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Background Data on use of interleukin (IL)-1 blockers in kidney transplant recipients (KTRs) with familial Mediterranean fever (FMF) are very limited. We aimed to evaluate the efficacy and safety of anakinra and canakinumab in the transplantation setting. Methods In this retrospective cohort study, we included KTRs who suffered from AA amyloidosis caused by FMF and treated with anakinra or canakinumab (study group, n = 36). Using propensity score matching, we selected 36 patients without FMF or amyloidosis from our database of 696 KTRs as the control group. Primary outcomes were patient and graft survival. Biopsy-confirmed graft rejection, changes in estimated glomerular filtration rate (eGFR), high-sensitivity CRP (hsCRP), erythrocyte sedimentation rate (ESR), proteinuria and number of monthly attacks were secondary outcomes. Results All KTRs with FMF began IL-1 blocker therapy with anakinra and nine (25%) were switched to canakinumab. Overall death was more frequent in the study group (19.4% vs 0%) (P = .005); however, overall graft loss was comparable between study (27.8%) and control groups (36.1%) (P = .448). Five- and 10-year graft survival rates were significantly higher in the study group (94.4% and 83.3%, respectively) than in the control group (77.8% and 63.9%, respectively) (P = .014 and P Conclusions Anakinra and canakinumab are effective in KTRs suffering from FMF; however, the mortality rate may be of concern.

The impact of core 1,3-galactosyltransferase-specific molecular chaperon (COSMC) gene expression and methylation profile on clinical progression of IgA nephropathy (IgAN) is unclear. The aim of this study was to determine the clinical significance and the relation of the COSMC gene expression and methylation pattern with the progression of IgAN.Thirty-nine biopsy-confirmed IgAN patients, 11 healthy relatives and 20 healthy controls were recruited. The COSMC mRNA levels and methylation profile of COSMC gene promoter were measured using the quantitative real-time PCR. The galactose-deficient IgA1 (Gd-IgA1) levels were measured using ELISA in serum and cell culture supernatant. The effect of IL-4 and AZA on COSMC expression and methylation and the correlation of COSMC gene expression and methylation levels with baseline kidney function tests, histology and long-term outcomes were examined.The mean COSMC mRNA level was significantly lower, and serum Gd-IgA1 level was higher in IgAN patients compared with the control groups (p 0.001, and p = 0.001, respectively). The COSMC mRNA levels were correlated with intensity of hematuria (r = - 0.41, p = 0.009), serum creatinine level (r = - 0.37, p = 0.002) and eGFR (r = 0.36, p = 0.002). The COSMC methylation levels were correlated with age (r = 0.25, p = 0.04) and baseline eGFR (r = - 0.326, p = 0.006). Twenty IgAN patients (51.3%) reached to complete (5, 12.8%) or partial remission (15, 38.5%) after a median of 34.5 months (IQR, 13.75-71). In multivariable Cox regression analysis, COSMC mRNA expression (adjusted HR (aHR) 1.871, 95% CI 1.287-2.722, p = 0.001) and Oxford T score (aHR 0.355, 95% CI 0.146-0.859, p = 0.022) predicted the remission.COSMC mRNA level is a novel biomarker candidate to predict the remission in IgAN patients.

We sought to characterize the clinical profiles and outcomes of patients with coronavirus disease 2019 and comorbid kidney disease hospitalized at urban, Midwestern tertiary care hospital. MATERIAL AND METHODS: In this single-center observational study, we describe 205 patients with acute kidney injury (n=98), dialysis-dependent chronic kidney disease stage 5 (n=54), or kidney transplant (n=53), admitted during the first surge of the local pandemic from March 19 2020, to July 31 2021. RESULTS: Most patients in the cohort were African American (acute kidney injury, 51%; dialysis-dependent chronic kidney disease stage 5, 82%; kidney transplant, 62%), and obesity was common (acute kidney injury, 53%; dialysis-dependent chronic kidney disease stage 5, 44%; kidney transplant 56%). Mechanical ventilation was required in 50% of the acute kidney injury, 22% of the dialysis-dependent chronic kidney disease stage 5, and 13% of the kidney transplant recipients. Nearly half of the acute kidney injury patients (46%) died and 49% required replacement therapy, while in-hospital mortality was 24% in the dialysis-dependent chronic kidney disease stage 5 patients and 9% in the kidney transplant recipients. Logistic regression analysis identified older age and patient group as leading correlates of mortality, with lower death risk in the kidney transplant (24%; odds ratio (OR), 0.17; 95% CI 0.06–0.47) and dialysis dependent chronic kidney disease stage 5 (9%; OR, 0.36; 95% CI 0.16–0.78) patients compared to acute kidney injury patients (46%). Obesity was associated with 5-fold increased mortality risk in the coronavirus disease 2019 patients with acute kidney injury (OR, 5.32; 95% CI 1.41–20.03) but not in dependent dialysis chronic kidney disease stage 5 and kidney transplant patients. CONCLUSION: During the first surge of the pandemic, kidney patients hospitalized COVID-19 experienced high mortality, especially those with acute kidney injury, older age and obesity. Identifying those at highest risk for adverse outcomes may direct preventative strategies including counseling on vaccination.

