The effect of simvastatin and erythropoietin on renal fibrosis in rats with unilateral ureteral obstruction.

Prevention of fibrosis is a very important therapeutic strategy in the treatment of obstructive nephropathy (ON). The aim of this study is to show and compare the actions of Simvastatin (Simv) and Erythropoietin (Epo) in renal expression of nuclear factor kappa B (NFκB), transforming growth factor-ß (TGF-ß), basic fibroblast growth factor (bFGF), platelet-derived growth factor B (PDGF-B), fibronectin and development of interstitial fibrosis in rats with unilateral ureteral obstruction (UUO). A total of 48 Sprague-Dawley rats were allocated to 4 groups of sham, Epo, Simv and control. Unilateral ureteral ligation was performed on all rats except the Sham group. For interstitial fibrosis Masson's trichrome stain and for the expression of TGF-ß, PDGF-B, bFGF, NFκB and fibronectin, immunohistochemical methods were used. In the Epo and Simv groups, expression of TGF-ß and fibronectin and staining with Masson's trichrome were less compared to the control group. In addition, fibronectin expression in the Epo group was less than the Simv group. Unlike the Simv group, NFκB and bFGF expression in the Epo group were less when compared to the control group. Consequently, it was seen that both Epo and Simv prevented fibrosis in ON. Epo was superior in this effect by suppressing the expressions of NFκB and bFGF more effectively than Simv. Based on this finding, Epo might be a better agent than Simv in the prevention of fibrosis in ON.

Cryptosporidiosis: a rare and severe infection in a pediatric renal transplant recipient.

Cryptosporidium is an intracellular protozoan parasite that causes gastroenteritis in human. In immunocompromised individuals, cryptosporidium causes far more serious disease. There is no effective specific therapy for cryptosporidiosis, and spontaneous recovery is the rule in healthy individuals. However, immunocompromised patients need effective and prolonged therapy. Here, we present our clinical experience in a six-yr-old boy who underwent living-related donor renal transplantation and who was infected with Cryptosporidium spp. Our patient was successfully treated with antimicrobial agents consisting of spiramycin, nitazoxanide, and paromomycin. At the end of second week of therapy, his stool became negative for Cryptosporidium spp. antigen and spiramycin was discontinued. Nitazoxanide and paromomycin treatment was extended to four wk. With this case, we want to emphasize that cryptosporidiosis should be considered in the differential diagnosis of severe or persistent diarrhea in solid organ transplant recipients where rigorous antimicrobial therapy is needed.

Is serum cystatin C a better marker than serum creatinine for monitoring renal function in pediatric intensive care unit?

In critically ill patients, mild to moderate reductions in glomerular filtration rate are not instantly followed by parallel changes in serum creatinine (SCr). The aim of this study was to identify a value of serum cystatin C (cys-C) level as a marker for monitoring renal function in critically ill pediatric patients. Creatinine clearance was used to estimate glomeruler filtration rate (eGFR). The correlation between the inverse of serum cys-C and eGFR (r = -0.70, p < 0.0001) was better than the correlation between the inverse of SCr and eGFR (r = -0.27, p = 0.008). Serum cys-C was found to be superior to SCr to predict renal impairment (area under the curve for cys-C, 0.932 and for SCr, 0.658). It can be concluded that cys-C is superior to SCr for the detection of renal impairment in critically ill children.

Acute renal failure with acyclovir treatment in a child with leukemia.

Acyclovir is an effective, frequently used antiviral agent. Adverse effects of this drug are well known and are especially seen with high doses and/or dehydration. In this article, we report a 6-year-old boy with leukemia with nonoliguric acute renal failure in normal hydration status after using acyclovir treatment. He had no preexisting renal impairment, and there were no additional symptoms. Dimercaptosuccinic acid radionucleid scyntigraphy and other laboratory findings revealed impairment of proximal tubule function, in addition to distal tubule. We emphasize that renal functions should be monitored carefully during treatment with acyclovir, and asymptomatic nephrotoxicity must be kept in mind.

A rare cause of recurrent hematuria in children: Nutcracker syndrome.

