Egon Balzar

Randomized trial of tacrolimus versus cyclosporin microemulsion in renal transplantation.

Abstract This study was undertaken to compare the efficacy and safety of tacrolimus (Tac) with the microemulsion formulation of cyclosporin (CyA) in children undergoing renal transplantation. A 6-month, randomized, prospective, open, parallel group study with an open extension phase was conducted in 18 centers from nine European countries. In total, 196 pediatric patients (<18 years) were randomly assigned (1:1) to receive either Tac (n=103) or CyA microemulsion (n=93) administered concomitantly with azathioprine and corticosteroids. The primary endpoint was incidence and time to first acute rejection. Baselinecharacteristics were comparable between treatment groups. Tac therapy resulted in a significantly lower incidence of acute re-jection (36.9%) compared with CyA therapy (59.1%) (P=0.003). The incidence of corticosteroid-resistant rejection was also significantly lower in the Tac group compared with the CyA group (7.8% vs. 25.8%, P=0.001). The differences were also significant for biopsy-confirmed acute rejection (16.5% vs. 39.8%, P<0.001). At 1 year, patient survival was similar (96.1% vs. 96.6%), while 10 grafts were lost in the Tac group compared with 17 graft losses in the CyA group (P=0.06). At 1 year, mean glomerular filtration rate (Schwartz estimate) was significantly higher in the Tac group (62±20 ml/min per 1.73 m2, n=84) than in the CyA group (56±21 ml/min per 1.73 m2, n=74, P=0.03). The most frequent adverse events during the first 6 months were hypertension (68.9% vs. 61.3%), hypomagnesemia (34.0% vs. 12.9%, P=0.001), and urinary tract infection (29.1% vs. 33.3%). Statistically significant differences (P<0.05) were observed for diarrhea (13.6% vs. 3.2%), hypertrichosis (0.0% vs. 7.5%), flu syndrome (0.0% vs. 5.4%), and gum hyperplasia (0.0% vs. 5.4%). In previously non-diabetic children, the incidence of long-term (>30 days) insulin use was 3.0% (Tac) and 2.2% (CyA). Post-transplant lymphoproliferative disease was observed in 1 patient in the Tac group and 2 patients in the CyA group. In conclusion, Tac was significantly more effective than CyA microemulsion in preventing acute rejection after renal transplantation in a pediatric population. The overall safety profiles of the two regimens were comparable.

Reproducible erythroid aplasia caused by mycophenolate mofetil

Abstract Anemia secondary to mycophenolate mofetil (MMF) was recently described in experimental animals. A clinical association between MMF and anemia has been observed, but there are no proven reports. We describe a girl with chronic graft failure who developed erythroid aplasia under immunosuppression with MMF. She showed prompt resolution when MMF was discontinued and a recurrence of this clinical course when MMF was restarted. As re-challenge with a medication is the most definitive approach for showing a direct relationship between the drug and the side effect, this case clearly demonstrates that MMF can cause erythroid aplasia.

Urinary tract infections beyond the early post-transplant period in pediatric renal graft recipients

ZusammenfassungHintergrundHarnwegsinfekte sind eine häufige bakterielle Komplikation nach Nierentransplantation bei Erwachsenen und Kindern. Es existieren jedoch nur wenige Daten bei pädiatrischen Patienten in der Frühphase nach Nierentransplantation. Ziel dieser Studie war es, Häufigkeit, Risikofaktoren und Einfluss auf die Kurzzeit Transplantatfunktion von Harnwegsinfekten in der späteren Phase nach Nierentransplantation zu untersuchen.Patienten und MethodenIm Zeitraum von 1997 bis 2000 wurden 47 Kinder, die 58 Transplantate erhielten, untersucht. Sie waren zum Zeitpunkt der Analyse seit 3,5 Jahren transplantiert. Die Definition eines Harnwegsinfektes war eine signifikante Bakteriurie (>105 Keime/ml) und Symptome.Ergebnisse15 (32%) von den 47 Patienten hatten 1 bis 7 Harnwegsinfekte im Untersuchungszeitraum. Insgesamt wurden in den 3 Jahren 35 Harnwegsinfekte dokumentiert. Das mediane Alter bei Diagnose war 5,5 Jahre (1,8–24,2 Jahre). Geschlecht, Organquelle, Immunsuppression und Grundkrankheit hatten keinen Einfluss auf die Häufigkeit der Harnwegsinfekte. Während der Infektion kam es zu einem signifikantem Kreatininanstieg, während das C-reaktive Protein nicht anstieg.SchlussfolgerungUnsere Ergebnisse zeigen, dass Harnwegsinfekte auch nach der Frühphase nach Nierentransplantation ein häufiges aber meist harmloses Ereignis sind. Um Fragen über die Langzeitfolgen dieser Infekte auf die Transplantatfunktion zu beantworten, sind ausgedehntere Untersuchungen notwendig.SummaryBackgroundUrinary tract infection is a frequent bacterial complication after renal transplantation in adults and children, however there are only very limited data on children beyond the early post-transplant period. In this study we investigated urinary tract infections in pediatric outpatients who had received transplants more than six months previously. Incidence, risk factors and impact on short-term graft function were analyzed.Methods47 children who had received a total of 58 allografts were analyzed between 1997 and 2000. At the time of analysis they had had their transplants for an average of 3.5 years (range 0.5–9.4). Urinary tract infection was defined as the presence of both significant bacteriuria (>105 CFU/ml) and symptoms.ResultsOf the 47 patients, 15 (32%) had from 1 to 7 urinary tract infections each. In total 35 infections were recorded. Median age at urinary tract infection was 5.5 years (range 1.8–24.2). Gender, donor source, immunosuppression and underlying disease (urologic vs. nonurologic) did not influence the incidence of urinary tract infection. Creatinine but not C-reactive protein rose significantly during the infection.ConclusionsOur data suggest that urinary tract infection remains a frequent but mostly benign complication in the pediatric transplant population, even beyond the early post-transplant period. More extended studies are needed to assess the long-term effects on graft function.

