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The article discusses the different mechanisms underlying kidney allograft rejection as they take place following transplantation. The different barriers and obstacles to successful kidney transplantation as well as suggestions for improvement are highlighted.

Long-term survival of renal allografts depends on the chronic immune response and is probably influenced by the initial injury caused by ischemia and reperfusion. Hypoxia-inducible transcription factors (HIFs) are essential for adaptation to low oxygen. Normoxic inactivation of HIFs is regulated by oxygen-dependent hydroxylation of specific prolyl-residues by prolyl-hydroxylases (PHDs). Pharmacological inhibition of PHDs results in HIF accumulation with subsequent activation of tissue-protective genes. We examined the effect of donor treatment with a specific PHD inhibitor (FG-4497) on graft function in the Fisher--Lewis rat model of allogenic kidney transplantation (KTx). Orthotopic transplantation of the left donor kidney was performed after 24 h of cold storage. The right kidney was removed at the time of KTx (acute model) or at day 10 (chronic model). Donor animals received a single dose of FG-4497 (40 mg/kg i.v.) or vehicle 6 h before donor nephrectomy. Recipients were followed up for 10 days (acute model) or 24 weeks (chronic model). Donor preconditioning with FG-4497 resulted in HIF accumulation and induction of HIF target genes, which persisted beyond cold storage. It reduced acute renal injury (serum creatinine at day 10:0.66 [+ or -] 0.20 vs. 1.49 [+ or -] 1.36 mg/dL; P < 0.05) and early mortality in the acute model and improved long-term survival of recipient animals in the chronic model (mortality at 24 weeks: 3 of 16 vs. 7 of 13 vehicle-treated animals; P < 0.05). In conclusion, pretreatment of organ donors with FG-4497 improves short-and long-term outcomes after allogenic KTx. Inhibition of PHDs appears to be an attractive strategy for organ preservation that deserves clinical evaluation. hypoxia-inducible transcription factors | kidney injury | protection | transplantation doi/10.1073/pnas.0903978106

Calcineurin inhibitors like FK506 (tacrolimus) are routinely used for immunosuppression following transplantation. Its use is limited by many side effects, including renal tubular acidosis (RTA), mainly of the distal type. In this study, rats were treated with FK506 and at baseline (after 9 days) systemic acid-base status was similar to that in control animals. However, FK506-treated rats given N[H.sub.4]Cl in the drinking water for 2 days developed a more severe metabolic acidosis than control animals. Urine pH was more alkaline, but net acid excretion was normal. After 7 days of acid load, all differences related to acid-base homeostasis were equalized in both groups. Protein abundance of type IIa Na-Pi cotransporter, type 3 [Na.sup.+]/[H.sup.+] exchanger, and electrogenic [Na.sup.+]-bicarbonate cotransporter, and both a4 and B2 subunits of the vacuolar [H.sup.+]-ATPase were reduced under baseline conditions, while induction of metabolic acidosis enhanced protein abundance of these transporters in FK506-treated animals. In parallel, protein expression of AE1 was reduced at baseline and increased together with pendrin during N[H.sub.4]Cl loading in FK506 rats. Protein abundance of the [Na.sup.+]-bicarbonate cotransporter NBCnl was reduced under baseline conditions but remained downregulated during metabolic acidosis. Morphological analysis revealed an increase in the relative number of non-type A intercalated cells in the connecting tubule and cortical collecting duct at the expense of principal cells. Additionally, subcellular distribution of the a4 subunit of the vacuolar [H.sup.+]-ATPase was affected by FK506 with less luminal localization in the connecting tubule and outer medullary collecting duct. These data suggest that FK506 impacts on several major acid-base transport proteins in the kidney, and its use is associated with transient metabolic acidosis and altered expression of key renal acid-base transport proteins. anion exchanger; pendrin; [H.sup.+]-ATPase; collecting duct

While studies in animal models have linked Toll-like receptor (TLR) 4 signaling to kidney injury induced by ischemia and reperfusion, the relevance of TLR4 activation to allograft injury in human kidney transplants is unknown. Here we show that TLR4 is constitutively expressed within all donor kidneys but is significantly higher in deceased-, compared with living-donor organs. Tubules from deceased-but not living-donor kidneys also stained positively for high-mobility group box-1 (HMGB1), a known endogenous TLR4 ligand. In vitro stimulation of human tubular cells with HMGB1, in a TLR4-dependent system, confirmed that HMGB1 can stimulate proinflammatory responses through TLR4. To assess the functional significance of TLR4 in human kidney transplantation, we determined whether TLR4 mutations that confer diminished affinity for HMGB1 influence intragraft gene-expression profiles and immediate graft function. Compared with kidneys expressing WT alleles, kidneys with a TLR4 loss-of-function allele contained less TNF[alpha], MCP-1, and more heme oxygenase 1 (HO-1), and exhibited a higher rate of immediate graft function. These results represent previously undetected evidence that donor TLR4 contributes to graft inflammation and sterile injury following cold preservation and transplantation in humans. Targeting TLR4 signaling may have value in preventing or treating postischemic acute kidney injury after transplantation. delayed graft function | high mobility group box-1

The study explored the long-term renal outcomes of kidney donation by establishing vital status and the risk of end-stage renal disease (ESRD) in a group of kidney donors. Results show carefully-screened donors had a preserved glomerular filtration rate, normal albumin excretion and excellent quality of life, indicating survival and risk of ESRD similar to those in the general population.

A new approach for bone marrow and kidney transplant of a patient with renal disease with a HLA-mismatched living related donor is discussed. The transplantation is found to be extremely effective, as it leads to the discontinuation of the immunosuppressive therapy.

Abstract Recent studies considered that an increase in sympathetic activity (SA) may be responsible for left ventricular hypertrophy (LVH). Before and after renal transplantation (RT), we evaluated changes on left [...]

Abstract Impairment of longitudinal growth in children with chronic renal failure (CRF) is multifactorial. It is mainly due to disturbances in the growth hormone (GH)/insulin-like growth factor (IGF)/IGF-binding protein axis. [...]

Abstract The underlying mechanisms of urinary-tract infections (UTI) in renal transplant recipients are still not fully understood. In otherwise healthy children, bladder dysfunction increases the susceptibility to UTI. The aim [...]

Abstract We report a Caucasian boy of Italian descent with congenital nephrotic syndrome of the Finnish type (NPHS1, CNF, MIM 256300) who developed recurrence of proteinuria and hypoalbuminemia on the [...]

Abstract The rates of ureteric obstruction and complications for use of externally draining uretero-vesico-cutaneous (external) stents (Group 1: n=39) and the use of internal uretero-vesical (double-J) stents (Group 2: n=16), [...]

Abstract Mycophenolate mofetil (MMF) introduction with concurrent reduction in calcineurin inhibitors has been shown to be beneficial in chronic allograft nephropathy (CAN) in adults. MMF was introduced to 19 children [...]

