Course of renal allograft function after diagnosis and treatment of post‐transplant lymphoproliferative disorders in pediatric kidney transplant recipients

Abstract Background Post‐transplant lymphoproliferative disease (PTLD) is a life‐threatening complication in renal transplant recipients. Immunomodulatory and chemotherapeutic treatment potentially affect allograft function. The aim of this study was to evaluate graft function of pediatric kidney transplant recipients following diagnosis and standardized treatment of PTLD. Methods Patients were identified from the German Ped‐PTLD registry, and data on renal function were retrospectively retrieved from patient charts. For PTLD treatment, immunosuppressive therapy was reduced and all children received rituximab (375 mg/m2) for up to six doses. Two patients required additional low‐dose chemotherapy. Renal allograft function was monitored by consecutive measurements of estimated glomerular filtration rate (eGFR) at defined time points. Follow‐up was up to 60 months after PTLD. Results Twenty patients were included in this cohort analysis. Median time from transplantation to PTLD was 2.4 years. Histopathology showed monomorphic lesions in 16 and polymorphic in 4 patients. Two patients experienced PTLD relapse after 2 and 14 months. Range‐based analysis of variance showed stable allograft function in 17 of 20 patients (85%). Mean eGFR increased during early treatment phase. One patient experienced graft rejection 5.3 years after diagnosis of PTLD. Another patient developed recurrence of primary renal disease (focal‐segmental glomerulosclerosis) and lost his renal allograft 3.8 years post‐transplant (2.0 years after PTLD diagnosis). Conclusion Treatment of PTLD with rituximab with or without low‐dose chemotherapy in combination with reduced immunosuppression, mostly comprising of an mTOR inhibitor‐based, calcineurin inhibitor‐free regimen, is associated with stable graft function and favorable graft survival in pediatric renal transplant patients

Hepatic safety and efficacy of immunomodulatory drugs used in patients with autoimmune hepatitis.

BACKGROUND AND AIMS There is little data on the hepatic efficacy and safety of immunomodulatory drugs used in patients with autoimmune hepatitis (AIH), despite their established use in dermatology, rheumatology and inflammatory bowel diseases (IBD). Our aim was to collect real-life data on the experience of expert centres in treating AIH patients with these drugs, considered unconventional for AIH management. METHODS Online survey among hepatology centres being part of the European Reference Network on Hepatological Diseases (ERN RARE-LIVER). RESULTS 25 AIH patients have been reported. Ten were female, median age at diagnosis was 28 years; median follow-up was 17 months. All had initially received AIH-standard treatment. AIH-unconventional treatment was initiated for concomitant autoimmune diseases in 15 cases: nine for IBD (five vedolizumab and four ustekinumab), and one each for following diseases: autoinflammatory syndrome (tocilizumab), chronic urticaria (omalizumab), rheumatoid arthritis (abatacept), psoriasis (guselkumab), psoriatric arthritis (secukinumab, followed by ustekinumab) and alopecia (ruxolitinib). Three patients were treated with immunomodulatory drugs for side effects of previous treatments, including two patients with IBD treated with vedolizumab and ustekinumab, respectively, and one treated with belimumab. At the end of follow-up, 13 patients were in complete biochemical response, the patient on omalizumab had a relapse, and four patients with concomitant IBD had insufficient response. Seven patients were treated for lack of biochemical remission, of whom six with belimumab, all initially reaching complete biochemical response, but five relapsing during follow-up; and one with secukinumab, having concomitant rheumatoid arthritis and ankylosing spondylitis, reaching complete biochemical response. Only the patient on abatacept received unconventional treatment as monotherapy. Side effects were reported in two patients on belimumab: one recurrent soft tissue infections, one fatigue and arthralgia. CONCLUSION Among 25 AIH patients who were treated with immunomodulatory drugs for different reasons, the majority had a fovorable course, relapse was frequent in difficult-to-treat patients who received belimumab, and four with concomitant IBD had insufficient response

Global Variation of Nutritional Status in Children Undergoing Chronic Peritoneal Dialysis : A Longitudinal Study of the International Pediatric Peritoneal Dialysis Network

While children approaching end-stage kidney disease (ESKD) are considered at risk of uremic anorexia and underweight they are also exposed to the global obesity epidemic. We sought to investigate the variation of nutritional status in children undergoing chronic peritoneal dialysis (CPD) around the globe. The distribution and course of body mass index (BMI) standard deviation score over time was examined prospectively in 1001 children and adolescents from 35 countries starting CPD who were followed in the International Pediatric PD Network (IPPN) Registry. The overall prevalence of underweight, and overweight/obesity at start of CPD was 8.9% and 19.7%, respectively. Underweight was most prevalent in South and Southeast Asia (20%), Central Europe (16.7%) and Turkey (15.2%), whereas overweight and obesity were most common in the Middle East (40%) and the US (33%). BMI SDS at PD initiation was associated positively with current eGFR and gastrostomy feeding prior to PD start. Over the course of PD BMI SDS tended to increase on CPD in underweight and normal weight children, whereas it decreased in initially overweight patients. In infancy, mortality risk was amplified by obesity, whereas in older children mortality was markedly increased in association with underweight. Both underweight and overweight are prevalent in pediatric ESKD, with the prevalence varying across the globe. Late dialysis start is associated with underweight, while enteral feeding can lead to obesity. Nutritional abnormalities tend to attenuate with time on dialysis. Mortality risk appears increased with obesity in infants and with underweight in older children.Peer reviewe

