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Wedekin M, Ehrich JHH, Pape L. Effective treatment of anemia in pediatric kidney transplant recipients with methoxy polyethylene glycol-epoetin beta. Pediatr Transplantation 2011: 15: 329-333. © 2011 John Wiley & Sons A/S. MPG-EPO is a continuous erythropoietin receptor activator with a longer half-life than darbepoetin, hence requires less frequent injections. It has been successfully used in adults, but currently, there are no published data available for its use in children. This pilot study was performed to verify the effect of MPG-EPO on Hb levels in children. Twelve patients (age 6.4-17.2 yr) were treated with MPG-EPO as an individual 'Heilversuch' according to German law after RTx. Five patients were switched from DA, and seven were naïve to erythropoietin. Over a period of six months, Hb levels were measured monthly. A median MPG-EPO dose of 2.5 μg/kg was administered intravenously in a single dose every four wk. The median Hb value increased in naïve patients from 9.9 to 11.2 g/dL (median, p = 0.004) and from 10.3 to 11.6 g/dL (median, p = 0.39) in patients switched from DA to MPG-EPO. No adverse events secondary to MPG-EPO therapy were detected. Our results indicate that a once-monthly injection of MPG-EPO is an effective treatment of anemia in children after renal transplantation. Larger randomized trials will have to confirm our findings. [ABSTRACT FROM AUTHOR]

Corticosteroid-resistant nephrotic syndrome (CRNS) with focal and segmental glomerulosclerosis (FSGS) is a heterogeneous disorder and the most severe and frequent type of all glomerulopathies in children leading to end-stage renal failure. The podocyte is at the center of development and progress of FSGS; this unique cell type plays a major role in the integrity of glomerular structure and permeability.The rate of complete remission of CRNS after induction therapy using different immunosuppressant agents is reported to range between 30% and 84%, depending on the treatment schedule and on the underlying defects of FSGS. Children with genetic types of FSGS barely respond to immunosuppressant therapies and over-treatment prior to transplantation should be avoided. The response of children with an idiopathic type of FSGS to immunosuppressants is superior to those with genetic FSGS. However, many children with idiopathic FSGS do not enter complete remission if they are under-treated, for example, with short-term immunosuppressant monotherapies. If immunosuppressant treatment fails, these patients will have to undergo renal transplantation. However, as unknown pathogenetic mechanisms may persist, more than one-third of these patients with idiopathic FSGS develop a rapid recurrence of CRNS that responds poorly to further long-term therapeutic attempts.In contrast with previously published data, this review takes into account recently identified genetic etiologies of CRNS, and superior results with long-term combination therapy in idiopathic forms to avoid over- and under-treatment. [ABSTRACT FROM AUTHOR]

Malaria infections repeatedly have been reported to induce nephrotic syndrome and acute renal failure. Questions have been raised whether the association of a nephrotic syndrome with quartan malaria was only coincidental, and whether the acute renal failure was a specific or unspecific consequence of Plasmodium falciparum infection. This review attempts to answer questions about “chronic quartan malaria nephropathy” and “acute falciparum malaria nephropathy”. The literature review was performed on all publications on kidney involvement in human and experimental malarial infections accessible in PubMed or available at the library of the London School of Hygiene and Tropical Medicine. The association of a nephrotic syndrome with quartan malaria was mostly described before 1975 in children and rarely in adult patients living in areas endemic for Plasmodium malariae. The pooled data on malaria-induced acute renal failure included children and adults acquiring falciparum malaria in endemic areas either as natives or as travellers from non-tropical countries. Non-immunes (not living in endemic areas) had a higher risk of developing acute renal failure than semi-immunes (living in endemic areas). Children with cerebral malaria had a higher rate and more severe course of acute renal failure than children with mild malaria. Today, there is no evidence of a dominant role of steroid-resistant and chronic “malarial glomerulopathies” in children with a nephrotic syndrome in Africa. Acute renal failure was a frequent and serious complication of falciparum malaria in non-immune adults. However, recently it has been reported more often in semi-immune African children with associated morbidity and mortality. [ABSTRACT FROM AUTHOR]

