Polyomavirus BK infection in pediatric kidney-allograft recipients: a single-center analysis of incidence, risk factors, and novel therapeutic approaches.

BACKGROUND: Although a growing body of literature regarding polyoma BK virus (BKV) infection and associated interstitial nephritis in kidney-allograft recipients is becoming available, the impact of BKV infection in the pediatric population has not been fully evaluated. METHODS: In a retrospective analysis, we performed polymerase chain reaction (PCR) assays for BKV DNA in serum and urine samples from 100 pediatric kidney-allograft recipients referred to our institution in the last 5 years. RESULTS: BKV viruria was observed in 26 of 100 patients, whereas BKV viremia was demonstrated in 5 patients. Serum creatinine was significantly higher in recipients with positive BK viremia compared with BKV DNA-negative patients (mean 2.66 vs. 1.14 mg/100 mL). Renal biopsy performed in 3 of 5 patients showed graft damage consistent with interstitial nephropathy. In the univariate analysis, negative antibody status of the recipient and the presence of mycophenolate mofetil in baseline immunosuppression were the two factors predictive of active BKV infection. CONCLUSIONS: Our study shows that BKV-associated nephropathy is a relevant complication in the pediatric kidney transplantation setting also. Identification of patients at risk of developing virus-associated nephropathy, through prospective quantification of viral load, could improve clinical outcome by allowing the use of timely preemptive therapy guided by BKV DNA levels.

[Acute effects of peritoneal dialysis on muscle protein turnover]. / Effetti acuti della dialisi peritoneale sul metabolismo proteico.

BACKGROUND: Despite continuing glucose absorption and stimulation of insulin secretion, wasting is common in patients with chronic renal failure (CRF) treated with peritoneal dialysis. METHODS: To evaluate if peritoneal dialysis per se has any effect(s) on muscle protein turnover we employed the forearm perfusion method associated with the kinetics of 3H-phenylalanine in seventeen patients with CRF in the basal state and: a) during the systemic hyperinsulinemia associated with peritoneal dialysis (6 patients) (200-240 min); b) during locally-induced hyperinsulinemia, without systemic effects on aminoacid (AA) availability (6 patients) (80-120 min); c) in time-controls (5 patients) (80-240 min). RESULTS: Peritoneal dialysis and local infusion of insulin in the brachial artery (0.01 mU/min/kg) induced a similar degree of systemic or local, moderate hyperinsulinemia (19+/-4 e 21+/-3 microU/ml, respectively). During both protocols an insulin-related inhibition of muscle protein degradation occurred; however peritoneal dialysis caused a 20% decrease in forearm phenylalanine rate of disposal (an index of muscle protein synthesis), which correlated with the decline of arterial BCAA and potassium, which were removed via the peritoneal fluid. Furthermore, a persistent negative net phenylalanine and AA balance across the forearm was observed during peritoneal dialysis, while the negative basal net phenylalanine and AA balance was reversed to a positive or neutral one during local hyperinsulinemia. CONCLUSIONS: We conclude that in CRF patients even a modest elevation in local insulin levels is followed by an anabolic muscle response, while the same effect is not observed during the systemic hyperinsulinemia associated with substrate removal which occurs during peritoneal dialysis. In this setting the antiproteolytic effect of hyperinsulinemia is offset by a decrease in muscle protein synthesis which is accounted for by a decrease in AA availability. Our data indicate that protein metabolism during peritoneal dialysis is characterized not only by decreased, but also less efficient, turnover rates.

Phenylalanine hydroxylation across the kidney in humans rapid communication.

UNLABELLED: Phenylalanine hydroxylation across the kidney in humans. BACKGROUND: Although phenylalanine hydroxylase activity is detectable in in vitro renal tissue preparations, no data on in vivo phenylalanine hydroxylation across the human kidney, as well as on its possible contribution to whole-body hydroxylation, currently exist. METHODS: To this aim, we have measured whole-body, renal, and splanchnic phenylalanine hydroxylation to tyrosine, as well as phenylalanine and tyrosine rates of appearance (Ra) and disposal (Rd), in postabsorptive subjects by means of renal and splanchnic arteriovenous catheterization combined with phenylalanine and tyrosine isotope infusions. RESULTS: In the kidney, a relevant phenylalanine hydroxylation activity was detected (3.51 +/- 0.97 micromol/min x 1.73 m2 of body surface), whereas it was 2.48 +/- 1. 35 micromol/min x 1.73 m2 across the splanchnic area. These two sites together accounted for virtually the entire whole-body phenylalanine hydroxylation. Renal production of tyrosine from phenylalanine hydroxylation accounted for approximately 13% of whole-body tyrosine Ra, whereas renal total tyrosine Ra accounted for approximately 34% of whole-body tyrosine Ra. In the splanchnic area, these figures were approximately 9 and 40%, respectively. Hydroxylation accounted for approximately 70% of phenylalanine Rd in the kidney, as opposed to approximately 8% in the splanchnic area. CONCLUSIONS: These data indicate that hydroxylation represents the major route of phenylalanine disposal within the kidney. The kidney and the splanchnic bed together account for all of the whole-body phenylalanine hydroxylation. These data also provide a further explanation for the reduced tyrosine pools occurring in uremia.