Comparing cystatin C and creatinine in the diagnosis of pediatric acute renal allograft dysfunction.

BACKGROUND: Allograft function following renal transplantation is commonly monitored using serum creatinine. Multiple cross-sectional studies have shown that serum cystatin C is superior to creatinine for detection of mild to moderate chronic kidney dysfunction. Recent data in adults indicate that cystatin C might also be a more sensitive marker of acute renal dysfunction. This study aims to compare cystatin C and creatinine for detection of acute allograft dysfunction in children using pediatric RIFLE (risk of renal dysfunction, injury to the kidney, failure or loss of kidney function, end stage renal disease) criteria for acute kidney injury. METHODS: Retrospective chart review of post-transplant period in 24 patients in whom creatinine and cystatin C were measured every day. Allograft dysfunction was defined as a sustained rise in marker concentration above the mean of the three preceding measurements. RESULTS: In total, there were 13 episodes of allograft dysfunction. Maximum RIFLE stages with creatinine were 'R' in 7, 'I' in 4, and 'F' in 2, with cystatin C 'R' in 6, 'I' in 4 and 'F' in 3, respectively. In 9/13 cases, both markers rose simultaneously, in three, the rise in creatinine preceded cystatin C by 1-5 days (median 4). In one case, the rise in cystatin C preceded creatinine by 1 day. The time lag was not statistically different. The maximum relative rise of creatinine was significantly higher than cystatin C. By multiple linear regression analysis, the maximum rise of cystatin C was related to the maximum rise of creatinine, but independent of patient age, gender, steroid dose, and anthropometric data. CONCLUSIONS: In this pediatric population, cystatin C was not superior to creatinine for the detection of acute allograft dysfunction.

Regional citrate anticoagulation is safe in intermittent high-flux haemodialysis treatment of children and adolescents with an increased risk of bleeding.

BACKGROUND: Regional citrate anticoagulation (RCA) is strongly recommended for adults with an increased risk of bleeding complications. The objective of this retrospective analysis was to evaluate an RCA protocol concerning feasibility and safety in intermittent high-flux haemodialysis (iHD) treatment in children and adolescents. METHODS: Eighteen children and adolescents aged 5-17 years (median 15 years) underwent 74 iHD treatment sessions with RCA. Twelve of 18 patients presented with overt local or diffuse haemorrhage before beginning the HD sessions, and six had an increased risk of haemorrhagic complications. Forty children on acute haemodialysis with general heparin anticoagulation, matched for bleeding risk, age and body surface area, served as a control group. Citrate 3% solution was begun with 3.3% blood flow rate, and calcium gluconate 10% substitution was started with 0.4% of blood flow rate. Citrate flow was adapted to achieve a post-filter ionized calcium of ≤0.30 mmol/L; calcium substitution was adapted to maintain the patients' serum calcium levels within the physiological range. Calcium-free dialysis fluid was used. The blood flow rate ranged from 3 to 5 mL per minute and kilogram body weight. RESULTS: Regional anticoagulation was successfully achieved within the extracorporeal blood circuit, while the coagulation of all 18 patients remained within physiological parameters. No adverse effects of RCA were observed. In all 18 children, neither new haemorrhage nor worsening of the bleeding situation occurred, and in 10/12 patients, bleeding stopped during dialysis with RCA. In contrast, one-third of the control group developed new haemorrhagic complications or presented with worsening of pre-existing bleeding during haemodialysis (P = 0.006). CONCLUSION: RCA is feasible, safe and effective in paediatric intermittent haemodialysis treatment.

Impact of computer-based patient education on illness-specific knowledge and renal function in adolescents after renal transplantation.

