Similar incidence of graft glomerulonephritis in recipients with definitively diagnosed glomerulonephritis and those with unknown etiology: a retrospective observational study.

OBJECTIVE: In China, most of the patients who underwent kidney transplants have unknown causes of end-stage renal disease (uESRD). However, little is known regarding the incidence of graft glomerulonephritis (GN) and graft survival in kidney transplant recipients (KTRs) with uESRD. METHODS: In this retrospective cohort study, 473 of the 565 KTRs who underwent kidney transplantation (KTx) from 2015 to 2020 were included. We mainly observed the occurrence of graft GN between uESRD group and definitively diagnosed GN group, and repeatedly compared after propensity score matching (PSM). RESULTS: The median follow-up was 50 months in 473 KTRs, and about 75% of KTRs of native kidney disease of unknown etiology. The total cumulative incidence of graft GN was 17%, and no difference was observed between the definitively diagnosed GN group and the uESRD group (p = 0.76). Further, PSM analysis also showed no difference in the incidence of graft GN between the 2 groups. Multivariable analysis disclosed males (p = 0.001), younger age (p = 0.03), and anti-endothelial cell anti-body (AECA) positive pre-KTx (p = 0.001) were independent risk factors for graft GN. CONCLUSIONS: The incidence of graft GN was similar between uESRD and definitively diagnosed GN group. The allograft survival was also similar between two groups.

Significance of Arterial Spin Labeling for Reducing Biopsies in Patients With Kidney Allograft Dysfunction.

BACKGROUND: Although biopsy is often entailed for managing patients with kidney allograft dysfunction, it is associated with potential complications of severe hemorrhage. Arterial spin labeling (ASL) is a non-invasive technique that assesses tissue perfusion. PURPOSE: To assess the utility of ASL for the discrimination of patients with post-transplant allograft dysfunction who do not need biopsy from those who need. STUDY TYPE: Prospective. SUBJECTS: Forty-six patients (34 males/12 females, aged 38.8 ± 9.5 years) with kidney allograft dysfunction, including 31 in which biopsy directly lead to changes in management (NECESSARY group) and 15 in which clinical management did not alter after biopsy (UNNECESSARY group). FIELD STRENGTH/SEQUENCE: 3.0 T and 3D fast-spin echo sequence. ASSESSMENT: All patients underwent both ASL scan and biopsies. The serum creatinine, proteinuria, pathologic results, and cortical ASL readings were obtained and compared between the two groups. STATISTICAL ANALYSES: Chi-square test, independent student t-test, Mann-Whitney U test, receiver-operating characteristic curve. A two-tailed P < 0.05 denoted statistical significance. RESULTS: The NECESSARY group presented with significantly elevated serum creatinine as compared with the UNNECESSARY group (1.87 ± 0.56 mg/dL vs. 1.31 ± 0.37 mg/dL). The acute composite score was significantly higher in the NECESSARY group than that in the UNNECESSARY group (7 [4-8] vs. 1 [0-2]). Cortical ASL in the NECESSARY group was significantly decreased as compared with the UNNECESSARY group (108.06 [69.96-134.92] mL/min/100 g vs. 153.48 [113.19-160.37] mL/min/100 g). Serum creatinine differentiated UNNCESSARY group from the NECESSARY group with an area under the curve (AUC) and specificity of 0.79 and 54.84%, respectively. By comparison, the cortical ASL yielded an AUC of 0.75 and a specificity of 70.97%. Notably, the specificity was increased to 90.30% by combined use of serum creatinine and cortical ASL. DATA CONCLUSION: The combined use of ASL and serum creatinine yielded a high specificity for selecting patients who may not need allograft biopsy. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

Phase-Change Based Oxygen Carriers Improve Acute Cerebral Hypoxia.

Stroke is the second leading cause of death worldwide, and hypoxia is a major crisis of the brain after stroke. Therefore, providing oxygen to the brain microenvironment can effectively protect neurons from damage caused by cerebral hypoxia. However, there is a lack of timely and effective means of oxygen delivery clinically to the brain for acute cerebral hypoxia. Here, a phase-change based nano oxygen carrier is reported, which can undergo a phase change in response to increasing temperature in the brain, leading to oxygen release. The nano oxygen carrier demonstrate intracerebral oxygen delivery capacity and is able to release oxygen in the hypoxic and inflammatory region of the brain. In the acute ischemic stroke mouse model, the nano oxygen carrier can effectively reduce the area of cerebral infarction and decrease the level of inflammation triggered by cerebral hypoxia. By taking advantage of the increase in temperature during cerebral hypoxia, phase-change oxygen carrier proposes a new intracerebral oxygen delivery strategy for reducing acute cerebral hypoxia.

