Impact of Everolimus and Low-Dose Cyclosporin on Cytomegalovirus Replication and Disease in Pediatric Renal Transplantation.

In order to investigate the hypothesis that the mammalian target of rapamycin inhibitor everolimus (EVR) shows anticytomegalovirus (CMV) activity in pediatric patients, we analyzed the impact of EVR-based immunosuppressive therapy on CMV replication and disease in a large cohort (n = 301) of pediatric kidney allograft recipients. The EVR cohort (n = 59), who also received low-dose cyclosporin, was compared with a control cohort (n = 242), who was administered standard-dose cyclosporin or tacrolimus and an antimetabolite, mostly mycophenolate mofetil (91.7%). Multivariate analysis revealed an 83% lower risk of CMV replication in the EVR cohort than in the control cohort (p = 0.005). In CMV high-risk (donor+/recipient-) patients (n = 88), the EVR-based regimen was associated with a significantly lower rate of CMV disease (0% vs. 14.3%, p = 0.046) than the standard regimen. In patients who had received chemoprophylaxis with (val-)ganciclovir (n = 63), the CMV-free survival rates at 1 year and 3 years posttransplant (100%) were significantly (p = 0.015) higher in the EVR cohort (n = 15) than in the control cohort (n = 48; 1 year, 75.0%; 3 years, 63.3%). Our data suggest that in pediatric patients at high risk of CMV, an EVR-based immunosuppressive regimen is associated with a lower risk of CMV disease than a standard-dose calcineurin inhibitor-based regimen.

Hydrothorax in 2 children on CAPD: review of clinical approach and treatment options.

Pleural effusions are seen relatively common in end-stage renal disease (ESRD) patients, on the other hand, hydrothorax secondary to pleuroperitoneal leak in continuous ambulatory peritoneal dialysis (CAPD) patients is rare. Since treatment modalities differ widely from that of other causes of pleural effusion seen in CAPD patients such as uremia, volume overload, congestive heart failure, infection and malignancy, pleuroperitoneal leak should always be kept in mind in the differential diagnosis and should be excluded urgently. To draw attention to this point, in this paper, 2 children on CAPD who developed a hydrothorax secondary to a pleuroperitoneal communication are presented with an overview of diagnostic tools and treatment modalities.

Intravenous pulse cyclophosphamide therapy in focal segmental glomerulosclerosis.

AIMS: We herein report the results of intravenous pulse cyclophosphamide (IVCP) therapy of 5 patients with steroid-resistant focal segmental glomerulosclerosis (FSGS). All patients had been treated with oral and intravenous pulse methylprednisolone and failed to respond to steroids from onset and were considered as primary steroid-resistant. Before starting IVCP, all patients were also treated with other immunosuppressive drugs with or without steroids, but none of them responded to such therapies and no patient had any NPSH2 gene mutations. METHODS: IVCP was given monthly at a dose of 500 mg/m2 for 6 months. At the end of 6 months, IVCP was discontinued in case there was no response. Otherwise, IVCP was continued for every 2 months. Oral prednisone was given concurrently at 60 mg/m2 daily for 6 weeks and then 40 mg/m2 on alternate days for 4 weeks. Prednisone was then tapered to 10 mg/m2 alternate days and continued during the therapy period. RESULTS: Only 1 of these patients achieved remission after IVCP while 4 patients showed no response to IVCP. 2 patients who did not achieve remission progressed to end-stage renal disease (ESRD) and 2 others who had not been treated with cyclosporine before underwent cyclosporine therapy. None of our patients has suffered from adverse effects of IVCP. CONCLUSION: We found that IVCP had a limited beneficial effect in treatment of steroid-resistant FSGS and it may be suggested that IVCP can be tried to treat steroid-resistant patients, also for patients with primary steroid resistance and those who do not respond to other immunosuppressive therapies.

A child with Beckwith-Wiedemann syndrome and posterior urethral valves.

Beckwith-Wiedemann syndrome is a somatic overgrowth syndrome characterized by a variable incidence of congenital anomalies, including hemihypertrophy, omphalocele, macroglossia and renal malformations. We report a child with Beckwith-Wiedemann syndrome and posterior urethral valves. Urethral valve resection was successfully performed under general anesthesia after voiding cystourethrography. This is the first report of Beckwith-Wiedemann syndrome associated with posterior urethral valves.

Mycophenolate mofetil in children with multidrug-resistant nephrotic syndrome.

