Early proteinuria after renal transplantation and allograft outcomes.

BACKGROUND: Proteinuria is among the major and nonspecific sign of the renal disease. It is well known that late-onset proteinuria after renal transplantation has been associated with poor allograft outcomes and with mortality. Knowledge about the impact of early proteinuria on the various outcomes is limited. We have evaluated the utility of measuring early proteinuria in the management of pediatric renal transplant recipients. METHODS: We analyzed the effect of proteinuria at 3 months of posttransplantation on allograft rejection, graft loss, and estimated glomerular filtration rate (GFR) at 3 years. Proteinuria was assessed using 24-hour urine protein excretion. Renal biopsy was performed when elevated creatinine levels were elevated during routine follow-up and an acute rejection episode was proven with biopsy. RESULTS: Sixty-seven pediatric renal transplant recipients were included to the study. Mean follow-up time after transplantation was 48.8 ± 12.1 months. Thirty-nine recipients (58%) have proteinuria >500 mg/d. The relationship could not be shown between proteinuria at posttransplant month 3 and other outcomes parameters, such as graft loss and lower estimated GFR. A significant positive correlation between acute rejection and the proteinuria at posttransplant month 3 was shown. CONCLUSION: We demonstrated that early proteinuria is a common finding in children after transplantation. Posttransplant early proteinuria cannot be used as a long-term prognostic marker of poor renal outcome. However, early proteinuria is associated with an high risk of acute rejection episodes. This would permit an opportunity for early intervention.

Value of early diethylentriamine penta-acetic acid renograms in predicting late allograft outcomes.

BACKGROUND: Tc-99m-diethylentriamine penta-acetic acid (DTPA) renal scintigraphy is useful, noninvasive diagnostic tool for the management and follow-up of the transplanted kidney. There have not been any studies of the predictive value of DTPA renal scintigraphy for short- and long-term allograft functions. Our aim was to reveal the significance of different perfusion-uptake patterns observed on Tc-99m-DTPA renal scintigraphy for long-term graft outcomes. METHODS: We retrospectively analyzed 59 renal transplanted children (30 male and 29 female). All patients were underwent DTPA on posttransplant day 7. Perfusion- and function-related parameters of DTPA (the ratio of peak perfusion counts to plateau counts [P:PL], the ratio of counts at peak perfusion to counts at peak uptake [P:U], and glomerular filtration rate [GFR] calculated using commercially available software) were studied. The mean P:PL and P:U calculated using the half-moon-shaped background region of interest. A renal time activity curve was generated for evaluate perfusion- and function-related parameters. The patterns were classified and the value of these early DTPA parameters in predicting long-term graft function was analyzed. RESULTS: The mean age of patients was 16.69 ± 4.77 years. The mean posttransplant follow-up time was 3.5 ± 0.4 years. Thirty-nine patients received living-related donor allografts and the remaining 20 were from deceased donors. Thirteen children suffered ≥ 1 acute rejection episode. Eight patients lost their grafts during follow-up. Mean GFR value at year 3 was 80.61 ± 39.03 mL/1.73 m(2) BSA/min. There was a significant difference for mean creatinine values at year 3 between recipients with normal perfusion and function and normal P:PL with decreased P:U patterns in early DTPA (P < .05). The normal P:PL with decreased P:U pattern is associated with lowest GFR value at posttransplant year 3. There was also a significant difference for mean GFR values at year 3 between recipients with normal perfusion and function and acute tubular necrosis (P < .05). Acute rejection episodes and graft loss were mostly seen in recipient with a decreased P:PL with or without decreased P:U pattern in early DTPA. The decreased P:PL with or without decreased P:U pattern may be associated with high risk of acute rejection episodes and graft loss. CONCLUSION: Posttransplant early perfusion uptake patterns observed on Tc-99m-DTPA renal scintigraphy can be used as a long-term prognostic marker of poor renal outcomes. This would permit an opportunity for early intervention.

Neurocognitive functions in pediatric renal transplant patients.

