Use of a Belatacept-based Immunosuppression for Kidney Transplantation From Donors After Circulatory Death: A Paired Kidney Analysis.

Background: Efficacy and safety of belatacept have not been specifically reported for kidney transplantations from donors after circulatory death. Methods: In this retrospective multicenter paired kidney study, we compared the outcome of kidney transplantations with a belatacept-based to a calcineurin inhibitor (CNI)-based immunosuppression. We included all kidney transplant recipients from donors after uncontrolled or controlled circulatory death performed in our center between February 2015 and October 2020 and treated with belatacept (n = 31). The control group included the recipients of the contralateral kidney that were treated with CNI in 8 other centers (tacrolimus n = 29, cyclosporine n = 2). Results: There was no difference in the rate of delayed graft function. A higher incidence of biopsy-proven rejections was noted in the belatacept group (24 versus 6 episodes). Estimated glomerular filtration rate (eGFR) was significantly higher in the belatacept group at 3-, 12-, and 36-mo posttransplant, but the slope of eGFR was similar in the 2 groups. During a mean follow-up of 4.1 y, 12 patients discontinued belatacept and 2 patients were switched from CNI to belatacept. For patients who remained on belatacept, eGFR mean value and slope were significantly higher during the whole follow-up. At 5 y, eGFR was 80.7 ± 18.5 with belatacept versus 56.3 ± 22.0 mL/min/1.73 m2 with CNI (P = 0.003). No significant difference in graft and patient survival was observed. Conclusions: The use of belatacept for kidney transplants from either uncontrolled or controlled donors after circulatory death resulted in a better medium-term renal function for patients remaining on belatacept despite similar rates of delayed graft function and higher rates of cellular rejection.

Clinical and Prognostic Factors in Patients with IgG4-Related Kidney Disease.

BACKGROUND: IgG4-related kidney disease is a major manifestation of IgG4-related disease, a systemic fibroinflammatory disorder. However, the clinical and prognostic kidney-related factors in patients with IgG4-related kidney disease are insufficiently defined. METHODS: We conducted an observational cohort study using data from 35 sites in two European countries. Clinical, biologic, imaging, and histopathologic data; treatment modalities; and outcomes were collected from medical records. Logistic regression was performed to identify the possible factors related to an eGFR ≤30 ml/min per 1.73 m 2 at the last follow-up. Cox proportional hazards model was performed to assess the factors associated with the risk of relapse. RESULTS: We studied 101 adult patients with IgG4-related disease with a median follow-up of 24 (11-58) months. Of these, 87 (86%) patients were male, and the median age was 68 (57-76) years. Eighty-three (82%) patients had IgG4-related kidney disease confirmed by kidney biopsy, with all biopsies showing tubulointerstitial involvement and 16 showing glomerular lesions. Ninety (89%) patients were treated with corticosteroids, and 18 (18%) patients received rituximab as first-line therapy. At the last follow-up, the eGFR was below 30 ml/min per 1.73 m 2 in 32% of patients; 34 (34%) patients experienced a relapse, while 12 (13%) patients had died. By Cox survival analysis, the number of organs involved (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.01 to 1.55) and low C3 and C4 concentrations (HR, 2.31; 95% CI, 1.10 to 4.85) were independently associated with a higher risk of relapse, whereas first-line therapy with rituximab was protective (HR, 0.22; 95% CI, 0.06 to 0.78). At their last follow-up, 19 (19%) patients had an eGFR ≤30 ml/min per 1.73 m 2 . Age (odd ratio [OR], 1.11; 95% CI, 1.03 to 1.20), peak serum creatinine (OR, 2.74; 95% CI, 1.71 to 5.47), and serum IgG4 level ≥5 g/L (OR, 4.46; 95% CI, 1.23 to 19.40) were independently predictive for severe CKD. CONCLUSIONS: IgG4-related kidney disease predominantly affected middle-aged men and manifested as tubulointerstitial nephritis with potential glomerular involvement. Complement consumption and the number of organs involved were associated with a higher relapse rate, whereas first-line therapy with rituximab was associated with lower relapse rate. Patients with high serum IgG4 concentrations (≥5 g/L) had more severe kidney disease.

