Hyperleptinemia and its relation with peripheral C34(+)CD7(+) stem cells in renal transplant recipients.

OBJECTIVES: Leptin, the Ob gene product, centrally regulates weight control. Transplant recipients are exposed to many factors affecting body mass. Leptin has been reported to activate the peripheral immune system. In this study, we evaluated serum leptin levels and factors contributing to hyperleptinemia; the relationship between serum leptin levels and lymphoid stem and mature cells; and their role in the rejection process in renal transplant recipients. MATERIALS AND METHODS: Sixty-three renal transplant recipients were included in the study. Patients were grouped according to serum leptin percentiles as hypoleptinemic (n=17), normoleptinemic (n=32), and hyperleptinemic (n=14). We determined serum leptin levels by radioimmunoassay and absolute number of CD34(+), CD7(+), CD34(+)CD7(+) lymphoid stem cells, CD4(+) and CD8(+) lymphocytes in peripheral blood by flow cytometry. RESULTS: The hyperleptinemic patients constituted 22.3% of the transplant patient. The mean peripheral blood CD34(+)CD7(+) lymphocyte count was significantly higher in hyperleptinemic patients than in normo- or hypoleptinemic patients (6.9, 6.1, and 44.3 cells/mm(3), respectively, P<0.05). There were no significant differences in the mean CD34(+), CD7(+), CD8(+), and CD4(+) lymphocyte count and CD4/CD8 ratio among the groups with respect to serum leptin levels. CD34(+)CD7(+) lymphocyte count was positively correlated with serum leptin levels (r=0.416, P<0.05). CONCLUSIONS: Hyperleptinemia is not rare during the posttransplant period. Our data support the results of previous experimental studies that have demonstrated the effect of the leptin hormone on lymphoid stem cells. The central and peripheral effects of leptin may differ on lymphoid stem cells and a serum threshold level may apply for the central effects.

Two neurofibromatosis type 1 cases associated with rhabdomyosarcoma of bladder, one with a large deletion in the NF1 gene.

Neurofibromatosis type 1 (NF1) is the most common neurogenetic disorder, affecting approximately 1 in 3,500 individuals worldwide. Mutations of the NF1 tumor suppressor gene predispose individuals to a variety of benign and malignant tumors. Rhabdomyosarcoma (RMS) is an uncommon malignant soft tissue sarcoma and is also a rare tumor type in NF1 patients. We report two cases of NF1 with RMS. The first is that of an infant with overlapping phenotypic features of NF1 and Noonan syndrome (NS) who presented with RMS of the bladder. The second infant likewise exhibited NF1 features and was also associated with bladder RMS. DNA samples were extracted from peripheral blood and tumor tissue samples. We performed loss of heterozygosity (LOH) analysis of the NF1 gene by using seven intragenic markers (IVS27AAAT2.1, IVS27EVI-20, IVS27AC24.8, IVS27AC28.4, M98509, IVS27AC33.1, IVS38TG53.0) and one extragenic polymorphic marker (3'NF1). A large deletion was detected in the NF1 gene in the NF1-Noonan syndrome (NF-NS) case associated with RMS.

Global fibrinolytic capacity in children on dialysis.

UNLABELLED: Disturbances of coagulation and fibrinolysis have been reported in patients with chronic uremia. Studies of different coagulation and fibrinolysis parameters in regularly dialyzed patients have yielded conflicting results. Global fibrinolytic capacity (GFC) examines the function of the entire fibrinolytic system. This assay is a sensitive and reliable method for evaluating the fibrinolytic function of plasma in vitro. In this study, GFC was used as a screening test to investigate the effects of two different dialysis modalities on the fibrinolytic system on children on long-term dialysis. MATERIALS AND METHODS: The study included 12 children (age range, 11-20 years; mean age, 15.9+/-3.3 years) who were undergoing regular hemodialysis (HD) and 12 children (age range, 10-15 years; mean age, 13.1+/-1.7 years) who were undergoing continuous ambulatory peritoneal dialysis (CAPD). Thirteen healthy age- and sex-matched subjects served as controls. Each sample was investigated for complete blood count and serum levels of C-reactive protein, serum electrolytes, total cholesterol, triglyceride, fibrinogen, total protein and albumin. A GFC assay was also done in each case. RESULTS: The mean GFC in the CAPD group was lower than that in the HD and control groups (p<0.05). There was no significant difference between the mean GFC values of HD patients and controls. The mean serum albumin level was lower in CAPD patients than in HD patients (p<0.05), and there was also a positive correlation between serum albumin level and GFC in patient groups(r=0.52, p<0.05). Global fibrinolytic capacity was positively correlated with hemoglobin level and negatively correlated with weekly erythropoietin dose per kg body weight (r=0.56 and r=-0.49, respectively; p<0.05). CONCLUSION: The results suggest that CAPD patients have decreased fibrinolytic capacity compared to HD patients. Hypoalbuminemia and erythropoietin treatment may contribute to suppression of fibrinolytic function CAPD patients.