AIM: The aim of the present study is to report our clinical experiences with MMF in problematic children with chronic glomerulonephritis resistant to corticosteroids and/or other immunosuppressive drugs. PATIENTS AND METHODS: Ten patients with chronic glomerulonephritis resistant to treatment with corticosteroids and other immunosuppressive drugs were treated with mycophenolate mofetil (MMF). Causes of chronic glomerulonephritis were mesangial proliferative glomerulonephritis (4), membranoproliferative glomerulonephritis (3), chronic sclerosing glomerulonephritis (1), focal segmental glomerulosclerosis (1), diffuse endo- and extracapillary proliferative glomerulonephritis (1). MMF 15 mg/kg was used in combination with low-dose corticosteroids and angiotensin-converting enzyme inhibitors. RESULTS: During 24 weeks of MMF therapy, no significant changes were detected in mean serum creatinine, albumin and proteinuria. Severe leukopenia was seen in 1 patient. Additional adverse effects, including nausea and diarrhea, were observed in another patient when the dosage was increased to 20 mg/kg per day. During MMF treatment proteinuria decreased slightly without remission in 6 of 10 patients. CONCLUSION: Further data and clinical trials are needed to evaluate the possible role of MMF in the treatment of chronic glomerulonephritis of similar etiologies in pediatric patients.

Renal function in children with sickle cell anemia.

BACKGROUND: Patients with sickle cell anemia have various forms of renal dysfunction. SUBJECTS, MATERIALS AND METHODS: The purpose of this study is to demonstrate the abnormalities of HbSS patients' renal function in childhood. Renal function studies were performed in 55 patients with homozygote sickle cell anemia and compared with 13 healthy children. The blood and timed urine samples were obtained for hematological and biochemical determinations. RESULTS: Mean serum creatinine, sodium, phosphorus and calcium levels were not statistically different between patients and controls. Mean serum potassium and uric acid levels were significantly higher in patients than in controls. Mean tubular phosphate reabsorption (p < 0.001) and fractional excretion of potassium (p < 0.05) were lower in patients than in the control. There were no significant differences in fractional excretion of sodium and uric acid between patients and controls. Patients had significantly higher urine pH and significantly lower specific gravity and osmolality than controls. Also, there were no significant differences in urinary protein/ creatinine, urinary N-acetyl-beta-D-glucosaminidase/creatinine and urinary malondialdehyde/creatinine between patients and controls. CONCLUSION: Thus, significant proximal tubular dysfunction is not a common feature but distal tubular abnormality is the most consistent renal functional derangement of patients with SCA in childhood.

99Tcm-N,N-ethylenedicysteine scintigraphy in children with various renal disorders: a comparative study with 99Tcm-MAG3.

We evaluated the clinical usefulness of 99Tcm-N,N-ethylenedicysteine (99Tcm-EC), a new renal tubular agent, in normal children and in children with various renal disorders and compared it with 99Tcm-mercaptoacetyltriglycine (99Tcm-MAG3). In a first group of children (Group 1), which included 15 patients and 4 normal children, both 99Tcm-EC and 99Tcm-MAG3 renal scintigraphy were performed within a period of 1-5 days. In a second group (Group 2), consisting of 12 patients, only 99Tcm-EC scintigraphy was performed. In the normal children, renograms, differential renal function (DRF) ratios and semi-quantitative parameters of the two agents were similar. For 99Tcm-EC and 99Tcm-MAG3, the mean (+/- S.D.) time to peak activity (Tmax) values were 3.2 +/- 0.5 and 3.1 +/- 0.4 min respectively, and the mean time from peak activity to 50% activity (T1/2) values were 6.3 +/- 0.5 and 6.4 +/- 0.4 min respectively. The mean parenchymal transit time index (PTTI) and mean whole-kidney transit time index (WKTTI) for 99Tcm-EC were 1.7 +/- 0.3 and 2.8 +/- 0.4 respectively, and for 99Tcm-MAG3 they were 1.8 +/- 0.2 and 3.0 +/- 0.3 min respectively. There were also no significant differences between these parameters for the two agents in children with various renal disorders, and the correlation coefficients (r) for DRF, Tmax, T1/2, PTTI and WKTTI were 0.99, 0.98, 0.94, 0.77 and 0.63 respectively. We conclude that 99Tcm-EC has excellent imaging characteristics in children, and even has some advantages over 99Tcm-MAG3. We suggest this agent can be used routinely with children.

Urinary nephrocalcin excretion in children with urolithiasis.

The aim of this study was to investigate the role of nephrocalcin in childhood urolithiasis. Forty-one patients with urinary stones and 25 age- and sex-matched healthy controls were admitted to the study. Blood and timed urine samples were taken from both patient and control groups for biochemical analysis. Serum and urine creatinine (Cr) and urinary nephrocalcin (NC) were measured. NC excretion was expressed as a NC/Cr (mg/g) ratio. NC-PreA/Cr and NC-D/Cr ratios were found to be significantly higher in patients than in the control group. No statistically significant differences were found in NC-A/Cr, NC-B/Cr, NC-C/Cr ratios between the patient and control groups. The high NC-PreA/Cr ratio (p = 0.012) observed in stone-forming patients indicates that this ratio may also be an important stimulatory factor for urinary stone disease.