Invasive bacillary angiomatosis in a kidney transplant recipient: A challenging case on belatacept immunosuppression.

Bacillary angiomatosis is a disseminated vascular proliferative disease caused by aerobic gram-negative bacilli Bartonella henselae or Bartonella quintana. Bacillary angiomatosis is mostly described in immunosuppressed patients with HIV infection and organ transplant recipients. We describe the case of a female aged 75 years who is a kidney transplant recipient who was admitted for a 3-month history of intermittent fever, chills, vomiting, and a 12-kg weight loss. The maintenance immunosuppression was based on prednisone, mycophenolate, and monthly infusions of belatacept. Physical examination was unremarkable. Laboratory investigations revealed elevated blood acute phase proteins but all blood cultures were negative. Serological tests for Bartonella were negative. Thoracoabdominal computed tomography scan and transesophageal echocardiography were normal. A Positron Emission Tomography scan showed a hypermetabolic mass in the duodenopancreatic region, with multiple hepatic and splenic lesions. Histological findings of spleen and pancreatic biopsies were not conclusive. The histopathological examination of a celiac lymph node biopsy finally demonstrated bacillary angiomatosis. The diagnosis of bacillary angiomatosis in immunocompromised patients is most often delayed in the absence of skin involvement. A high index of clinical suspicion is needed when interpreting negative results.

Natural Antibodies Are Associated With Rejection and Long-term Renal Allograft Loss in a Multicenter International Cohort.

BACKGROUND: Potentially harmful nonhuman leukocyte antigen antibodies have been identified in renal transplantation, including natural immunoglobulin G antibodies (Nabs) reactive to varied antigenic structures, including apoptotic cells. METHODS: In this retrospective, multicenter study, we assessed Nabs by reactivity to apoptotic cells in sera collected from 980 kidney transplant recipients across 4 centers to determine their association with graft outcomes. RESULTS: Elevated pretransplant Nabs were associated with graft loss (hazard ratio [HR] 2.71; 95% confidence interval [CI], 1.15-6.39; P = 0.0232), the composite endpoint of graft loss or severe graft dysfunction (HR 2.40; 95% CI, 1.13-5.10; P = 0.0232), and T cell-mediated rejection (odds ratio [OR] 1.77; 95% CI, 1.07-3.02; P = 0.0310). High pretransplant Nabs together with donor-specific antibodies (DSAs) were associated with increased risk of composite outcomes (HR 6.31; 95% CI, 1.81-22.0; P = 0.0039). In patients with high pretransplant Nabs, the subsequent development of posttransplant Nabs was associated with both T cell-mediated rejection (OR 3.64; 95% CI, 1.61-8.36; P = 0.0021) and mixed rejection (OR 3.10; 95% CI, 1.02-9.75; P = 0.0473). Finally, elevated pre- and posttransplant Nabs combined with DSAs were associated with increased risk of composite outcomes (HR 3.97; 95% CI, 1.51-10.43; P = 0.0052) and T cell-mediated rejection (OR 7.28; 95% CI, 2.16-25.96; P = 0.0016). CONCLUSIONS: The presence of pre- and posttransplant Nabs, together with DSAs, was associated with increased risk of poor graft outcomes and rejection after renal transplantation.

Pathological spectrum of hereditary transthyretin renal amyloidosis and clinicopathologic correlation: a French observational study.

