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Background: In 1998, a survey of the European Society for Paediatric Nephrology (ESPN) revealed substantial disparities in pediatric renal care among European countries. Therefore, ESPN aimed at harmonizing renal care in all European countries in the following 20 years. In 2017, we conducted a survey to evaluate the current status of renal health policies for children in Europe., Methods: A 33-question web-based survey was designed and sent to presidents or representatives of national societies of pediatric nephrology in 44 European countries., Results: Data was reported from 42 (95.5%) countries. The number of pediatric nephrologists per million child population increased from 1998 to 2017 in 70% of countries. Pediatric dialysis facilities for acute kidney injury and end-stage kidney disease were available in 95% of countries. The availability of pediatric kidney transplantation increased from 55 to 93% of countries. Considerable variation was found in the current availability of allied health professionals, including psychosocial and nutritional support, high-tech diagnostic methods, and treatment with expensive drugs for children with kidney diseases between different European countries., Conclusions: The 20-year follow-up analysis of pediatric renal care services in European countries revealed that pediatric nephrology has become a well-established subspecialty in pediatrics and nephrology in 2017. The ESPN will continue its efforts to further improve pediatric renal care for European children by harmonizing remaining disparities of renal care services.

A computerized Urine Protein Expert System (UPES) measuring creatinine, total protein, albumin, IgG, alpha(1)-microglobulin, alpha(2)-macroglobulin, and N-acetyl-beta-D-glucosaminidase, 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.

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.

Background: The aim of renal replacement therapy in children is to restore their potential for normal growth and development in order to reach mature adulthood. Because pediatric kidney transplantation started in the late 1960s, it is now possible to document the progress and outcome of these patients from transplantation in childhood to survival into adulthood., Methods: In this single-center study, all 150 children born before December 1977 and having received a kidney transplant between 1970 and 1993 were selected for long-term follow-up. The mean age at transplantation was 12.1 years (range 3.2 to 16.7), and the mean follow-up was 13.1 years (range 2.0 to 25.0). In December 1995, 124 grown-up patients with a mean age of 25.4 years (range 18.4 to 40.3) were alive, 89 with a functioning graft. Fifty had the first graft functioning longer than 10 years. The fate of all patients was traced, and those living were analyzed in regard to their somatic and socioeconomic states., Results: The actuarial 25-year survival rate for the patients was 81%, and for the first graft it was 31%. The best graft survival rates were observed after living related donation, preemptive transplantation, and immunosuppression with cyclosporine. The latter benefit, however, vanished after eight years. The mean creatinine clearance declined over the years from 76 to 45 ml/min/1.73 m2, and the incidence of hypertension increased to more than 80% of the patients. Malignancies occurred in 2.6%. Final height was stunted in 44% of noncystinotic patients, whereas all patients with cystinosis were extremely growth retarded. Twenty-seven percent suffered from additional disabilities. A majority of adult patients were rehabilitated in regard to education and socioeconomic status, and 14% were unemployed., Conclusions: The results indicate that renal transplantation in children leads to a high degree of rehabilitation in adulthood. The life of a kidney transplant, however, is limited, which points out the need for more specific immunosuppression with fewer side-effects in order to reach the goal of lifelong graft function.

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.

Background: Between 1967 and 1990, 820 successful pregnancies in 718 women on renal replacement therapy (RRT) were reported to the EDTA Registry., Methods: This study analyses data on repeated successful pregnancies in 102 of these women, of whom 99 had two and three had three pregnancies., Results: Primary renal diseases were mainly glomerulonephritis (41%), pyelonephritis (32%), and congenital malformations such as cystic diseases and hypoplasia or dysplasia (3%). Mean age at start of RRT was 21 years +/-5 SD. Ninety-four per cent of the women had the same transplant during the first and second pregnancies; 85% of these were alive with their first graft and 9% with a second graft; 4% were retransplanted after the first pregnancy and 2% were back on dialysis during the second pregnancy. Of the mothers with two successful pregnancies, two-thirds had a serum creatinine below 121 micromol/l after the first or after the second pregnancy. Six mothers lost their first graft after the first pregnancy. None of the mothers had died after delivery of the second or third baby. Several features of the first and the second pregnancy in these mothers were quite similar. Mean gestational age was 36 weeks+/-3SD during first and second pregnancy. Mean birth weight (height) of the first child was 2490 g+/-660 SD (48 cm+/-4 SD) and 2587 g+/-639 SD (50 cm+/-3 SD) of the second child (NS). Neonatal mortality was 4% after the first and second delivery; congenital abnormalities were found in five and three children respectively., Conclusions: Fourteen per cent of mothers who had a successful pregnancy on RRT subsequently had a second baby. Repeated pregnancies should not adversely affect graft function and/or fetal development provided that graft function was well preserved at the time of conception.

