Imaging of bone in the diagnostics of renal osteodystrophy in children with chronic renal failure.

BACKGROUND: In the last two decades considerable advances have been made in the development of imaging tests of the skeletal system. This progress in diagnostic techniques, along with the growing availability of the tests, renders it necessary to review and evaluate their suitability for daily clinical practice. The aim of this article is to compare the results of radiological testing of bone with densitometrical, histomorphometric, and biochemical tests in children with chronic renal failure. MATERIAL AND METHODS: The research involved 31 children with renal failure, of whom 10 were being treated conservatively, 17 by continuous ambulatory peritoneal dialysis (CADO), and 4 by hemodialysis (HD). In all these children, radiological examinations of bone were performed in the arms, knees, and hips, along with tests for the serum concentration of parathormone (iPTH), calcium (Ca), and phosphates (P), and for the activity of alkaline phosphatase (AP). Bone density tests by the DXA method and bone biopsies were also performed. On the basis of radiological evaluation, the patients were divided into two groups: Group I, consisting of 14 children with a normal bone structure image, and Group II, consisting of 17 children with bone atrophy. RESULTS: No statistically significant differences were discovered in the mean values of the tested biochemical parameters between the two groups. The mineral density of total body was normal in 9 of the 14 patients in Group I (64%), and in 7 of 17 (41%) from Group II. The mineral density of total lumbar spine gave similar results. Lower bone density results were obtained in Group II than in Group I, though only in the case of the lumbar spine were the differences statistically significant. In Group I, 5 cases were discovered of chronic osteodystrophy without osteomalacia and hyperparathyroidism (NB), 2 cases of adynamic bone disease (ABD), 4 cases of hyperparathyroidism (HP), 2 cases of moderate hyperparathyroidism (MHP), and one mixed form (Mix); in Group II, there were 6 NBs, 2 ABDs, 1 case of osteomalacia (OM), 5 HPs, and 3 mixed. Radiological examinations revealed one male in Group I with features of prior Perthes's disease, one with fibrous cortical defect, and four cases of valgity of the coxa valga. In Group II, there were 3 children with radiological changes typical for osteomalacia, and in 1 case typical radiological signs of hyperparathyroidism. CONCLUSIONS: Given the lack of consistency in the results of the tests here presented, an entire panel of available tests should be performed for the comprehensive evaluation of the status of the skeleton.

[Results of treatment with recombinant human growth hormone in children with growth retardation in end-stage renal disease]. / Wyniki leczenia rekombinowanym ludzkim hormonem wzrostu niskoroslosci dzieci ze schylkowa niewydolnoscia nerek.

The aim of the study was to estimate the results of recombinant human growth hormone (rhGH) treatment in children with end-stage renal disease (ESRD). 60 growth retarded children with ESRD (mean age 11.2 +/- 7.2 years) were treated with rhGH at a dose of 1-1.1 IU/kg/week. The time of observation was 24 months. Thirty children completed first year, 18--second year of treatment. The mean growth velocity prior to the treatment was 3.03 +/- 1.9, during first year of the study--7.52 +/- 2.42, during second year 6.68 +/- 2.87 cm/year. The negative correlation between growth velocity and patient's age (r = -0.39; p < 0.05) suggest the better growth results in younger children during rhGH treatment. The rhGH therapy is effective method of treatment in growth retarded children with ESRD. Side effects are rare.

Donor DNA can be detected in recipient tissues during rejection of allograft.

The main source of donor DNA in recipients of allograft are "passenger" cells. It is claimed that they are responsible for the posttransplantation microchimerism and prolongation of allograft survival. We have observed that besides cellular microchimerism, donor DNA can be found in the recipient tissues at the time of rejection of the allograft. In this study, we provide evidence for the presence in the recipient of both DNA in "passenger cells" and free DNA in tissues at the terminal stage of rejection. Male BN (RT1 n) rat heart or skin was transplanted to female LEW (RT1 l) rats followed by a vascularized bone marrow in a hindlimb transplant. In another group, heart and skin were transplanted followed by immediate i.v. infusion of donor-type bone marrow cells. CsA was given in a dose of 17 mg/kg body weight for 30 days, then the rats were followed up until day 100 unless rejection occurred earlier. LEW blood, spleen, mesenteric node and bone marrow cells were stained with moAb OX27 specific for BN but not LEW. Genomic male DNA was isolated and amplified with SRY oligonucleotide. At day 30 and day 100 cellular microchimerism was detected in blood, spleen, nodes and bone marrow cells. Donor DNA was detected in recipient skin, liver and heart extracts, as well as lymphoid organs, at the time of rejection of allograft, but not when the rats were maintained on CsA. Taken together, donor DNAwas detected in recipient tissues at the time of heart or skin rejection. It appeared to be released from cells of rejecting grafts and not from "passenger" cells, representing only a minor cellular mass compared with the graft.