BACKGROUND: Cardiac and neurological involvements are the main clinical features of hereditary transthyretin (ATTRv) amyloidosis. Few data are available about ATTRv amyloid nephropathy (ATTRvN). METHODS: We retrospectively included 30 patients with biopsy-proven ATTRvN [V30M (26/30) including two domino liver recipients, S77Y (2/30), V122I (1/30) and S50R (1/30) variants] from two French reference centers. We described the pathological features by comparing amyloid deposits distribution to patients with AL or AA amyloidosis, and sought to determine clinicopathological correlation with known disease-modifying factors such as TTR variant, gender and age at diagnosis. RESULTS: In comparison with AL and AA amyloidosis, ATTRv patients had similar glomerular, arteriolar and arterial amyloid deposits, but more cortical and medullary tubulointerstitial (33%, 44%, 77%, P = .03) involvement. While the presence of glomerular deposits is associated with the range of proteinuria, some patients with abundant glomerular ATTRv amyloidosis had no significant proteinuria. V30M patients had more glomerular (100% and 25%, odds ratio = 114, 95% confidence interval 3.85-3395.00, P = .001) deposits, and higher estimated glomerular filtration rate [50 (interquartile range 44-82) and 27 (interquartile range 6-31) mL/min/1.73 m², P = .004] than non-V30M patients. We did not find difference in amyloid deposition according to gender or age at diagnosis. CONCLUSION: ATTRvN affects all kidney compartments, but compared with AL/AA amyloidosis, ATTRvN seems to involve more frequently tubulointerstitial areas. V30M patients represents the dominant face of the disease with a higher risk of glomerular/arteriolar involvement. ATTRvN should thus be considered in patients, and potential relatives, with ATTRv amyloidosis and kidney dysfunction, regardless of proteinuria level.

Microbiology and outcomes of polymicrobial peritonitis associated with peritoneal dialysis: a register-based cohort study from the French Language Peritoneal Dialysis Registry.

BACKGROUND: Previous studies have reported that polymicrobial peritonitis in peritoneal dialysis (PD) is associated with poor outcomes, but recent data from European cohorts are scarce. METHODS: We included from the French Language Peritoneal Dialysis Registry all patients ≥18 years of age who started PD between January 2014 and November 2020. We compared microbiology and patient characteristics associated with mono- and polymicrobial peritonitis. We assessed patient outcomes after a first polymicrobial peritonitis using survival analysis with competing events. We differentiated microorganisms isolated from dialysis effluent as enteric or non-enteric pathogens. RESULTS: A total of 8848 patients contributed 13 023 patient-years of follow-up and 3348 culture-positive peritonitis episodes, including 251 polymicrobial ones. This corresponded to rates of 0.32 and 0.02 episodes/patient-year, respectively. For most patients (72%) who experienced polymicrobial peritonitis, this was their first peritonitis episode. Enteric pathogens were more frequently isolated in polymicrobial than in monomicrobial peritonitis (57 versus 44%; P < .001). In both cases of peritonitis with and without enteric pathogens, the polymicrobial versus monomicrobial character of the peritonitis was not associated with mortality in patients who did not switch to haemodialysis {adjusted cause-specific hazard ratio [acsHR] 1.2 [95% confidence interval (CI) 0.3-5.0], P = .78 and 1.1 [95% CI 0.7-1.8], P = .73, respectively}. However, the risks of death and switch to haemodialysis were higher for monomicrobial peritonitis with enteric pathogens compared with those without [acsHR 1.3 (95% CI 1.1-1.7), P = .02 and 1.9 (95% CI 1.5-2.4), P < .0001, respectively]. CONCLUSION: Isolation of enteric pathogens, rather than the polymicrobial character of the peritonitis, is associated with poorer outcomes.

Absence of Mortality Differences Between the First and Second COVID-19 Waves in Kidney Transplant Recipients.