Interactive CBE holds potential to increase IRK and IRB in adolescents following transplantation. An experimental design assessed the effect of CBE on IRK and renal function in adolescents after transplantation (N = 50, aged 15-20 yr). The IGr (N = 26) completed a nine-item questionnaire (9-iQ) covering IRK and IRB prior to completing CBE at three consecutive time points (T0-T2). The CGr (N = 24) received standard care. Renal function was determined by GFR 12 months before, at start of intervention, and at three, six, and 12 months after intervention (T-1; T0; T3; T4; T5). Overall IRK improved significantly over time (p < 0.0001) for IGr patients relative to CGr. Analysis of IRK demonstrated a significant increase in knowledge from T0 to T1 (p < 0.028) and from T1 to T2 (p < 0.045) in the IGr when compared to the CGr. With respect to IRB, a tendency to improve was seen (p = 0.06). The GFR gradient was stable in the IGr relative to a significant decrease in the CGr (p < 0.001). Our data suggest that interactive CBE improves IRK in adolescent renal transplant recipients. In addition, these programmes demonstrate improvements on IRB.

Renal replacement therapy in infants with chronic renal failure in the first year of life.

BACKGROUND AND OBJECTIVES: Although results of renal replacement therapy (RRT) in small children have improved during recent years, data about RRT in neonates are scarce. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a retrospective study, we analyzed the outcome of infants who had chronic kidney disease and started RRT within their first year of life. Between 1997 and 2008, all 29 infants who were younger than 1 yr, had end-stage renal failure, and underwent RRT (dialysis or transplantation) at Hannover Medical School were analyzed for up to 12 yr. RESULTS: Twenty-seven of 29 infants with chronic kidney disease received peritoneal dialysis, starting at a mean age of 112 d; two children received preemptive renal transplantation (RTx). During follow-up, 21 of 29 children survived with RTx. The 5-yr patient and graft survival rate after RTx was 95.5%. Six of 29 children died, one with a functioning graft and five while on peritoneal dialysis. The main causes of death were severe cardiovascular and cerebral comorbidities. The mean GFR at last follow-up of patients who underwent RTx (mean time after RTx 5.1 yr) was 63.2 ml/min per 1.73 m(2). CONCLUSIONS: RRT in infants who are younger than 1 year offers excellent chances of survival and should be offered to all infants who do not have severe, life-limiting extrarenal comorbidity. Contrary to previous observations, the long-term outcome of infants may be comparable to that of older children who undergo RRT.

Efficacy and safety of basiliximab in pediatric renal transplant patients receiving cyclosporine, mycophenolate mofetil, and steroids.

BACKGROUND: Basiliximab, a monoclonal CD25 antibody has proofed effective in reducing acute rejection episodes in adults in various immunosuppressive regimens. The effect of basiliximab in the pediatric population is controversial. METHODS: In a 12-month, double-blind, placebo-controlled trial, renal transplant patients aged 1 to 18 years were randomized to basiliximab or placebo with cyclosporine microemulsion, mycophenolate mofetil, and corticosteroids. The intent-to-treat population comprised 192 patients (100 basiliximab and 92 placebo). RESULTS: The primary efficacy endpoint, time to first biopsy-proven acute rejection episode, or treatment failure by month 6, occurred in 16.7% of basiliximab-treated patients and 21.7% of placebo-treated patients (Kaplan-Meier estimates; hazard ratio 0.72, two-sided 90% confidence interval 0.416-1.26, n.s.). The rate and severity of subclinical rejections in protocol biopsies performed at 6 months posttransplant was higher in the basiliximab group (25.0%) than in the placebo group (11.7%). Patient and death-censored graft survival at 12 months was 97% and 99%, respectively, in the basiliximab cohort, and 100% and 99% among placebo-treated patients (n.s.). Renal function was similar in both treatment groups, and there were no significant between-treatment differences in the incidence of adverse events or infections. CONCLUSIONS: Addition of basiliximab induction to a regimen of cyclosporine microemulsion, mycophenolate mofetil, and steroids resulted in a numerically lower but not significant incidence of biopsy-proven acute rejection versus placebo and excellent graft and patient survival at 1 year in pediatric renal transplant recipients. Whether this numerical difference is a true therapeutic benefit in view of the higher rate and severity of subclinical rejections in the basiliximab group in the protocol biopsy will be investigated in a long-term follow-up study.