Abstract Focal segmental glomerulosclerosis (FSGS) is known to recur in approximately 30% of renal allografts with graft loss in about half of these cases. The exact etiology remains unclear, though [...]

Abstract Corticosteroids have played a central role in the evolution of renal transplant as the modality of choice for renal replacement in end stage kidney disease. Their use is associated [...]

Abstract Corticosteroids are still a cornerstone in the immunosuppressive regimen in pediatric renal transplant recipients despite their numerous side effects, such as inhibition of longitudinal growth, body disfigurement, arterial hypertension, [...]

Abstract The common observation of Epstein-Barr virus (EBV) viremia in pediatric recipients of renal transplants and the occurrence of an EBV-related pulmonary leiomyoma prompted us to intensify the follow-up of [...]

Byline: Erwin Kitzmueller (1), Andreas Vecsei (2), Judith Pichler (1), Michael Bohm (1), Thomas Muller (1), Regina Vargha (1), Dagmar Csaicsich (1), Christoph Aufricht (1,3) Keywords: Renal transplantation; Arterial hypertension; Left ventricular hypertrophy; Cardiac remodeling; Cardiovascular complications Abstract: Cardiovascular events are among the most frequent causes for long-term morbidity and mortality in children after renal transplantation. The aim of this study was to analyze the effects of post-transplant changes in arterial hypertension, as assessed by 24-h ambulatory blood pressure measurement (ABPM), on myocardial architecture, as assessed by echocardiography. In a retrospective chart review analysis, 39 children were identified in whom 24-h ABPM and echocardiography had been assessed within a 3-month interval after a mean of 4 years post transplantation 20 repeated pairs of measurements after a mean of 2 years of follow-up were available to analyze the longitudinal effects of post-transplant changes of blood pressure control on left ventricular mass index (LVMI). Arterial hypertension (59%) and left ventricular hypertrophy (50%) were highly prevalent in children after renal transplantation. Renal allograft function and number of antihypertensive medications, but not ABPM variables, were correlated with LVMI at the initial observation. However, at repeat assessment, a significant correlation between ABPM and LVMI was found. In the longitudinal assessment, left ventricular remodeling was dependent on change of dosage of cyclosporine and interval changes of blood pressure levels. Hence, control of blood pressure correlates with changes of LVMI in children with renal allografts. These results clearly underline the importance of blood pressure control for the maintenance of the myocardial architecture. Author Affiliation: (1) Department of Pediatrics, AKH Wien, Vienna, Austria (2) St. Anna Kinderspital, Vienna, Austria (3) Kinderdialyse, Universitatsklinik fur Kinder- und Jugendheilkunde, AKH Wien, Wahringer Guertel 18--20, 1090 Vienna, Austria Article History: Registration Date: 17/09/2004 Received Date: 08/01/2004 Accepted Date: 12/08/2004 Online Date: 27/10/2004 Article note: E. Kitzmueller and A. Vecsei contributed equally to this work

Byline: Horacio A. Repetto (1,3), Laila Rodriguez-Rilo (1), Esteban Mendaro (2), Laura Basso (1), Hugo Galvez (1), Gabriela Morrone (1), Luis A. Vazquez (1) Keywords: Hypertension; Transplant; Renovascular; Angioplasty; Stent Abstract: Percutaneous treatment of renal artery stenosis (RAS) is an accepted procedure and numerous reports have been published. However, experience with its use in RAS in the transplanted kidney in children is scarce. Since 1994 we have diagnosed RAS in seven children with the use of Doppler ultrasonography (US), confirming it with percutaneous angiography (PAG). In six of the seven patients percutaneous transluminal angioplasty (PTA) was performed. In one patient a metallic stent was placed due to the extension of the arterial lesion, and a second stent was placed in another child when a re-stenosis was diagnosed 1 month after the PTA. All patients presented with hypertension (de novo or 30% increase over previous values). After ruling out acute rejection, calcineurin inhibitor toxicity, and urinary obstruction, US was performed and, when an increase in arterial flux velocity was registered, PAG was also performed. Six children showed an increase in serum creatinine (Cr) and proteinuria. Blood pressure decreased after the procedure and Cr returned to previous levels in all children. One of the grafts was lost due to chronic transplant rejection 7 years later. The other children have a functioning kidney. Although this is a small group of patients, the consistently good results and the lack of reported experience prompted us to communicate our preliminary observation. Author Affiliation: (1) Departamento de Transplante Pediatrico, Instituto de Nefrologia, Buenos Aires, Argentina (2) Departamento de Imagenes, Hospital Sagrada Familia, Buenos Aires, Argentina (3) Cervino 3900, 1425, Buenos Aires, Argentina Article History: Registration Date: 05/08/2004 Received Date: 02/04/2004 Accepted Date: 26/07/2004 Online Date: 22/10/2004

Byline: Thomas J. Neuhaus (1) Keywords: Vaccination; Safety; Immunogenicity; Efficacy; Chronic renal failure; Dialysis; Renal transplantation Abstract: The prevention of systemic viral and bacterial infections by effective vaccination represents an essential task of pediatric nephrologists caring for children with chronic renal failure (CRF) undergoing renal transplantation (RTPL) with life-long immunosuppression. This review addresses three issues: risk of vaccine-preventable diseases, safety, immunogenicity, and clinical efficacy of available vaccines, and implementation of immunization guidelines. Infections (including vaccine-preventable infections) represent the leading cause of morbidity and mortality in children on dialysis and after RTPL. Vaccination in children with CRF and after RTPL is safe and does not cause reactivation of an immune-related renal disease or rejection after RTPL. Children with CRF generally produce protective serum antibodies to primary vaccinations with killed or component vaccines and live virus vaccines some children on dialysis and after RTPL may not respond optimally, requiring repeated vaccination. Proof of vaccine efficacy is absence of disease, which can only be confirmed in large cohort studies. A few observational studies provide evidence that vaccination has contributed significantly, at least in the western hemisphere, to the low prevalence of vaccine-preventable diseases among children with CRF. Close cooperation between the local pediatrician/practitioner and the pediatric nephrologist is essential for successful implementation of the vaccination schedule. Author Affiliation: (1) Nephrology Unit, University Children&apos;s Hospital, Steinwiesstrasse 75, 8032 Zurich, Switzerland Article History: Registration Date: 14/07/2004 Received Date: 22/09/2003 Accepted Date: 24/06/2004 Online Date: 21/10/2004