Effect of congenital heart disease on renal function in childhood.

BACKGROUND: Nephropathy is a well-known complication of congenital heart disease (CHD), and the risk of developing renal impairment is particularly high in patients with cyanotic CHD. Most investigations of renal impairment in CHD have involved patients 20 years and older. This study investigated renal tubule function in pediatric patients with CHD, and compared findings in cyanotic and acyanotic groups. METHODS: Twenty children with acyanotic CHD, 23 children with cyanotic CHD, and 13 healthy children were enrolled. Blood and early morning urine samples were collected from each subject to measure urinary concentrations of sodium, microalbumin, creatinine, beta(2)-microglobulin, and N-acetyl-beta-D-glucosaminidase (NAG). RESULTS: The age and sex distributions in the three groups were similar. Median fractional excretion of sodium (FeNa) and urinary NAG/creatinine were significantly higher in the cyanotic group than in the control group (p = 0.022 and p = 0.002, respectively). There were no statistically significant differences among the groups with respect to urinary beta(2)-microglobulin/creatinine, urinary microalbumin/creatinine or glomerular filtration rate. CONCLUSION: Tubular injury can be detected before glomerular injury occurs even within the first decade of life in patients with cyanotic CHD.

Autoimmune thyroiditis with associated proteinuria: report of two patients.

The association of renal disease and autoimmune thyroid disorders has been reported previously. Renal findings associated with autoimmune thyroiditis present more commonly as proteinuria ranging from mild to nephrotic levels. We report here two adolescent girls with hyperthyroidism associated with transient proteinuria correlated with thyroid hormone levels. They had positive antithyroid peroxidase and antithyroglobulin antibodies. Ultrasonographic and scintigraphic findings of the thyroid gland were consistent with Graves' disease in both. Their renal functions were normal except proteinuria (daily protein excretion of 13.5 mg/m2/h in patient 1 and 11 mg/m2/h in patient 2). When they became euthyroid on antithyroid treatment, proteinuria decreased without associated hematuria and/or hypertension. In conclusion, patients with autoimmune thyroid disease should be assessed for the possibility of proteinuria and the etiological investigation of proteinuria should include evaluation of thyroid functions.

Cerebellar vermis hypoplasia in a patient with Bardet-Biedl syndrome.

Laurence-Moon-Bardet-Biedl syndome is an autosomal recessive condition characterized by retinal dystrophy, obesity, mental retardation, distal limb anomaly, hypogonadism, and renal dysfunction. The symptoms vary among families and even among affected siblings. Certain clinical signs have been used to identify subgroups of patients with this complex condition. Laurence-Moon syndrome as a distinct entity is rare and features paraplegia in the absence of polydactyly or obesity. Bardet-Biedl syndrome is characterized by distal limb anomaly, obesity, and renal involvement, but neurologic symptoms are very unusual. We report a patient exhibiting characteristic features of Bardet-Biedl syndrome in addition to cerebellar vermis hypoplasia and mega cisterna magna.

Neurofibromatosis--Noonan's syndrome with associated rhabdomyosarcoma of the urinary bladder in an infant: case report.