Background: The Union of National European Paediatric Societies and Associations was founded in 1976 in Rotterdam. Thirty years later, the authors--former presidents and secretaries general--present a retrospective on the activities and achievements of UNEPSA. In 2006, 36 of 46 (78%) European countries, including some countries of the former Soviet Union, were members of UNEPSA. UNEPSA has created a forum for the mutual discussion of matters concerning paediatrics. UNEPSA is closely linked with the International Pediatric Association (IPA). It was never UNEPSA's ambition to promote a uniform European paediatrics. In the 30 years of its existence, it became clear that the diversity of paediatric care in different countries in Europe is extreme. During the "cold war", UNEPSA was able to cross boundaries between socialist and capitalist countries in Europe, and it was due to the activity of individual members of the UNEPSA council that clinical co-operation and research activities were initiated crossing many political borders. Annual meetings of national paediatric presidents focus on the most urgent problems of paediatric health care. "Europaediatrics" became the tri-annual congress for all general paediatricians and paediatric sub-specialists in Europe. The main research activities of UNEPSA concentrated on identifying the demography of primary, secondary and tertiary care paediatrics in Europe.Conclusion: UNEPSA is an active paediatric association representing more than three quarters of all European countries. After 30 years, it is still an expanding and vital instrument in improving the medical care of all children and the co-operation of their carers in Europe. [ABSTRACT FROM AUTHOR]

Clinical trials in adult liver and heart recipients have shown that management of cyclosporine (CsA) dose with 2-h levels (C2) leads to lower rejection rates and serum creatinine levels compared with C0 monitoring. Therefore, we investigated whether C2 monitoring might also improve late graft survival after kidney transplantation in children. To date, no results in adult renal transplantation and in pediatric transplantation have been published. Forty-nine stable pediatric kidney recipients with a minimum time of 1 year after transplantation (mean=7±5 years) entered the study. None of the patients had experienced an acute rejection up to 6 months before entering the study. CsA dosing was based on C0 monitoring for the first 6 months and then based on C2 monitoring for the following 6 months. C0 and C2 levels were measured at 4-weekly intervals. Percentage decline in glomerular filtration rate (GFR) and mean coefficients of variation of CsA levels (Cvar) were calculated and compared during the 6-months periods. At the beginning of the study, the mean calculated GFR was 53±15 ml/min per 1.73 m2. During the 6 months of C0 monitoring, the mean GFR decreased to 49±12 m/min per 1.73 m2 (P=0.001, paired t-test). Six months after switching to C2 monitoring, the mean GFR remained stable, at 49±15 ml/min per 1.73 m2 (P=0.3 paired t-test). The largest increase in GFR (3.9±7.9%) was found in patients with a decrease of their CsA dose of more than 5% under C2 monitoring. Cvar was significantly lower under C2 than under C0 monitoring (0.24±0.10 vs. 0.30±0.15, P=0.02, unpaired t-test). We conclude that the switch to C2 monitoring helped to identify patients with CsA overdosing as well as to reduce variation in CsA level, which resulted in a halt in GFR decline. [ABSTRACT FROM AUTHOR]

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/m2/day). Pred was stopped in 10 of 13 patients. The mean GFR was 55 mL/min/1.73 m2 (SD 24) one yr before switch, 45 mL/min/1.73 m2 (SD 16, p < 0.05) at the time of switch and 47 mL/min/1.73 m2 (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 μg/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. [ABSTRACT FROM AUTHOR]

For over 30 years cyclophosphamide (CYC) and chlorambucil (CHL) have been used to treat children with relapsing steroid-sensitive nephrotic syndrome (SSNS). A meta-analysis on treatment protocols, efficacy, and side effects of CYC and CHL was performed from the literature. Thirty-eight studies comprising 1,504 children and 1,573 courses of cytotoxic drug therapy were systematically evaluated. Relapse-free survival rates increased with the cumulative dosage of CHL and CYC and were higher in children with frequently relapsing than steroid-dependent NS. The fatality rate of the treatment was approximately 1%. Leukopenia occurred in one-third of patients treated with either drug. Severe bacterial infections developed in 1.5% of the patients under CYC and in 6.8% under CHL. Seizures were observed in 3.6% of children treated with CHL. Malignancies were observed in 14 children after high doses of either drug. Females rarely developed permanent gonadal damage. However, no safe threshold for a cumulative amount of CYC was found in males, but there was a marked increase in the risk of oligo- or azoospermia with higher cumulative doses. From this meta-analysis we recommend CYC 2–3 mg/kg body weight for 8–12 weeks as the standard scheme. CHL has higher rates of severe side effects and should be considered a second-line drug. [ABSTRACT FROM AUTHOR]