Neurocognitive dysfunction is one of the major complications of chronic renal failure (CRF). Uremic state during CRF encompasses a wide spectrum of neurobehavioral and neurological disturbances. Recent studies showed that the pathophysiology of neurocognitive dysfunction in CRF is related to plasma levels of uremic solutes. Successful renal transplantation improves renal, metabolic, and endocrine functions and the quality of life. The aim of our study was to determine the state of neurocognitive function in pediatric renal transplant recipients. We prospectively performed a neurological examination and neuropsychological test battery (Bender-Gestalt Test, Cancellation Test, and Visual and Auditory Number Assay Test) in 20 pediatric renal transplant recipients between 6 and 16 years of age. Twenty healthy children and 20 children with CRF were included in the study as the control groups. Mean age of the renal transplant recipients was 13.50 ± 3.40 years old. Mean evaluation time after transplantation was 2.0 ± 0.5 years. Bender-Gestalt Test result was abnormal in 40% of patients. The results of the Cancellation Test and the Visual and Auditory Number Assay Test showed significant decline in pediatric renal transplant patients when compared with the control. We found that neurocognitive dysfunction was frequent in pediatric renal transplantation patients. Awareness of this potential problem may be helpful for early recognition and treatment. Our findings suggest that periodic neurocognitive assessments may be indicated in transplant recipients.

Comparison of basiliximab and daclizumab with triple immunosuppression in renal transplantation.

PURPOSE: Graft rejection is a serious problem despite immunosuppressive agents. Immunosuppression has been achieved with monoclonal antibodies (mAb) that bind specifically to the α subunit of the interleukin (IL)-2 receptor present on activated T lymphocytes. We explored the effects of two of the mAbs-daclizumab and basiliximab-on graft function. MATERIALS AND METHODS: Our 1543 renal transplant recipients received baseline therapy with cyclosporine or tacrolimus plus corticosteroids and mycophenolate mofetil. In addition standard dosages intravenously of daclizumab (n=156) or basiliximab (n=45) in were administered intravenously to 201 renal transplant patients who included 122 men and 79 women of overall mean age of 30±13.7 years. RESULTS: Patient and donor characteristics including age, sex, causes of renal failure, presence of comorbidities, panel-reactive antibodies, and numbers of human leukocyte antigen-mismatched were similar between the groups. During a mean follow-up of 27±20 months, biopsy-proven acute rejection was observed in three patients in the basiliximab group and 23 in the daclizumab group. Cytomegalovirus infection occurred in 13 patients. There was no case of posttransplant lymphoproliferative disorder. Three polyoma BK nephropathies were detected in the daclizumab group. No hypersensitivity reaction occurred in either group. One-year patient survival was 100% in the basiliximab group and 99% in the daclizumab group, with graft survivals of 95% versus 94%, respectively. The mean creatinine levels at discharge were 2 mg/dL versus 2.3 mg/dL and at 12 months, 1.3 mg/dL versus 1.2 mg/dL, respectively. CONCLUSIONS: Acute rejection episodes remain a significant risk factor for the development of graft dysfunction and poor long-term graft survival. IL-2R antagonists were effective antibody therapies. There was no apparent difference between basiliximab and daclizumab treatment.

Preemptive living donor renal transplantation: a single-center experience.