Neurofibromatosis 1 is an autosomal dominant disorder. Noonan's syndrome is known to be associated with neurofibromatoses. Patients with neurofibromatosis are predisposed to developing malignant tumors. The relationship between the genetic changes in the neurofibromin gene and mechanisms associated with tumor development in neurofibromatosis has been investigated. A non-sense mutation C2446T --> R816X of the neurofibromin gene has been detected in some patients with the neurofibromatosis 1-Noonan's syndrome phenotype. We describe a case of an infant with the overlapping features of neurofibromatosis 1 and Noonan's syndrome who presented with rhabdomyosarcoma of the urinary bladder. The genetic analysis of our patient revealed neither mutation in the neurofibromatosis 1-guanosine triphosphatase-activating protein-related domain nor the R816X nonsense mutation. The phenotypic and genotypic features of neurofibromatosis, Noonan's syndrome, and cases with the overlapping features of both syndromes have been reviewed. The presentation of our case underlines the importance of careful examination for the clinical features of neurofibromatosis and phenotypic traits of associated diseases, especially in patients with malignant tumors.

Severe iron deficiency anemia in a child with idiopathic pulmonary hemosiderosis: a case report.

We report a case of idiopathic pulmonary hemosiderosis (IPH) in a three-year-old male patient who presented with severe iron deficiency anemia. The child had been diagnosed with iron deficiency anemia nine months earlier and had received multiple blood transfusions, but the cause of his anemia had not been established. The diagnosis of IPH was made after a biopsy of the left lung showed large numbers of hemosiderin-filled macrophages in the alveoli. He did not respond to standard dose corticosteroid (CS) treatment (2 mg/kg/d). However, high-dose short-term CS treatment was successful in two episodes of acute respiratory hemorrhage in this patient. We conclude that IPH should always be considered when investigating the cause of iron deficiency anemia. A more rapid diagnosis in this case could have prevented unnecessary investigations and blood transfusions. We also suggest that high-dose short-term CS treatment should be kept in mind, especially in patients who do not respond to a standard dose.

Biochemical markers of bone turnover in the diagnosis of renal osteodystrophy in dialyzed children.

In this study we investigated the value of biochemical markers of bone turnover in the diagnosis of renal osteodystrophy in dialysis patients. The study was carried out in 22 chronic renal failure patients (mean age: 16.1 +/- 4.5) being treated with chronic dialysis. There were three groups according to intact parathormone (iPTH) levels: Group I (n: 6): iPTH levels were less than 200 pg/ml; Group II (n: 9): iPTH levels were between 201 and 500 pg/ml; and Group III (n: 7). iPTH levels were higher than 501 pg/ml. We investigated iPTH, bone alkaline phosphatase, total serum alkaline phosphatase, osteocalcin, serum type 1 procollagen peptide (PICP) and insulin-like growth factor-1 (IGF-1) levels in all patients. In group III mean bone alkaline phosphatase level (126.0 +/- 10.95) was significantly higher than in both group I and group II (52.16 +/- 22.8, 57.35 +/- 16.21) (p < 0.001). Mean osteocalcin level (35.13 +/- 2.93) in group I was significantly lower than in group III (40.52 +/- 2.83) (p < 0.05). Serum alkaline phosphatase, PICP and IGF-1 levels were not different between the groups (p > 0.05). There was a significant positive correlation between bone alkaline phosphatase and iPTH (r = 0.80, p < 0.0001). Serum osteocalcin correlated with both bone alkaline phosphatase and iPTH (correlation) coefficients were r = 0.44 and r = 0.51 respectively, p < 0.05). It is concluded that bone alkaline phosphatase and osteoocalcin combined with iPTH level seem to be useful noninvasive markers of bone metabolism in dialysis patients.

Beneficial role of intravenous calcitriol on bone mineral density in children with severe secondary hyperparathyroidism.

OBJECTIVES: In this prospective study, the effect of calcitriol therapy on bone mineral density and osteopenia in patients with severe secondary hyperparathyroidism has been investigated. MATERIALS AND METHODS: The study was carried out on 24 chronic dialysis patients consisting of 13 boys and 11 girls, aged between 8-18 years. Patients were divided into 3 groups according to the severity of hyperparathyroidism and therapy regimens. Group I consisted of 5 patients with normal parathormon levels who did not receive calcitriol therapy. In group II and III, there were patients with secondary hyperparathyroidism. Group II consisted of 10 patients receiving oral calcitriol therapy. Group III consisted of 9 patients receiving intravenous (i.v.) calcitriol. Bone mineral density was measured by dual energy x-ray absorptiometry. Osteopenia was defined as a Z-score worse than -2. Bone mineral density was assessed as baseline and at the end of one year. RESULTS: A significant improvement was observed in Z-score in the group III whereas the mean value of Z-score tended to be worse in group I and it was not significantly different in group II from the initial values. The better Z-score in group III was associated with more effective stabilization of alkaline phosphatase level and bone specific alkaline phosphatases (BAP) concentrations. CONCLUSION: Significant improvement of Z-score in group III suggested the beneficial role in i.v. administration of calcitriol in chronic dialysis patients.

