Kidney transplantation fails to provide adequate growth in children with chronic kidney disease born small for gestational age.

BACKGROUND: Children with chronic kidney disease are frequently born small for gestational age (SGA) and prone to disproportionately short stature. It is unclear how SGA affects growth after kidney transplantation (KTx). METHODS: Linear growth (height, sitting height, and leg length) was prospectively investigated in a cohort of 322 pediatric KTx recipients, with a mean follow-up of 4.9 years. Sitting height index (ratio of sitting height to total body height) was used to assess body proportions. Predictors of growth outcome in KTx patients with (n = 94) and without (n = 228) an SGA history were evaluated by the use of linear mixed-effects models. RESULTS: Mean z-scores for all linear body dimensions were lower in SGA compared with non-SGA patients (p < 0.001). SGA patients presented with higher target height deficit and degree of body disproportion (p < 0.001). The latter was mainly due to reduced leg growth during childhood. Pubertal trunk growth was diminished in SGA patients, and the pubertal growth spurt of legs was delayed in both groups, resulting in further impairment of adult height, which was more frequently reduced in SGA than in non-SGA patients (50 % vs 18 %, p < 0.001). Use of growth hormone treatment in the pre-transplant period, preemptive KTx, transplant function, and control of metabolic acidosis were the only potentially modifiable correlates of post-transplant growth in SGA groups. By contrast, living related KTx, steroid exposure, and degree of anemia proved to be correlates in non-SGA only. CONCLUSIONS: In children born SGA, growth outcome after KTx is significantly more impaired and affected by different clinical parameters compared with non-SGA patients.

Acute and chronic antibody-mediated rejection in pediatric kidney transplantation.

Acute antibody-mediated rejection is a diagnostic challenge in renal transplantation medicine. However, it is an important diagnosis to make, since chronic antibody-mediated rejection (CAMR) is the main cause of long-term graft loss. Antibody-mediated rejection is diagnosed by detecting donor-specific antibodies (DSAs) in the blood in combination with observing typical histomorphological signs in kidney biopsy, as described in the Banff classification. Therapy is based on the removal of DSAs by administering intravenous immunoglobulins (IVIGs), plasmapheresis, or immunoadsorption. Reoccurrence of antibodies is diminished by the use of rituximab, increased immunosuppression, and in some cases additional experimental substances. A combination of these techniques has been shown to be successful in the majority of cases of acute and chronic antibody-mediated rejection. Routine DSA monitoring is warranted for early detection of antibody-mediated rejection.

Neurological involvement in children with E. coli O104:H4-induced hemolytic uremic syndrome.

BACKGROUND: The aim of this study was to analyze the neurological involvement and outcome in pediatric patients with hemolytic uremic syndrome (HUS) during the 2011 epidemic caused by Escherichia coli O104:H4. METHODS: Clinical data and data from magnetic resonance imaging (MRI) scans and electroencephalography (EEG) during the acute phase of the disease and during follow-up at 3 and 6 months were analyzed in 50 patients. Twenty-five of these patients underwent neuropsychological testing (WISC IV) during follow-up. RESULTS: Neurological involvement (stupor or coma, seizures, visual disturbances, paresis, myocloni) was initially observed in 14/50 (28%) patients. One patient died. EEG abnormalities were more frequent in patients with neurological involvement than in those without (12/14 vs. 13/25, respectively). Cranial MRI scans were analyzed in nine patients with neurological involvement, of whom five showed abnormal findings. At the 3- and 6-month follow-ups, EEG abnormalities were found in 14/40 (35%) and 7/36 (19%) patients, respectively, whereas 28/42 (67%) and 17/39 (44%) patients, respectively, complained about on-going reduced performance. Neuropsychological testing showed a slightly lower global intelligence quotient in patients with neurological involvement versus those without (113.4 ± 2.8 vs. 119.4 ± 1.8, respectively). CONCLUSIONS: Neurological involvement was frequent in our cohort. Accordingly, the incidence of pathological EEG findings was high, even in patients without clinical signs of neurological involvement. Nevertheless, major neurological sequelae were rare, and neuropsychological outcome was favorable after 6 months.

mTOR inhibitors in pediatric kidney transplantation.

