Early tocilizumab treatment was associated with survival benefits in hospitalized kidney transplants with severe COVID-19 infection: A prospective cohort study.

BACKGROUND: The potential of Tocilizumab (TCZ) in preventing the cytokine storm caused by COVID-19 infection has been observed, while the survival benefits were inconclusive in solid-organ transplant recipients. We aimed to explore whether the timing of TCZ administration holds significance in the clinical course of COVID-19 infection and identify predicative factors of TCZ efficacy. METHODS: We conducted a prospective cohort study between December 2022, and January 2023. Early TCZ use referred to administration within 6 days after symptoms onset, while late TCZ use indicated administration after 6 days. The primary endpoint was 30-day mortality. RESULTS: Twenty-seven kidney transplant recipients with severe COVID-19 infection were enrolled, with 10 in the early use group and 17 in the late use group. In the early use group, ferritin, lactate dehydrogenase (LDH), C-reactive protein (CRP) and brain natriuretic peptide(BNP) levels had shown significant inhibitions comparing to the late use group, and those inflammatory cytokines demonstrated a noticeable decreasing trend after TCZ administration, whereas only CRP levels decreased in the late use group. The Kaplan-Meier survival curve demonstrated that the early use group had a higher likelihood of survival (P = 0.0078). Receiver Operating Characteristic (ROC) analyses revealed that the time from symptoms to TCZ use (AUC: 0.645), LDH (AUC: 0.803), CRP (AUC: 0.787), and IL-6 (AUC: 0.725) were potential predictive factors of TCZ efficacy. TCZ use within 6 days from symptoms onset, with CRP < 73.5 mg/L, LDH < 435.5 IU/L, and IL-6 < 103.5 pg/mL, had higher survival rates (P = 0.008, P = 0.009, P < 0.001, P < 0.001). CONCLUSION: This study highlights the survival benefits of early TCZ use and the predicative role of cytokines levels in predicting TCZ efficacy in kidney transplant recipients with severe COVID-19 infection.

Human umbilical cord mesenchymal stem cells derived extracellular vesicles ameliorate kidney ischemia-reperfusion injury by suppression of senescent tubular epithelial cells - Experimental Study.

BACKGROUND: Human umbilical cord mesenchymal stem cells derived extracellular vesicles (HUMSC-EVs) have drawn much interest in kidney transplantation, mainly because of their renoprotection by alleviating cell injury and stimulating tissue repair. Cellular senescence has been proven to play a dual regulatory role in kidney ischemia-reperfusion injury (IRI), and the regulation of HUMSC-EVs on tubular epithelial cell senescence may be a potential therapeutic target. MATERIALS AND METHODS: In vitro, the hypoxia-reoxygenation of human kidney-2 cells was used to simulate kidney IRI, and the regulation of HUMSC-EVs on human kidney-2 cells was detected. Transcriptome sequencing of human kidney-2 cells was used to explore the potential regulatory mechanism. In vivo, adult male mice were divided into five groups: control group, IRI group, HUMSC-EVs treatment group, senolytics treatment group (dasatinib + quercetin), and combined treatments group (HUMSC-EVs and senolytics). Kidney function, senescent features of tubular epithelial cells, acute kidney injury, and chronic interstitial fibrosis in mice were detected to explore the renoprotection effects of HUMSC-EVs. RESULTS: Kidney IRI significantly up-regulated expressions of LaminB1, p53, p21, p16, senescence-associated beta-galactosidase, and apoptosis of tubular epithelial cells. In the mouse kidney IRI model, kidney subcapsular injection of HUMSC-EVs significantly improved kidney function, reducing the senescent features of tubular epithelial cells and alleviating acute kidney injury and chronic interstitial fibrosis. HUMSC-EVs mainly achieved renoprotection by regulating Bax/Bcl-2-dependent apoptosis during acute kidney injury and mostly reduced tubular atrophy and kidney interstitial fibrosis by regulating Ras-pERK-Ets1-p53 pathway-dependent cell senescence. Oral administration of senolytics also alleviated kidney injury induced by IRI, while the combined treatments of HUMSC-EVs and senolytics had better renoprotection effects. CONCLUSIONS: The combination of HUMSC-EVs and senolytics alleviated acute kidney injury and chronic interstitial fibrosis by dynamic regulation of cell senescence and apoptosis, which provides a therapeutic potential strategy for organ preservation and tissue repair in kidney transplantation.

