Efficacy of corticosteroids in prevention of acute kidney injury in neonates undergoing cardiac surgery-A randomized controlled trial.

BACKGROUND: Heart surgery requiring cardiopulmonary bypass (CPB) causes an inflammatory response which may further induce acute kidney injury (AKI). In the present randomized controlled study we evaluated whether corticosteroids can prevent CPB related AKI in neonates undergoing heart surgery. METHODS: Forty neonates were randomized to receive 2 mg/kg methylprednisolone followed by hydrocortisone infusion 0.2 mg/kg/h perioperatively with tapering doses for 5 days, or placebo administered in a similar fashion. The primary outcome was the inflammatory response (plasma concentrations of interleukins 6 and 10). The correspondence of the interleukin concentrations with AKI was analysed as secondary outcome. In addition, plasma and urine neutrophil gelatinase-associated lipocalin (NGAL), plasma cystatin C, and urine kidney injury molecule-1 (KIM-1) levels were measured. RESULTS: Six patients (15%) developed post-operative AKI. No significant difference in the AKI occurrence between the treatment (n = 2) and the placebo (n = 4) groups could be found (risk ratio 2.00, 95% confidence interval 0.41-9.71; P = .661) despite significant reduction in inflammatory response in the treatment group. One patient in the treatment group and two patients in the placebo group required acute peritoneal dialysis. Plasma creatinine and cystatin C or urine NGAL and KIM-1 concentrations did not differ between the treatment and the placebo group. CONCLUSIONS: Significantly reduced inflammatory reaction induced by corticosteroid treatment in neonates undergoing cardiac surgery did not reduce the incidence of AKI defined by KDIGO classification or decrease the rise of AKI biomarkers.

Human leucocyte antigens B*08, DRB1*03 and DRB1*13 are significantly associated with autoimmune liver and biliary diseases in Finnish children.

AIM: The human leucocyte antigen (HLA) allele and haplotype frequencies of the Finnish population are unique because of the restricted and homogenous gene population. There are no published data on HLA genotype associations in paediatric autoimmune liver diseases in Scandinavia. This study characterised the HLA genotypes of children with autoimmune liver or biliary disease in Finland. METHODS: The study cohort comprised 19 paediatric patients (13 female) aged three years to 15 years treated for autoimmune liver or biliary disease at the Children's Hospital, Helsinki University Hospital, between 2000 and 2011, and followed up for four years and three months to 14.6 years. We genotyped HLA-B and HLA-DRB1 in the children, and the HLA antigen frequencies were compared with 19 807 records from the Finnish Bone Marrow Donor Registry. RESULTS: All paediatric patients with autoimmune liver or biliary disease had either autoimmune HLA haplotype B*08;DRB1*03 or DRB1*13. These were significantly more common among patients with autoimmune hepatitis, primary sclerosing cholangitis and autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome than the Finnish control population. HLA RB1*04 was not found in the study cohort. CONCLUSION: Our study found that B*08, DRB1*03 and DRB1*13 were significantly associated with autoimmune liver and biliary diseases in Finnish paediatric patients.

A case of primary JC polyomavirus infection-associated nephropathy.

A 15-year-old boy with a posterior urethral valve received a deceased donor kidney transplant (KT) in March 2011. Basiliximab induction followed by tacrolimus-based triple medication was used as immunosuppression. Eleven months after KT, the graft function deteriorated and the biopsy demonstrated interstitial nephritis suggestive of acute rejection. BK polyomavirus (BKPyV) surveillance in urine and plasma was negative. The patient received methylprednisolone pulses and anti-thymocyte globulin. Immunohistochemistry was positive for simian virus 40 (SV40) large T-antigen (LTag) in the biopsies, and quantitative polymerase chain reaction for JC polyomavirus (JCPyV) indicated high viral loads in urine and borderline levels in plasma. Immunosuppression was reduced and follow-up biopsies showed tubular atrophy and interstitial fibrosis. Two years after KT, antibody-mediated rejection resulted in graft loss and return to hemodialysis. Retrospective serologic work-up indicated a primary JCPyV infection with seroconversion first for IgM, followed by IgG, but no indication of BKPyV infection. In the SV40 LTag positive biopsies, JCPyV deoxyribonucleic acid (DNA) with archetype noncoding control region was detected, while BKPyV DNA was undetectable. To the best of our knowledge, this is the first reported case of primary JCPyV infection as the cause of PyV-associated nephropathy in KT.