Renal complications in children with malignancies primarily arise from renal parenchymal tumors, ”tumor lysis syndrome,” and malignant infiltration or obstruction of the urinary tract. Therapy-associated renal side effects may develop following surgical and cytostatic treatment or be induced by radiotherapy. Clinically, both acute renal failure, for example following cisplatin, or chronic dysfunction, following ifosfamide and resulting in growth failure, are observed. Frequencies of renal impairment in these patients are, however, not well established, but terminal renal failure is a rare event: pediatric malignancies account for only 0.9% of patients on renal replacement therapy; the majority of these patients had been treated for a bilateral nephroblastoma. Since potentially serious long-term renal sequelae may evolve following both single measures and additive nephrotoxic effects, long-term monitoring of growth, blood pressure, and renal function is mandatory for a great proportion of former pediatric oncology patients. Future research should prospectively address frequencies of long-term renal impairment in these patients and should establish the prognosis of renal dysfunction. Only these data will ultimately allow risk-adopted use of potentially nephrotoxic treatment modalities and adequate counselling of patients. [ABSTRACT FROM AUTHOR]

Twenty-four-hour ambulatory blood pressure monitoring (ABPM) has many advantages for the diagnosis and follow-up of hypertension at all ages. This technique has so far not been documented as applicable to the very young. We studied the feasibility of ABPM in 61 healthy children and in 40 patients with renal diseases and/or hypertension, aged less than 6 years. A satisfactory ABPM profile (recording time = 24 h and > 30 good recordings) was obtained in 77% of the healthy children. The mean number of good blood pressure (BP) measurements per 24 h increased with age from 46 (3-4 years) to 58 (6 years). The mean (± SD) systolic and diastolic BPs of healthy 3- to 6-year-old children (n = 47) were 110 ± 5/67 ± 5 mmHg during the day-time and 100 ± 5/58 ± 5 mmHg at night. In addition to the nocturnal decrease in BP, ABPM detected a second, day-time dip in BP during bed rest after lunch. Ninety percent of patients with renal disease and/or hypertension had successful ABPM recordings for 24 h, with an age-dependent increase in the mean number of reliable readings from 34 (< 2 years) to 48 (4 years). In 5 of 10 children with hypertensive results obtained by casual BP measurements, elevated BP was not confirmed by ABPM. We conclude that ABPM is a useful tool for the diagnosis and evaluation of hypertension in children under 6 years of age. [ABSTRACT FROM AUTHOR]

The European Dialysis and Transplant Association (EDTA) Registry was established in the mid 1960s and its annual reports for many years provided important information on the treatment of children in Europe with renal diseases. The last report of the former European Renal Association (ERA)-EDTA Registry, based in London, was in 1996. Unfortunately, shortly thereafter, for a number of reasons the Registry collapsed. However, in June 2000 the ERA-EDTA Registry was re-established in Amsterdam, The Netherlands, and the first report of this new European Registry on renal replacement therapy is now published. Effective collaboration of single national registries with the new ERA Registry is important for the future development of new successful treatment strategies in pediatric renal medicine. [ABSTRACT FROM AUTHOR]

Renal replacement therapy has become available for the majority of patients suffering from severe congenital chronic kidney disease (CKD). Data on the long-term neurocognitive outcome and the impact of early kidney transplantation (KTx) in this setting is unclear. Neurocognitive outcomes in 15 patients (11 male) with isolated congenital CKD (stage 3-5) requiring KTx at a mean age of 2.8 ± 1.3 were assessed at a mean age of 8.3 ± 1.4 years. Patients underwent neurological examination and testing for neuromotor and neurocognitive function using three independent tests. Pre-emptive KTx was performed in six patients, and nine patients were dialyzed prior to KTx for a mean period of 11.1 ± 8.6 months. Neuromotor function was abnormal in 8/15 patients. HAWIK-III showed a global intelligence quotient (IQ) of 93.5 ± 11.4 ( P = 0.05) due to a significantly reduced performance IQ of 89.1 ± 11.3 ( P < 0.01). In three patients, the global IQ was clinically significantly reduced by >1 SD to <85. In patients with neuromotor dysfunction, performance IQ was lower than in patients with normal neuromotor function (83.8 ± 10.2 vs. 96.2 ± 9.0, P = 0.04). Time on dialysis was inversely correlated to verbal IQ ( r = 0.78, P = 0.02). Pre-emptive KTx and duration of dialysis treatment <3 months was associated with superior neurocognitive outcome. Early (pre-emptive) KTx results in superior long-term neurocognitive outcome in children with severe congenital CKD. [ABSTRACT FROM AUTHOR]

