Unusual manifestation of posttransplant lymphoproliferative disorder in the esophagus.

Early manifestations of posttransplant lymphoproliferative disorders (PTLD) are mainly associated with a primary Epstein-Barr virus (EBV) infection. Rapid increases in peripheral blood EBV DNA load are supposed to reliably predict PTLD. We report a boy who 6 months after living-related kidney transplantation presented with an extranodal esophageal manifestation of PTLD. Despite a primary EBV infection with tonsillitis, the peripheral blood EBV DNA remained low, hiding the progression to PTLD.

Serum insulin-like growth factors (IGFs) and IGF binding proteins 1, 2, and 3 in children with chronic renal failure: relationship to height and glomerular filtration rate. The European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood.

Serum levels of insulin-like growth factor I (IGF-I), IGF-II, and IGF binding protein 1 (IGFBP-1), IGFBP-2, and IGFBP-3 were measured in 94 children with chronic renal failure (CRF). The results were compared with their respective age-dependent normal ranges, and the relationship with height and residual glomerular filtration rate (GFR) was examined. Each IGF and IGFBP was quantified by specific RIA. Serum IGF-I and IGF-II levels were in the normal range throughout their entire childhood in the vast majority of cases. The mean age-related IGF-I (0.07 +/- 0.14 SD score) and IGF-II levels (0.06 +/- 0.11 SD) were similar. Age-related IGF-II but not IGF-I levels showed a weak inverse linear correlation with residual GFRs (r = -0.24, P < 0.02). Mean age-related IGFBP-1 serum levels (1.04 +/- 0.09 SD) were slightly elevated, whereas mean age-related serum IGFBP-2 levels (3.25 +/- 0.20 SD) and serum IGFBP-3 levels (2.61 +/- 0.12 SD) were markedly elevated. Significant inverse correlations were found between GFRs and age-related IGFBP-1 (r = -0.42, P < 0.001), IG-FBP-2 (r = -0.56, P < 0.001), and IGFBP-3 (r = -0.28, P < 0.005), but the increase in IGFBP-2 with declining GFR was relatively more pronounced than the respective increase in IGFBP-1 and IGFBP-3. The correlation between age-related IGF-I and relative height in prepubertal children with CRF (n = 54, r = 0.43, P < 0.001) was lower than in prepubertal controls (n = 68, r = 0.67, P < 0.001), and the slope of the regression line was significantly less steep, indicating that the normal relationship between IGF-I and height is disturbed in CRF. The normal relationship between IGFBP-3 and height was disrupted in CRF. Forward stepwise regression analysis revealed that height in CRF is correlated with IGF-I and inversely correlated with IGFBP-2. We conclude that the imbalance between normal IGFs and excessive IGFBP serum levels in CRF plays a pathogenic role in the growth failure of these children.

Reduced concentration of serum growth hormone (GH)-binding protein in children with chronic renal failure: correlation with GH insensitivity. The European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood. The German Study Group for Growth Hormone Treatment in Chronic Renal Failure.

Growth retardation in children with chronic renal failure (CRF) despite normal or elevated GH levels indicates a peripheral insensitivity to the action of GH. One possible molecular mechanism is a reduced density of GH receptors in GH target organs. In humans, the circulating high affinity GH binding protein (GHBP) is thought to reflect GH receptor expression, because it is derived from the extra-cellular domain of the GH receptor by proteolytic cleavage. We, therefore, analyzed serum GHBP levels by ligand-mediated immunofunctional assay in 126 children with CRF compared to reference values obtained by analysis of 773 healthy children. In 77% of CRF patients, serum GHBP concentrations were below the mean for age- and gender-matched controls. The decrease in serum GHBP levels was related to the degree of renal dysfunction. In advanced CRF (glomerular filtration rate, < 35 mL/min.1.73 m2), mean age- and gender-adjusted GHBP levels were -1.40 +/- 0.18 SD score; 36% of patients had GHBP levels below the normal range (< -2 SD score). Children with end-stage renal disease (n = 26) had the lowest GHBP levels (-2.25 +/- 0.22 SD score). Multiple linear regression analysis revealed that body mass index, rather than glomerular filtration rate, is the prevailing determinant of serum GHBP levels in CRF. GHBP levels correlated with both the spontaneous growth rate ( r = 0.44; P < 0.0001) and the growth response to GH therapy (r = 0.48; P < 0.005), indicating decreased sensitivity to both endogenous and exogenous GH. Subcutaneous GH therapy did not consistently affect serum GHBP levels after 3 months of treatment. It is suggested that low GHBP levels in children with CRF represent a quantitative tissue GH receptor deficiency as one of the molecular mechanisms of GH insensitivity.

