The CERTAIN Registry: a novel, web-based registry and research platform for pediatric renal transplantation in Europe.

BACKGROUND: The results of pediatric renal transplantation have improved markedly in the last decade. However, a number of relevant clinical problems remain, such as organ damage caused by chronic rejection, long-term toxicity of immunosuppressive therapy, difficulty in developing tolerance-inducing protocols, secondary cardiovascular comorbidity, post-transplantation lymphoproliferative disease, suboptimal longitudinal growth, quality of life, adherence to immunosuppressive medication, and structured transition programs to adult care. These unmet clinical needs require intense collaborative and interdisciplinary clinical research. We recently founded the Cooperative European Paediatric Renal TransplAnt INitiative (CERTAIN; www.certain-registry.eu) as a research network and platform built on a novel, web-based registry. RESULTS: The registry's dataset provides essential information on generic kidney transplantation-related topics and also captures pediatric-specific topics, such as growth, physical and psychosocial development, and adherence. Due to its flexibility the system can be used as follows: (1) as a registry capturing a minimal or an extended dataset; (2) as a center and/or country-specific transplantation database; or (3) as a patient-specific electronic transplantation chart. The data can be exported directly from the CERTAIN web application into statistical software packages for scientific analyses. The rights regarding data ownership, evaluation, and publications are regulated in the registry's rules of procedure. Data quality is ensured by automatic software validation and a manual data review process. To avoid redundant data entry, CERTAIN has established interfaces for data change with Eurotransplant, the Collaborative Transplant Study (CTS), and the registry of the European Society of Pediatric Nephrology (ESPN) and European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) (ESPN/ERA-EDTA registry). CERTAIN fulfils all regulatory and ethical requirements of the European Union and Germany, in particular, regarding patients' data privacy and security. CONCLUSION: Using modern information technology, the recently established multinational CERTAIN Registry fills a gap in Europe for collaborative 5 research and quality assurance in the field of pediatric renal transplantation.

How often do we face side effects of sirolimus in pediatric renal transplantation?

We analyzed 25 pediatric renal transplantation patients on sirolimus (SRL) therapy to assess changes in serum creatinine, glomerular filtration rate, electrolytes, triglycerides, cholesterol, and side effects. Mean time to initiate SRL therapy was 3.2 years. The serum creatinine levels of patients on SRL treatment at 1, 6, 12, and 24 months were 1.67 ± 1.15 mg/dL, 1.18 ± 0.52 mg/dL, 1.24 ± 0.32 mg/dL, 1.15 ± 0.31 mg/dL, and 1.17 ± 0.12 mg/dL, respectively. We observed proteinuria in 3, hyperlipidemia in 5, and anemia in 2 patients, but none had the treatment discontinued. We diagnosed interstitial pneumonia in (n = 1), nasal acneiform lesions (n = 1), and lower extremity edema (n = 1). Hypokalemia developed in 1 subject with high blood SRL levels. In the follow-up period there was no case of acute rejection episode during SRL therapy.

Henoch-Schönlein nephritis: a nationwide study.

BACKGROUND/AIM: The aim of this retrospective study was to evaluate the presentation, clinical and pathological manifestations and outcome of the Henoch-Schönlein purpura (HSP) nephritis in children. METHODS: Clinical and laboratory data of 443 children with HSP nephritis aged between 3 and 16 years from 16 pediatric nephrology reference centers were analyzed retrospectively. The biopsy findings were graded according to the classification developed by the International Study of Kidney Disease in Children (ISKDC). RESULTS: Renal biopsy was performed in 179 of the patients with HSP nephritis. The most common presenting clinical finding in patients who were biopsied was nephrotic range proteinuria (25%) which was followed by nephritic-nephrotic syndrome (23.5%). The biopsy findings according to the ISKDC were as follows: class I: 8.3%; II: 44.1%; III: 36.3%; IV: 6.7%; V: 3.3%; VI: 1.1%. All of the patients who developed end-stage renal disease had nephritic-nephrotic syndrome at presentation. Of 443 patients, 87.2% had a favorable outcome and 12.8% had an unfavorable outcome. The overall percentage of children who developed end-stage renal disease at follow-up was 1.1%. Logistic regression analysis did not show any association of initial symptoms and histology with outcome. CONCLUSION: In the presented cohort, the presence of crescents in the first biopsy or presenting clinical findings did not seem to predict the outcome of HSP nephritis in children. We conclude that children with HSP nephritis even with isolated microscopic hematuria and/or mild proteinuria should be followed closely.

