Project description:Several human polyomaviruses of unknown prevalence and pathogenicity have been identified, including human polyomavirus 9 (HPyV9). To determine rates of HPyV9 infection among immunosuppressed patients, we screened serum samples from 101 kidney transplant patients in the Netherlands for HPyV9 DNA and seroreactivity. A total of 21 patients had positive results for HPyV9 DNA; positivity rates peaked at 3 months after transplantation, but the highest viral loads were measured just after transplantation. During 18 months of follow-up, HPyV9 seroprevalence increased from 33% to 46% among transplant patients; seroprevalence remained stable at ≈30% in a control group of healthy blood donors in whom no HPyV9 DNA was detected. Further analysis revealed an association between detection of HPyV9 and detection of BK polyomavirus but not of cytomegalovirus. Our data indicate that HPyV9 infection is frequent in kidney transplant patients, but the nature of infection-endogenous or donor-derived-and pathogenic potential of this virus remain unknown.
Project description:Cryptococcosis is the third most common cause of invasive fungal infection in solid organ transplant recipients and cryptococcal meningitis (CM) its main clinical presentation. CM outcomes, as well as its clinical features and radiological characteristics, have not yet been considered on a large scale in the context of kidney transplantation (KT). We performed a nationwide retrospective study of adult patients diagnosed with cryptococcosis after KT between 2002 and 2020 across 30 clinical centers in France. We sought to describe overall and graft survival based on whether KT patients with cryptococcosis developed CM or not. Clinical indicators of CNS involvement and brain radiological characteristics were assessed. Eighty-eight cases of cryptococcosis were diagnosed during the study period, with 61 (69.3%) cases of CM. Mortality was high (32.8%) at 12 months (M12) but not significantly different whether or not patients presented with CM. Baseline hyponatremia and at least one neurological symptom were independently associated with CM (p < 0.001). Positive serum cryptococcal antigen at diagnosis was also significantly associated with CM (p < 0.001). On magnetic resonance imaging (MRI), three patterns of brain injury were identified: parenchymal, meningeal, and vascular lesions. Although CM does not affect graft function directly, it entails a grim prognosis.
Project description:Hepatitis E virus (HEV) is a leading cause of waterborne acute hepatitis in developing countries. In Europe, HEV causes a zoonotic disease and is hyperendemic in southern France. Four HEV genotypes (1 to 4) have been defined, and the most used classification divides them into 24 subtypes. Autochthonous European HEV strains belong in majority to genotype 3. Subtypes 3c, 3f, and 3e are representative of the HEV diversity in France. HEV causes chronic hepatitis in solid-organ transplant recipients in Europe, and viral characteristics associated with chronicity are poorly documented. We sequenced 343-nucleotide-long HEV genomic fragments from the serum of eight chronically infected kidney transplant recipients and a near-full-length genome in one case. We identified in four patients (50%) HEV of subtype 3i, not described previously in France. If shorter genomic fragments were used in phylogenetic analyses, these HEV sequences were clustered with open reading frame 2 (ORF2) fragments labeled as subtype 3c. At least five of the eight HEV 3i sequences recovered from humans in our phylogenetic analyses were from chronically infected kidney transplant recipients. These data show that the description of the prevalence and geographical distribution of HEV subtypes may be partially inaccurate and that criteria for classification as 3i and 3c should be clarified. Extended molecular virology analyses are required to improve knowledge of HEV epidemiology and determinants of chronic HEV infection.
Project description:OBJECTIVE:Native Americans suffer from lower rates of kidney transplantation compared with whites. Our goal was to elicit patients' perceptions of and attitudes about kidney transplant and the impact of financial burden and cultural taboos. DESIGN:This is an exploratory qualitative interview study of 12 Native American patients recruited after completion of the kidney transplant evaluation. SETTING:Semistructured interviews were conducted. Interviews were coded using inductive methods, followed by interpretive coding by the investigators. RESULTS:Thematic analysis revealed the following themes: (1) experience with kidney transplant education by the healthcare team; (2) cultural beliefs regarding kidney transplant; (3) personal motivation and attitude towards kidney transplant; (4) financial burden of kidney transplant and post-transplant care and (5) attitude about living donation.Most participants were educated about transplant as a treatment option after dialysis initiation. All patients in this study recognised that some taboos exist about the process of organ procurement and transplantation; however, the traditional views did not negatively impact their decision to pursue kidney transplant evaluation. Patients shared the common theme of preferring an organ from a living rather than a deceased person; however, the majority did not have a living donor and preferred not to receive an organ from a family member. Most patients did not perceive transplant-related cost as negatively impacting their attitude about receiving a transplant even for patients with below poverty level income. CONCLUSIONS:Native American patients presenting for kidney transplant were less likely to be educated about transplant before dialysis initiation; did not perceive financial burden and cultural beliefs were not discussed as obstacles to transplant. While a living donor was the preferred option, enthusiasm for living donation from family members was limited.
Project description:The post kidney transplant period is associated with insulin resistance partly due to corticosteroids. Patients on minimal corticosteroid therapy receiving tacrolimus (FK506) for immunosuppression also are affected. FK506 inhibits calcineurin in immune cells. Skeletal muscle calcineurin, which also might be inhibited, mediates exercise-induced transcription leading to more insulin-sensitive muscle. This study was performed to determine if gene transcription responses to exercise are lower in patients awaiting kidney transplant or 3 months post-transplant on a low-steroid, FK506 protocol.
Project description:Bufavirus (BuV) and human parvovirus 4 (PARV4) belong to the Parvoviridae family. We assessed BuV and PARV4 DNA presence by real-time PCR analysis in stool, blood and respiratory samples collected in patients from Marseille and Nice, two large cities in the South-East of France. Bu-V DNA was detected in diarrheic stool samples from 92 patients (3.6% of 2583 patients), particularly men and adults, and patients from the nephrology and the infectious disease departments. Among the patients with a BuV-positive stool sample and for whom at least one blood sample was available (n = 30 patients), BuV DNA was detected also in 3 blood samples. In contrast, BuV DNA was not detected in any of the respiratory samples from 23 patients with BuV-positive stool. BuV detection rate was comparable in stool samples from patients with and without diarrhea. We did not detect PARV4 DNA in any of the stool specimens (n = 2583 patients). Our results suggest that PARV4 fecal-oral transmission is rare or non-existent in the South-East of France while BuV circulates with a relatively high rate in this area.