Acute kidney injury in an infant with severe combined immunodeficiency: Questions

An adolescent with lupus nephritis presenting with fever, lymphadenomegaly, and arthralgia: Questions

Hypokalemia in a pediatric patient on continuous renal replacement therapy: Questions

An adolescent with lupus nephritis presenting with fever, lymphadenomegaly, and arthralgia: Answers

Is eculizumab indicated in patients with atypical hemolytic uremic syndrome already on prolonged dialysis? A case report and review of the literature Abstract Background Eculizumab has caused a revolution in the treatment and prognosis of atypical hemolytic uremic syndrome. Early initiation of treatment is recommended to increase chances of renal recovery. Case-diagnosis/treatment We describe a boy with atypical hemolytic uremic syndrome who started eculizumab therapy after being on dialysis for 4.5 months, with complete anuria. With treatment, he was weaned off dialysis. Conclusion We review the evidence in the literature and discuss the possible mechanism by which eculizumab induces renal recovery even in patients already on prolonged dialysis. This case report highlights the importance of a treatment trial with eculizumab, even in patients already on prolonged dialysis.

Hypokalemia in a pediatric patient on continuous renal replacement therapy: Answers

Subclinical myocardial disease in patients with primary hyperoxaluria and preserved left ventricular ejection fraction: a two-dimensional speckle-tracking imaging study Abstract Background Primary hyperoxaluria (PH) is characterized by progressive chronic kidney disease (CKD) and systemic oxalate deposition. Myocardial dysfunction might be present early in the course of the disease. However, this hypothesis has not yet been tested in the PH population. Therefore, we aimed to determine whether strain imaging using two-dimensional speckle tracking echocardiography (2D-STE) might detect subclinical myocardial disease in otherwise asymptomatic PH patients. Methods Prospective study of pediatric and adolescent PH patients with preserved LV ejection fraction (LV EF) and without renal replacement therapy. Subjects underwent conventional echocardiography and 2D-STE. Global (GLS) and segmental peak systolic LV longitudinal strain (LS) measurements were obtained. Data were compared with age- and gender-matched controls, and Z-scores were calculated as appropriate. Results Fifteen PH patients (age 14.1 ± 5.9 years; 13/15 in CKD stages 1–2) were studied. Although LV EF was preserved (63 ± 6%) in patients, GLS was significantly impaired (GLS − 17.1 ± 2.2% vs − 22.4 ± 1.9%, p < 0.001). This was mainly due to decreased LS values in the apical segments (p < 0.05). Echocardiographic indices of ventricular wall thickness were significantly increased in patients compared to controls (all p < 0.03). GLS correlated significantly with Z-scores of diastolic interventricular wall thickness (r = − 0.57, p = 0.025) and moderately with serum creatinine levels (r = 0.53, p = 0.044). No correlation was found between GLS and blood pressure measurements. Conclusions Subclinical myocardial disease is already present early in the course of disease in PH patients with preserved LV EF and some degree of renal dysfunction, but without overt systemic oxalosis. Current recommendations to screen only PH patients with advanced CKD for cardiac disease should be revised accordingly.

What’s new in autoinflammation? Abstract The pathogenesis of autoinflammatory diseases has shed light on the concept of inflammation in general and on our understanding of the role of the innate immune system. The autoinflammatory diseases have a large spectrum with varying features of inflammation. The most common autoinflammatory diseases are those associated with periodic fevers. The delay in diagnosis of these four common diseases (familial Mediterranean fever, cryopyrin-associated periodic fever syndrome, mevalonate kinase deficiency, and TNF receptor-associated periodic fever syndrome) results in secondary amyloidosis of the kidney. The new work towards classification criteria for these diseases is presented. Recently a group of autoinflammatory diseases that are associated with vasculitis have also been identified. These are stimulators of interferon genes (STING)-associated vasculopathy of infancy (SAVI), which is a monogenic defect associated with excessive activity in interferon alpha and deficiency of adenosine deaminase 2, which is characterized by a polyarteritis nodosa-like picture. These monogenic diseases are now in our differential diagnosis of vasculitides. Secondary amyloidosis is a complication of autoinflammatory diseases. Understanding the inflammatory mechanisms in these diseases has led to the use of targeted biologics for this complication. It is hoped that enlightening the mechanisms underlying these monogenic autoinflammatory diseases will also teach us about the pathways in common diseases.

The role of CD47 in pathogenesis and treatment of renal ischemia reperfusion injury Abstract Ischemia reperfusion (IR) injury is a process defined by the temporary loss of blood flow and tissue perfusion followed later by restoration of the same. Brief periods of IR can be tolerated with little permanent deficit, but sensitivity varies for different target cells and tissues. Ischemia reperfusion injuries have multiple causes including peripheral vascular disease and surgical interventions that disrupt soft tissue and organ perfusion as occurs in general and reconstructive surgery. Ischemia reperfusion injury is especially prominent in organ transplantation where substantial effort has been focused on protecting the transplanted organ from the consequences of IR. A number of factors mediate IR injury including the production of reactive oxygen species and inflammatory cell infiltration and activation. In the kidney, IR injury is a major cause of acute injury and secondary loss of renal function. Transplant-initiated renal IR is also a stimulus for innate and adaptive immune-mediated transplant dysfunction. The cell surface molecule CD47 negatively modulates cell and tissue responses to stress through limitation of specific homeostatic pathways and initiation of cell death pathways. Herein, a summary of the maladaptive activities of renal CD47 will be considered as well as the possible therapeutic benefit of interfering with CD47 to limit renal IR.

Infrequent tacrolimus-induced nephrotoxicity in French patients with steroid-dependent nephrotic syndrome Abstract Background Chronic nephrotoxicity with potentially irreversible lesions is a major concern regarding calcineurin inhibitor (CNI) treatment in children with severe forms of idiopathic nephrotic syndrome (INS). Case-diagnosis/Treatment We retrospectively included all children on CNI for steroid-dependent INS with a duration of CNI treatment of more than 1 year. Only patients in whom CNI could not be replaced by mycophenolate mofetil were included. All included patients underwent a kidney biopsy. All results were expressed as median and range. Twenty-one children (6 girls) were included. Age at disease onset was 49 (29–66) months and treatment duration on CNI was 30 (20–45) months. Age at kidney biopsy was 108 (78–170) months. Number of relapses was 7 (3–9) since disease onset. Serum creatinine level was transiently and moderately increased in two patients. Kidney biopsy revealed minimal change disease in 20/21 patients and focal segmental glomerulosclerosis in 1/21. Evidence for chronic CNI nephrotoxicity was found in one patient revealed by arteriolar hyalinosis and fibrosis in 50% of glomeruli. Conclusions CNI-induced chronic nephrotoxicity was infrequent. In patients who require long-term and/or high-dose CNI treatment, kidney biopsies might be useful to exclude chronic CNI-induced lesions.