Renal transplantation is considered preemptive if it occurs before initiation of dialysis. In our experience and in the literature, preemptive transplantation has been shown not only to reduce the costs of renal replacement therapy but also to avoid the long-term adverse effects of dialysis. Preemptive renal transplantation therefore is associated with better survival of both the allograft and the recipient. Our aim was to evaluate the outcomes of preemptive renal transplantation experience at our center. Since 1985, 1385 renal transplantations have been performed at our center. We retrospectively analyzed the 16/1385 recipients (11 male, 5 female) of overall mean age of 28.5 +/- 15 years who underwent preemptive procedures. The causes of end-stage renal failure were focal segmental glomerulosclerosis (n = 5), vesicular ureteral reflux (n = 4), Berger disease (n = 2), polycystic renal disease (n = 2), and others (n = 3). Ten patients were adults, the remaining six, children. The mean creatinine clearance and plasma creatinine levels of the recipients before renal transplantation were 13.5 +/- 8.5 mL/min and 6.7 +/- 2.4 mg/dL, respectively. All renal transplantations were performed from living related donors. The mean preoperative serum creatinine levels, mean glomerular filtration rate, and creatinine clearance rates of the donors were 0.8 +/- 0.1 mg/dL, 61.6 +/- 6.5 mL/min, and 112.5 12 mL/min, respectively. Two episodes of acute cellular rejection and one of humoral rejection occurred during a mean follow-up of 48.7 +/- 14 months (range = 25-76 months). The two patients who experienced graft losses due to humoral rejection or chronic rejection were retransplanted 2 and 48 months thereafter, respectively. At this time all patients are alive with good renal function. In conclusion, our single-center results are promising for preemptive renal transplantation as the optimal, least-expensive mode of treatment for end-stage renal disease.

Frequency of urinary tract infection in pediatric liver transplantation candidates.

An increased frequency of infections has been reported in patients with chronic liver disease. The tendency of patients in this population to acquire UTI is not completely understood. We aimed at investigating the incidence of UTI in children with cirrhosis, before liver transplantation. Twenty-six children (9 girls, 17 boys; mean age, 7.66 +/- 5.73 yr) with chronic liver disease who had undergone liver transplantation between 2002 and 2004 were included. On admission for liver transplantation, patients were examined for presence of UTI. Serum biochemistry, complete blood cell count, urinalysis and culture, glomerular filtration rate, and abdominal ultrasonography were performed prior to liver transplantation. Ten of 26 patients (38.5%) were found to have symptomatic UTI. Urine cultures revealed E. coli in five (50%), Klebsiella pneumoniae in three (30%), Enterococcus faecalis in one (10%), and Enterobacter aeruginosa in one (10%) patient(s), respectively, as etiologic factors. The etiologies of chronic liver disease in our patients with UTI were BA in five, PFIC in three, Wilson's disease in one, and alpha-1 antitrypsin deficiency in one patient. We found a significantly greater number of UTIs in patients with biliary atresia than in those without biliary atresia (p < 0.05). The mean age of the patients with UTI was 2.75 +/- 3.49 yr, which was significantly lower than in those without UTI (9.75 +/- 4.86 yr, p < 0.05). Levels for white blood cells, thrombocytes, ALT, and alkaline phosphatase were significantly higher in patients with UTI than in those without UTI. There were no significant differences between the groups with regard to serum albumin, bilirubin, AST, GGT, BUN, or creatinine levels, glomerular filtration rate, duration of disease, and PELD scores. In patients with bacteriuria, renal USG revealed normal findings in all, but except one patient who had pelvicalyceal dilatation. Scintigraphic findings demonstrated acute pyelonephritis in six (60%) patients with UTI. VCUG demonstrated vesicoureteral reflux in two patients. In conclusion, symptomatic UTI is common in children with cirrhosis. It occurs more frequently in patients with biliary atresia than it does in patients with other types of chronic liver disease. In febrile children with chronic liver disease, UTI should be considered in the differential diagnosis.

[Hemicentral retinal artery occlusion associated with moyamoya syndrome]. / Hemizentralarterienverschluss bei Moyamoya-Syndrom.

Moyamoya syndrome is a rare cerebrovascular disorder characterized by bilateral progressive supraclinoidal stenosis or occlusion of the internal carotid artery and development of collateral vessels in the lenticulostriate region. The syndrome manifests itself in association with another disease or other clinical symptoms. We present the case of a 12-year-old girl with hemicentral retinal artery occlusion due to moyamoya syndrome associated with clinical and laboratory findings of presumed systemic lupus erythematosus.

pH-induced intracellular protein transport.

A new mechanism of selective transport and localization of proteins inside any living cell is presented. The mechanism is based on pH-induced protein trapping. It is shown that spontaneous and unique spatial redistribution of different proteins is possible in any aqueous solution with stable non-uniform distribution of H(+) ions. This phenomenon was observed in artificial systems with fixed non-uniform pH distribution and in living cells.

