Reduction of proteinuria during intensified antihypertensive therapy in children after renal transplantation.

BACKGROUND: Proteinuria together with hypertension are known risk factors for poor allograft as well as patient survivals after renal transplantation. In adults, proteinuria can be reduced by lowering blood pressure and by using angiotensin-converting enzyme inhibitors. In children, no study has investigated the antiproteinuric effects of antihypertensive therapy. Herein we investigated changes in proteinuria among a subgroup of children with proteinuria>or=200 mg/m2d in an interventional study primary aimed to improve the efficacy of antihypertensive therapy. PATIENTS AND METHODS: Twelve children with proteinuria>or=200 mg/m2d were included in the study. Proteinuria was investigated at baseline and at 1 year after changes in antihypertensive therapy. Blood pressure (BP) was measured using ambulatory BP monitoring. RESULTS: The median protein excretion of 226 mg/m2/d (range, 41-1478 mg/m2/d) at 1 year before the study did not change significantly at study baseline (278 mg/m2/d; range, 205-1264 mg/m2/d), but decreased significantly to 199 mg/m2/d (range, 65-749 mg/m2/d) after 1 year (P<.05 vs baseline). The number of antihypertensive drugs was increased from 1.6+/-1.0 to 2.2+/-0.9 drugs/patient after 1 year (P<.05). The use of different classes of antihypertensive drugs did not change significantly. Mean ambulatory systolic and diastolic BP at daytime and diastolic BP at nighttime did not change significantly after 1 year; mean ambulatory systolic BP at night decreased from 1.60+/-1.54 to 1.04+/-0.97 standard deviation score (P<.05). Graft function did not change significantly. CONCLUSION: We demonstrated that proteinuria among children after renal transplantation was reduced by intensified antihypertensive therapy using all classes of antihypertensive drugs.

Recurrence of nephrotic proteinuria in children with focal segmental glomerulosclerosis after renal transplantation treated with plasmapheresis and immunoadsorption: case reports.

Idiopathic focal segmental glomerulosclerosis (FSGS) is believed to be caused by a circulating permeability factor. FSGS recurrence is common after transplantation. The treatment is still a matter of debate; plasmapheresis (PE) and immunoadsorption (IA) are often used. We report on PE and IA in the treatment of two children with recurrent nephrotic proteinuria. Patient 1 was a 16-year-old girl who had recurrence of nephrotic proteinuria on the first day after transplantation (proteinuria-19 g/d). Primary immunosuppressive therapy was changed to high-dose cyclosporine and cyclophosphamide; plasmapheresis was started on day 4. Altogether we performed 53 PE and 38 IA procedures. During the first month, PE procedures were performed with no more than a 2-day interval between sessions, and the girl achieved partial remission (proteinuria 3 g/d). PE was then stopped. After 2 months, a relapse of heavy proteinuria occurred. This relapse was successfully treated again with intensified PE treatment. After achieving remission, a chronic PE regimen was started (PE once a week), similar to the previous series. The child remained in partial remission. Seven months after renal transplantation, she was switched from PE to IA, because of severe hypoproteinemia. Graft biopsy performed at 4 months showed effacement of the foot processes. At the present time she has a good graft function and 3 g/d proteinuria. Patient 2 was a 13-year-old girl with FSGS since 9 years. On the second day after renal transplantation she developed nephrotic proteinuria (proteinuria-14 g/d), which was treated with 39 PE and 16 IA treatments. She went into complete remission on the intensified PE regimen, had one relapse, and was switched to chronic IA. Graft biopsy performed at 2 weeks after transplantation showed effacement of the foot processes. At the present time she has good graft function and low proteinuria (0.3 g/d). In conclusion, intensified PE or IA treatments induced remission of recurrent nephrotic range proteinuria. Chronic PE or IA can maintain patients with frequent relapses in long-term remission.

Worldwide variation of dialysis-associated peritonitis in children.

Peritonitis is the most common cause of dialysis failure in children on chronic peritoneal dialysis. We performed a prospective study of 501 peritonitis episodes in 44 pediatric dialysis centers located in 14 countries that examined peritonitis etiology, efficiency of opinion-based management guidelines, and final outcomes. Culture-negative incidence varied significantly from 11% in North America to 67% in Mexico. Argentina and North America had the highest rate of Gram-negative episodes. Pseudomonas-based peritonitis was eightfold more common in the United States than in Europe, and correlated with the frequency of exit site cleansing and topical mupirocin administration. Significant regional variation in antibiotic susceptibility was noted for the first generation cephalosporins and aminoglycosides. Initial response rates to standardized empiric antibiotic treatment did not differ between regions; however, final outcomes were significantly less favorable in Eastern Europe. The wide regional variation in culture-negative peritonitis, and the distribution and antibiotic susceptibilities of causative bacteria needs to be taken into consideration when the guidelines for empiric therapy of pediatric dialysis-associated peritonitis are revised.