Cytosolic perfluorocarbon delivery to platelets via albumin for antithrombotic therapy.

Thrombosis is a major contributor to global disease burden. Antiplatelet therapy is the critical approach to prevent thrombosis by reducing platelet reactivity. However, classical antiplatelet strategies generally interfere with platelet integrin αIIbß3-mediated platelet activation, thereby facing severe bleeding risk. To break the limitation, we described an integrin αIIbß3-independent antiplatelet method by cytosolic delivery of nanoscale perfluorocarbon (PFC) to platelets via albumin carrier. Denatured albumin was found to build high affinity with platelets to mediate cytosolic PFC delivery. While, cytosolic PFC impaired cytoskeleton reorganization during platelet activation to inhibit relevant platelet functions, but avoided to interfere with integrin αIIbß3. We proved that this αIIbß3-indenpendent antiplatelet pattern showed potential antiplatelet effect with low bleeding risk to prevent thrombosis in various thrombosis models. Together, cytosolic PFC delivery via albumin is a promising antiplatelet approach, and will provide an alternative regimen for current antithrombotic therapy.

Poor outcomes of proliferative glomerulonephritis with monoclonal IgG deposits in renal allografts: a retrospective multicenter study.

BACKGROUND: Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) in renal allografts is a rare, renal-limited disease. No study has reported the long-term outcomes and prognostic features of PGNMID in renal allografts in the Chinese population. METHODS: We retrospectively included transplant patients diagnosed with PGNMID who underwent renal allograft biopsy at three transplant centers from April 2012 to July 2020. We observed the clinicopathologic features, explored the long-term graft survival, and investigated the characteristics associated with the prognosis. RESULTS: A total of 13 transplant patients with PGNMID were included, out of 3821 biopsies. The mean follow-up time was 55 months since kidney transplantation (KTx). At diagnosis, all patients presented with proteinuria (100%) and most of them with hematuria (92%). IgG3κ (69%) was the main immunofluorescence (IF) subtype. The median graft survival of the total cohort was 17 months from diagnosis and 49 months from kidney transplantation. During follow-up, 9 patients needed dialysis and 2 out of 9 patients who progressed to dialysis died of infection. Primary membranoproliferative glomerulonephritis (MPGN) (P = 0.014) and MPGN pattern at diagnostic biopsy (P < 0.001) were associated with a higher risk of graft loss. CONCLUSIONS: The long-term outcome of allograft PGNMID was relatively poor in the Chinese population. Primary MPGN and MPGN pattern in renal allograft were associated with  poor outcomes.

Controlling the quantity of γ-Fe inside multiwall carbon nano-onions: the key role of sulfur.

One of the most interesting structural features of multiwall carbon onions (MWCNOs) and nanotubes (MWCNTs) is the excellent chemical stability, which allows in situ encapsulation of chosen magnetic materials of interest and multifunctional applications. In this letter, we present an innovative chemical vapour synthesis (CVS) approach, in which the inclusion of small quantities of sulfur during the pyrolysis of ferrocene/dichlorobenzene mixtures allows for an important control in the relative abundance of FCC γ-Fe, up to a maximum value of ∼86.5% (structural- and phase-control). The variation in the relative percentage of the encapsulated Fe-based phases was estimated by employing X-ray diffraction (XRD) and Rietveld refinement analyses. The magnetic characterization was achieved by employing superconducting quantum interference device (SQUID) magnetometry, with zero field cooled (ZFC) and field cooled (FC) curves acquired at applied fields of 300 Oe and ∼50 000 Oe.

Perfusion and oxygenation in allografts with transplant renal artery stenosis: Evaluation with functional magnetic resonance imaging.