Quantization of 2D hole gas in conductive hydrogenated diamond surfaces observed by electron field emission.

Discrete jumps are observed in the emitted current density (J) versus extraction electric field (E) curves in electron field emission measurements from a conductive, hydrogen-terminated air-exposed diamond surface. These jumps are well reproduced by computations based on the assumption that a 2D nanoscale quantum system with discrete energy levels exists in the diamond near-surface layer. The present results confirm the formation of well-defined quantum states of holes in the 2D surface layer present on hydrogenated air-exposed diamond surfaces.

Renal transplantation in children.

INTRODUCTION: Various immunological, metabolic, and technical factors render pediatric recipients with end-stage renal disease unique from their adult counterparts. In addition, the potential for complications after renal transplantation is far greater in children than in adults. In this study, we retrospectively analyzed 83 pediatric recipients who underwent kidney transplantation at our institution from 1975 to 2004. MATERIALS AND METHODS: From November 1975 to December 2004, 1523 renal transplantations were performed at our institution with 56 procedures in 83 pediatric patients (44 boys and 39 girls; age range, 7 to 17 years; mean age, 14.9 +/- 2.2 years). RESULTS: Long-term follow-up revealed the following morbidities in 14 (16.3%) recipients: lymphocele in 7 (8.1%) patients, perirenal hematoma in 2 (2.3%), graft renal artery stenosis in 2 (2.3%), ureteral stenosis in 2 (2.3%), and ureteral anastomotic leak in 1 (1.2%). Six (7.2%) recipients with a functioning graft died during follow-up (five deaths were infection related, and the cause of one death was unknown). Five grafts failed (four for immunological reasons and one as a result of recurrent disease). The 1-, 3-, 5-year patient and graft survival rates were 98%, 93%, 92% and 91%, 78%, 67% for living related transplantations versus 98%, 91%, 90% and 92%, 76%, 65% for cadaveric transplantations, respectively. DISCUSSION: Better outcomes for renal transplantation in children may be obtained by strict adherence to precise surgical techniques, better immunosuppressive management, and early diagnosis/effective treatment of complications.

Relationship between chronic inflammation and cardiovascular risk factors in children on maintenance hemodialysis.

Cardiovascular disease is one of the most important causes of morbidity and mortality in children with end-stage renal failure. Chronic inflammation and malnutrition have been suggested to be risk factors for cardiovascular disease. However, to date, biomarkers of inflammation have not been well studied in children. The aim of this study was to investigate the relation between chronic inflammation and cardiovascular risk factors in children on hemodialysis therapy. Twenty-seven patients on hemodialysis (14 girls, 13 boys) of mean age 15.3 +/- 2.4 years and 20 healthy children (13 girls, 7 boys) of mean age 14.3 +/- 2.7 years were included the study. C-reactive protein (CRP), albumin, prealbumin, transferrin, ferritin, and fibrinogen were measured as the markers of inflammation. The levels of CRP, ferritin, and erythrocyte sedimentation rate among hemodialysis patients were significantly higher than those of control subjects (P < .001 for all). Albumin and transferrin levels were found to be lower than those of control group (P = .02 and P < .001, respectively). CRP levels were negatively correlated with albumin, prealbumin, apoprotein A1, HDL, and hemoglobin levels, and positively correlated with erythropoietin/Htc ratios. This study suggests that hemodialyzed children are exposed to chronic inflammation. In addition, CRP may be an indicator of chronic inflammation related to cardiovascular risk factors, such as malnutrition, dyslipidemia, and anemia. In conclusion, we suggest that the risk of cardiovascular disease could be reduced by defining markers of chronic inflammation and malnutrition in hemodialyzed children and by taking necessary measures at an early stage.

Relationship between leptin and bone mineral density in renal transplant recipients.