[Improved control of hypertension and its effect on graft function in children after renal transplantation]. / Zlepsená kontrola hypertenze a její vliv na funkci stepu u detí po transplantaci ledviny.

BACKGROUND: Hypertension in patients after renal transplantation (RTx) is associated with impaired graft functions and graft survival. Control of hypertension in children after RTx is low--only 20-50 % of children have well controlled hypertension. The aim of this interventional study is to improve blood pressure control and to investigate whether the improved control will improve the graft survival. METHODS AND RESULTS: 36 children after RTx (mean age 13.9 +/- 4.4 years, time after RTx 2.7 +/- 2.4) fulfilled the inclusion criteria. Ambulatory blood pressure monitoring (ABPM) and graft function were examined. In children with uncontrolled hypertension, the dose and number of antihypertensive drugs were increased to reach BP <95th centile. ABPM was repeated after 12 months. After 12 months day-time and night-time BP dropped non-significantly, however prevalence of uncontrolled hypertension improved significantly from 42 % to 34 % (p<0.05). Number of antihypertensive drugs increased from 2.1 +/- 0.9 to 2.4 +/- 0.8 drugs per patient (p<0.05), namely that of ACE-inhibitors (from 19% to 27%, p<0.05). Graft function decreased by 3.6 ml/min/1.73m2/year (p<0.05). CONCLUSIONS: This 12 months interventional trial demonstrated that control of hypertension in children after RTx can be improved by increasing number of prescribed antihypertensive drugs. The decline of graft function was lower comparing with previous trials.

Prevention and treatment of renal osteodystrophy in children on chronic renal failure: European guidelines.

Childhood renal osteodystrophy (ROD) is the consequence of disturbances of the calcium-regulating hormones vitamin D and parathyroid hormone (PTH) as well as of the somatotroph hormone axis associated with local modulation of bone and growth cartilage function. The resulting growth retardation and the potentially rapid onset of ROD in children are different from ROD in adults. The biochemical changes of ROD as well as its prevention and treatment affect calcium and phosphorus homeostasis and are directly associated with the development of cardiovascular disease in pediatric renal patients. The aims of the clinical and biochemical surveillance of pediatric patients with CRF or on dialysis are prevention of hyperphosphatemia, avoidance of hypercalcemia and keeping the calcium phosphorus product below 5 mmol(2)/l(2). The PTH levels should be within the normal range in chronic renal failure (CRF) and up to 2-3 times the upper limit of normal levels in dialysed children. Prevention of ROD is expected to result in improved growth and less vascular calcification.

Proteinuria in children after renal transplantation.

Proteinuria is associated with poor long-term allograft as well as patient survival among adults after renal transplantation. In children, there are no studies focusing primarily on posttransplant proteinuria. The aim of this cross-sectional study was to investigate the prevalence of and possible risk factors associated with proteinuria. Thirty-three children (mean age of 13.7 +/- 4.3 years; mean time after renal transplantation = 2.3 +/- 2.2 years) were eligible for the study. There was an 82% prevalence of proteinuria (> or =96 mg/m2/d) with nephrotic range proteinuria (> or =960 mg/m2/d) in 12% of children. The mean urinary protein excretion was 256 +/- 299 mg/m2/d (range = 47 to 1264). Children with hypertension, as defined by ambulatory blood pressure monitoring, showed significantly higher proteinuria than normotensive children (382 +/- 435 vs 163 +/- 79 mg/m2/d, P < .05). Children with a history of a previous acute rejection episode showed significantly higher proteinuria than children who never had an episode (416 +/- 445 vs 165 +/- 91 mg/m2/d, P < .05). Children with proteinuria did not show statistically different graft function than children without proteinuria. No statistically significant correlation was observed between proteinuria and ambulatory blood pressure values or graft function. In conclusion, proteinuria is a frequent finding also in children after renal transplantation; it is associated with hypertension and a history of rejection episodes.