HLAs in children with minimal change disease and other types of nephrotic syndrome in the southern part of Turkey.

The aim of this study was to investigate the human leukocyte antigen (HLA) profile of children with nephrotic syndrome in the southern part of Turkey. Seventy-eight children with nephrotic syndrome were studied for the frequency of class I and class II human leukocyte antigens. Forty-seven of them were steroid sensitive nephrotic syndrome (minimal change disease-MCD) and 31 were other types of nephrotic syndrome. The results were compared with 133 healthy subjects for HLA groups. HLA B13, Cw5, Cw7, DR4, DR7, DRw10, Drw15(2) and DQ2 in the MCD group and HLA A31, B8, B13, B17, Cw2, Cw6, Cw7, DRw10 and DRw12 in the non-MCD group were found significantly increased when compared to healthy controls. MCD patients with frequent relapses had higher frequencies of both Cw6 and DR1 (p < 0.005) and MCD patients with infrequent relapses had a higher frequency of Cw7 (p < 0.05). In conclusion, HLA groups may help in the early diagnosis of these variants.

Evaluation of renal functions in children with congenital heart disease before and after cardiac angiography.

Radiocontrast nephrotoxicity, which has increased in incidence with widespread use of radiological methods in medicine, is a serious complication of radiocontrast materials. In this study, we have prospectively investigated whether children with cyanotic congenital heart disease are at risk for radiocontrast nephrotoxicity with the use of a nonionic low osmolar contrast agent. Thirty-five children (17 cyanotic and 18 acyanotic patients) who underwent diagnostic cardiac catheterization were subjects of the study. The age range was from five days to 13 years. The volume of contrast material was 3.11 +/- 1.37 ml/kg in cyanotic patients and 2.67 +/- 0.86 ml/kg in acyanotic patients. Blood samples and timed urine samples were taken from all patients 24 hours before and 48 hours after cardiac catheterization. Blood urea nitrogen, creatinine, sodium, and phosphorus in serum, and creatinine and N-acetyl-beta-D-glucosamine in urine were analyzed. There was not a statistically significant difference between the values before and after angiography. As a result, we could find no evidence of radiocontrast nephrotoxicity with the use of a nonionic contrast agent in cyanotic and acyanotic patients who underwent cardiac angiography.

Neutrophil chemotaxis in children with extrinsic bronchial asthma.

Chemotactic activities of neutrophils were studied in 20 patients with bronchial asthma and 20 healthy matched controls. Chemotaxis studies were performed by the millipore filter technique using modified Boyden chambers. Mean neutrophil chemotactic activities of asthma and control groups were 17.82 +/- 7.87 microns and 14.09 +/- 6.07 microns; mean chemotactic indexes were 2.04 +/- 0.44 and 1.84 +/- 0.60 and mean random migrations were 9.53 +/- 4.61 microns and 7.93 +/- 3.33 microns, respectively. No significant difference was found between the two groups (p > 0.05).

The role of endothelin in radiocontrast nephropathy.

In the present study we investigated the role of endothelin and AT II in radiocontrast nephropathy induced in rats with reduced renal mass (70-75%). Thirty-five male Wistar albino rats weighing between 280 and 400 g were anaesthetized with ketamine (130 mg/kg b.w.) and right total, left 50% nephrectomy were performed. After this operation, the rats were kept under observation for six to eight weeks and then they were randomly separated into three groups. Group I rats were infused with 8.9 ml/kg (or 2.9 g of iodine/kg body weight) Na diatrizoate (Urovision, 1,500 mosm/kg). Group II rats were infused with 0.9% NaCl in an equal volume with the radiocontrast material. Group III rats were given 4.5% NaCl that had the same volume and osmolality as the radiocontrast material. Two hours after the drug infusions, blood and accumulated urine samples were collected from all the rats and tested for endothelin, AT II, BUN, creatinine, uric acid, electrolytes, calcium and phosphorus. We found that the plasma endothelin levels in Group I (77.64 +/- 29.62 pg/ml) were significantly higher than in Group II (20.52 +/- 5.83 pg/ml) and Group III (15.04 +/- 5.15 pg/ml) (t = 8.34 and t = 9.14, respectively, p < 0.001). Therefore elevation in circulating endothelin might have been an additional factor leading to the radiocontrast-induced nephrotoxicity.

Acute changes in endothelin after hemodialysis in children.

