Atypical hemolytic uremic syndrome (aHUS) emerged during the last decade as a disease largely of complement dysregulation. This advance facilitated the development of novel, rational treatment options targeting terminal complement activation, e.g., using an anti-C5 antibody (eculizumab). We review treatment and patient management issues related to this therapeutic approach. We present consensus clinical practice recommendations generated by HUS International, an international expert group of clinicians and basic scientists with a focused interest in HUS. We aim to address the following questions of high relevance to daily clinical practice: Which complement investigations should be done and when? What is the importance of anti-factor H antibody detection? Who should be treated with eculizumab? Is plasma exchange therapy still needed? When should eculizumab therapy be initiated? How and when should complement blockade be monitored? Can the approved treatment schedule be modified? What approach should be taken to kidney and/or combined liver-kidney transplantation? How should we limit the risk of meningococcal infection under complement blockade therapy? A pressing question today regards the treatment duration. We discuss the need for prospective studies to establish evidence-based criteria for the continuation or cessation of anticomplement therapy in patients with and without identified complement mutations.

Objective To ascertain the aetiology and epidemiology of non-neurogenic bladder sphincter dysfunction (NNBSD) by assessing the results of prospective video-urodynamic studies (VUD) in 1000 children. Patients and methods During a 4-year study period (January 1995 to December 1998) 1000 children prospectively underwent VUD to further define their NNBSD. After a noninvasive screening assessment consisting of a history, voiding diary, clinical examination, urine analysis, ultrasonography and uroflowmetry, those children who would benefit from further VUD were selected. The selection criteria included a history of urinary tract infection (UTI), a small bladder capacity not responding to training, dysfunctional uroflow, ultrasonographic abnormalities and resistance to therapy. During the study period 3500 children were screened for incontinence problems, including monosymptomatic nocturnal enuresis; 1000 of these were selected for VUD (524 boys and 476 girls). Results The urodynamic diagnosis was of normal bladder-sphincter function in 62 (6.2%, male : female 44 : 56), urge syndrome in 582 (58%, 58 : 42), dysfunctional voiding in 316 (32%, 49 : 51) and 'lazy bladder' in 40 (4%, 20 : 80). Boys diagnosed with a 'lazy bladder' were younger than those with urge syndrome and dysfunctional voiding. Girls with dysfunctional voiding were younger than those with urge syndrome. The incidence of UTI was significantly higher in girls than in boys; boys with NNBSD had no greater risk for UTI and in girls the general risk was 34%. Only in girls with a lazy bladder was there a significantly higher incidence of UTI (53%). Reflux occurred equally in all groups, with an overall incidence of 15%. The incidence of obstipation was significantly higher in girls with a lazy bladder, and overall was 17%. Conclusion These results from a large series provide a new insight into the epidemiology and pathophysiology of NNBSD. The age distribution provides evidence against a dysfunctional voiding sequence. The risk of developing UTI in NNBSD is greater only in girls.In children with a lazy bladder the risk is also significantly higher, indicating that residual urine is a greater risk factor than detrusor instability. Urge syndrome and dysfunctional voiding in girls carry the same risk for developing UTI, indicating that bladder instability is a higher risk factor for UTI than detrusor sphincter discoordination. All dysfunctions carry an equal risk for developing secondary reflux. Children with NNBSD have different primary diseases but all have a common risk of incontinence, UTIs, reflux and obstipation.

Candesartan cilexetil dose-dependently decreases blood pressure and albuminuria in hypertensive infants and is generally well tolerated.

Levamisole has been considered the least toxic and least expensive steroid-sparing drug for preventing relapses of steroid-sensitive idiopathic nephrotic syndrome (SSINS). However, evidence for this is limited as previous randomized clinical trials were found to have methodological limitations. Therefore, we conducted an international multicenter, placebo-controlled, double-blind, randomized clinical trial to reassess its usefulness in prevention of relapses in children with SSINS. The efficacy and safety of one year of levamisole treatment in children with SSINS and frequent relapses were evaluated. The primary analysis cohort consisted of 99 patients from 6 countries. Between 100 days and 12 months after the start of study medication, the time to relapse (primary endpoint) was significantly increased in the levamisole compared to the placebo group (hazard ratio 0.22 [95% confidence interval 0.11-0.43]). Significantly, after 12 months of treatment, six percent of placebo patients versus 26 percent of levamisole patients were still in remission. During this period, the most frequent serious adverse event (four of 50 patients) possibly related to levamisole was asymptomatic moderate neutropenia, which was reversible spontaneously or after treatment discontinuation. Thus, in children with SSINS and frequent relapses, levamisole prolonged the time to relapse and also prevented recurrence during one year of treatment compared to prednisone alone. However, regular blood controls are necessary for safety issues.

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