Tubulointerstitial nephritis and uveitis: an immunological disorder?

A 14-year-old boy with tubulointerstitial nephritis and uveitis (TINU syndrome) is described. Nephropathy improved without systemic cortisone treatment, whereas uveitis relapsed and was treated with topical steroids. Blood cell immunological analysis and serum analysis revealed signs of cytotoxic T-cell, macrophage and granulocyte activation, which declined as the clinical symptoms improved. This may be interpreted as an indication of their significance as markers in the pathogenesis of this syndrome or as part of a microbial-triggered immune response.

Reduction of delayed renal allograft function using sequential immunosuppression

Abstract  Previous data suggested that outcome in small children with cadaveric renal transplantation might be improved with sequential therapy. This protocol combines augmented immunosuppression [by including antibody induction (ATG)] with avoidance of nephrotoxic medication in the immediate postoperative phase (by delayed start of cyclosporin therapy). In this report, we describe effects of this approach in 12 consecutively transplanted small children of less than 5 years of age (mean 3.2 years) who received a cadaveric renal graft at our institution between 1991 and 1998. Up to 1996 triple therapy (prednisolone, azathioprine, cyclosporin) and since 1997 sequential therapy (prednisolone, azathioprine, ATG until serum creatinine <2 mg/dl, then cyclosporin) was used for immunosuppression. Five children had delayed graft function (45.4%), all of whom were treated with triple therapy including cyclosporin from the very beginning, whereas children treated by the sequential protocol gained immediate graft function (P<0.05). There was no statistical difference between the two protocols concerning frequency or severity of rejections (67% vs. 60%, all steroid responsive), difference in the incidence of either bacterial or viral infections, or between the incidence of hypertension. Although not reaching statistical significance, 1-year graft survival rates also increased from 60% for triple therapy to 80% for sequential therapy. In conclusion, our findings confirm previous stud- ies showing that outcome in small children under- going renal transplantation may be improved by specially tailored treatment protocols such as sequential therapy.

MRI in the diagnosis of a peritoneal leak in continuous ambulatory peritoneal dialysis

Abstract. Mechanical problems in continuous ambulatory peritoneal dialysis (CAPD) can result in ultrafiltration failure and disruption of CAPD therapy. The recently described tool of CT peritoneography with water-soluble contrast medium has the disadvantage of radiation and instillation of nephrotoxic substances. We report a child with a peritoneal leak diagnosed by MRI after instillation of a gadodiamide-dialysate mixture. This method provided good anatomical detail without radiation or nephrotoxic agents.