Ex Vivo Surgical Removal Versus Conservative Management of Small Asymptomatic Kidney Stones in Living Donors and Long-term Kidney Transplant Outcomes.

BACKGROUND: Donors with small asymptomatic kidney stones have been increasingly accepted because of organ shortages and advances in endoscopic urology. This study aims to evaluate and compare long-term living-donor kidney transplant outcomes following ex vivo surgical removal versus conservative management of donors' gifted asymptomatic stones. METHODS: Between January 2007 and December 2021, 119 kidney transplant recipients received stone-bearing kidneys, divided into the removal group (N = 63) and observation group (N = 56). We evaluated posttransplant stone events, urinary infections, kidney function, delayed graft function, length of hospital stay, and survival outcomes. RESULTS: After a median follow-up of 75.5 mo, the removal group had a 10.9% lower absolute incidence of stone events (7/56 [12.5%] versus 1/63 [1.6%]; hazard ratio, 0.08; 95% confidence interval, 0.01-0.77) and a 14.3% lower absolute incidence of urinary infections (16/56 [28.6%] versus 9/63 [14.3%]; hazard ratio, 0.42; 95% confidence interval, 0.19-0.95) than the observation group. The removal group also showed superior kidney graft function. The 2 groups had comparable length of hospital stay (11.0 versus 12.0 d; P = 0.297) and exhibited similar delayed graft function incidence (1/56 [1.8%] versus 2/63 [3.2%]; P = 1.000) and urinary stricture incidence (1/56 [1.8%] versus 3/63 [4.8%]; P = 0.621). Graft survival (P = 0.350) and patient survival (P = 0.260) were comparable between 2 groups. Subgroup analyses in recipients who received kidneys with stones <4 mm also reported similar results. CONCLUSIONS: Ex vivo surgical removal might outperform conservative management for donors' gifted asymptomatic kidney stones, improving long-term transplant outcomes and reducing stone events without increasing perioperative complications, even for stones <4 mm.

Risk for Donor-Derived Syphilis after Kidney Transplantation, China, 2007-2022.

To evaluate the risk of acquiring syphilis from a donated kidney, we evaluated kidney transplantation pairs from West China Hospital, Sichuan, China, during 2007-2022. Donor-derived syphilis was rare. Risk may be higher if donors have active syphilis and may be reduced if recipients receive ceftriaxone.

Effect of pretransplant dialysis modalities on pancreas-kidney transplant outcomes: a systematic review and meta-analysis.

BACKGROUND: The impact of different pretransplant dialysis modalities on post-transplant outcomes for pancreas-kidney transplantation is currently unclear. This study aims to assess the association between pretransplant dialysis modalities [hemodialysis (HD) and peritoneal dialysis] and outcomes following pancreas-kidney transplantation. METHODS: The authors searched PubMed, EMBASE, and the Cochrane Library for relevant studies published from inception until 1 December 2023. The authors included studies that examined the relationship between pretransplant dialysis modalities and clinical outcomes for pancreas-kidney transplantation. The primary outcomes considered were patient, pancreas and kidney graft survival, and intra-abdominal infection. RESULTS: A total of 13 studies involving 1503 pancreas-kidney transplant recipients were included. Pretransplant HD was associated with improved pancreas graft survival (hazard ratio = 0.71, 95% confidence interval: 0.51-0.99, I ²=12%) and a decreased risk of intra-abdominal infection [odds ratio (OR)=0.69, 95% CI: 0.51-0.93, I ²=5%). However, no significant association was found between the dialysis modalities and patient or kidney graft survival. Furthermore, pretransplant HD was linked to a reduced risk of anastomotic leak (OR=0.32, 95% CI: 0.161-0.68, I ²=0%) and graft thrombosis (OR=0.56, 95% CI: 0.33-0.96, I ²=20%). CONCLUSION: Pretransplant HD is the preferred dialysis modality while awaiting pancreas-kidney transplantation, although well-designed prospective studies are needed to confirm these findings.