Alport syndrome inevitably leads to end-stage renal disease and there are no therapies known to improve outcome. Here we determined whether angiotensin-converting enzyme inhibitors can delay time to dialysis and improve life expectancy in three generations of Alport families. Patients were categorized by renal function at the initiation of therapy and included 33 with hematuria or microalbuminuria, 115 with proteinuria, 26 with impaired renal function, and 109 untreated relatives. Patients were followed for a period whose mean duration exceeded two decades. Untreated relatives started dialysis at a median age of 22 years. Treatment of those with impaired renal function significantly delayed dialysis to a median age of 25, while treatment of those with proteinuria delayed dialysis to a median age of 40. Significantly, no patient with hematuria or microalbuminuria advanced to renal failure so far. Sibling pairs confirmed these results, showing that earlier therapy in younger patients significantly delayed dialysis by 13 years compared to later or no therapy in older siblings. Therapy significantly improved life expectancy beyond the median age of 55 years of the no-treatment cohort. Thus, Alport syndrome is treatable with angiotensin-converting enzyme inhibition to delay renal failure and therapy improves life expectancy in a time-dependent manner. This supports the need for early diagnosis and early nephroprotective therapy in oligosymptomatic patients. [ABSTRACT FROM AUTHOR]

Beil S, Drube J, Gluer S, Lehner F, Ehrich JHH, Pape L. End-stage renal disease due to ARPKD in the first months of life: Transplantation or dialysis? – Two case reports. Pediatr Transplantation 2010: 14:E75–E78. © 2009 John Wiley & Sons A/S. ARPKD with renal insufficiency during the first months of life is a clinical challenge. We report on two children with ARPKD with massively enlarged kidneys requiring renal replacement therapy in early infancy. Patient 1 developed pulmonary insufficiency due to massively enlarged kidneys. At the age of six months the girl was listed for KT as “high urgency” on the Eurotransplant waiting list. A kidney from a deceased donor was pre-emptively transplanted and simultaneous nephrectomy performed. No postoperative complications were observed, and the patient was discharged from in-patient care 42 days after transplantation. Unexpectedly, she died at the age of one yr due to cerebral vascular spasms of unknown origin. Patient 2 was transferred at the age of three months to our clinic with life-threatening pulmonary insufficiency. Pre-emptive KT was not possible; therefore, bilateral nephrectomy was performed and PD begun. The boy is still doing well on PD one yr later. Pre-emptive KT and bilateral nephrectomy followed by PD are two options for infants with ARPKD and excessive kidney enlargement. PD could be complicated and in some cases become impossible by peritoneal damage during nephrectomy. On the other hand, KT covers a high risk of infections caused by immunosuppression. The decision, which method to choose, should be driven by the individual situation of the patient and the expertise of the center. [ABSTRACT FROM AUTHOR]

Berding G, Geisler S, Melter M, Marquardt P, Lühr A, Scheller F, Knoop BO, Pfister E-D, Pape L, Bischoff L, Knapp WH, Ehrich JHH. Estimation of glomerular filtration rate in liver-transplanted children: Comparison of simplified procedures using 51Cr-EDTA and endogenous markers with Sapirstein’s method as a reference standard. Pediatr Transplantation 2010: 14:786–795. © 2010 John Wiley & Sons A/S. This study evaluated simple procedures for GFR determination in 48 liver-transplanted children. After injection of 51Cr-EDTA, blood samples were obtained up to four h, and activity retention in the body was measured for 60 min with scintillation probes. As a reference, GFR was calculated according to Sapirstein. Simplified calculations were performed according to Brochner-Mortensen, Russel, Devaux and Oberhausen. Additionally, GFR was determined using plasma creatinine and cystatin C according to Schwartz and Filler, respectively. The reference revealed mildly reduced GFR (62 ± 20 mL/min/1.73 m2). Russel’s method provided the highest degree of correlation ( r2 = 0.95), the smallest bias in GFR determination (−2%), and only one false exclusion plus one false diagnosis of chronic kidney disease. Oberhausen’s method with blood sampling at one h post-injection performed slightly worse ( r2 = 0.67, bias: 3%). All other methods resulted in significantly different GFR estimates compared to the reference. Nevertheless, notably, the second narrowest 95% limits of agreement (−31% to 45%) was observed using cystatin C. In conclusion, this data implies to prefer Russel’s method as a simplified procedure, and if patients cannot be available long enough (four h) for measurements, Oberhausen’s method instead. If radiotracer methods are not available at all or for screening GFR, cystatin C appears to be the procedure of choice. [ABSTRACT FROM AUTHOR]

