A possible role for nitric oxide in modulating the functional cyclosporine toxicity by arginine

A possible role for nitric oxide in modulating the functional cyclosporine toxicity by arginine. The renal damage consequent to cyclosporine A (CsA) administration ranges from hemodynamic alterations to irreversible chronic lesions. The initial vasoconstriction depends upon the imbalance between the various modulators of the renal vascular tone, among which the most powerful are endothelins and nitric oxide (NO). CsA could play a crucial role by inhibiting the Ca++/calmodulin-mediated activation of the constitutive NO synthase (NOS) isoform, which converts L-arginine (L-Arg) into NO and citrulline, with a 1:1 stoichiometry. To investigate the possibility of modulating CsA nephrotoxicity with L-Arg we studied six groups (G) of Lewis rats treated with daily gavage up to eight weeks: G1, CsA 40 mg/kg; G2, G1 plus L-Arg 300 mg/kg; G3, G2 plus the competitive inhibitor of NOS, NG-nitro-L-Arg (L-NNA); G4, L-Arg alone; G5, L-NNA alone; and G6, controls receiving vehicle alone. After eight weeks L-Arg treated rats were protected against the toxic effects of CsA [creatinine (Cr) values, G2, 0.62 ± 0.05 mg/dl vs. G1, 0.99 ± 0.16 mg/dl, P < 0.001; proteinuria (P), G2, 7.2 ± 1.02 mg/day vs. G1, 15.1 ± 1.9 mg/day, P < 0.01]. The administration of L-NNA abolished the protective effect of L-Arg (G3, Cr 1.23 ± 0.16 mg/dl; P 16.9 = 2.3; P < 0.02 and P < 0.005, respectively vs. G2). The levels of Cr in G2 rats were superimposable to control groups. The NOS activity, evaluated by measuring [3H]citrulline formation from [3H]L-Arg in kidney homogenates, was blocked by L-NNA in G5 (0.019 ± 0.009 pmol/min/mg proteins vs. G6 0.047 ± 0.002, P < 0.01). NOS activity was significantly increased versus controls in G1 (0.110 ± 0.032, P < 0.01) and G2 (0.088 ± 0.009, P < 0.02), while L-NNA reversed this phenomenon (G3, 0.052 ± 0.03). The expression of mRNA encoding for cNOS and iNOS was only slightly increased in CsA-treated rats. We suggest that CsA treatment increases NOS activity in the kidney by a mechanism which does not require a de novo synthesis of the enzyme. Such an increase, that may be devoted to counterbalance the vasoconstrictive effects of the drug, is unable to reduce the toxic effect of CsA in the absence of exogenous L-Arg. Administration of L-Arg is likely to reduce CsA nephrotoxicity by accomplishing the higher request of activated NOS for its substrate, thus potentiating NO synthesis in the kidney.

[Children on peritoneal dialysis and enteral feeding: indications and outcomes]

Despite improvements in overall prognosis, in the quality of life and in growth targets, children on peritoneal dialysis are subject to a high risk of growth retardation, especially if the disease begins in the early stages of life. In these patients, spontaneous feeding often does not provide an adequate intake of nutrients and early start of enteral nutrition needs to be considered. An intensive nutritional approach should always be established early and can be technically achieved using either a naso-gastric tube or a gastrostomy. In Italy, the first approach often involves the use of a naso-gastric tube despite epidemiological data suggesting the superiority of gastrostomy when the required outcome is improvement in growth parameters. Particular attention should be paid to the technique of gastrostomy. Despite this intensive approach, not all patients achieve the desired outcome of adequate growth probably because not all the possible mechanisms involved have yet been discovered

Peritoneal dialysis in infants: the experience of the Italian Registry of Paediatric Chronic Dialysis

Although chronic peritoneal dialysis (CPD) is considered the replacement therapy of choice for infants with end-stage renal failure, many questions persist about treatment risks and outcomes

