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Alper Soylu

Publications and source records attributed to Alper Soylu.

At least 19 recordsLinked to original sources
PubMed2006

Positional cloning uncovers mutations in PLCE1 responsible for a nephrotic syndrome variant that may be reversible.

Nephrotic syndrome, a malfunction of the kidney glomerular filter, leads to proteinuria, edema and, in steroid-resistant nephrotic syndrome, end-stage kidney disease. Using positional cloning, we identified mutations in the phospholipase C epsilon gene (PLCE1) as causing early-onset nephrotic syndrome with end-stage kidney disease. Kidney histology of affected individuals showed diffuse mesangial sclerosis (DMS). Using immunofluorescence, we found PLCepsilon1 expression in developing and mature glomerular podocytes and showed that DMS represents an arrest of normal glomerular development. We identified IQ motif-containing GTPase-activating protein 1 as a new interaction partner of PLCepsilon1. Two siblings with a missense mutation in an exon encoding the PLCepsilon1 catalytic domain showed histology characteristic of focal segmental glomerulosclerosis. Notably, two other affected individuals responded to therapy, making this the first report of a molecular cause of nephrotic syndrome that may resolve after therapy. These findings, together with the zebrafish model of human nephrotic syndrome generated by plce1 knockdown, open new inroads into pathophysiology and treatment mechanisms of nephrotic syndrome.

Animals↗
PubMed2006

Paracellin-1 gene mutation with multiple congenital abnormalities.

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is an autosomal recessive renal tubular disorder characterized by renal magnesium wasting, hypercalciuria, advanced nephrocalcinosis and progressive renal failure. Mutations in the paracellin-1 (CLDN16) gene have been defined as the underlying genetic defect. The tubular disorders and progression in renal failure are usually resistant to magnesium substitution and hydrochlorothiazide therapy, but hypomagnesemia may improve with advanced renal insufficiency. We present a patient with a homozygous truncating CLDN16 gene mutation (W237X) who had early onset of renal insufficiency despite early diagnosis at 2 months. He also had additional abnormalities including horseshoe kidney, neonatal teeth, atypical face, cardiac abnormalities including coarctation of the aorta associated with atrial and ventricular septal defects, umbilical hernia and hypertrichosis. To the best of our knowledge, this is the youngest case diagnosed as familial hypomagnesemia with hypercalciuria and nephrocalcinosis and the first case having such additional congenital abnormalities independent of the disease itself.

Abnormalities, Multiple↗
PubMed2006

Medullary sponge kidney associated with distal renal tubular acidosis in a 5-year-old girl.

INTRODUCTION: Medullary sponge kidney (MSK) is characterized by cystic dilatation of the inner medullary collecting ducts, which causes the kidneys to resemble a sponge. CASE REPORT: Although distal renal tubular acidosis (dRTA) is commonly observed in patients with MSK, we report a 5-year-old girl with MSK who had features of both dRTA (nephrocalcinosis, hypercalciuria, hypocitraturia) and proximal tubular dysfunction (hyperuricosuria, impaired tubular phosphate reabsorption and proteinuria). DISCUSSION: Metabolic acidosis, hypercalciuria, hypocitraturia, tubular phosphate reabsorption and growth retardation in the patient improved with alkali therapy.

Acidosis, Renal Tubular↗
PubMed2006

Relationship of increased renal cortical echogenicity with clinical and laboratory findings in pediatric renal disease.