General health, health-related quality of life and sexual health after pediatric liver transplantation: a nationwide study.

The long-term impact of pediatric liver transplantation (LT) and its complications on general health, health-related quality of life (HRQoL) and sexual health were assessed. We conducted a national cross-sectional study of all pediatric recipients who underwent LT between 1987 and 2007. Of 66 survivors, 57 participants (86%) were compared to randomly chosen healthy controls (n = 141) at 10.7 ± 6.6 years posttransplant. PedsQL4.0, SF-36, DISF-SR and AUDIT questionnaires for appropriate age groups were used. Patients and controls <7 years had similar HRQoL and 54% of patients aged over 7 scored within the controls' normal range on all HRQoL domains. In adult survivors, physical functioning and general health were decreased (p < 0.05). Biliary complications, reoperations and obesity were independently associated with reduced HRQoL (p < 0.05 for all). Still 64% of adult survivors considered their health excellent. Sexual health was similar to controls but LT recipients may experience problems with their orgasm strength (p = 0.050) and condom-based contraception was more common after LT than among controls (58% and 12%, p < 0.001). In conclusion, normal HRQoL and sexual health are achievable post-LT.

Cholesterol metabolism altered and FGF21 levels high after pediatric liver transplantation despite normal serum lipids.

Liver transplantation (LT) predisposes to metabolic derangements and increases the risk for cardiovascular disease. We conducted a national cross-sectional study of all pediatric recipients who underwent LT between 1987 and 2007. We measured serum levels of noncholesterol sterols (surrogate markers of cholesterol synthesis and intestinal absorption) and fibroblast growth factor 21 (FGF21) in 49 patients (74% of survivors) at a median of 10 years posttransplant and in 93 controls matched for age and gender. Although serum cholesterol levels were similar in patients and controls, patients displayed increased whole-body synthesis and decreased intestinal absorption of cholesterol compared with controls (lathosterol to cholesterol ratio 129 ± 55 vs. 96 ± 41, respectively, p < 0.001; campesterol to cholesterol ratio 233 ± 91 vs. 316 ± 107, respectively; p < 0.001). Azathioprine (r =-0.383, p = 0.007) and low-dose methylpredisolone (r =-0.492, p < 0.001) were negatively associated with lathosterol/sitosterol ratio reflecting a favorable effect on cholesterol metabolism. FGF21 levels were higher in patients than in controls (248 pg/mL vs. 77 pg/mL, p < 0.001). In healthy controls, FGF21 was associated with cholesterol metabolism, an association missing in LT recipients. Normal serum lipids are achievable in long-term survivors of pediatric LT, but changes in cholesterol metabolism and increased FGF21 levels may explicate later cardiovascular risk.

Antigenic differences in nuclear proteins of normal liver and hepatoma. Identification of a nuclear protein present in hepatocytes but absent in hepatoma cells.