Nutcracker syndrome (NCS), the left renal vein hypertension due to compression between aorta and superior mesenteric artery, may present with hematuria, flank pain and proteinuria. We report a 6-year-old girl with episodic macroscopic hematuria who was diagnosed as NCS with Doppler ultrasound and 3D computerized tomography angiography. She was managed conservatively with spontaneous resolution of macroscopic hematuria. With this case we would like to emphasize that in children with hematuria and orthostatic proteinuria without an apparent cause, a great index of suspicion and appropriate imaging is necessary for the diagnosis of NCS.

Effect of rosiglitazone on cisplatin-induced nephrotoxicity.

AIM: Nephrotoxicity is a major side effect of cisplatin (Cis), a widely used chemotherapeutic drug. Recent studies have strongly suggested that inflammatory mechanisms may play an important role in the pathogenesis of Cis nephrotoxicity. Rosiglitazone (Ros), a peroxisome proliferator-activated receptor-gamma agonist has been recently demonstrated to regulate inflammation by modulating the production of inflammatory mediators and adhesion molecules. The aim of this study was to evaluate the effect of Ros on the prevention of Cis-induced nephrotoxicity. METHODS: Eighteen male Sprague-Dawley rats weighing 150-200 g were included in the study. The rats were randomly divided into three groups: group 1: Cis-treated group; group 2: Cis-Ros-treated group; group 3: saline-treated group. Blood urea nitrogen (BUN) and serum creatinine concentrations were measured. In addition, extent of histological renal tubular injury in each animal was graded histologically. RESULTS: Mean BUN and serum creatinine concentrations were significantly lower in group 3 than in group 1 (p<0.05) and group 2 (p<0.05). There were no significant differences in terms of BUN and serum creatinine concentrations between groups 1 and 2 (p>0.05). Acute tubular injury with karyomegalic changes in corticomedullary junction was significantly higher in groups 1 and 2 than group 3 (p<0.05). However, there were no significant differences between groups 1 and 2 (p>0.05). CONCLUSION: This study indicates that post-insult administration of Ros does not seem to have a beneficial effect on prevention and severity of nephrotoxicity induced by Cis.

Acute pancreatitis as a presenting feature of Henoch-Schönlein purpura.

Henoch-Schönlein purpura (HSP) is the most common small vessel vasculitis of childhood. It is characterized by nonthrombocytopenic palpable purpura, abdominal pain, arthritis, and glomerulonephritis. Although HSP is typically known to be self-limited, serious complications can occur. Acute pancreatitis rarely presents as a complication of HSP. It is even rarer as an initial presenting feature of HSP, before the occurrence of characteristic palpable purpura. Herein, we report a 12-year-old girl with HSP who atypically presented with acute pancreatitis.

Hemolytic Uremic Syndrome in an Infant with Primary Hyperoxaluria Type II: An Unreported Clinical Association.

A 6-month-old boy presented with acute renal failure, thrombocytopenia, and severe non-immune hemolytic anemia. Infection by Shiga-like toxin-producing Escherichia coli and other causes of microangiopathic hemolysis were ruled out, leading to a diagnosis of atypical hemolytic uremic syndrome (aHUS). Neither pathogenic variants in HUS-associated genes nor anti-factor H antibodies were identified. Copy number variation analysis uncovered 4 copies of complement factor H related genes, CFHR1-CFHR4, conceivably leading to higher than normal levels of the corresponding proteins. However, this abnormality was also found in the healthy relatives, neither explaining the disease nor the excessive complement deposition on endothelial cells detected by an ex-vivo test. Whole-exome sequencing revealed a pathogenic homozygous variant in GRHPR encoding the glyoxylate and hydroxypyruvate reductase. Recessive GRHPR mutations cause primary hyperoxaluria type 2 (PH2). The presence of renal calculi in the patient and elevated oxalate levels in the urine were consistent with the genetic diagnosis of PH2. We hypothesize that, in this patient, hyperoxaluria caused by the GRHPR genetic defect triggered endothelial perturbation and complement activation, which was amplified by impaired factor H regulatory activity due to the increased -CFHR1-CFHR4 copy numbers, resulting in aHUS.

Characteristics of pruritus in children on peritoneal dialysis.