Continuous renal surface cooling technique (CSCT) in robotic-assisted kidney transplantation: technique and outcomes from a high-volume center: a prospective cohort study.

BACKGROUND: Robot-assisted kidney transplantation (RAKT) surgery is an advanced minimally invasive technique, albeit with extended surgical and kidney ischemia time. To safeguard kidney function, the authors have devised a continuous surface cooling method (CSCT) for intraoperative kidney cooling. MATERIALS AND METHODS: Patients receiving RAKT were divided into CSCT group and conventional group. The CSCT is a custom-designed apparatus composed of a single-layer plastic bag, featuring an inflow and an outflow that create a closed circuit for the continuous flow of cooling saline. The conventional group utilized ice slush for kidney graft cooling (Vattikuti Urology Institute-Medanta Technique, VUIMT). Patients who underwent open renal transplantation during the same period were also included in the study. All patients were subject to a minimum 2-month follow-up. And 1:3 propensity score matching was used to minimize selection bias. RESULTS: A total of 144 patients underwent CSCT, 47 underwent VUIMT, and 196 underwent open surgery were included in the study, while after matching, 129, 43, 129 patients were included in the three groups, respectively. The median follow-up time was 19 months. None of the patients experienced delayed graft function, patient mortality, or graft loss. After introducing the kidney into the abdominal cavity for 20 minutes, the surface temperature of the kidney in the CSCT group was notably lower compared to the VUIMT group (15.42±0.88 vs. 21.74±2.53°C, P =0.001). This temperature disparity became more pronounced at 65 min (19.74±1.61 vs. 29.82±1.63°C, P <0.001). At both 3 and 7 days post-transplantation, creatinine levels in the VUIMT group were significantly higher than those in the CSCT and open surgery groups (at 3 days, 244.13±45.61 vs. 182.51±55.47 in CSCT group, P <0.001, or vs. 182.77±61.32 in the open surgery group, P <0.001; at 7 days, 162.42±54.86 vs. 143.11±44.32 in the CSCT group, P <0.001, or vs. 135.23±45.27 in the open surgery group, P <0.001). No differences were observed in blood creatinine, estimated glomerular filtration rate, and perioperative complications between the CSCT and open surgery groups. CONCLUSION: The CSCT presents a significant advantage over the traditional VUIMT method in terms of kidney cooling and early postoperative kidney function preservation. Additional research is required to ascertain whether the CSCT can enhance the long-term prognosis of kidney transplant recipients.

Sarcopenic obesity is associated with adverse outcomes after kidney transplantation: a retrospective cohort study.

PURPOSE: Sarcopenia was found to be a poor prognostic factor in kidney transplant recipients, but the role of sarcopenia obesity remains unclear. This study aimed to explore the effect of sarcopenic obesity on kidney transplantation. METHODS: A retrospective analysis was performed on kidney transplant recipients between 2015 and 2019. Pretransplant CT scans were utilized to assess sarcopenia and visceral obesity. Based on the presence or absence of sarcopenia and visceral obesity, the recipients were classified into four distinct groups. RESULTS: The recipients were categorized into four groups based on their characteristics: the nonsarcopenic nonobesity group (n = 493, 49.85%), the nonsarcopenic obesity group (n = 248, 25.08%), the sarcopenic nonobesity group (n = 188, 19.01%), and the sarcopenic obesity group (n = 60, 6.07%). Multivariate analysis, identified sarcopenic obesity was as an independent risk factor for mortality following kidney transplantation (adjusted hazard ratio, 5.861; 95% confidence interval [CI]: 1.627-21.108; P = 0.007). Additionally, sarcopenic obesity was associated with an increased risk of delayed graft function (adjusted odds ratio [aOR], 3.342; 95% CI 1.421-7.745; P = 0.005), perioperative incision infection (aOR, 9.654; 95% CI 1.572-60.648; P = 0.011), perioperative pulmonary infection (aOR, 2.557; 95% CI 1.208-5.215; P = 0.011), and readmission within 3 months (aOR, 2.100; 95% CI 1.051-4.017; P = 0.029). While sarcopenic obesity was found to be associated with impaired graft renal function, it did not show a significant correlation with death-censored graft survival or quality of life. CONCLUSION: The presence of sarcopenic obesity prior to kidney transplantation represents an independent risk factor for mortality, and it is also linked to a range of unfavorable outcomes.