Byline: Rainer Buscher (1), Udo Vester (1), A.-M. Wingen (1), Peter F. Hoyer (1) Keywords: Arterial hypertension; Renal transplantation; Graft survival; Ambulatory 24-h blood pressure monitoring; Renin-angiotensin-aldosterone system; Genetic polymorphism Abstract: Arterial hypertension is common in pediatric renal allograft recipients. While the causes are multifactorial, including chronic graft rejection, immunosuppressive therapy, and renal vascular disorders, the effect of hypertension on renal allograft function is detrimental. As in adults, if not treated early and aggressively, hypertension may lead to cardiovascular damage and graft failure. Pathophysiological changes in the arteries and kidney after renal transplantation and the impact of receptor regulation have not been studied extensively in children. For identifying children with hypertension following renal transplantation casual blood pressure measurements do not accurately reflect average arterial blood pressure and circadian blood pressure rhythm. Ambulatory 24-h blood pressure monitoring should regularly be applied in transplant patients. The purpose of this review is to analyze pathophysiological aspects of risk factors for arterial hypertension and underline the importance of regular blood pressure monitoring and early therapeutic intervention. Author Affiliation: (1) Department of Pediatric Nephrology, University Hospital, Hufelandstrasse 55, 45122 Essen, Germany Article History: Registration Date: 14/07/2004 Received Date: 08/04/2004 Accepted Date: 29/06/2004 Online Date: 10/09/2004

Byline: Luis Aldamiz-Echevarria (1), Alfredo Vallo (2), Pablo Sanjurjo (1), Javier Elorz (1), Jose Angel Prieto (1), Jose Ignacio Ruiz (1), Juan Rodriguez-Soriano (2,3) Keywords: Renal transplantation; Atherogenesis; Diet; Fatty acids; Plasma plasminogen activator inhibitor-1 activity; Insulin resistance; Plasma homocysteine concentration Abstract: Cardiovascular disease is one of the main causes of morbidity and mortality in recipients of renal transplants. Although the risk for cardiovascular disease is in part genetically determined, it may also be influenced by diet. The aim of the present study was to analyze the cross-sectional association of dietary intake of nutrients with biochemical markers of atherogenic risk. The influence of diet on the plasma profile of fatty acids was specifically investigated. Twenty-nine children and adolescents (mean age 14 years, range 6--18 years) with stable renal transplants and on a normal diet recorded their food intake for a period of 3 days. The mean calorie intake was 40.6 kcal/kg per day (protein provided 16% of total calories, carbohydrates 45%, and fat 39%). Plasma levels of total cholesterol and low-density lipoprotein-cholesterol were significantly and positively related to intake of monounsaturated fatty acids ( r =0.66, P =0.007 and r =0.62, P =0.02, respectively) and to plasma levels of elaidic acid, a trans fatty acid ( r =0.43, P =0.02 and r =0.54, P =0.01, respectively). Insulin resistance, estimated from values of plasma glucose ( r =0.70, P =0.03), plasma insulin ( r =0.59, P =0.02), and HOMA index ( r =0.62, P =0.01), was also directly related to the intake of monounsaturated fatty acids. Plasma plasminogen activator inhibitor-1 activity correlated positively with total fat intake ( r =0.59, P =0.04). Plasma levels of homocysteine were negatively related to the intake of carbohydrates ( r =-0.62, P =0.02). We conclude that reasonable dietary recommendations to minimize the atherogenic risk in children with stable renal transplants should include a protein intake adjusted to the requirements for age, a large intake of carbohydrates leading to a low glycemic load, and a fat intake of less than 30% of the total calorie intake. The amount of monounsaturated and trans fatty acids in the diet should be especially limited. A sufficient intake of polyunsaturated fatty acids, with an adequate ratio between [omega]6 and [omega]3 components, should also be provided. Author Affiliation: (1) Division of Metabolism, Department of Pediatrics, Hospital de Cruces, Basque University School of Medicine, Bilbao, Pais Vasco, Spain (2) Division of Nephrology, Department of Pediatrics, Hospital de Cruces, Basque University School of Medicine, Bilbao, Pais Vasco, Spain (3) Department of Pediatrics, Hospital de Cruces, Plaza de Cruces s/n, 48903 Baracaldo, Vizcaya, Spain Article History: Registration Date: 19/05/2004 Received Date: 22/01/2004 Accepted Date: 14/05/2004 Online Date: 16/07/2004

Byline: Claire Chavatte (1), Genevieve Guest (2), Virginie Proust (1), Christine Le Bihan (4), Francois Gimenez (1), Anne Maisin (5), Chantal Loirat (5), Agnes Mogenet (3), Jean-Louis Bresson (3), Regis Hankard (6), Michel Broyer (2), Patrick Niaudet (2), Eric Singlas (1) Keywords: Glucocorticoid; Growth; Renal transplantation; Pharmacokinetics Abstract: Long-term glucocorticoid treatment contributes to the growth retardation in children after renal transplantation. We investigated whether determination of prednisone (PN) and prednisolone (PL) in plasma and PN, PL, and 6-[beta]-hydroxyprednisolone ([beta]OH-PL) in urine could help to predict growth. PN and PL pharmacokinetics were studied in 36 children, from 5 to 15 years of age, receiving daily (D) or alternate-day (AD) oral PN treatment. Statural growth velocity was evaluated over a 1-year period. We compared three groups of children according to the growth kinetics during the study year (catch-up, stable, or decline) for clinical and pharmacokinetic parameters. A multiple linear regression analysis was performed in order to determine pharmacokinetic parameters able to explain height 1 year after inclusion. Height at the beginning of the study, creatinine clearance, and type of D or AD treatment explained 94.2% of height variance 1 year after inclusion. Only PL clearance was associated with growth evolution, but introduction of PL clearance in the multivariate model did not improve the variance of height accounted for by the previous model. We, therefore, do not recommend using glucocorticoid pharmacokinetics to predict growth retardation in children with renal transplantation. Author Affiliation: (1) Service Pharmacie, Hopital Necker Enfants Malades, 149 rue de Sevres, 75015 Paris, France (2) Nephrologie Pediatrique, Hopital Necker Enfants Malades, 149 rue de Sevres, 75015 Paris, France (3) Centre d&apos;Investigation Clinique, Hopital Necker Enfants Malades, 149 rue de Sevres, 75015 Paris, France (4) Biostatistique et Informatique Medicale, Hopital Necker Enfants Malades, 149 rue de Sevres, 75015 Paris, France (5) Nephrologie Pediatrique, Hopital Robert Debre, Paris, France (6) Centre d&apos;Investigation Clinique, Hopital Robert Debre, Paris, France Article History: Registration Date: 06/04/2004 Received Date: 22/09/2003 Accepted Date: 24/03/2004 Online Date: 03/06/2004