BACKGROUND: Transplant renal artery stenosis (TRAS) has been shown to reduce kidney perfusion leading to post-operative hypertension. We aimed to measure the perfusion and oxygenation changes in TRAS with arterial spin labeling (ASL) and blood oxygen level-dependent (BOLD) imaging, respectively. METHODS: In this single-center prospective study, a total of seven patients with TRAS and seven age- and sex-matched normal kidney transplant recipients underwent both ASL and BOLD imaging. Moreover, measurements of ASL and BOLD were also performed in five patients after successful angioplasty for TRAS. RESULTS: Allograft cortical perfusion as measured by ASL in the TRAS group was significantly decreased as compared with normal control group (129.9 ± 46.6 ml/100 g vs. 202.4 ± 47.7 ml/100 g, P = .01). Interestingly, allograft oxygenation as indicated by R2* derived from BOLD in both the cortex (16.42 ± 1.90 Hz vs. 18.25 ± 4.34 Hz, P = .33) and the medulla (30.34 ± 2.35 Hz vs. 30.43 ± 6.85 Hz, P = .97) showed no statistical difference between the TRAS and normal control group. In addition, both cortical and medullary oxygenation remained unchanged despite significantly improved cortical perfusion in those undergone successful angioplasty. CONCLUSION: Cortical and medullary oxygenation were preserved in the presence of reduced allograft perfusion in clinically significant TRAS. Prospective larger studies are needed to conclusively establish perfusion and oxygenation changes in TRAS.

Early graft loss due to acute thrombotic microangiopathy accompanied by complement gene variants in living-related kidney transplantation: case series report.

BACKGROUND: Recently, early graft loss has become very rare in living-related kidney transplantation (LKT) as a result of decreased risk of hyperacute rejection and improvements in immunosuppressive regimens. Post-transplant acute thrombotic microangiopathy (TMA) is a rare, multi-factorial disease that often occurs shortly after kidney transplantation and is usually resistant to treatment with dismal renal outcomes. The complement genetic variants may accelerate the development of TMA. However, the complement genetic test was seldom performed in unknown native kidney disease recipients scheduled for LKT. CASE PRESENTATION: We reported three cases of unknown native kidney diseases who had fulminant TMA in the allograft shortly after LKT. Both the donors and the recipients were noted to carry complement genetic variants, which were identified by genetic testing after transplantation. However, all recipients were refractory to treatment and had allograft loss within 3 months after LKT. CONCLUSION: This case series highlights the suggestion to screen complement gene variants in both the donors and the recipients with unknown native kidney diseases scheduled for LKT.

De novo systemic atypical hemolytic uremic syndrome in an ABO-incompatible living kidney transplant recipient with a novel pathogenic CFHR1 gene mutation successfully treated with eculizumab: a case report.

De novo systemic atypical hemolytic uremic syndrome (aHUS) post-kidney transplant is an uncommon entity associated with unfavorable outcome. We herein report a case of systemic and fulminant de novo aHUS accompanied by heart and respiratory failure in a 48-year-old male receiving ABO-incompatible living-related kidney transplant who was successfully treated with the anti-C5 monoclonal antibody eculizumab with complete recovery of allograft function. Genetic testing demonstrated a novel pathogenic heterozygous complement factor H-related 1 gene mutation in both the donor and the recipient. Our study highlights the high risks of post-transplant aHUS due to the complement gene mutations in both donor and recipient in living-related transplantation. Early intervention with eculizumab may be effective for reversing systemic aHUS in kidney transplant recipients.

Time-dependent cardiac structural and functional changes after kidney transplantation: a multi-parametric cardiac magnetic resonance study.

OBJECTIVES: To map time-dependent cardiac structural and functional change patterns after renal transplantation (KT) using cardiac magnetic resonance (CMR). METHODS: Fifty-three patients with pre-KT and post-KT CMR exams were retrospectively analyzed. Patients were divided into three groups according to the time of post-KT CMR: group 1 (3 months post-KT, n = 16), group 2 (6 months post-KT, n = 21), and group 3 (over 9 months post-KT, n = 16). Twenty-one age- and sex-matched healthy controls (HC) were recruited for the study. CMR-derived left ventricular (LV) volumes, LV mass index (LVMi), LV ejection fraction (LVEF), global radial strain (GRS), global circumferential strain (GCS), global longitudinal strain (GLS), and native T1 value were compared. The association between the changes of CMR parameters was assessed. RESULTS: LVMi post-KT decreased in groups 2 (p < 0.001) and 3 (p = 0.004) but both groups had higher LVMi values compared to HC (both p < 0.001). GLS post-KT was decreased in group 1 (p = 0.021), but slightly increased in group 2 (p = 0.728) and group 3 (p = 0.100) without significant difference. GLS post-KT in group 3 was not different from HC (p = 0.104). LVEF, GRS, and GCS post-KT in groups 2 and 3 significantly increased and showed no significant difference from HC. The post-KT native T1 value in all three groups significantly decreased; however, no group showed any significant difference from HC. The change of LVEF was associated with the change of GCS, GRS, and GLS. CONCLUSIONS: Although GRS, GCS, GLS, and native T1 values reversed to normal level, LVMi remained impaired in median 14 months after KT. KEY POINTS: • Kidney transplantation has favorable effects on cardiac structure and function. • In a median 14 months of follow-up after KT, left ventricle strain and native T1 value reversed to normal level while LV mass index (LVMi) did not. Left ventricular hypertrophy may help to explain why KT recipients are still at increased cardiovascular risk. • The reason for the decrease of native T1 value after KT may be more than myocardial fibrosis and needs to be further studied.

