[Rheumatic joint disease in childhood and adolescence ]. / Rheumatische Gelenkerkrankungen im Kindes- und Jugendalter.

Rheumatic joint disease in childhood and adolescence is relatively rare. In the general population, 1 child with juvenile arthritis accounts for 100 adult patients with rheumatoid arthritis. At disease onset 50% of affected children are between 2 and 6 years of age. Symptoms are often subtle and pain is usually not the leading symptom. Early treatment of juvenile arthritis is essential in order to prevent long-term sequelae in affected children. Many children are introduced to a pediatric rheumatologist only with considerable delay. Therapy is based on NSAIDs, intra-articular steroid injections, and immunosuppressive drugs. In severe cases patients are treated with biologics. Physical and occupational therapy are important supportive measures in the treatment.

[Rheumatic joint disease in childhood and adolescence]. / Rheumatische Gelenkerkrankungen im Kindes- und Jugendalter.

Rheumatic joint disease in childhood and adolescence is relatively rare. In the general population, 1 child with juvenile arthritis accounts for 100 adult patients with rheumatoid arthritis. At disease onset 50% of affected children are between 2 and 6 years of age. Symptoms are often subtle and pain is usually not the leading symptom. Early treatment of juvenile arthritis is essential in order to prevent long-term sequelae in affected children. Many children are introduced to a pediatric rheumatologist only with considerable delay. Therapy is based on NSAIDs, intra-articular steroid injections, and immunosuppressive drugs. In severe cases patients are treated with biologics. Physical and occupational therapy are important supportive measures in the treatment.

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.

Anuria during pneumoperitoneum in infants and children: a prospective study.

INTRODUCTION: Transient oliguria during laparoscopic surgery is a known phenomenon. Currently, no data on the impact of pneumoperitoneum on renal function in children are available. PATIENTS AND METHODS: Thirty children with normal kidney function, who underwent laparoscopic surgery, were included in a prospective study. A transurethral catheter was placed to measure urine output during and 6 hours after operation. Renal blood flow (resistive index) was evaluated by Doppler ultrasound of a segmental renal artery before surgery, every 15 minutes during laparoscopy, and after 24 hours. Blood and urine samples were studied before and 24 hours after surgery. Hemodynamic parameters were monitored continuously during standardized anesthesia, including a standardized intravenous infusion regimen. RESULTS: Urine output decreased within 45 minutes of pneumoperitoneum in all patients. Of 8 children younger than 1 year, 7 (88%) developed anuria vs 3 of 22 (14%) children aged 1 to 15 years (P < .001). Nine children 1 year and older (32%) developed oliguria. There was a significant recovering in the mean urine output until 5 to 6 hours after pneumoperitoneum in both age groups. No significant alterations of the renal blood flow (resistive index) and the serum and urine levels of cystatin C, creatinine, and urea nitrogen were evident until 24 hours postoperatively. The volume of infusion during pneumoperitoneum did not correlate with urine output. CONCLUSION: Pneumoperitoneum leads to anuria in most children younger than 1 year and to oliguria in about one third of older children. This is a completely reversible phenomenon. Urine output should not be taken into consideration for calculating intravenous fluid administration during pneumoperitoneum in children.

Cyclosporin A monitoring by 2-h levels: preliminary target levels in stable pediatric kidney transplant recipients.

Clinical trials in adults have shown that management of transplanted patients with cyclosporin A (CsA) 2-h levels (C2) lead to superior outcome compared with monitoring of 12-h trough levels (C0). In both adults and children, C2 levels enabled a better estimation of the area under the curve concentration than C0 levels. Therefore, it can be suspected that C2 monitoring might also lead to a better outcome in children. Until now C2 target levels for children have not been defined. We measured C2 levels in 101 stable pediatric kidney recipients with a minimum time of 1 yr after transplantation. C2 levels were compared with changes in glomerular filtration rate (GFR) 6 months later. Median C2 levels in children after renal transplantation were 714 ng/mL (95% confidence interval 654-774). Patients with C2 levels below 750 ng/mL had a significantly higher percentage of decline in GFR than patients with C2 levels above 750 ng/mL (p < 0.05). In children with C2 levels below 500 ng/mL three acute rejections occurred in comparison with no rejection in the remaining patients (p < 0.05). We conclude that the lower C2 target level should be above 750 ng/mL in stable pediatric transplant recipients. An upper target level above 1000 ng/mL should be avoided. The question, whether C2 monitoring in pediatric kidney recipients is superior to C0 monitoring, is yet to be answered.

A meta-analysis of cytotoxic treatment for frequently relapsing nephrotic syndrome in children.

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.

Primary hyperoxaluria type 1 causing end-stage renal disease in a 45-year-old patient.

