The effectiveness of nirmatrelvir/ritonavir regimen in hospitalized renal transplant patients with prolonged COVID-19 infection: a multicenter clinical experience.

OBJECTIVES: Effectiveness of nirmatrelvir/ritonavir (NR) in kidney transplant recipients (KTRs) infected COVID-19 for more than 5 days has not been evaluated. METHODS: In this multicenter retrospective study, 85 KTRs with COVID-19 were enrolled, including 50 moderate, 21 severe, and 14 critical patients. RESULTS: The median time from onset to starting NR treatment was 14 (IQR, 11-19) days. Before NR treatment, 96.5% patients reduced use of antimetabolites. They also stopped using calcineurin inhibitors (CNI) 12-24 hours before NR treatment, with CNI concentrations well-controlled during NR treatment. The use of intravenous corticosteroids increased with COVID-19 severity. The median time to reach viral negative conversion was 5 (IQR, 4-8) days for all patients. For moderate and severe COVID-19 patients, they had a low rate of ICU admission (1.4%), exacerbation requiring upgraded oxygen therapy (5.6%), and dialysis (2.8%); no intubation and mechanical ventilation, and no deaths were observed. Patients with critical COVID-19 had a low mortality rate (7.1%). CONCLUSIONS: A regimen including NR for clearing SARS-CoV-2 along with reducing immunosuppressants and using intravenous corticosteroids is associated with lower rates of exacerbation and mortality in KTRs who have moderate to critical SARS-CoV-2 infection and the virus still present after 5 days.

Combining Clinical Parameters and Acute Tubular Injury Grading Is Superior in Predicting the Prognosis of Deceased-Donor Kidney Transplantation: A 7-Year Observational Study.

Background: We developed a pragmatic dichotomous grading criterion to stratify the acute tubular injury (ATI) of deceased-donor kidneys. We intended to verify the predictive value of this criterion for the prognosis of deceased-donor kidney transplantation. Methods: The allografts with ATI were classified into severe and mild groups. Severe ATI was defined as the presence of extreme and diffuse flattening of the tubular epithelial cells, or denudement of the tubular basement membrane. The clinical delayed graft function (DGF) risk index was calculated based on a regression model for posttransplant DGF using 17 clinical parameters related to donor-recipient characteristics. Results: A total of 140 recipients were enrolled: 18 severe and 122 mild ATI. Compared with the mild ATI group, the severe ATI group had more donors after cardiac death, higher median donor terminal serum creatinine level (dScr), and longer median cold ischemia time. Severe ATI had a higher DGF rate (55.6% vs 14.6%, p < 0.001), longer DGF recovery time (49.6 vs 26.3 days, p < 0.001), and a lower estimated glomerular filtration rate (eGFR) at 1 month (23.5 vs 54.0 ml/min/1.73 m2, p < 0.001), 3 months (40.4 vs 59.0, p = 0.001), and 6 months after transplant (46.8 vs 60.3, p = 0.033). However, there was no significant difference in eGFR at 1 year or beyond, graft, and patient survival. The predictive value of combined dScr with ATI severity for DGF rate and DGF recovery time was superior to that of dScr alone. The predictive value of the combined DGF risk index with ATI severity for DGF was also better than that of the DGF risk index alone; however, the association of the DGF risk index with DGF recovery time was not identified. Chronic lesions including glomerulosclerosis, interstitial fibrosis, arterial intimal fibrosis, and arteriolar hyalinosis were associated with declined posttransplant 1-year eGFR. Conclusion: Based on our pragmatic dichotomous grading criterion for ATI in a preimplantation biopsy, donor kidneys with severe ATI increased DGF risk, prolonged DGF recovery, and decreased short-term graft function but demonstrated favorable long-term graft function. Our grading method can offer additive valuable information for assessing donor kidneys with acute kidney injury and may act as an effective supplementary index of the Banff criteria.

Metagenomic analysis reveals gestational diabetes mellitus-related microbial regulators of glucose tolerance.

AIMS: Recent studies have suggested a possible association between microbiota and gestational diabetes (GDM). However, the results are inconsistent. Our objective was to investigate further the relationship between GDM and microbiota and verify the potential microbial marker. METHODS: Two complementary approaches were used for the demonstration. First, we compared the gut microbial composition of 23 GDM patients and 26 non-GDM ethnically Chinese Han pregnant women, by using whole-metagenome shotgun sequencing of their stool samples collected at the third trimester. Second, we used Q-PCR (quantitative polymerase chain reaction) to evaluate the gut microbial composition in the stool samples from another cohort of 150 Chinese pregnant women (113 Control and 37 GDM), to further confirm the potential microbial marker. RESULTS: The gut microbiota of GDM women show lower albeit not statistically significant (p = 0.18) alpha diversity at the species level than non-GDM women. However, the species-level beta-diversity or between-sample diversity measured by Bray-Curtis distance shows significant differences (p < 2.2e-16) between the two groups. The species Bacteroides dorei positively correlated with both OGTT (oral glucose tolerance test) 0-Hour (p = 0.0099) and OGTT 1-Hour (p = 0.0070). There is a similar trend between Bacteroides sp. 3_1_33FAA and both OGTT 0-Hour (p = 0.014) and OGTT 1-Hour (p = 0.0101) response variables. The species Alistipes putredinis negatively correlated with OGTT 1-Hour (p = 0.0172) and OGTT 2-Hour (p = 0.0147). Q-PCR validation further confirmed the association between the glucose tolerance loci of Bacteroides dorei and OGTT response. CONCLUSIONS: Gut microbiome is related to the diabetic status of Chinese women during pregnancy. Specific species such as Bacteroides dorei associate with glucose response and could be potential monitoring and therapeutic microbial markers for GDM.