BACKGROUND/AIMS: The aim of this study was to evaluate the characteristics of pruritus in pediatric patients undergoing peritoneal dialysis. PATIENTS AND METHODS: Twenty-seven patients (16 females, 11 males), aged between 5 and 18 years, were evaluated for the presence, intensity, onset, activation time, duration, characteristics, localization and increasing factors for pruritus. The intensity of pruritus was scored using a visual analog scale. Patients were grouped according to the existence of pruritus and other clinical and laboratory parameters (dialysis duration, dialysis adequacy, hemoglobin, blood urea nitrogen, creatinine, Ca, P, albumin, bicarbonate, parathyroid hormone (PTH), C-reactive protein (CRP)) were compared between the 2 groups. RESULTS: The mean age of patients was 11.85 +/- 4.4 years. There were 21 patients (77.7%) without pruritus and 6 patients with pruritus (22.2%). Serum P, PTH, CRP levels and CaxP product were significantly higher in patients with pruritus compared to patients without pruritus (p = 0.027, p = 0.03, p < 0.026, p = 0.031, respectively). In a stepwise logistic regression model, P (p = 0.01), CaxP product (p = 0.09), PTH (p = 0.03) and CRP (p = 0.02) were independently associated with pruritus. CONCLUSION: Our study indicates that pruritus remains a common but not troublesome symptom in children on peritoneal dialysis. Higher serum P, CaxP product, PTH and CRP concentrations appear to be important factors associated with uremic pruritus in this group.

Charcoal haemoperfusion in amitriptyline poisoning: experience in 20 children.

AIM: Tricyclic antidepressant (TCA) toxicity is common among children and adults due to widespread use. Amitriptyline (AT) is one of the most commonly prescribed TCAs. Current guidelines do not recommend charcoal haemoperfusion (HP) for AT overdose due to high protein binding and large volume of distribution. However evidence regarding the efficacy of charcoal HP in addition to supportive measures is accumulating in the published reports. METHODS: Here we report our experience in 20 children (15 girls, 5 boys) with acute AT overdose aged between 1.5 and 15 years, successfully managed with HP in our institution between January 2000 and February 2007. RESULTS: The HP indications were mainly severe initial cardiac and respiratory involvement. After HP, all patients recovered dramatically with a mean hospital stay of 4 days (range: 2-12). Only one patient developed neurological sequelae due to prolonged hypoxia secondary to respiratory arrest. CONCLUSION: To our knowledge this is the largest case series reporting the efficacy of charcoal HP in acute AT overdose in children. Based on our findings, charcoal HP seems to be an effective treatment modality, especially in prompt correction of severe life-threatening cardiac and respiratory findings in children with serious AT overdose and resulting in a reduction of morbidity and mortality.

Cerebral vasculitis in a child with Henoch-Schönlein purpura and familial Mediterranean fever.

In this case report, a 10-year-old girl with Henoch-Schönlein purpura (HSP) with severe central nervous system involvement and also having familial Mediterranean fever (FMF) is presented.

Low protein Z levels in children with nephrotic syndrome.

Acquired deficiency of anticoagulant proteins, due to loss in the urine, has been proposed as one of the major thrombogenic alterations in nephrotic syndrome (NS). Protein Z (PZ) is a single-chain vitamin K-dependent glycoprotein. Low PZ levels are reported to be a risk factor for thrombosis. The aim of this study was to investigate protein Z and other natural anticoagulant levels in children with NS. Thirty children aged between 1.5 and 12 years with NS (Groups I and II) and 19 age-and-sex-matched healthy controls (Group III) were enrolled into the study. Patients were divided into two groups: Group I (proteinuria >40 mg/m2/hr) and Group II (patients in remission). Plasma PZ levels in Group I were significantly lower than Group II (p=0.009) and group III (p=0.018). Plasma levels of AT III for Group I were significantly lower than for Groups II and III (p=0.009, p=0.005, respectively). Protein C levels in Group I were higher than in Group II and Group III (p=0.002, p=0.000, respectively). Protein Z levels positively correlated with serum total protein and albumin levels (p=0.003, p=0.003, respectively) and negatively with the degree of proteinuria (p=0.000). Protein Z levels were positively correlated with AT III (r=0.037, p=0.04). Along with the other coagulation abnormalities, decreased protein Z may contribute to increased risk of thromboembolic complications in children with NS. The negative correlation between proteinuria and PZ level suggests the possibility of renal PZ loss. Further studies are needed to investigate the mechanism and role of decreased PZ in NS.