Brachydactyly short-stature hypertension syndrome: a case with associated vascular malformations.

Brachydactyly short-stature hypertension syndrome, also known as hypertension-with-brachydactyly (HTNB) syndrome, is a rare autosomal dominant disorder that was first described by Bilginturan and colleagues in 1973. Many familial cases of HTNB have been reported, but the first sporadic case of this condition was published only recently. This article describes a case of HTNB syndrome in a 16-year-old boy. Although Doppler ultrasonography of the kidneys and renal arteries showed normal findings, magnetic resonance angiography showed an aberrant right posterior inferior cerebellar artery, early bifurcation of the left renal artery, and irregularity and stenosis of the inferior dominant branch of this artery. The patient's father was in chronic renal failure of which the primary pathology was unknown. We speculate that the described case is the second documented sporadic case of HTNB syndrome. This disorder should be included in the differential diagnosis of patients with short stature and hypertension of unknown aetiology. Such individuals should be carefully examined for brachydactyly and for cerebral-cerebellar and renal vascular malformations.

Effect of obesity on inflammatory markers and renal functions.

AIM: To examine the relationship between inflammation criteria and body mass index in otherwise-healthy obese schoolchildren and to evaluate the effect of obesity on renal functions. METHODS: Sixty-five otherwise-healthy obese children (median age 10.8 y, range 7.1-16.5 y; median body mass index 26.8 kg/m(2), range 19.9-38.7 kg/m(2)) and 20 healthy controls (median age 12.4 y, range 10.1-17.1 y; median body mass index 18.8 kg/m(2), range 17.3-23.1 kg/m(2)) were included. Blood and urine samples were taken from every child. RESULTS: Children in the obese and control groups had similar age and sex distributions (p>0.05). Inflammatory mediators were higher in obese children (p<0.05). A significant positive correlation was found between glomerular filtration rate and body mass index in the whole study group (r=0.39, p=0.001). A positive correlation was found between body mass index standard deviation and inflammatory mediators and glomerular filtration rate. No significant difference existed regarding protein and microalbumin excretion in the urine. CONCLUSION: Inflammatory mediators increased significantly in obese children, and the glomerular filtration rate increased as the body mass index increased. To prevent obesity-related complications in adulthood, it is important to take measures to prevent development of obesity during childhood.

Assessment of left ventricular diastolic function by Doppler tissue imaging in children with end-stage renal disease.

AIM: To evaluate left ventricular (LV) diastolic function in children with end-stage renal disease (ESRD) using conventional pulsed-Doppler echocardiography and Doppler tissue imaging (DTI), and to compare the findings with these two modalities. METHODS: Twenty-four children with ESRD and 22 healthy age- and sex-matched control subjects were assessed with conventional Doppler echocardiography and DTI. The scans of the renal disease patients were done after a dialysis session. Parameters related to LV systolic and diastolic function were compared in the ESRD and control groups. RESULTS: The ESRD patients had lower mean mitral E/A ratio both according to conventional Doppler echocardiography and TDI than the control subjects. The ESRD group also had significantly longer isovolumetric relaxation time (116+/-31 ms vs 97+/-3.1 ms, respectively; p<0.001), and significantly longer deceleration time (235+/-44 ms vs 202+/-35 ms, respectively; p<0.01) than the control group. CONCLUSION: DTI findings correlate well with conventional Doppler echocardiography findings. Children with ESRD show, after dialysis, echocardiographic signs of LV diastolic dysfunction.

Unusual presentation of IgA nephropathy in childhood: a case report.