Byline: Thomas Lucke (1,4), Katja M. Marwedel (2), Nele K. Kanzelmeyer (1), Akira Hori (3), Gisela Offner (1), Hans-Heinrich Kreipe (2), Jochen H. H. Ehrich (1), Anibh M. Das (1) Keywords: Atherosclerosis; Vascular dysfunction; Schimke-immuno-osseous dysplasia; Vaso-occlusive disease Abstract: Schimke-immuno-osseous dysplasia (SIOD) is a multisystem disorder caused by a mutation of the chromatin remodeling protein. The main clinical findings are spondyloepiphyseal dysplasia with dysproportional growth deficiency, nephrotic syndrome with focal and segmental glomerulosclerosis, and defective cellular immunity. Transitory ischemic attacks due to vaso-occlusive processes are still an untreatable and life-limiting complication in patients with SIOD. The underlying pathophysiology of vaso-occlusive processes in SIOD is unclear. We report the clinical and pathological findings of the eldest published patient with the severe form of SIOD, who died at the age of 23 years due to pulmonary hypertension with subsequent right heart failure. The autopsy revealed a severe generalized atherosclerosis including the brain, heart, and pulmonary arteries. However, the kidney that was transplanted at the age of 5 years showed a good graft function without glomerular sclerosis and with only minimal nephrosclerosis on histology. Thus, the absence of severe vaso-occlusive processes in the transplanted organ and in the severely atherosclerotic host may indicate that the vaso-occlusive processes in SIOD are not caused by post-transplant cardiovascular morbidity such as arterial hypertension and hyperlipidemia. Instead, vascular factors of the host such as endothelial dysfunction may explain the pathophysiology of atherosclerosis in SIOD. Author Affiliation: (1) Department of Pediatrics, Hanover Medical School, 30623 Hannover, Germany (2) Department of Pathology, Hanover Medical School, 30623 Hannover, Germany (3) Department of Neuropathology, Hanover Medical School, 30623 Hannover, Germany (4) Carl-Neuberg Strasse 1, 30623 Hannover, Germany Article History: Registration Date: 22/01/2004 Received Date: 21/07/2003 Accepted Date: 02/01/2004 Online Date: 31/03/2004

Byline: Arvind Nagra (1), Richard S. Trompeter (1), Oswald N. Fernando (1), Geoff Koffman (1), John D. Taylor (1), Rozanne Lord (1), Carol Hutchinson (1), Caoimhe O&apos;Sullivan (2), Lesley Rees (1) Keywords: Graft thrombosis; Heparin; Paediatric renal transplantation Abstract: Graft thrombosis is an important cause of early (&lt 4 weeks) renal graft loss. Reports show that heparin reduces the incidence of early renal allograft thrombosis. Routine peri-operative administration of unfractionated heparin was introduced in our unit in 1994. We conducted a retrospective study of 254 transplants, undertaken in children, between 1987 and 2000. There were 126 children who did not receive heparin (group 1) and 128 who did (group 2). Recipient characteristics and immunosuppression were similar in both groups. The incidence of graft loss secondary to thrombosis was compared between the groups. Variables previously identified with increased risk of graft loss, including donor age, recipient age, cold ischaemia time (CIT), multiple donor vessels, surgical complications, and side of graft donation, were examined using logistic regression. Thrombosis occurred in 14 grafts in group 1 and 11 grafts in group 2 (odds ratio 0.7, 95% confidence interval 0.3--1.6, P=not significant). The mean time to graft loss was similar in groups 1 and 2 (6.6, SD 3.9, range 2--12 days and 7.9, SD 4.4, range 1--14 days, respectively) (P=0.445). Young recipient age (P=0.006), young donor age (P=0.009), increasing CIT (P=0.007), and surgical complications (P=0.002) increased the risk of graft thrombosis. A reduction in the incidence of early renal allograft thrombosis upon introduction of heparin was not demonstrated. Author Affiliation: (1) Renal Unit, Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street, London, WCIN 3JH, UK (2) Research Development Department, University College London Hospitals, Hampstead Road, London, UK Article History: Registration Date: 25/02/2004 Received Date: 15/09/2003 Accepted Date: 13/02/2004 Online Date: 12/03/2004

Byline: Joshua Yehuda Kausman (1), Harley Robert Powell (1), Colin Lindsay Jones (1) Keywords: Anemia; Iron deficiency; Erythropoietin; Kidney transplantation; Angiotensin converting enzyme inhibitor Abstract: The aim of this study was to establish the prevalence of anemia in stable pediatric renal transplant recipients and to examine the association of anemia with renal function, immunosuppressants, angiotensin converting enzyme inhibitors, and growth, as well as iron, vitamin B.sub.12, and folate stores. This is a cross-sectional study of the 50 renal transplant recipients currently followed at our center. Patient data were collected regarding hematological parameters, growth, medications, renal function, underlying renal disease, delayed graft function, episodes of rejection, and iron or erythropoietin therapy post transplantation. The mean hemoglobin level (Hb) was 110 g/l and the overall prevalence of anemia was 60%, including 30% who were severely anemic (Hb&lt 100 g/l). There was a high rate of iron deficiency (34%) and serum iron was the parameter of iron metabolism most closely associated with anemia. Hb in patients with low serum iron was 90.7 g/l versus 114.4 g/l in those with normal serum iron (P&lt 0.01). Both univariate and multiple linear regression determined tacrolimus dose and creatinine clearance to be significant factors associated with anemia. Tacrolimus dose correlated with a 10 g/l reduction in Hb for every increase of tacrolimus dose of 0.054 mg/kg per day (P=0.001). The dose of mycophenolate was positively correlated with Hb, but this was likely to be confounded by our practice of dose reduction in the setting of anemia. Angiotensin converting enzyme inhibitor use was not associated with anemia. Severely anemic patients tended to be shorter, with a mean Z-score for height of --1.8 compared with --0.9 for those with normal Hb (P=0.02). Anemia is a significant and common problem in pediatric renal transplant patients. Deteriorating renal function is an important cause, but other factors like iron deficiency and immunosuppression are involved. Definition of iron deficiency is difficult and serum iron may be a valuable indicator. Medication doses, nutritional status, need for erythropoietin and iron, as well as poor graft function and growth require systematic scrutiny in the care of the anemic renal transplant recipient. Author Affiliation: (1) Department of Nephrology, Royal Children&apos;s Hospital, Flemington Road, 3052, Parkville, Victoria, Australia Article History: Registration Date: 22/01/2004 Received Date: 25/08/2003 Accepted Date: 06/01/2004 Online Date: 09/03/2004

Byline: Joshua Yehuda Kausman (1), Gino Rene Somers (2), David Michael Francis (1), Colin Lindsay Jones (1) Keywords: Kidney transplantation; BK virus; Polyomavirus; Kidney neoplasms Abstract: While most BK virus infections are asymptomatic, immunosuppression has been associated with BK virus reactivation and impaired graft function or ureteric ulceration in renal transplant patients and hemorrhagic cystitis in bone marrow transplant patients. Oncogenicity is also postulated and this is the first report of a child with a carcinoma of the donor renal pelvis following BK virus allograft nephropathy. Removal of the primary tumor and cessation of immunosuppression led to regression of secondary tumors and a return to health. Author Affiliation: (1) Department of Nephrology, Royal Children&apos;s Hospital, Flemington Road, Parkville, Victoria 3052, Australia (2) Department of Anatomical Pathology, Royal Children&apos;s Hospital, Flemington Road, Parkville, Victoria 3052, Australia Article History: Registration Date: 23/12/2003 Received Date: 08/08/2003 Accepted Date: 12/12/2003 Online Date: 24/02/2004

