Post-transplant diabetes mellitus in children following renal transplantation.

PTDM plays a role in chronic allograft nephropathy and decreases graft and patient survival. Considering the serious outcome of chronic hyperglycemia, the importance of early recognition and the few data in children, in this retrospective analysis we studied the characteristics and risk factors of PTDM in 45 pediatric renal transplant recipients receiving Tac or CyA-based immunosuppression. Fasting blood sampling and OGTT were performed. PTDM has been developed in six patients (13%), while seven children (16%) had IGT, with the overall incidence of a glucose metabolic disorder of 29% in pediatric renal transplants. Patients in the PTDM + IGT group were younger and had higher systolic blood pressure and serum triglyceride level than children with normal glucose tolerance. Multivariate analysis identified Tac treatment, Tac trough level, steroid pulse therapy and family history of diabetes to be associated with the onset of PTDM. In pediatric renal transplants, OGTT and frequent assessment of blood glucose levels might be essential not only in the post-transplant management, but also prior to transplantation, particularly with family history of diabetes. Careful monitoring and modified protocols help to minimize the side effects of Tac and corticosteroids.

In vitro effect of human recombinant growth hormone on lymphocyte and granulocyte function of healthy and uremic children.

The recombinant human growth hormone (rhGH), currently used in supraphysiological doses to promote growth acceleration in chronic renal failure children (CRF), also has the ability to influence their impaired immune functions. The effect of human growth hormone on the lymphoproliferative response in vitro was analyzed in the peripheral blood lymphocytes of 25 healthy and 11 uremic children. In 72% of the uremic cases and in 60% of the healthy individual children the hormone increased the lymphoproliferation alone, and/or when used in combination with phytohaemagglutinine. The range of the effective hormone concentrations differed individually. Using semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) a great variation in the gene expression of growth hormone- (GH)-receptor in peripheral lymphocytes was detected. The respiratory burst activity of peripheral polymorphonuclear leukocytes (PMN) in vitro, in response to GH alone and when combined with suboptimal dose of phorbolester (PMA), was assessed by measuring luminol enhanced chemiluminescence in ten uremic and 18 healthy children. In six out of the ten of the CRF patients and in eight out of 18 of the healthy children the GH enhanced the oxidative burst activity of granulocytes provoked by a suboptimal dose of PMA. However, the effective doses (10, 50 and 300 ng/ml) and incubation times (0, 45 and 90 min) showed individual variations. Our data suggest that rhGH treatment in uremic children could be advantageous considering this population's enhanced susceptibility to bacterial, viral and fungal infections.

Effect of propranolol on heart rate variability in patients with end-stage renal disease: a double-blind, placebo-controlled, randomized crossover pilot trial.

BACKGROUND: Low heart rate variability (HRV) is an independent risk factor of cardiac mortality in patients with end-stage renal disease (ESRD). It has been explained by uremic parasympathetic neuropathy. Sympathetic overactivity can also reduce HRV. Our aim was to determine whether there is vagal activity in ESRD patients that is masked by sympathetic activity. METHODS: The effect of propranolol on HRV was examined in 13 patients with ESRD, aged 20.1 +/- 7.6 years without diabetes. All patients were given intravenous propranolol (0.05 mg/kg) once and placebo once in a randomized, double-blind way, with an interval of 6.6 days (mean, range: 2-9). Propranolol was administered before hemodialysis treatment, after 40 minutes supine resting period. HRV was registered for 10 minutes, during supine, before and after the injection. Patients' HRV data were compared to that of 29 age-matched healthy controls. RESULTS: Initially, both high-(HFV) and low-frequency (LFV) bands of heart rate variability were lower in ESRD patients compared to controls (p < 0.001 for both). Propranolol resulted in a significant increase of HFV (propranolol: AlgHFV = 0.182 (0.027 - 0.337), placebo: deltalgHFV = -0.029 (-0.128 - +0.070); p = 0.032). Elevation of LFV was not significant. Six patients had an elevated plasma norepinephrine and/or epinephrine level. Plasma dopamine level was elevated in all but 1 patient (mean: 432 pmol/l, 95% CI: 320-543) and showed an inverse relationship with the increase of IgHFV secondary to propranolol (r = -0.66, p = 0.014). CONCLUSIONS: Low HFV of ESRD patients can be improved by beta-adrenergic blockade. It demonstrates that there is some vagal activity in ESRD that is masked by sympathetic activity. Therefore, altered sympathovagal balance of ESRD patients should be taken into consideration in the assessment of vagal uremic neuropathy.

