-CoV, MERS-CoV, SARS-CoV-2) is characterized by a cytokine storm, with secretion of numerous proinflammatory cytokines.5Lau SKP Lau CCY Chan K-H et al.Delayed induction of proinflammatory cytokines and suppression of innate antiviral response by the novel Middle East respiratory syndrome coronavirus: implications for pathogenesis and treatment.J Gen Virol. 2013; 94: 2679-2690Crossref PubMed Scopus (290) Google Scholar,6Huang C Wang Y Li X et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan.China. Lancet. 2020; 395: 497-506Abstract Full Text Full Text PDF PubMed Scopus (28192) Google Scholar We hypothesize that the mild clinical course of COVID-19 observed in our immunocompromised patient may have been, at least in part, related to belatacept-related blockade of massive cytokines/chemokines production. Additional clinical investigation in larger sample sizes and longer follow-up periods are required to corroborate this possibility. The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation. The data that support the findings of this study are available from the corresponding author upon reasonable request.

There is a need for accurate, robust, non-invasive methods to provide early diagnosis of graft lesions after kidney transplantation. A multitude of proteomic biomarkers for the major kidney allograft disease phenotypes defined by the BANFF classification criteria have been described in literature. None of these biomarkers have been established in the clinic. A key reason for this is the lack of clinical validation which is difficult, as even the gold standard of diagnosis, kidney biopsy, is often ambiguous. The semantic clustering by ReviGO on top of transcriptomic pathway analysis is evaluated to connect histological and transcriptomic kidney allograft disease characteristics with proteomic biomarker qualification. By using public data generated in microarray studies of kidney allograft tissue, biological processes and key molecules specifically associated with the different kidney allograft disease phenotypes are identified. Semantic clustering holds the promise to guide adaptation of proteomic marker panels to molecular pathology. This can support the development of noninvasive tests (e.g. in urine, by capillary electrophoresis mass spectrometry) that simultaneously detect diverse kidney allograft phenotypes with high accuracy and sensitivity.

Cancer is a heterogeneous multifactorial disease, which continues to be one of the main causes of death worldwide. Despite the extensive efforts for establishing accurate diagnostic assays and efficient therapeutic schemes, disease prevalence is on the rise, in part, however, also due to improved early detection. For years, studies were focused on genomics and transcriptomics, aiming at the discovery of new tests with diagnostic or prognostic potential. However, cancer phenotypic characteristics seem most likely to be a direct reflection of changes in protein metabolism and function, which are also the targets of most drugs. Investigations at the protein level are therefore advantageous particularly in the case of in-depth characterization of tumor progression and invasiveness. Innovative high-throughput proteomic technologies are available to accurately evaluate cancer formation and progression and to investigate the functional role of key proteins in cancer. Employing these new highly sensitive proteomic technologies, cancer biomarkers may be detectable that contribute to diagnosis and guide curative treatment when still possible. In this review, the recent advances in proteomic biomarker research in cancer are outlined, with special emphasis placed on the identification of diagnostic and prognostic biomarkers for solid tumors. In view of the increasing number of screening programs and clinical trials investigating new treatment options, we discuss the molecular connections of the biomarkers as well as their potential as clinically useful tools for diagnosis, risk stratification and therapy monitoring of solid tumors.

Acute kidney injury (AKI) is a severe and frequent condition in hospitalized patients. Currently, no efficient therapy of AKI is available. Therefore, efforts focus on early prevention and potentially early initiation of renal replacement therapy to improve the outcome in AKI. The detection of AKI in hospitalized patients implies the need for early, accurate, robust, and easily accessible biomarkers of AKI evolution and outcome prediction because only a narrow window exists to implement the earlier-described measures. Even more challenging is the multifactorial origin of AKI and the fact that the changes of molecular expression induced by AKI are difficult to distinguish from those of the diseases associated or causing AKI as shock or sepsis. During the past decade, a considerable number of protein biomarkers for AKI have been described and we expect from recent advances in the field of omics technologies that this number will increase further in the future and be extended to other sorts of biomolecules, such as RNAs, lipids, and metabolites. However, most of these biomarkers are poorly defined by their AKI-associated molecular context. In this review, we describe the state-of-the-art tissue and biofluid proteomic and metabolomic technologies and new bioinformatics approaches for proteomic and metabolomic pathway and molecular interaction analysis. In the second part of the review, we focus on AKI-associated proteomic and metabolomic biomarkers and briefly outline their pathophysiological context in AKI.

Rejection is one of the key factors that determine the long-term allograft function and survival in renal transplant patients. Reliable and timely diagnosis is important to treat rejection as early as possible. Allograft biopsies are not suitable for continuous monitoring of rejection. Thus, there is an unmet need for non-invasive methods to diagnose acute and chronic rejection. Proteomics in urine and blood samples has been explored for this purpose in 29 studies conducted since 2003. This review describes the different proteomic approaches and summarizes the results from the studies that examined proteomics for the rejection diagnoses. The potential limitations and open questions in establishing proteomic markers for rejection are discussed, including ongoing trials and future challenges to this topic.