Byline: Rokshana Shroff (1), Lesley Rees (1) Keywords: Post-transplant lymphoproliferative disorder; Epstein-Barr virus Abstract: The Epstein-Barr virus (EBV)-induced post-transplant lymphoproliferative disorder (PTLD) affects 1%--10% of all paediatric renal transplant recipients. This is a heterogeneous group of conditions characterised by EBV-driven proliferation of B-lymphocytes in the face of impaired T-cell immune surveillance. The risk factors predisposing to PTLD are becoming better understood, but its pathogenesis and myriad of clinical and histological features remain poorly defined. While new treatment modalities are being tried with variable success, regular EBV surveillance and carefully monitored reduction of immunosuppression remain the mainstay of treatment. In this review, we have presented the current knowledge of this increasingly common complication in renal transplant recipients. Author Affiliation: (1) Department of Nephrourology, Great Ormond Street Hospital for Children, London, WC1 N 3JH, UK Article History: Registration Date: 09/12/2003 Received Date: 05/06/2003 Accepted Date: 10/10/2003 Online Date: 21/02/2004 Article note: An editorial commentary to this article can be found at http://dx.doi.org/10.1007/s00467-004-1412-5

Byline: Line M. Vautour (1,5), L. Joseph Melton (1,3), Bart L. Clarke (3), Sara J. Achenbach (2), Ann L. Oberg (2), James T. McCarthy (4) Keywords: Diabetes mellitus; Epidemiology; Fracture; Osteoporosis; Renal transplantation Abstract: Abnormal bone metabolism is a recognized complication of end-stage renal disease, but fracture risk following renal transplantation has not been well quantified. We followed the 86 Olmsted County, Minnesota, residents who underwent initial renal transplantation in 1965--1995 for 911 person-years (median, 10.6 years per subject) in a retrospective cohort study. Fractures, and possible risk factors, were assessed through review of each subject's complete community medical records. Altogether, 117 fractures were observed during follow-up extending to 33 years. The cumulative incidence of any fracture at 15 years was 60% versus 20% expected (P&lt 0.001). There was a significantly increased risk of fractures generally [standardized incidence ratio (SIR), 4.8 95% CI, 3.6--6.4] and vertebral (SIR, 23.1 95% CI, 12.3--39.6) and foot fractures (SIR, 8.4 95% CI, 5.1--12.9) especially. Age at first transplantation, renal failure due to diabetes, pancreas transplantation, peripheral neuropathy, peripheral vascular disease and blindness were all associated with overall fracture risk. In a multivariate analysis, however, only age and diabetic nephropathy were independent predictors of fracture risk generally, while higher activity status was protective. Diabetes was the only independent predictor of lower limb fractures, whereas age and osteoporosis history predicted vertebral fractures. Cumulative corticosteroid dosage was not associated with increased fracture risk in this analysis. Despite the fact that our patients had few risk factors for preexisting bone disease attendant to postmenopausal osteoporosis, prior corticosteroid use or renal osteodystrophy, these data indicate that renal transplantation is associated with a significant increase in fracture risk among unselected patients in the community. Diabetic patients, particularly, experience excess lower limb fractures. Patients and their care providers should be aware of this elevated fracture risk, which continues long-term. Author Affiliation: (1) Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, Minn., USA (2) Division of Biostatistics, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minn., USA (3) Division of Endocrinology, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA (4) Division of Nephrology, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minn., USA (5) Department of Medicine, McGill University, Montreal, Canada Article History: Received Date: 01/04/2003 Accepted Date: 27/08/2003 Online Date: 09/12/2003 Article note: Presented at the 24th Annual Meeting of the American Society of Bone and Mineral Research in San Antonio, Tex., USA.

Byline: C. Berczi (1,4), L. Asztalos (1), Z. Kincses (1), A. Balogh (1,2), L. LAcsey (1,3), G. Balazs (1), G. Lukacs (1) Keywords: Kidney transplantation; PTH; Alfacalcidol; Bone densitometry Abstract: The aim of this observational study was to compare the effect of calcium and alfacalcidol supplementation on the regression of hyperparathyroidism and on prevention of osteopenia in patients up to 3 years after renal transplantation. Two historical cohorts were compared for that purpose. One hundred and fifty-nine patients received calcium carbonate supplement (group 1), while 81 patients were treated with alfacalcidol (group 2). Serum Ca, phosphate (P), Mg, creatinine, alkaline phosphatase (AP) and parathyroid hormone (PTH) levels were determined before and after transplantation in the two groups, for 3 years. Femoral neck and lumbar spine bone mineral density (BMD) was measured only at 3 and 6 months and 1, 2 and 3 years after transplantation. At baseline there was no difference in age or sex ratio, but prevalence in post-menopausal women was higher in group 1 (6.9% versus 1.2%). Duration on dialysis was comparable but prevalence of interstitial and undetermined nephropathies was higher in group 1. Baseline serum concentrations of PTH, Ca and P were comparable in both groups. After transplantation, plasma creatinine decreased to comparable levels in both groups. Immunosuppression by triple therapy was more prevalent in group 2, so that cumulative dose of steroid was higher in group 1, especially at 1 month because of higher incidence of acute rejections (51% versus 13%). Mean intact PTH levels decreased in both groups, from 18 pmol/l to 8.4 and 7.9 at 3 years, but the decrease was significantly greater with alfacalcidol at 6 and 12 months. At 3 months, BMD were comparable at both sites. From 3 months to 3 years after kidney transplantation, mean lumbar spine BMD significantly increased from 0.963 to 1.054 g/cm.sup.2 in group 1, whereas there was no significant decrease (1.048 to 1.006 g/cm.sup.2) in group 2, the difference in changes being significant (P&lt 0.05). Femoral neck BMD was not significantly increased in either group (0.932 to 0.993 g/cm.sup.2 in group 1, and 0.850 to 0.907 g/cm.sup.2 in group 2). Expressed as percentages, these changes were +9.4% and --4% for lumbar BMD and +6.5% and +6.7% for femoral neck, for groups 1 and 2, respectively. Prevalence of osteopenia was not significantly lower at 3 years in group 1 (45% and 51%) than in group 2. During the follow-up period, osteonecrosis was diagnosed in six patients (3.8%) in group 1 and in nine (11%) in group 2. In conclusion, alfacalcidol compared to CaCO.sub.3 supplement suppressed hyperparathyroidism more rapidly and strongly. In spite of higher osteopenia risk in the CaCO.sub.3 group, lumbar BMD increase was greater and incidence of osteonecrosis higher in this group, suggesting better bone protection with CaCO.sub.3 than with alfacalcidol. Author Affiliation: (1) 1st Department of Surgery, University of Debrecen, Debrecen, Hungary (2) Department of Gynecology, University of Debrecen, Debrecen, Hungary (3) 10th Dialysis Centre of Eurocare, Debrecen, Hungary (4) Kesmark str.7/C, 4029, Debrecen, Hungary Article History: Received Date: 13/11/2002 Accepted Date: 07/01/2003 Online Date: 16/04/2003