Conversion from mycophenolate mofetil to mizoribine in the early stages of BK polyomavirus infection could improve kidney allograft prognosis: a single-center study from China.

BACKGROUND: Some studies have suggested mizoribine (MZR) could inhibit the replication of BK polyomavirus (BKPyV). The purpose of this study was to explore whether conversion from mycophenolate mofetil (MMF) to MZR in the early stages of BKPyV infection can improve kidney allograft prognosis. METHODS: Twenty-one kidney transplant recipients with BKPyV viruria/viremia and ten with BK polyomavirus-associated allograft nephropathy (BKPyVAN) received MZR conversion therapy were retrospectively identified. The clearance rate of urine and blood BKPyV DNA, change of serum creatinine (SCr), uric acid (UA), hemoglobin (HB), white blood cell (WBC), lymphocyte ratio, platelet (PLT), routine urinalysis, panel reactive antibody (PRA), and gastrointestinal disorders during follow-up of the 2 groups were evaluated and compared. RESULTS: After MZR conversion therapy, the clearance rate of urine and blood viral load in BKPyV viruria/viremia group were 85.7 and 100 %, while that in BKPyVAN were 40 and 87.5 %, respectively. Stable SCr were observed in all cases of BKPyV viruria/viremia group, while that of BKPyVAN was only 40 % (P < 0.001) and one even progressed to end-stage renal disease. The results of routine urinalysis in the two groups showed no significant changes before and after MZR conversion therapy. However, in BKPyV viruria/viremia group, four cases developed acute rejection and one had positive PRA-II but no donor specific antibody, requiring conversion back to MMF. Hyperuricemia was the common adverse effect of MZR. CONCLUSIONS: Conversion from MMF to MZR could help clear BKPyV infection. As compared to BKPyVAN, patients who underwent initiation of MZR conversion therapy in the early stages of BKPyV infection maintained stable allograft function. Prospective studies with larger sample size are needed to ascertain this preliminary finding.

Generation and Characterization of Mouse Models of C3 Glomerulonephritis With CFI D288G and P467S Mutations.

C3 glomerulopathy (C3GP) is a disease entity caused by abnormality of the complement alternative pathway (AP) and characterized by C3 deposition in glomeruli. Many variations or mutations of complement factors are believed to underlie the susceptibility to C3GP, but there is a lack of experimental evidence. We have recently reported a patient with C3 glomerulonephritis (C3GN) and compound heterozygosity of two novel variations in the complement factor (CFI). Here, we generated a mouse model to mimic the CFI variations for studying pathogenicity of CFI variations in C3GN development. We used the CRISPR/Cas9 system to make mutant mouse lines that carried D288G and P467S mutations in CFI, respectively, and crossed them to generate mice with compound heterozygosity of CFI D288G and P467S. The mice were all normal in either SPF (specific pathogen free) or regular environment. When treated with lipopolysaccharides (LPS), a bacterial endotoxin that mimics infection and sepsis, the mice developed albuminuria, kidney function impairment, and C3 glomerular deposition at levels comparable with the wild-type mice. The mice with other genotypes concerning CFI D288G and P467S were also tested in parallel. Unexpectedly, we found that the D288G homozygotes all developed severe mesangial deposition of C3 in the LPS model, indicating that CFI D288G variation was involved in the C3 deposition, a key feature of C3GN. The mouse lines generated in the present study can be used to further study the role of CFI variations in C3GN development; in addition, they may be used to screen and test infections and environmental factors capable of triggering C3GN.

Detection of renal allograft fibrosis with MRI: arterial spin labeling outperforms reduced field-of-view IVIM.