Successful solid organ transplantation from septicemic cadaveric donors: case report.

Systemic donor infections especially with gram-negative organisms are regarded as an absolute contraindication to cadaveric organ donation for transplantation. This is largely due to fear of transmitting the pathogenic organisms to the immunosuppressed recipient. However, due to the current shortage of organs available for transplantation, clinicians are faced with the option to use organs from infected donors. Between 1996 to January 2006, we collected 44 solid organs. Two out of nine donors had microorganisms from blood cultured. Case 1 was of 23-year old woman whose cause of brain death was intracerebral bleeding due to a traffic accident. The donor had stayed 9 days in the intensive care unit prior to brain death. Two kidneys, two livers (split), and or heart were used. Klebsiella was the organism on blood culture. Case 2 was of 35-year-old man; cause of brain death was cerebral hematoma due to traffic accident. The donor had stayed 6 days prior to brain death onset. The liver and two kidneys were used. Acinetobacter baumannii was yielded upon blood culture. All donors were treated with appropriate antibiotics for at least 48 hours prior to organ procurement with consequent negative blood cultures, while the recipients received the same culture-specific antibiotics for 10 days following transplantation. One donor (case 1) heart and both donor corneas were not used due to infection. All patients are alive with excellent graft function at a median of 90 days following transplantation. In conclusion, our results suggested that bacteremic donors with severe sepsis under proper treatment can be considered for transplantation.

BK virus-associated nephropathy in two pediatric kidney recipients.

Posttransplant renal dysfunction episodes can result from a variety of causes, including polyomavirus (BK virus)-associated nephropathy (PVAN). It is a well-recognized entity with a high incidence of graft failure. The delicate balance of viral infection and immune regulation in the transplant population would allow development of successful long-term strategies. In this presentation, we have described two PVAN cases of our institution and reviewed the literature.

Osteoprotegerin and RANKL serum levels and their relationship with serum ghrelin in children with chronic renal failure and on dialysis.

BACKGROUND: Osteoprotegerin (OPG) and receptor activator of the nuclear factor kappaB ligand (RANKL) constitute a complex system of mediators involved in the regulation of bone resorption process. Ghrelin, a growth hormone secretagogue, has been shown to modulate proliferation and differentiation of osteoblasts. The present study was carried out to evaluate the serum concentrations of OPG and sRANKL in children with chronic renal impairment (CRI) and on dialysis, and to establish a possible relationship between their serum levels and that of ghrelin. METHODS: 33 patients including 10 patients with CRI, 12 peritoneal dialysis (PD) and 11 hemodialysis (HD) patients and 22 healthy controls were enrolled into the study. OPG, sRANKL and ghrelin levels were studied with radioimmunoassay. RESULTS: Serum OPG levels in CRI, PD and HD groups were significantly higher than the healthy controls (p = 0.002, p < 0.001, p < 0.001, respectively) whereas sRANKL levels were significantly lower than the healthy controls (p = 0.03, p = 0.01, p = 0.001, respectively). Ghrelin levels were significantly higher in CRI, PD and HD groups compared to healthy controls (p = 0.001, p < 0.001, p < 0.001, respectively). We observed a negative correlation between the sRANKL and OPG levels (r = -0.27, p = 0.04) as well as between sRANKL and ghrelin levels (r = -0.31, p = 0.02). OPG levels showed a positive correlation with ghrelin levels (r = 0.63, p < 0.001). CONCLUSION: We found a lower RANKL bioactivity index in children with CRI and on dialysis. The mechanism and the role of elevated OPG and low sRANKL in uremia are unclear, but they might partly represent a compensatory mechanism to the negative balance of bone remodeling in renal bone disease in children. Additionally, we demonstrated for the first time that ghrelin and the RANKL/OPG system have a close relationship in CRF. Therefore, ghrelin may be of importance in mediating the effects of the RANKL/OPG system in renal bone disease.