[Bone mineral density in children with end-stage renal disease]. / Badanie gestosci kosci u dzieci ze schylkowa niewydolnoscia nerek.

The aim of the study was to evaluate bone mineralisation in comparison to chronological age, bone age and high age in children with end-stage renal disease. Fourty-four patients (16 female, 28 male) aged 7-16 years were examined. DXA bone densitometry of total body, bone age evaluated by Greulich-Pyle method and high age were performed in all patients. In our patients bone, and high age were significantly decreased in comparison to chronological age. In contrast mean value of Z-score TG BMD bone and high age compared to mean value of Z-score TB BMD for chronological age were increased significantly. We conclude that bone mineralisation should be compared with or high age not to chronological age in patients with end-stage renal disease.

[Risk factors of adynamic bone disease in children with end-stage renal failure: personal experience]. / Czynniki ryzyka adynamicznej choroby kosci u dzieci ze schylkowa niewydolnoscia nerek--doswiadczenia wlasne.

The aim of the study was to estimate predisposing factors which can cause adynamic bone disease (ABD) and biochemical markers, bone densitometry results, bone histomorphometry in 17 children with this from of the renal osteodystrophy. Half of these of patients were treated with alphacalcidol pulses. In 47% of patients hypercalcemic episodes were noted, 76% had PTH level < 50 pg/ml. Four patients with osteoporosis (low bone volume at histological analysis) were distinguished. Two of them were treated with corticosteroids, 1 was immobilized for a long time.

[Bone metabolism markers and bone histomorphometry in children with chronic renal failure in predialysis period during growth hormone treatment]. / Markery metabolizmu kostnego u dzieci z przewlekla niewydolnoscia nerek leczonych hormonem wzrostu w okresie przeddializacyjnym.

The aim of the study was to estimate biochemical bone metabolism markers and bone histomorphometric parameters in children with chronic renal failure (CRF) treated with recombinant human growth hormone (rhGH). Twelve children with CRF aged 2-13.4 years were treated with rhGH 1-1.1 IU/kg per week and alfacalcidol. Bone biopsies were performed before and after 12 months of therapy. An increase in the biochemical markers of bone formation and bone resorption were noted. A statistically significant increase in mineral apposition rate (MAR) was observed in bone histomorphometry. The administration of active vitamin D metabolites enable proper bone mineralization in fast growing children with CRF during rhGH treatment.

[Effect of lipid lowering diet on serum lipids in peritoneal dialysis patients]. / Wplyw diety hipolipemizujacej na profil lipidowy surowicy chorych ze schylkowa niewydolnoscia nerek leczonych dializa otrzewnowa.

The aim of the study was to assess an effect of lipid lowering diet on serum lipids in peritoneal dialysis patients. Total cholesterol (TC) decreased after 3 months of low-fat diet from 203.7 mg/dl to 181 mg/dl, probably due to increased P/S ratio (PUFA/SFA) from 0.4 to 0.57. After another 3 months of the diet, a decrease in P/S ratio and concomitant increase in TC and LDL-C levels were found. Nutritional status of patients during lipid lowering diet was stable.

[CAPD treatment in children with renal amyloidosis]. / Leczenie dializa otrzewnowa dzieci z amyloidoza nerek.

The aim of the study was to summarize the experience in the treatment of chronic renal failure due to secondary amyloidosis in the course of juvenile rheumatoid arthritis. Fourteen children aged 7.5-17.7 years were treated with dialysis; 12 with CAPD, 2 with HD. Our results indicate that CAPD is a proper dialysis technique for children with amyloidosis, despite a high rate of complications in early period of CAPD, such as: bleeding, leaks, hernias, and impaired wound healing.

