Trine Tangeraas

Long-term outcome of pediatric renal transplantation: the Norwegian experience in three eras 1970-2006.

Abstract:  During the years 1970–2006, 251 renal transplantations were performed in 178 children in Norway. The proportion of LD was 84%. Transplantations were performed preemptively in 52%. Pretransplant dialysis time was median three months. Structural abnormalities and hereditary renal disorders constituted 69% of end‐stage renal diseases, 29% were caused by glomerulopathies and other acquired disorders and 2% of unknown cause. Patient survival rates were 94.2, 93.5, and 84.4% at five, 10, and 20 yr, respectively. The most frequent cause of death was infections followed by cardiovascular events. For recipients of living donor grafts (n = 149), survival of first transplant was 82, 68.8, and 45.1% at five, 10, and 20 yr, respectively, and was significantly higher than for recipients of deceased donor organs (n = 29; log rank, p = 0.008). The only significant predictor for better transplant survival when modeled with multiple regression analysis adjusted for pretransplant dialysis, diagnosis, donor age, sex and immunosuppressive era, was the use of LD compared with DD (HR = 2.1, 95% CI [1.1–4.0], p = 0.02). The acute rejection rate declined significantly from 61.5% in 1970–1982 to 14.5% in 2000–2006 (log rank, p = 0.002). It remains to be seen whether the reduction in acute rejection rate and present immunosuppressive therapy will have a positive impact on long‐term graft survival in years to come.

Angiotensin II type 1 receptor antibodies in childhood kidney transplantation

Angiotensin II type 1 receptor antibodies (AT1RAb) have emerged as non‐HLA Ab present in patients with acute AMR and risk of graft loss. Furthermore, AT1RAb have been shown to increase angiotensin II sensitivity which may play a role in the development of CVD and hypertension. Data on AT1RAb in stable transplant recipients are lacking. The aim of this study was to analyze the levels of AT1RAb in a cohort of stable patients after kidney transplantation (tx) in childhood. A cross‐sectional study of 30 children (median age 14, range 3–19 yr, median time since tx five yr) and 28 adults who were transplanted in childhood (median age 26, range 20–40 yr, median time since tx 18 yr) transplanted between 1993–2006 and 1983–2002, respectively, was performed. Healthy controls were 51 healthy children (5–8 yr) and 199 healthy donors (median age 56.5 yr, range 42–83 yr). Plasma AT1RAb were analyzed by immunoassay. Median total AT1RAb IgG concentration was significantly higher in the pediatric‐tx group as compared to the adult‐tx group (40.0 and 10.95 U/mL, p < 0.0001). For both groups, the tx group showed higher levels: the pediatric‐tx group vs. control group (40.0 vs. 13.3 U/mL, p = 0.0006) and the adult‐tx group vs. adult control group (10.95 vs. 6.5 U/mL, p < 0.0001). Age was the strongest indicator of high levels of AT1RAb IgG (p = 0.0003). AT1RAb total IgG levels are significantly higher in a stable pediatric‐tx cohort as compared to adult‐tx patients and healthy controls of comparable age groups. The relevance of our findings in relation to age, time since tx, previous or future rejection, and CVD risk merits future studies.

Rescue of kidney function in a toddler with anti-GBM nephritis

Anti-glomerular basement membrane (anti-GBM) nephritis is rare in childhood with few published cases. We report a 19-month-old boy with rapidly progressive glomerulonephritis (RPGN) due to anti-GBM nephritis. Treatment was started under 2 weeks after presentation and included plasma exchange, intravenous high-dose methylprednisolone, intravenous cyclophosphamide and mycophenolate as mainstay medication. The treatment was rapidly effective with immediate decrease in anti-GBM titres and plasma creatinine. Three years after presentation, the boy has normal kidney function, blood pressure and no residual disease. The successful outcome was likely due to the rapid recognition of the anti-GBM antibodies as the cause of RPGN and aggressive primary treatment.

An intronic variation in SLC52A1 causes exon skipping and transient riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency

Vitamin B2, riboflavin is essential for cellular function, as it participates in a diversity of redox reactions central to human metabolism, through its role as precursor for the cofactors flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which are electron carriers. The electron transfer flavoprotein (ETF) and its dehydrogenase (ETFDH), uses FAD as cofactor. The ETF and ETFDH are forming the electron transport pathway for many mitochondrial flavoprotein dehydrogenases involved in fatty acid, amino acid and choline metabolism. A variation in either ETF or ETFDH causes multiple acyl-CoA dehydrogenation deficiency (MADD), but genetic variations in the riboflavin metabolism or transportation of riboflavin can also cause MADD. The most common variations are located in the riboflavin transporter 2 (RFVT2) and 3 (RFVT3), that are highly expressed in brain and intestinal tissues, respectively. Deficiency of riboflavin transporter 1 (RFVT1), encoded by the SLC52A1 gene, highly expressed in the placenta, has only been reported once. We here report a case of transient MADD, caused by a heterozygous intronic variation, c.1134+11G>A, in the SLC52A1 gene encoding RFVT1. This variation creates a binding site for the splice inhibitory hnRNP A1 protein and causes exon 4 skipping. Riboflavin deficiency and maternal malnutrition during pregnancy might have been the determining factor in the outcome of this case.

Small effort, high impact: Focus on physical activity improves oxygen uptake (VO2peak), quality of life, and mental health after pediatric renal transplantation

This study estimates the effects on peak oxygen uptake (VO2 peak), QoL, and mental health after the introduction of an adjusted post‐transplant follow‐up program, that is, early physiotherapy and focus on the importance of physical activity. VO2 peak was measured by a treadmill exercise test in 20 renal‐transplanted children on the adjusted post‐transplant follow‐up and compared with a group of 22 patients investigated in a previously, before the implementation of our new follow‐up routines. PedsQL and The Strengths and Difficulties Questionnaire (SDQ) were used to assess QoL and mental health in 45 patients on the new as compared to 32 patients on the previous follow‐up strategy. The patients exposed to early physiotherapy and a higher focus on physical activity had significantly higher VO2 peak (44.3 vs 33.5 mL kg−1 min−1, P = .031) in addition to improved QoL (P = .003) and mental health scores (P = .012). The cardiovascular risk profile was similar in both groups aside from significantly higher triglycerides in the present cohort. Small efforts as early physiotherapy and increased focus on physical activity after pediatric renal transplantation have significant impact on cardiorespiratory fitness, QoL, and mental health. The importance of physical activity should therefore be emphasized in follow‐up programs.