The mammalian target of the rapamycin (mTOR) inhibitors sirolimus and everolimus are increasingly being used in pediatric kidney transplantation in different combinations and doses. Several studies have shown beneficial effects of using mTOR inhibitors in children after pediatric renal transplantation. A switch to a low-dose calcineurin inhibitor (CNI) and mTOR inhibitor has been proven to stabilize the glomerular filtration rate. Additionally, de novo studies using a low-dose CNI and an mTOR inhibitor have shown good graft survival and a low number of rejections. Side effects of mTOR inhibitors, such as hyperlipidemia, wound healing problems, and proteinuria, mainly occur if high doses are given and if treatment is not combined with a CNI. Lower doses of mTOR inhibitors do not result in growth impairment or reduced testosterone levels. Treatment with mTOR inhibitors is also associated with a lower number of viral infections, especially cytomegalovirus. Due to their antiproliferative effect, mTOR inhibitors could theoretically reduce the risk of post-transplant lymphoproliferative disease. mTOR inhibitors, especially in combination with low-dose CNIs, can safely be used in children after kidney transplantation as de novo therapy or for conversion from CNI- and mycophenolate mofetil-based regimens.

Longitudinal growth on an everolimus- versus an MMF-based steroid-free immunosuppressive regimen in paediatric renal transplant recipients.

Concerns have been raised that mammalian target of rapamycin inhibitors in pediatric transplant recipients might interfere with longitudinal bone growth by inhibition of growth factor signaling and growth plate chondrocyte proliferation. We therefore undertook a prospective nested, case-control study on longitudinal growth over 2 years in steroid-free pediatric renal transplant recipients. Fourteen patients on a steroid-free maintenance immunosuppressive regimen consisting of low-dose everolimus (EVR) in conjunction with low-dose cyclosporine (CsA) were compared to a matched cohort of 14 steroid-free patients on a standard dose mycophenolate mofetil (MMF) regimen in conjunction with a standard dose calcineurin inhibitor (CNI). The mean change in height standard deviation (SD) score in the first study year was 0.31 ± 0.71 SD score in the EVR group compared to 0.31 ± 0.64 SD score in the MMF group (P = 0.20). For the entire study period of 2 years, the change in height SD score in the EVR group was 0.43 ± 0.81 SDS compared to 0.75 ± 0.85 SDS in the MMF group (P = 0.32). The percentage of prepubertal patients experiencing catch-up growth, defined as an increase in height SD score ≥0.5 in 2 years, was similar in the EVR group (5/8, 65%) and the MMF group (6/8, 75%; P = 1.00). Longitudinal growth over 2 years in steroid-free pediatric patients on low-dose EVR and CsA is not different to that of a matched steroid-free control group on an immunosuppressive regimen with standard-dose CNI and MMF. Hence, low-dose EVR does not appear to negatively impact short-term growth in pediatric renal transplant recipients.

Glomerular mRNA expression of prothrombotic and antithrombotic factors in renal transplants with thrombotic microangiopathy.