Schwerk N, Hartmann C, Baumann U, Pape L, Ehrich JHH, Hansen G. Chronic Mycoplasma pneumoniae infection in a child after renal transplantation. Pediatr Transplantation 2010: 14: E26–E29. © 2009 John Wiley & Sons A/S. Mycoplasma pneumoniae has rarely been reported in renal transplant recipients. We present the case of a 10-yr-old boy with a six-month history of chronic cough, recurrent pyrexia, and weight loss three yr after RTx. The patient's post-transplant course was complicated by recurrence of NS that resolved with plasmapheresis and PTLD, which was successfully treated with an anti-CD20 monoclonal antibody. Chest X-ray showed a round mass-like lesion in the left upper lobe; MRT, PET, and bronchoscopy ruled out a PTLD. BAL fluid revealed M. pneumoniae-DNA. A three-wk course of macrolide therapy induced rapid recovery. We conclude that M. pneumoniae infection should be considered in immunosuppressed patients with long-lasting respiratory complaints and fever of unknown origin. Antibiotic treatment should be given for a minimum of three wk. [ABSTRACT FROM AUTHOR]

Recent progress in proteomic analysis and strategies for the identification of clinically useful biomarkers in biofluids has led to the identification of urine as an excellent non-invasive reservoir for biomarkers of disease. Urinary biomarkers have been identified and validated on independent cohorts in different high-incidence adult renal diseases, including diabetic nephropathy, chronic kidney disease and immunoglobulin A-nephropathy, but also in extrarenal disease, such as coronary artery disease. Unfortunately, this type of research is underrepresented in the pediatric population. Here, we present the rare studies in the pediatric population that identified potential clinically useful urinary biomarkers in ureteropelvic junction (UPJ) obstruction and renal Fanconi syndrome. These studies, although limited in number, clearly show the potential of urinary proteomics, especially in the pediatric population. It is anticipated that the advances made in the adult population, the lessons learned on the use of appropriate statistics and the inclusion of independent blinded validation cohorts in these types of studies will rapidly lead to clinical useful urinary biomarkers for other pediatric (renal) disease in a population where non-invasive analysis is particularly appreciated. [ABSTRACT FROM AUTHOR]

Background. The renal Fanconi syndrome (FS) is characterized by renal glucosuria, loss of electrolytes, bicarbonate and lactate, generalized hyperaminoaciduria and low-molecular-weight proteinuria. We studied the urinary low-molecular-weight proteome to identify excreted peptides indicative of a pathogenetic mechanism leading to tubular dysfunction. [ABSTRACT FROM PUBLISHER]

SIOD is a multisystem disorder caused by a mutant chromatin remodelling protein. The main clinical findings are spondyloepiphyseal dysplasia with disproportionate growth restriction, defective cellular immunity, and steroid-resistant nephrotic syndrome secondary to biopsy proven FSGS leading to ESRF. Concerning ESRF, kidney transplantation is the therapy of choice since FSGS does not recur in the graft. However, with respect to the underlying immune disorder and the increased susceptibility to life threatening infections, the question of the optimal immunosuppressive therapy after renal transplantation remains unresolved. Under conventional immunosuppressive regimens some SIOD patients have developed severe disseminated cutaneous papilloma virus infections or EBV associated lymphoproliferative disease. We present several cases of children with SIOD (four of five had SMARCAL1 mutations) and monotherapy maintenance immunosuppression after renal transplantation and compare them with 13 patients from the SIOD registry. We have found that post-renal transplantation immunosuppressive monotherapy results in a good outcome with a reduced number of severe infections. Due to the underlying immunodeficiency in SIOD, limited immunosuppression may be possible without increasing the risk of acute or chronic rejection. [ABSTRACT FROM AUTHOR]

This study was designed to compare three urinary protein expert systems for profiling proteinuria in children with kidney diseases. Freshly voided urine specimens were collected from 61 children with glomerular diseases, 19 children with tubular diseases and 25 healthy children aged 3–16 years. The urinary protein expert systems were: (1) albumin/total protein ratio (APR), (2) α-1-microglobulin/α-1-microglobulin + albumin algorithm (AAA), and (3) the complex urine protein expert system (UPES, PROTIS) algorithm. APR correctly identified glomerular proteinuria in 47/61 children, tubular proteinuria in 16/19 children and normal proteinuria in 23/25 healthy children. AAA correctly identified glomerular proteinuria in 61/61 children and tubular proteinuria in 18/19 children, and 25/25 healthy children were characterized as having no abnormal proteinuria. AAA was not influenced by the stage of chronic kidney disease. UPES differentiated the type of proteinuria in children with glomerular diseases into glomerular (50/61 patients) and mixed glomerulo-tubular (6/61 patients). Tubular proteinuria was identified in 16/19 patients and described as mixed glomerulo-tubular proteinuria in 3/19 patients. Mixed glomerulo-tubular proteinuria was found only in children with chronic kidney disease stages 2–5 of glomerular and tubular diseases. In conclusion, the AAA and UPES had the highest accuracy levels. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Renal Arterial Resistance Index" in the July 10, 2003 issue.