Myosteatosis is associated with poor survival after kidney transplantation: a large retrospective cohort validation.

PURPOSE: We aim to establish diagnostic thresholds of sarcopenia and myosteatosis based on CT measurements, and to validate their prognostic value in a large cohort of kidney transplant recipients. METHODS: Local healthy population with abdominal CT between 2010 and 2022, and patients underwent kidney transplantation between 2015 and 2019 at our center were retrospectively included. The skeletal muscle index and muscle attenuation of abdominal muscles were calculated based on CT image at the middle of the third lumbar vertebra. Primary endpoints included all-cause mortality and death censored allograft survival. RESULTS: Age- and sex-specific thresholds for sarcopenia and myosteatosis were established based on 1598 healthy local population. The final patient cohort consisted of 992 kidney transplant recipients (median age 34 years, interquartile range 28-44 years; 694 males), including 33 (3.3%) with sarcopenia and 95 (9.5%) with myosteatosis. Multivariate analysis revealed myosteatosis (adjusted hazard ratio = 3.08, p = 0.022) was an independent baseline risk factor of mortality after adjusting for age, the history of cancer, and the history of cardiovascular event. Multivariate analysis found preemptive transplantation (adjusted hazard ratio = 0.36, p = 0.037) was an independent protective factor of allograft loss. No difference was found in the prognosis between kidney transplant recipients with and without sarcopenia. CONCLUSION: Myosteatosis was an independent risk factor of mortality after kidney transplantation, but sarcopenia was not. Neither sarcopenia nor myosteatosis was associated with graft loss.

Effect of pretransplant sarcopenia on patient and graft outcomes in solid organ transplant recipients: A systematic review and meta-analysis.

The relationship between sarcopenia and prognosis in solid organ transplantation recipients (SOTr) remains unverified. We aimed to quantify the prevalence of pretransplant sarcopenia and its effect on patient and graft survival in SOTr. We used PubMed, EMBASE, Cochrane Library and Web of Science to search relevant studies published in English (from inception to December 31, 2021). Prospective and retrospective cohort studies that reported the prevalence of sarcopenia before transplant or the association between sarcopenia and clinical outcomes in SOTr were included. Primary outcomes were the prevalence of sarcopenia and its impact on patient and graft survival. Secondary outcomes included perioperative complications, acute rejection, length of hospital stay, length of intensive care unit stay (ICU LOS) and early readmission. Thirty-nine studies involving 5792 patients were included. Pooled prevalence of sarcopenia amongst SOTr candidates was 40 % (95 % confidence interval [CI]: 34%-47 % and I2 = 97 %). Sarcopenia was associated with increased risk of death (hazard ratio [HR] = 1.87, 95 % CI: 1.46-2.41 and I2 = 60 %), poor graft survival (HR = 1.71, 95 % CI: 1.16-2.54 and I2 = 57 %) and increased liver graft loss (HR = 1.43, 95 % CI: 1.03-1.99 and I2 = 38 %). Patients with sarcopenia demonstrated increased incidence of perioperative complications (risk ratio [RR] = 1.34, 95 % CI: 1.17-1.53 and I2 = 40 %), long ICU LOS (mean difference = 2.31 days, 95 % CI: 0.58-4.04 and I2 = 97 %) and decreased risk of acute rejection (RR = 0.61, 95 % CI: 0.42-0.89 and I2 = 0 %). In Conclusion, sarcopenia is prevalent in SOTr candidates and associated with death and graft loss. Identifying sarcopenia before transplantation and intervening may improve long-term outcomes.