BACKGROUND: Thrombotic microangiopathy (TMA) in renal transplants (rTx-TMA) is a serious complication and is usually either recurrent TMA (RecTMA) due to humoral rejection (HR-TMA) or due to calcineurin inhibitor toxicity (CNI-TMA). Although the triggers are known, our knowledge about the thrombogenic transcriptome changes in the microvessels is rudimentary. METHODS: We examined the expression of several prothrombotic and antithrombotic genes in 25 biopsies with rTx-TMA (6 RecTMA, 9 HR-TMA, and 10 CNI-TMA) and 8 controls. RNA from microdissected glomeruli of paraffin-embedded tissue was isolated and mRNA transcripts were quantified with real-time polymerase chain reaction after preamplification. Results were correlated with clinicopathologic parameters. RESULTS: Glomerular mRNA expression of KLF2, KLF4, and tPA was lower and that of PAI-1 was higher in rTx-TMA than in the controls. Glomerular mRNA expression of KLF2 and KLF4 correlated with that of tPA and inversely with that of PAI-1 in rTx-TMA. The mRNA expression of complement regulators CD46 and CD59 were higher in rTx-TMA than in the controls. Only in HR-TMA were glomerular ADAMTS13 and CD55 down-regulated. CONCLUSIONS: The glomerular capillary bed seems to contribute to all subtypes of rTx-TMA by down-regulation of the endothelial transcription factors KLF2 and KLF4, indicating dedifferentiation with subsequent up-regulation of PAI-1 and down-regulation of tPA, resulting in inhibition of local fibrinolysis. Decreased glomerular expression of ADAMTS13 and CD55 could be an additional pathway toward microthrombosis exclusively in HR-TMA.

Comprehensive analysis of glomerular mRNA expression of pro- and antithrombotic genes in atypical haemolytic-uremic syndrome (aHUS).

Atypical haemolytic-uremic syndrome (aHUS) is, in most cases, due to hereditary or acquired defects in complement regulation and a life-threatening disease. Despite the rapidly grown knowledge about the primary defects in aHUS, the pathogenesis that links complement dysregulation with microthrombus formation in aHUS is still unknown. Thus, we examined the glomerular microvascular expression of pro- and antithrombotic genes. Glomeruli were microdissected from 12 archival paraffin-embedded biopsies with aHUS and from seven control biopsies. Glomerular mRNA expression was quantified by single real-time PCR reactions after preamplification. In addition immunostains were performed for plasminogen activator inhibitor 1 (PAI-1) and for tissue plasminogen activator (tPA). Results were compared between cases and controls and with clinical data. Glomeruli in aHUS had increased mRNA expression of antifibrinolytic, prothrombotic PAI-1, antithrombotic thrombomodulin (THBD) and CD73 and decreased expression of profibrinolytic, antithrombotic tPA compared to controls. Impaired fibrinolysis due to increased microvascular expression of the antifibrinolytic PAI-1 in combination with the decreased expression of the profibrinolytic tPA seems to be a final common pathway in renal thrombotic microangiopathy that is also effective in aHUS. The concomitant induction of antithrombotic transcripts likely indicates counterregulatory efforts, demonstrating that the capillary bed is not a passive victim of complement attack. Future research should investigate if and how complement activation could induce the reported shift in the expression of PAI-1 and tPA.

Correlations with six-month protocol biopsy findings in pediatric transplant recipients on low- and regular-dose CNI regimens.

Protocol biopsies (PB) are seldom performed after pediatric kidney transplantation (KTx), and factors influencing PB results have not previously been investigated. We performed PB in 79 children six months after KTx and evaluated the results using Banff 2007 criteria. Complications such as bleeding or infections were not detected. The influence of different variables on PB results was evaluated by covariance analysis. Children treated with a low-dose calcineurin inhibitor (CNI) together with an mTOR inhibitor exhibited decreased subclinical rejection (0% vs. 19%, p = 0.001) and decreased interstitial fibrosis and tubular atrophy (IF/TA) (15% vs. 42%, p = 0.013) compared with patients treated with a conventional regimen consisting of normal-dose CNI and mycophenolate mofetil. Children with IF/TA had a lower GFR four wk after Tx (83 ± 22 vs. 62 ± 20 mL/min/1.73 m(2) , p = 0.001). Cold ischemia time, living-related donors, pre-emptive KTx, and donor age did not influence PB results. Treatment with low-dose CNI and mTOR inhibitor and high GFR directly after Tx are the main factors associated with less inflammation and fibrosis in PB and might therefore lead to better long-term graft function.

Development and validation of a new statistical model for prognosis of long-term graft function after pediatric kidney transplantation.