PURPOSE: To correlate the clinical and laboratory findings with increased renal cortical echogenicity in children with acute renal diseases. MATERIALS AND METHODS: Children with increased renal cortical echogenicity were evaluated retrospectively. Laboratory findings and final diagnoses were reviewed. Patients with increased echogenity were classified into group 1 (mild; grade I) or group 2 (more severe; grades II and III). RESULTS: There were 7 newborns and 114 children (67 male, 47 female) with increased renal cortical echogenicity with a mean (+/-SD) age of 7.0 (+/-4.4) years. The clinical diagnosis was anatomic abnormality (including vesicoureteral reflux, ureteropelvic junction obstruction, ureterovesical junction obstruction, double collecting system) in 9%, urinary tract infection in 21%, urolithiasis in 6%, nephrotic syndrome in 20%, glomerulonephritis in 32%, and other diseases in 12%. Hyperechogenicity was bilateral in 72%, right-sided in 19%, and left-sided in 9%. There were 81 patients in group 1 and 33 patients in group 2 (grade II, 29; grade III, 4). There was no statistically significant difference between the groups with regard to age, sex, and serum blood urea nitrogen level, serum creatinine level, uric acid level, urine pH, and specific gravity. Hematuria was more frequent in group 2, whereas proteinuria and pyuria incidences were similar in the 2 groups. In patients with hematuria, glomerulonephritis was the most common cause. CONCLUSIONS: Glomerulonephritis is the most frequent acute disease causing increased renal echogenicity in childhood, and higher echogenicity is more likely to be associated with hematuria.

Acute Disease↗
PubMed2006

Febrile myalgia syndrome in familial Mediterranean fever.

Familial Mediterranean fever is characterized by recurrent polyserositis episodes associated with fever. However, the clinical spectrum of this disease has been expanded recently and myalgia is now a frequently recognized component. Protracted febrile myalgia syndrome was first described in patients with familial Mediterranean fever in 1994. This syndrome is characterized by severe paralyzing myalgia, high fever, abdominal pain, diarrhea, arthritis/arthralgia, and transient vasculitic rashes mimicking Henoch-Schonlein purpura. Recently, we evaluated 6 patients with the clinical picture of protracted febrile myalgia syndrome in our clinic. One of them was a patient with known familial Mediterranean fever, but the others were subsequently diagnosed to have familial Mediterranean fever by mutational analyses. Thus, introduction of genetic analysis would possibly change the diagnostic criteria for familial Mediterranean fever. In addition, all 6 patients presented in the spring months when streptococcal infections are at their peak rate and 3 of them had elevated ASO levels indicating that streptococci could be one of the agents triggering protracted febrile myalgia syndrome.

Child↗
PubMed2006

Effects of lactational cyclosporine A use on rat pups.

We aimed to evaluate the structural and functional changes in the thymus and kidneys of rat pups whose mothers were given cyclosporine A (CsA) during lactational period. Six adult nursing Wistar rats and their 30 pups were studied. Rat pups were divided into four groups as follows: 21-day treated group and 21-day placebo group, each including 10 breastfeeding pups sacrificed on the 21st day, whose mothers were given CsA or placebo, respectively (infancy groups) and, 60-day treated group and 60-day placebo group, each including five breastfeeding pups sacrificed on the 60th day, whose mothers were given CsA or placebo, respectively (puberty groups). While CsA levels of mother rats were very high, CsA levels of 21-day treated group pups were zero. There were no renal histomorphometric differences between study and control pups in both age groups. Renal function parameters showed significant differences between study and control pups in the infancy group: the 21-day treated group pups had significantly lower urine volume, proteinuria, FE(Na) and urinary NAG/creatinine ratio. GFR was also lower in the 21-day treated group, but the difference was not significant, and serum creatinine levels were also not different. Renal function differences were not present among the pubertal pups. Thymic corticomedullary ratio of the 21-day treated group was significantly higher than the 21-day placebo group, while there was no difference between the 60-day treated group and 60-day placebo group. There were no significant changes in the number and distribution of CD3+, CD4+, and CD8+ thymocytes between study and control pups in both age groups. In conclusion, breastfeeding by CsA-treated mother rats induced structural alterations in the thymus and functional changes in the kidneys of the rat pups during infancy. Disturbances in the kidneys and thymus mostly improved after CsA exposure was over.

Acetylglucosaminidase↗
PubMed2005

In vitro analysis of the effect of hyperbilirubinemia on rabbit ureter and bladder.