Primary hyperoxaluria type 1 (PH1) is caused by deficiency of peroxisomal alanine-glyoxylate aminotransferase which is in humans exclusively expressed in liver cells. The disease is inherited as an autosomal recessive trait, and initial symptoms usually occur in early childhood. Up to the age of 25 years, 90% of the patients are symptomatic, and many patients develop end-stage renal failure. Pronounced medical care is necessary in PH1 patients to prevent generalized oxalosis with complications due to bone disease and peripheral gangrene. The rather short survival of patients on hemodialysis is caused by sudden arrhythmias and heart block. As no dialysis procedure is able to remove the daily produced oxalate, early transplantation is mandatory. Our 45-year-old patient is remarkable on the basis of the late manifestations of PH1. The diagnosis was delayed by unspecific symptoms of nephrolithiasis with recurrent pyelonephritis. Clinical course and diagnostic cornerstones of primary hyperoxaluria are outlined. The principles of conservative treatment and experiences with dialysis and transplantation are discussed.

Obstructive airway disease caused by Moraxella catarrhalis after renal transplantation.

We report a case of severe acute obstructive airway disease 2 months after renal transplantation in a 16-year-old patient with Biedl-Bardet syndrome who was transplanted for end-stage renal failure secondary to cystic kidney disease. Symptoms of severe obstructive airway disease developed 2 months after transplantation under immunosuppression with prednisone, azathioprine, and tacrolimus. The patient did not develop signs of infection; progressive shortness of breath remained the only symptom for several weeks. After extensive diagnostic evaluation, bronchoalveolar lavage revealed Moraxella catarrhalis as the single infectious agent. After 3 weeks of appropriate antibiotic therapy, symptoms of obstructive airway disease were completely relieved. This atypical presentation of Moraxella infection in an immunocompromised host represents a rare complication of renal transplantation, especially in young patients. Special aspects such as frequency, diagnosis, differential diagnosis, and management of this rare complication of renal transplantation in a pediatric patient are discussed.

Bone metabolism and mineral density following renal transplantation.

AIM: To study bone turnover following renal transplantation using a panel of biochemical markers and to correlate the results with both areal and volumetric bone mineral density (BMD). PATIENTS: A total of 31 patients aged 18.1 years were transplanted 5.4 years before this study. Control patients (n = 31) were age and gender matched. METHODS: In addition to measurement of biochemical markers, BMD was measured by single photon absorptiometry and peripheral quantitative computed tomography on the non-dominant radius. RESULTS: Patients had reduced glomerular filtration rate, raised concentrations of serum phosphate, serum procollagene type I carboxy terminal propeptide, osteocalcin, and serum procollagene type I cross linked carboxy terminal telopeptide. The differences were still significant if only patients with normal intact parathyroid hormone were considered. BMD single photon absorptiometry Z score for age was significantly decreased. Following standardisation for height the differences were no longer present. With volumetric techniques patients had normal trabecular but decreased cortical and total BMD compared to age matched controls, but there was no difference from height matched controls. CONCLUSION: Markers of bone turnover are increased following renal transplantation. However, the biochemical analysis did not allow conclusions to be drawn on the bone mineral content. BMD single photon absorptiometry Z score corrected for height and BMD measured by quantitative computed tomography compared to height matched controls were normal in paediatric renal transplantation patients. Height matched controls should be used in both areal and volumetric BMD measurements in states of growth failure.

Effect of the synthetic glucocorticoid, deflazacort, on body growth, pulsatile secretion of GH and thymolysis in the rat.

DESIGN: Deflazacort (DFZ) is a relatively new glucocorticoid that has been reported to exhibit fewer side-effects than other commonly used corticosteroids. The present study was designed to test the effects of DFZ on thymus gland involution (thymolysis), as compared with body growth and the secretory pattern of GH in the rat. Beginning at 38 days of age, male animals were treated for 8 consecutive days by s.c. injection of DFZ (0.15mg/day), cortisone (CORT) (5mg/day) or vehicle (control, CTRL). RESULTS: Both glucocorticoids had a similar thymolytic effect and caused growth failure, but the growth rate for the DFZ group was significantly higher than that of the CORT group. On day 46, pulsatile GH secretion was quantitated by blood sampling via an indwelling catheter at 10 min intervals for 6h. GH was assayed by RIA and analyzed by multiparameter deconvolution. CORT caused an increase in pulse frequency (5.8+/-0.4 (s.e.m.)) in comparison to DFZ (4.4+/-0. 4) and CTRL (3.8+/-0.3). Both glucocorticoids significantly shortened the interval between secretory bursts. In CTRL animals the interval between bursts was 69.3+/-4.5 min. In DFZ animals this was reduced to 58.5+/-7.1 min, and in CORT rats it was further reduced to 47.0+/-2.6 min. The mass of GH secreted per burst was reduced in CORT animals (52% of CTRL), while DFZ did not alter this parameter. A similar trend was observed for total GH production, with CORT causing a reduction and DFZ not affecting the secretion. CONCLUSION: Rats treated with glucocorticoid show a profound thymolytic effect, as well as important changes in growth. While CORT suppresses GH secretion and alters its pulsatile mode of release, DFZ causes a less significant alteration in the pattern of GH secretion and does not negatively affect the overall amount of GH secreted.