Renal concentrating capacity is linked to blood pressure in children with autosomal dominant polycystic kidney disease.

Impaired glomerular filtration rate (GFR) is a risk factor for the development of hypertension in patients with autosomal dominant polycystic kidney disease (ADPKD). However, markers of tubular function were not tested whether they are linked to hypertension or blood pressure (BP) level. The aim of our study was to investigate the relationship between renal concentrating capacity and BP in children with ADPKD. Fifty-three children (mean age 11.8+/-4.4 years) were investigated. Standardized renal concentrating capacity test was performed after nasal drop application of desmopressin, BP was measured by ambulatory BP monitoring (ABPM). Renal concentrating capacity was decreased in 58 % of children. The prevalence of hypertension was significantly higher in children with decreased renal concentrating capacity (35 %) than in children with normal renal concentrating capacity (5 %) (p<0.05). Significant negative correlations were found between renal concentrating capacity, ambulatory BP and number of renal cysts (r = -0.29 to -0.39, p<0.05 to p<0.01). In conclusion, the concentrating capacity is decreased in about half of the patients and is linked to BP. Decreased renal concentrating capacity should be considered.

Ambulatory blood pressure monitoring in children after renal transplantation.

Arterial hypertension is a common complication in children after renal transplantation and the control of hypertension is often difficult. This retrospective investigates the prevalence and rate of control of hypertension using ambulatory blood pressure monitoring (ABPM) in 45 children (mean age 14.1 +/- 4.3 years, mean time after renal transplantation 2.2 +/- 2.7 years), all on cyclosporine or tacrolimus, azathioprine or mycophenolate mofetil plus daily steroids. The overall prevalence of hypertension was 82%. None of the transplanted children had normal blood pressure without antihypertensive therapy (ie, spontaneous normotension). Twenty percent of children had untreated hypertension, 18% had controlled hypertension, and 62% had uncontrolled hypertension. Prevalence of the nondipping phenomenon was 53%. The mean number of antihypertensive drugs (without diuretic monotherapy) in treated patients was 1.9 drugs per patient. The prevalence of arterial hypertension in children after renal transplantation is high and the control of hypertension is often unsatisfactorily low.

[Renal transplantation in children in the Czech Republic]. / Wyniki przeszczepiania nerek u dzieci w Republice Czeskiej.

The aim of the study is to review results of pediatric renal transplantation in center in Prague, Czech Republic. Results are compared with the registry data from Europe and United States. Patients, who underwent RTx at the University Hospital Motol, Prague (Czech Republic) between 1977 and the end of 1999, were analyzed. Since 1977 128 Rtx from cadaveric donors were performed in children in mean age 12.8 +/- 4.1 years. In 1977-1987, patients were treated with prednisone and azathioprine, and since 1988, cyclosporine A, added to prednisone and azathioprine. Sequential quadruple immunosuppression was used only in few highly sensitized patients. Acute graft rejections were treated with methylprednisolone pulses, antithymocyte globulin and monoclonal antibodies OKT3, in selected cases. In 1988 and 1999 cyclosporine A was replaced by tacrolimus as initial immunosuppression in some patients. The number of Tx ranged between 5 and 13 per year. Patients and graft survival were significantly lower in the first time period 1977-1987 with a median patients 5-year survival rate of only 50% and graft survival 30%. In the last period (1988-1999) 5-year patients survival is 90% and 5-year graft survival is 68% (p = 0.01). Two cases of posttransplant lymphoproliferative disease were diagnosed so far. One of them died several months after RTx, the other received cytostatic therapy for Hodgkin tumor and graft function was maintained. Main causes of graft failure were chronic rejection followed by acute steroid resistant rejections, severe cytomegalovirus infections, noncompliance, vascular thrombosis, and recurrence of original disease.

Treatment of peripubertal children after renal transplantation (RTX) with recombinant human growth hormone: auxological data and effects on insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) during 24 months.