INTRODUCTION: Leptin plays an important role in regulating appetite and energy expenditure and also functions in the neuroendocrine, hematopoietic, and immune systems, among others. Leptin may be involved in modulating bone mineralization. The relationship between leptin and bone mineral density (BMD) is not clear. This study examined the relationship between BMD and serum leptin levels in renal transplant recipients. MATERIALS AND METHODS: Forty-one patients (28 men and 13 women; age 16 to 55 years) were grouped according to percentile of serum leptin level hypoleptinemic (<5th percentile, n = 14), normoleptinemic (between the 5th and 95th percentiles, n = 19), or hyperleptinemic (>95th percentile, n = 8). The patients also were grouped according to lumbar z score) and total femur z scores (>-2 vs <-2 for both). RESULTS: The groups with different leptin statuses were compared with respect to age, sex distribution, and body mass index. Mean lumbar z score and mean lumbar BMD were higher in the hyperleptinemic group than in the normo- and hypoleptinemic groups (P < .05 for all). Considering the 42 patients overall, those with lumbar z scores >-2 had higher mean serum leptin/BMI than those with lumbar z scores <-2 (0.55 +/- 0.65 vs 0.18 +/- 0.23, respectively, P < .05). Serum leptin/BMI ratio was correlated with lumbar z score (r = .38, P < .05) and lumbar BMD (r = .32, P < .05). CONCLUSION: In conclusion, the data indicate that elevated leptin level is associated with increased bone mass at lumbar sites in renal transplant recipients. This suggest that increased leptin has a bone-sparing effect, especially in the lumbar region, in this patient group.

Negative superdiffusion due to inhomogeneous convection.

Fractional transport of particles on a comb structure in the presence of an inhomogeneous convection flow is studied [Baskin and Iomin, Phys. Rev. Lett. 93, 120603 (2004)]. The large scale asymptotics is considered. It is shown that a contaminant spreads superdiffusively in the direction opposite to the convection flow. Conditions for the realization of this effect are discussed in detail.

Nephrolithiasis associated with ceftriaxone therapy: a prospective study in 51 children.

BACKGROUND: Ceftriaxone, a third generation cephalosporin, is widely used for treating infection during childhood. The kidneys eliminate approximately 33-67% of this agent, and the remainder is eliminated via the biliary system. Ceftriaxone may bind with calcium ions and form insoluble precipitate leading to biliary pseudolithiasis. The aim of this study was to assess whether ceftriaxone associated nephrolithiasis develops by the same mechanism, and whether this condition is dose related. METHODS: The study involved 51 children with various infections. Of these, 24 were hospitalized with severe infection and received 100 mg/kg/day ceftriaxone divided into two equal intravenous doses. The other 27 patients received a single daily intramuscular injection of 50 mg/kg/day. Serum and urine parameters were evaluated before and after treatment, and abdominal ultrasonographic examinations were also carried out before and after treatment. RESULTS: Serum urea, creatinine, and calcium levels were normal in all patients before and after treatment. Post-treatment ultrasound identified nephrolithiasis in four (7.8%) of the 51 subjects. The stones were all of small size (2 mm). Comparison of the groups with and without nephrolithiasis revealed no significant differences with respect to age, sex distribution, duration of treatment, or dose/route of administration of ceftriaxone. The renal stones disappeared spontaneously in three of the four cases, but were still present in one patient 7 months after ceftriaxone treatment. CONCLUSIONS: Conclusions: The study showed that children taking a 7 day course of normal or high dose ceftriaxone may develop small sized asymptomatic renal stones. The overall incidence of nephrolithiasis in this study was 7.8%.

Superdiffusion on a comb structure.

We study specific properties of particles transport by exploring an exact solvable model, a so-called comb structure, where diffusive transport of particles leads to subdiffusion. A performance of the Lévy-like process enriches this transport phenomenon. It is shown that an inhomogeneous convection flow is a mechanism for the realization of the Lévy-like process. It leads to superdiffusion of particles on the comb structure. This superdiffusion is an enhanced one with an arbitrary large transport exponent, but all moments are finite. A frontier case of superdiffusion, where the transport exponent approaches infinity, is studied. The log-normal distribution with the exponentially fast superdiffusion is obtained for this case.