A nuclear antigen was detected in the mouse liver nonhistone protein fraction by using antibodies to whole liver cells. The antigen was purified to homogeneity from perchloric acid extracts of liver tissue. It gave a single band corresponding to tool wt 21,000 in sodium dodecyl sulfate gel electrophoresis. Amino acid and carbohydrate analysis showed predominance of the acidic amino acids, lack of proline, and absence of carbohydrate. Immunofluorescence staining of liver sections confirmed the nuclear localization of the antigen. Its tissue distribution was studied by using radioimmunoassay. Of the various tissues extracted for analysis, the liver contained the highest amounts of the antigen, about 1 mug/mg of solubilized liver protein. Other tissues examined showed 2-4 percent of the amount of antigen present in the liver. Two transplantable hepatomas in C3H/HeJ and C57L/J mice, respectively, and three spontaneous C3H hepatomas showed greatly decreased levels of the antigen compared to normal liver. The amount of antigen in hepatomas varied from nondetectable to 2 percent of the amount of antigen found in the livers of the mice. The antigen was also found in the blood. The antigen was found in high concentrations (up to 13 mg/ml) in the urine of normal mice. This suggests identity with the previously known mouse urinary protein (MUP). In addition to the extremely high urinary output, the properties found to be shared by MUP and the nuclear antigen included similar serum concentrations (2-60 mug/ml), a sex difference with lower values in females, same molecular size as determined by gel filtration, and immunological identity. The nuclear localization of MUP and its disappearance from hepatomas suggest that it may have an important regulatory function.

Impaired bone health in adolescents after liver transplantation.

Long-term complications related to immunosuppressive medication are an important problem after liver transplantation (OLT). This study was carried out to evaluate the bone health and risk factors for osteoporosis and fractures in 40 pediatric liver transplant recipients. The results of 208 longitudinal bone mineral density (BMD) measurements were analyzed retrospectively. In addition, a dual-energy X-ray absorptiometry was performed to assess the bone mineral content more precisely and to detect subclinical vertebral fractures (VF). The median age of the patients was 14 years and mean postoperative follow-up 7.0 years. The results showed that over half (58%) had lumbar spine (LS) Z-score

Successful liver-kidney transplantation in two children with aHUS caused by a mutation in complement factor H.

A 12-month-old boy and his 16-year-old aunt became acutely ill 6 months apart and were diagnosed to have atypical hemolytic uremic syndrome (aHUS). Genetic analysis revealed heterozygous R1215Q mutation in complement factor H (CFH) in both patients. The same mutation was found in five healthy adult relatives indicating incomplete penetrance of the disease. The patients developed terminal renal failure and experienced reversible neurological symptoms in spite of plasma exchange (PE) therapy. In both cases, liver-kidney transplantation was successfully performed 6 months after the onset of the disease. To minimize complement activation and prevent thrombotic microangiopathy or overt thrombotic events due to the malfunctioning CFH, extensive PE with fresh frozen plasma was performed pre- and perioperatively and anticoagulation was started a few hours after the operation. No circulatory complications appeared and all four grafts started to function immediately. Also, no recurrence or other major clinical setbacks have appeared during the postoperative follow-up (15 and 9 months) and the grafts show excellent function. While more experience is needed, it seems that liver-kidney transplantation combined with pre- and perioperative PE is a rational option in the management of patients with aHUS caused by CFH mutation.

Effect of specific immunotherapy with preimmunization against alpha-fetoprotein on a mouse transplantable hepatoma.

Antibodies to autologous alpha-fetoprotein (AFP) were produced in mice by immunization with rat AFP. C57L/J mice with or without such antibodies were inoculated sc or ip with controlled numbers of cells of the syngeneic, AFP-producing, BW 7756 hepatoma. There was a linear relationship between circulating AFP and tumor mass, with elevated AFP being detectable earlier than the tumor. The AFP levels of the immunized mice were generally lower than those of control mice, and tumors could be detected before elevated concentrations of AFP appeared in the circulation. An extensive series of transplantations with varying protocols for immunization did not protect against tumor and did not affect the rate of tumor growth.

Differential expression of alpha-fetoprotein and gamma-glutamyltranspeptidase in chemical and spontaneous hepatocarcinogenesis.