Acute dislocation of the patella. A correlative pathoanatomic study.

The objective of our study was to elucidate the characteristic pathoanatomy associated with patellar dislocation and report the preliminary results of early surgical repair. Twenty-three patients with documented patellar dislocation had standard radiographs and a magnetic resonance imaging scan. Intraarticular lesions were evaluated and treated arthroscopically followed by an open exploration of the medial aspect of the knee in 16 patients. Twelve patients were observed for a minimum of 2 years after surgical repair (average, 34 months). Eleven patients returned for a follow-up examination. Magnetic resonance imaging revealed effusion (100%), tears of the femoral insertion of the medial patellofemoral ligament (87%), increased signal in the vastus medialis muscle (78%), and lateral femoral condyle (87%) and medial patellar (30%) bone bruises. Arthroscopic examination revealed osteochondral lesions involving the patella and the lateral femoral condyle in 68% of cases. Open surgical exploration revealed tears of the medial patellofemoral ligament off the femur in 15 of 16 patients (94%). After medial patellofemoral ligament repair, none of the patients experienced recurrent dislocation. Overall 58% of the results were considered to be good or excellent and 42% were fair. Fifty-eight percent of the group returned to their previous sport with no or minor limitations.

Hamstring muscle injuries among water skiers. Functional outcome and prevention.

Water skiing is associated with severe injuries to the proximal hamstring muscles. We wanted to define the mechanism of injury, describe the associated pathologic changes, determine the functional limitations of patients, and suggest measures to prevent injury. Twelve patients with water skiing-related hamstring injuries were included. Six patients were experienced skiers and six were novices. The mechanism of injury was identical in five of six novice skiers. Each sustained the injury while attempting to get up on one or two skis from a submerged position. In contrast, the expert skiers all sustained injury secondary to a fall while skiing. Physical examination documented evidence of complete or partial avulsion of the proximal hamstring muscle origins in all patients. In addition, six patients had magnetic resonance imaging or computed tomography scans that confirmed the location and extent of the tear. Convalescence ranged from 3 months to 1.5 years before the patient could return to vigorous activities. Seven patients (58%) returned to most of their preinjury sports, albeit at a lower level. Five patients (42%), all with complete disruptions, were unable to run or participate in sports requiring agility. Two of these patients required delayed surgical repairs because of persistent functional limitations.

Changes of urinary enzyme activity after endoscopic treatment of vesico-ureteric reflux.

The urinary enzymes Gamma Glutamyl Transferase (GGT), Alkaline Phosphatase (ALP), Leucine-Arylamidase (LAS), and Dipeptidyl-Peptidase-IV (DPP-IV) were measured before and after endoscopic treatment of vesico-ureteric reflux (VUR) in two groups of twenty children. Ten patients had undergone successful endoscopic corrective surgery for VUR, another 10 patients had unsuccessful endoscopic intervention. After successful treatment the activity of LAS in the urine did not change, but GGT, ALP and DPP-IV activity in the urine was 2-5 times higher than before treatment (P < 0.03 for all three enzymes). Considerable changes of urinary enzyme activity were not observed following unsuccessful endoscopic treatment. Our data and the literature are contradictory. However, this contradiction might be explained by the differences in urine sampling methods. Our patients received the same chemoprophylactic drug at the time of both urine samplings, a point not considered by other researchers. The extent of increase of enzyme activity after endoscopic treatment of VUR did not reach the level that would permit the use of investigated enzymes for screening, because the observed changes did not exceed the limits of the normal range.