The utility of kidney procurement biopsies is controversial. Understanding the current landscape of how clinicians obtain and use biopsies in organ evaluation may help inform consensus-building efforts.An electronic survey was distributed to clinicians at US kidney transplant programs (April 22, 2021-June 30, 2021) to evaluate donor biopsy indications, frequency, processing and interpretation, and impact of findings on practices.Responses from staff involved in organ acceptance (73% surgeons, 20% nephrologists, 6% coordinators) at 95 transplant centers were analyzed, representing 40% of US transplant centers and 50% of recent deceased donor kidney transplant volume. More than a third of centers (35%) reported obtaining procurement biopsies on most-to-all kidneys. Most clinicians decided when to biopsy jointly with the Organ Procurement Organization (OPO) (82%) based on formal criteria for the decision (72%), although 41% reported having requested a biopsy outside of the criteria. Most respondents used a semiquantitative scoring system for interpretation (57%). Many respondents reported rarely or never having access to renal specialty pathologists (37%) or to telepathology (59%). Most respondents reported that a favorable biopsy result would encourage them to accept a "marginal" donor kidney (72%); nearly half (46%) indicated that an unfavorable biopsy result would lead to decline of a standard criteria kidney.Procurement biopsies are commonly used in organ acceptance decisions despite inconsistent access to experienced renal pathologists and heterogeneous approaches to criteria, scoring, and interpretation. Ongoing study and consensus building are needed to direct procurement biopsy practice toward increasing organ utilization and reducing allocation inefficiency.

We compared the outcomes associated with plasma exchange (PE), double filtration plasmapheresis (DFPP), or immunoadsorption (IA) in the treatment of late antibody mediated rejection (AMR).Sixty-nine kidney transplantation (KTx) recipients with late AMR were retrospectively categorized according to management with PE (n = 30), DFPP (n = 22) or IA (n = 17). Allograft loss was compared across treatment groups by Kaplan-Meier analysis and Cox regression.Study groups were similar regarding age, sex, donor type, kidney function, donor specific antibodies, and post-KTx follow-up time. Five-year graft survival trended higher with IA (70.6%) compared to PE (36.7%) and DFPP (27.3%) (p = 0.06). In multivariate Cox regression, baseline eGFR (HR per ml/min/1.73 mThese results motivate the need for continued assessment of rituximab and plasmapheresis in larger studies.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic created unprecedented challenges for solid organ transplant centers worldwide. We sought to assess an international perspective on COVID-19 vaccine mandates and rationales for or against mandate policies. METHODS: We administered an electronic survey to staff at transplant centers outside the United States (October 14, 2021–January 28, 2022) assessing the reasons cited by transplant centers for or against implementing a COVID-19 vaccine mandate. Each responding center was represented once in the analysis. RESULTS: Respondents (N=90) represented 27 countries on five continents. Half (51%) of responding transplant center representatives reported implementing a COVID-19 vaccine mandate, 38% did not, and 12% were unsure. Staff at centers implementing a vaccine mandate cited efficacy of pretransplant vaccination versus post-transplant vaccination, importance for public health, and minimizing exposure of other patients as rationale for the mandate. Of centers with a mandate, the majority (81%) of the centers mandate vaccination regardless of prior SARS-CoV-2 infection status and regardless of prevaccination spike-protein antibody titer or other markers of prior infection. Only 27% of centers with a vaccine mandate for transplant candidates also extended a vaccine requirement to living donor candidates. Centers not implementing a vaccine mandate cited concerns for undue pressure on transplant candidates, insufficient evidence to support vaccine mandates, equity, and legal considerations. CONCLUSIONS: The approach to pretransplant COVID-19 vaccination mandate policies at international transplant centers is heterogeneous. International transplant centers with a vaccine mandate were more willing to extend vaccine requirements to candidates’ support persons, cohabitants, and living donors. Broader stakeholder engagement to overcome vaccine hesitancy across the world is needed to increase the acceptance of pretransplant COVID-19 vaccination to protect the health of transplant patients.