The expression of two markers of fetal liver, alpha-fetoprotein (AFP) and gamma-glutamyltranspeptidase (GGT), was studied in chemical and spontaneous hepatocarcinogenesis in mice. Serum AFP concentration increased within 3 weeks 3 weeks from the commencement of feeding of o-aminoazotuluene. This early elevation subsided about 3 months after the beginning of the administration of the carcinogen. A new, sustained elevation of the serum AFP level followed at 5 to 6 months accompanied by the appearance of liver tumors. In immunofluorescence, some small oval cells and scattered adult-type hepatocytes contained AFP during the early stage of chemical carcinogenesis. During the later phase, AFP was detected in a few of the nodular areas, in solitary hepatocytes, and in groups of carcinoma cells. GGT activity in the liver increased within 1 week after the carcinogen regimen was started, preceding the early increase of AFP production. At the final stage, the chemically induced hepatomas contained about 80 times more GGT than did normal liver. In histochemical staining, proliferating oval cells and small areas of hepatocytes stained for GGT during the early weeks, and later most nodules, small areas of nonnodular parenchyma, and carcinomas contained GGT. During spontaneous carcinogenesis in male C3HeB/FeJ mice, premalignant lesions, accompanied by a slight increase of serum AFP, precede the appearance of liver tumors. No cells staining for AFP were detected during this early stage. Once overt liver cancers had developed, AFP was readily detectable in the tumors and was localized to some but not all carcinoma cells. The corresponding serum AFP levels were highly elevated. In contrast to the high levels of GGT found during chemical carcinogenesis, no elevation of GGT was found in livers at various stages of spontaneous carcinogenesis, including cancers in eight individual mice. These results indicate that the production of AFP and GGT is not turned on as a single "genetic package," and that these two markers differ in their behaviour in liver carcinogenesis.

Mulibrey nanism: clinical features and diagnostic criteria.

Mulibrey nanism (MUL) is an autosomal recessive disease caused by mutations in the TRIM37 gene encoding the peroxisomal TRIM37 protein of unknown function. In this work, we analysed the clinical characteristics of 85 Finnish patients with MUL, most of whom were homozygous for the Finn major mutation of TRIM37. The patients' hospital records from birth to the time of the diagnosis at age 0.02-52 years (median 2.1 years) were retrospectively analysed. All except four of the patients (95%) had a prenatal onset growth failure without postnatal catch up growth. The mean length standard deviation score (SDS) was -3.1 and -4.0 at birth and at diagnosis, respectively. In infancy, feeding difficulties, and respiratory tract infections were the most common problems. Congestive heart failure and pericardial constriction were diagnosed during infancy in 12% and 6% of the patients, respectively. At the time of the diagnosis, characteristic craniofacial features of scaphocephaly, facial triangularity, high and broad forehead, and low nasal bridge were evident in over 90% of the patients. In addition, practically all patients were gracile and had thin extremities. Other findings included a peculiar high-pitched voice (96%), yellowish dots in ocular fundi (79%), cutaneous naevi flammei (65%), hepatomegaly (45%), and fibrous dysplasia of long bones (25%). Mild muscular hypotonicity (68%) was the only neurological abnormality. The clinical features of the Finnish patients with MUL formed a distinct entity. The most consistent findings were growth failure and characteristic craniofacial features. However, organ manifestations varied considerably in early childhood. Based on these findings, we propose new diagnostic criteria for MUL.

Human polyoma virus in kidney transplants: SV40 T-antigen demonstration in the urine.

We wanted to develop an immunostaining method of urine cytopreparations to detect polyoma virus infection by using fresh urine samples and staining with the monoclonal SV40 antibody and to compare the findings to the demonstration of decoy cells in the urine or to kidney histology. Routine urine samples from pediatric kidney transplant patients were collected either early after transplantation or later, cytocentrifuged, and immunostained with SV40-T-antibody. The number of SV40-T-antigen-positive epithelial cells was counted in the cytopreparations and compared to the findings in routine urine cytology and transplant histology. Immunostaining of urine cytology with SV40-T-ab demonstrated clearly that the infected epithelial cells and the rate of infection could be estimated by semiquantitative counting. There was strong correlation between the findings in the urine and in the biopsies, but in the urine preparations the number of infected cells was much higher than in the biopsies. The high number of SV40-positive cells in the urine also correlated to the severity of clinical infection and to the state of transplant. Immunostaining of urine cytology with SV40-T-antibody seems to be useful in the diagnosis and follow-up of polyoma virus reactivation disease in transplant patients, especially in children with renal transplants.