OBJECTIVE: To compare the value of reduced field-of-view (FOV) intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) and arterial spin labeling (ASL) for assessing renal allograft fibrosis and predicting long-term dysfunction. METHODS: This prospective study included 175 renal transplant recipients undergoing reduced FOV IVIM DWI, ASL, and biopsies. Renal allograft fibrosis was categorized into ci0, ci1, ci2, and ci3 fibrosis according to biopsy results. A total of 83 participants followed for a median of 39 (IQR, 21-42) months were dichotomized into stable and impaired allograft function groups based on follow-up estimated glomerular filtration rate. Total apparent diffusion coefficient (ADCT), pure diffusion ADC, pseudo-perfusion ADC, perfusion fraction f from IVIM DWI, and renal blood flow (RBF) from ASL were calculated and compared. The area under the receiver operating characteristic curve (AUC) was calculated to assess the diagnostic and predictive performances. RESULTS: RBF was different in ci0 vs ci1 (147.9 ± 46.3 vs 126.0 ± 49.4 ml/min/100 g, p = .02) and ci2 vs ci3 (92.9 ± 46.9 vs 70.8 ± 37.8 ml/min/100 g, p = .03). RBF in the stable group was higher than that in the impaired group (144.73 ± 49.33 vs 102.19 ± 47.58 ml/min/100 g, p < .001). AUCs in distinguishing renal allograft fibrosis and predicting long-term allograft dysfunction for RBF were higher than cortical ADCT (ci0 vs ci1-3, 0.76 vs 0.59, p < .001; ci0-1 vs ci2-3, 0.79 vs 0.68, p = .01; ci0-2 vs ci3, 0.79 vs 0.68, p = .01; 0.76 vs 0.60, p = .04, respectively). CONCLUSION: Compared to reduced FOV IVIM DWI, ASL was a more promising technique for noninvasively distinguishing renal allograft fibrosis degree and predicting long-term allograft dysfunction. KEY POINTS: • Compared to total ADC from rFOV IVIM DWI, RBF from ASL can distinguish no fibrosis (ci0) vs mild fibrosis (ci1) (p = .02) and moderate fibrosis (ci2) vs severe fibrosis (ci3) (p = .04). • RBF had superior performance than diffusion parameters in discriminating fibrosis (no fibrosis [ci0] vs fibrosis [ci1-3], mild fibrosis [ci0-1] vs moderate to severe fibrosis [ci2-3], non-severe [ci0-2] vs severe [ci3] fibrosis; AUC = 0.76 vs 0.59, p < .001; 0.79 vs 0.68, p = .01; 0.79 vs 0.68, p = .01). • Compared to reduced FOV IVIM DWI, ASL was a more promising technique for noninvasively predicting long-term allograft dysfunction (AUC = 0.76 vs 0.60, p = .04).

Is the level of HLA eplet mismatch a risk factor for graft loss among kidney transplant recipients who have already formed de novo donor specific antibody?

Eplet mismatches are associated with de novo DSA (dnDSA) and antibody mediated rejection (ABMR) among the general kidney transplant population. However, it is unclear whether the level of eplet mismatch can be used for risk stratification among patients with dnDSA. We performed a retrospective observational study of kidney transplant recipients with dnDSA (n = 44) transplanted between 10/2007 and 5/2014 to evaluate eplet mismatch as a risk factor for ABMR and allograft loss among dnDSA patients. High resolution typing was inferred from by imputation based on ethnicity and NMDP haplotypes, and the eplet mismatch was calculated using the Epvix algorithm. Biopsies (N = 151) from 95.3%(42/44) of patients were reviewed. The mean (SD) eplet mismatch was 69.8(22.8). The ABMR incidence was 71.4% (30/42) and 5 year death censored allograft survival was 67.4% during the mean (SD) follow-up of 5.3 (3.1) years. ABMR and death-censored allograft survival were not correlated with eplet mismatch among dnDSA patients. However, medication adherence and dnDSA MFI < 3000 were associated with reduced ABMR incidence. Among patients with both of these favorable characteristics, only 35.7% (15/42) developed ABMR. In conclusion, the level of eplet mismatch does not correlate with ABMR or allograft loss among high risk kidney transplant patients with dnDSA.

Effect of human umbilical cord-derived mesenchymal stem cells on lung damage in severe COVID-19 patients: a randomized, double-blind, placebo-controlled phase 2 trial.