Byline: D. Kovac (1), J. Lindic (1), A. Kandus (1), F. A. Bren (1) Keywords: Bone density Kidney transplantation Quantitative ultrasound Abstract: Bone loss after kidney transplantation is a significant complication of immunosuppressive treatment leading to a high prevalence of bone fracture in these patients. The purpose of this study was to determine the usefulness of quantitative ultrasound (QUS) of the calcaneus in comparison with dual X-ray absorptiometry (DXA) of the lumbar spine in determining bone status and mineral changes in patients in the first 6 months after transplantation. Forty-six patients participated in the study (25 men and 21 women age range 26--62 years, 102+-66 months previously on dialysis). They were treated with cyclosporine, methylprednisolone, mycophenolate mofetil, and basiliximab. The 6-month cumulative steroid dose was 24.9+-3.7 mg/kg body weight. Calcaneal QUS (Sahara, Hologic, Waltham, Mass.) and DXA (Hologic QDR 4500) of the lumbar spine were done in all patients within 3 weeks after transplantation and 6 months thereafter. Bone mineral density (BMD) of the lumbar spine measured by DXA decreased from 0.892+-0.137 to 0.837+-0.126 g/cm.sup.2 (p&lt 0.0001) and the T score decreased from 1.84+-1.29 standard deviation (SD) to 2.35+-1.19 SD (p&lt 0.0001) in the first 6 months after transplantation. The QUS parameters of the calcaneus were broadband ultrasound attenuation (BUA), speed of sound (SOS), and quantitative ultrasound index (QUI). The QUS parameters did not change significantly after the first 6 months. All QUS parameters correlated significantly with DXA BMD of the lumbar spine immediately after transplantation and 6 months thereafter. Significant decrease of the lumbar spine BMD in the first 6 months after transplantation was not accompanied by significant changes of calcaneal QUS parameters. The calcaneal QUS does not reflect bone mineral changes occurring in the lumbar spine and could not be a substitute for a direct-site DXA of the lumbar spine in the early period after kidney transplantation. Author Affiliation: (1) Department of Nephrology, University Medical Center, Zaloska 7, 1000, Ljubljana, Slovenia Article History: Received Date: 09/07/2002 Accepted Date: 12/11/2002 Article note: Electronic Publication

Byline: V. Schwenger (1), E. Mundlein (2), E. E. Dagrosa (3), A. M. Fahr (4), M. Zeier (1), G. Mikus (5), K. Andrassy (1) Abstract: Background: Life-threatening infections with multiresistant gram-positive bacteria are increasing. Treatment with quinupristin/dalfopristin (Q-D) has turned out to be effective against such resistant pathogens. Patients and Methods: We report on treatment of six patients on dialysis (four with additional liver injury) and of one renal graft recipient with normal renal function who had severe infections caused by multiresistant Staphylococus epidermidis (1/7), methicillin-resistant Staphylococcus aureus (4/7) and vancomycin-resistant Enterococcus faecium (2/7). Results: Six out of seven patients were cured by therapy with Q-D in adjusted doses lasting for 10 to 34 days. Pharmacokinetics of Q-D and its metabolites were determined and remained within the therapeutic range, despite a modest increase of all compounds at the presumed steady state. The concentrations of the metabolites of Q-D were clearly lower than the parent drugs, including those of quinupristin-conjugated derivatives, which has not been reported previously. Conclusion: These preliminary results suggest that: a) neither quinupristin nor dalfopristin or its metabolites accumulated despite the long duration of treatment b) no adjustment of the standard dosage regimen (three times 7.5 mg/kg/day) is necessary in end-stage renal disease. Author Affiliation: (1) Dept. of Internal Medicine, University Hospital Heidelberg, Bergheimer Str. 56a, D-69115 Heidelberg, Germany. vedat.schwenger@med.uni-heidelberg.de, DE (2) Dept. of Internal Medicine, Fachkrankenhaus Neckargemund, Germany, DE (3) Aventis Pharma Germany, Bad Soden, Germany, DE (4) Laboratory Group Heidelberg, Germany, DE (5) Clinical Pharmacology, University Hospital Heidelberg, Germany, DE Article note: Received: March 28, 2002 * Revision accepted: May 6, 2002 V. Schwenger (corresponding author)

Byline: M. F. Gagnadoux (1), F. Lacaille (2), P. Niaudet (1), Y. Revillon (3), P. Jouvet (4), D. Jan (3), G. Guest (1), M. Charbit (1), M. Broyer (1) Keywords: Keywords Oxalosis; Renal transplant; Hepatorenal transplant Abstract: From 1990 to 2000, we performed eight liver-kidney transplants in eight children, aged 1--16 years, with end-stage renal failure (ESRF) due to primary hyperoxaluria (PH1). The duration of dialysis before transplantation ranged from 2 to 42 months (mean 14 months) and was &lt 1 year in four patients. Only the first patient underwent postoperative hemodialysis in the other five, we chose to induce maximal diuresis from the first hours with intravenous and intragastric hyperhydration (aY=3 l/m.sup.2 per day). High water intake with nocturnal tube hydration was maintained for 6 months to 5 years, as long as oxaluria exceeded 0.5 mmol/day. A quadruple sequential immunosuppressive regimen was used. Two patients died during liver graft surgery. The other six patients are alive and well, with a mean follow-up of 7.4 years (range 5--11 years). Patient and graft survival is 75% at 5 years. At latest follow-up, liver tests were normal in all six patients creatinine clearance ranged from 55 to 95 ml/min per 1.73 m.sup.2 (mean=74). Oxaluria was lower than 0.4 mmol/day in all patients (mean=0.22). The six patients underwent 15 renal biopsies, 1--11 years after transplantation. Chronic transplant nephropathy was present in four patients and mild cyclosporin nephrotoxicity in another. No oxalate crystals were seen and repeat ultrasonography has been consistently normal in all patients. The three patients with bone oxalosis showed progressive complete healing of bone lesions. All six children or adolescents now live a normal life. From this series, we conclude that early combined liver-kidney transplantation is the treatment of choice for children with ESRF due to primary hyperoxaluria. Author Affiliation: (1) Department of Pediatric Nephrology, Hopital Necker-Enfants Malades, 149 rue de Sevres, 75743 Paris Cedex 15, France. marie-france.gagnadoux@nck.ap-hop-paris.fr, FR (2) Department of Hepatology, Hopital Necker-Enfants Malades, 149 rue de Sevres, 75743 Paris Cedex 15, France, FR (3) Department of Surgery, Hopital Necker-Enfants Malades, 149 rue de Sevres, 75743 Paris Cedex 15, France, FR (4) Department of Intensive Care, Hopital Necker-Enfants Malades, 149 rue de Sevres, 75743 Paris Cedex 15, France, FR Article note: Received: 7 June 2001 / Revised: 7 August 2001 / Accepted: 7 August 2001