Pregnancy-specific beta 1-glycoprotein and chorionic gonadotropin-like immunoreactivity during the latter half of the cycle in women using intrauterine contraception.

In a cross-sectional study, the serum levels of pregnancy-specific beta 1-glycoprotein (PSBG), hCG, human LH, and progesterone were measured by RIAs during 94 mid or late luteal phases of 69 women using oral contraceptives. Subsequent spontaneous menstruation took place in every cycle. None of the women using oral contraceptives had any PSBG or hCG-like immunoreactivity in serum. In women with intrauterine devices, PSBG was found in six cycles (6.4%) and hCG-like immunoreactivity was demonstrated in one cycle only, where PSBG also was present. In two out of six PSBG-positive cycles, menstruation was delayed by 5 and 16 days. Although rare, the transient occurrence of trophoblastic antigens in women using intrauterine contraception is taken as evidence for an occult pregnancy in these apparently infertile cycles.

PIP: Serum levels of pregnancy-specific beta-1-glycoprotein (PSBG), human chorionic gonadotropin (hCG), human luteinizing hormone (LH), and progesterone were measured by radioimmunoassays during 94 mid- or late luteal phases of 69 women using IUDs and 34 women using oral contraceptives (OCs) in a cross-sectional study. hCG-like immunoreactivity was found in 1 of 94 cycles (1.1%) of women using IUD contraception, and in none of those taking OCs. The positive hCG reaction was found on Day 27 of the cycle. In the hCG-positive sample, hCG concentration was 19 mIU/ml. Cross-reaction by LH was unlikely since the LH concentration was 82 ng/ml, well below the cross-reacting level of the assay. PSBG was found in 6 of 94 cycles (6.4%) of IUD users, and in none of OC users. Levels varied from 11-21 ng/ml, and PSBG was found on Days 24-27 of the cycle. 1 cycle demonstrated both hCG and PSBG, and the PSBG concentration was 15 ng/ml. In trophoblastic antigen-positive IUD cycles, menstruation was delayed from the expected date by 3 or more days in 2 cases. In the case where both markers were found, menstruation was delayed by 16 days. Aside from menstrual delay in 2 subjects, no typical changes were noted in the bleeding pattern of those cycles where trophoblast-specific antigens were detected. Although rare, the transient occurrence of trophoblastic antigens in women using IUDs was taken as evidence for occult pregnancy in these apparently infertile cycles.

Comparison of conventional oral cyclosporine and cyclosporine microemulsion formulations in children with a liver transplant.

We studied 22 children (mean age: 8.42 years, range: 1.9-15.6 years) with a liver transplant to compare the pharmacokinetics of oral cyclosporine (CsA) microemulsion to the conventional formulation. The CsA treatment (mean dose: 5.9 mg/kg/day, range: 3.0-11.7 mg/kg/day) was converted 1:1 on a milligram-to-milligram basis to the microemulsion formulation. Five days after the conversion, the mean peak blood CsA concentration was higher (microemulsion: 963 ng/ml, range: 518-1864 ng/ml; conventional: 431 ng/ml, range: 98-888 ng/ml; P<0.0001) and it was reached faster (median time of peak concentration: 1.6 hr vs. 2.9 hr, range: 1.0-3.0 hr vs. 1.9-4.0 hr; P=0.0009). The absorption lasted on the average 19% longer after the conventional formulation. The area under the concentration versus time curve (AUC) was larger after the microemulsion formulation in all but one patient (P=0.001) by a mean factor of 1.80 (range: 0.72-3.04). The trough CsA level after the microemulsion formulation was more closely related to peak concentration (r2=0.86 vs. 0.45) and AUC (r2=0.84 vs. 0.47); thus, therapeutic drug monitoring may be more useful. After 6 months on the new formulation, the results for the whole group were similar, but in five children the AUC was comparable to the AUC obtained with the conventional formulation. No rejections occurred, and the liver and kidney functions remained unchanged. A 1:1 conversion can be safely performed in children, based on a 6-month follow-up. However, the total drug exposure changes in significant ways, which, on a long-term basis, may improve the immunosuppression in an underimmunosuppressed patient, but may increase the risk for dose-related adverse effects in others.