Pharmacokinetics and immunodynamics of basiliximab in pediatric renal transplant recipients on mycophenolate mofetil comedication.

BACKGROUND: The aim of this substudy within a prospective, multicenter, placebo-controlled trial was to assess the pharmacokinetics and immunodynamics of basiliximab in pediatric renal transplant recipients on comedication with mycophenolate mofetil (MMF). METHODS: Eighty-two patients aged 3 to 18 years, receiving cyclosporine microemulsion, MMF, corticosteroids, and basiliximab or placebo were investigated. Basiliximab serum concentrations were determined by ELISA, CD25+, and CD122+ T lymphocytes by flow cytometry. RESULTS: Basiliximab clearance adjusted to body surface area was significantly (P<0.05) greater in children versus adults, but the relatively higher basiliximab dose given to children yielded similar exposure compared with adolescents. A cross-study comparison revealed that MMF reduced basiliximab clearance and prolonged CD25 saturation duration from approximately 5 weeks in the absence of MMF to 10 weeks in the presence of MMF. Basiliximab led to a marked reduction of CD25+ T-cell fraction during the first 8 to 10 weeks posttransplant, but did not specifically affect CD122+ T cells. The majority of biopsy-proven acute rejection episodes (BPAR) were observed after interleukin (IL) 2-R desaturation, whereas about a quarter of BPARs occurred despite adequate IL2-R blockade. CONCLUSIONS: The currently recommended basiliximab dose for pediatric patients, when used with cyclosporine microemulsion and corticosteroids, yielded adequate drug exposure in children and adolescents also under MMF comedication. The observation that about a quarter of BPARs occurred despite adequate IL2-R blockade suggests that another T-cell activation pathway independent of the IL-2/IL-2R pathway is operative, for example, the IL-15 signaling pathway.

Multicenter trial of everolimus in pediatric renal transplant recipients: results at three year.

There are few prospective clinical trials of mTOR inhibitors (or proliferation signal inhibitors) combined with CNI inhibitors in de novo pediatric renal transplantation. Results reported here are from a multicenter, open-label study in de novo pediatric renal transplant patients (

Liver transplantation in a subject with familial hypercholesterolemia carrying the homozygous p.W577R LDL-receptor gene mutation.

Mutations within the low density lipoprotein (LDL)-receptor gene result in familial hypercholesterolemia, an autosomal dominant inherited disease. Clinical homozygous affected subjects die of premature coronary artery disease as early as in early childhood. We identified a girl at the age of five yr with clinical homozygous familial hypercholesterolemia presenting with achilles tendon xanthomas and arcus lipoides. Her total cholesterol reached up to 1050 mg/dL. Molecular characterization of the LDL-receptor gene revealed a homozygous p.W577R mutation. Despite intensive treatment interventions with the combination of diet, statins, colestipol, and LDL-apheresis, the patient developed symptomatic coronary artery disease at the age of 16 yr. Subsequently, orthotopic liver transplantation was performed to cure the defective LDL-receptor gene. Clinical follow-up for almost nine yr post-transplantation revealed excellent liver function, normal liver enzymes, normal LDL-cholesterol, and regression of both tendon xanthomas and symptomatic coronary artery disease. In conclusion, liver transplantation can effectively reduce LDL-cholesterol in a familial hypercholesterolemia recipient with subsequent regression of xanthomas and atherosclerosis. Timing is extremely important in these exceptional cases to exclude the demand for heart transplantation due to severe coronary artery disease. In addition, the identification of the LDL-receptor as etiology of clinical homozygous hypercholesterolemia is a prerequisite once liver transplantation is considered as therapeutic option.

Aetiology and outcome of acute and chronic renal failure in infants.