Introduction: SARS-CoV-2 pandemic evolved in 2 consecutive waves during 2020. Improvements in the management of COVID-19 led to a reduction in mortality rates among hospitalized patients during the second wave. Whether this progress benefited kidney transplant recipients (KTRs), a population particularly vulnerable to severe COVID-19, remained unclear. Methods: In France, 957 KTRs were hospitalized for COVID-19 in 2020 and their data were prospectively collected into the French Solid Organ Transplant (SOT) COVID registry. The presentation, management, and outcomes of the 359 KTRs diagnosed during the first wave were compared to those of the 598 of the second wave. Results: Baseline comorbidities were similar between KTRs of the 2 waves. Maintenance immunosuppression was reduced in most patients but withdrawal of antimetabolite (73.7% vs. 58.4%, P < 0.001) or calcineurin inhibitor (32.1% vs. 16.6%, P < 0.001) was less frequent during the second wave. Hydroxychloroquine and azithromycin that were commonly used during the first wave (21.7% and 30.9%, respectively) but were almost abandoned during the second wave. In contrast, the use of high dose corticosteroids doubled (19.5% vs. 41.6%, P < 0.001). Despite these changing trends in COVID-19 management, 60-day mortality was not statistically different between the 2 waves (25.3% vs. 23.9%; Log Rank, P = 0.48) and COVID-19 hospitalization period was not associated with death due to COVID-19 in multivariate analysis (Hazard ratio 0.89, 95% confidence interval 0.67-1.17, P = 0.4). Conclusion: We conclude that changing of therapeutic trends during 2020 did not reduce COVID-19 related mortality among KTRs. Our data indirectly support the importance of vaccination and neutralizing monoclonal anti-SARS-CoV-2 antibodies to protect KTRS from severe COVID-19.

Pregnancies and Gynecological Follow-Up after Solid Organ Transplantation: Experience of a Decade.

In recent years, solid organ transplantations, such as kidney or lung grafts, have been performed worldwide with an improvement of quality of life under immunosuppressive therapy and an increase in life expectancy, allowing young women to consider childbearing. In the current study, we conduct a retrospective study in two French centers for kidney and lung transplantations to evaluate the rate and outcomes of pregnancies, contraception and gynecological monitoring for women under 40 years old who underwent solid organ transplantation. Among 210 women, progestin was the most widely used contraceptive method. Of the 210 women, 24 (11.4%) conceived 33 pregnancies of which 25 (75.8%) were planned with an immunosuppressant therapy switch. Of the 33 pregnancies, 7 miscarried (21.2%) and 21 (63.7%) resulted in a live birth with a high rate of pre-eclampsia (50%). No graft rejections were observed during pregnancies. Among the deliveries, 19 were premature (90.5%, mostly due to induced delivery) and the C-section rate was high (52.4%). No particular pathology was identified among newborns. We conclude that pregnancies following solid organ transplantation are feasible, and while they are at an increased risk of pre-eclampsia and prematurity, they should still be permitted with close surveillance by a multidisciplinary care team.

Case Report: Post-Partum SARS-CoV-2 Infection After the First French Uterus Transplantation.

Absolute uterus factor infertility, whether congenital or acquired, renders the woman unable to carry a child. Although uterus transplantation (UTx) is being increasingly performed as a non-vital procedure to address this unfortunate condition, the immunosuppression required presents risks that are further compounded by pregnancy and during the puerperium period. These vulnerabilities require avoidance of SARS-CoV-2 infection in pregnant UTx recipients especially during the third trimester, as accumulating evidence reveals increased risks of morbidity and mortality. Here we describe a successful UTx case with delivery of a healthy child, but in which both mother and neonate developed asymptomatic SARS-CoV-2 infection seven days after RNA vaccination, on day 35 post-partum. Although the patient was successfully treated with a combination therapy comprised of two monoclonal antibodies, this case highlights the challenges associated with performing UTx in the era of Covid-19. More broadly, the risks of performing non-vital organ transplantation during a pandemic should be discussed among team members and prospective patients, weighing the risks against the benefits in improving the quality of life, which were considerable for our patient who achieved motherhood with the birth of a healthy child.

Long-term survival benefit from dual kidney transplantation using kidneys from donors with very extended criteria-a French cohort between 2002 and 2014.