Treatment of severe Coronavirus Disease 2019 (COVID-19) is challenging. We performed a phase 2 trial to assess the efficacy and safety of human umbilical cord-mesenchymal stem cells (UC-MSCs) to treat severe COVID-19 patients with lung damage, based on our phase 1 data. In this randomized, double-blind, and placebo-controlled trial, we recruited 101 severe COVID-19 patients with lung damage. They were randomly assigned at a 2:1 ratio to receive either UC-MSCs (4 × 107 cells per infusion) or placebo on day 0, 3, and 6. The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28. Other imaging outcomes, 6-minute walk test (6-MWT), maximum vital capacity, diffusing capacity, and adverse events were recorded and analyzed. In all, 100 COVID-19 patients were finally received either UC-MSCs (n = 65) or placebo (n = 35). UC-MSCs administration exerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo (the median difference was -13.31%, 95% CI -29.14%, 2.13%, P = 0.080). UC-MSCs significantly reduced the proportions of solid component lesion volume compared with the placebo (median difference: -15.45%; 95% CI -30.82%, -0.39%; P = 0.043). The 6-MWT showed an increased distance in patients treated with UC-MSCs (difference: 27.00 m; 95% CI 0.00, 57.00; P = 0.057). The incidence of adverse events was similar in the two groups. These results suggest that UC-MSCs treatment is a safe and potentially effective therapeutic approach for COVID-19 patients with lung damage. A phase 3 trial is required to evaluate effects on reducing mortality and preventing long-term pulmonary disability. (Funded by The National Key R&D Program of China and others. ClinicalTrials.gov number, NCT04288102.

Orderly aligned manganese-based nanotube arrays with controllable secondary structures.

By combining a hard template with a dynamic negative template, orderly aligned micrometer-length manganese nanotubes (Mn-NTs) decorated with nanopores on their walls as the secondary structure are successfully grown by electrodeposition in aqueous solution. These nanopores were characterized and analyzed statistically. It is found that these nanopores evolve along the growth direction of the Mn-NTs and their morphology is well controlled by the deposition potential. In addition, the morphology evolution of the nanopores exhibits distinguished size distribution compared with that found in conventional nanoporous foam grown solely by the dynamic template approach, which is attributed to the nanoconfinement of the hard template.

Early detection of subclinical pathology in patients with stable kidney graft function by arterial spin labeling.

OBJECTIVES: To evaluate the utility of arterial spin labeling (ASL) for the identification of kidney allografts with underlying pathologies, particularly those with stable graft function. METHODS: A total of 75 patients, including 18 stable grafts with normal histology (normal group), 21 stable grafts with biopsy-proven pathology (subclinical pathology group), and 36 with unstable graft function (unstable graft group), were prospectively examined by ASL magnetic resonance imaging. Receiver operating characteristic curves were generated to calculate the area under the curve (AUC), sensitivity, and specificity. RESULTS: Patient demographics among the 3 groups were comparable. Compared with the normal group, kidney allograft cortical ASL values decreased in the subclinical pathology group and the unstable graft group (204.7 ± 44.9 ml/min/100 g vs 152.5 ± 38.9 ml/min/100 g vs 92.3 ± 37.4 ml/min/100 g, p < 0.001). The AUC, sensitivity, and specificity for discriminating allografts with pathologic changes from normal allografts were 0.92 (95% CI, 0.83-0.97), 71.9%, and 100% respectively by cortical ASL and 0.82 (95% CI, 0.72-0.90), 54.4%, and 100% respectively by serum creatinine. The cortical ASL identified allografts with subclinical pathology among patients with stable graft function with an AUC of 0.80 (95% CI, 0.64-0.91), sensitivity of 57.1%, and specificity of 88.9%. Combined use of proteinuria and cortical ASL could improve the sensitivity and specificity to 76.2% and 100% respectively for distinguishing the subclinical pathology group from the normal group. CONCLUSIONS: Cortical ASL is useful for the identification of allografts with underlying pathologies. More importantly, ASL showed promise as a non-invasive tool for the clinical translation of identifying kidney allografts with subclinical pathology. KEY POINTS: • Cortical ASL values were decreased in kidney allografts with subclinical pathologic changes as compared with normal allografts (152.5 ± 38.9 ml/min/100 g vs 204.7 ± 44.9 ml/min/100 g, p < 0.001). • Cortical ASL differentiated allografts with pathologic changes and subclinical pathology group from normal group with an AUC of 0.92 (95% CI, 0.83-0.97) and 0.80 (95% CI, 0.64-0.91) respectively. • Cortical ASL discriminated allografts with underlying pathologic changes from normal allografts with a specificity of 100%, and combined use of proteinuria and cortical ASL values could also achieve 100% specificity for discriminating allografts with subclinical pathology from normal allografts.