IGRA-based INH regimen for prevention of active tuberculosis after kidney transplantation: A single-centre retrospective study.

OBJECTIVES: To evaluate the effectiveness and safety of Interferon-gamma release Assay (IGRA)-based isoniazid (INH) prophylaxis strategy to prevent tuberculosis (TB) infection in kidney transplantation (KT) with a risk of TB occurrence. METHODS: Adult KT recipients (KTRs) between June 2014 and July 2021 were retrospectively enrolled. The development of active TB after KT was evaluated. RESULTS: Of 925 KTRs, 111 (12.0%) developed active TB. Among the 501 KTRs at a risk of TB occurrence, 70 (14.0%) patients developed active TB, while 41 (9.7%) of 424 patients without risk factors developed active TB (P = 0.05). Two hundred thirty-nine KTRs received IGRA test with 62 (25.9%) were positive. None of IGRA positive patients (0/40) receiving INH prophylaxis developed active TB, whereas 8 out of 22 patients who had positive IGRA results without INH prophylaxis developed active TB (0 vs. 36.4%, P < 0.01). Of note, for those in risk group but with negative IGRA result, no active TB was found even without INH prophylaxis. Although alanine aminotransferase and aspartate aminotransferase in INH prevention group were higher than those before treatment, they did not exceed three-fold of limit of reference range. CONCLUSIONS: IGRA-based INH treatment is an effective and safe protocol to prevent the development of active TB in KTRs.

Risk factors and outcomes of IgA nephropathy recurrence after kidney transplantation: a systematic review and meta-analysis.

Background: IgA nephropathy may recur in patients receiving kidney transplantation due to IgA nephropathy induced renal failure. The risk factors for recurrence are still at issue. The aim of this study was to conduct a systematic review and meta-analysis to assess risk factors and outcomes for IgA nephropathy recurrence. Methods: We used PubMed, EMBASE, Cochrane Library, Web of Science, Scopus, CNKI, WanFang, VIP and CBM to search for relevant studies published in English and Chinese. Cohort or case-control studies reporting risk factors or outcomes for IgA nephropathy recurrence were included. Results: Fifty-eight studies were included. Compare to no recurrence group, those with IgAN recurrence had younger age (mean difference [MD]=-4.27 years; risk ratio [RR]=0.96), younger donor age (MD=-2.19 years), shorter time from IgA nephropathy diagnosis to end stage renal disease (MD=-1.84 years; RR=0.94), shorter time on dialysis (MD=-3.14 months), lower human leukocyte-antigen (HLA) mismatches (MD=-0.11) and HLA-DR mismatches (MD=-0.13). HLA-B46 antigen (RR=0.39), anti-IL-2-R antibodies induction (RR=0.68), mycophenolate mofetil (RR=0.69), and pretransplant tonsillectomy (RR=0.43) were associated with less IgAN recurrence. Of note, male recipient gender (RR=1.17), related donor (RR=1.53), retransplantation (RR=1.43), hemodialysis (RR=1.68), no induction therapy (RR=1.73), mTOR inhibitor (RR=1.51), angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers (RR=1.63) were risk factors for IgAN recurrence. Recurrence increased the risk of graft loss (RR=2.19). Conclusions: This study summarized the risk factors for recurrence of IgA nephropathy after kidney transplantation. Well-designed prospective studies are warranted for validation. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=377480, identifier CRD42022377480.

Higher serum selenium concentration is associated with lower risk of all-cause and cardiovascular mortality among individuals with chronic kidney disease: A population-based cohort study of NHANES.