Background This study aims to examine the association of LIM zinc finger domain containing 1 (LIMS1) genotype with allograft rejection in an independent kidney transplant cohort. Methods We genotyped 841 kidney transplant recipients for the LIMS1 rs893403 variant by Sanger sequencing followed by polymerase chain reaction confirmation of the deletion. Recipients who were homozygous for the LIMS1 rs893403 genotype GG were compared with the AA/AG genotypes. The primary outcome was T cell–mediated or antibody-mediated rejection (TCMR or ABMR, respectively) and secondary outcome was allograft loss. Results After a median follow-up of 11.4 years, the rate of TCMR was higher in recipients with the GG genotype (n = 200) compared with the AA/AG genotypes (n = 641) [25 (12.5%) versus 35 (5.5%); P = 0.001] while ABMR did not differ by genotype [18 (9.0%) versus 62 (9.7%)]. Recipients with the GG genotype had 2.4 times higher risk of TCMR than those who did not have this genotype [adjusted hazard ratio2.43 (95% confidence interval 1.44–4.12); P = 0.001]. A total of 189 (22.5%) recipients lost their allografts during follow-up. Kaplan–Meier estimates of 5-year (94.3% versus 94.4%; P = 0.99) and 10-year graft survival rates (86.9% versus 83.4%; P = 0.31) did not differ significantly in the GG versus AA/AG groups. Conclusions Our study demonstrates that recipient LIMS1 risk genotype is associated with an increased risk of TCMR after kidney transplantation, confirming the role of the LIMS1 locus in allograft rejection. These findings may have clinical implications for the prediction and clinical management of kidney transplant rejection by pretransplant genetic testing of recipients and donors for LIMS1 risk genotype.

Background We aimed to investigate the effects of glomerular C3 deposition on clinical, histopathological features, and outcomes of patients with primary membranous nephropathy (MN). Methods A total of 261 patients with biopsy-proven primary MN, who were on follow up for at least 6 months, were included in the study. The patients were grouped according to their C3 immunostaining in kidney biopsy samples at the time of diagnosis: Low intensity [LI; (C3 1 +)] and high intensity [HI; (C3 2 + or C3 3 +)]. The primary outcome was the development of kidney failure. Complete (CR) or partial remission (PR) was defined as secondary outcome. Results Sixteen patients reached the primary outcome after a median follow-up of 33.8 months. Patients in the high intensity group (119 cases) had lower eGFR and higher proteinuria at admission and last follow-up compared to patients in the low intensity group (142 cases). Also, more patients in the high intensity group reached the primary outcome compared to patients in the low intensity group: twelve patients (10.1%) in the high intensity group and four patients (2.8%) in the low intensity group reached the primary outcome (p = 0.015). Kaplan-Meier analysis demonstrated that patients in the high intensity group had a higher risk for kidney failure (p = 0.02). In multivariate logistic regression analysis, high intensity C3 deposition and initial estimated glomerular filtration rate (eGFR) indepenently predicted primary outcome. Conclusion Extensive glomerular C3 deposition is a predictor of kidney failure in patients with MN.

Pharmacogenetic profiling of transplant recipients demonstrates that the marked variation in the metabolism of immunosuppressive medications, particularly tacrolimus, is related to genetic variants. Patients of African ancestry are less likely to carry loss-of-function (LoF) variants in theThe CYP3A5 phenotype status was identified in 438 adult kidney transplant (KTx) recipients (96% were African American) using 3 LoF alleles (Among the cohort, 23% had a rapid, 47% intermediate, and 30% a slow metabolism phenotype based on genotype. At 3 y, the rate of death censored graft failure and all cause graft failure was highest in the rapid metabolism phenotype and lowest in the intermediate metabolism phenotype group. First-year Medicare reimbursement differed significantly by genotype (rapid: $79 535, intermediate: $72 796, slow: $79 346,Pharmacogenomic assessment of African American KTx recipients may be useful to guide therapy when as