Insulin-like growth factor-binding protein-6 levels are elevated in serum of children with chronic renal failure: a report of the Southwest Pediatric Nephrology Study Group.

Previous studies suggest that growth retardation in children with chronic renal failure (CRF) results in part from inhibition of insulin-like growth factor (IGF) action by excess serum IGF-binding proteins (IGFBPs). Excess IGFBPs in CRF serum include IGFBP-1, -2, and -3 and a diffuse approximately 24- to 28-kDa IGFBP band identified by [125I]IGF ligand blot. The present studies characterized this diffuse approximately 24- to 28-kDa band. Initial studies identified this band as IGFBP-6, because it was immunoprecipitated by antiserum raised against a synthetic peptide of human IGFBP-6 (hIGFBP-6). Additional [125I]IGF ligand blots found that the immunoprecipitated band was 1) recognized by [125I]IGF-II but not [125I]IGF-1, 2) more abundant in CRF than in normal serum, and 3) more abundant in serum from dialyzed than nondialyzed prepubertal CRF children. Using the hIGFBP-6 antiserum in a specific and sensitive RIA, we found that serum IGFBP-6 levels were 4.7 +/- 1.7 nmol/L in 10 normal prepubertal children, 21.4 +/- 6.1 nmol/L in 44 nondialyzed prepubertal CRF children, 73.5 +/- 14.4 nmol/L in 7 dialyzed prepubertal CRF children, and 94.6 +/- 26.2 nmol/L in 14 dialyzed pubertal CRF children. IGFBP-6 levels were also elevated in 71 nondialyzed European children with CRF. In nondialyzed CRF children, serum IGFBP-6 levels 1) correlated inversely with the glomerular filtration rate, 2) did not correlate with height SD score, and 3) were not altered by 12 months of daily recombinant hGH treatment. In summary, a specific antiserum and RIA were used to demonstrate elevated levels of intact IGF-II-binding IGFBP-6 in serum of CRF children. We postulate that the excess IGFBP-6 may modulate the action of IGF-II on target tissues.

Ciprofloxacin-induced acute renal failure in a patient with cystic fibrosis.

Acute renal failure is a rare adverse reaction of antibiotic therapy with quinolones seldom seen in young patients. We report an 18-year-old young woman with cystic fibrosis who experienced a pronounced decline in renal function after oral treatment with ciprofloxacin for 3 weeks. Withdrawal of the drug led to normalization of renal function after 10 days.

Type III hyperlipoproteinemia in a child with hemolytic uremic syndrome.

The case of a 6-year-old girl with severe hyperlipoproteinemia and chronic renal failure that developed after hemolytic uremic syndrome (HUS) is reported. The patient was homozygous for apolipoprotein (apo) E2, and her very-low-density lipoprotein (VLDL)-cholesterol/serum-triglyceride (TG) ratio of 0.63 was unusually high. She was consistently diagnosed to have type III hyperlipoproteinemia (HLP). This is the first report of type III HLP in a child with chronic renal disease.

Evaluation of protein intake by dietary diaries and urea-N excretion in children with chronic renal failure. European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood.