BACKGROUND: This national multicentre retrospective cohort study aimed to assess the long-term outcomes of dual kidney transplantation (DKT) and compare them with those obtained from single kidney transplantation (SKT). METHODS: Our first analysis concerned all first transplants performed between May 2002 and December 2014, from marginal donors, defined as brain death donors older than 65 years, with an estimated glomerular filtration rate (eGFR) lower than 90 mL/min/1.73 m2. The second analysis was restricted to transplants adequately allocated according to the French DKT program based on donor eGFR: DKT for eGFR between 30 and 60, SKT for eGFR between 60 and 90 mL/min/1.73 m2. Recipients younger than 65 years or with a panel-reactive antibody percentage ≥25% were excluded. RESULTS: The first analysis included 461 DKT and 1131 SKT. DKT donors were significantly older (77.6 versus 74 years), had a more frequent history of hypertension and a lower eGFR (55.1 versus 63.6 mL/min/1.73 m2). While primary nonfunction and delayed graft function did not differ between SKT and DKT, 1-year eGFR was lower in SKT recipients (39 versus 49 mL/min/1.73 m2, P < 0.001). Graft survival was significantly better in DKT, even after adjustment for recipient and donor risk factors. Nevertheless, patient survival did not differ between these groups. The second analysis included 293 DKT and 687 SKT adequately allocated with donor eGFR and displayed similar results but with a smaller benefit in terms of graft survival. CONCLUSIONS: In a context of organ shortage, DKT is a good option for optimizing the use of kidneys from very expanded criteria donors.

[Kidney transplantation in the elderly: A benefit for all patients?] / Transplantation rénale du sujet âgé : un bénéfice pour tous ?

Age per se should not be a contraindication to kidney transplantation. The first studies have shown a benefit for the survival of elderly eligible patients getting a kidney transplant compared to be maintained on the waiting list. However, more recent data suggest that this benefit is not as constant, notably with a significant early mortality period. The eligibility of elderly patients for transplantation must be based on the usual consideration of co-morbidities, but should also include, for some patients, a geriatric evaluation to detect clinical symptoms of frailty. The decision to transplant an elderly recipient must also integrate the characteristics of the donors, since the use of donors with increasingly expanding criteria can have a negative impact on the survival of these patients.

The spectrum of kidney biopsies in hospitalized patients with COVID-19, acute kidney injury, and/or proteinuria.

We report a multicentric retrospective case series of patients with COVID-19 who developed acute kidney injury and/or proteinuria and underwent a kidney biopsy in the Paris and its metropolitan area. Forty-seven patients (80.9% men) with COVID-19 who underwent a kidney biopsy between March 08 and May 19, 2020 were included. Median age was 63 years IQR [52-69]. Comorbidities included hypertension (66.0%), diabetes mellitus (27.7%), obesity (27.7%), history of chronic kidney (25.5%), cardiac (38.6%) and respiratory (27.3%) diseases. Initial symptoms were fever (85.1%), cough (63.8%), shortness of breath (55.3%), and diarrhea (23.4%). Almost all patients developed acute kidney injury (97.9%) and 63.8% required renal replacement therapy. Kidney biopsy showed two main histopathological patterns, including acute tubular injury in 20 (42.6%) patients, and glomerular injury consisting of collapsing glomerulopathy and focal segmental glomerulosclerosis in 17 (36.2%) patients. Two (4.3%) patients had acute vascular nephropathy, while eight (17%) had alternative diagnosis most likely unrelated to COVID-19. Acute tubular injury occurred almost invariably in the setting of severe forms of COVID-19, whereas patients with glomerular injury had various profiles of COVID-19 severity and collapsing glomerulopathy was only observed in patients harboring a combination of APOL1 risk variants. At last follow-up, 16 of the 30 patients who initially required dialysis were still on dialysis, and 9 died. The present study describes the spectrum of kidney lesions in patients with COVID-19. While acute tubular injury is correlated with COVID-19 severity, the pattern of glomerular injury is intimately associated with the expression of APOL1 risk variants.

Higher mortality risk among kidney transplant recipients than among estimated glomerular filtration rate-matched patients with CKD-preliminary results.