BACKGROUND: The aetiology and outcome of acute (ARF) and chronic renal failure (CRF) in infants were analysed in a retrospective study. METHODS: Between January 1997 and April 2004 all children <1 year of age with a serum creatinine >100 mumol/l at Hannover Medical School were followed up for up to 6 years. One hundred and nineteen children with a serum creatinine >100 mumol/l were identified, 70 infants suffering from ARF and 49 from chronic kidney disease (CKD), stages 3-5. RESULTS: Renal failure was caused in 49/119 (41%) by congenital and in 70/119 (59%) by acquired diseases. The aetiology of ARF (n = 70) included cardiac (27%), prematurity (27%), septic (10%), hepatic (9%), renal (9%) and other (18%) causes. Twelve infants needed transient dialysis treatment. Renal function recovered in all surviving children. The mortality rate was 37%. Causes of death were unrelated to kidney function. Twenty-one of 49 infants with CKD were dialyzed with a median age of 65 days at the start of dialysis, and 23/49 children received a kidney transplant (RTx). The 5-year patient and graft survival for RTx-children of 95.5% was not different from older children. The 5-year patient survival rate of 26 children with CKD without RTx was 63%. The causes of death were parental refusal of therapy in neonates (n = 4) and life-threatening extra-renal comorbidity (n = 3). CONCLUSION: Renal replacement therapy offers good chances of survival in infants without life-threatening comorbidity. Patient survival of infants treated for CKD in the first year of life was comparable to that of older children.

CNS or bone marrow involvement as risk factors for poor survival in post-transplantation lymphoproliferative disorders in children after solid organ transplantation.

PURPOSE: To identify prognostic factors of survival in pediatric post-transplantation lymphoproliferative disorder (PTLD) after solid organ transplantation. PATIENTS AND METHODS: A multicenter, retrospective case analysis of 55 pediatric solid organ graft recipients (kidney, liver, heart/lung) developing PTLD were reported to the German Pediatric-PTLD registry. Patient charts were analyzed for tumor characteristics (histology, immunophenotypes, cytogenetics, Epstein-Barr virus [EBV] detection), stage, treatment, and outcome. Probability of overall and event-free survival was analyzed in defined subgroups using univariate and Cox regression analyses. RESULTS: PTLD was diagnosed at a median time of 29 months after organ transplantation, with a significantly shorter lag time in liver (0.83 years) versus heart or renal graft recipients (3.33 and 3.10 years, respectively; P = .001). The 5-year overall and event-free survival was 68% and 59%, respectively, with 59% of patients surviving 10 years. Stage IV disease with bone marrow and/or CNS involvement was associated independently with poor survival (P = .0005). No differences in outcome were observed between early- and late-onset PTLD, monomorphic or polymorphic PTLD, and EBV-positive or EBV-negative PTLD, respectively. Patients with Burkitt or Burkitt-like PTLD and c-myc translocations had short survival (< 1 year). CONCLUSION: Stage IV disease is an independent risk factor for poor survival in pediatric PTLD patients. Prospective multicenter trials are needed to delineate additional risk factors and to assess treatment approaches for pediatric PTLD.

Reversal of loss of glomerular filtration rate in children with transplant nephropathy after switch to everolimus and low-dose cyclosporine A.

Until now there have been no good therapeutic options in children with biopsy-proven transplant nephropathy (TN) and loss of glomerular filtration rate (GFR) while receiving cyclosporine A (CsA), mycophenolate mofetil (MMF) and prednisolone (Pred). In 13 kidney transplanted children (mean age 13 yr, SD 4) with CsA/MMF/Pred immunosuppression, renal biopsy revealed significant TN. MMF was discontinued, CsA dose was reduced to 50% and Everolimus was started (1.6 mg/m(2)/day). Pred was stopped in 10 of 13 patients. The mean GFR was 55 mL/min/1.73 m(2) (SD 24) one yr before switch, 45 mL/min/1.73 m(2) (SD 16, p < 0.05) at the time of switch and 47 mL/min/1.73 m(2) (SD 18, p < 0.05) 12 months later. There were no severe side-effects or acute rejections. Lactate dehydrogenase, cholesterol, creatine kinase, and U-albumin/creatinine ratio did not increase significantly. After six months, the mean certican-C0 level was 4.0 microg/L (SD 1.5) and mean CsA-C0 level was 52 ng/mL (SD 23). The GFR of transplanted kidneys in children with TN improved by changing immunosuppression from CsA/MMF/Pred to everolimus and low-dose CsA.

