JC polyomavirus-specific antibody responses in pediatric kidney transplant recipients.

BKPyV is widely recognized in KTRs, but little is known about rates of primary and secondary JCPyV exposure in pediatric KTRs. We evaluated JCPyV exposure in pediatric KTRs using antibody responses in the first 12 months post-transplant. Of 46 children transplanted between 2009 and 2014, 6 lacked any samples for serologic testing, leaving 40 KTRs for study. JCPyV-specific IgG and IgM antibodies were measured using a normalized VLP ELISA. Significant JCPyV exposure was defined as IgG seroconversion, increasing IgG levels of >0.5 nOD units, or IgM detection. Of 40 recipients (median age 3.2 years), 11 (27.5%) were seropositive, 20 (50%) seronegative for JCPyV-IgG, while 9 (22.5%) had no specimen at the time of transplantation, but were confirmed as seronegative in post-transplant samples. Of 29 (72.5%) at risk, JCPyV-IgG seroconversion occurred in 15/29 (51.7%) including JCPyV-IgM in 6 patients (20.7%). Two patients (6.9%) developed only JCPyV-IgM. Among JCPyV-IgG-positive KTRs, six (12.5%) had significant IgG increases. Altogether 23 of 40 patients (57.5%) had serological evidence of primary or secondary JCPyV exposure. In these patients, kidney function tended to be lower during the 2 years of follow-up, but only one patient lost the graft due to JCPyV nephropathy. Thus, JCPyV exposure is common in pediatric KTR and may present serologically as primary or secondary infection. Although only one case of JC-PyVAN occurred, a trend toward lower renal function was seen. Dedicated studies of larger cohorts are warranted to define impact of JCPyV in pediatric KTR.

BK polyomavirus viremia and antibody responses of pediatric kidney transplant recipients in Finland.

BACKGROUND: BKPyV is an important cause of premature graft failure after KT. Most clinical studies describe BKPyV infection in adult KT patients. We studied the prevalence of post-transplant BKPyV viremia, serology, and graft function in pediatric KT recipients. METHODS: Forty-six pediatric patients transplanted between 2009 and 2014 were followed up for BKPyV DNAemia by plasma PCR for median 2.3 (range: 1-6) years. BKPyV-specific antibodies were retrospectively analyzed using virus-like particle ELISA. GFR was measured annually by 51 Cr-EDTA clearance, and serum samples were screened for DSAs by Luminex assay. RESULTS: BKPyV viremia was demonstrated in nine patients at a median of 6 months post-KT. Early BKPyV viremia at 3 months post-KT associated with decreased concomitant GFR and tendency for decreased subsequent graft function. Three of nine patients with BKPyV viremia developed DSA, all against class II antigens. PyVAN developed to four patients and responded to judicious reduction in IS. One graft was lost later due to ABMR. BKPyV-IgG was found in 18 of 31 patients (58%) tested at transplantation, and seven recipients seroconverted after transplantation with a significant increase in IgG levels with IgM. Finally, BKPyV-IgG was detectable in 31 of 40 patients (78%) at the end of the study. CONCLUSIONS: Post-transplant BKPyV viremia in pediatric KT patients may alter graft function and contribute to progression of chronic allograft injury. BKPyV-IgG predicts past exposure. Low or absent BKPyV-specific antibody levels were seen pretransplant in 42% of tested patients, but were not predictive of prolonged replication or poor outcome.

Anemia and low-grade inflammation in pediatric kidney transplant recipients.

BACKGROUND: Anemia and low-grade inflammation are reported to be associated with impaired long-term graft outcome in renal transplant (RTx) recipients. In this study, hemoglobin (Hb) and inflammation marker levels were correlated with measured glomerular filtration rate (GFR) in 128 pediatric RTx recipients over a median follow-up period of 10 years. METHODS: Serum levels of erythropoietin (EPO), hepcidin-25, high-sensitivity C-reactive protein (CRP) (hsCRP) and interleukin-6 (IL-6) were analyzed by enzyme-linked immunosorbent assays, and GFR was analyzed by 51Cr-EDTA clearance. RESULTS: The median levels of Hb (115 g/L), hsCRP (0.4 mg/L) and IL-6 (1.4 pg/mL) and the median erythrocyte sedimentation rate (ESR; 19 mm/h) remained stable after the first post-operative year. However, approximately half of the patients had a normocytic, normochromic anemia, and one-third had elevated levels of hsCRP (>1 mg/L) and ESR (>25 mm/h), indicating continuous low-grade inflammation. Low Hb levels preceded increased fibrosis in protocol biopsies taken at 1.5 and 3 years after transplantation and preceded decreased GFR by several years. Hb levels showed an inverse correlation with EPO levels (r = -0.206, p = 0.038) and ESR (r = -0.369, p < 0.001), but not with hepcidin-25, hsCRP or IL-6 levels. The levels of the major inflammatory markers IL-6 and hsCRP did not show a significant correlation with GFR at either the early maintenance phase or later. In the multivariable analysis, low Hb levels performed better than any other marker with respect to predicting concomitant and subsequent GFR. CONCLUSIONS: Anemia, but not elevated inflammatory indices, was associated with poor concomitant and subsequent graft function during a 10-year follow-up in pediatric RTx patients.