BACKGROUND Massively parallel sequencing (MPS) has propelled precision medicine into the next generation. With genetic data more accessible than ever, the focus has now shifted from obtaining data to converting the acquired data into applicable clinical information. A major obstacle to such task arises when there is limited knowledge of the phenotypic spectrum of a genetic entity, limiting the application of virtual panels and prioritization of genetic candidates. METHOD We performed in-depth clinical, imaging and histological phenotyping of an index family presenting with extremely early-onset hypertension and kidney disease. We then performed genetic investigations on the proband, starting with a limited MPS panel testing for monogenic causes of arterial hypertension. This was followed by Genomics England 100 000 Genomes Project whole genome sequencing (WGS) and application of a 26-gene virtual panel for ‘extreme early-onset hypertension’. Subsequently, we reviewed the 100 000 Genomes Project rare disease data for patients recruited with extreme early-onset hypertension. We also conducted a literature review to identify any existing studies correlating TTC21B mutations and systemic hypertension. RESULTS The proband (Table 1, II.1) was a 3.5-year-old girl presenting with severe hypertension, proteinuria, kidney failure, left ventricular hypertrophy, liver function test abnormalities and growth retardation. A kidney ultrasound scan showed bilateral small kidneys with loss of corticomedullary differentiation. Kidney biopsy showed sclerosed glomeruli, severe tubular atrophy with tubulointerstitial fibrosis in addition to arteriolar changes in secondary to systemic hypertension. Her sibling (Table 1, II.2) equally presented with early-onset hypertension and progressive kidney disease. MPS panel testing and WGS virtual panel for early-onset hypertension both failed to identify pathogenic variants. Manual curation of WGS data then revealed a heterozygous nonsense variant p.(Gln834Ter) in conjunction with a heterozygous missense variant p.(Pro209Leu) in TTC21B, both of which were predicted to be pathogenic according to ACMG criteria. This was missed as the gene did not form part of the hypertension virtual panel. TTC21B mutations have been previously associated with typical ciliopathies such as nephronophthisis (NPHP) and Jeune asphyxiating thoracic dystrophy, but only recently implicated in glomerular kidney disease such as focal segmental glomerulosclerosis (FSGS). Literature review suggests roles for TTC21B (IFT139) both in the primary cilium and in podocyte cytoskeleton, revealing a striking association between TTC21B missense variants and early-onset hypertension. Searching the 100 000 Genomes Project revealed one additional case of arterial hypertension and mild proteinuria explained by biallelic mutations in TTC21B. CONCLUSION In conclusion, biallelic mutations in TTC21B produce a spectrum of phenotypes from typical ciliopathies to kidney-limited phenotypes. The latter are mostly encountered in patients carrying two missense, often hypomorphic, variants, and are characterized by lesions of the glomerular as well as the tubulointerstitial compartment, resembling both FSGS and NPHP. Increased clinical recognition of this mixed glomerular and tubulointerstitial disease with often mild or absent features of a typical ciliopathy as well as inclusion of TTC21B on gene panels for early-onset arterial hypertension may shorten the diagnostic odyssey for patients affected by this rare tubuloglomerular kidney disease.

Purpose of Review To provide a comprehensive update on the role of genetic testing for the evaluation of kidney transplant recipient and living donor candidates. Recent Findings The evaluation of candidates for living donor transplantation and their potential donors occurs within an ever-changing landscape impacted by new evidence and risk assessment techniques. Criteria that were once considered contraindications to living kidney donation are now viewed as standard of care, while new tools identify novel risk markers that were unrecognized in past decades. Recent work suggests that nearly 10% of a cohort of patients with chronic/end-stage kidney disease had an identifiable genetic etiology, many whose original cause of renal disease was either unknown or misdiagnosed. Some also had an incidentally found genetic variant, unrelated to their nephropathy, but medically actionable. These patterns illustrate the substantial potential for genetic testing to better guide the selection of living donors and recipients, but guidance on the proper application and interpretation of novel technologies is in its infancy. In this review, we examine the utility of genetic testing in various kidney conditions, and discuss risks and unresolved challenges. Suggested algorithms in the context of related and unrelated donation are offered. Summary Genetic testing is a rapidly evolving strategy for the evaluation of candidates for living donor transplantation and their potential donors that has potential to improve risk assessment and optimize the safety of donation.