Immunoglobulin A (IgA) nephropathy is the most common form of primary glomerulonephritis worldwide, and approximately 20% to 30% of adult patients with the disorder develop chronic renal failure within 20 years. This type of nephropathy is also an important risk factor for chronic renal failure in children. The pathogenesis of IgA nephropathy is still unknown, and treatment remains controversial. Microscopic hematuria and recurrent episodes of macroscopic hematuria are the most common clinical manifestations of this condition in children. This article describes the case of a young girl who presented with steroid-resistant nephrotic syndrome unaccompanied by hematuria. Renal biopsy findings were consistent with IgA nephropathy. The patient's condition was a rare clinical manifestation of IgA nephropathy.

Glycosaminoglycans in childhood urinary tract infections.

It has been suggested that urinary glycosaminoglycans (GAGs) form a natural defense mechanism against urinary tract infections (UTIs). This study investigated whether urinary GAGs play a role in pediatric UTIs, and whether urinary GAG level can be used to differentiate upper UTI from lower UTI. Forty-one children with UTIs (33 girls and eight boys; mean age 5.4+/-3.7 years) and 46 age- and sex-matched healthy children (35 girls and 11 boys; mean age 6.6+/-3.9 years) were included in the study. Urinary GAG levels were measured at the onset of acute infection and after a 10-day course of antibiotic treatment. Group GAG findings were compared, and comparisons were also made with the patients divided according to sex and according to UTI type (upper versus lower). The mean urinary GAG level in the patient group at the onset of acute infection (pretreatment) was significantly higher than the mean level in the control group (132.2+/-104.8 mg/g vs 42.2+/-27.1 mg/g creatinine, respectively; P <0.01). In the patient group, the mean urinary GAG level after antimicrobial therapy was significantly lower than the pretreatment level (75.9+/-52.1 mg/g vs 132.2+/-104.8 mg/g creatinine, respectively; P <0.01). However, the mean post-treatment level was still higher than the mean level in the controls ( P <0.05). There was no significant difference in urinary GAG levels when patients were categorized as upper versus lower UTI ( P >0.05). The study results suggest that GAGs play an important role in the pathogenesis of UTIs in children, and that measurement of urinary GAGs may be a valuable noninvasive method for evaluating UTIs in this patient group. However, this assay cannot be used to differentiate upper UTI from lower UTI in children.

Acute renal failure and mortality after open-heart surgery in infants.

Acute renal failure (ARF) is a major complication in infants who undergo cardiac surgery. The aim of this investigation was to identify possible risk factors for ARF and mortality in this patients group. Out of 64 patients, 21 (32.8%) cases developed acute renal failure and overall mortality rate was 25%. The mortality rate was higher in the infants who developed ARF than those who did not (66.7% and 4.7%, respectively, p<0.05). Also, ARF was positively correlated with mortality (r:0.70, p<0.0001). The nonsurvivors had lower mean serum albumin than did the survivors (p<0.05), and serum albumin level was negatively correlated with mortality (r= -0.34, p< 0.05). For the patients with serum albumin level <3.5 g/dL, the unadjusted odds ratio for mortality was 4.3 (CI 95%:1.05-17.86). Total bypass time and aorta clamping time were significantly longer in the nonsurvivor group than in the survivor group (p<0.05 for both). In conclusion, the significant risk factors for mortality in these patients were development of ARF, low serum albumin level, and long total bypass and aorta clamping times, which may be predictive of poor prognosis.

Acute renal failure in the neonatal period.