An association of renal and cardiac manifestations can be observed in a variety of diseases. The pathogenetic factors may include, firstly, a disturbance of organ development due to chromosomal aberration or an underlying syndrome or, secondly, infectious, immunologic and metabolic factors. In addition, primarily isolated diseases of the heart or the kidney may lead to damage of the previously unaffected organ. The present article gives a review on renal diseases associated with heart diseases in children and adults.

Patients with congenital cyanotic heart disease may develop a glomerulopathy with proteinuria and impaired renal function. In order to investigate this problem we conducted a study on 27 patients with uncorrected cyanotic heart disease who were between 1 day and 25 years old. As a consequence of hypoxaemia haematocrit was elevated to 57%. Proteinuria was above 150 mg/day/1.73 m2 body surface in 12 patients. Only one of 9 children under 10 years of age had pathological proteinuria presenting as isolated albuminuria. Seven out of 10 patients between 11 and 20 years had an elevated proteinuria with a glomerular pattern. Creatinine clearance was normal in these patients. All four patients above 20 years of age had a considerable glomerular proteinuria with a mean excretion of 5.7 g/24 h/1.73 m2 body surface. These patients suffered additionally from chronic cardiac failure and creatinine clearance was below the normal range. There was a clear relationship between pathological proteinuria and age of the patients and thus duration of hypoxaemia. Patients with pathological proteinuria had a significant higher erythrocyte count (7.3 +/- 1.3 vs 5.6 +/- 1.4 10(12)/l p less than 0.01) and a lower mean corpuscular haemoglobin. In summary, children with persistent congenital cyanotic heart disease have substantial risk of developing a glomerulopathy if the cyanosis remains unchanged for more than ten years.

Classical autoimmune nephropathies rarely occur during childhood. They include the glomerulonephritis and tubulointerstitial nephritis caused by antibasement membrane antibodies and the systemic lupus erythematosus. The autoimmune pathogenesis of glomerulopathies such as minimal change disease and different forms of tubulointerstitial nephritis which are more frequent in children is not proven yet. The possible mechanisms of autoimmune disorders affecting the kidneys are 1. the genetic predisposition, 2. a defect in the immune system, 3. exogenous agents leading to cross-reactivity or polyclonal B cell stimulation, and 4. endogenous agents leading to immunogenic autoantigens. This review summarizes the current knowledge on the autoimmune pathogenesis of nephropathies derived from investigations in humans and animal experiments.

Malaria infection leads to renal involvement. Reversible proteinuria accompanies many plasmodial infections. Chronic malarial nephrotic syndrome is specifically associated with quartan malaria. Acute renal failure is restricted to infections with Plasmodium falciparum. The pathogenesis of renal involvement during malarial infections includes immunological mechanisms. It is now realized that there exist at least two types of immunological processes: acute transient immune-complex glomerulonephritis with reversible proteinuria and chronic immune-complex glomerulonephritis with irreversible nephrotic syndrome.