Anti-LDL Receptor-Related Protein 2 (Anti-LRP2) nephropathy is a rare form of kidney disease that affects the older patients and is characterized with acute kidney injury (AKI) and progressive renal tubular injury associated with IgG immune complex deposits along the basement membrane of proximal tubules, and circulating autoantibodies to the proximal tubule brush border protein LRP2 (megalin). We present the case of a 79-year-old man who was hospitalized for worsening malaise, abdominal distention and bilateral lower extremity edema, diagnosed with AKI and had nephrotic range proteinuria. Percutaneous kidney biopsy revealed tubulointerstitial nephritis with IgG immune complex deposits along the basement membrane of proximal tubules and brush borders. Immunofluorescence staining for LRP2 (megalin) showed similar granular tubular basement membrane deposits along the proximal tubules and proximal tubule brush borders. Electron microscopy revealed global podocyte foot process effacement. The patient was started on oral prednisolone 1 mg/kg and rituximab at a dose of 375 mg/m2 once weekly for 4 weeks with gradual tapering of prednisone. This case with AKI and nephrotic syndrome highlights the significant morphologic overlap with minimal change disease and anti-LRP2 nephropathy, which is associated with autoantibodies to the tubular brush border protein LRP2/megalin.

Monogenic disorders of the kidney typically affect either the glomerular or tubulointerstitial compartment producing a distinct set of clinical phenotypes. Primary focal segmental glomerulosclerosis (FSGS), for instance, is characterized by glomerular scarring with proteinuria and hypertension while nephronophthisis (NPHP) is associated with interstitial fibrosis and tubular atrophy, salt wasting, and low- to normal blood pressure. For both diseases, an expanding number of non-overlapping genes with roles in glomerular filtration or primary cilium homeostasis, respectively, have been identified. TTC21B, encoding IFT139, however has been associated with disorders of both the glomerular and tubulointerstitial compartment, and linked with defective podocyte cytoskeleton and ciliary transport, respectively. Starting from a case report of extreme early-onset hypertension, proteinuria, and progressive kidney disease, as well as data from the Genomics England 100,000 Genomes Project, we illustrate here the difficulties in assigning this mixed phenotype to the correct genetic diagnosis. Careful literature review supports the notion that biallelic, often hypomorph, missense variants in TTC21B are commonly associated with early-onset hypertension and histological features of both FSGS and NPHP. Increased clinical recognition of this mixed glomerular and tubulointerstitial disease with often mild or absent features of a typical ciliopathy as well as inclusion of TTC21B on gene panels for early-onset arterial hypertension might shorten the diagnostic odyssey for patients affected by this rare tubuloglomerular kidney disease.

Silicate stones are extraordinarily rare in human beings, but when present, they are often associated with ingestion of Magnesium Trisilicate, an antacid medication. However, there have been few case reports of patients who developed silicate stones, without ingestion of Magnesium Trisilicate. Hereby, we present the case of a 67-year-old man who developed acute kidney injury due to obstructive uropathy, detected during his scheduled chemotherapy for his relapsing multiple myeloma. Abdominal ultrasound and CT scan imaging demonstrated multiple non-mobile calcifications in the bladder neck/prostate bed. Stone analysis showed a material resembling silica. This case with silicate urinary tract stone highlights this extra-rare urinary stone in a patient without any identified source of silicate. DOI: 10.52547/ijkd.7044.

An electronic survey canvassing current policies of transplant centers regarding a COVID-19 vaccine mandate for transplant candidates and living donors was distributed to clinicians at US solid organ transplant centers performing transplants from October 14, 2021-November 15, 2021. Responses were received from staff at 141 unique transplant centers. These respondents represented 56.4% of US transplant centers, and responding centers performed 78.5% of kidney transplants and 82.4% of liver transplants in the year prior to survey administration. Only 35.7% of centers reported implementing a vaccine mandate, while 60.7% reported that vaccination was not required. A minority (42%) of responding centers with a vaccine mandate for transplant candidates also mandated vaccination for living organ donors. Centers with a vaccine mandate most frequently cited clinical evidence supporting the efficacy of pre-transplant vaccination (82%) and stewardship obligations to ensure organs were transplanted into the lowest risk patients (64%). Centers without a vaccine mandate cited a variety of reasons including administrative, equity, and legal considerations for their decision. Transplant centers in the United States exhibit significant heterogeneity in COVID-19 vaccination mandate policies for transplant candidates. While all centers encourage vaccination, most centers have not mandated COVID-19 vaccination for candidates and living donors, citing administrative opposition, legal prohibitions, and concern about equity in access to transplants.