Early clinical course of biopsy-proven IgA vasculitis nephritis

Background IgA vasculitis (IgAV) is the most common form of systemic vasculitis in childhood and frequently involves the kidney. A minority of patients with IgA vasculitis nephritis (IgAVN), especially those presenting with heavy proteinuria and/or kidney failure at onset, are at risk of chronic end-stage kidney disease. For deciding upon treatment intensity, knowledge of the short-term clinical course of IgAVN is needed to improve treatment algorithms. Methods For this retrospective multicenter study, the medical records of 66 children with biopsy-proven IgAVN were reviewed. Age, gender, medical history and therapeutic interventions were recorded. Laboratory data included serum creatinine, albumin, urinary protein excretion (UPE) and glomerular filtration rate (eGFR). Threshold values were determined for each parameter, full remission was defined as no proteinuria and eGFR > 90 ml/min/1.73m(2). Results Median age at onset of IgAVN was 8.9 years. 14.1% of the children presented with nephrotic syndrome, 50% had an eGFR below 90 ml/min/1.73 m(2) and 51.5% showed cellular crescents in renal histology. The treatment regimens varied notably. Forty-four patients were treated with immunosuppression; 17 patients with crescents or nephrotic syndrome were treated with corticosteroid (CS) pulse therapy. After 6 months, UPE had decreased from 3.7 to 0.3 g/g creatinine and the proportion of patients with a decreased eGFR had fallen from 50.0% to 35.5%. Thirteen children (26.5%) achieved full remission within 6 months. Conclusions In most patients with IgAVN proteinuria decreases slowly and kidney function improves, but full remission is reached only in a minority after 6 months. Persistent heavy proteinuria in the first two months rarely developed into long-term proteinuria. Therefore, decisions for more intense treatment should take into account the course of UPE over time. For a comparison of treatment effects, patient numbers were too small. Prospective, randomized controlled trials are necessary to clarify risk factors and the effect of immunosuppressive therapies

Prenatal parental decision-making and postnatal outcome in renal oligohydramnios

Background Previous studies on renal oligohydramnios (ROH) report highly variable outcome and identify early onset of ROH and presence of extrarenal manifestations as predictors of adverse outcome in most cases. Data on termination of pregnancy (TOP) and associated parental decision-making processes are mostly missing, but context-sensitive for the interpretation of these findings. We provide here a comprehensive analysis on the diagnosis, prenatal decision-making and postnatal clinical course in all pregnancies with ROH at our medical centre over an 8-year period. Methods We report retrospective chart review data on 103 consecutive pregnancies from 2008 to 2015 with a median follow-up of 554 days. Results After ROH diagnosis, 38 families opted for TOP. This decision was associated with onset of ROH (p < 0.001), underlying renal disease (p = 0.001) and presence of extrarenal manifestations (p = 0.02). Eight infants died in utero and 8 cases were lost to follow-up. Of the 49 liveborn children, 11 received palliative and 38 underwent active care. Overall survival of the latter group was 84.2% (n = 32) corresponding to 31% of all pregnancies (32 out of 103) analysed. One third of the surviving infants needed renal replacement therapy during the first 6 weeks of life. Conclusions Over one third of pregnancies with ROH were terminated and the parental decision was based on risk factors associated with adverse outcome. Neonatal death was rare in the actively treated infants and the overall outcome promising. Our study illustrates that only careful analysis of the whole process, from prenatal diagnosis via parental decision-making to postnatal outcome, allows sensible interpretation of outcome data

Bone and Mineral Metabolism in Children with Nephropathic Cystinosis Compared with other CKD Entities

Context: Children with nephropathic cystinosis (NC) show persistent hypophosphatemia, due to Fanconi syndrome, as well as mineral and bone disorders related to chronic kidney disease (CKD); however, systematic analyses are lacking. Objective: To compare biochemical parameters of bone and mineral metabolism between children with NC and controls across all stages of CKD. Design: Cross-sectional multicenter study. Setting: Hospital clinics. Patients: Forty-nine children with NC, 80 CKD controls of the same age and CKD stage. Main outcome measures: Fibroblast growth factor 23 (FGF23), soluble Klotho, bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRAP5b), sclerostin, osteoprotegerin (OPG), biochemical parameters related to mineral metabolism, and skeletal comorbidity. Results: Despite Fanconi syndrome medication, NC patients showed an 11-fold increased risk of short stature, bone deformities, and/or requirement for skeletal surgery compared with CKD controls. This was associated with a higher frequency of risk factors such as hypophosphatemia, hypocalcemia, low parathyroid hormone (PTH), metabolic acidosis, and a specific CKD stage-dependent pattern of bone marker alterations. Pretransplant NC patients in mild to moderate CKD showed a delayed increase or lacked an increase in FGF23 and sclerostin, and increased BAP, TRAP5b, and OPG concentrations compared with CKD controls. Post-transplant, BAP and OPG returned to normal, TRAP5b further increased, whereas FGF23 and PTH were less elevated compared with CKD controls and associated with higher serum phosphate. Conclusions: Patients with NC show more severe skeletal comorbidity associated with distinct CKD stage-dependent alterations of bone metabolism than CKD controls, suggesting impaired mineralization and increased bone resorption, which is only partially normalized after renal transplantation