Spontaneous resolution of intrauterine pelvic dilatations after birth is an expected outcome. In nonobstructive pelvic dilatations, changes in ureteral and bladder physiology may also play a part. We aimed to demonstrate the effect of increased concentrations of bilirubin on ureteral and bladder muscles in vitro. Normal and pathologic concentrations of bilirubin (3.5x10(-7)-10(-5)M and 10(-4)-4x10(-4)M, respectively) caused no change in the basal ureter tension (343.9+/-29.4 mg). Normal concentrations of bilirubin caused no difference in basal bladder tension (430.2+/-70.2 mg), but pathologic concentrations caused a decrease of 303.8+/-52.9 mg. Normal and pathologic amounts of bilirubin were cumulatively applied to rabbit ureteral and bladder tissues both after reaching basal tension and when contracted with KCl (80 mM and 120 mM KCl for ureter and bladder, respectively). The cumulative addition of normal bilirubin concentrations to the ureteral tissues precontracted with KCl produced 86.4+/-7.2% relaxation, while the addition of pathologic bilirubin concentrations produced a relaxation of 133.9+/-17.4%, which was significantly higher (p=0.04). Similarly, the addition of normal concentrations of bilirubin to the bladder tissues precontracted with KCl produced a maximal relaxation of 35.3+/-2.2%, while pathologic concentrations produced a maximal relaxation of 53.5+/-3.5%, which was significantly higher (0.001). Consequently, high concentrations of bilirubin caused a mild relaxation in basal ureteral and bladder tensions, while pathologically increased concentrations led to significant relaxation in both types of precontracted tissues. We suggest that high bilirubin levels may partly but not directly contribute to the spontaneous recovery of hydronephrosis because of the relaxation effect on bladder while probably causing susceptibility to urinary tract infections because of relaxation of both ureteral and bladder tissues.

Animals↗
PubMed2005

An adolescent girl with Meyer-Betz syndrome.

Idiopathic paroxysmal rhabdomyolysis indicating a classical triad of symptoms consisting of muscle pain, weakness, and discolored urine is known as "Meyer-Betz syndrome". It may result in acute renal failure due to precipitation of the myoglobin casts in the tubuli or to the direct toxic effects of myoglobin to the tubular epithelium. On the other hand, outcome may be uneventful. In this study, we reported the case of a 16-year-old girl who was admitted with red-colored urine after a slight exertion. She had tenderness and weakness in upper parts of her legs and bilateral flank pain. She had a positive urine dipstick test for heme despite absent red cells on microscopic examination. White cell count, liver function tests, serum creatine kinase (CK), lactate dehydrogenase (LDH), and urine myoglobin levels were raised. All metabolic tests were in normal ranges and EMG was normal. A muscle biopsy performed after recurrent exertional rhabdomyolysis attacks demonstrated normal findings and ruled out metabolic disorders. At the time of attacks, hydration along with alkalinization was applied and she did not experience renal failure. She was advised to avoid strenuous physical exertion and had an uneventful outcome for the last 5 months. We reported the clinical course and follow-up of an adolescent girl with Meyer-Betz syndrome.

Adolescent↗
PubMed2005

Efficacy of COX-2 inhibitors in a case of congenital nephrogenic diabetes insipidus.

A 17-month-old boy presented with failure to thrive, polyuria, and vomiting. He had been diagnosed clinically with nephrogenic diabetes insipidus and treated by amiloride and hydrochlorothiazide combination without a satisfactory outcome at another center since 1 year of age. The diagnosis was confirmed by genetic analysis (AVPR2mutation), and the treatment was modified to include rofecoxib (a selective cyclooxygenase-2 inhibitor) in addition to hydrochlorothiazide and amiloride. This combination along with a low-salt diet resulted in a dramatic decrease in urinary free-water loss, while no side effect was noted. Because of prohibition of rofecoxib, it had to be substituted first by indomethacin and then by ibuprofen. However, both drugs were ineffective in controlling water diuresis. Thus, we had to replace these drugs by celecoxib (another selective cyclooxygenase-2 inhibitor). We conclude that the combination hydrochlorothiazide/amiloride/cyclooxygenase-2 inhibitor could be successfully used to treat congenital nephrogenic diabetes insipidus.