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. [ABSTRACT FROM AUTHOR]

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 × 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°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 μmol/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 μmol/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. [ABSTRACT FROM AUTHOR]

Pape L, Mengel M, Offner G, Melter M, Ehrich JHH, Strehlau J. Renal arterial resistance index and computerized quantification of fibrosis as a combined predictive tool in chronic allograft nephropathy.Pediatr Transplantation 2004.© 2004 Blackwell MunksgaardThe renal arterial resistance index (RI) and the PicroSiriusRed 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In primary focal and segmental glomerulosclerosis (FSGS) renal prognosis is poor if no remission of proteinuria can be achieved with treatment. Currently, most children with FSGS are treated with cyclosporine and steroids after establishing steroid resistance, and approximately 60% of patients benefit from this therapy. For the remaining 40%, no generally approved therapeutic recommendations exist for children. We treated nine children with cyclosporine-resistant primary FSGS with plasma exchange (PE), two with relapsing FSGS after renal transplantation and seven with FSGS in their native kidneys. Three patients did not respond to PE, but five came into complete remission and one patient achieved partial remission. Three patients relapsed between 6 weeks and 2 years following cessation of PE, and were subsequently treated with plasma immunadsorption (PIA), which also reliably reduced proteinuria. The patients without response to PE tended to have a longer duration of the disease. We conclude that PE and PIA are a useful option for treatment of steroid- and cyclosporine-resistant FSGS, particularly if applied early in the course of the disease. Although more demanding on supportive resources, PIA seems preferable to PE, since there is no necessity for additional albumin or fresh-frozen plasma, as with PE. [ABSTRACT FROM AUTHOR]

A computerized Urine Protein Expert System (UPES) measuring creatinine, total protein, albumin, IgG, α[sub 1]-microglobulin, α[sub 2]-macroglobulin, and N-acetyl-β-Dglucosaminidase, together with urine dipstick testing for granulocyte esterase and hemoglobin pseudoperoxidase, and measurement of serum creatinine had been found to be useful in adults for differentiating between renal disorders. The objective of this study was to investigate UPES for identifying the different types of proteinuria and their underlying prerenal, glomerular, tubular, and postrenal causes in 146 children characterized by routine and invasive nephrological investigations. UPES proved to be a useful tool in pediatric renal patients after refinements were implemented in the program. Comparing UPES with the pediatric nephrologist's interpretation of all available clinical and laboratory data, UPES diagnosed glomerulopathies in 46 (75%) of 61 patients. In a further 23% it suggested glomerular involvement by indicating either a disturbed glomerular permeability or increased excretion of albumin. Tubular proteinuria was correctly described by UPES in 23 (100%) patients with different tubulopathies. UPES revealed normal kidney function in all healthy children and all children with remission of renal disorders. Therefore, UPES can be regarded as a useful tool in the automated differentiation of renal diseases in children. [ABSTRACT FROM AUTHOR]

Kidney function was studied in 80 Gambian children with cerebral malaria, 73 children with mild malaria, and in 19 children with other febrile illnesses. Serum creatinine was measured, and the excretion in urine of immunoglobulin G, transferrin, albumin and alpha 1 microglobulin was determined. Twenty-five percent of children with cerebral malaria, and 4% of children with mild malaria had an elevated serum creatinine above 62 mumol/l. Increased urinary protein excretion was frequent: 53% of children with cerebral malaria had a glomerulo-tubular pattern of protein excretion, and 46% a tubular pattern. Median albuminuria was 68 mg/l in children with cerebral malaria, 18 mg/l in children with mild malaria, and 9 mg/l in febrile children with other diseases (P < 0.0001). There was no significant association between the proteinuria and height of fever or the degree of parasitaemia, and there was no significant association between death and signs of renal impairment. Renal involvement is common in children with malaria in The Gambia, with prerenal, glomerular, and tubulo-interstitial factors contributing. It is more pronounced in children with cerebral malaria than in those with mild malaria. However, renal dysfunction is relatively mild and does not indicate a worse prognosis. [ABSTRACT FROM AUTHOR]