BACKGROUND: No adequate statistical model has been established to estimate future glomerular filtration rate (GFR) in children after kidney transplantation (KTX). Equations based on simple linear regression analysis as used in adults are not established in children. METHODS: An optimal prognostic model of GFR was generated for 63 children at 3-7 years after KTX. The main regression model for prediction of the log-transformed GFR (logGFR) included the mean monthly change of GFR in the period 3-24 months after KTX (∆GFR), the baseline GFR at 3 months (bGFR), and an intercept. Additionally, we investigated if the inclusion of cofactors leads to more precise predictions. The model was validated by leave-one-out cross-validation for years 3-7 after KTX. Prognostic quality was determined with the mean squared error (MSE) and mean absolute error (MAE). Results were compared with the simple linear regression model used in adults. RESULTS: The following statistical model was calculated for every prognosis year (i = 3, …, 7):[Formula: see text] [Formula: see text] Comparison of the new statistical model and the simple linear model for adults led to relevantly lower MSEs and MAEs for the new model (year 7: New model: MSE 0.1, MAE 0.3/adult model: MSE 1069, MAE 18). The benefit of inclusion of cofactors was not relevant. CONCLUSIONS: This statistical model is able to predict long-term graft function in children with very high precision.

Everolimus in pediatric transplantation.

PURPOSE OF REVIEW: The use of everolimus has recently emerged for solid-organ transplantation in children. This review gives an overview of the relevant studies and clinical trials involving the immunosuppressive effects of everolimus in child organ transplant. RECENT FINDINGS: The use of everolimus in pediatric organ transplantation is associated with a decrease in calcineurin inhibitor-related toxicity, better renal function, a low number of acute rejections, and an acceptable side-effect profile. Particularly, the use of everolimus reduces the incidence of virus infection and the risk of posttransplant lymphoproliferative disease. SUMMARY: Everolimus is an effective agent with several advantages for pediatric solid-organ transplantation. Future prospective, randomized controlled trials will have to be performed in order to validate the findings of these pilot trials.

An outbreak of Shiga toxin-producing Escherichia coli O104:H4 hemolytic uremic syndrome in Germany: presentation and short-term outcome in children.

BACKGROUND: In May and June 2011 the largest known outbreak of hemolytic uremic syndrome (HUS) occurred in northern Germany. Because, quite unusually, a large number of adults was affected and the causative Escherichia coli strain, serotype O104:H4, showed an atypical virulence factor pattern, it was speculated that this outbreak was associated with an aggressive course and an unfavorable prognosis also in children. METHODS: Retrospective analysis of medical records of 90 children and comparison to previous outbreak and sporadic case series. RESULTS: Median age was unusually high (11.5 years) compared with that in historical series. Only 1 patient (1.1%) died in the acute phase. Most patients (67/90 [74%]) received supportive care only. Renal replacement therapy was required in 64 of 90 (71%) of the children. Neurological complications, mainly seizures and altered mental stage, were present in 23 of 90 (26%) patients. Ten patients received plasmapheresis, 6 eculizumab, and 7 a combination of both. After a median follow-up of 4 months, renal function normalized in 85 of 90 (94%) patients, whereas 3 patients had chronic kidney disease stage 3 or 4, and 1 patient (1.1%) still requires dialysis. Complete neurological recovery occurred in 18 of 23 patients. Mild to moderate and major residual neurological changes were present in 3 patients and 1 patient, respectively, although all patients were still improving. CONCLUSIONS: E. coli O104:H4 caused the largest HUS outbreak in children reported in detail to date and most patients received supportive treatment only. Initial morbidity, as well as short-term outcome, due to this pathogen, is comparable to previous pediatric series of Shiga toxin-producing E. coli HUS.

The influence of low donor age, living related donation and pre-emptive transplantation on end-organ damage based on arterial hypertension after paediatric kidney transplantation.