OBJECTIVE: To evaluate growth and endocrine parameters in RTX children with GH treatment during 24 months. SUBJECTS: 18 children (13 boys), age 13.1 yr (8.0-16.6), bone age 10.1 yr (5.4-15.3). Patients were 2.8 yr (0.5-7.5) after RTX and had immunosuppressive therapy, prednisone 0.16 mg/kg/d (0.08-0.68). METHODS: GH (4 IU/m2/day s.c.) was given and patients were seen every 3 months for evaluation of height, height velocity, bone age, and hormone parameters. Serum IGF-I was determined by RIA, IGFBP-3 by RIA and Western ligand blotting (WLB). Renal function and adverse effects (GFR, glucose tolerance, rejection episodes) were monitored. RESULTS: Height (+1 SDS) and height velocity (+2.2 SDS) increased significantly during 24 months GH treatment, but delta BA/delta CA was 1.7 and 1.5 during the first and second treatment year, respectively, and all patients entered puberty during the treatment period. GFR decreased slightly during 2 yr (p = 0.048), two patients had chronic rejection and GH therapy was terminated in one patient because of glucose intolerance. The ratio IGF-I/IGFBP-3 rose during the first year (p = 0.002) indicating more bioavailable IGF-I. IGFBP-3 determined by WLB was decreased, but IGFBP-1, -2 and -4 were elevated as compared to a standard. CONCLUSIONS: GH treatment increased height and growth rate in children after RTX. This may be due to significant changes in IGF-I and IGFBP-3 relationship. However, bone maturation was also accelerated thus diminishing height potential. From month 12 to 24 a continuous decrease of IGF-I was observed. There was a slight but significant deterioration of graft function. Adverse events that led to termination of GH therapy were observed in 3 of 18 patients.

Estimation of peritoneal mass transport by three-pore model in children.

BACKGROUND: Computerized modeling is increasingly used to optimize the efficacy of peritoneal dialysis (PD). The Personal Dialysis Capacity (PDC) test is a new tool to model PD efficacy based on the three-pore model of peritoneal mass transport. We sought to evaluate (i) whether the PDC test is applicable to children on chronic PD, and (ii) whether the physiological mass transport coefficients defined in the three pore model are dependent on age or body size in childhood. METHODS: A validation study was performed in 32 pediatric chronic PD patients. Twenty tests were performed using a standard CAPD regimen, and 22 tests using a simplified automated PD (APD) protocol. Test accuracy and precision were evaluated by comparison of predicted with measured 24-hour dialysate clearances of urea, creatinine, beta2-microglobulin and albumin and ultrafiltration rates. Long-term reproducibility was assessed in 16 patients by repeated clearance studies after a median time interval of 10 weeks. RESULTS: While daily clearances of urea and creatinine were predicted with good precision and accuracy with both test protocols (concordance correlation coefficients 0.90 to 0.98, mean difference predicted-calculated -0.6 to +0.6 ml/min/1.73 m2), ultrafiltration rates were predicted more closely by the APD (r = 0.97) than by the CAPD test (0.80). Middle and large molecule clearances were predicted less precisely in both test settings (r = 0.48 to 0.83). Re-test reproducibility was slightly lower than the predictive precision observed in the original test (r = 0.80 to 0.91). The calculated total peritoneal pore area increased in absolute terms, decreased with body size when standardized to weight, and was independent of body size when normalized to body surface area. The body size-normalized fluid reabsorption rate was slightly increased in young infants compared to older children or adults. CONCLUSIONS: The PDC test permits to model peritoneal solute and water transport with remarkable precision in children of all age groups. While the peritoneal pore area is a linear function of body surface area, fluid reabsorption appears to be slightly increased in young infants.

[Growth hormone therapy in prepubertal children with chronic renal insufficiency]. / Liecba rastovým hormónom u prepubertálnych detí v chronickej renálnej insuficiencii.

BACKGROUND: Growth retardation is a serious problem in children with chronic renal failure (CRF) despite normal endogenous growth hormone (GH) secretion. Intensive medical care and dialysis do not improve height velocity. The aim of the study was to evaluate the efficacy of GH therapy in children with growth retardation secondary to CRF. METHODS AND RESULTS: Biosynthetic growth hormone was given to 7 prepubertal children (five boys and 2 girls, age with a range 3.5-14.5 years) with severe growth retardation and CRF during 1 year. The dosage of GH was 1 IU/kg/per week. GH was given daily, sc. The patients had a full examination every 3 months. Six children completed the study. Height velocity improved with GH therapy in 5 children. Renal function deterioration was accelerated in 2 children. The serum alkaline phosphatase concentration increased and the serum calcium concentration decreased during GH treatment in all children. Glucose, thyroid gland hormone concentration and lipid concentrations remained constant. CONCLUSIONS: The study showed clearly that treatment with biosynthetic GH gave an impressive improvement of height velocity in growth retarded prepubertal children with CRF.