Objectives. This study evaluated the extent of thyroid abnormalities in a remote iodine-deficient area of the ivory Coast. Methods. Ultrasonography was used in detecting the presence of goiter. Results. The overall prevalence rates of goiter were 64.7% among females and 53.3% among males. In children aged 6 to 15 years (n = 314), the prevalence of goiter was 62% regardless of sex. Thyroid volume increased steadily with age, with significantly larger goiters in women 25 years and older. Frequency of cysts and calcifications did not correlate with sex. Conclusions. Especially in developing countries, prophylaxis of iodine deficiency disorders must be improved in iodine-deficient areas to prevent substantial morbidity, which is more severe in women and elderly persons. (Am J Public Health. 1999;89:1857-1861) [ABSTRACT FROM AUTHOR]

Cyclosporine is a powerful immunosuppressant with a narrow therapeutic window and considerable inter- and intrapatient variability. The pre-dose trough concentration (C[sub min] ) is commonly used for therapeutic drug monitoring. With the new microemulsion (Neoral), intrapatient variability was reduced. However, the usefulness of Neoral C[sub min] was questioned. Firstly, because of the improved and more-rapid absorption, accidental intake before blood sampling has a greater impact on C[sub min] than with classic cyclosporine. Secondly, C[sub min] may be low despite high drug exposure, due to rapid clearance in children. A full pharmacokinetic (PK) profile with determination of the area under the curve (AUC) is expensive and cumbersome, and therefore a search for an abbreviated AUC began. Here, we present a retrospective analysis of 84 PK profiles from 78 pediatric renal transplant recipients. By analysis of rejection episodes and toxicity, we estimated a target AUC above 5,000 ng×h/ml in the early post-transplant period and 3,900 ng×h/ml beyond 100 days. The abbreviated AUC using the 2- and 6-h concentrations (C2 and C6) and a simple estimate derived from the 3-h concentration (C3) were equally well correlated with the AUC. From our data, we recommend a target C3 at approximately 800 ng/ml early after transplantation and 450–550 ng/ml beyond 100 days. [ABSTRACT FROM AUTHOR]

Reported frequencies of non-compliance in children with end-stage renal disease range from 8% to 70% with a mean around 40%. Sequelae amount to momentous emotional and financial burdens, including the loss of 7% of transplanted organs. Reasons for non-compliance have too often been attributed selectively to the patients (e.g., emotional, mental, social, or communication problems). Compared with general compliance research, this selective attribution appears to be too simplistic. Selective attribution neglects the patients’ experiences within the context of disease and treatment and prevents open communication about non-compliance. Research on personal reasons for non-compliance is scarce. In psychological interviews, a third of our 85 patients with end-stage renal disease (34 boys, 51 girls, mean age 12.7 years, range 7.4–19.3 years) communicated psychologically meaningful reasons for non-compliance, frequently related to interrelational and systemic treatment conditions. Patients indirectly asked for more communication about their subjective reasons for non-compliance. [ABSTRACT FROM AUTHOR]

Ganciclovir alone or in combination with hyperimmunoglobulin is replacing other treatment modalities for the prophylactic treatment of cytomegalovirus (CMV) infections. No dose recommendations are available for oral ganciclovir therapy in children with impaired renal function after renal transplantation of a kidney from a CMV IgG-positive donor. We undertook a pharmacokinetic study in 14 pediatric renal transplant recipients who were CMV IgG negative and had received a graft from a CMV IgG-positive donor. We estimated the daily dosage of oral ganciclovir in relation to the glomerular filtration rate (GFR). Oral ganciclovir was administered ar a starting dose of 3 × 1 g for children with a weight above 50 kg, 3 × 750 mg for children between 50 and 37.5 kg, and 3 × 500 mg for children between 37.5 and 24 kg. The starting dose was reduced by 50% for GFR values ≤50 ml/min per 1.73 m² and by 75% for GFR values ≤25 ml/min per 1.73 m². The daily dose was divided into three daily doses unless GFR was < 40 ml/ min per 1.73 m², when only two daily doses were given. Doses were adjusted according to the measured plasma trough concentrations (c) using the simple formula: C[sub ganciclovir](measured)/C[sub ganciclovir](desired) = dosage rate(used)/ dosage rate(adjusted). Mean stable plasma trough concentration was 0.91 ± 0.68 μg/ml. The dosage rate, adjusted to a trough concentration of 1.0 μg/ml, correlated with the GFR. The dose per day could be calculated according to a simple equation for a GFR < 100 ml/min per 1.73 m²: dosage per day (mg/kg per day) = GFR. No CMV disease developed in any of the patients during oral ganciclovir, but 1 patient developed an acute rejection episode and a positive pp65 antigen 5 weeks after discontinuation of ganciclovir. The drug was well tolerated and without side effects. [ABSTRACT FROM AUTHOR]