Background The coronavirus disease 2019 (COVID‐19) pandemic has created unprecedented challenges for solid organ transplant programs worldwide. The aim of this study is to assess an international perspective on challenges faced by kidney transplant programs. Methods We administered an electronic survey instrument from 03/01/2021 to 08/06/2021 to staff at transplant programs outside the United States that comprised of 10 questions addressing the management of kidney transplant candidates with asymptomatic COVID‐19 infection or unvaccinated who receive an organ offer. Results Respondents (n = 62) represented 19 countries on 5 continents. Overall, 90.3% of respondents encourage vaccination on the waiting list and prior to planned living donor transplant. 12% of respondents reported that they have decided to inactivate unsensitized candidates (cPRA

IgA nephropathy (IgAN) is a progressive form of kidney disease defined by glomerular deposition of IgA. We performed a genome-wide association study involving 10,146 kidney biopsy-diagnosed IgAN cases and 28,751 matched controls across 17 international cohorts. We defined 30 independent genome-wide significant risk loci jointly explaining 11% of disease risk. A total of 16 loci were novel, including TNFSF4, REL, CD28, CXCL8/PF4V1, LY86, LYN, ANXA3, TNFSF8/15, REEP3, ZMIZ1, RELA, ETS1, IGH, IRF8, TNFRSF13B and FCAR. The SNP-based heritability of IgAN was estimated at 23%. We observed a positive genetic correlation between IgAN and total serum IgA levels, allergy, tonsillectomy, and several infections, and a negative correlation with inflammatory bowel disease. All significant non-HLA loci shared with serum IgA levels had a concordant effect on the risk of IgAN. Moreover, IgAN loci were globally enriched in gene orthologs causing abnormal IgA levels when genetically manipulated in mice. The explained heritability was enriched in the regulatory elements of cells from the immune and hematopoietic systems and intestinal mucosa, providing support for the pathogenic role of extra-renal tissues. The polygenic risk of IgAN was associated with early disease onset, increased lifetime risk of kidney failure, as well as hematuria and several other traits in a phenome-wide association study of 590,515 individuals. In the comprehensive functional annotation analysis of candidate causal genes across genome-wide significant loci, we observed the convergence of biological candidates on a common set of inflammatory signaling pathways and cytokine ligand-receptor pairs, prioritizing potential new drug targets.

The aim of this study was to evaluate the interactions among serum levels of galactose-deficient IgA1 (Gd-IgA1), oxidative stress and macrophage infiltration and their clinical correlates in patients with IgA Nephropathy (IgAN). A total of 47 patients with biopsy-proven primary IgAN, aged between 16 and 79 years, with a follow-up period ≥ 1 year or who showed progression to end stage kidney disease (ESKD) regardless the duration of follow-up were included. Study endpoint was the progression to ESKD. Serum Gd-IgA1 and advanced oxidation protein product (AOPP) levels were measured using ELISA assays. Kidney biopsies were evaluated according to the Oxford MEST-C scoring, with C4d and CD68 staining. Seventeen patients (36%) experienced ESKD during a median follow-up time of 6 years (IQR 3.7–7.5). Serum AOPP levels were correlated with the intensity of glomerular C3 deposition (r = 0.325, p = 0.026), glomerular (r = 0.423, p = 0.003) and interstitial CD68 + cell count (r = 0.298, p = 0.042) and Gd-IgA1 levels (r = 0.289, p = 0.049). Serum Gd-IgA1 levels were correlated with the intensity of C3 deposition (r = 0.447, p = 0.002). eGFR at biopsy (adjusted HR (aHR) 0.979 p = 0.011), and E score (aHR, 8.305, p = 0.001) were associated with progression to ESKD in multivariate analysis. 5-year ESKD-free survival rate was significantly lower in patients with higher E score compared to patients with E score 0 [p = 0.021]. An increased number of macrophages in the glomerular and tubulointerstitial area may play a role in oxidative stress and complement system activation. Endocapillary hypercellularity is a predictive factor for poor prognosis in IgAN.

The coronavirus disease 2019 (COVID-19) pandemic has created unprecedented challenges for solid organ transplant programs. While transplant activity has largely recovered, appropriate management of deceased donor candidates who are asymptomatic but have positive nucleic acid test (NAT) for COVID-19 is unclear as this may reflect active infection or prolonged viral shedding. Furthermore, candidates who are unvaccinated or partially vaccinated continue to receive donor offers. In the absence of prospective data, transplant professionals at U.S. adult kidney transplant centers were surveyed to determine community practice (N: 92 centers, capturing 40.8% of centers and 56.6% of transplants performed). The majority (96.8%) of responding centers declined organs for asymptomatic NAT+ patients without documented prior infection. However, 31.6% of centers proceeded with kidney transplant in NAT+ patients who were at least 30 days from initial diagnosis with negative chest imaging. Less than 7% of programs reported inactivating patients who were unvaccinated or partially vaccinated. In conclusion, despite national recommendations to wait for negative testing, many centers are proceeding with transplant in patients with positive tests due to presumed viral shedding. Furthermore, very few centers are requiring COVID-19 vaccination prior to transplantation despite early evidence suggesting reduced immunogenicity in transplant patients on immunosuppression. This article is protected by copyright. All rights reserved.

