Plasma D-dimer levels are associated with disease progression in diabetic nephropathy: a two-center cohort study.

BACKGROUND: This study aimed to investigate the relationship between plasma D-dimer levels, clinicopathological features, and clinical outcomes in patients with biopsy-proven diabetic nephropathy (DN). METHODS: A total of 137 patients with biopsy-proven DN were enrolled in this two-center cohort study. Patients were stratified into tertiles based on plasma D-dimer levels. We investigated the relationship between plasma D-dimer levels and clinical outcomes, including a composite of death, a 40% decline in estimated glomerular filtration rate (e-GFR) from baseline, or end-stage renal disease (ESRD) (defined as e-GFR < 15 mL/min/1.73 m2 or need for renal replacement therapy including hemodialysis, peritoneal dialysis, or kidney transplantation), assessed using Cox regression models with adjustment for confounders. RESULTS: At baseline, the mean age was 52.61 ± 11.63 years, and the mean e-GFR was 58.02 ± 28.77 mL/min/1.73 m2. During a median 26-month follow-up period, 65 (47% of patients) achieved clinical outcomes. Compared with the low plasma D-dimer level group, those with higher plasma D-dimer levels were more likely to have higher 24-h proteinuria (p = .002), lower e-GFR (p = .001), lower hemoglobin (p = .001), a higher glomerular lesion class (p = .03), and higher interstitial fibrosis and tubular atrophy (IFTA) scores (p = .002). After adjustment for demographic, DN-specific covariates, and treatments, it was observed that a higher tertile of plasma D-dimer was nonlinearly associated with an increased risk of the clinical outcomes (Hazard Ratio (HR) for tertile 2 vs. 1, 1.7; 95% Confidence Interval (CI), 0.80-3.75; HR for tertile 3 vs. 1, 2.2; 95% CI, 0.93-5.27; p for trend = .001) in the Cox proportional hazards models. CONCLUSION: In this study, DN patients with higher levels of plasma D-dimer had higher 24-h proteinuria, lower e-GFR, a higher glomerular lesion class, and higher IFTA scores. Furthermore, a high level of plasma D-dimer was nonlinearly associated with DN progression.

The application of podocyte antigen PLA2R and anti-PLA2R antibody in the diagnosis and treatment of membranous nephropathy.

BACKGROUND: The application of podocyte antigen M-type phospholipase A2 receptor (PLA2R, GAg) and serum anti-PLA2R antibody (SAb) in predicting the prognosis of membrane nephropathy (MN) was controversial. METHOD: 328 biopsy-proven MN patients were divided into three phenotypes, 182 MN patients with GAg+/SAb+, 118 MN patients with GAg+/SAb-, and 28 MN patients with GAg-/SAb-. The baseline clinicopathological characteristics, therapy response, and prognosis were compared among the three groups. Cox regression analysis was performed to assess predictors of remission. Anti-PLA2R antibody was analyzed by receiver operating characteristic curve to find the optimal titer for MN diagnosis. RESULT: Lower eGFR (p = 0.009), higher UPCR (p < 0.001), and lower serum albumin (p < 0.001) were observed in GAg+/SAb+ MN patients, compared to GAg+/SAb- MN patients. More GAg+/SAb+ MN patients received cyclophosphamide (CTX) combined with glucocorticoids and calcineurin inhibitors (CNI) based therapy than the other two groups (p = 0.015 and p = 0.023, respectively). No significant difference was observed among the three groups in terms of complete remission, relapse, and developing ESRD. SAb+ status was an independent predictor for no remission (hazard ratio 1.378, 95% confidence interval 1.023 to 1.855; p = 0.035). The optimal cutoff value for anti-PLA2R antibody to predict MN was 2.055 RU/mL (sensibility 0.802, specificity 0.970). CONCLUSION: GAg+/SAb+ MN patients were related to more severe clinical manifestations and more requisition of immunosuppressive treatment. Positive anti-PLA2R antibody was an independent predictor for no remission. An anti-PLA2R antibody above 2.055 RU/mL can be a suggestive indicator of MN diagnosis in patients with proteinuria.