In 1988 a European multicentre, randomized trial was started in order to analyse the influence of protein intake on the progression of chronic renal failure in children. Compliance to the dietary prescriptions, i.e. protein intake, was checked by written dietary diaries and in addition by urinary urea-N excretion. This provided a unique chance to compare both methods in non-hospitalized children. Of a total of 200 patients 123 were selected, in whom at least 4 consecutive dietary diaries plus 4 completely collected 24-hour urine samples were available. Whereas urea-N excretion and simultaneously recorded protein intake did not correlate well, mean urinary urea-N excretion and mean protein intake of at least 4 observations in each patient correlated highly (r = 0.803, p = 0.0001). The difference between protein-N intake and urea-N excretion was not a constant amount of 0.031 g/kg/day as proposed by Maroni et al. [1985] but figured at 0.085 +/- 0.061 g/kg/day and was highly correlated to protein intake (r = 0.839, p = 0.0001). The correlation of protein intake and urea-N excretion was best described by the formula: protein-intake (g/kg/day) = (urea-N excretion [g/kg/day]x 15.39) -0.8 or protein intake (g/kg/day) = urea-N excretion (g/kg/day) x 9.5. Maroni's formula underestimated the high protein intake of young children. In only a few patients dietary diaries severely underestimated protein intake as compared to calculation by urea-N excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Spontaneous remissions in frequently relapsing and steroid dependent idiopathic nephrotic syndrome.

We studied retrospectively the clinical course of 32 steroid sensitive nephrotic children with frequent relapses with or without steroid dependency associated with minimal glomerular lesions. Six hundred twenty-seven relapses were traced during a mean observation period of 7 years per patient. The median period between the beginning of significant proteinuria and the start of prednisone therapy was 5 days (range 0-194 days). At least one spontaneous remission occurred in 10 of the 15 frequent relapsers and in 11 of the 17 steroid dependent patients. Twenty-three percent of the relapses in frequent relapsers and 10% of the relapses in steroid dependent patients remitted spontaneously. The disappearance of proteinuria was documented in 79% of these relapses between day 4 and day 14 after onset. A delay of up to 10 days in starting prednisone therapy did not influence the further course of this or the subsequent relapse. Our results suggest that this delay is justified in the absence of progressive clinical signs and may, by the occurrence of spontaneous remissions, contribute to reduce the total amount of steroids needed.

Increased aggregation with normal surface charge and deformability of red blood cells in children with nephrotic syndrome.

Hemorheological risk factors for thromboembolic disease were evaluated in 25 pediatric patients with idiopathic nephrotic syndrome (NS). In patients with increased proteinuria (greater than 100 mg/m2/24 h) red blood cell (RBC) aggregation and plasma viscosity were significantly increased when compared with patients in remission (less than 100 mg/m2/24 h) and with healthy controls. RBC surface charge was normal during increased proteinuria and remission. RBC aggregation correlated positively with plasma viscosity, fibrinogen, alpha 2-macroglobulin, immunoglobulin M, and the degree of proteinuria, and negatively with plasma albumin levels. RBC aggregation showed no correlation to RBC surface charge. Hematocrit and RBC deformability (rheoscope) were similar in both patient groups and in controls. Increased RBC aggregation and plasma viscosity may contribute to the increased risk of venous thromboembolism in NS.

24-hour blood pressure monitoring in children and adolescents after recovery from hemolytic uremic syndrome.