Urinary enzyme excretion and proteinuria were studied in 316 children with different underlying diseases. Activities on N-acetyl-beta-D-glucosaminidase and alanine aminopeptidase decreased progressively with age in the urine of 66 healthy prematures, newborns, infants or children. In 51 children with nephrotic syndrome, tubulopathies or chronic renal failure, excretion of NAG and AAP rose 3 to 30 fold. Contrary to molecular weight dependent protein analysis, determination of enzymuria did not allow to differentiate between glomerular and tubular disorders. After renal transplantation, 31 out of 52 children had a pathological enzymuria. NAG and AAP were more frequently elevated during treatment with cyclosporine A (21/29), than with azathioprine (10/23). The influence of nephrotoxic drugs upon enzymuria was documented in 14 children with cystic fibrosis or septicaemia treated with tobramycin. Activities of NAG and AAP rose transiently, whereas proteinuria remained almost unchanged. Only three out of 45 children receiving nonsteroidal antiinflammatory drug therapy for juvenile rheumatoid arthritis or spondylarthritis showed a pathological increase in enzymuria. Mean urinary NAG and AAP excretion in 154 children with insulin dependent diabetes mellitus were not different from controls and were unrelated to either duration of disease or HbA1 concentration. The determinations of urinary enzymes as non-invasive tests of renal integrity in medicine and toxicology provide a very sensitive indicator of renal damage. The assays of NAG and AAP have proven to be most valuable; however, due to a lack of specificity for the type and origin of renal dysfunction, these urinary enzyme assays are most useful when carried out in conjunction with electrophoretic analyses of proteinuria.

Renal involvement (RI)--defined as proteinuria greater than 150 mg per 24 h with haematuria or impaired glomerular filtration rate--was studied in 80 patients with infective endocarditis (IE). Proteinuria was measured quantitatively and further differentiated by the SDS-polyacrylamide-gel electrophoresis. RI was found in 40 patients (50%) with proteinuria from 150 to 8000 mg per 24 h. SDS-PAGE revealed a tubular protein pattern in 17 patients, a glomerular pattern in 6 and a glomerulo-tubular pattern in 17. Mortality rate was significantly higher in patients with RI (40%) than in those without (7.5%), and was not related to the type of infected valve, infective organisms, method of treatment (surgical or medical) or embolic events. Following successful treatment of IE, 18 out of 23 patients showed complete normalization of renal function. Renal involvement in patients with IE may be of prognostic significance--indicating an impaired prognosis.

Multiple pathogenetic mechanisms can lead to dysfunctions or malformations of the liver and kidneys in children and adults. The association of renal and hepatic abnormalities can be found in different congenital malformation syndromes. Hereditary metabolic disorders are capable of alternating liver and kidney function. Immunologic, toxic and septic diseases may damage both organ systems. In patients with liver cirrhosis, both glomerular and tubular dysfunctions can be observed. In the course of liver transplantations, an increased rate of renal dysfunction was observed. This survey summarizes the main clinical syndromes of renal involvement associated with liver disease.

Unlabelled: A clinical study of 204 patients with unilateral multicystic renal dysplasia referred to 30 nephrology departments was undertaken to assess the frequency of complications in children who underwent nephrectomy (n = 40) versus those who were treated conservatively (n = 164). Six patients required antihypertensive treatment, 30 (13% of girls, 17% of boys) had at least one episode of urinary tract infection. The number of clinical complications did not differ in patients who underwent nephrectomy in comparison to those who did not. The dysplastic kidney decreased in size in 65% of kidneys with repeated ultrasound values; no change occurred in 16%, while an increase in maximal diameter was observed in 19%. Contralateral kidney length of more than 2 standard deviation scores (SDS) was seen in 30% of patients. There is evidence for a slight impairment of renal function in the whole study group given by a median of serum creatinine level of 0.63 SDS in all patients available for analysis. Among those 35 patients with contralateral anomalies (mainly obstructive changes and vesico-ureteral reflux), all 3 patients with contralateral changes suggestive of hypoplasia and 22% with obstruction, but only 1/7 (14%) with reflux showed elevated serum creatinine level >2 SDS.Conclusion: Renal function seems to be slightly impaired in patients with unilateral multicystic renal dysplasia. The apparent tendency to regression of the dysplastic kidney and no difference in the number of complications justify a conservative management rather than operative intervention. [ABSTRACT FROM AUTHOR]