Background: Selenium is an essential nutrient and trace element required for human health and plays an important role in antioxidative and anti-inflammatory processes. However, the long-term impact of selenium levels on the health of patients with chronic kidney disease remains unclear. Method: Participants in this study were 3,063 CKD adults from the Third National Health and Nutrition Examination Survey (NHANES 1999-2000, 2003-2004, and 2011-2018). The mortality status and the cause of death of the study participants were obtained from the National Death Index records. For all-cause and cardiovascular disease (CVD) mortality, the models employed to estimate hazard ratios (HRs) and 95% CI were Cox proportional hazard models and competing risk models, respectively. Result: During the follow-up period, 884 deaths occurred, including 336 heart-disease-associated deaths. The median (IQR) concentration of serum selenium was 181.7 (156.1, 201.5) µg/L. After full adjustment, serum selenium levels were associated with a decreased risk of mortality in patients with CKD, including all-cause and CVD mortality (P < 0.001). The multivariate-adjusted HRs (95%CI) were 0.684 (0.549-0.852) for all-cause mortality (P trend < 0.001) and 0.513 (0.356-0.739) for CVD mortality (P trend < 0.001) when selenium concentrations were compared according to the extreme quartiles. Selenium levels are inversely associated with an increased risk of all-cause mortality and CVD mortality. Similar results were observed in subgroup and sensitivity analyses. Conclusion: Higher serum selenium concentration was independently associated with a decreased risk of all-cause and CVD mortality in patients with CKD.

Optimizing the use of nirmatrelvir/ritonavir in solid organ transplant recipients with COVID-19: A review of immunosuppressant adjustment strategies.

The coronavirus disease 2019 (COVID-19) pandemic has caused a significant burden of morbidity and mortality worldwide, with solid organ transplant recipients (SOTRs) being particularly vulnerable. Nirmatrelvir and ritonavir have demonstrated the potential for reducing the risk of hospitalization and death in patients with mild-to-moderate COVID-19. However, ritonavir has a strong drug-drug interaction with CYP3A-dependent drugs such as calcineurin inhibitors, potentially leading to rapid increases in blood concentration. As SOTRs are commonly prescribed immunosuppressants, co-administration with nirmatrelvir/ritonavir requires careful consideration. To address this issue, we conducted a literature review to evaluate the use and adverse effects of nirmatrelvir/ritonavir in SOTRs and explore feasible immunosuppressant adjustment regimens. Our findings suggest that nirmatrelvir/ritonavir could be a feasible treatment option for COVID-19 in SOTRs, provided that appropriate immunosuppressive drug management is in place during co-administration. Although prescribing the novel anti-SARS-CoV-2 drug to transplant recipients poses challenges, potential strategies to overcome these issues are discussed. Further studies are needed to determine the optimal dosing strategies of nirmatrelvir/ritonavir, immunosuppressant adjustment, and monitoring in this patient population.

Torque-teno virus for the prediction of graft rejection and infection disease after kidney transplantation: A systematic review and meta-analysis.

Torque teno virus (TTV) is a promising novel marker for quantifying the immune function in solid organ recipients, whose diagnostic accuracy of acute rejection (AR) and infection after kidney transplantation (KT) has not been evaluated. We performed a systematic review and meta-analysis to evaluate the diagnostic accuracy of TTV for discriminating AR and infection after KT. Eleven studies were included in the meta-analysis. Seven studies focused on the diagnostic accuracy of TTV for AR, and the pooled analysis indicated patients who developed AR had a significant lower TTV viral DNA load (log10 copies/mL, MD: -0.74, p < 0.01). The pooled sensitivity, specificity, and area under the receiver operating characteristics curve for TTV in AR differentiation were 0.61 (0.36-0.82), 0.81 (0.64-0.91), and 0.79 (0.75-0.82), respectively. The overall diagnostic odds ratio (DOR) was 6.74 (2.60-17.50), positive likelihood ratio (PLR) was 3.22 (1.75-5.95), and negative likelihood ratio (NLR) was 0.48 (0.27-0.84), respectively. Similarly, seven studies investigated the infection discrimination and found that patients who subsequently developed posttransplant infection had higher plasma TTV DNA loads (log10 copies/mL, MD: 0.65; p < 0.01) than those remaiing infection-free. Pooled sensitivity, specificity, and area under the receiver operating characteristics curve for TTV in infection differentiation were 0.72 (0.39-0.91), 0.57 (0.30-0.80), and 0.68 (0.64-0.72), respectively. The overall DOR was 3.28 (95% confidence interval [CI]: 2.08-5.17), the pooled PLR and NLR were 1.65 (95% CI: 1.25-2.18) and 0.50 (95% CI: 0.29-0.86), respectively. TTV might be a modest indicator for risk stratification of AR after KT, but it is a poor to discriminate posttransplant infection.

