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G Offner

Publications and source records attributed to G Offner.

At least 19 recordsLinked to original sources
PubMed2006

Superior long-term graft function and better growth of grafts in children receiving kidneys from paediatric compared with adult donors.

BACKGROUND: Organs from paediatric donors are often not accepted for paediatric recipients because previous reports suggested inferior graft function for small kidneys transplanted in children. On the other hand, studies have shown that kidneys of adult donors transplanted into children down-regulate filtration after transplantation and may not increase their function to the need of the growing child. METHODS: We assessed 64 male and 35 female (total n = 99) white children aged <10 years (male: mean 5.1 years, SD 2.8; female: mean 5.8 years, SD 3.4) who had received cadaveric kidney transplants at our centre between 1990 and 2005. Mean observation time was 5.9 years, SD 4.0. The children were divided into two groups depending on the kidney donor age: 63 children (mean age 5.0 years, SD 2.9) received an organ of an adult, and 39 (mean age 6.4 years, SD 3.4) of a paediatric donor. Immunosuppression was performed with prednisolone, cyclosporin A microemulsion+/-mycophenolate mofetil. RESULTS: Three to five years after transplantation the calculated glomerular filtration rate corrected to body surface was significantly higher in recipients of paediatric organs. The size of paediatric grafts doubled in the first years after transplantation while adult grafts had a stable size. Graft survival was comparable in both groups during observation time. CONCLUSIONS: We conclude that paediatric donor kidneys should be given preferentially to paediatric recipients due to better long-term function.

Adolescent↗
PubMed2006

Kidney transplantation without prior dialysis in children: the Eurotransplant experience.

Kidney transplantation without prior dialysis may prevent dialysis-associated morbidity. We analyzed the outcome of 1113 first kidney transplants in children performed between 1990 and 2000 in the Eurotransplant community. Enlistment for a deceased donor kidney before start of dialysis (127/895, 14%) made dialysis redundant in 55% of cases. Mean residual creatinine clearance at transplantation of these patients was 8 mL/min/1.73 m(2). Pre-emptive transplantations of deceased donor kidneys showed less acute rejections (52% vs. 37% rejection-free at 3 years, p = 0.039), compared to transplantations following dialysis. The difference in graft survival between non-dialyzed and dialyzed patients (82% vs. 69% at 6 year) did not reach statistical significance (p = 0.055). No differences were noted after living donor transplantation. Multivariate analysis showed that the period of transplantation was the strongest predictor of graft survival (p < 0.001). Congenital structural abnormalities such as primary kidney disease predominated in nondialyzed patients as compared to dialyzed patients (p < 0.001); this factor did not influence graft survival. Based on our conclusion that pre-emptive transplantation is at least as good as post-dialysis transplantation, as well as on quality of life arguments, we recommend to consider pre-emptive transplantation in children with end-stage renal failure.

Adolescent↗
PubMed2006

Living related kidney donation as an advantage for growth of children independent of glomerular filtration rate.

Seventy-two pediatric kidney recipients of living related donors (LRD) and 145 of cadaveric donors (CAD) were analyzed for height standard deviation scores (Ht-SDS) and glomerular filtration rates (GFR) directly after transplantation and over the following 5 years. GFR was significantly higher immediately after transplantation in LRD compared with CAD recipients; however, GFR was not different during the 5-year follow-up period. Although Ht-SDS was comparable at the time of transplantation in both groups, it was significantly higher among LRD recipients over the next 5 years. Multivariate and covariate analyses showed that Ht-SDS after 5 years was mainly influenced only by CAD vs LRD and not by GFR or other factors, namely, donor age, rejections, time of dialysis, preemptive transplantation, age at transplantation, or immunosuppression. Thus, children receiving grafts from LRD showed a better catch-up growth independent of the GFR than those after CAD transplantation. We concluded that the period of donor death and prolonged cold ischemia in CAD grafts may lead to changes in gene expression of cytokines and other mediator molecules that affect bone metabolism. Better growth seems to be an additional factor supporting the policy of LRD kidney transplantation as the best option in children.

Adolescent↗
PubMed2006

Nodular B-cell aggregates associated with treatment refractory renal transplant rejection resolved by rituximab.