Kanzelmeyer NK, Ahlenstiel T, Drube J, Froede K, Kreuzer M, Broecker V, Ehrich JHH, Melk A, Pape L. Protocol biopsy-driven interventions after pediatric renal transplantation. Pediatr Transplantation 2010: 14:1012-1018 © 2010 John Wiley & Sons A/S. The therapeutic value of protocol biopsies (PBs) in renal transplant recipients remains unclear. We performed protocol biopsies in 57 children six months after transplantation. We increased the CNI dose in patients with borderline findings. In cases of Banff grade Ia, six prednisolone IV-pulses were given and the CNI dose was increased. CNI toxicity and polyomavirus nephropathy led to a reduction in the CNI dose. GFR was compared with a control group of 51 children with no PBs transplanted in the same period. Forty-two percent of PBs had no pathological changes, 24% IF/TA. Borderline findings were detected in 11%, Banff grade Ia in 15% (CNI), toxicity in 8%, and one case showed polyomavirus nephropathy. GFR after 1.5 and 2.5 yr was similar in both groups. GFR 3.5 yr after transplantation was significantly higher in the intervention group (57 ± 17 vs. 46 ± 20). Patients treated with low-dose CNI and everolimus had a significantly lower number of pathological findings in PBs. The performance of protocol biopsies followed by a standardized treatment algorithm led to better graft function 3.5 yr after transplantation. Prospective randomized studies to confirm our findings are needed. [ABSTRACT FROM AUTHOR]

Pape L, Ehrich JHH, Offner G. Long-term follow-up of pediatric transplant recipients: mycophenolic acid trough levels are not a good indicator for long-term graft function. Clin Transplant 2004 DOI: 10.1111/j.1399-0012.2004.00229.x © Blackwell Munksgaard, 2004 Mycophenolate mofetil (MMF) has the potential of decreasing acute rejection episodes early following renal transplantation. Pharmocokinetic monitoring of mycophenolic acid (MPA) trough levels is performed by many centers. MMF has also proved successful in improving long-term graft function in patients with chronic allograft nephropathy (CAN). However, no data for long-term monitoring of MPA in children have yet been published. MMF therapy with a dose of 600 mg/m2 twice daily was initiated in 42 children (median age 9.4 yr, range 1.4–15.1) after a median period of 3.8 yr (range 1.0–10.6) post-transplantation – according to significant increases in serum creatinine. CAN was diagnosed by renal biopsy and the amount of fibrosis was quantified with PicroSiriusRed staining. MMF therapy was combined with ciclosporin A and prednisolone. MPA-C0-levels, measured by high-pressure liquid chromatography, were tested every 3 months. In 12 children a full MPA area under the curve concentration (AUC) was measured. The glomerular filtration rate ( GFR) was calculated at the start of MMF therapy and 2 yr later. After initiation of MMF, the calculated GFR did not decrease further in 22 children and mean GFR remained stable for 2 yr in the whole study group. There was a significant correlation between MPA levels 75 min after administration and the full AUC ( r = 0.94, p < 0.001) but no correlation between trough levels and AUC ( r = −0.07, p > 0.05). The mean MPA trough level was 2.8 ± 1.3 ng/mL. The intra-individual coefficient of variation was 2.6 ± 1.4. There was no correlation between mean MPA trough levels and GFR development after 2 yr ( r = 0.03, p > 0.05). In children with an MPA level below 1.2 mg/L (n = 5), the mean GFR decline was no different to those with a higher level (p > 0.05). Drug monitoring of MPA trough levels had no impact on long-term graft function in kidney recipients. MPA levels taken 75 min after administration showed a high correlation with MPA-AUC whereas C0-levels did not correlate. The value of C75 drug measurements for monitoring renal allograft survival will have to be judged in future studies. [ABSTRACT FROM AUTHOR]

Summary The extent to which growth after renal transplantation differs between children with a living related donor graft (LRD) and those with a cadaveric donor graft (CAD) is unclear. We retrospectively studied growth in the 5 years after transplantation in 30 boys who received LRD and 21 who received CAD. Height was similar in both groups after transplantation but was greater in LRD than in CAD recipients during follow-up. LRD recipients were taller at all ages, and had greater growth velocity in infancy and during puberty. Glomerular filtration rate (GFR) was higher immediately after transplantation in LRD than in CAD recipients, but did not differ between the groups during follow-up. GFR and other factors did not affect height 5 years after transplantation. These findings support use of LRD as the preferred option in children. [ABSTRACT FROM AUTHOR]