Triple immunosuppression with or without basiliximab in pediatric renal transplantation: acute rejection rates at one year.

Acute rejection (AR) is a major determinant of chronic allograft dysfunction and graft survival. This study evaluated the effect of basiliximab on AR in pediatric renal transplantation on triple immunosuppression. Forty-three transplantations (25 males and 18 females; mean age 14.9 +/- 3.6 years) were performed between 1996 and 2002. Thirteen of the grafts came from cadaveric donors and 30 from living-related donors. All patients were placed on immunosuppression with prednisolone + (azathioprine or mycophenolate mofetil) + (cyclosporine [CYA] or tacrolimus). Basiliximab was also administered in 20 cases. The respective rates of biopsy-proven AR in the basiliximab group (BG) and the standard-regimen group (N-BG) were 0% vs 17.4% (P >.05) at 1 month posttransplantation; 0% vs 26.1% (P <.05) at 3 months; 0% vs 26.1% (P <.05) at 6 months, and 7.1% vs 26.1% (P >.05) at 12 months. In the N-BG group the 1- and 3-year graft survival rates were 91.3% (21/23) and 83.3% (15/18), respectively. The mean glomerular filtration rate (GFR) in the first year after the transplantation was 75 +/- 33 mL/min/1.73 m(2) in the N-BG and 98 +/- 21 mL/min/1.73 m(2) in the BG patients (P <.05). Basiliximab significantly reduced the rates of acute rejection at 3 and 6 months after pediatric renal transplantation. The GFR in the first year was significantly higher among the patients treated with basiliximab, which was well tolerated by all patients and caused no significant adverse effects. The effect of basiliximab on long-term graft survival and chronic allograft dysfunction deserves further investigation.

Pattern of human leukocyte antigens in Turkish children with celiac disease.

BACKGROUND: Regional variations in the human leukocyte antigen (HLA) distribution patterns of celiac disease (CD) have been reported. The aim of the present study was to assess the distribution of HLA class I and class II in Turkish children with CD and to compare the findings with a control group. METHODS: Human leukocyte antigen typing was performed in 33 children with CD and in 77 healthy individuals, who served as controls, by using standard National Institutes of Health lymphocytotoxicity techniques. RESULTS: A positive association was found between HLA A2 (42 vs 19% for sick subjects compared with healthy controls, respectively), B8 (39 vs. 9% for sick subjects compared with healthy controls, respectively), CW7 (45 vs. 25% for sick subjects compared with healthy controls, respectively), DR3 (70 vs. 17% for sick subjects compared with healthy controls, respectively), DR7 (30 vs. 13% for sick subjects compared with healthy controls, respectively) and DQ2 (52 vs. 34% for sick subjects compared with healthy controls, respectively). The combinations of DR3-DQ2 (30 vs. 12% for sick subjects compared with healthy controls, respectively), DR3-DR4 (21 vs. 1% for sick subjects compared with healthy controls, respectively) and DR7-DQ2 (21 vs. 6% for sick subjects compared with healthy controls, respectively) were also found to be significantly important in children with CD. The highest relative risk (RR) was for HLA B8 in class I (RR 6.50), for DR3 (RR 11.30) in class II and for combination of DR3-DR4 (RR 20.46). The highest etiologic fraction (EF) was for the DR3 antigen (EF 0.55). CONCLUSIONS: The present study emphasizes that HLA genotypes are an important background to CD development, but some additional susceptibility factors remain to be identified.

A stormy transplant case with happy ending.