Donor-specific HLA antibodies and graft function in children after renal transplantation.

BACKGROUND: The presence of circulating donor-specific human leukocyte antigen antibodies (HLA-DSA) has been associated with chronic antibody-mediated rejection, leading to progressive graft dysfunction and poor graft survival.The aim of this study was to investigate the incidence and significance of HLA-DSA in paediatric renal transplantation(RTx) patients. METHODS: A total of 294 post-transplant serum samples from 123 RTx patients were retrospectively analysed for HLA antibodies. Positive samples were further tested for HLADSA by a Luminex Single Antigen bead assay. The antibody findings were correlated to measured glomerular filtration rate(GFR) and clinical outcome. RESULTS: HLA antibodies were detected in half of the routine samples (140/294) taken 1 month to 10 years after RTx, and 40% (62/140) of these were HLA-DSA. Overall, one-third(42/123) of the patients had HLA-DSA, which mostly(65%) reacted against class II antigens. Detection of HLADSA was not associated with poor GFR at the time of sampling, and no exceptional deterioration of GFR after the HLA-DSA detection was noted in individual patients regardless of the antibody level. The presence of HLA-DSA in the first 2 years posttransplantation was not associated with poorer graft function later on. CONCLUSION: Detection of HLA antibodies is common in children after RTx, and this finding, as such, does not predict any deterioration of graft function.

Blood pressure profiles 5 to 10 years after transplant in pediatric solid organ recipients.

Arterial hypertension is a major risk factor for cardiovascular disease after solid organ transplantation, emphasizing the need for blood pressure (BP) monitoring. The authors studied 24-hour ambulatory BP monitoring (ABPM) parameters (index, load, dipping) and their predictive value with regard to hypertension as well as correlations with graft function and metabolic parameters such as obesity and dyslipidemias. The ABPM profiles of 111 renal, 29 heart, and 13 liver transplant recipients were retrospectively analyzed 5 to 10 years after transplant (median 5.1 years). The BP profiles among the different transplant groups were similar. The BP index and load were abnormal especially at nighttime and the nocturnal BP dipping was often blunted (in 49% to 83% of the patients). The BP variables were found to be equally valued when assessing hypertension. BP load of 50% instead of 25% seems to be a more adequate cutoff value. The BP variables correlated poorly with the metabolic parameters and kidney function. Antihypertensive medication did not notably change the ABPM profile in renal transplant recipients. Hypertension, including nocturnal hypertension, is present in children receiving solid organ transplant, underlining the importance of use of ABPM in the follow-up of these patients.

Histopathology and biomarkers in prediction of renal function in children after kidney transplantation.

BACKGROUND: Early detection of chronic allograft injury is a major challenge after kidney transplantation (RTx) in adults and children. We correlated the expression of four immunohistochemical biomarkers, P-selectin glycoprotein ligand-1 (PSGL-1), vimentin, α-smooth muscle actin (α-SMA) and collagen IV, to the kidney graft histology and function in pediatric RTx patients. METHODS: We analyzed the histopathology and immunohistochemical stainings of 165 biopsies from 56 patients. Histopathology was scored according to Banff '05 classification and biomarker expression semiquantitatively. Glomerular filtration rate (GFR) was measured annually by (51)Cr-EDTA clearance. RESULTS: In protocol biopsies, the expression of all four biomarkers correlated with the interstitial fibrosis and tubular atrophy (IF/TA) changes, which increased during the first 36months after RTx. At the time of 18month biopsy, we observed the deterioration of GFR in patients with high (≥2) IF/TA score (50 vs. 68ml/min/1.73m(2), p=0.004) or collagen IV expression (45 vs. 65ml/min/1.73m(2), p=0.016). Intense stainings of IF/TA, collagen IV and vimentin are also associated with poor GFR at 36 and 48months, however, the biomarker scores revealed no additional predictive value for concomitant or late GFR compared to IF/TA score. Patients with high and low biomarker expressions showed no significant differences in annual deterioration of GFR, which declined on average 2.2ml/min/1.73m(2)/year over the 7years follow-up. CONCLUSIONS: Overall, the results suggest that traditional histopathology is a sufficient predictor for graft function, and the routine use of these histochemical markers as surrogates for graft function deterioration is questioned.