Byline: R. N. Fine (1), M. Ho (2), A. Tejani (3) Keywords: Keywords Renal transplantation; Final adult height Abstract: Final adult height following renal transplantation was assessed in 237 recipients enrolled in NAPRTCS before the ages of 11 (girls) and 12 (boys) years and followed for at least 6 months with a functioning graft at or after 18 years of age. The overall change in standardized height (SDS) from baseline to final adult height (FH) was 0.0 however, delta SDS was significantly better for the youngest recipients (6--8 years) than for the older age group. Retarded FH was associated with higher average prednisone dosage and better FH was associated with good graft function. Low baseline SDS was also predictive of retarded FH. Final adult height continues to be suboptimal in the cyclosporine A era. Author Affiliation: (1) Department of Pediatrics, SUNY at Stony Brook, Stony Brook, NY 11794--8111, USA. RFINE@mail.som.sunysb.edu, US (2) Emmes Corp., Rockville, Maryland, USA, US (3) Westchester Medical Center, Valhalla, New York, USA, US Article note: Received: 7 June 2001 / Revised: 5 October 2001 / Accepted: 5 October 2001

Byline: A. Humar (1), L. Arrazola (1), M. Mauer (2), A. J. Matas (1), J. S. Najarian (1) Keywords: Keywords Kidney transplants; Infants; Minimum age Abstract: The optimal age for transplantation in children with end-stage renal disease remains controversial. Many centers have adopted a policy of waiting until such children reach a certain minimum age or weight, maintaining them on chronic dialysis until then. Their policy is based on historical data showing inferior graft survival in very young children. We feel that with proper donor selection and recipient care, comparable results can be achieved in very young age groups. We herein present our results with kidney transplantation in children &lt 1 year old. Between 1 January 1984 and 31 December 1999, we performed 321 kidney transplants in children a$?13 years at the University of Minnesota. We analyzed our results in three age groups: &lt 1 year (n=30), 1 through 4 years (n=122), and 5 through 13 years (n=169). We found no significant differences in patient or graft survival rates between the three groups. Almost all our infant (&lt 1 year) recipients underwent primary transplants from living donors (LDs). However, even when we compared results only of primary LD transplants between the three groups, we found no significant differences. To date, all our infant recipients are alive and well, 24 (80%) with a functioning original graft. Causes of the 6 graft losses were chronic rejection (n=3), vascular thrombosis (n=2), and recurrent disease (n=1). Infants had significantly lower incidences of acute and chronic rejection compared with older recipients, but a tendency to higher incidences of delayed graft function and vascular thrombosis. Infants had significant increases in weight post transplant: the mean standard deviation score rose from --2.8 pre transplant to --0.2 by age 5 years and to +1.8 by age 10 years. The improvement in height was less marked: the mean standard deviation rose from --3.2 pre transplant to --1.6 by age 5 years and to --1.4 by age 10 years. Kidney transplant results in very young children can be comparable to those in older children. There need be no minimum age for performing a kidney transplant. The timing of the transplant should not be based on age or size alone. Author Affiliation: (1) Department of Surgery, University of Minnesota, MMC 195, 420 Delaware Street SE, Minneapolis, MN 55455, USA. abhinav.humar--2@tc.umm.edu, US (2) Department of Pediatrics, University of Minnesota, Minneapolis, USA, US Article note: Received: 7 June 2001 / Revised: 3 August 2001 / Accepted: 3 August 2001

Byline: U. B. Berg (1) Keywords: Keywords Glomerular filtration rate; Effective renal plasma flow; Renal hemodynamics; Nephron mass; Rejections Abstract: Of 125 children undergoing kidney transplantation (tx), 87 received their grafts from living donors. Renal function of recipients (R) and donors (D) was assessed by glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) determined by clearances of inulin and para-aminohippuric acid. Rs were investigated yearly and Ds on alternate years. Within 5 months of tx, absolute GFR and ERPF (ml/min) were significantly lower in R than in D, and the differences in absolute GFR and ERPF between D and R were directly related to the difference in body surface area (BSA) between the two subjects. R and D pairs were repeatedly followed for 4, 6, and 8 years and the absolute GFR of R did not change during follow-up, while relative GFR decreased. Relative GFR decreased most in R, with the greatest difference in BSA between D and R at tx. In the donors, however, both absolute and relative GFR increased significantly up to 8 years. In conclusion, renal function of the two kidneys from the donor, i.e., the grafted kidney in the R and the single native kidney of the D, differed. The native kidney showed a capacity to increase its absolute and relative function with time. The grafted kidney, however, did not show an increase in absolute GFR, resulting in decrease in relative GFR, and the greater difference in BSA between D and R at tx, the greater fall in relative GFR of the R. Author Affiliation: (1) Department of Pediatrics, Karolinska Institutet, Huddinge University Hospital, 14186 Stockholm, Sweden. ulla.berg@klinvet.ki.se, SE Article note: Received: 7 June 2001 / Revised: 30 July 2001 / Accepted: 30 July 2001

Byline: Henry Morgan (1), Iqtidar Khan (1), Aijaz Hashmi (2), Diane Hebert (1), Brian W. McCrindle (2), J. W. Balfe (1) Keywords: Keywords Renal transplantation; Ambulatory blood pressure monitoring; Hypertension; Left ventricular hypertrophy Abstract: Hypertension occurs commonly following renal transplantation and may cause end organ damage, such as cardiac hypertrophy. This study seeks to determine which features of hypertension are related to cardiac hypertrophy in children after renal transplantation. Ambulatory blood pressure monitoring (ABPM) was performed in 45 pediatric patients, 4.9+-3.0 years after renal transplantation. ABPM data were related to clinical features and echocardiographic measurements. Hypertension was demonstrated in 33% of patients by casual blood pressure (BP) measurement and in 40% by ABPM. The mean percentage nighttime decline in BP (dipping) was 8.9+-5.0% for systolic and 13.9+-7.7% for diastolic BP. Abnormal dipping (&lt 10%) was seen in 58% of patients. BP load (percentage of BP recordings above 95th percentile) was &gt 30% in 44% of patients. Patients taking antihypertensive medication had more abnormal dipping and greater nighttime BP load. The prevalence of left ventricular hypertrophy was 72% before transplantation, 75% after transplantation, and 54% near to ABPM. Left ventricular mass (LVM) indexed to height.sup.3 decreased significantly after transplantation. (40.2+-14.7 vs. 35.0+-8.3 g/m.sup.3, P=0.0002). There was no significant relationship between ABPM data and LVM. ABPM was not able to differentiate those patients with persistently elevated LVM. The results suggest that hypertension is not always associated with cardiac hypertrophy following pediatric renal transplantation. Author Affiliation: (1) Department of Pediatrics, Division of Nephrology, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, Canada, M5G 1X8. bill.balfe@sickkids.ca, CA (2) Department of Pediatrics, Division of Cardiology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada, CA Article note: Received: 7 December 2000 / Revised: 25 May 2001 / Accepted: 29 May 2001