Chronische Peritonealdialyse bei Kindern: Ergebnisse der Kinderdialyse Wien

SummaryBackgroundPeritoneal Dialysis (PD) has been increasingly used as primary renal replacement therapy in children over the last 10 years. The aim of this study was to investigate complications of PD and compare the collected data with our own historical data and data from the literature.Patients and methods33 children (17 boys, mean age 4,9 years) who underwent PD for the first time due to chronic renal failure between 1994 and 2003 were enrolled in this retrospective survey.Results398 months on PD in total, with a mean time of 12 months per patient were investigated. The occurrence rate of peritonitis was one per 14,2 months and for exit-site-infection one per 13,2 months. 23 children underwent renal transplantation, one child was switched to hemodialysis, two children died (one because of PD-unrelated circumstances), reflecting a 1-year survival rate of 94%.ConclusionsPeritoneal dialysis has become the most frequently used modality of renal replacement therapy in children, with a trend towards smaller children and infants. PD can be managed safely and successfully in children of all age groups, including even newborns.ZusammenfassungHintergrundIn den letzten 10 Jahren kam es zu einem starken Ansteigen des Einsatzes der Peritonealdialyse als primäre Nierenersatztherapie bei Kindern. Ziel dieser Studie war es, die Komplikationen unter diesen geänderten Bedingungen zu untersuchen und mit unseren historischen Ergebnissen und aktuellen Daten aus der Literatur zu vergleichen.Patienten und Methoden33 Kinder (17 Knaben, mittleres Alter 4,9 Jahre, davon 14 Kinder unter 2 Jahren), die zwischen 1994 und 2003 aufgrund eines chronischen Nierenversagens erstmals eine Peritonealdialyse benötigten, wurden in die retrospektive Untersuchung eingeschlossen.ErgebnisseBei einer gesamten Beobachtungszeit von 398 Dialysemonaten betrug die durchschnittliche Zeit an der Peritonealdialyse 12 Monate. Dabei wurde eine Peritonitis in 14,2 Behandlungsmonaten beobachtet. Katheteraustrittsinfektionen traten in 1/13,2 Monaten auf. Bei 23 Kindern wurde eine Nierentransplantation, bei einem Kind ein Wechsel zur Hämodialyse durchgeführt, 2 Kinder verstarben, davon eines an nicht dialyseasszzierten Komplikationen. Dies entspricht einem 1-Jahresüberleben von 94%.SchlussfolgerungDie Peritonealdialyse entwickelte sich zur häufigsten Dialysemodalität im Kindesalter mit einem deutlichen Wandel hin zur Behandlung von kleineren Kindern und Säuglingen. Die Peritonealdialyse kann als Nierenersatztherapie ab dem Zeitpunkt der Geburt erfolgreich und sicher durchgeführt werden.BACKGROUND Peritoneal Dialysis (PD) has been increasingly used as primary renal replacement therapy in children over the last 10 years. The aim of this study was to investigate complications of PD and compare the collected data with our own historical data and data from the literature. PATIENTS AND METHODS 33 children (17 boys, mean age 4.9 years) who underwent PD for the first time due to chronic renal failure between 1994 and 2003 were enrolled in this retrospective survey. RESULTS 398 months on PD in total, with a mean time of 12 months per patient were investigated. The occurrence rate of peritonitis was one per 14.2 months and for exit-site-infection one per 13.2 months. 23 children underwent renal transplantation, one child was switched to hemodialysis, two children died (one because of PD-unrelated circumstances), reflecting a 1-year survival rate of 94%. CONCLUSIONS Peritoneal dialysis has become the most frequently used modality of renal replacement therapy in children, with a trend towards smaller children and infants. PD can be managed safely and successfully in children of all age groups, including even newborns.

Low serial serum neopterin does not predict low risk for chronic renal graft rejection

Abstract Research has provided new and potent immunosuppressants which can potentially stop ongoing rejection. Subclinical rejection is a particular problem in the pediatric age group and early identification of children at risk is of the utmost importance. Neopterin has been previously shown to be a non-specific but sensitive marker for immunologic activity. In this study we hypothesized that low serum neopterin in the 1st year after transplantation predicts a low risk of chronic rejection. We retrospectively analyzed serial neopterin data obtained beyond the early postoperative period in 21 children and correlated the peak and average with glomerular filtration rate (GFR) loss during the subsequent years (P=0.63, NS, r=0.10). Our results show that serum neopterin did not differ between the majority of children who developed chronic transplant dysfunction and children with stable transplant function beyond the early post-transplant period. Thus serum neopterin failed to delineate a low-risk population who might be spared more invasive diagnostic procedures such as protocol biopsy.

Use of prostaglandin I2 in three small children at high risk of early renal graft thrombosis

We report the use of prostaglandin I2 (PGI2) in three small children weighing less than 15 kg at high risk of graft thrombosis after cadaveric renal transplantation complicated by acute tubular necrosis. PGI2 was started at a dose of 5 ng/kg per min within the first 6 h after transplantation, and was continued for 12–15 days. Before and during PGI2 infusion, color-coded and pulsed Doppler sonography was performed. We found immediate restoration of diastolic flow, consistent with a decrease in vascular resistance. During the subsequent days, the sonographically assessed flow pattern and clinical graft function improved gradually. None of the three consecutively treated children developed graft thrombosis or lost his graft; no clinically relevant bleeding or adverse hemodynamic or pulmonary effects were seen.

Renal transplant hemodynamics in children: Prospective analysis of colour coded versus pulsed Doppler sonography

In 30 children with renal allografts the diagnostic validity of pulsed Doppler (PD) versus colour coded Doppler (CD) sonography was assessed prospectively. 46 PD examinations were performed calculating the resistive index (RI) in the segmental arteries in comparison to 46 CD scans, where renal blood flow throughout the grey-scale image was displayed. In addition, point-spectral analysis with calculation of the RI was also performed on the CD scans. The time for examination ranged from five to ten minutes for the PD and from three to five minutes for the CD study. Concordant findings for the PD and CD technique were generally obtained (normal blood flow pattern on PD — excellent visualization of renal blood flow on CD, reduced or reversed diastolic flow on PD — poor visualization of renal blood flow on CD). There was close correlation of the RI values obtained by the PD and CD scans. CD sonography facilitated point-spectral analysis in shortening the time for examination. The ability to visualize focal hemodynamic alterations provided a higher diagnostic accuracy in comparison to PD sonography.