BACKGROUND: To date, no study has described the pre-transplant and transplant risk factors for end-organ damage based on arterial hypertension in children after kidney transplantation (KTX). METHODS: A retrospective chart review was performed of 206 children with KTX between 1991 and 2007. Patients<120 cm were excluded as no validated percentiles for 24-h ambulant blood pressure monitoring (ABPM) exist. Complete data sets were available for 116 patients. Data were recorded at 12, 24 and 36 months post- KTX. We analysed the influence of donor age, age at transplantation, pre-emptive transplantation, living or deceased transplantation and glomerular filtration rate (GFR) on the presence of end-organ damage, ABPM, ABPM standard deviation score and the numbers of anti-hypertensives used. RESULTS: Lower donor age and the decade of transplantation were associated with less detection of end-organ damage (P=0.001). A lower need for anti-hypertensive medication (P=0.001) was detected in children who received organs from living donors and from deceased donors with a donor age<35 years and who were transplanted pre-emptively. Low recipient age was the only factor associated with lower ABPM (P=0.001). In our study, the type of immunosuppressive regimen and the GFR had no influence on the blood pressure. CONCLUSIONS: It may be speculated that the risk of arterial hypertension and associated end-organ damage in children after KTX could be reduced by using organs from young donors with an advantage for living related and pre-emptive donation.

Pediatric kidney transplantation followed by de novo therapy with everolimus, low-dose cyclosporine A, and steroid elimination: 3-year data.

BACKGROUND: Acute rejections and infections continue to cause substantial problems for pediatric kidney transplant (KTX) patients because defining an immunosuppressive protocol capable of preventing both has been challenging. Previously, we initiated a prospective trial to evaluate an immunosuppressive regimen designed to achieve this goal. Herein, we present the results of the 3-year follow-up of this trial. METHODS: After KTX, 20 children (median age 12 years, range 1-17 years) received basiliximab, cyclosporine A (CsA) (trough-level=C0 200-250 ng/mL), and prednisolone. Two weeks post-KTX, everolimus (1.6 mg/m/day) treatment was started (C0 4-6 ng/mL), and the CsA dose was reduced by 50% (C0 75-100 ng/mL, after 6 months: C0 50-75 ng/mL). Prednisolone treatment was gradually withdrawn and was completely stopped at 9 months post-KTX. RESULTS: There was no loss of follow-up and no graft or patient loss during the 3-year period. Indication biopsies showed no acute rejection (Banff ≥IA). One of the patients had signs of chronic humoral rejection. Mean glomerular filtration rate measured at 1 year and 3 years post-KTX was 71±25 and 61±27 mL/min/1.73 m, respectively. In patients transitioned to adult care, mean glomerular filtration rate at 3 years was 49±13 mL/min/1.73 m (P<0.05). No cases of posttransplant lymphoproliferative disorder posttransplant lymphoproliferative disorder or polyoma nephropathy were diagnosed. After 3 years, 17 of 20 patients remained on the original immunosuppressive regimen. CONCLUSIONS: A treatment regimen consisting of de novo immunosuppression with basiliximab, CsA, and prednisolone, followed by treatment with everolimus and low-dose CsA combined with steroid withdrawal may be a promising therapy after pediatric KTX.

Once-daily tacrolimus extended-release formulation: 1 year after conversion in stable pediatric kidney transplant recipients.

It is speculated that a once-daily dosage of immunosuppression can increase adherence and thereby graft survival. Until now, there have been no studies on once-daily use of Tacrolimus extended-release formulation (TAC-ER) in children following pediatric kidney transplantation. In 11 stable pediatric kidney recipients >10 years, efficacy, safety, and tolerability of a switch to TAC-ER were observed over one year. Adherence was determined by use of the BAASIS-Scale Interview and comparison of individual variability of Tacrolimus trough levels. Over the observation period, two acute rejections were observed in one girl with nonadherence and repeated Tacrolimus trough levels of 0 ng/m. Beside this, there were no acute rejections in this trial. TAC dose was increased in 3/11 patients and decreased in 2/11 patients within the course of the study. Six patients did not require a dose adjustment. All but one patient had a maximum of 1 dose change during therapy. Mean Tacrolimus dose, trough levels, and Glomerular filtration rates were also stable. Adherence, as measured by BAASIS-Scale Interview and coefficient of variation of Tacrolimus trough levels, was good at all times. It is concluded that conversion to Tac-ER is safe in low-risk children following pediatric kidney transplantation.