Donor-Derived Human Parvovirus B19 Infection in Kidney Transplantation.

Background: Donor-derived human parvovirus B19 (B19V) infections are rarely reported. Thus, its incidence in kidney transplantation is still unknown due to lack of surveillance studies. Similarly, whether the donor needs to be routinely screened for B19V and whether the kidneys from those with B19V DNAemia could be accepted also remain unknown. Methods: This retrospective study aims to evaluate the donor-derived B19V infections occurring in 823 living and 1,225 deceased donor kidney transplantations from January 2016 to December 2020. The serum viral load of living donors and their corresponding recipients was evaluated before and after transplantation. Meanwhile, for the deceased donor kidney transplantation, the serum viral load of recipients was only tested after transplantation; if recipients of a deceased donor subsequently developed B19V infection, the serum viral load of recipients and their corresponding donors before transplantation would then be further traced. Results: A total of 15 living donors were B19V DNAemia positive before the donation, of which B19V DNAemia occurred in three corresponding recipients. In deceased donor kidney transplantation, DNAemia occurred simultaneously in 18 recipients and their corresponding nine donors. A progressive decline in hemoglobin and reticulocyte count could be observed in one living donor recipient and other 11 deceased donor recipients, which were all well controlled by treatment eventually. Conclusion: The incidence of donor-derived B19V infection was 0.4% and 1.5% in living and deceased kidney transplantations, respectively. B19V was seemingly unnecessary to be routinely screened for the donor. Moreover, kidneys of the donors with B19V infection were acceptable.

Foscarnet Therapy for Pure Red Cell Aplasia Related to Human Parvovirus B19 Infection in Kidney Transplant Recipients: A Preliminary Exploration.

BACKGROUND: Parvovirus B19-associated pure red cell aplasia (PVB19-PRCA) is an uncommon but serious complication after kidney transplantation. Currently, intravenous immunoglobulin (IVIG) is preferred as the first-line treatment for PVB19-PRCA, but presents with disadvantages of disease recurrence and expensive cost. In this context, we propose that foscarnet therapy for kidney transplantation recipients (KTR) with PVB19-PRCA may be an alternative scenario. No related study has been reported, and we performed this study to assess the efficacy and safety of foscarnet for PVB19-associated PRCA in KTR. METHODS: We conducted a retrospective review of PVB19-PRCA in KTR at our center over 9-year period. The data on therapy and outcomes in all cases treated with foscarnet are detailed records and summarized. RESULTS: Among our 68 patients, PVB19-PRCA was confirmed in 50 based on inclusion/exclusion criteria. All patients presented with refractory anemia and low reticulocyte percentage (<0.5%), the mean hemoglobin of patients was 79.8±12.6g/L at the time of PVB19-PRCA was identified. The median serum genome copy number of parvovirus B19 at diagnosis was 9.6 log10 copies per milliliter. A total of 11 patients received foscarnet therapy, of 10 patients responded well to the treatment and maintained no recurrence. But 1 patient had a poor response to foscarnet therapy. Except for this patient, the mean hemoglobin level gradually increased from 68.5±9.3 g/L to 73.2±8.8 g/L, and the mean percentage of reticulocytes steadily increased from 0.1±0.0% to 7.6±2.9% after foscarnet therapy. The median serum genome copy number of parvovirus B19 decreased from 9.8 log10 to 6.1 log10 copies per milliliter. There was no significant difference (P=0.61, 0.60) in serum creatinine and glomerular filtration rate before and after foscarnet treatment. At the latest follow-up, the mean hemoglobin was 131.5±12.5 g/L and the hemoglobin correction occurred in all patients. CONCLUSION: Foscarnet therapy doesn't seem to be worse than IVIG for PVB19-PRCA in KTR, and it can be an alternative option.

Application of Metagenomic Next-Generation Sequencing to Diagnose Pneumocystis jirovecii Pneumonia in Kidney Transplantation Recipients.