Infections in pediatric kidney and liver transplant patients after perioperative hospitalization.

BACKGROUND: Infectious complications are a major cause of morbidity and mortality after organ transplantation. There are several reports on infections during the first months after transplantation, but there are very few data regarding infections in long-term survivors of pediatric organ transplantation. METHODS: The incidence and type of infections were retrospectively analyzed in 56 children who underwent 59 liver or renal transplantations. Follow-up was begun when the patient was sent home after a successful operation. All of the children received triple immunosuppression. RESULTS: During a mean follow-up of 4.8 years (total, 286 patient years), 1540 episodes of infection were recorded. The median incidence was 4.8 episodes/patient year. The greatest number was seen in the smallest children, 3 to 6 months after transplantation. Viral upper respiratory tract infections were the most common problem, accounting for half of the episodes (2.7 episodes/patient year). Gastroenteritis was the second most common viral infection. Only 45 episodes of infection with herpesviruses were recorded, and seven of those were caused by cytomegalovirus. Otitis media and sinusitis were the most common bacterial infections and complicated upper respiratory infection in 23% of episodes. Thirty-nine episodes of urinary tract infections were diagnosed, thirty-one in children with renal transplants. Other bacterial infections were rare, and only three episodes of verified bacterial sepsis were diagnosed. CONCLUSION: The frequency and type of infections in children with liver and renal transplants who are on triple immunosuppression are quite similar to those in age-matched healthy children.

Kidney function after 1:1 conversion to the cyclosporine microemulsion formulation in children with liver allografts.

BACKGROUND: One-to-one (mg:mg) conversion from the conventional to the microemulsion formulation of cyclosporine (CsA) is advocated as a simple way to use the new therapeutic regimen. However, the potentially harmful effects of the conversion on kidney function in nonrenal transplant recipients are poorly known. METHODS: Renal effects of the conversion were prospectively investigated in 22 pediatric liver transplant recipients (mean age, 8.4 years; mean time from transplantation, 3.2 years). Patients were followed for 12 months. Pharmacokinetic studies were performed at baseline and 5 days and 6 and 12 months after conversion. RESULTS: Peak concentration, minimum concentration, average steady state concentration, and area under the concentration-versus-time curve increased by 60-130% after conversion. Graft losses, progressive deterioration of graft function, and acute rejection episodes did not occur. The mean glomerular filtration rate (GFR) was 103 ml/min/1.73 m2 at baseline and 100 ml/min/1.73 m2 after 12 months. However, 6 of the 22 patients showed at least a 15% (range, 16-38%) decrease in GFR between baseline and 6 months (P<0.01). They had a significantly higher increase in average steady state concentration between baseline and 6 months than the six patients with the best outcome in GFR during the same time period (164 ng/ml vs. 53 ng/ml, P<0.05). At this point (6 months), target CsA trough levels were reduced by 20-30%, while the mean area under the concentration-versus-time curve remained above that obtained at baseline. The GFR of three of the six patients subsequently improved. CONCLUSIONS: One-to-one conversion can be performed safely in liver transplant recipients if strict follow-up is feasible.

Liposomal amphotericin B prevents invasive fungal infections in liver transplant recipients. A randomized, placebo-controlled study.

Eighty-six consecutive liver transplant recipients were prospectively randomized in a double-blind, placebo-controlled antifungal prophylaxis study. Seventy-seven patients received 5 days of prophylaxis starting during the transplantation with either liposomal amphotericin B (AmBisome) 1 mg/kg/day or placebo. Among 40 AmBisome-treated patients, no invasive Candida infection was seen during the first month, compared with 5 invasive Candida albicans infections among 37 control patients (P < 0.05). Furthermore, 1 placebo patient experienced Aspergillus niger pneumonia. Thus, the overall incidence of invasive fungal infections was 0/40 (0%) in the AmBisome group versus 6/37 (16%) in the placebo group (P < 0.01). Patient survival at 30 days was 92% versus 94% for AmBisome- and placebo-treated patients, respectively. One patient experienced backache related to AmBisome infusion. Two patients had transient thrombocytopenia possibly caused by AmBisome treatment. AmBisome was otherwise well tolerated. The total cost for all antifungal drugs used in both groups was equal. However, prophylaxis with AmBisome was $5000 less expensive than treatment of proven invasive fungal infections among placebo patients.