[Selective vitamin B12 absorption disorder (Imerslund-Gräsbeck syndrome)]. / Szelektív B12-vitamin felszívódási zavar (Imerslund-Gräsbeck syndroma).

The authors present a case of Imerslund-Gräsbeck syndrome, i. e. a familial megaloblastic anemia with proteinuria. The disease is due to congenital, selective malabsorption of vitamin B12. The subnormal absorption of vitamin B12 is not altered by orally given intrinsic factor, but parenteral vitamin B12 therapy results in complete recovery. Approximately 150 cases have been described in literature, the authors' case is the first in Hungary.

[Effect of dialysis on Na+/K+-ATP-ase activity in uremic children]. / A dialízis hatása a Na+/K(+)-ATP-áz aktivitásra uraemiás gyermekekben.

The enzyme Na+/K(+)-ATPase plays a central role in the regulation of transmembrane ionic transports. According to previous reports its activity decreased in uremic state. The activity of Na+/K(+)-ATPase in detergent pretreated erythrocytes was studied in seven uremic children prior to and following the hemodialysis (HD) session. Additionally, the level of endogenous digoxin like factors in the plasma (EDLF) was determined. Before the HD session the Na+/K(+)-ATPase activity decreased compared to the control value (mean +/- SD: 2078 +/- 527 vs 3245 +/- 362 nmol P/ml RBC/h, p < 0.01). Following HD it became normal (3366 +/- 952 nmol P/ml RBC/h, n.s.). Prior to the HD the EDLF level was higher, while after the HD no difference was noted from the control value (0.29 +/- 0.04, p < 0.05; 0.24 +/- 0.04 n. s. vs control; 0.21 +/- 0.04 ng/ml). Before the HD blood pressure was significantly elevated compared to the control (117 +/- 20/92 +/- 18 vs 95 +/- 2/64 +/- 2 Hgmm, p < 0.05). By the end of the HD it became normal (100 +/- 14/79 +/- 11, n.s.). Although no correlation was found between the EDLF level and Na+/K(+)-ATPase activity, a positive significant correlation was found between the changes of enzyme activity and the changes in the systolic (r = 0.83, p < 0.05) and diastolic (r = 0.82, p < 0.05) blood pressure during the HD. Our results indicate, that in uremic children the Na+/K+ pump is inhibited by a dialysable, blood-pressure regulator substance and so the enzyme activity elevates following the HD session. However, decreased blood pressure activates counterregulatory mechanisms, which-to lower extent-inhibit the activity of the pump.

[Molecular biological studies on patients with nephrogenic diabetes insipidus]. / Nephrogen diabetes insipidusos betegek molekuláris biológia vizsgálata.

Nephrogenic diabetes insipidus is a rare, mostly X-linked recessive disorder characterised by renal tubular resistance to the antidiuretic effect of arginine vasopressin. The gene responsible for the X-linked nephrogenic diabetes insipidus, the G-protein-coupled vasopressin V2-receptor, has been localised on the Xq28 region. In this study four patients were investigated with molecular genetic methods. Diagnosis was based on clinical symptoms and lack of increase of urinary osmolality after administration of the arginine vasopressin, or the synthetic vasopressin analogue DDAVP. Three different mutations (C112R, N317K, W323S) were found in three patients, while no mutation was detected in the fourth patient. Since earlier histiocytosis X has been diagnosed in this patient, this patient has probably central diabetes insipidus. Although the main symptoms of the disease can be found in all patients, there are significant differences in the seriousness of the symptoms as well as in some other symptoms. The explanations might be the different mutations in the V2-receptor gene and the various other genetic and environmental factors; these findings provide further evidence that X-linked nephrogen diabetes insipidus results from defects in the V2-receptor gene.