BACKGROUND: Although kidney transplantation prolongs survival relative to dialysis, it is associated with a higher death rate than in the general population. The objective of the present study was to assess and compare the risk of mortality and frequency of non-lethal cardiovascular (CV) events in kidney transplant recipients (KTRs) beyond 1 year after successful transplantation versus patients with chronic kidney disease (CKD) using propensity score-matched analysis of estimated glomerular filtration rate (eGFR) and other parameters. METHODS: After propensity score matching, we studied 340 KTRs from the French Données Informatisées et Validées en Transplantation cohort and 605 non-transplant patients with CKD (CKDps) from the French Chronic Kidney Disease-Renal Epidemiology and Information Network cohort. The mean ± standard deviation eGFR was 42 ± 13 and 41 ± 12 mL/min/ 1.73 m2, respectively (P = 0.649). Descriptive data were completed by a survival analysis with Cox regression models. RESULTS: After a median follow-up period of 2.8 years (KTRs 2.0 years, CKDp 2.9 years), 71 deaths were recorded (31 and 40 in the KTR and CKD groups, respectively). Univariate analysis showed that KTRs had a significantly greater risk of mortality than CKDps. In multivariable analysis, KTRs were found to have a 2.7-fold greater risk of mortality [hazard ratio 2.7 (95% confidence interval 1.6-4.7); P = 0.005]. There was no between-group difference concerning the risk of CV events (P = 0.448). CV death rates in KTRs (29.0%) approximated those of CKDps (22.5%), whereas death rates due to infections were higher in KTRs (19.4% versus 10.0%). CONCLUSION: Beyond 1 year after transplantation, KTRs, who possibly had a longer CKD history, had a significantly greater mortality risk than eGFR-matched CKDps. The excess risk was not associated with CV events.

CRISPR/Cas9-Engineered HLA-Deleted Glomerular Endothelial Cells as a Tool to Predict Pathogenic Non-HLA Antibodies in Kidney Transplant Recipients.

BACKGROUND: After kidney transplantation, donor-specific antibodies against human leukocyte antigen donor-specific antibodies (HLA-DSAs) drive antibody-mediated rejection (ABMR) and are associated with poor transplant outcomes. However, ABMR histology (ABMRh) is increasingly reported in kidney transplant recipients (KTRs) without HLA-DSAs, highlighting the emerging role of non-HLA antibodies (Abs). METHODS: W e designed a non-HLA Ab detection immunoassay (NHADIA) using HLA class I and II-deficient glomerular endothelial cells (CiGEnCΔHLA) that had been previously generated through CRISPR/Cas9-induced B2M and CIITA gene disruption. Flow cytometry assessed the reactivity to non-HLA antigens of pretransplantation serum samples from 389 consecutive KTRs. The intensity of the signal observed with the NHADIA was associated with post-transplant graft histology assessed in 951 adequate biopsy specimens. RESULTS: W e sequentially applied CRISPR/Cas9 to delete the B2M and CIITA genes to obtain a CiGEnCΔHLA clone. CiGEnCΔHLA cells remained indistinguishable from the parental cell line, CiGEnC, in terms of morphology and phenotype. Previous transplantation was the main determinant of the pretransplantation NHADIA result (P<0.001). Stratification of 3-month allograft biopsy specimens (n=298) according to pretransplantation NHADIA tertiles demonstrated that higher levels of non-HLA Abs positively correlated with increased glomerulitis (P=0.002), microvascular inflammation (P=0.003), and ABMRh (P=0.03). A pretransplantation NHADIA threshold of 1.87 strongly discriminated the KTRs with the highest risk of ABMRh (P=0.005, log-rank test). A multivariate Cox model confirmed that NHADIA status and HLA-DSAs were independent, yet synergistic, predictors of ABMRh. CONCLUSION: The NHADIA identifies non-HLA Abs and strongly predicts graft endothelial injury independent of HLA-DSAs.

COVID-19 severity in kidney transplant recipients is similar to nontransplant patients with similar comorbidities.