Young for young! Mandatory age-matched exchange of paediatric kidneys.

Some allocation systems include a mandatory donation of paediatric kidneys to children, others do not. Both approaches have medical and organisational advantages and disadvantages for adults and children. This article discusses why "young for young" is the best allocation system for children. Primary age-matched kidney allocation to children is one important factor leading to: (1) higher long-term glomerular filtration rates (GFRs) and graft survival and, thereby, to lesser need for dialysis; (2) better psychosocial rehabilitation, growth and development of children and, last but not least, (3) likely increase of the donor pool. As a consequence, health care costs will be reduced for children with end-stage renal failure. The chance of adults receiving an adequate kidney would be only minimally reduced by this policy. Therefore, we recommend an age-matched allocation programme giving children with end- stage kidney diseases a better prognosis.

Growth impairment shows an age-dependent pattern in boys with chronic kidney disease.

The impact of chronological age on longitudinal body growth from early childhood through adolescence using detailed anthropometric methods has not yet been studied in children with chronic kidney disease (CKD). We have evaluated growth failure by measuring four components of linear growth: body height (HT), sitting height (SHT), arm length (AL) and leg length (LL). Data were prospectively collected for up to 7 years on 190 boys (3-21 years old) with congenital or hereditary CKD (all had developed at least stage 2 CKD by the age of 10 years). Patients showed the most severe growth failure in early childhood, followed by an acceleration in growth in pre-puberty, a slowing-down of growth at puberty, as expected, and thereafter a late speeding-up of growth until early adulthood. This pattern was observed irrespective of the degree of CKD and different treatment modalities, such as conservative treatment, recombinant human growth hormone (rhGH) therapy or transplantation. LL showed the most dynamic growth changes of all the parameters evaluated and emerged as the best indicator of statural growth in children with CKD. A specific age-dependent pattern of physical growth was identified in pediatric male CKD patients. This growth pattern should be considered in the evaluation of individual growth and the assessment of treatment efficacy such as rhGH therapy.

ABO-incompatible kidney transplantation of an 8-yr-old girl with donor/recipient-constellation A1B/B.

BACKGROUND: Antigen-specific immunoadsorption combined with rituximab offers the possibility for ABO-incompatible kidney transplantation without splenectomy. PATIENT AND METHOD: An 8-year-old mentally retarded girl with steroid-resistant nephrotic syndrome and focal segmental glomerulosclerosis due to mitochondriopathy poorly tolerated hemodialysis. Paternal blood group A1B was incompatible with blood group B of the child. Therefore, we decided to perform the first ABO-incompatible renal transplantation in a child in Germany using antigen-specific immunoadsorption. Rituximab (1 x 375 mg/m2) was administered 2 weeks before the first immunoadsorption (Glycosorb) ABO A-column). Triple-drug immunosuppression (tacrolimus, mycophenolate mofetil and prednisolone) was simultaneously started with immunoadsorption. Initial tacrolimus levels were targeted between 15 and 20 ng/ml. Before transplantation, six immunoadsorptions were applied on days -9, -7, -4, -3, -2 and -1. Intravenous immunoglobulin (0.5 g/kg) was administered preoperatively. After transplantation, three immunoadsorptions were performed on days +4, +6 and +8. RESULTS: Before transplantation, antibody (Ab) titers against paternal erythrocytes (20 degrees C) were reduced from 1 : 64 to 1 : 4 by six antigen-specific immunoadsorptions. After transplantation, we performed three more immunoadsorptions and the Ab titers were stable between 1 : 1 and 1 : 8. One, 2 and 8 months later we observed increases in the Ab titer up to 1 : 32 requiring no change in immunosuppressive therapy. No side effects of immunoadsorption were observed. The girl had excellent initial graft function with a serum creatinine of 55 to 70 micromol/l. Two weeks after transplantation, graft biopsy showed no signs of rejection; there was focal positivity for C4d only. Twelve months after transplantation, renal function was stable, with a serum creatinine of 117 micromol/l. Episodes of rejection or severe infections were absent. CONCLUSION: ABO-incompatible transplantation using antigen-specific immunoadsorption and rituximab may serve as a suitable alternative for children urgently needing renal transplantation and missing a blood group-compatible donor.