Amiloride↗
PubMed2005

Megacalycosis: report of two cases.

Congenital megacalycosis is a rare renal disorder consisting of caliceal dilatation without evidence of renal pelvic or ureteral obstruction. Since its first description in 1963, only a few cases have been reported. The defect is mostly unilateral, shows male predominance and does not disrupt the renal functions. We report on two male patients with bilateral megacalycosis and different clinical presentations. The first case was diagnosed in adolescence during examination for a urinary tract infection and was followed-up uneventfully for nearly ten years. The second case was found to have megacalycosis during the assessment of antenatal hydronephrosis. We aimed to emphasize the importance of considering megacalycosis in the differential diagnosis of both antenatal hydronephrosis and other causes of caliceal dilatation to prevent unnecessary diagnostic and therapeutic interventions.

Adolescent↗
PubMed2005

A case of Takayasu disease with findings of incomplete Alagille syndrome.

A 16-year-old girl being followed up for Takayasu arteritis for the last 3 years was also found to have Alagille syndrome upon findings of atypical facies, posterior embryotoxon, high-pitched voice, osteopenia and hypogonadism. This case might imply a possible relationship between Takayasu arteritis and Alagille syndrome.

Adolescent↗
PubMed2005

Multisystemic leukocytoclastic vasculitis affecting the central nervous system.

Leukocytoclastic vasculitis is a self-limiting disease with rare systemic complications in the majority of patients. This report describes a 10-year-old male with leukocytoclastic vasculitis caused by an insect bite who presented with central nervous system, lung, kidney, and gastrointestinal involvement in addition to cutaneous findings. The diagnosis was confirmed by histopathologic examination of cerebral hematoma material. Initially, his symptoms improved with a treatment protocol including steroid, cyclophosphamide, intravenous immunoglobulin, and plasmapheresis, but the patient succumbed because of nosocomial sepsis.

Cerebral Hemorrhage↗
PubMed2004

Clinical quiz: a pediatric case presenting with fever and diffuse myalgia.

Familial Mediterranean fever (FMF) is a multisystem disease characterized by recurrent polyserositis episodes seen in certain ethnic groups. In recent years the clinical picture of FMF has been expanded and severe myalgia is a frequently recognized component of the syndrome. Protracted febrile myalgia syndrome (PFMS), characterized by severe paralyzing myalgia, high fever, abdominal pain, diarrhea, arthritis/arthralgia, and transient vasculitic rashes mimicking Henoch-Schonlein purpura, was first described in patients with FMF in 1994. We describe an 11-year-old Turkish girl with a second attack of PFMS before being diagnosed as having FMF, emphasizing the importance of myalgia for the diagnosis of FMF even in the absence of other symptoms.

Anti-Inflammatory Agents↗
PubMed2004

Two-hour post-dose cyclosporin A levels in adolescent renal transplant recipients in the late post-transplant period.

Although the success of renal transplantation is closely linked to the immunosuppression provided by cyclosporin A (CsA), the best way to monitor the blood levels of CsA is still not clear. Trough CsA levels (C(0)) are commonly used, but the 2-h post-dose CsA levels (C(2)) are reported to correlate better with area under the curve. The aim of this study was to evaluate the correlation of C(2) levels with allograft function in adolescent renal transplant recipients in the late post-transplant period (6 months after transplantation) compared with C(0 )levels. The data of 17 adolescent renal transplant recipients (12 males, 5 females) were evaluated retrospectively. The mean age at the time of transplantation was 15.212+/-2.918 years and the mean follow-up period was 53.172+/-34.090 months. C(0) levels correlated with oral CsA and diltiazem doses, while C(2) levels exhibited no correlation. When C(2) levels were classified as 0-400, 401-800, and 801-1200 ng/ml, no statistically significant difference was found between these groups with respect to glomerular filtration rate (P=0.830). Although 82% of the patients had C(2 )beneath the therapeutic level (<800 ng/ml), none had an acute rejection episode. In conclusion, optimum C(2) levels could be different from levels in the adult population. Furthermore, the correlation of C(2) levels with CsA dose seems to be weaker than in the adult population. Thus, further studies are needed to determine a more reliable predictor for CsA dose monitoring and target blood CsA levels in adolescent patients.