[Generalized tuberculosis as a cause of renal amyloidosis in a 9-year- old girl]. / Uogólniona gruzlica jako przyczyna wtórnej amyloidozy nerek u 9-letniej dziewczynki.

We present a case of a 9 years old girl with generalized tuberculosis diagnosed at the age of 5. Renal amyloidosis was diagnosed 21 months later. Clinically amyloidosis has been presented with steroid-resistant nephrotic syndrome, which within 15 months led to end stage renal failure. The girl is on automatic peritoneal dialysis with no signs of active tuberculosis up to now.

Bone biopsy results and serum bone turnover parameters in uremic children.

UNLABELLED: The aim of the study was to evaluate the prevalence of renal osteodystrophy types in children undergoing haemodialysis and continuous ambulatory peritoneal dialysis and to assess the usefulness of biochemical parameters in diagnosis of renal osteodystrophy. Bone biopsy and measurements of serum parathormone (iPTH) level, alkaline phosphatase (AP), osteocalcin (OC), procollagen 1C, calcium and phosphorus levels were performed in 51 children aged 11.5 +/- 2.9 y with end-stage renal failure. Renal osteodystrophy (ROD) was diagnosed as follows: adynamic bone disease (ABD) in 14 (27%); normal bone histology (NB) in 19 (37%), osteomalacia (OM) in 1 (2%), mixed lesion (Mix) in 5 (10%) and hyperparathyroidism (HP) in 12 (24%) children. There was no difference in prevalence of ROD types between children on CAPD and HD. We found significant differences in the mean value of iPTH, OC levels and AP activity in HP vs NB and HP vs ABD. The prevalence of ABD was significantly higher in patients with PTH below 50 pg/ml than in patients with PTH above 50 pg/ml (p < 0.05). In 69% of children with NB the iPTH level was between 50 and 150 pg/ml. Most HP cases (75%) were diagnosed in patients with iPTH above 200 pg/ml. A high correlation between BFR and iPTH, BFR and OC, AP levels was found. CONCLUSION: The biochemical markers of bone turnover have only limited value in the differentiation of renal osteodystrophy types.

Vitamin D metabolite requirements in dialysed children receiving recombinant human growth hormone.

BACKGROUND: The aim of the study was to assess the requirement of active vitamin D in dialysed children during treatment with recombinant human growth hormone (rhGH). METHODS: Twenty-six children (aged 5-15 years) were treated with rhGH for 6 months. The serum concentration of parathyroid hormone (PTH), alkaline phosphatase (AP), and calcium and phosphorus were measured in two groups of patients studied in the years 1994-1995 (group I) and 1995-1998 (group II) respectively. Group I received a constant dose of alfacalcidol that was sufficient to keep PTH below 200 pg/ml before rhGH treatment began. The serum PTH level was checked every 3 months. Alfacalcidol was administered to group II according to serum PTH levels checked on a monthly basis. RESULTS: In group I the PTH level increased after 3 and 6 months of rhGH treatment from mean level 73+/-60; 155+/-156 and 344+/-249 pg/ml respectively; P<0.05. AP activity increased after 6 months of treatment from 206+/-99 to 325+/-124 U/l respectively; P<0.01. The calcium level decreased from baseline after 3 months of treatment from 2.36+/-0.21 to 2.17+/-0.12 mmol/l respectively; P<0.05. In group II AP activity increased after 3 and 6 months of treatment from 272+/-169 to 332+/-192 and 404. 9+/-219.8 U/l respectively; P<0.01. The mean level of phosphorus decreased after 6 months from 2.15+/-0.28 to 1.70+/-0.39 mmol/l respectively; P<0.01. In group II the mean dose of alfacalcidol increased by 60.9%. CONCLUSIONS: In children with end-stage renal failure, higher doses of vitamin D are needed during rhGH treatment. During rhGH treatment, frequent control of serum PTH level is necessary.

DNA from rejecting allografts can be detected in recipient nonlymphoid tissues.