A randomized crossover trial comparing sevelamer with calcium acetate in children with CKD.

BACKGROUND: A multicenter, randomized, open-label, crossover study was performed to compare the efficacy and safety of sevelamer, a calcium-free phosphate binder, with calcium acetate in pediatric patients with chronic kidney disease (CKD). METHODS: Children (age, 0.9 to 18 years) with CKD undergoing hemodialysis or peritoneal dialysis or with a glomerular filtration rate of 20 or greater and less than 60 mL/min/1.73 m2 (> or = 0.33 and < 1.00 mL/s/1.73 m2) were randomly assigned to the following treatment scheme: 2 weeks of washout followed by 8 weeks of treatment with either sevelamer or calcium acetate in a crossover fashion. Phosphorus, calcium, and intact parathyroid hormone in serum were measured every 2 weeks, and phosphate binder dosages were adjusted, if needed. Serum lipid and vitamin concentrations were measured at the beginning and end of each treatment period. The primary end point was the decrease in serum phosphorus levels after 8 weeks of treatment. RESULTS: Forty-four patients were screened. Altogether, data for 18 patients (5 girls) aged 12.4 +/- 4.1 years were used for the crossover analysis. There was no significant difference in serum phosphorus levels at 8 weeks after the start of treatment in both groups. Total cholesterol (-27%) and low-density lipoprotein cholesterol (-34%) levels decreased significantly with sevelamer treatment (P < 0.02 and P < 0.005). An increased incidence of hypercalcemia (P < 0.0005) was observed with calcium acetate treatment, whereas metabolic acidosis was more frequent with sevelamer treatment (P < 0.005). CONCLUSION: Treatment of children with CKD with sevelamer and calcium acetate provides similar phosphorus level control. The marked decrease in lipid levels and lower rate of hypercalcemia may augment the long-term benefit of sevelamer.

Paediatric kidney transplantation in small children-- a single centre experience.

Kidney transplantation (KTx) remains a challenging procedure in small children. This study presents our centre results. From 1983 to 2004, 40 of 442 paediatric KTx were performed in children with a body weight <11 kg. Median body weight was 9.2 kg (range: 7.2-10.9), median age was 2.7 years (range: 0.9-5.9). Preoperative dialysis was performed in 87.5%. In 24 cases (60%) grafts came from cadaveric (CAD) and in 16 cases (40%) from living related donors (LRD). Median donor age of CAD was 8 years (range: 1-40). The overall 1-, 5-, 10-, 15-year patient survival was 93%, 90%, 90% and 87% respectively. The overall 1-, 5-, 10-, 15-year graft survival was 90%, 80%, 66% and 56% respectively. There was no significant difference in survival of CAD or LRD grafts. Median follow-up was 13.7 years. Initial graft function rate was 100% for LRD and 79% for CAD. The relative glomerular filtration rate (GFR) showed no statistical difference between CAD and LRD. Main reasons for graft loss were chronic transplant nephropathy. Paediatric KTx is the treatment of choice even in very small children. Living donor KTx is the preferable donor source in terms of primary graft function and timing to transplantation.