Acute rejection episodes leading to treatment refractory early graft loss are increasingly rare events in living related renal transplantation today. Pathophysiologic pathways often remain unsolved. We report on tubulointerstitial and vascular rejection developing within 2 weeks after transplantation in a 12-year-old boy treated with cyclosporine, mycophenolate, steroids and double blinded basiliximab. Despite steroid pulses, switch to tacrolimus and ATG serum creatinine peaked at 347 micromol/L with imminent graft loss and ongoing C4d negative cellular vascular rejection. Permanent gain of function was only achieved after a single dose of rituximab. Retrospectively CD20+ nodular B-cell aggregates could be demonstrated in all three biopsies obtained prior to rituximab and resolved concomitantly with functional improvement. Our case for the first time demonstrates resolution of nodular CD20+ infiltrates and decline of OX40, NF-kappaB and CTL transcription shortly after rituximab indicating a B-cell facilitated C4d negative pathway. Single dose rituximab may effectively reverse even long-lasting refractory rejection.

Antibodies, Monoclonal↗
PubMed2004

Cyclosporine in pediatric kidney transplantation.

Before the era of cyclosporine (CsA), immunosuppression with azathioprine and steroids resulted in high rejection rates and severe growth retardation in pediatric renal transplant recipients. In the early 1980s, immunosuppression with CsA was introduced for children. Because of differences in metabolism rates and relation of weight and body surface area, special pediatric dosing regimens and monitoring strategies had to be developed. Use of CsA led to a decreased number of acute rejections and, consequently, to a marked increase in graft survival rates. The growth rates of transplanted children were significantly higher under CsA-based immunosuppression than with classical regimens. This was due to a decreased need of steroid co-administration. Main side effects of CsA in children were nephrotoxicity and hirsutism. The introduction of CsA microemulsion in the 1990s led to more reliable absorption profiles and to a lower interindividual variability of CsA area-under-the-curve concentrations and thus to another improvement in rejection rates. New monitoring strategies, based on CsA levels taken 2 hours' postdose, seem promising. In pediatric transplantation, CsA is often successfully combined with an antibody-induction therapy in order to reduce the number of early acute rejections. Combination with mycophenolate mofetil reduces the appearance of chronic rejection. Additional therapy with ToR inhibitors might enforce a reduction of CsA doses and therefore lead to a reduction of CsA toxic effects.

Age Factors↗
PubMed2004

A single center clinical experience in intensive care management of 104 pediatric renal transplantations between 1998 and 2002.

Only a few publications about the treatment in the intensive care unit (ICU) after pediatric renal transplantation have been published yet. As there are no guidelines, we hereby describe the results and recommendations of our transplant unit. A total of 104 renal transplantations have been performed in 96 children at our center since 1998. The age of the children has ranged from 6 months to 18 yr and their body weight from 6 kg to 110 kg. A special fluid management was performed in order to avoid hypotension and hypoperfusion of the graft. Systolic arterial pressure was kept at elevated levels above 100 mmHg during the first day after transplantation. The children remained on the respirator for 4-8 h after transplantation. Anticoagulation was performed using low dose heparin because of the size mismatch of the anastomosed vessels. The mean time in the ICU for the pediatric patients aged <3 yr was 2 days and for children older than 3 yr was 1 day. The main complications after renal transplantation in the ICU were disorders of electrolytes, acute renal failure because of a non-functioning graft (12%), bleeding from the anastomoses (4%), arterial or venous thrombosis (1%), arterial hypertension and pulmonary edema, defined as radiographic evidence (1%). In case of non-function peritoneal- or hemodialysis were performed in the ICU. Young children were more frequently affected than older children. From 1998-2002 one patient died during the ICU time. The 3 yr graft survival rate was 90%. To sum up, children undergoing renal transplantation should be treated in a specialized unit postoperatively to avoid early non-functioning of the graft and extrarenal complications. General guidelines for postoperative care should be established.

Adolescent↗
PubMed2004

Long-term follow-up of pediatric transplant recipients: mycophenolic acid trough levels are not a good indicator for long-term graft function.

