Alper Soylu

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 PLCε1 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 PLCε1. Two siblings with a missense mutation in an exon encoding the PLCε1 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.

Carbamazepine and valproic acid: effects on the serum lipids and liver functions in children.

We aimed to determine the effects of carbamazepine, which induces liver microsomal enzymes, and valproic acid on the serum lipids and liver function test results in epileptic children. Thirty-eight epileptic children (18 males, 20 females, mean age 8.6 +/- 3.9 years) were evaluated for serum lipids and liver function test results at the onset and the second and sixth months of antiepileptic therapy. The results of the children receiving carbamazepine (n = 31) and valproic acid (n = 7) were compared. In addition, the values obtained at different periods of treatment were compared within each group. The differences in the serum lipid levels and liver function test results of the children in the carbamazepine group and the valproic acid group were not statistically significant throughout the study. However, the total cholesterol, low-density lipoprotein, total cholesterol/high-density lipoprotein, and gamma glutamyl transferase levels were significantly increased in the carbamazepine group during treatment (P < 0.05) but not in the valproic acid group. Carbamazepine treatment alters the serum lipid profile of the children in such a way that it facilitates the development of atherosclerosis. Valproic acid does not alter the levels of the serum lipids.

Posterior leukoencephalopathy syndrome in poststreptococcal acute glomerulonephritis

Abstract Reversible posterior leukoencephalopathy syndrome is an increasingly recognized brain disorder most commonly associated with hypertension, toxemia of pregnancy, or the use of immunosuppressive agents. Its clinical features include headache, decreased alertness, mental abnormalities, such as confusion, diminished spontaneity of speech, changed behavior ranging from drowsiness to stupor, seizures, vomiting, and abnormalities of visual perception like cortical blindness. Magnetic resonance imaging shows edematous lesions primarily involving the posterior supratentorial white matter and corticomedullary junction. We describe a 7-year-old uremic girl who developed neurological symptoms of posterior leukoencephalophaty syndrome during the course of acute poststreptococcal glomerulonephritis. Since the symptoms first appeared 24 h after a hypertensive crisis and the patient was uremic at the time of symptoms, we decided to report this patient to discuss the differential diagnosis of neurological symptoms developing during the course of acute poststreptococcal glomerulonephritis.

Evaluation of the effect of acetyl L-carnitine on experimental cisplatin nephrotoxicity.

Background/Aims: To evaluate the protective effects of acetyl L-carnitine (ALCAR) on cisplatin-induced nephrotoxicity in rats, and to gain insights into the possible protective mechanisms of ALCAR against nephrotoxicity. Methods: Twenty-eight Wistar rats were divided into four groups. Group 1 was administered saline only, group 2 was administered ALCAR, group 3 was administered cisplatin, and group 4 was administered ALCAR prior to cisplatin. Rats were sacrificed after 72 h of cisplatin/saline infusion. Serum creatinine and glomerular filtration rate values were obtained, and kidney samples were examined by light and electron microscopy. Apoptotic cell death and caspase-3, 8 and 9 activities were studied immunohistochemically. Results: In group 4, ALCAR administration resulted in an improvement in kidney function tests. Histopathological findings confirmed the biochemical data. Whilst the fusion of the foot processes of podocytes was observed in group 3, they were intact in group 4 on electron-microscopic examination. Apoptotic cell death and caspase-3, 8 and 9 activities were also decreased in group 4 compared to group 3. Conclusions: Antioxidative, antiapoptotic and anti-inflammatory properties of ALCAR were supported by the findings that this agent improves kidney function tests and has the effects of tissue protection and inhibition of apoptosis in cisplatin-induced nephrotoxicity.

Henoch-Schönlein nephritis: a nationwide study.

Background/Aim: The aim of this retrospective study was to evaluate the presentation, clinical and pathological manifestations and outcome of the Henoch-Schönlein purpura (HSP) nephritis in children. Methods: Clinical and laboratory data of 443 children with HSP nephritis aged between 3 and 16 years from 16 pediatric nephrology reference centers were analyzed retrospectively. The biopsy findings were graded according to the classification developed by the International Study of Kidney Disease in Children (ISKDC). Results: Renal biopsy was performed in 179 of the patients with HSP nephritis. The most common presenting clinical finding in patients who were biopsied was nephrotic range proteinuria (25%) which was followed by nephritic-nephrotic syndrome (23.5%). The biopsy findings according to the ISKDC were as follows: class I: 8.3%; II: 44.1%; III: 36.3%; IV: 6.7%; V: 3.3%; VI: 1.1%. All of the patients who developed end-stage renal disease had nephritic-nephrotic syndrome at presentation. Of 443 patients, 87.2% had a favorable outcome and 12.8% had an unfavorable outcome. The overall percentage of children who developed end-stage renal disease at follow-up was 1.1%. Logistic regression analysis did not show any association of initial symptoms and histology with outcome. Conclusion: In the presented cohort, the presence of crescents in the first biopsy or presenting clinical findings did not seem to predict the outcome of HSP nephritis in children. We conclude that children with HSP nephritis even with isolated microscopic hematuria and/or mild proteinuria should be followed closely.