It has been shown in adult kidney transplant recipients that a conversion from MMF to EC-MPS significantly reduced the GI related symptom burden. No such study exists on children with GI problems while receiving MMF therapy. Ten paediatric kidney transplant recipients (mean age 14.5 yr, s.d. 4.5) receiving triple immunosuppression (Cyclosporin A or Tacrolimus + MMF + Prednisolone) with severe GI symptoms were converted to an equimolar dose of EC-MPS. The GSRS was completed before and at four wk after the switch, and GFR was determined for a mean period of six months. Values were compared by the paired t-test. Mean GSRS improved significantly after the switch to EC-MPS in all but one patient, from 2.1 (s.d. 0.9) to 1.1 (s.d. 0.6). The differences could be found in all four subscales. Graft function did not change after conversion to EC-MPS. In children with moderate or severe GI symptoms while receiving MMF, conversion to EC-MPS led to significantly reduced GI symptoms. [ABSTRACT FROM AUTHOR]

Many children with a late steroid-resistant nephrotic syndrome (SRNS) and focal glomerulosclerosis have a poor prognosis and enter end-stage renal failure (ESRF) within five years. Reports are scarce on the long-term follow-up of patients entering remission while receiving immunosuppressive therapy after steroids have failed. A two-year-old boy with focal and segmental glomerulosclerosis having both late steroid and cyclophosphamide resistance entered complete remission of the SRNS almost two years after starting induction therapy with cyclosporine A (CSA). During the 15-year follow-up, the patient experienced five relapses during CSA maintenance therapy. All relapses were successfully treated within 10 days by intravenous methylprednisolone pulses in addition to CSA. The relapses were accompanied by a drop in the glomerular filtration rate (GFR). At the age of 18 years, the patient had grade II chronic kidney disease (GFR=61 ml/min/1.73 m2). At the age of 14 years, mycophenolate mofetil (MMF) was added to the maintenance therapy and the CSA dosage was reduced. Two renal biopsies at the ages of 10 and 18 years failed to detect CSA nephrotoxicity. We conclude that children with SRNS may have long-term benefit from a combination therapy using intravenous methylprednisolone pulses and CSA. [ABSTRACT FROM AUTHOR]

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

Central diabetes insipidus is clinically masked in dialysis patients. We report a 12-year-old girl receiving a living-related donor graft for renal failure from Alport syndrome, in whom a craniopharyngioma had been resected 6 months before transplantation. Pretransplant evaluation had documented central hypothyroidism, growth hormone deficiency, and presumptive hypogonadotropic hypogonadism. The corticotropinreleasing factor test had been normal. Four hours after transplantation, urine output exceeded 1,000 ml/h without diuretic therapy. Serum sodium concentration was 155 mmol/1, serum osmolality 333 mmol/kg, and plasma antidiuretic hormone 4.9 ng/1, while urine osmolality was 233 mmol/kg. Desmopressin acetate was started by continuous intravenous infusion at 1 7mu;g/day. Serum electrolytes rapidly normalized, urine output stabilized at 2 1/day. The patient was discharged 4 weeks after transplantation with good allograft function, receiving intranasal desmopressin acetate 10 μg twice daily. Pre-existing central diabetes insipidus is unmasked after successful kidney transplantation, leading to rapid dehydration and hypernatremia, which can be prevented by prompt institution of desmopressin therapy. [ABSTRACT FROM AUTHOR]

A 12-year-old girl with short stature due to idiopathic Fanconi syndrome and chronic renal failure was treated with recombinant human growth hormone (rhGH). There was no family history of diabetes mellitus and the glucose tolerance before treatment was normal. Intravenous glucose tolerance tests were performed before, during and after treatment. Two months after starting rhGH the early phase of insulin secretion (1-+3-min values) was diminished, and the patient developed manifest diabetes mellitus with hyperglycemia and an elevated hemoglobin A[sub 1c]. Following discontinuation of rhGH, glucose tolerance slowly returned to normal. [ABSTRACT FROM AUTHOR]