BACKGROUND: Mycophenolate mofetil (MMF) has the potential of decreasing acute rejection episodes early following renal transplantation. Pharmocokinetic monitoring of mycophenolic acid (MPA) trough levels is performed by many centers. MMF has also proved successful in improving long-term graft function in patients with chronic allograft nephropathy (CAN). However, no data for long-term monitoring of MPA in children have yet been published. METHODS: MMF therapy with a dose of 600 mg/m2 twice daily was initiated in 42 children (median age 9.4 yr, range 1.4-15.1) after a median period of 3.8 yr (range 1.0-10.6) post-transplantation-- according to significant increases in serum creatinine. CAN was diagnosed by renal biopsy and the amount of fibrosis was quantified with PicroSiriusRed staining. MMF therapy was combined with ciclosporin A and prednisolone. MPA-C0-levels, measured by high-pressure liquid chromatography, were tested every 3 months. In 12 children a full MPA area under the curve concentration (AUC) was measured. The glomerular filtration rate (GFR) was calculated at the start of MMF therapy and 2 yr later. RESULTS: After initiation of MMF, the calculated GFR did not decrease further in 22 children and mean GFR remained stable for 2 yr in the whole study group. There was a significant correlation between MPA levels 75 min after administration and the full AUC (r = 0.94, p < 0.001) but no correlation between trough levels and AUC (r = -0.07, p > 0.05). The mean MPA trough level was 2.8 +/- 1.3 ng/mL. The intra-individual coefficient of variation was 2.6 +/- 1.4. There was no correlation between mean MPA trough levels and GFR development after 2 yr (r = 0.03, p > 0.05). In children with an MPA level below 1.2 mg/L (n = 5), the mean GFR decline was no different to those with a higher level (p > 0.05). CONCLUSIONS: Drug monitoring of MPA trough levels had no impact on long-term graft function in kidney recipients. MPA levels taken 75 min after administration showed a high correlation with MPA-AUC whereas C0-levels did not correlate. The value of C75 drug measurements for monitoring renal allograft survival will have to be judged in future studies.

Adolescent↗
PubMed2003

Alterations of cyclosporin A metabolism induced by mycophenolate mofetil.

Unexpectedly lower CsA 2-h levels were found in patients who received additional immunosuppression by MMF in our center. The aim of this study is to prove whether there are differences in CsA metabolization when MMF is added to treatment. In 33 children who received an immunosuppression of prednisolone and CsA as well as in 15 children who were treated with additional MMF, C2 and C0 were taken. In 11 children, full AUC of CsA were obtained. C2 levels differed significantly (p < 0.05) between patients treated with (617 +/- 230 ng/mL) and without MMF (750 +/- 271 ng/mL) but with similar CsA dosages. C2 correlated better with the AUC than CsA levels at other time points with r = 0.95. The equation AUC = 139 + 6.17 x C2 was calculated to match best in a C2-limited sampling strategy. This formula proved to be safer than equations that had been published before. According to our findings, we suspect that MMF alters the CsA metabolism. When MMF is used in pediatric transplant recipients, either target values of CsA have to be changed or patients may require higher doses of CsA.

Adolescent↗
PubMed2003

Cyclosporin A monitoring by 2-h levels: preliminary target levels in stable pediatric kidney transplant recipients.

Clinical trials in adults have shown that management of transplanted patients with cyclosporin A (CsA) 2-h levels (C2) lead to superior outcome compared with monitoring of 12-h trough levels (C0). In both adults and children, C2 levels enabled a better estimation of the area under the curve concentration than C0 levels. Therefore, it can be suspected that C2 monitoring might also lead to a better outcome in children. Until now C2 target levels for children have not been defined. We measured C2 levels in 101 stable pediatric kidney recipients with a minimum time of 1 yr after transplantation. C2 levels were compared with changes in glomerular filtration rate (GFR) 6 months later. Median C2 levels in children after renal transplantation were 714 ng/mL (95% confidence interval 654-774). Patients with C2 levels below 750 ng/mL had a significantly higher percentage of decline in GFR than patients with C2 levels above 750 ng/mL (p < 0.05). In children with C2 levels below 500 ng/mL three acute rejections occurred in comparison with no rejection in the remaining patients (p < 0.05). We conclude that the lower C2 target level should be above 750 ng/mL in stable pediatric transplant recipients. An upper target level above 1000 ng/mL should be avoided. The question, whether C2 monitoring in pediatric kidney recipients is superior to C0 monitoring, is yet to be answered.

Child↗
PubMed2002

The beta2-microglobulin/cystatin C ratio--a potential marker of post-transplant lymphoproliferative disease.