The clinical value of urinary N-acetyl-beta-D-glucosaminidase levels in childhood age group.

N-acetyl-beta-D-glucosaminidase is a high molecular-weight lysosomal enzyme found in many tissues of the body. It cannot pass into glomerular ultrafiltrate due to its high molecular weight. However, this enzyme shows high activity in renal proximal tubular cells, and leaks into the tubular fluid as the ultrafiltrate passes through proximal tubules. When proximal tubular cells are injured due to to any disease process including glomerular proteinuria, nephrolithiasis, hyperglycemia, interstitial nephritis, transplant rejection or nephrotoxic agents such as antibiotics, antiepileptics, or radiocontrast agents, its urine level increases and thus is used as a reflection of proximal tubular cell necrosis. However, the clinical use of urinary N-acetyl-beta-D-glucosaminidase determination is limited in childhood because of certain technical problems. In addition, the urinary level of this enzyme changes with the maturational level of proximal tubular cells. Thus, difficulties are involved in assessing normal urine levels of this enzyme for age. On the other hand, successive measurements of urinary N-acetyl-beta-D-glucosaminidase during the longitudinal follow-up of the patients may enhance its clinical use as an indicator of ongoing tubular injury.

Systemic lupus erythematosus presenting with normocomplementemic urticarial vasculitis in a 4-year-old girl

cytoclastic vasculitis of dermal vessels are the hallmarks of urticarial vasculitis.1 Urticarial vasculitis has been reported to be associated with connective tissue diseases, such as systemic lupus erythematosus (SLE), mixed cryoglobulinemia, drug reactions, hepatitis B antigenemia and malignant disease.1,2 Hypocomplementemic urticarial vasculitis (HUV) has been reported to be more strongly associated with SLE and patients with this form of urticarial vasculitis have been determined to have more severe multisystem disease in comparison with patients who have normocomplementemic urticarial vasculitis (NUV).3,4 In a recently published broadbased report, the average age at which urticarial vasculitis was diagnosed was 43 and 51 years for patients with HUV and NUV, respectively.1 In addition, in that study, the youngest patients with HUV and NUV were 15 and 7 years, respectively. In the present study, we report on a 4-year-old girl with NUV whose symptoms began at the age of 1 year and whose clinical picture progressed to SLE at the age of 4 years.

Effect of socioeconomic status on the blood pressure in children living in a developing country

Abstract Background: Lower socioeconomic status has been reported to favor higher blood pressure both during childhood and adulthood, because obesity is more prevalent among this population. The aim of the present study was to evaluate the effect of socioeconomic status on blood pressure and prevalence of obesity among children living in a developing country.

Pauci-immune necrotizing crescentic glomerulonephritis with crescentic and full moon extracapillary proliferation: clinico-pathologic correlation and follow-up study.

The prognostic value of the type and extent of extracapillary proliferation (ECP) in pauci-immune necrotizing crescentic glomerulonephitis (PIGN) was evaluated in this study. In 141 PIGN cases, all glomeruli with ECP were grouped according to type (cellular, fibrocellular and fibrous) and extent of the lesions in Bowmans space; (segmental, semicircumferential and circumferential, which might be termed full moon-FM). Cases with cellular and fibrous lesions involving ≥ 50% of glomeruli with ECP were classified as cellular and fibrous groups, respectively, while the remaining cases were classified as fibrocellular. Cases with segmental and circumferential (FM glomerulus) lesions involving ≥ 50% of glomeruli with ECP were classified as ECPI and ECPIII (FM) groups, respectively, while the rest were classified as ECPII. All the cases were classified according to Berden et al. Significant results were only nearly obtained for the FM group, including the need for dialysis. The Cox regression model revealed a 2.6-fold risk for FM cases regarding dialysis requirement. We propose that the percentage of FM glomeruli should be noted in the pathology report, and cases with more than 50% of FM glomeruli (FM group) should be identified in the group with increased risk of dialysis requirement. Our series also suggests that classification according to Berden et al. is of clinical relevance.

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

IntroductionMedullary sponge kidney (MSK) is characterized by cystic dilatation of the inner medullary collecting ducts, which causes the kidneys to resemble a sponge.Case reportAlthough 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).DiscussionMetabolic acidosis, hypercalciuria, hypocitraturia, tubular phosphate reabsorption and growth retardation in the patient improved with alkali therapy.