Acute renal failure (ARF) is a common problem in the neonatal intensive care unit (NICU). In most cases, ARF is associated with a primary condition such as sepsis, metabolic diseases, perinatal asphyxia and/or prematurity. This retrospective study investigated the course of illness, therapeutic interventions, early prognosis and risk factors associated with development of ARF in the neonatal period. A total of 1311 neonates were treated in our NICU during the 42-month study period, and 45 of these babies had ARF. This condition was defined as serum creatinine level above 1.5 mg/dL despite normal maternal renal function. The data collected for each ARF case were contributing condition, cause and clinical course of ARF, gestational age and birth weight, age at the time of diagnosis, treatment, presence of perinatal risk factors and need for mechanical ventilation. The frequency of ARF in the NICU during the study period was 3.4%. Premature newborns constituted 31.1% of the cases. The mean birth weight in the group was 2863 +/- 1082 g, and the mean age at diagnosis was 6.2 +/- 7.4 days. The causes of ARF were categorized as prerenal in 29 patients (64.4%), renal in 14 patients (31.1%) and postrenal in 2 patients (4.4%). Forty-seven percent of the cases were nonoliguric ARF. Asphyxia was the most common condition that contributed to ARF (40.0%), followed by sepsis/metabolic disease (22.2%) and feeding problems (17.8%). Therapeutic interventions were supportive in 77.8% of the cases, and dialysis was required in the other 22.2%. The mortality rate in the 45 ARF cases was 24.4%. Acute renal failure of renal origin, need for dialysis, and need for mechanical ventilation were associated with significantly increased mortality (p<0.05). There were no statistical correlations between mortality rate and perinatal risk factors, oliguria, prematurity or blood urea nitrogen and creatinine levels. The study showed that, at our institution, ARF in the neonatal period is frequently associated with preventable conditions, specifically asphyxia, sepsis and feeding problems. Supportive therapy is effective in most cases of neonatal ARF. Acute renal failure of renal origin, need for dialysis, and need for mechanical ventilation were identified as indicators of poor prognosis in these infants. Early recognition of risk factors and rapid effective treatment of contributing conditions will reduce mortality in neonatal ARF.

Gabapentin versus levodopa for the treatment of Restless Legs Syndrome in hemodialysis patients: an open-label study.

BACKGROUND: Restless Legs Syndrome (RLS), a common problem increasing morbidity and mortality in hemodialysis (HD) patients, affects 20-30% of uremic patients. Our aim was to find the efficacy of gabapentin in the treatment of RLS in HD patients by comparing a largely used drug, levodopa. METHODS: Patients with RLS answered three questionnaires (RLS rating scale proposed by IRLSSG, the Short Form (SF)-36 and the Pittsburgh Sleep Quality Index) for the evaluation of severity of RLS, effects on quality of life and quality of sleep. RESULTS: Fifteen patients (4.7%) (5 F, 10 M) with a mean age of 45.8+/-15.3 years got RLS diagnosis. When we compare the two drugs for severity of RLS symptoms relief, the effect of gabapentin was more significant (p<0.001). Gabapentin significantly improved general health, body pain and social functions (p<0.001). Moreover, regarding sleep parameters, gabapentin was significantly superior to levodopa for sleep quality, sleep latency (p<0.001) and sleep disturbance (p<0.000). CONCLUSION: To our knowledge this was the first study comparing gabapentin and levodopa efficacy for the treatment of RLS in HD patients. Our results suggested that gabapentin is an effective drug for the management of RLS in hemodialysis patients.

Congenital cataract, microphthalmia, hypoplasia of corpus callosum and hypogenitalism: report and review of Micro syndrome.

We report on a 7-month-old boy with Micro syndrome who was referred for assessment of mental-motor retardation and reduced vision with cataract. The characteristics of Micro syndrome are mental retardation, microcephaly, congenital cataract, microcornea, microphthalmia, agenesis/hypoplasia of the corpus callosum, and hypogenitalism. The differential diagnosis includes cerebro-oculo-facio-skeletal syndrome (COFS); a syndrome involving cataract, arthrogryposis, microcephaly, and kyphoscoliosis (CAMAK); a syndrome with cataract, microcephaly, failure to thrive, and kyphoscoliosis (CAMFAK); Martsolf syndrome; Neu-Laxova syndrome; Lenz microphthalmia syndrome; and Smith-Lemli-Opitz syndrome. Till date, no renal malformations have been reported in Micro syndrome. Our patient had fusion of the lower poles of the kidneys and his left kidney was ectopic. Ocular findings are the most reliable neonatal diagnostic signs of Micro syndrome. Minör anomalies in Micro syndrome may be subtle and therefore not of significant diagnostic value. Micro syndrome is an autosomal recessive trait. Till date, most reported cases have been in individuals of Muslim origin. In countries with high rates of consanguineous marriage, such as Turkey, it is important that physicians be able to recognize this syndrome. Micro syndrome should be considered in any infant with congenital cataract.