Regional citrate anticoagulation--a safe and effective procedure in pediatric apheresis therapy.

Regional citrate anticoagulation (RCA) has been considered to be a standard component of pediatric apheresis therapy for more than a decade. However, data on dosing recommendations and evaluations of the effectiveness and safety of anticoagulation are rarely found in published reports. The aim of this retrospective analysis was to present our single-center experience with RCA in pediatric apheresis therapy with the aim of developing an operating procedure. Five children aged 7-14 years underwent a total of 72 (range 3-44) therapeutic apheresis sessions with RCA in the form of immunoadsorption therapy (2 patients), low-density lipoprotein (LDL)-apheresis (1 patient), and plasmapheresis (two patients). A 3% citrate solution was used. Citrate flow was started at 4.0% of the blood flow velocity and was adapted to match post-filter ionized calcium levels ≤ 0.30 mmol/l. Once the patient's ionized calcium fell to <1.05 mmol/l, an intravenous 10% calcium gluconate solution was administered. Twenty pediatric apheresis patients who received standard heparinization, matched for age, body surface area, processed plasma volume, and blood flow velocity, were enrolled in the study as a comparison group. No side effects were experienced in 72 apheresis session. The 3% citrate solution had to be reduced gradually during the apheresis session and was infused at a mean of 2.8-3.8% of the blood flow rate. Serum bicarbonate levels before and after the apheresis session with RCA [23.9 (range 18.9-30.1) vs. 26.3 (20.2-33.0) mmol/l, respectively] were significantly different (p=0.013). All patients required intravenous calcium substitution to maintain serum calcium levels within the physiological range. Due to the administration of the 3% citrate solution and calcium, all patients significantly gained weight during the procedure, with a median weight gain of 2.5% (p<0.001). The extra fluid load caused problems in patients with kidney failure. Our regimen with RCA is safe, feasible, and effective in pediatric therapeutic apheresis therapy. For RCA in apheresis, we recommend (1) a citrate (3%) flow of 3.3% of the blood flow, (2) prophylactic intravenous calcium substitution from the beginning, and (3) a more highly concentrated citrate solution in the case of oliguric patients.

The bone and mineral disorder of children undergoing chronic peritoneal dialysis.

The mineral and bone disorder of chronic kidney disease remains a challenging complication in pediatric end-stage renal disease. Here, we assessed symptoms, risk factors and management of this disorder in 890 children and adolescents from 24 countries reported to the International Pediatric Peritoneal Dialysis Network Registry. Signs of this disease were most common in North American patients. The prevalence of hyperphosphatemia increased with age from 6% in young infants to 81% in adolescents. Serum parathyroid hormone (PTH) was outside the guideline targets in the majority of patients and associated with low calcium, high phosphorus, acidosis, dialysis vintage and female gender. Serum calcium was associated with dialytic calcium exposure, serum phosphorus with low residual renal function and pubertal status. PTH levels were highest in Latin America and lowest in Europe. Vitamin D and its active analogs were most frequently administered in Europe; calcium-free phosphate binders and cinacalcet in North America. Clinical and radiological symptoms markedly increased when PTH exceeded 300 pg/ml, the risk of hypercalcemia increased with levels below 100 pg/ml, and time-averaged PTH concentrations above 500 pg/ml were associated with impaired longitudinal growth. Hence, the symptoms and management of the mineral and bone disorder of chronic kidney disease in children on peritoneal dialysis showed substantial regional variation. Our findings support a PTH target range of 100-300 pg/ml in the pediatric age group.

Management of regional citrate anticoagulation in pediatric high-flux dialysis: activated coagulation time versus post-filter ionized calcium.