The main source of donor DNA in recipients of allograft are "passenger" cells. They are claimed to be responsible for the posttransplantation microchimerism and prolongation of allograft survival. We have noticed that beside of the cellular microchimerism, donor DNA can be found in the recipient tissues at the time of rejection of allograft. In this study we provide evidence for presence in the recipient of both, DNA in "passenger cells" and free DNA in tissues at terminal stage of rejection. Male BN (RTIn) rat heart or skin were transplanted to female LEW (RTII) rats followed by a vascularized bone marrow in hind-limb transplant. CsA was given in a dose of 17mg/kg b.w. for 30 days, then rats were followed until day 100 unless rejection occurred earlier. LEW blood, spleen, mesenteric node and bone marrow cells were stained with moAb OX27 specific for BN but not LEW. Genomic male DNA was isolated and amplified with SRY oligonucleotide. At day 30 and 100 cellular microchimerism was detected in blood, spleen, nodes and bone marrow cells. Donor DNA was detected in recipient skin, liver and heart extracts, beside of lymphoid organs, at the time of rejection of allograft but not when rats were maintained on CsA. Taken together, donor DNA can be detected in recipient tissues at the time of heart or skin rejection. It seems to be released from cells of rejecting grafts and not from "passenger" cells representing only a minor cellular mass compared with the graft.

Microchimerism following allogeneic vascularized bone marrow transplantation--its possible role in induction of posttransplantation tolerance.

We have noticed that bone marrow transplanted in a vascularized limb graft providing a continuous supply of donor BMC may prolong the survival time of skin graft from the same donor. The question arises whether the raised microchimerism plays a role in the prolonged survival of skin allograft. The aim of the study was to follow the development of microchimerism after allogeneic vascularized bone marrow transplantation (VBMTx) concomitantly with the rejection processes of transplanted skin. The BN rats served as donors and LEW rats as recipients of VBMTx and free skin flap allograft. Hind limb was transplanted followed by a full-thickness skin graft on the dorsum. Cellular microchimerism was investigated in recipients of VBMTx and skin grafts in blood, spleen, mesenteric lymph node and bone marrow with monoclonal antibody OX27 directed against MHC class I polymorthic RTI on BN cells and quantitatively analysed in FACStar. In VBMTx group free skin flap survived 70 days after weaning of CsA. Intravenous infusion of BMC in suspension equivalent to that grafted in hind limb did not prolong skin graft survival after cessation of CsA therapy. Donor-derived cells could be detected in VBMTx recipients as long 70 days after wearing of CsA but not in recipients of i.v. suspension BMC grafting.

Tolerance induction following allogeneic vascularized bone marrow transplantation--the possible role of microchimerism.

We have noticed that bone marrow transplanted in a vascularized limb graft, providing a continuous supply of donor bone marrow cells (BMC), may prolong the survival time of a skin graft from the same donor. The question arises whether the microchimerism raised plays a role in the prolonged survival of skin allografts. The aim of the study was to follow the development of microchimerism after allogeneic vascularized bone marrow transplantation (VBMTx) concomitantly with the rejection process of transplanted skin. Brown Norway (BN) rats served as donors and Lewis rats as recipients of VBMTx and free skin flap allografts. A hind limb was transplanted, followed by a full-thickness skin graft on the dorsum. Cellular microchimerism was investigated in recipients of VBMTx and skin grafts in blood, spleen, mesenteric lymph node, and bone marrow with the monoclonal antibody OX27 directed against MHC class I polymorphic RT1 on BN cells and quantitatively analyzed in a FACStar. In the VBMTx group, the free skin flap survived 70 days after weaning off cyclosporine A (CsA). An intravenous infusion of BMC in suspension equivalent to that grafted in the hind limb did not prolong skin graft survival after cessation of CsA therapy. Donor-derived cells could be detected in VBMTx recipients as long 70 days after weaning off CsA but not in recipients of i.v. suspension BMC grafting.

The influence of growth hormone treatment on bone metabolism in dialysis patients.

Bone formation markers, PTH intact, and bone mineral density were evaluated in 12 children with end stage renal disease during recombinant human growth hormone (rhGH) treatment. Bone biopsies before rhGH therapy revealed: osteitis fibrosa in one patient, mild lesions in eight, adynamic bone disease in one, and a normal histology in two. PTH intact increased after six months of rhGH in seven children, and was significantly higher in them than in the control group. A positive correlation between PICP concentration after one month and growth velocity within 12 months of rhGH was found. Higher doses of vitamin D are needed in growing children treated with rhGH.