Vascular endothelial growth factor in Henoch-Schonlein purpura.

OBJECTIVE: To investigate the possible role of vascular endothelial growth factor (VEGF) in the pathogenesis of Henoch-Schonlein purpura (IHSP). METHODS: Plasma VEGF levels were determined in 22 children by ELISA. Ten age matched healthy children served as controls. VEGF expression was evaluated by immunohistochemistry within the cutaneous vasculitic lesion as well as the nonaffected skin and in the skin specimens during the resolution of the disease. RESULTS. Plasma VEGF levels in pg/ml (mean +/- SE) were significantly higher during the acute phase (407.8 +/- 64.92) when compared with the levels seen during the resolution phase (202.17 +/- 26.6; p < 0.002) and in healthy controls (135 +/- 22.8; p < 0.001). Analysis showed that there was a correlation with erythrocyte sedimentation rate. C-reactive protein, white blood cell and platelet count. In all skin specimens, the intensity of the staining of VEGF in the epidermis, dermis, and vascular endothelial bed were evaluated and scored from (+) to (++++). VEGF expression in the epidermis and the vascular bed was more intense in resolving lesions compared with acute vasculitic lesions (p < 0.05). CONCLUSION: Our results suggest that as a potent permeability, chemotactic, and migratory factor, VEGF may play a crucial role in the morphological and functional changes of the vascular bed and inflammatory reaction in HSP.

The significance of antineutrophil cytoplasmic antibody in microscopic polyangitis and classic polyarteritis nodosa.

AIMS: To describe the distribution and features of classic polyarteritis nodosa (PAN) and microscopic polyarteritis (MPA) and the importance of antineutrophil cytoplasmic antibody (ANCA) in childhood PAN. METHODS: Classic PAN was diagnosed in 15 patients based on the presence of aneurysms on angiography in 10 patients and of necrotising vasculitis in medium sized arteries in five. MPA was diagnosed in 10 patients, based on characteristic findings at renal biopsy in six and by the presence of small sized necrotising arteritis in four. Serum ANCA was detected initially by indirect immunofluorescence (IIF) followed by an immunoassay for myeloperoxidase (MPO) in each case. RESULTS: The median age of the patients with classic PAN and MPA was 12 (range 8-17) and 9.5 (range 5-14) respectively. None of the patients with classic PAN had renal failure. Six of the patients with MPA presented with renal failure; four progressed to chronic renal failure. Clinically evident pulmonary-renal syndrome was present in three of the 10 patients with MPA. IIF for ANCA in classic PAN was negative in nine, showed mild staining patterns in six, and in one MPO-ELISA was mildly increased. IIF for ANCA in MPA revealed very strong perinuclear ANCA staining in nine and atypical staining in one. In MPA, median MPO-ELISA level was 42.5 EU/ml (range 20-250). Treatment of childhood PAN was satisfactory with effective treatment; however relapses did occur. CONCLUSION: ANCA is useful in the diagnosis and follow up of MPA.

Comparative study of cefixime alone versus intramuscular ceftizoxime followed by cefixime in the treatment of urinary tract infections in children.

Urinary tract infections (UTI) can cause acute morbidity and may result in severe problems, including hypertension and reduced renal function. Diagnosis of UTI is extremely important since prompt treatment may prevent damage. In the present study we compared the efficacy of oral cefixime to initial intramuscular ceftizoxime followed by cefixime for the treatment of UTI in children. Fifty-four children were studied. They were randomized to receive either oral cefixime 8 mg/kg/day for 10 days or initial intramuscular ceftizoxime (Cefizox) 50 mg/kg twice a day for 2 days followed by oral cefixime for 8 days. Treatment groups were comparable regarding age, sex, clinical, and laboratory findings. Escherichia coli was isolated from 80% of patients. Repeat urine cultures were sterile within 24 hours in all children. Cure rates were comparable in both groups (92% vs 86% at the end of treatment). No serious adverse effects were observed. We concluded that oral cefixime is a safe and effective alternative treatment.