Background The use of Hepatitis C (HCV) NAT positive allografts remains unusual and is clustered at few centers. We conducted a contemporary literature review to assess whether patient and clinician attitudes toward viremic organs impact acceptance. Methods Databases including PubMed, MEDLINE, and SCOPUS databases were reviewed to identify studies focused on evaluating patient and provider perceptions of HCV NAT positive organ use within the DAA era (January 2015-April 2021). Search included MeSH terms related to Hepatitis C, transplantation, and patient and clinician attitudes. Two investigators extracted study characteristics including information on willingness to accept viremic organs, HCV-specific outcomes knowledge, HCV-specific concerns, and factors that contributed to acceptance or non-acceptance. Results Eight studies met all inclusion criteria. These included three pretransplant patient-directed studies, two post-transplant patient-directed studies, one pre- and post-transplant patient-directed study, and two clinician-directed studies. Common themes identified were concerns regarding HCV cure rates, viremic organ quality, DAA cost, stigma, and the possibility of HCV transmission to household members. The perception of decreased waitlist time was associated with viremic organ acceptance. Physician trust played a mixed role in acceptance patterns. Conclusions Knowledge of high cure rates, shorter waitlist times, and higher organ quality appear to have the highest impact on organ acceptance.

Rationale & Objective Posttransplant diabetes mellitus (DM) after kidney transplantation increases morbidity and mortality, particularly in older and obese recipients. We aimed to examine the impact of immunosuppression selection on the risk of posttransplant DM among both older and obese kidney transplant recipients. Study Design Retrospective database study. Setting & Participants Kidney-only transplant recipients aged ≥18 years from 2005 to 2016 in the United States from US Renal Data System records, which integrate Organ Procurement and Transplantation Network/United Network for Organ Sharing records with Medicare billing claims. Exposures Various immunosuppression regimens in the first 3 months after transplant. Outcomes Development of DM >3 months-to-1 year posttransplant. Analytical Approach We used multivariable Cox regression to compare the incidence of posttransplant DM by immunosuppression regimen with the reference regimen of thymoglobulin (TMG) or alemtuzumab (ALEM) with tacrolimus + mycophenolic acid + prednisone using inverse propensity weighting. Results 12.7% of kidney transplant recipients developed posttransplant DM with higher incidences in older (≥55 years vs, Graphical abstract

Alport syndrome spectrum can be considered as a group of genetic diseases affecting the major basement membrane collagen type IV network in various organs including the ear, eye, and kidney. The living donor candidate evaluation is an ever-changing landscape. Recently, next-generation sequence (NGS) panels have become readily available and provide opportunities to genetically screen recipient and donor candidates for collagen network gene variants. In this review, our aim is to provide a comprehensive update on the role of genetic testing for the evaluation of potential living kidney donors to kidney candidates with Alport syndrome spectrum. We examine the utility of genetic testing in the evaluation of potential donors for recipients with Alport syndrome spectrum, and discuss risks and unresolved challenges. Suggested algorithms in the context of related and unrelated donation are offered. In contemporary practice, an approach to the evaluation of living donor candidates for transplant candidates with Alport syndrome spectrum can incorporate genetic testing in algorithms tailored for donor-recipient relationship status. Ongoing research is needed to inform optimal practice.

The aim of this study was to evaluate the interactions among serum levels of galactose-deficient IgA1 (Gd-IgA1), oxidative stress and macrophage infiltration and their clinical correlates in patients with IgA Nephropathy (IgAN).A total of 47 patients with biopsy-proven primary IgAN, aged between 16 and 79 years, with a follow-up period ≥ 1 year or who showed progression to end stage kidney disease (ESKD) regardless the duration of follow-up were included. Study endpoint was the progression to ESKD. Serum Gd-IgA1 and advanced oxidation protein product (AOPP) levels were measured using ELISA assays. Kidney biopsies were evaluated according to the Oxford MEST-C scoring, with C4d and CD68 staining.Seventeen patients (36%) experienced ESKD during a median follow-up time of 6 years (IQR 3.7-7.5). Serum AOPP levels were correlated with the intensity of glomerular C3 deposition (r = 0.325, p = 0.026), glomerular (r = 0.423, p = 0.003) and interstitial CD68 + cell count (r = 0.298, p = 0.042) and Gd-IgA1 levels (r = 0.289, p = 0.049). Serum Gd-IgA1 levels were correlated with the intensity of C3 deposition (r = 0.447, p = 0.002). eGFR at biopsy (adjusted HR (aHR) 0.979 p = 0.011), and E score (aHR, 8.305, p = 0.001) were associated with progression to ESKD in multivariate analysis. 5-year ESKD-free survival rate was significantly lower in patients with higher E score compared to patients with E score 0 [p = 0.021].An increased number of macrophages in the glomerular and tubulointerstitial area may play a role in oxidative stress and complement system activation. Endocapillary hypercellularity is a predictive factor for poor prognosis in IgAN.