The purpose of this study was to investigate the acute changes in endothelin (ET) levels immediately after hemodialysis and to determine whether these changes vary with the use of different membranes and hemodialysis solutions. Ten children were included in the study. Three different hemodialysis sessions were performed on all patients: session 1, acetate-based dialysate and polycarbonate membrane; session 2, bicarbonate-based dialysate and polycarbonate membrane; session 3, acetate-based dialysate and polysulfone membrane. In all cases blood samples were obtained before and after dialysis. Pre- and post-hemodialysis ET levels of the patients with acetate-based dialysate and polycarbonate membrane were 33.68 +/- 11.51 pg/ml and 28.27 +/- 12.85 pg/ml, respectively. The fall in ET levels after this session was statistically significant (P = 0.015). We did not observe a statistically significant change in ET levels in the other sessions. Post-dialysis mean arterial pressure values were significantly lower than the pre-dialysis values in all three dialysis sessions (P < 0.01). A positive correlation was observed between plasma ET levels and blood urea nitrogen and serum potassium; a negative correlation was observed between plasma ET levels and hematocrit.

Continuous cervical epidural anesthesia in hand surgery.

Regional anesthesia, with its known benefits such as increased blood flow, reduced cost, and security, is a method of choice for hand surgery. Recently, the authors have switched from axillary block to continuous cervical epidural anesthesia, which has several advantages such as low cost, a pain-free postoperative period, better control of tourniquet pain, and the avoidance of a motor block so that early active motion is possible. Continuous cervical epidural anesthesia is a safe and reliable method, providing a sensory block with an infusion rate of 4 ml/hr ultracaine (articaine 2 percent), and a motor block when the dosage is increased to 8 ml/hr ultracaine (articaine 2 percent). Postoperatively, only 4 ml/hr ultracaine (articaine 2 percent) is sufficient to provide a sensory block. The method provides both good perfusion and a lower local anesthetic drug dosage than axillary block.

Treatment of hyperkalemia in children with intravenous salbutamol.

The aim of this study is to investigate the efficacy and safety of intravenous salbutamol in hyperkalemia. Fourteen children with chronic renal failure, three with acute renal failure and hyperkalemia were treated by intravenous infusions of 4 micrograms/kg salbutamol. Reductions in the mean plasma potassium (K+) concentrations obtained at 40 to 120 min after therapy were statistically significant when compared with the mean plasma K+ concentration at the beginning of therapy (P < 0.01).

Influence of enalapril on experimental cyclosporin A nephrotoxicity.

The purpose of this study was to investigate if enalapril could be administered with cyclosporin A (CyA) to reduce its nephrotoxicity. Sixty rats were divided into five groups: group I, Control group; group II, rat treated with oral enalapril; group III, rats treated with CyA: group IV, rats treated with CyA and enalapril; group V, rats treated with enalapril before the CyA therapy. At the end of the therapy mean serum creatinine concentrations were not statistically different between the groups (P > 0.05), in groups treated with CyA there were no statistically significant differences between mean CyA levels (P > 0.05), and mean blood urea nitrogen levels of the groups treated with CyA were significantly elevated (P < 0.05) compared with groups not treated with CyA. Morphologically acute CyA nephrotoxicity was evaluated by the following features: (1) tubular vacuolization, (2) tubular necrosis, (3) tubular microcalcification, and (4) peritubular capillary congestion. These lesions were scored semiquantitatively on a scale from 0 to 4+. The most common tubular pathology was tubular vacuolization, which was more severe in groups III and IV. Tubular necrosis was most severe in group III. In conclusion, enalapril seems to suppress the severest form of CyA nephrotoxicity, namely tubular necrosis, if administered prior to CyA treatment.

Efficacy and side effects of cyclosporin A in nephrotic syndrome of childhood.

The efficacy and side effects of the oral administration of cyclosporin A (Cyc-A) were investigated in 13 children with the nephrotic syndrome. Two of these children were steroid-dependent, 9 were resistant to steroids, and 2 displayed frequent relapses. The diagnosis of 6 patients was mesangioproliferative glomerulonephritis (MezPGN), of another 6 mesangiocapillary glomerulonephritis, and of 1 minimal change disease. Cyc-A was administered for 6 months at a dosage of 7 mg/kg/day with continual monitoring of the serum levels. At the end of the treatment period, 7 of the patients (53.8%) had a total remission, 5 (38.4%) a partial remission, and 1 (7.8%) did not respond to treatment. While total remission was achieved in 4 patients who had responded well to steroids, this was true for only 3 (33.3%) of the 9 patients who had not benefited from steroids. The effects and side effects of Cyc-A on histopathological morphology were also investigated by means of posttreatment biopsies. While histopathological improvement was seen in 3 patients with MezPGN, there was evidence of deterioration in 1 patient with MLH.