A 12-year-old female patient with end-stage renal failure whose primary disease was reflux nephropathy, was first admitted for augmentation cystoplasty by using an ileum segment because of contracted urinary bladder. Four months later, she had a renal transplantation from her father on March 28th 1997. The first three days after the operation were uneventful. On the fourth day, she presented a severe rejection episode and was treated with steroid and ATG. A urinary fistula developed and she underwent surgery again on the 14th postoperative day. At surgery, apical resection + omentoplasty + nephrostomy + DJ replacement were performed. The postoperative period after the second operation was full of problems for both the patient and the transplantation team. She was discharged from hospital on the 40th postoperative day with excellent renal function (a serum creatinine level of 1 mg/dl) and with full recovery.

Desmopressin versus indomethacin treatment in primary nocturnal enuresis and the role of prostaglandins.

OBJECTIVES: To compare the efficacy of desmopressin and indomethacin and also determine the prostaglandin E2 (PGE2) concentrations in the patient and control groups. METHODS: Eighty-five children with primary nocturnal enuresis were followed up for a baseline period of 4 weeks, during which they recorded wet and dry nights. After this period, the patients were divided into three groups that used desmopressin, indomethacin, or placebo for 4 weeks. The dosage of desmopressin (group A, n = 31 ) was 20 microg/day and the dosage of indomethacin (group B, n = 29) was 100 mg/day. The placebo group (group C) consisted of 25 patients. We determined the serum PGE2 and urine PGE2 concentrations before and after treatment in the three groups and in a control group. RESULTS: Treatment with desmopressin and indomethacin resulted in significantly more dry nights during the 4 weeks of observation than did placebo (P <0.005). The number of dry nights was also significantly different in the desmopressin group than in the indomethacin group (P <0.01). In the total patient group, the mean serum and urine PGE2 concentrations were significantly different from the control group's serum and urine PGE2 concentrations (P <0.001). There was a significant decrease in the serum and urine PGE2 concentrations in group A and group B after the treatment period (P <0.01). CONCLUSIONS: Desmopressin and indomethacin were found to be more effective than placebo. We conclude that prostaglandins have an important role in the pathophysiology of primary nocturnal enuresis.

Urinary and serum type III collagen: markers of renal fibrosis.

BACKGROUND: The progression of chronic renal failure is characterized by the progressive fibrosis of the kidneys. Such fibrosis reflects the increased deposition of collagens (I, III, and IV) as well as fibronectin within scarred kidneys. In this study, we determined whether changes in renal extracellular matrix (ECM) components are reflected by parallel changes in their circulating or urinary levels. PATIENTS AND METHODS: We studied 40 patients with a range of subacute and chronic nephropathies who underwent a renal biopsy. At the time of the biopsy, their serum and urinary levels of collagens III (amino terminal peptide of procollagen III; PIIINP) and IV, as well as fibronectin were measured. Clinical, biochemical and histological parameters were correlated. Multiple regression analysis was applied to determine the predictive value of circulating and urinary ECM components for the severity of renal fibrosis. RESULTS: We noted an increase in circulating and urinary levels of collagens III and IV but not fibronectin in patients with nephropathies compared to healthy volunteers. Increased immunoreactivity for these ECM components was also detected in kidney biopsies when compared to normal kidneys. A strong positive correlation was detected between circulating and urinary procollagen III (PIIINP) and the severity of renal interstitial fibrosis (serum PIIINP: r = 0.49, P < 0.01; urine PIIINP: r = 0.51, P < 0.01). CONCLUSION: We conclude that the measurements of urinary collagen III (PIIINP), and to a lesser extent serum collagen III (PIIINP), are useful indicators of the extent of renal fibrosis. This may have diagnostic implications and may prove useful for the monitoring of disease progression.

Myofibroblasts and the progression of diabetic nephropathy.