Focal segmental glomerulosclerosis (FSGS), an important cause of end-stage kidney disease (ESKD), covers a spectrum of clinicopathological syndromes sharing a common glomerular lesion, based on an injury of podocytes caused by diverse insults to glomeruli. Although it is well expressed in many reports that the term FSGS is not useful and applicable to a single disease, particularly in genetic studies, FSGS continues to be used as a single clinical diagnosis. Distinguishing genetic forms of FSGS is important for the treatment and overall prognosis because secondary forms of FSGS, produced by rare pathogenic variations in podocyte genes, are not good candidates for immunosuppressive treatment. Over the past decade, several next generation sequencing (NGS) methods have been used to investigate the patients with steroid resistance nephrotic syndrome (SRNS) or FSGS. Pathogenic variants in COL4A3, COL4A4, or COL4A5 genes have been frequently identified in patients with histologic diagnosis of FSGS. The contribution of these mostly heterozygous genetic variations in FSGS pathogenesis and the clinical course of patients with these variations have not been well characterized. This review emphasizes the importance of appropriate approach in selection and diagnosis of cases and interpretation of the genetic data in these studies and suggests a detailed review of existing clinical variant databases using newly available population genetic data.

The United States has faced an unprecedented opioid crisis in recent years, which has led to an increase in opioid overdose-related deaths and, consequently, an increase in the number of potential deceased donors available for transplantation. This new pool of potential organ donors is composed of younger donors with higher infectious disease transmission risk. The use of organs from these donors requires appropriate patient education, informed consent, and post-transplant monitoring practices. Prescription opioid use is also an important component of the evaluation of transplant and living donor candidates because it may impact outcomes and eligibility for the procedures. In kidney transplant recipients, prescription opioid use predicts a higher risk of mortality, graft loss, and post-transplant complications. These effects seem to be proportional to the levels of opioid use, and to parallel patterns in other transplant populations such as liver, heart and lung recipients. Among living kidney donors, predonation prescription opioid use is associated with an increased risk of re-admission after nephrectomy. Overall, the opioid epidemic creates educational needs for patients awaiting deceased donor transplant, and also impacts the evaluation and care of transplant candidates. Among transplant candidates and recipients, the identification of patients with chronic opioid use should prompt multidisciplinary evaluation and management strategies to minimize risks.

The scope of the impact of the Coronavirus disease 19 (COVID‐19) pandemic on living donor kidney transplantation (LDKT) practices across the world is not well defined. We received survey responses from 204 transplant centers internationally from May to June 2020 regarding the impact of the COVID‐19 pandemic on LDKT practices. Respondents represented 16 countries on 5 continents. Overall, 75% of responding centers reported that LDKT surgery was on hold (from 67% of North American centers to 91% of European centers). The majority (59%) of centers reported that new donor evaluations were stopped (from 46% of North American centers to 86% of European centers), with additional 23% of centers reporting important decrease in evaluations. Only 10% of centers reported slight variations on their evaluations. For the centers that continued donor evaluations, 40% performed in‐person visits, 68% by video, and 42% by telephone. Center concerns for donor (82%) and recipient (76%) safety were the leading barriers to LDKT during the pandemic, followed by patients concerns (48%), and government restrictions (46%). European centers reported more barriers related to staff limitations while North and Latin American centers were more concerned with testing capacity and insufficient resources including protective equipment. As LDKT resumes, 96% of the programs intend to screen donor and recipient pairs for coronavirus infection, most of them with polymerase chain reaction testing of nasopharyngeal swab samples. The COVID‐19 pandemic has had broad impact on all aspects of LDKT practice. Ongoing research and consensus‐building are needed to guide safe reopening of LDKT programs.