Adolescent↗
PubMed2004

Frequent vaccination and immune complex deposition in unilateral nephrectomized mice.

The aim of this study was to investigate the effect of increased number and frequency of vaccination on immune complex deposition in the choroid plexus and glomeruli of non-nephrectomized and unilateral nephrectomized mice. Fifty-five non-nephrectomized, 40 nephrectomized, and 7 control Swiss albino mice were used. Half of each group was vaccinated only with diphtheria-tetanus and the other half with multiple vaccines, which are used in pediatric practice. Each group was divided into subgroups, which were vaccinated with increasing frequency. No immune deposits were detected in the choroid plexus of any vaccinated mice. There were immune deposits in glomeruli in 2 of 55 (3.6%) of the non-nephrectomized and in 3 of 40 (7.5%) of the nephrectomized mice (P=0.199). The difference between the diphtheria-tetanus and multiple vaccine groups in non-nephrectomized (P=0.236) and nephrectomized (P=1.000) mice was not significant. A significant positive correlation between increased frequency of vaccination and glomerular immune complex deposition 8 weeks after the last immunization was detected in the multiple vaccine group of nephrectomized mice (P=0.048, r=0.447). Our results suggest that the large number and frequent doses of vaccines would not lead to immune complex deposition in choroid plexus and do not significantly increase the deposition of immune complexes in glomeruli in unilateral nephrectomized mice compared with non-nephrectomized mice.

Animals↗
PubMed2004

Epidermal growth factor receptor expression in human renal allograft biopsies: an immunohistochemical study.

OBJECTIVE: Epidermal growth factor receptor (EGFR) expression has been implicated in the progression of many tumors related to cell proliferation, differentiation, invasion and inhibition of apoptosis, and EGFR-targeted therapy options are under development. EGFR expression has been identified in normal and diseased native kidneys. However, its expression in renal allografts and its relation to rejection remains unclear. We aimed to investigate EGFR expression in renal allograft biopsies. MATERIAL AND METHODS: Sections from 52 renal allograft and 11 implantation biopsies were stained by EGFR antibody with streptavidin-biotin-immunoperoxidase method. Immunostaining of EGFR in renal tubules was scored semiquantitatively and the percentage of glomeruli expressing EGFR was determined. The results were correlated with Banff scores and serum creatinine values. RESULTS: Tubular EGFR expression was observed in 81.8% of implantation and 92.3% of allograft biopsies. Glomerular EGFR expression was identified in 18.2% of implantation and in 26.9% of allograft biopsies. The mean percentage (%) of glomeruli-expressing EGFR was 3.73+/-0.84 for implantation biopsies and 7.9+/-0.17 for allograft biopsies (p = 0.53, Mann Whitney U test). For implantation biopsies, tubular EGFR expression scores were 1.90+/-2.11 and for allograft biopsies, 2.89+/-2.01 (p = 0.08, Mann Whitney U test). Tubular EGFR expression was moderately correlated with interstitial fibrosis and tubular atrophy for allograft biopsies (p = 0.04, r = 0.3 and p = 0.04, r = 0.3, respectively, Spearman's rank correlation). CONCLUSIONS: These findings suggest a possible role of EGFR expression in renal scarring in the course of chronic allograft nephropathy, probably involved in a complex pathway.

Adolescent↗