Kidney transplanted children come of age.

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.

Chronic renal failure: an overview from a pediatric perspective.

We present data on the costs and impact of chronic renal failure, the primary renal diseases leading to end-stage renal disease in children, and review the adaptive responses and the pathophysiology and complications of uremia in experimental animals and in man. A treatment strategy is summarized.

Does tacrolimus cause more severe anemia than cyclosporine A in children after renal transplantation?

Initial reports indicated the possibility of severe anemia associated with tacrolimus (TC) therapy. We investigated the degree of anemia under TC treatment in comparison to cyclosporine A (CsA) treatment in children after renal transplantation. A cross-sectional analysis of 95 children successfully transplanted for at least 3 months was performed. Eighty-five children received CsA and 10 TC. TC-treated patients were compared with CsA-treated patients who were matched according to age, gender, creatinine clearance, and time after transplantation. No patient received additional therapy with mycophenolate mofetil or azathioprine. The creatinine clearance of the whole group of transplanted children was 58 ml/min per 1.73 m2. The patients within the matched-pair analysis had a lower creatinine clearance (TC 46 and CsA 48 ml/min per 1.73 m2). The hemoglobin was 10.3 g/dl for the TC-treated children and 10.4 g/dl among the CsA-treated patients. Numerically, EPO was higher and iron lower in the TC group than in the CsA group. Among children with functioning renal grafts, a correlation exists between Hb and creatinine clearance. A significant difference in the degree of anemia between TC- and CsA-treated children could not be found.

Non-compliance following renal transplantation in children and adolescents.

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.

Writing Amish culture into genes: biological reductionism in a study of manic depression.

Critical realism is used to explore the problem of reductionism in a classic (the Amish Study) and widely-cited study of manic depression. Along with related ideas drawn from the works of R.C. Lewontin, Arthur Kleinman, and Byron Good, it is shown that natural and social scientists deploy atomistic and holistic reductionism; this, in turn, leads to the construction of artificially 'closed systems' through the control of variables or exogenous forces. The psychiatric genetic studies of the Amish were predicated on the assumption that Amish society is homogeneous and unchanging and, therefore, closed. We conclude by arguing that interactions between behaviors and genes, where they exist, take place only within open systems, characterized by multiple mechanisms-social and biological-that together co-determine any event. To move forward, it is argued, behavior and gene research requires recognition and resolution of the philosophical conundrums that accompany reductionism.

Growth hormone and insulin-like growth factor in non-uremic acidosis and uremic acidosis.

Growth retardation is a cardinal feature of children with renal tubular acidosis. This is reversible by correcting the non-uremic acidosis with alkali therapy. Sodium bicarbonate solutions or citrate solutions have been used for this purpose. However, the odious taste of these medications almost invariably causes medical noncompliance. The persistent and often profound metabolic acidosis from medical noncompliance, precipitates hypercalciuria and hypocitraturia, and increases the risk of nephrocalcinosis. The mechanism of the growth retardation in renal tubular acidosis is thought to be related to a blunting of anterior pituitary growth hormone secretion. In experimental metabolic acidosis, the growth hormone secretory pulse areas are reduced. Just as importantly, hepatic growth hormone receptor expression and IGF-I mRNA were blunted in metabolic acidosis. In uremia, growth retardation is secondary to a host of factors including metabolic acidosis, renal osteodystrophy, and the side effects of treatment such as corticosteroids, which compound the growth retardation. Growth hormone secretion by individual pituitary cells was stimulated by corticosteroids but, paradoxically, the total number of somatotropes was suppressed. In uremia, the secretion of growth hormone was not different from controls at any level of growth-hormone-releasing hormone challenges. Hepatic IGF-I mRNA was markedly reduced in uremic rats. Growth hormone receptor expression was significantly reduced in uremic acidotic rats. The growth hormone and IGF-I expression on the growth plate of the long bone of uremic rats was reduced. IGF-I immunoreactivity was present in both the hypertrophic and proliferative zones. The lack of growth of the proliferative zones suggested growth hormone and IGF-I resistance in uremic chondrocytes.