Overexpression of miR-92a attenuates kidney ischemia-reperfusion injury and improves kidney preservation by inhibiting MEK4/JNK1-related autophagy.

BACKGROUND: Kidney ischemia-reperfusion injury is inevitable in kidney transplantation, and is essential for primary graft dysfunction and delayed graft function. Our previous study has proved that miR-92a could ameliorate kidney ischemia-reperfusion injury, but the mechanism has not been studied. METHODS: This study conducted further research on the role of miR-92a in kidney ischemia-reperfusion injury and organ preservation. In vivo, mice models of bilateral kidney ischemia (30 min), cold preservation after ischemia (cold preservation time of 6, 12, and 24 h), and ischemia-reperfusion (reperfusion time of 24, 48, and 72 h) were established. Before or after modeling, the model mice were injected with miR-92a-agomir through the caudal vein. In vitro, the hypoxia-reoxygenation of HK-2 cells was used to simulate ischemia-reperfusion injury. RESULTS: Kidney ischemia and ischemia-reperfusion significantly damaged kidney function, decreased the expression of miR-92a, and increased apoptosis and autophagy in kidneys. miR-92a agomir tail vein injection significantly increased the expression of miR-92a in kidneys, improved kidney function, and alleviated kidney injury, and the intervention before modeling achieved a better effect than after. Moreover, miR-92a agomir significantly reduced the apoptosis and autophagy in HK-2 cells induced by hypoxia, hypoxia-reoxygenation, and rapamycin, while miR-92a antagomir had opposite effects. Furthermore, mitogen-activated protein kinase, c-Jun NH (2) terminal kinase, caspase 3, Beclin 1, and microtubule-associated protein 1 light chain 3B were inhibited by overexpression of miR-92a both in vivo and in vitro, which in turn reduced apoptosis and autophagy. CONCLUSIONS: Our results prove that overexpression of miR-92a attenuated kidney ischemia-reperfusion injury and improved kidney preservation, and intervention before ischemia-reperfusion provides better protection than after.

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.

Exogenous pericyte delivery protects the mouse kidney from chronic ischemic injury.

Pericytes are considered reparative mesenchymal stem cell-like cells, but their ability to ameliorate chronic ischemic kidney injury is unknown. We hypothesized that pericytes would exhibit renoprotective effects in murine renal artery stenosis (RAS). Porcine kidney-derived pericytes (5 × 105) or vehicle were injected into the carotid artery 2 wk after the induction of unilateral RAS in mice. The stenotic kidney glomerular filtration rate and tissue oxygenation were measured 2 wk later using magnetic resonance imaging. We subsequently compared kidney oxidative stress, inflammation, apoptosis, fibrosis, and systemic levels of oxidative and inflammatory cytokines. Treatment of xenogeneic pericytes ameliorated the RAS-induced loss of perfusion, glomerular filtration rate, and atrophy in stenotic kidneys and restored cortical and medullary oxygenation but did not blunt hypertension. Ex vivo, pericytes injection partially mitigated RAS-induced renal inflammation, fibrosis, oxidative stress, apoptosis, and senescence. Furthermore, coculture with pericytes in vitro protected pig kidney-1 tubular cells from injury. In conclusion, exogenous delivery of renal pericytes protects the poststenotic mouse kidney from ischemic injury, underscoring the therapeutic potential role of pericytes in subjects with ischemic kidney disease.NEW & NOTEWORTHY Our study demonstrates a novel pericyte-based therapy for the injured kidney. The beneficial effect of pericyte delivery appears to be mediated by ameliorating oxidative stress, inflammation, cellular apoptosis, and senescence in the stenotic kidney and improved tissue hypoxia, vascular loss, fibrosis, and tubular atrophy. Our data may form the basis for pericyte-based therapy, and additional research studies are needed to gain further insight into their role in improving renal function.