Higher rates of severe COVID-19 have been reported in kidney transplant recipients (KTRs) compared to nontransplant patients. We aimed to determine if poorer outcomes were specifically related to chronic immunosuppression or underlying comorbidities. We used a 1:1 propensity score-matching method to compare survival and severe disease-free survival (defined as death and/or need for intensive care unit [ICU]) incidence in hospitalized KTRs and nontransplant control patients between February 26 and May 22, 2020. Patients were matched for risk factors of severe COVID-19: age, sex, body mass index, diabetes mellitus, preexisting cardiopathy, chronic lung disease, and basal renal function. We included 100 KTRs (median age [interquartile range (IQR)]) 64.7 years (55.3-73.1) in three French transplant centers. After a median follow-up of 13 days (7-30), transfer to ICU was required for 34 patients (34%) and death occurred in 26 patients (26%). Overall, 43 patients (43%) developed a severe disease during a median follow-up of 8.5 days (2-14). Propensity score matching to a large French cohort of 2017 patients hospitalized in 24 centers, revealed that survival was similar between KTRs and matched nontransplant patients with respective 30-day survival of 62.9% and 71% (p = .38) and severe disease-free 30-day survival of 50.6% and 47.5% (p = .91). These findings suggest that severity of COVID-19 in KTRs is related to their associated comorbidities and not to chronic immunosuppression.

Is COVID-19 infection more severe in kidney transplant recipients?

There are no studies which have compared the risk of severe COVID-19 and related mortality between transplant recipients and nontransplant patients. We enrolled two groups of patients hospitalized for COVID-19, that is, kidney transplant recipients (KTR) from the French Registry of Solid Organ Transplant (n = 306) and a single-center cohort of nontransplant patients (n = 795). An analysis was performed among subgroups matched for age and risk factors for severe COVID-19 or mortality. Severe COVID-19 was defined as admission (or transfer) to an intensive care unit, need for mechanical ventilation, or death. Transplant recipients were younger and had more comorbidities compared to nontransplant patients. They presented with higher creatinine levels and developed more episodes of acute kidney injury. After matching, the 30-day cumulative incidence of severe COVID-19 did not differ between KTR and nontransplant patients; however, 30-day COVID-19-related mortality was significantly higher in KTR (17.9% vs 11.4%, respectively, p = .038). Age >60 years, cardiovascular disease, dyspnea, fever, lymphopenia, and C-reactive protein (CRP) were associated with severe COVID-19 in univariate analysis, whereas transplant status and serum creatinine levels were not. Age >60 years, hypertension, cardiovascular disease, diabetes, CRP >60 mg/L, lymphopenia, kidney transplant status (HR = 1.55), and creatinine level >115 µmol/L (HR = 2.32) were associated with COVID-19-related mortality in univariate analysis. In multivariable analysis, cardiovascular disease, dyspnea, and fever were associated with severe disease, whereas age >60 years, cardiovascular disease, dyspnea, fever, and creatinine level>115 µmol/L retained their independent associations with mortality. KTR had a higher COVID-19-related mortality compared to nontransplant hospitalized patients.

Deciphering the Prognostic and Predictive Value of Urinary CXCL10 in Kidney Recipients With BK Virus Reactivation.

BK virus (BKV) replication increases urinary chemokine C-X-C motif ligand 10 (uCXCL10) levels in kidney transplant recipients (KTRs). Here, we investigated uCXCL10 levels across different stages of BKV replication as a prognostic and predictive marker for functional decline in KTRs after BKV-DNAemia. uCXCL10 was assessed in a cross-sectional study (474 paired urine/blood/biopsy samples and a longitudinal study (1,184 samples from 60 KTRs with BKV-DNAemia). uCXCL10 levels gradually increased with urine (P-value < 0.0001) and blood BKV viral load (P < 0.05) but were similar in the viruria and no BKV groups (P > 0.99). In viremic patients, uCXCL10 at biopsy was associated with graft functional decline [HR = 1.65, 95% CI (1.08-2.51), P = 0.02], irrespective of baseline eGFR, blood viral load, or BKVN diagnosis. uCXL10/cr (threshold: 12.86 ng/mmol) discriminated patients with a low risk of graft function decline from high-risk patients (P = 0.01). In the longitudinal study, the uCXCL10 and BKV-DNAemia trajectories were superimposable. Stratification using the same uCXCL10/cr threshold at first viremia predicted the subsequent inflammatory response, assessed by time-adjusted uCXCL10/cr AUC (P < 0.001), and graft functional decline (P = 0.03). In KTRs, uCXCL10 increases in BKV-DNAemia but not in isolated viruria. uCXCL10/cr is a prognostic biomarker of eGFR decrease, and a 12.86 ng/ml threshold predicts higher inflammatory burdens and poor renal outcomes.