[Changes in urinary enzyme activity following silicon therapy of vesico-ureteral reflux]. / A vizeletenzimek aktivitásváltozása vesicoureteralis reflux szilikonnal végzett kezelésében.

The urinary enzymes Gamma Glutamyl Transferase (GGT), Alkaline Phosphatase (ALP), Leucine-Arylamidase (LAS) and Dipeptidyl-Peptidase-IV (DPP-IV) were measured before and after endoscopic treatment of vesico-ureteric reflux (VUR) in two groups of twenty children's. Ten patients had undergone successful endoscopic corrective surgery for VUR, another 10 patients had unsuccessful endoscopic intervention. After successful treatment the activity of LAS in the urine did not change, but that of GGT, ALP and DDP-IV activity in the urine was 2-5 times higher than before treatment (P < 0.03 for all three enzymes). Considerable changes of urinary enzymes' activity were not observed following unsuccessful endoscopic treatment. Our data and the literature are contradictory. However this contradiction might be explained by the differences in urine sampling methods. Our patients received the same chemoprofilactic drug at the time of both urine sampling, a point not considered by other researchers. The extent of increase of enzyme activity after endoscopic treatment of VUR did not reach the level that would permit the use of investigated enzymes for screening, because the observed changes did not exceed the limits of the normal range.

[Normal values of calcium and oxalate excretion in children]. / A kalcium- és oxalátürítés normálértékei gyermekekben.

Aim of the study was to establish normal values for calcium/creatinine (Ca/cr) and oxalate/creatinine (Ox/cr) ratio in infants and children. Urine probes of 416 healthy children (25 infants aged 1-7 days and 391 children aged 1 month-14.5 years) were analysed. Oxalate was measured by ion-chromatography. Urinary Ca2+/cr was normally distributed, Ox/cr had log-normal distribution. Ca/cr was the lowest in the first days of life, the highest between 7 month-1.5 years (mean +/- SD = 0.39 +/- 0.28 mmol/mmol), a slight decrease could be observed until 14 years (0.34 +/- 0.18). The highest Ox/cr values were measured during the first month of life (geometric mean/range/ = 133 /61-280 mmol/mmol/), followed by gradual decrease until 14 years (25/6-73/). The measurement of Ca2+/cr and Ox/cr in first morning urine samples is suitable for screening of hypercalciuria and hyperoxaluria. The interpretation of the values requires age specific reference values. Both calcium and oxalate determinations should be the part of the evaluation of patients with hematuria, hypercalciuria or nephrolithiasis.

[Hepatitis G virus infection in hemodialyzed children and adults following kidney transplantation]. / Hepatitis G vírus infekció vesetranszplantált és dializált gyermek és felnött betegekben.

Recently, a new human virus hepatitis G virus was identified. The aim of the present study was to use a combination of the reverse transcription-polymerase chain reaction and a new test for antibodies to the viral envelope protein E2 to assess the prevalence of hepatitis G virus infection in sera of children and adults treated with hemodialysis or peritoneal dialysis as well as in sera of those who underwent renal transplantation. Hepatitis G virus RNA prevalence was higher in the shole group of patients with renal failure than in control group. The difference between hepatitis RNA prevalence in transplanted group and in control group was found to be significant. Anti-E2, which are is considered as an indicator of a past hepatitis G virus infection, were detected in the similar rate in the treated and control subjects. Time on hemodialysis was significantly longer in hepatitis G virus infected patients as compared to uninfected patients and all patients with hepatitis G virus RNA have a history of blood transfusions. Patients with renal failure treated with dialysis or subjected to renal transplantation are at increased risk of acquiring the hepatitis G virus infection. Higher rates of the hepatitis G virus RNA and similar prevalence of anti-E2 in patients with renal failure as compared to controls suggest that the rate of hepatitis G virus infection resolution in immunosuppressed patients with renal failure might be lower than in immunocompetent subjects.

H1N1 vaccination in pediatric renal transplant patients.