BACKGROUND: The cellular mediators of progressive renal fibrosis in diabetic nephropathy remain unknown. Myofibroblasts have been implicated in the pathogenesis of experimental and clinical renal fibrosis. Their role in the progression of diabetic nephropathy is the subject of this study. SUBJECTS AND METHODS: We have studied by immuno-histochemistry the expression of cytoskeletal proteins associated with the activation of myofibroblasts; alpha-smooth-muscle actin (alpha-SMA), vimentin (Vi) and desmin (D), in the kidneys of 25 patients with diabetic nephropathy (5 patients had a superimposed glomerulonephritis). Comparisons were made with normal tissue from three kidneys removed for renal-cell carcinoma. Correlations were studied between clinical and biochemical parameters with the expression of renal cytoskeletal proteins. RESULTS: In normal kidneys, cells expressing alpha-SMA were confined to the vascular media and adventitia while immunoreactive Vi was detected in glomerular epithelial cells. In diabetic kidneys, cells expressing alpha-SMA were detected primarily in the renal interstitium and to a lesser extent in some glomeruli in association with mesangial proliferation. Vimentin immunostain decreased in glomeruli displaying diabetic hyalinosis and sclerosis. By contrast, strong Vi immunoreactivity was noted in atrophic diabetic tubules and to a lesser extent in the interstitium. Desmin was not detected in either normal or diabetic kidneys. Close correlations were observed between the expression of renal cytoskeletal proteins and the progression of renal insufficiency. Interstitial alpha-SMA proved to be a predictor of progressive diabetic nephropathy (R2 for 1/serum Cr slope = 0.608, P = 0.00001). This predictive value was superior to, and independent from, that of the best conventional histological predictive parameters; tubular atrophy (R2 = 0.477, P = 0.00004) and interstitial fibrosis (R2 = 0.28, P = 0.001). CONCLUSION: We have demonstrated in this study the neoexpression of cytoskeletal proteins within diabetic kidneys. This has allowed the identification of new predicting histological markers for the progression of diabetic nephropathy.

Renal fibrosis: insights into pathogenesis and treatment.

The progression of chronic renal failure is characterised histologically by glomerulosclerosis, tubulointerstitial fibrosis and vascular sclerosis. Recent research has identified common mechanisms underlying these fibrotic processes. In particular, the scarring process within the glomeruli and the tubulointerstitium involves the infiltration by inflammatory cells including monocytes, the activation of intrinsic renal cells as well as interactions between infiltrating and resident cells. These interactions depend, to a large extent, on the release by these cells of chemokines, cytokines and growth factors. These factors are in turn involved in the induction of cellular proliferation within the kidney and the stimulation of the synthesis and deposition of extracellular collagenous matrix. Fibrosis is believed to result from excessive synthesis of extracellular matrix and a concommitant decrease in its breakdown. This fibrotic process resulting in end stage renal insufficiency bears strong similarities to that taking place within cirrhotic livers or fibrotic lungs. The new insights in our understanding of renal fibrosis have opened the way to new interventions aimed at its prevention. This may ultimately slow the progression of chronic renal insufficiency and decrease the number of patients requiring dialysis replacement therapy.

Circulating adhesion molecules ICAM-1, E-selectin, and von Willebrand factor in Henoch-Schönlein purpura.

Adhesion molecules play an important part in leucocyte transendothelial migration and thus may provide a useful marker of surface expression at inflammatory sites. In 20 patients with Henoch-Schönlein purpura serum intercellular adhesion molecule 1 (ICAM-1), E-selectin, and plasma von Willebrand factor (vWF) were determined by ELISA during the active and inactive phase of the disease. Twelve healthy children were studied as a control group. Serum ICAM-1 concentrations increased during the active phase of the disease and differed significantly compared with the inactive phase (p < 0.05). However ICAM-1 in the active phase did not differ significantly compared with controls (p = 0.08). Serum E-selectin concentrations did not differ in the active and inactive phase of the disease. By contrast, vWF increased in the active phase of the disease and differed significantly compared with inactive disease and control groups (p < 0.01). Considering the adhesion molecules and vWF, only vWF correlated well with the C reactive protein measurement in the active phase, which is considered a good marker of disease activity. These data suggest that plasma vWF is a good marker of vascular inflammation and endothelial damage. Circulating ICAM-1 might be an additional parameter in some of the patients.