Splenic Vessels as a Rescue for Pediatric Kidney Retransplantation in Children With Iliac-caval Agenesis or Thrombosis

Background.Unavailability of the iliac-caval system due to thrombosis or aberrant anatomy may preclude kidney transplantation (KT) in small infants, exposing them to the complications of long-term dialysis. A tailored approach may enable KT also in these difficult patients. Methods.We report the cases of 2 pediatric patients with a history of long-term hemodialysis, a previously failed KT, pending exhaustion of vascular accesses for dialysis, and unsuitability of the iliac-caval axis as a site for KT. Both patients were successfully managed by using splenic vessels as a source of arterial inflow or venous drainage during KT. Notably, one patient also had a previous liver transplant. Results.Both kidney grafts showed primary function. Posttransplant courses were uneventful, and no rejection episode was observed. At 64- and 10-mo follow-ups, both children had optimal renal function and excellent quality of life. Conclusions.When the iliac-caval system is unavailable, kidney graft implantation on splenic vessels represents a safe and effective option for pediatric KT

Encapsulating peritoneal sclerosis in paediatric peritoneal dialysis patients: the experience of the Italian Registry of Pediatric Chronic Dialysis

Paediatric literature about encapsulating peritoneal sclerosis (EPS) is limited and comes primarily from anecdotic experiences. In this study, we described the incidence and characteristics of EPS in a large paediatric chronic peritoneal dialysis (CPD) patient population

Corrigendum to “A multicenter retrospective study of calcineurin inhibitors in nephrotic syndrome secondary to podocyte gene variants.”

DOI of original article: https://doi.org/10.1016/j.kint.2023.02.022 The authors regret to report that Hee Gyung Kang, Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea, inadvertently was not included in the list of authors of the published article. The collaborator was removed from the Acknowledgments. This has been corrected in the article online. The authors would like to apologize for any inconvenience caused.</p

Mineral Metabolism in European Children Living with a Renal Transplant: A European Society for Paediatric Nephrology/European Renal Association–European Dialysis and Transplant Association Registry Study

Background and objectives Data on mineral metabolism in pediatric renal transplant recipients largely arise from small single-center studies. In adult patients, abnormal mineral levels are related to a higher risk of graft failure. This study used data from the European Society for Paediatric Nephrology/European Renal Association–European Dialysis and Transplant Association Registry to study the prevalence and potential determinants of mineral abnormalities, as well as the predictive value of a disturbed mineral level on graft survival in a large cohort of European pediatric renal transplant recipients.Design, setting, participants, & measurements This study included 1237 children (0–17 years) from 10 European countries, who had serum calcium, phosphorus, and parathyroid hormone measurements from 2000 onward. Abnormalities of mineral metabolism were defined according to European guidelines on prevention and treatment of renal osteodystrophy in children on chronic renal failure.Results Abnormal serum phosphorus levels were observed in 25% (14% hypophosphatemia and 11% hyperphosphatemia), altered serum calcium in 30% (19% hypocalcemia, 11% hypercalcemia), and hyperparathyroidism in 41% of the patients. A longer time since transplantation was associated with a lower risk of having mineral levels above target range. Serum phosphorus levels were inversely associated with eGFR, and levels above the recommended targets were associated with a higher risk of graft failure independently of eGFR.Conclusions Abnormalities in mineral metabolism are common after pediatric renal transplantation in Europe and are associated with graft dysfunction

Mineral metabolism in European children living with a renal transplant: a European society for paediatric nephrology/european renal association-European dialysis and transplant association registry study

Data on mineral metabolism in pediatric renal transplant recipients largely arise from small single-center studies. In adult patients, abnormal mineral levels are related to a higher risk of graft failure. This study used data from the European Society for Paediatric Nephrology/European Renal Association-European Dialysis and Transplant Association Registry to study the prevalence and potential determinants of mineral abnormalities, as well as the predictive value of a disturbed mineral level on graft survival in a large cohort of European pediatric renal transplant recipients