BACKGROUND: Solid organ transplant recipients undergoing immunosuppressive therapy are considered to be at high risk of serious infectious complications. In 2009, a new influenza pandemic caused serious infections and deaths, especially among children and immunocompromised patients. Herein we have reported the safety and efficacy of a single-shot monovalent whole-virus vaccine against H1N1 infection in the pediatric renal transplant population. METHODS: In November and December 2009, we vaccinated 37 renal transplant children and adolescents and measured their antibody responses. Seroprotection, seroconversion, and seroconversion factors were analyzed at 21 days after vaccination. RESULTS: None of the vaccinated patients experienced vaccine-related side effects. None of the patients had an H1N1 influenza infection after vaccination. All of the patients showed elevations in antibody titer at 21 days after vaccination. In contrast, only 29.72% of the patients achieved a safe seroprotection level and only 18.75% a safe seroconversion rate. More intense immunosuppressive treatment displayed negative effect on seroprotection and seroconversion, and antibody production significantly increased with age. No other factor was observed to influence seroprotection. CONCLUSIONS: We recommend vaccination of children and adolescent renal transplant recipients against H1N1 virus. However, a single shot of vaccine may not be sufficient; to achieve seroprotection, a booster vaccination and measurement of the antibody response are needed to assure protection of our patients.

Heat shock protein polymorphism predisposes to urinary tract malformations and renal transplantation in children.

BACKGROUND: Anatomical malformations of the kidney and urinary tract account for 17% of pediatric renal transplantation procedures. Heat shock proteins (HSPs) are molecular chaperones with a protective function that promotes cell survival. HSP72 is an endogenous ligand for toll-like receptor TLR4, thereby stimulating innate immunity. Both in adults and children, decreased expression of HSP70s is associated with a number of kidney diseases. OBJECTIVE: To assess the prevalence of HSPA1A G(190)C, HSPA1B A(1267)G, and TLR4 A(896)G polymorphisms in children who had undergone kidney transplantation. PATIENTS AND METHODS: Genotypes were analyzed using allele-specific polymerase chain reaction in 41 pediatric recipients. Allelic prevalence was related to reference values in 65 age- and sex-matched healthy children. RESULTS: Clinical data did not reveal a difference between any of the groups. HSPA1B (1267)GG genotype and HSPA1B (1267)G allele were observed more frequently in the transplant recipients compared with the control group: AA vs AG: odds ratio [OR], 12.6; 95% confidence interval [CI], 1.58-100.0; P = .004; AA vs GG: OR, 20.80; 95% CI, 2.32-187.00; P = .01; and A vs G: OR, 2.10; 95% CI, 1.19-3.07; P = .01. Furthermore, the prevalence of the HSPA1B (1267)GG genotype was greater in transplant recipients with vs without urinary tract malformations: AG vs GG: OR, 0.10; 95% CI, 0.09-0.48; P = .007. No differences were observed in the other studied polymorphisms. CONCLUSION: Our findings suggest an association between the carrier status of HSPA1B (1267)G with urinary tract malformations, leading to end-stage renal disease requiring kidney transplantation. This observation raises further questions about the clinical and therapeutic relevance of this polymorphism to pediatric nephrology.

The use of human recombinant erythropoietin in children on chronic dialysis.

Human recombinant erythropoietin (r-HuEPO, EprexR) was administered to 8 children with chronic renal failure and high transfusion requirement. The hormone was given i.v. 2-3 times per week at the end of the dialysis. The selected initial dose (160 U/kg/week) was gradually raised up to a maximum of 400 U/kg/week. Anaemia normalised by the tenth week. The aimed target haematocrit was 0.33, the average maintenance dose was 250-300 U/kg/week. The absolute reticulocyte count seemed to be a more sensitive indicator of the actual erythropoietin effect than the haematocrit level. No major adverse effects (convulsion, progressive hypertension, thrombosis) were observed during treatment with r-HuEPO. The need for transfusions decreased dramatically, no transfusion was needed following the second week of treatment. The general condition improved substantially. In one hyperimmunized child the cytotoxic antibody titer decreased by 75 per cent.

