A juvenile, female renal transplant recipient suffered two acute rejection episodes: the first on posttransplant day 31 while taking cyclosporine, prednisone, and mycophenolate mofetil (MMF); and the second on posttransplant day 67, when she was taking tacrolimus, prednisone, and MMF. Dosage of MMF was initially started at 2 g/d (corresponding to 600 mg MMF/m2 twice daily.), but was reduced to 250 mg/d to 500 mg/d after severe diarrhea and a paralytic ileus on posttransplant day 16. During therapy with tacrolimus, prednisone, and MMF, predose plasma mycophenolic acid (MPA) concentrations varied from 1.1 mg/L to 8.2 mg/L (median 3.0 mg/L). On posttransplant day 91, a 12-hour pharmacokinetic profile was obtained. The concentrations of MPA and its metabolites were determined with a validated high-performance liquid chromatography (HPLC) procedure. After oral MMF (250 mg) administration, the MPA concentration showed an atypical decline from a predose concentration of 6.0 mg/L to a value of 3.8 mg/L at 75 minutes postdose, and 3.4 mg/L at 6 hours postdose, before returning to 6.0 mg/L after 12 hours. The 12-hour area under the concentration–time curve (AUC) values for MPA and its major metabolite the phenolic glucuronide MPAG were 55.1 mg·h/L and 800 mg·h/L, respectively. An unusually high concentration (12-h AUC, 165 mg·h/L) of the phenolic glucose conjugate of MPA was found. The apparent renal clearance of MPAG was only 2.2 mL/min. Her creatinine clearance was 30 mL/min. MPAG clearances have been reported to range from approximately. 5.5 mL/min to 35 mL/min at a creatinine clearance of approximately 30 mL/min in renal transplant recipients. The authors' findings suggest that conjugation and clearance of MPA through the kidney is strongly impaired in this patient. The relatively high predose MPA concentrations could result from an enhanced enterohepatic circulation of MPA and its metabolites.
Problemstellung: Der sekundäre Hyperparathyreoidismus (sHPT) stellt einen wesentliche Faktor in der Pathogenese der renalen Osteopathie und für die erhöhte kardiovaskuläre Morbidität/Mortalität bei Patienten mit chronischer Niereninsuffizienz (CKD) dar. Bei Erwachsenen CKD-Patienten, insbesondere bei solchen mit einem erhöhtem Calcium-Phosphat-Produkt (Ca x P), ist die Behandlung mit Calcimimetika (Cinacalcet), eine anerkannte Therapieoption. Diese führen durch selektive Hemmung der Nebenschilddrüse zu einer dosisabhängigen PTH-Senkung. Langzeitergebnisse zur Cinacalcet-Therapie bei Kindern und Jugendlichen mit sHPT fehlen.
The choice and timing of kidney replacement therapy (KRT) is influenced by clinical factors, laboratory features, feasibility issues, family preferences, and clinicians' attitudes. We analyzed the factors associated with KRT modality and timing in a multicenter, multinational prospective pediatric cohort study.
A gradual decline in the glomerular filtration rate (GFR) is a general problem in patients after renal transplantation that may be due to several factors.The glomerular filtration rate (GFR) was estimated using the corrected Schwartz formula in 16 pediatric renal transplant recipients over a period of 5 years post-transplant. Several potential risk factors for graft outcome were analyzed. The mean age of the patients (8 female, 8 male) at the time of transplantation was 11.1 years (range: 2.7-17.3). All patients received a cadaveric renal graft for the first time. Immunosuppression consisted of cyclosporine in combination with steroids in all children treated; 3 patients received azathioprine in addition. Blood pressure (BP) was monitored regularly and its extent was expressed by an antihypertensive treatment (AHT) score.At the end of the first post-transplant year the mean GFR was 88 +/- 24 ml/min/1.73 m2. During the following 4 years the GFR declined to 68 +/- 29 ml/min/1.73 m2 representing an overall GFR loss of 20 ml/min/1.73 m2 (23%). With regard to the GFR loss, 2 groups could be distinguished. The first group of 7 patients showed a significant GFR decrease from 89 +/- 26 to 49 +/- 27 ml/min/1.73 m2 (p = 0.0025), whereas the second group of 9 patients had a relatively constant GFR during the 5 years (87 +/- 26 and 83 +/- 24 ml/min/1.73 m2). In each group, two acute rejections were observed in the first post-transplant year. Blood pressure, expressed by an AHT score, increased in Group 1 moresso than in Group 2 during the 5 years.During the course of a 5-year period post-transplant the GFR declined significantly in 7 of 16 patients. One of the factors responsible for GFR loss is probably the increase in blood pressure.
We investigated the effects of nutritional vitamin D supplementation on markers of bone and mineral metabolism, i.e. serum levels of fibroblast growth factor 23 (FGF23), Klotho, bone alkaline phosphatase (BAP) and sclerostin, in two cohorts with chronic kidney disease (CKD).In all, 80 vitamin D-deficient children were selected: 40 with mild to moderate CKD from the ERGO study, a randomized trial of ergocalciferol supplementation [estimated glomerular filtration rate (eGFR) 55 mL/min/1.73 m2], and 40 with advanced CKD from the observational Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) study (eGFR 24 mL/min/1.73 m2). In each study, vitamin D supplementation was started in 20 children and 20 matched children not receiving vitamin D served as controls. Measures were taken at baseline and after a median period of 8 months. Age- and gender-related standard deviation scores (SDSs) were calculated.Before vitamin D supplementation, children in the ERGO study had normal FGF23 (median 0.31 SDS) and BAP (-0.10 SDS) but decreased Klotho and sclerostin (-0.77 and -1.04 SDS, respectively), whereas 4C patients had increased FGF23 (3.87 SDS), BAP (0.78 SDS) and sclerostin (0.76 SDS) but normal Klotho (-0.27 SDS) levels. Vitamin D supplementation further increased FGF23 in 4C but not in ERGO patients. Serum Klotho and sclerostin normalized with vitamin D supplementation in ERGO but remained unchanged in 4C patients. BAP levels were unchanged in all patients. In the total cohort, significant effects of vitamin D supplementation were noted for Klotho at eGFR 40-70 mL/min/1.73 m2.Vitamin D supplementation normalized Klotho and sclerostin in children with mild to moderate CKD but further increased FGF23 in advanced CKD.
Hantaviren können die Nephropathia epidemica auslösen. In diesem Jahr kam es zu einer kleinen Epidemie v.a. in Süddeutschland. Wir berichten über eine 11-jährige Patientin, die nach unspezifischen Allgemeinsymptomen an einer akuten Niereninsuffizienz erkrankte. Es zeigte sich eine Oligurie und kontinuierlicher Anstieg der Retentionsparameter (Harnstoff 30 mmol/l, Kreatinin 700 μmol/l), große Proteinurie (5,1g/g Krea) ohne Mikrohämaturie und normotone Blutdruckwerte. Sonografisch fanden sich bds. hyperechogene und vergößerte Nieren. Die daraufhin durchgeführte Nierenbiopsie ergab den Befund einer ausgeprägten hämorrhagischen tubulointerstitiellen Nephritis, passend zu der Verdachtsdiagnose einer akuten Nephropathia epidemica. Der serologische Befund bestätigte die Hanta-Virus-Infektion. Durch hohe Flüssigkeitsumsätze von bis zu 5 L/d konnte eine Dialysebehandlung abgewendet werden. Innerhalb einer Woche normalisierten sich die Retentionsparameter, die Proteinurie sistierte.
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