Summary: Background and objectives: Atypical hemolytic uremic syndrome (aHUS) is a rare complement-mediated kidney disease that was first recognized in children but also affects adults. This study assessed the disease presentation and outcome in a nationwide cohort of patients with aHUS according to the age at onset and the underlying complement abnormalities. Design, setting, participants, & measurements: A total of 214 patients with aHUS were enrolled between 2000 and 2008 and screened for mutations in the six susceptibility factors for aHUS and for anti–factor H antibodies. Results: Onset of aHUS occurred as frequently during adulthood (58.4%) as during childhood (41.6%). The percentages of patients who developed the disease were 23%, 40%, 70%, and 98% by age 2, 18, 40, and 60 years, respectively. Mortality was higher in children than in adults (6.7% versus 0.8% at 1 year) (P=0.02), but progression to ESRD after the first aHUS episode was more frequent in adults (46% versus 16%; P<0.001). Sixty-one percent of patients had mutations in their complement genes. The renal outcome was not significantly different in adults regardless of genetic background. Only membrane cofactor protein (MCP) and undetermined aHUS were less severe in children than adults. The frequency of relapse after 1 year was 92% in children with MCP-associated HUS and approximately 30% in all other subgroups. Conclusion: Mortality rate was higher in children than adults with aHUS, but renal prognosis was worse in adults than children. In children, the prognosis strongly depends on the genetic background.

C3 glomerulopathy is a recently introduced pathological entity whose original definition was glomerular pathology characterized by C3 accumulation with absent or scanty immunoglobulin deposition. In August 2012, an invited group of experts (comprising the authors of this document) in renal pathology, nephrology, complement biology, and complement therapeutics met to discuss C3 glomerulopathy in the first C3 Glomerulopathy Meeting. The objectives were to reach a consensus on: the definition of C3 glomerulopathy, appropriate complement investigations that should be performed in these patients, and how complement therapeutics should be explored in the condition. This meeting report represents the current consensus view of the group.

Urea cycle disorders (UCDs) are inborn errors of ammonia detoxification/arginine synthesis due to defects affecting the catalysts of the Krebs-Henseleit cycle (five core enzymes, one activating enzyme and one mitochondrial ornithine/citrulline antiporter) with an estimated incidence of 1:8.000. Patients present with hyperammonemia either shortly after birth (~50%) or, later at any age, leading to death or to severe neurological handicap in many survivors. Despite the existence of effective therapy with alternative pathway therapy and liver transplantation, outcomes remain poor. This may be related to underrecognition and delayed diagnosis due to the nonspecific clinical presentation and insufficient awareness of health care professionals because of disease rarity. These guidelines aim at providing a trans-European consensus to: guide practitioners, set standards of care and help awareness campaigns. To achieve these goals, the guidelines were developed using a Delphi methodology, by having professionals on UCDs across seven European countries to gather all the existing evidence, score it according to the SIGN evidence level system and draw a series of statements supported by an associated level of evidence. The guidelines were revised by external specialist consultants, unrelated authorities in the field of UCDs and practicing pediatricians in training. Although the evidence degree did hardly ever exceed level C (evidence from non-analytical studies like case reports and series), it was sufficient to guide practice on both acute and chronic presentations, address diagnosis, management, monitoring, outcomes, and psychosocial and ethical issues. Also, it identified knowledge voids that must be filled by future research. We believe these guidelines will help to: harmonise practice, set common standards and spread good practices with a positive impact on the outcomes of UCD patients.

Pheochromocytoma or secreting paraganglioma may recur after initial surgery. Diagnostic methods have improved in recent decades. We determined whether features at presentation have changed over time and are associated with long-term outcome. In 192 patients with pheochromocytoma/paraganglioma seen between 1975 and 2003, we compared time from onset of hypertension to first operation, total metanephrine excretion, tumor size and site, the proportion of cases presenting as incidentalomas, and the probability of recurrence according to date of operation (divided into quartiles). The duration of hypertension and tumor size at first operation decreased significantly over time. Right-sided adrenal tumors were more frequent and larger, excreted greater amounts of metanephrines, and presented more frequently as incidentalomas than left-sided tumors. Age, familial disease, and tumor site and size were independent predictors of recurrence. The risk of recurrence was 3.4-fold higher in patients with familial disease than in those with sporadic tumors; it was, respectively, 3.1- and 11.2-fold higher in patients with right adrenal and extraadrenal tumors than in patients with left adrenal tumors. In conclusion, pheochromocytomas/paragangliomas can now be diagnosed earlier, with smaller tumors, and more frequently as incidentalomas. Familial, right adrenal, and extraadrenal tumors recur more frequently than left adrenal tumors.