Comparison of ceftriaxone versus cefotaxime for childhood upper urinary tract infections.

It is very important to treat patients with upper urinary tract infections (UTIs) promptly and effectively because of the potential sequelae. In the present study we compare the efficacy of the two cephalosporins, ceftriaxone and cefotaxime, in childhood pyelonephritis. The study protocal included 10 days of drug therapy. Both in patients receiving ceftriaxone and cefotaxime, successful eradication was achieved at the second day of therapy. The overall cure rate was significantly better in the ceftriaxone group than the cefotaxime group in terms of recurrence and reinfections (p < 0.05). Furthermore, in the complicated group, ceftriaxone was slightly superior to cefotaxime, approaching significance in terms of preventing recurrent infections. No serious adverse effects were observed in either of the groups. The present study has shown that ceftriaxone exhibits favorable clinical and bacteriologic efficacy in patients with complicated and uncomplicated upper UTI. Once-daily injection of ceftriaxone in children is also an attractive advantage of the drug when compared to twice-daily cefotaxime.

Effects of secondary hyperparathyroidism on cardiac function in pediatric patients on hemodialysis.

Cardiovascular complications are an important cause of morbidity and mortality in chronic hemodialysis patients. In order to examine the effect of parathyroid hormone (PTH) and vitamin D on left ventricular functions, 11 patients between the ages of 13 and 18 years on regular hemodialysis were investigated using M-mode echocardiography and systolic time intervals. The ratio of the pre-ejection period to the left ventricular ejection time was found to be 0.38 +/- 0.02 (range (0.25 +/- )>50) and was elevated above normal in five of the 11 patients examined. Four of these patients has hypertension and one had severe anemia. The left ventricular ejection fraction was 55 +/- 2.54% and fractional fiber shortening was 31.55 +/- 2.26%, both of which were within normal limits for age. Although the velocity of circumferential fiber shortening was within normal limits in the majority of cases, the mean value was 1.437 +/- 0.11 circ/s, which is above normal for this age period. PTH levels were between one and 4.70 ng/ml. All of the hemodialysis patients had been receiving 1 alpha hydroxy-cholecalciferol and had normal calcium levels. Although they had high PTH levels, most of these patients displayed normal myocardial contractility. No significant correlation was obtained between increment in PTH levels and myocardial function indices. These results imply that PTH is not the only factor affecting myocardial functions. Since all of these patients have received vitamin D therapy for long periods, we suggest that vitamin D may have prevented the deleterious effect of PTH on myocardial function.

Familial membranoproliferative glomerulonephritis.

Four and two male sibs of two separate families who had biopsy-proven membranoproliferative glomerulonephritis (MPGN) are presented. In the first family four sibs of the first-degree consanguineous marriage showed the clinical picture of nephrotic syndrome without hypocomplementaemia at initial laboratory findings. In the second family two affected sibs showed nephrotic and nephritic syndromes on admission. Family investigations showed normal serum complement, immunoglobulins, T-cell subsets, urine analysis, and serum biochemistry. HLA typing in the two families revealed a common antigen HLA A2 in all affected sibs. Some other reports give suggestive evidence of MPGN in siblings but this is the first report that showed the occurrence of MPGN in four sibs. Our data strengthened the concept that genetic factors are involved in the development of MPGN but additional immunogenetic studies will shed light on the genetic aspects of the disease.

Acute renal failure due to acute pyelonephritis.

We report a case of acute renal failure due to acute pyelonephritis with microabscess formation. Despite antibiotic therapy renal function deteriorated, necessitating peritoneal dialysis. Although rare, acute pyelonephritis is an important consideration in the differential diagnosis of acute renal failure, and prompt antibiotic therapy is crucial to insure a favourable outcome.