Four-year data after pediatric renal transplantation: a randomized trial of tacrolimus vs. cyclosporin microemulsion.

This study was undertaken to compare the efficacy and safety of tacrolimus (Tac) with cyclosporin microemulsion (CyA) in pediatric renal recipients. 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 yr) were randomly assigned (1:1) to receive either Tac (n = 103) or CyA (n = 93) administered concomitantly with azathioprine and corticosteroids. The primary endpoint was incidence and time to first acute rejection (intent-to-treat). Baseline characteristics were comparable between treatment groups. Excluding deceased patients (n = 9) and patients lost to follow-up (n = 31, mostly transferred to adult care), 95% of 2-yr data (159 of 167 possible patients), 87% of 3-yr data (142 of 163) and 73% of 4-yr data (114 of 156) were retrieved. At 1 yr Tac therapy resulted in a significantly lower incidence of acute rejection (36.9%) compared with CyA (59.1%, p = 0.003). The incidence of corticosteroid-resistant rejection was also significantly lower with Tac (7.8% vs. 25.8%, p = 0.001). At 4 yr, patient survival was similar (94% vs. 92%, p = 0.86) but graft survival significantly favored Tac (86% vs. 69%; p = 0.025, log-rank test), respectively. At 1 yr, the mean glomerular filtration rate (GFR) (Schwartz formula, ml/min/1.73 m(2)) was 64.9 +/- 20.7 (n = 84) vs. 57.8 +/- 21.9 (n = 77, p = 0.0355), at 2 yr 64.9 +/- 19.8 (n = 71) vs. 51.7 +/- 20.3 (n = 66, p = 0.0002), at 3 yr 66.7 +/- 26.4 (n = 81) vs. 53.0 +/- 23.3 (n = 55, p = 0.0022), and at 4 yr 71.5 +/- 22.9 (n = 51) vs. 53.0 +/- 21.6 (n = 44, p = 0.0001) for Tac vs. CyA, respectively. Cholesterol remained significantly higher with CyA throughout follow-up. Three patients in each arm developed post-transplant lymphoproliferative disease. Incidence of insulin-dependent diabetes mellitus was not different. Tac was significantly more effective than CyA in preventing acute rejection in pediatric renal recipients. Renal function and graft survival were also superior with Tac. Glomerular filtration rate appears to be an useful surrogate marker for long-term outcome.

Renal arterial resistance index and computerized quantification of fibrosis as a combined predictive tool in chronic allograft nephropathy.

The renal arterial resistance index (RI) and the PicroSirius-Red stained cortical fractional interstitial fibrosis volume (VintFib) proved to be two independent methods that are reliable predictive factors of poor renal allograft outcome. No data have been published, which define the correlation between ultrasound assessment and quantitative morphologic changes. Renal biopsies were performed in 56 children according to increases in s-creatinine >10%. VintFib was calculated by computerized image analysis. RI was determined in two segmental arteries, 1 yr after transplantation and at the time-point of biopsy. RIs 1 yr after transplantation correlated significantly with RIs at time of biopsy (r = 0.58, p < 0.001). VintFib was higher in children with a RI = 80 than in children with a RI < 80 (mean VintFib = 9.5 +/- 3.2% vs. 5.2 +/- 5.1%, p = 0.004). In children with VintFib > 10%, the mean RI was 77 +/- 5 compared with 69 +/- 6 in patients with VintFib < 10% (p = 0.0002). The highest positive predictive value to detect the risk of decline of GFR at 2 yr after biopsy was 98% when an RI = 80% was associated with a VintFib > 10%. For VintFib > 10% or RI = 80 alone, it was 87% or 67%, respectively. The combined measurement of RI and VintFib is a reliable predictive tool for the risk of developing long-term graft dysfunction after kidney transplantation.