24-hour blood pressure monitoring is a valuable method for the diagnosis of arterial hypertension as well as for assessment of the diurnal rhythm of the arterial blood pressure (BP). The nocturnal decrease of blood pressure ("dipping") may be attenuated or abolished in children with advanced renal failure and glomerular diseases. Arterial hypertension is a longlasting problem in children who had recovered from hemolytic uremic syndrome (HUS). We therefore performed BP monitoring in 11 children and adolescents (age 1.3 to 18.8 years, 6 males, 5 females) after HUS using a portable oscillometric device (SpaceLabs 90207). Six of the subjects had a normal renal function (group A). The other 5 patients had impaired renal function with a glomerular filtration rate <60 ml/min/1.73 m2 (group B). Nocturnal dipping was calculated as nocturnal mean blood pressure minus diurnal mean blood pressure given in per cent of diurnal mean blood pressure. Two of the patients in group A had diurnal mean BP above the 95th percentile of the German collaboration study, but none of the group was hypertensive during the night, and nocturnal dipping was 13.6% (9.7-15.5%, median and range) for systolic BP and 23.7% (15.5-29.9%) for diastolic BP which is very similar to healthy children. All of the patients had a normal diurnal BP rhythm. From patients of group B, 4 had elevated diurnal mean BP and also 4 were hypertensive during the night. Nocturnal dipping was 1.4% (0.7-4.1%) for systolic and 6.8% (0-10.7%) for diastolic BP which is clearly attenuated compared to group A. We therefore conclude that arterial hypertension is more common in patients after HUS if they have impaired renal function, and diurnal rhythm of arterial blood pressure is attenuated in these patients. However, nocturnal dipping of blood pressure is not disturbed in children after HUS without renal insufficiency, even if they were hypertensive.

Variability of peritoneal equilibration test in children on continuous peritoneal dialysis by repeated testing with solutions of different osmolarity.

To evaluate (1) differences in the peritoneal equilibration test (PET) achieved using continuous peritoneal dialysis (CPD) solutions containing different amounts of glucose and (2) intraindividual reproducibility of PETs performed twice within an interval of 8 months on CPD, we investigated 39 PETs in 13 children aged 2.4-19.0 years (median 10.6 years) on stable CPD regimens. The fill volume was 1 L/m2 body surface area. We used a standard CPD solution (Fresenius) with a 2.3% glucose content (groups 2.3a and 2.3b) two times within an interval of 1-8 months. A third test was done between the two with a CPD solution of 1.5% glucose (group 1.5). Equilibration quotients, that is, substrate concentration in dialysis fluid divided by substrate concentration in plasma (D/P), did not show any statistically significant differences between groups 1.5 and 2.3a or between groups 2.3a and 2.3b. A significant difference was seen in the decline of glucose content of dialysate between groups 1.5 and 2.3 but not between groups 2.3a and 2.3b. Ultrafiltration was higher in groups 2.3a and 2.3b compared with group 1.5. Inter- and intraindividual variability between solute transfer was small during follow-up in stable CPD patients. Different glucose contents of 1.5 and 2.3 g/dL dialysis fluid had no measurable influence on PET results of stable CPD patients. For standard PETs, reducing the glucose content of dialysis fluid to isoosmolarity is not necessary.

Clearance and removal of oxalate in children on intensified dialysis for primary hyperoxaluria type 1.

Patients with end-stage renal failure owing to primary hyperoxaluria type 1 (PH1) receive dialysis while waiting for transplantation. So far, dialysis has not been shown to overcome the problem of ongoing oxalate production and deposition at extrarenal sites. We report on six children with PH1 who had to be dialyzed for a median period of 2.5 years while awaiting liver transplantation. Aiming at preventing oxalate tissue accretion, oxalate mass transfer was studied and dialysis intensified accordingly. Mean plasma oxalate concentration was between 51 and 137 micromol/l. In three of the six patients with a urinary output between 630 and 3140 ml, urinary removal of oxalate was between 5.6 and 12.4 mmol/week/1.73 m2. Hemodialysis (HD) in five of the six patients demonstrated a mean oxalate dialysance between 158 and 444 l/week/1.73 m2. Peritoneal dialysis (PD) in two of the six patients showed mean oxalate clearances of 66 and 103 l/week/1.73 m2. One patient received HD and PD. By adding all modes of elimination, a mean total oxalate mass between 10.1 and 24.1 mmol/week/1.73 m2 was removed. Dialysis is still necessary as a temporary therapy for a number of patients with PH1. Dialysis should be instituted pre-emptively and maximally exploited by intensified HD/PD treatment protocols, without, however, cutting back urinary output.

Characterisation and specificity of glomerular basement membrane antigens identified by sera of patients with anti-GBM nephritis.