BACKGROUND: As a consequence of more intensified immunosuppression, post-transplant lymphoproliferative disease (PTLD) is increasingly observed in patients after solid-organ transplantation. Beta2-microglobulin, a low-molecular weight protein (MW 11.8 kDa), is produced by all nucleated cells as part of the HLA complex. Its serum concentration is directly correlated with prognosis in patients with lymphatic neoplasms. Like other low-molecular weight proteins, beta2-microglobulin is eliminated by glomerular filtration. This complicates its use as a tumor marker in renal insufficiency. Cystatin C, a low-molecular weight protein of 13.3 kDa, is a new marker of kidney function largely unaffected by extrarenal disease. We, therefore, sought to assess the potential of the beta2-microglobulin/cystatin C ratio (beta2M/Cys) as a marker of lymphoproliferation. PATIENTS AND METHODS: Beta2M/Cys was determined by particle-enhanced immunonephelometry in sera from 132 children with different degrees of renal insufficiency, 5 of whom had lymphoproliferative disease. Renal function was assessed using the Schwartz formula. RESULTS: Beta2M/Cys was constant between 1.2 and 2.4 mg/mg for Schwartz GFR > or = 40 ml/min x 1.73 m2. With lower GFR, beta2M/Cys rose progressively, maximum values being found in the hemodialysis patients (4.85-11.73). Healthy renal transplant recipients had beta2M/Cys comparable to controls. With acute lymphoproliferative disease, all but one patient had significantly elevated beta2M/Cys between 2.68 and 3.68 mg/mg, which returned to normal in remission (1.67-2.35 mg/mg). The sensitivity of a beta2M/Cys ratio > 2.4 mg/mg for the detection of PTLD was 80%, the specificity 100%, positive predictive value 100%, negative predictive value 90%. CONCLUSION: The beta2-microglobulin/cystatin C ratio is a promising parameter of lymphoproliferation in patients with normal or mildly impaired renal function.

Biomarkers↗
PubMed2001

Patients at risk for development of posttransplant lymphoproliferative disorder: plasma versus peripheral blood mononuclear cells as material for quantification of Epstein-Barr viral load by using real-time quantitative polymerase chain reaction.

BACKGROUND: Early diagnosis of Epstein-Barr virus (EBV)-associated posttransplant lymphoproliferative disorder (PTLD) is required to detect a stage of disease that is more likely to respond to treatment. Elevated levels of EBV DNA were found in peripheral blood of patients at the onset of PTLD. METHODS: To compare plasma and peripheral blood mononuclear cells (PBMCs) as material for real-time quantitative polymerase chain reaction (RQ-PCR) measurement of Epstein-Barr viral load, we used two sets of primers and probes specific for the BAM HI-K or BAM HI-W region of the EBV genome. RESULTS: Patients with PTLD had a median viral load of 19,200 EBV genomes/microg DNA (n=9) or 3,225 EBV genomes/100 microl plasma (n=5), being significantly higher compared with immunosuppressed patients with primary (n=9) or reactivated (n=20) EBV infection or immunosuppressed patients without serological signs of active EBV infection (n=67) (P<0.001). Hence, a value of greater than 5,000 EBV genomes/microg PBMC DNA was considered as a diagnostic parameter for PTLD with a sensitivity and specificity of 1.00 or 0.89, respectively. When plasma was analyzed, however, a value of greater than 1,000 EBV genomes/100 microl plasma had both a sensitivity and specificity of 1.00 for the diagnosis of PTLD. During remission of PTLD, viral load was more effectively cleared in plasma compared with PBMCs. In plasma of nonimmunosuppressed individuals, even a qualitative detection of EBV-related sequences was sensitive and specific for the diagnosis of primary EBV infection, whereas for analysis of PBMC DNA a quantitative parameter had to be considered to differentiate healthy individuals (< 100 EBV genomes/microg PBMC DNA) from patients with primary EBV infection (>100 EBV genomes/microg PBMC DNA). CONCLUSION: Although both PBMCs and plasma were useful as material for EBV-specific RQ-PCR in immunosuppressed patients and nonimmunosuppressed individuals, the specificity of analysis seemed to be higher if plasma was taken for analysis.

Adolescent↗
PubMed2001

Perioperative management of central diabetes insipidus in kidney transplantation.