Recent years has seen an increasing use of regional citrate anticoagulation in pediatric dialysis. Several approaches have been described for monitoring anticoagulation in the extracorporeal circuit, such as serum citrate levels, post-filter ionized calcium (iCa), and activated coagulation time (ACT). However, no standard recommendations have yet been established for applying any of these parameters, especially for iCa. The objective of this retrospective analysis was to establish adequate coagulation management using post-filter iCa values. Normal values for ACTester-based ACT were established using a group of 64 children who were divided into two subgroups, with one subgroup comprising children without chronic kidney disease or coagulation disorder (age 1.2-17.5 years, median 9.7 years) and one consisting of 32 uremic patients (age 0.6-17.5 years, median 13.7 years). In a second group of 13 patients (aged 7-17 years), all of whom were undergoing high-flux dialysis (HD) with regional citrate anticoagulation (RCA), we assessed 73 post-filter blood samples for ionized calcium and ACT. A receiver operating characteristic graph was used to identify the iCa threshold needed to achieve adequate anticoagulation. Normal values for ACT were 90 s [2 standard deviations (SD) 72-109] in healthy children and 94 s (2 SD 75-113) in the uremic children. There was no statistically significant difference between the groups. In the children undergoing HD with RCA, the post-filter iCa level correlated with ACT (r = -0.94, p < 0.001). A post-filter iCa level of < or = 0.30 mmol/l reliably predicted an ACT >120 s. Our citrate protocol [citrate 3% rate (ml/h) approximately blood flow rate (ml/min) x 2] meets the established criteria with a high sensitivity. Based on these results, we conclude that the post-filter iCa level can be reliably used for the management of extracorporeal anticoagulation with citrate in pediatric HD. We recommend the application of our citrate prescription protocol in the setting of pediatric intermittent hemodialysis.

Self-adjustment of phosphate binder dose to meal phosphorus content improves management of hyperphosphataemia in children with chronic kidney disease.

BACKGROUND: Hyperphosphataemia in patients with chronic kidney disease (CKD) is associated with mineral and bone disorder and increased cardiovascular mortality. Despite phosphate binders (PB), nutrition counselling and dialysis therapy, the prevalence of hyperphosphataemia remains unacceptably high. It was hypothesized that an inadequate relation of PB dose to meal inorganic phosphorus (iP) content may be an important factor for failure of phosphate management. METHODS: The innovative 'Phosphate Education Program' (PEP) bases on patient empowerment to eye-estimate meal iP content by newly defined 'Phosphate Units' (PU; 1 PU per 100 mg phosphorus) and self-adjust PB dosage to dietary iP intake by an individually prescribed PB/PU ratio (PB pills per PU). In a prospective study, 16 children (aged 4-17 years) with CKD and their parents were trained with the PEP concept and followed up for 24 weeks for changes in serum electrolyte levels, dietary behaviour and PB dose. RESULTS: Within 6 weeks after PEP training, the percentage of children with serum phosphate (PO) >1.78 mmol/l dropped from 63% (10/16) to 31% (5/16). Mean serum PO level decreased from 1.94 ± 0.23 at baseline to 1.68 ± 0.30 (SD) mmol/l in Week 7-12 (P = 0.02) and to 1.78 ± 0.36 (SD) mmol/l in Week 19-24 (P = 0.2), whereas serum calcium [2.66 ± 0.3 vs 2.60 ± 0.23 (SD) mmol/l in Weeks 7-12 (P = 0.45) and 2.66 ± 0.23 (SD) mmol/l in Week 19-24 (P = 0.21)] and serum potassium [4.69 ± 0.48 vs 4.58 ± 0.68 (SD) mmol/l in Week 7-12 (P = 0.40) and 4.65 ± 0.49 (SD) mmol/l in Week 19-24 (P = 0.73)] remained unchanged. The mean daily PB dose rose from 6.3 ± 2.9 to 8.2 ± 5.4 (SD) pills during observation period with an increased meal-to-meal variability (P = 0.04). Dietary iP intake was not affected by PEP concept. CONCLUSION: The empowerment of children with CKD and their parents to self-adjust PB dose to eye-estimated meal iP content significantly improved management of hyperphosphataemia without reducing dietary iP intake.