The sera of 21 patients positive for antibodies against GBM in indirect immunofluorescence tests were examined by immunoblotting. We demonstrated antibodies against 50, 48, 43 and 29 kD molecular weight peptides in 20 of 21 sera using collagenase-digested GBM, in 19 of 21 using trypsin-digested GBM, and in 10 of 21 using elastase-digested GBM. Although the spectrum of molecular weights of the antigenic proteins was similar in all three digests, they differed with respect to preservation of antigenicity upon reduction with mercaptoethanol. Many of the sera of patients and controls reacted with proteins unrelated to GBM, e.g. albumin and prealbumin. Furthermore, some control sera reacted with one single peptide of the above-mentioned specific GBM peptides. Our results suggest that the highly purified 29 kD peptide of the collagenase digest or the 50 kD peptide of the trypsin digest provide the best antigens to develop a screening test for antibodies against GBM. However, serum antibodies against these antigens will not be absolutely specific for anti-GBM antibody-mediated nephritis, as shown by the immunoblot experiments.

[Kawasaki syndrome--a new disease?]. / Das Kawasaki Syndrom--eine neue Krankheit? (author's transl)

Kawasaki recognized in 1967 the acute febrile mucocutaneous lymph node syndrome (MCLS) as a well defined entity among a variety of hitherto unidentified atypical exanthems. The etiology is uncertain. There are close relations to infantile polyarteritis nodosa (IPN) which is probably the severe variant of Kawasaki's disease. Histologically it is a generalized necrotizing vasculitis, most probably caused by circulating immune complexes. The disease is supposed to be initiated by various infections in patients with certain predispositions. Considerations about etiology and pathogenesis as well as relations to IPN are mainly discussed theoretically. Therefore it is recommended to investigate the Kawasaki syndrome following a devised protocol.

[Quality of life following renal transplantation in childhood]. / Lebensqualität nach Nierentransplantation im Kindesalter.

The goal of renal transplantation is to achieve the best possible quality of life in patients with terminal renal failure. To evaluate some aspects of quality of life in patients with renal grafts during childhood of our center, data on medical, educational and professional rehabilitation were collected retrospectively. Between 1972 and 1997 135 renal transplantations had been performed in 123 patients below the age of 18 years. 12-year graft survival of patients transplanted before 1983 figured at 21% and rose to 62% during the following years, after introduction of cyclosporine A into the immunosuppressive regimen. The proportion of patients in the respective age group attending a secondary school (16%) was lower and of those attending elementary school (71%) or a school for disabled and handicapped children (11%) was higher than usual in the German population. But, 83% of all patients reached a school degree. After school 78% proceeded with a vocational training or university. 89% of patients completing professional training were employed at last observation as compared to only 60% of those who never finished a professional training. Renal replacement therapy starting already during the early phase of education is difficult to coordinate with normal schooling. Considering these health- and time-related obstacles, the degree of educational and professional rehabilitation of the patients is good. But, there is a need for special support accompanying educational and professional training.

Acute renal failure in an infant with partial deficiency of hypoxanthine-guanine phosphoribosyltransferase.

A three week old boy presented with pneumonia, weight loss, metabolic acidosis and renal failure (serum creatinine 3.1 mg/100 ml, uric acid 11.5 mg/100 ml). Renal biopsy revealed severe crystal nephropathy. Low activity of hypoxanthine-guanine phosphoribosyltransferase (HPRT) in erythrocytes and fibroblasts suggested a partial deficiency of the enzyme. A family study proved the mother to be heterozygous and the maternal grandfather to be hemizygous for HPRT deficiency. The grandfather developed gouty nephropathy and uraemia. The propositus was treated with allopurinol and kept on low purine diet and high fluid intake with sodium bicarbonate. Thereafter GFR gradually improved. At the age of two and a half years, growth and psychomotor development were normal, but ultrasound examination still revealed a dense renal parenchyma. Partial HPRT deficiency is a newly recognised treatable form of renal failure in the newborn.