Donor‐specific anti‐HLA antibodies in pediatric renal transplant recipients with creeping creatinine: Prevalence,histological correlations,and impact on patient and graft survival

Donor‐specific anti‐HLA antibodies (DSA) causing CAMR are responsible for a high proportion of long‐term graft failures after RTX. We studied the prevalence of DSA in RTX children biopsied for creeping Cr, its relationship with NA, and patient and graft survival according to histopathology. Between 2008 and 2013, 92 children were biopsied at a median of 38 months post‐RTX. At biopsy, the prevalence of DSA was 49% and C4d 70%. NA rate was 45%, higher in adolescents (60%). Most frequent diagnoses were CAMR (72%) and interstitial fibrosis with tubular atrophy (IFTA) (28%). Forty‐five of 66 patients with CAMR (68%) had detectable DSA. Twenty‐one DSA‐negative patients with CAMR had histological damage (IFTA + C4d positivity). C4d was detected in 64 of 66 biopsies with CAMR. Recipients with IFTA alone had neither C4d, nor detectable DSA, and were adherent. Graft survival at five yr was 89% in patients with CAMR, 79% in those with CAMR + TCMR Banff I, 33% in those with CAMR + TCMR Banff II, and 96% in those with IFTA. ABMR and complement activation were frequent in children biopsied for creeping Cr. Recipients with DSA were more likely to be non‐adherent and have CAMR or CAMR + TCMR and worse graft survival.     

Mycoplasma pneumoniae detection with PCR in renal tissue of a patient with acute glomerulonephritis

Renal disease concurrent with a Mycoplasma pneumoniae infection is uncommon. In this report we describe the clinical outcome of a 6-year-old patient who presented with a rapidly progressive glomerulonephritis that required dialysis. A kidney biopsy was performed, and the results revealed membranoprolipherative glomerulonephritis. The IgM serology was positive, and M. pneumoniae DNA was detected in a renal biopsy sample using a nested-PCR assay. The outcome was good.     

Lack of correlation between SIV-Nef evolution and rapid disease progression in morphine-dependent nonhuman primate model of AIDS

Six morphine-dependent and two control macaques were infected in an SIV/SHIV nonhuman primate model of AIDS. Three animals in the morphine group rapidly developed clinical disease and died within the timeframe of this study. The sequence evolution of nef in plasma virus was assessed at 4, 12, and 20 weeks postinfection. Cloned sequences were compared phylogenetically against each other as well as against the inoculum virus clones to determine the effect of morphine and rate of disease progression on diversity and divergence, respectively. Unlike our earlier studies of tat and env, nef evolution was not affected by morphine abuse or by rapid disease progression. The results suggest that although the evolution of other loci is inversely correlated to the onset and rate of clinical disease, differential evolution of nef is related neither to drug abuse nor to rapid progression within the first 20 weeks of infection.     

Conversion to sirolimus in pediatric renal transplant patients: a single-center experience

We studied efficacy and safety of conversion from CNI- to SRL-based immunosuppression in 92 kidney TX recipients, mainly due to CAN (69%). Median time of conversion was 31 months (r: 0.3-165); median time of follow-up: 36 months (r: 2-102). In the whole group mean eGFR increased from 53 ± 22 to 67 ± 26mL/min/1.73 m(2) at three months (p = 0.02) and did not change subsequently. Patients with grade I CAN had higher eGFR than those with grade II CAN. Patient and graft survival was 96% and 70% 10 yr after conversion. Patients with grade I CAN had better graft survival than those with grade II CAN: 89% vs. 65% at six yr (p = 0.02) post conversion. There were two episodes of BPAR. Baseline proteinuria >20 mg/kg/day (HR: 10) and baseline eGFR <50 mL/min/1.73 m(2) (HR: 8) were independent predictors of graft loss. Sixty-seven of 92 subjects had ≥1 AEs: diarrhea (n = 52), urinary tract infections (n = 35), and lower respiratory tract infections (n = 12) were the most frequent. Patients with >2 AEs had SRL blood levels >9 ng/mL at month 3 (p = 0.01). In conclusion, patients converted from CNI to SRL had good graft survival and tolerable but frequent AEs. Independent predictors of graft loss were baseline proteinuria and eGFR.     

Correlation between SIV Tat evolution and AIDS progression in cerebrospinal fluid of morphine-dependent and control macaques infected with SIV and SHIV

Morphine abuse has been associated with higher virus replication and accelerated disease progression in a non-human primate model of AIDS. In our previous report, we have shown that 50% of morphine-addicted macaques progress rapidly and that 2/3 of the rapid progressors exhibit severe neuropathogenesis. In this report, we examined the sequence evolution of the SIV Tat protein, known to participate in AIDS neuropathology, in the cerebrospinal fluid (CSF) of morphine-dependent and control macaques over the first 20 weeks of infection. The CSF SIV Tat evolution was found to be inversely related with disease progression, and the highly neuropathogenic inoculum clone sequence was the prevalent CSF form in rapid progressors. Divergence from the inoculum clone was significantly greater in both morphine-dependent normal progressors and control macaques than in the morphine-dependent rapid progressors. Furthermore, we also found evidence of a trend that morphine alters the type of mutation, resulting in an enhanced ratio of transitions to transversions (Ts:Tv). Rapid disease exacerbates this trend and appears to influence the distribution of nonsynonymous changes in the first exon of SIV tat, with a clear majority of mutations occurring in the C-terminal half of the protein where the known functionally important domains reside. Thus, morphine abuse may change the nature and extent of mutations that drive viral evolution.