BACKGROUND Pneumocystis jirovecii pneumonia (PJP) is one of the common opportunistic infections diagnosed in kidney transplantation recipients. It is difficult to identify early by use of classic tools such as Grocott-Gomori stains and polymerase chain reaction (PCR). Metagenomic next-generation sequencing (mNGS) is accurate, unbiased, and sensitive, and is promising in PJP diagnosis. MATERIAL AND METHODS Data on kidney transplantation patients diagnosed with PJP were retrospectively analyzed. The sensitivity and specificity of different tools such as mNGS, laboratory tests, and Grocott-Gomori stains for PJP diagnosis were compared. All recipients were treated with trimethoprim-sulfamethoxazole (TMP-SMX). RESULTS There were a total of 12 kidney transplantation recipients diagnosed with PJP based on mNGS in our center from January 01, 2020 to October 27, 2020. Highly variable numbers of sequence reads for P. jiroveci (19 to 1041285) showed diagnostic significance. Bronchoalveolar lavage fluid (BALF) samples were tested by Grocott-Gomori staining, with only 6 of 11 (54.5%) positive. Other routine laboratory tests like routine blood tests, blood biochemistry, procalcitonin (PCT), immune function, (1,3)-ß-d-glucan (BG), serum galactomannan (GM), and C-reactive protein (CRP) showed even lower efficacy. TMP-SMX appeared to be the ideal therapy for kidney transplantation recipients with PJP. CONCLUSIONS mNGS has utility in the diagnosis of PJP and mixed infections in kidney transplantation recipients, and TMP-SMX could be the ideal therapeutic drug for kidney transplantation recipients suffering from PJP.

Cross-host evolution of severe acute respiratory syndrome coronavirus in palm civet and human.

The genomic sequences of severe acute respiratory syndrome coronaviruses from human and palm civet of the 2003/2004 outbreak in the city of Guangzhou, China, were nearly identical. Phylogenetic analysis suggested an independent viral invasion from animal to human in this new episode. Combining all existing data but excluding singletons, we identified 202 single-nucleotide variations. Among them, 17 are polymorphic in palm civets only. The ratio of nonsynonymous/synonymous nucleotide substitution in palm civets collected 1 yr apart from different geographic locations is very high, suggesting a rapid evolving process of viral proteins in civet as well, much like their adaptation in the human host in the early 2002-2003 epidemic. Major genetic variations in some critical genes, particularly the Spike gene, seemed essential for the transition from animal-to-human transmission to human-to-human transmission, which eventually caused the first severe acute respiratory syndrome outbreak of 2002/2003.

Civets are equally susceptible to experimental infection by two different severe acute respiratory syndrome coronavirus isolates.

Severe acute respiratory syndrome (SARS) was caused by a novel virus now known as SARS coronavirus (SARS-CoV). The discovery of SARS-CoV-like viruses in masked palm civets (Paguma larvata) raises the possibility that civets play a role in SARS-CoV transmission. To test the susceptibility of civets to experimental infection by different SARS-CoV isolates, 10 civets were inoculated with two human isolates of SARS-CoV, BJ01 (with a 29-nucleotide deletion) and GZ01 (without the 29-nucleotide deletion). All inoculated animals displayed clinical symptoms, such as fever, lethargy, and loss of aggressiveness, and the infection was confirmed by virus isolation, detection of viral genomic RNA, and serum-neutralizing antibodies. Our data show that civets were equally susceptible to SARS-CoV isolates GZ01 and BJ01.

Antibodies to SARS coronavirus in civets.

Using three different assays, we examined 103 serum samples collected from different civet farms and a market in China in June 2003 and January 2004. While civets on farms were largely free from SARS-CoV infection, approximately 80% of the animals from one animal market in Guangzhou contained significant levels of antibody to SARS-CoV, which suggests no widespread infection among civets resident on farms, and the infection of civets in the market might be associated with trading activities under the conditions of overcrowding and mixing of various animal species.