The serum hormone levels, phosphate complex concentrations and enzyme activities in haemodialysed and kidney-transplanted children.

The serum hormone (T3, FT3, T4, FT4, TSH, hTG, a-hTG, GH, PTH, PRL, Cortisol) concentrations, the inorganic phosphate complexes (HPO2-4, H2PO-4, NaHPO-4, KHPO-4, CaHPO4, MgHPO4) and the enzyme activities (Amylase, Lipase, AP, ACE, GOT, GPT, psi-ChE, CK, gamma-GT, LDH) were investigated in 13 haemodialysed children, 7 kidney-transplanted children and in 15 healthy controls. This study confirmed that the kidney plays an important role in the metabolism of hormones. Prior to kidney transplantation 8 of the 11 tested hormone levels of haemodialysed children significantly differed from those of healthy controls, however, after kidney transplantation only two parameters did. The effect of dialysis is the least on the CaHPO4 complex among the different inorganic phosphate complexes. This may play a role in vascular calcification in chronic renal failure patients. The amylase and lipase activity were elevated in haemodialysed group, while in kidney-transplanted children the angiotensin converting enzyme (ACE) and alkaline phosphatase (AP) differed from those of the control group.

Therapeutic efficacy of corticosteroid injections in the acromioclavicular joint.

There is debate among orthopaedists about the efficacy of steroid therapy to treat painful joints. Using an uncontrolled, retrospective study, we examined the usefulness of local corticosteroid injections in thirty-one patients (twenty-four men, seven women) with isolated AC joint arthropathy. No patients had signs of impingement or rotator cuff disease. All injections were performed using a standardized technique with each patient receiving 1cc Celestone/Soluspan or Dexamethasone and 2cc Lidocaine. At an average follow-up of nineteen months, patients were asked to answer questions regarding activity of daily living, according to the American Shoulder and Elbow Surgeons (ASES) format, average level of pain, length of pain relief from steroid injection, and time to return to full activity. Four patients could not be contacted for follow-up questions and, therefore, were excluded from the study leaving twenty-seven patients. Pain and function improved in twenty-five of twenty-seven (93%) patients after injection. Mean duration of improvement was twenty days (range, two hours to three months). Two patients reported continued relief at 1.5 and two years after injection. Due to persistent, insidious pain, eighteen of twenty-seven (67%) patients underwent distal clavicle excision an average of four months after injection. Overall, twenty-two of twenty-seven (81%) patients failed to obtain long-term relief from the injection. The results of this study suggest that the administration of local corticosteroids into the AC joint may provide short-term pain relief, but does not alter the natural progression of disease.

Omniflex modular femoral component. Two- to five-year results.

A prospective study was completed on 106 consecutive cementless arthroplasties (94 patients) to determine the clinical and radiographic outcome. Ninety-two hips (81 patients) had complete follow-up data. The average age was 46 years, and the average follow-up period was 41 months (24-63 months). Clinically 94% had no or slight pain. Two patients had activity-limiting thigh pain. Most patients had no or slight limp and walked without support. Patients had similar outcomes regardless of their bone type. Ninety-three percent of hips were radiographically stable. Six were loose; three of those had major intraoperative fractures. Stable stems were characterized by middle and distal zone endosteal condensation and cortical hypertrophy; these occurred primarily in the distal zones for unstable implants. Calcar resorption was noted in 38% of hips with collars and in 68% without collars (p = 0.015). Endosteal erosions were seen in six hips (6.5%) and were related only to the patient's activity level (p = 0.021). Seven hips were revised, two for delayed sepsis, one for loosening after trauma, one for intraoperative fracture, and three for aseptic loosening. The Omniflex implant system provides acceptable but not outstanding results in a wide array of femoral geometries. The early difficulty with femoral fractures has been significantly reduced by using a prophylactic cerclage cable.