Kidney transplantation improves the clinical outcomes of Acute Intermittent Porphyria.

BACKGROUND: Acute Intermittent Porphyria (AIP) is a rare inherited autosomal dominant disorder of heme biosynthesis. Porphyria-associated kidney disease occurs in more than 50% of the patients with AIP, and end stage renal disease (ESRD) can be a devastating complication for AIP patients. The outcomes of AIP patients after kidney transplantation are poorly known. METHODS: We examined the outcomes of 11 individuals with AIP, identified as kidney transplant recipients in the French Porphyria Center Registry. RESULTS: AIP had been diagnosed on average 19 years before the diagnosis of ESRD except for one patient in whom the diagnosis of AIP had been made 5 years after the initiation of dialysis. Median follow-up after transplantation was 9 years. A patient died 2 months after transplantation from a cardiac arrest and a patient who received a donation after cardiac death experienced a primary non-function. No rejection episode and no noticeable adverse event occurred after transplantation. Serum creatinine was on average 117 µmol/l, and proteinuria <0.5 g/l in all patients at last follow up. All usually prescribed drugs after transplantation are authorized except for trimethoprim/sulfamethoxazole. Critically, acute porphyria attacks almost disappeared after kidney transplantation, and skin lesions resolved in all patients. CONCLUSION: Kidney transplantation is the treatment of choice for AIP patients with ESRD and dramatically reduces the disease activity.

An initial report from the French SOT COVID Registry suggests high mortality due to COVID-19 in recipients of kidney transplants.

Notwithstanding the ongoing coronavirus disease-2019 (Covid-19) pandemic, information on its clinical presentation and prognosis in recipients of a kidney transplant remain scanty. The aim of this registry-based observational study was to explore characteristics and clinical outcomes of recipients of kidney transplants included in the French nationwide Registry of Solid Organ Transplant Recipients with Covid-19. Covid-19 was diagnosed in symptomatic patients who had a positive PCR assay for SARS-CoV-2 or having typical lung lesions on imaging. Clinical and laboratory characteristics, management of immunosuppression, treatment for Covid-19, and clinical outcomes (hospitalization, admission to intensive care unit, mechanical ventilation, or death) were recorded. Risk factors for severe disease or death were determined. Of the 279 patients, 243 were admitted to hospital and 36 were managed at home. The median age of hospitalized patients was 61.6 years; most had comorbidities (hypertension, 90.1%; overweight, 63.8%; diabetes, 41.3%; cardiovascular disease, 36.2%). Fever, cough, dyspnea, and diarrhea were the most common symptoms on admission. Laboratory findings revealed mild inflammation frequently accompanied by lymphopenia. Immunosuppressive drugs were generally withdrawn (calcineurin inhibitors: 28.7%; antimetabolites: 70.8%). Treatment was mainly based on hydroxychloroquine (24.7%), antiviral drugs (7.8%), and tocilizumab (5.3%). Severe Covid-19 occurred in 106 patients (46%). Forty-three hospitalized patients died (30-day mortality 22.8%). Multivariable analysis identified overweight, fever, and dyspnea as independent risk factors for severe disease, whereas age over 60 years, cardiovascular disease, and dyspnea were independently associated with mortality. Thus, Covid-19 in recipients of kidney transplants portends a high mortality rate. Proper management of immunosuppression and tailored treatment of this population remain challenging.