[The effect of decreasing serum calcium in serum during hemodialysis on PTH levels in children with end stage renal disease]. / Wplyw obnizenia stezenia wapnia w surowicy podczas hemodializy na poziom PTH intact u dzieci ze schylkowa niewydolnoscia nerek.

The aim of our study was to evaluate serum Ca and PTH intact levels in children during one hemodialysis session using a low calcium level dialysate (1.25 mEq/l). The study was performed in 6 children with end-stage renal disease. We analysed the parameters of calcium-phosphorus metabolism in children 18 months before the test. In 5 of children the increase of PTH level during hemodialysis was lower than in healthy people. In 3 patients with hyperparathyroidism the basal PTH (PTHb) level before the test was high and increased by 45%, 67% and 118% during hypocalcemic stimulation. In 2 patients suppression of parathyroid function was diagnosed due to low serum PTHb level and small increase during hypocalcemic stimulation. Despite low basal PTH level, one of the patients respond to hypocalcemic stimulation like healthy subjects. Dynamic monitoring of the PTH level during hypocalcemic stimulation is a very useful method of estimation parathyroid gland function and adjusting doses of vitamin D metabolites.

[Correlation between osteocalcin and bone histomorphometry in children with chronic renal failure]. / Zaleznosc miedzy osteokalcyna a wskaznikami histomorfometrycznymi kosci u dzieci z przewlekla niewydolnoscia nerek.

The study was performed in 17 children with chronic renal failure, 7 were on hemodialysis, 6 on continuous ambulatory peritoneal dialysis, 4 were treated conservatively. In all, serum levels of alkaline phosphatase, PTH intact and osteocalcin were measured and bone biopsy was performed. We analyzed correlations between biochemical markers of bone metabolism and histomorphometric parameters. The lowest mean serum osteocalcin levels were found in children with adynamic bone disease, the highest with osteitis fibrosa. The serum osteocalcin level was significantly correlated with the dynamic parameter of bone formation rate (BFR), which suggests that this biochemical marker can be of use in discriminating between renal osteopathy with low and high bone turnover. Lack of correlation between serum osteocalcin level and mineralizing surface confirms it significance as a good marker of osteoblastic activity in bone formation but not in bone mineralization.

[Long-term efficacy of hepatitis B vaccine in children with chronic renal failure]. / Odlegle wyniki szczepien przeciw wirusowemu zapaleniu watroby typu B u dzieci z przewlekla niewydolnoscia nerek.

The aim of the study was to determine the duration of post vaccination immunity and antibody persistence in children in different stages of chronic renal failure. The study was performed in 25 children and time of observation was 12-36 months. After completing vaccination seroprotection rate was 92% in non-dialysed children and 77% in dialysed. After 36 months of observation seroprotection was found in 90% of patients, none of them was infected by HBV. We conclude that in case of decrease in antibody titer below 100 mIU/ml the booster dose of vaccine is indicated.

Prolongation of heart graft survival and spleen suppressor cell activity after donor specific blood transfusions in rats differing across the MHC.

The aim of the study was the prolongation of heart allograft survival in rats after DST (donor specific blood transfusion), the characterization of T and B lymphocyte phenotypes in peripheral blood, spleen and lymph nodes and the evaluation of specific and nonspecific suppressor cell activity of spleen and blood lymphocytes of DST rats. Pretreatment of Wistar recipients with one, two and three doses of DST-s prolonged the heterotopic August graft survival to 11.0, 12.3 and 11.4 days, respectively (rats differed across the MHC). Spleen lymphocytes of transfused rats showed significant nonspecific suppressive activity in culture with syngeneic spleen lymphocytes of nontransfused rats stimulated with PHA, but not in culture with blood lymphocytes. Blood lymphocytes of transfused rats did not show any nonspecific suppressive activity. Spleen and blood lymphocytes of transfused rats did not demonstrate any specific suppressive activity in allogeneic MLC. The ratio of W3/25+/OX8+ (Th+/Tsup/cyt+) cells in peripheral blood was found increased in DST rats due to the decrease in the percentage of OX8+ cells whereas the opposite effect was observed with spleen cells (increase in the percentage of OX8+ cells after one DST). The number of OX6+ (Ia positive) cells and B cells in all transfused rats was found unchanged comparing with untreated animals.