Transplant outcomes of 100 cases of living-donor ABO-incompatible kidney transplantation.

BACKGROUND: Although ABO-incompatible (ABOi) kidney transplantation (KT) has been performed successfully, a standard preconditioning regimen has not been established. Based on the initial antidonor ABO antibody titers, an individualized preconditioning regimen is developed, and this study explored the efficacy and safety of the regimen. METHODS: From September 1, 2014, to September 1, 2020, we performed 1668 consecutive living-donor KTs, including 100 ABOi and 1568 ABO-compatible (ABOc) KTs. ABOi KT recipients (KTRs) with a lower antibody titer (≤1:8) were administered oral immunosuppressive drugs (OIs) before KT, while patients with a medium titer (1:16) received OIs plus antibody-removal therapy (plasma exchange/double-filtration plasmapheresis), patients with a higher titer (≥1:32) were in addition received rituximab (Rit). Competing risk analyses were conducted to estimate the cumulative incidence of infection, acute rejection (AR), graft loss, and patient death. RESULTS: After propensity score analyses, 100 ABOi KTRs and 200 matched ABOc KTRs were selected. There were no significant differences in graft and patient survival between the ABOi and ABOc groups (P  = 0.787, P  = 0.386, respectively). After using the individualized preconditioning regimen, ABOi KTRs showed a similar cumulative incidence of AR (10.0% υs . 10.5%, P  = 0.346). Among the ABOi KTRs, the Rit-free group had a similar cumulative incidence of AR ( P  = 0.714) compared to that of the Rit-treated group. Multivariate competing risk analyses revealed that a Rit-free regimen reduced the risk of infection (HR: 0.31; 95% CI: 0.12-0.78, P  = 0.013). Notably, antibody titer rebound was more common in ABOi KTRs receiving a Rit-free preconditioning regimen ( P  = 0.013) than those receiving Rit. ABOi KTRs with antibody titer rebound had a 2.72-fold risk of AR (HR: 2.72, 95% CI: 1.01-7.31, P  = 0.048). ABOi KTRs had similar serum creatinine and estimated glomerular filtration rate compared to those of ABOc KTRs after the first year. CONCLUSIONS: An individualized preconditioning regimen can achieve comparable graft and patient survival rates in ABOi KT with ABOc KT. Rit-free preconditioning effectively prevented AR without increasing the risk of infectious events in those with lower initial titers; however, antibody titer rebound should be monitored.

A CRISPR-based ultrasensitive assay detects attomolar concentrations of SARS-CoV-2 antibodies in clinical samples.

CRISPR diagnostics are powerful tools for detecting nucleic acids but are generally not deployable for the detection of clinically important proteins. Here, we report an ultrasensitive CRISPR-based antibody detection (UCAD) assay that translates the detection of anti-SARS-CoV-2 antibodies into CRISPR-based nucleic acid detection in a homogeneous solution and is 10,000 times more sensitive than the classic immunoassays. Clinical validation using serum samples collected from the general population (n = 197), demonstrates that UCAD has 100% sensitivity and 98.5% specificity. With ultrahigh sensitivity, UCAD enables the quantitative analysis of serum anti-SARS-CoV-2 levels in vaccinated kidney transplant recipients who are shown to produce "undetectable" anti-SARS-CoV-2 using standard immunoassay. Because of the high sensitivity and simplicity, we anticipate that, upon further clinical validation against large cohorts of clinical samples, UCAD will find wide applications for clinical uses in both centralized laboratories and point-of-care settings.