Graft function 5-7 years after renal transplantation in early childhood.

BACKGROUND: Low recipient age is still a risk factor for graft failure after kidney transplantation (Tx). Detailed prospective reports on long-term graft function in small children after renal Tx are still lacking. METHODS: Forty-nine kidney allograft recipients who received transplants before the age of 5 years were followed prospectively. The most common disease was congenital nephrotic syndrome of the Finnish type. Twenty patients were recipients of living related donors (LRD), and 29 were cadaveric kidney (CAD) recipients. All patients received triple immunosuppression. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), sodium, urate, and potassium handling, and concentrating capacity were studied for up to 7 years after Tx. RESULTS: Patient survival 7 years after Tx was 100% for LRD and 96% for CAD recipients. Graft survival was 94% for LRD and 79% for CAD recipients (P=NS) and 89% and 83% for children >2 years and <2 years of age at Tx, respectively (P=NS). Five years after Tx, GFR was 70 vs. 64 and ERPF was 380 vs. 310 ml/min/1.73 m2 for LRD and CAD recipients, respectively (P=NS). Mean absolute GFR remained stable. GFR was lower in children who received transplants at <2 years than in children who received transplants at >2 years of age, 54 vs. 75 ml/min/1.73 m2 (P=0.02). Sodium handling remained intact, but hyperuricemia was seen in 43-67%; 17-33% showed abnormal handling of potassium; and most patients had a subnormal concentrating capacity. CONCLUSIONS: Excellent long-term graft survival and good graft function can be achieved with triple immunosuppression, even in young CAD kidney recipients.

Recombinant human growth hormone treatment. Its effect on renal allograft function and histology.

Our objective was to investigate the effects of recombinant human growth hormone (rhGH) treatment on long-term renal allograft function and histopathology. RhGH is a potent therapy for poor growth after renal transplantation. However, rhGH has proinflammatory properties and may induce acute rejection or accelerate chronic rejection. Nine prepubertal rhGH-treated renal transplanted children and nine pair-matched controls were studied 18 (before the start of rhGH) and 36 months after transplantation (mean duration of rhGH-treatment 14 months). 51Cr-EDTA- and PAH-clearances were performed. A protocol renal biopsy was done at 36 months. Growth showed significant improvement during rhGH (P<0.01). One graft loss occurred in both groups. One acute rejection was seen in the control group. There was no difference in the rate pf change in 51Cr-EDTA-or PAH-clearance between the two groups. Histopathological findings were mostly mild. One new onset chronic rejection developed in both groups. Proximal tubular atrophy was more extensive in the rhGH-treated patients (P<0.05), but there was no uniform trend toward more severe findings. RhGH improved growth, and no significant differences were seen in allograft function or histopathology; however, larger trials controlled for pretreatment renal function and immunosuppression are needed.

Fine-needle aspiration biopsy allows early detection of acute rejection in children after renal transplantation.

UNLABELLED: analysis detected rejections often before clinical signs. Half of the patients had increased serum creatinine concentration and 38% had fever at the time of rejection diagnosis. Both signs were present in only 19% of the episodes. A decrease in urine output (>20%) was seen in a third of the episodes. The rejections responded well to oral methylprednisolone (3 mg/kg/day), and lymphoglobulins were needed in only 12% of the episodes. More than 90% of the rejections were completely reversible and no transplant was lost because of acute rejection. CONCLUSION: The results indicate that FNAB is a safe and sensitive method for the diagnosis and follow-up of acute cellular rejection in pediatric recipients of different ages.