Dietary habits and metabolic control in adolescents and young adults with phenylketonuria: self-imposed protein restriction may be harmful.

BACKGROUND: In untreated patients, phenylketonuria (PKU) results in severe encephalopathy with mental retardation. A protein-restricted diet is recommended which can be relaxed in adolescence/adulthood. METHODS: We contacted all 72 adult/adolescent PKU patients who had been treated in our center during early childhood. Some still regularly attended our outpatient clinics, while others were lost for follow-up, giving 51 patients in our study. We asked all patients to complete a dietary protocol as well as a questionnaire on quality of life. Blood and urine were analyzed and body impedance plethysmography and cerebral MRI were performed. RESULTS: 42 % of the patients followed protein restriction supplemented with amino acid mixtures (AAM), others had a vegan diet with (8 %) or without (14 %) AAM; 36 % said they were eating normally and did not need any AAM. However, based on dietary protocols and blood urea levels, protein intake was restricted in this patient group. None of the patients examined had serious nutritional deficits. Phenylalanine levels were higher in patients not taking AAM. MRI of the brain was not different from those following protein restriction and taking AAM. The lesions score and mood correlated best with the cumulative phenylalanine values during the first 10 years of life. CONCLUSION: In summary, 50 % of adult/adolescent patients from our center did not take AAM at the start of our survey although they unknowingly followed self-imposed protein restriction. They had no overt nutritional deficits; however, long-term brain function may be compromised. Our study emphasizes the need for specialized metabolic care in PKU during adulthood.

State of pediatric kidney transplantation in 2011.

Fifty years ago children with renal failure died due to the lack of adequate therapy. Today, the implementation of dialysis procedures, such as peritoneal dialysis and hemodialysis as well as kidney transplantation, has become almost standard care for pediatric patients. Even infants can now be dialyzed or receive transplants. A kidney transplant allows for a 20-year patient survival in >90% of patients and almost age-appropriate mental and physical development. A better transplant survival is achieved with a living organ donation than with a post-mortem donation. It has been shown that kidneys from deceased juvenile and young adult donors should be allocated primarily to children as they obtain significantly better transplant function in the short and medium term than adults. Unfortunately, the problem of a long waiting period for a postmortem donated kidneys for children in the Eurotransplant area remains. Although, the allocation system for children was amended in December 2010, it remains to be seen whether this change will positively influence waiting times. New immunosuppressive regimens have resulted in significantly improved long-term transplant function and transplant survival. The main challenge, however, concerns chronic humoral transplant rejection, therapy for recurrence of the underlying disease, and the execution of AB0 incompatible transplantations.

De novo therapy with everolimus, low-dose ciclosporine A, basiliximab and steroid elimination in pediatric kidney transplantation.

The number of acute rejections and infections after pediatric kidney transplantation (KTX) could not be reduced in the last years. To reduce these events, we investigated a new immunosuppressive protocol in a prospective trial. After KTX, 20 children (median age 12 years, range 1-17) were initially treated with Basiliximab, ciclosporine A (CsA) (trough-level = C0 200-250 ng/mL) and prednisolone. After 2 weeks, CsA dose was reduced to 50% (C0 75-100 ng/mL, after 6 months: 50-75 ng/mL) and everolimus (1.6 mg/m²) /day) was started (C0 3-6 ng/mL). Six months after KTX prednisolone was set to alternate dose and stopped 3 months later. All 20 protocol biopsies 6 months after KTX showed no acute rejection or borderline findings. Indication biopsies resulted in no acute rejections and two borderline findings. Mean glomerular filtration rate (GFR) 1 year after KTX was 71 ± 25 mL/min/1.73 m². Without cytomegalovirus (CMV)-prophylaxis, only two primary CMV infections were seen despite a donor/recipient-CMV-constellation pos./neg. in 10/20 children. In pediatric KTX, de novo immunosuppression with low-dose CsA, everolimus and steroid withdrawal after 9 months led to promising results according to numbers of acute rejections and infections. Further follow up is needed. Future larger trials will have to confirm our findings.

Protocol biopsy-driven interventions after pediatric renal transplantation.

The therapeutic value of protocol biopsies (PBs) in renal transplant recipients remains unclear. We performed protocol biopsies in 57 children six months after transplantation. We increased the CNI dose in patients with borderline findings. In cases of Banff grade Ia, six prednisolone IV-pulses were given and the CNI dose was increased. CNI toxicity and polyomavirus nephropathy led to a reduction in the CNI dose. GFR was compared with a control group of 51 children with no PBs transplanted in the same period. Forty-two percent of PBs had no pathological changes, 24% IF/TA. Borderline findings were detected in 11%, Banff grade Ia in 15% (CNI), toxicity in 8%, and one case showed polyomavirus nephropathy. GFR after 1.5 and 2.5 yr was similar in both groups. GFR 3.5 yr after transplantation was significantly higher in the intervention group (57 ± 17 vs. 46 ± 20). Patients treated with low-dose CNI and everolimus had a significantly lower number of pathological findings in PBs. The performance of protocol biopsies followed by a standardized treatment algorithm led to better graft function 3.5 yr after transplantation. Prospective randomized studies to confirm our findings are needed.

Vaso-occlusion in Schimke-immuno-osseous dysplasia: is the NO pathway involved?

Schimke-immuno-osseous dysplasia (SIOD) is an autosomal recessive disorder with the main clinical findings of spondyloepiphyseal dysplasia, nephrotic syndrome, and defective cellular immunity. Vaso-occlusive processes, especially generalized atherosclerosis, are a life-limiting complication in patients with severe SIOD. The nitric oxide synthase (NOS) oxidizes L-arginine to nitric oxide (NO). NO is a potent vasodilator with inhibitory effects on platelet aggregation and the development of atherosclerosis. We hypothesized that reduced NO production due to antagonism of NOS by asymmetric dimethylarginine (ADMA) would be a possible pathophysiological mechanism for vaso-occlusion in SIOD. We tested this hypothesis in 10 patients with SIOD and 10 age-matched healthy controls. Plasma and urine levels of nitrite and nitrate, the indicators of NO synthesis, and of ADMA, an endogenous NOS inhibitor, in children suffering from SIOD were not significantly different from those in the age-matched healthy controls. Our results suggest that the L-arginine/NO pathway is not altered in SIOD. Antagonism of NOS by ADMA does not seem to be the cause of premature general atherosclerosis in SIOD. The underlying pathology of vaso-occlusion in SIOD still remains unclear.