Central diabetes insipidus is clinically masked in dialysis patients. We report a 12-year-old girl receiving a living-related donor graft for renal failure from Alport syndrome, in whom a craniopharyngioma had been resected 6 months before transplantation. Pretransplant evaluation had documented central hypothyroidism, growth hormone deficiency, and presumptive hypogonadotropic hypogonadism. The corticotropin-releasing factor test had been normal. Four hours after transplantation, urine output exceeded 1,000 ml/h without diuretic therapy. Serum sodium concentration was 155 mmol/l, serum osmolality 333 mmol/kg, and plasma antidiuretic hormone 4.9 ng/l, while urine osmolality was 233 mmol/kg. Desmopressin acetate was started by continuous intravenous infusion at 1 microgram/day. Serum electrolytes rapidly normalized, urine output stabilized at 2 l/day. The patient was discharged 4 weeks after transplantation with good allograft function, receiving intranasal desmopressin acetate 10 micrograms twice daily. Pre-existing central diabetes insipidus is unmasked after successful kidney transplantation, leading to rapid dehydration and hypernatremia, which can be prevented by prompt institution of desmopressin therapy.

Child↗
PubMed2001

Renal retransplantation of children: is a policy 'first cadaver donor, then live donor' an acceptable option?

Retransplantation is often a necessity for children with end-stage renal disease (ESRD), as kidney graft survival is still not infinite. If a suitable live donor is present, the current policy is to use the live donor first, in order to obtain excellent long-term outcome and to prevent human leucocyte antigen (HLA) sensitization. Data from the Eurotransplant International Foundation were analyzed to determine whether the sequence, first a cadaveric donor then a live donor, is acceptable. Between January 1 1983 and December 31 1995, 1305 children received a first renal transplant; 269 of them had a second transplant during the same period. Follow-up of at least 1 yr was available. Categories were made according to the sequence of renal donor source: 217 patients were classified as first cadaver and second cadaver (1cad-2cad) transplant, 26 as first cadaver and second live (1cad-2liv) donor transplant, 23 as first live donor and second cadaver (1liv-2cad) transplant and three patients had two subsequent live donor transplants (1liv-2liv). When a live donor transplant was carried out, either first or second, the donor age was always higher, and the chance of a pre-emptive transplantation or short stay on dialysis was higher, compared with a cadaver transplant. The re-graft survival rate of the '1cad-2liv' was better than the '1cad-2cad' and '1liv-2cad' transplants. At 5 yr, the survival was 76%, 49%, and 61%, respectively. These data suggest that, when a suitable live donor is not available for a first transplantation owing to medical and/or familial reservations, a policy of 'first a cadaver donor then a live donor' transplantation is a viable option and should even be promoted. The pre-emptive stage of the second transplant, probably with a live donor, is additionally advantageous.

Adolescent↗
PubMed2001

Long-term treatment with growth hormone in short children with nephropathic cystinosis.

OBJECTIVE: The objective was to assess the efficacy and safety of growth hormone (GH) treatment in severely growth retarded children with nephropathic cystinosis during conservative treatment and during renal replacement therapy. STUDY DESIGN: The design was an open-labeled prospective trial with a run-in period of 1 year. RESULTS: A total of 74 children with cystinosis (age 3.0 to 18 years) were treated with GH over a mean period of 3.1 years (range 1 to 10 years); 52 patients were receiving conservative treatment (mean age 7.1 years), 7 were receiving dialysis (12.5 years), and 15 had received a renal transplant (14.8 years). The mean standardized height (SD score) was -4.0 in the conservative treatment group, -4.4 in the dialysis group, and -4.9 in the renal transplant group. During the first treatment year, height velocity doubled in the conservative treatment group, increased by 80% in the dialysis group, and increased by 45% in renal transplant group. Within 3 years the height SD score increased by +1.6 (P <.001) in prepubertal patients receiving conservative treatment, and percentile parallel growth was maintained thereafter. These effects of GH were less expressed in peripubertal patients receiving renal replacement therapy. No major side effects were observed. CONCLUSION: Long-term GH treatment is safe and effective in young children with nephropathic cystinosis. GH treatment should be started early in the course of the disease if adequate nutrition and cysteamine treatment do not prevent growth retardation.

Adolescent↗
PubMed2000

Interleukin-2 receptor antibody-induced alterations of ciclosporin dose requirements in paediatric transplant recipients.

In a retrospective analysis of paediatric renal-transplant recipients receiving basiliximab, we noted significantly increased blood concentrations of cyclosporin, early cyclosporin toxicity, and a lower dose requirement within the first 10 days compared with controls. As the CD25 saturation fades at days 28-50, cyclosporin concentrations decline and 20% higher doses are required to maintain adequate trough concentrations. We suggest that an interleukin-2 receptor-mediated alteration of the cytochrome P450 system causes this systemic drug interaction and propose that the initial ciclosporin dose should be limited to 400 mg/m2 if used in combination with basiliximab.

Antibodies, Monoclonal↗