Byline: L. Dello Strologo (1), C. Pontesilli (1), G. Montini (2), F. Ginevri (3), G. Ardissino (4), P. Campagnano (5), A. Pastore (5), G. Federici (5), G. Rizzoni (1) Keywords: Keywords Tacrolimus; Renal hemodynamics; Kidney transplantation Abstract: Like cyclosporine (CsA), tacrolimus acts through the inhibition of renal phosphatase calcineurin. CsA induces reversible vasoconstriction, causing a transient reduction of renal plasma flow in patients with renal transplantation. The aim of this study was to determine the effect of tacrolimus on renal plasma flow in renal transplanted children. Eight children were studied with a median age of 10.6 years, a mean glomerular filtration rate (inulin clearance) of 55 ml/min per 1.73 m.sup.2 (range 29--95), and a mean follow-up after transplantation of 5.6 months. Effective renal plasma flow (ERPF) was studied in each patient for 12 h after tacrolimus administration. Clearan- ces were obtained every 2 h for 12 h after drug administration. Tacrolimus pharmacokinetics was also studied. Average ERPF at the start of the test was 289 ml/min per 1.73 m.sup.2 (range 177--404, SD+-106). Variation in each of the 2-h periods was not significant, although a mild reduction of plasma flow was observed in three of the eight children. No correlation was found between tacrolimus AUC, peak, or trough levels and renal blood flow variations. Despite the relatively small number of patients studied, these data suggest that, in vivo, a therapeutic oral dose of tacrolimus is not necessarily followed by a significant reduction of ERPF in renal transplanted children. Author Affiliation: (1) Nephrology and Dialysis Department, Bambino Gesu Children&apos;s Hospital and Research Institute, Piazza S. Onofrio 4, 00165 Rome, Italy. dellostrologo@opbg.net, IT (2) Department of Pediatrics, University of Padua, Padua, Italy, IT (3) Nephrology Unit, G. Gaslini Institute, Genoa, Italy, IT (4) Dialysis Unit, Department of Pediatrics, University of Milan, Milan, Italy, IT (5) Clinical Biochemistry Laboratory, Bambino Gesu Children&apos;s Hospital and Research Institute, Rome, Italy, IT Article note: Received: 15 November 2000 / Revised: 3 April 2001 / Accepted: 16 May 2001

Byline: A. Swiatecka-Urban (1), Clotilde Garcia (2), Dianne Feuerstein (3), Samuel Suzuki (4), Prasad Devarajan (2), Richard Schechner (3), Stuart Greenstein (3), Vivian Tellis (3), Frederick Kaskel (2) Keywords: Keywords Basiliximab; Tacrolimus; Target levels; Post-transplant lymphoproliferative disease; Post-transplant diabetes mellitus Abstract: Thirty-two children and adolescents received their renal transplant at the Montefiore Medical Center, in New York, between October 1996 and May 2000. Twenty-four patients received basiliximab, in addition to tacrolimus and steroids (basiliximab group). The remaining eight patients received only tacrolimus and steroids (non-basiliximab group). The 1-year patient survival rate was 100% in both groups. The 1-year graft survival rate was 87.5% for the basiliximab group and 75% for the non-basiliximab group (P=0.45). The rates of acute rejection in the basiliximab and non-basiliximab groups were 26% and 43%, respectively (P=0.36). However, in recipients with a$?3 HLA mismatches, the rate of acute rejection was zero in the basiliximab group, and 40% in the non-basiliximab group (P=0.04). The beneficial effect occurred despite the fact that tacrolimus was maintained at below the target levels. There were no adverse events directly attributable to the administration of basiliximab. There were no cases of opportunistic infections or post-transplant lymphoproliferative disease. In summary, addition of basiliximab to tacrolimus and prednisone significantly decreased the rate of acute rejection in well-matched patients. Moreover, this effect was manifest at lower, and therefore less toxic, tacrolimus levels. Author Affiliation: (1) Ira Greifer Pediatric Kidney Center, 3326 Bainbridge Avenue, Bronx, NY 10467, USA. ajaswurban001@worldnet.att.net, US (2) Department of Pediatrics, Division of Nephrology, Children&apos;s Hospital at Montefiore, Albert Einstein College of Medicine, 111 East 210th Street, Bronx, NY 10467, USA, US (3) Department of Surgery, Division of Transplantation, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA, US (4) Department of Biomedical Statistics, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA, US Article note: Received: 19 December 2000 / Revised: 23 April 2001 / Accepted: 24 April 2001

Byline: Anna Maria Hibbs (1), Bojana Bznik-Cizman (2), Martha Guttenberg (3), Beth Goldberg (1), K. Meyers (1) Keywords: KeywordsaAnti-GBM disease; Cytomegalovirus; Ulcerative colitis; HLA Abstract: A renal transplant was performed in a 6-year-old boy who developed end stage renal disease (ESRD) after presenting with antiglomerular basement membrane (anti-GBM) disease. At 10 years of age he developed ulcerative colitis while being immunosuppressed with cyclosporin, prednisone, and azothioprine. He had a pancolectomy, and at 14 years has no symptoms of ulcerative colitis or anti-GBM disease. HLA typing revealed that he was homozygous for HLA DR2. The co-occurrence of anti-GBM disease and ulcerative colitis has not previously been described. Although there is no known common etiology for these two autoimmune diseases, we propose that the patient&apos;s homozygosity at HLA DR2 may have predisposed him to both. Author Affiliation: (1) Division of Nephrology, The Children&apos;s Hospital of Philadelphia, 34th St. and Civic Center Blvd., Philadelphia, PA 19104, and the University of Pennsylvania Medical School, Philadelphia, PA 19104-4399, USA e-mail: meyersk@email.chop.edu Tel.: +1-215-5902449, Fax: +1-215-5903705, US (2) Department of Immunology and Infectious Diseases, The Children&apos;s Hospital of Philadelphia, 34th St. and Civic Center Blvd., Philadelphia, PA 19104, and the University of Pennsylvania Medical School, Philadelphia, PA 19104, USA, US (3) Department of Pathology, The Children&apos;s Hospital of Philadelphia, 34th St. and Civic Center Blvd., Philadelphia, PA 19104, and the University of Pennsylvania Medical School, Philadelphia, PA 19104, USA, US Article note: Received: 21 September 2000 / Revised: 26 January 2001 / Accepted: 1 February 2001