Maud Cousin

Insights From the Use in Clinical Practice of Eculizumab in Adult Patients With Atypical Hemolytic Uremic Syndrome Affecting the Native Kidneys: An Analysis of 19 Cases

BACKGROUND Atypical hemolytic uremic syndrome (aHUS) is a devastating form of renal thrombotic microangiopathy. Despite plasma exchange, the standard treatment of aHUS for decades, the renal prognosis for patients with aHUS has remained poor. We assessed the off-trial use of eculizumab in adult patients with aHUS affecting the native kidneys. STUDY DESIGN A retrospective study was conducted. aHUS was defined as the presence of 3 or more of the following: acute kidney injury (serum creatinine >1.4 mg/dL [120 μmol/L]), mechanical hemolytic anemia, thrombocytopenia, and the presence of thrombotic microangiopathy features in a kidney biopsy specimen. Patients who had received 4 or more weekly 900-mg infusions of eculizumab were included. SETTING & PARTICIPANTS 19 patients were identified through a query sent to all French nephrology centers. OUTCOMES & MEASUREMENTS Evolution of kidney function, hemolysis, and thrombocytopenia after the initiation of eculizumab therapy. RESULTS All patients had acute kidney injury (serum creatinine range, 2.2-17.0 mg/dL) and 12 required hemodialysis. Thirteen patients carried a mutation in 1 complement gene and 1 had anti-factor H antibodies. For first-line therapy, 16 patients underwent plasma exchange and 3 patients received eculizumab. Median time between aHUS onset and eculizumab therapy initiation was 6 (range, 1-60) days and median time to platelet count normalization after eculizumab therapy initiation was 6 (range, 2-42) days. At the 3-month follow-up, 4 patients still required dialysis, 8 had non-dialysis-dependent chronic kidney disease, and 7 had normalized kidney function. At last follow-up (range, 4-22 months), 3 patients remained dialysis dependent, 7 had non-dialysis-dependent chronic kidney disease (estimated glomerular filtration rate, 17-55 mL/min/1.73 m(2)), and 9 had normal kidney function. Risks of reaching end-stage renal disease within 3 months and 1 year of aHUS onset were reduced by half in eculizumab-treated patients compared with recent historical controls. LIMITATIONS Retrospective study and use of historical controls. CONCLUSIONS Our data indicate that eculizumab improves kidney disease outcome in patients with aHUS.

Role of Angiotensin II in the Remodeling Induced by a Chronic Increase in Flow in Rat Mesenteric Resistance Arteries

Angiotensin II is a potent growth factor involved in arterial wall homeostasis. In resistance arteries, chronic increases in blood flow induce a rise in diameter associated with arterial wall hypertrophy. Nevertheless, the role of angiotensin II in this remodeling is unknown. We investigated the effect of blocking angiotensin II production or receptor activation on flow-induced remodeling of mesenteric resistance arteries. Arteries were ligated in vivo to generate high-flow arteries compared with normal flow (control) vessels located at a distance. Arteries were isolated after 1 week for in vitro analysis. Arterial diameter, media surface, endothelial NO synthase expression, superoxide production, and extracellular signal–regulated kinase 1/2 phosphorylation were higher in high-flow than in control arteries. Angiotensin-converting enzyme inhibition (perindopril) and angiotensin II type 1 receptor blockade (candesartan) prevented arterial wall hypertrophy without affecting diameter enlargement. The nonselective vasodilator hydralazine had no effect on remodeling. Although perindopril and candesartan increased endothelial NO synthase expression in high-flow arteries, hypertrophy remained in rats treated with NG-nitro-l-arginine methyl ester and mice lacking endothelial NO synthase. Perindopril and candesartan reduced oxidative stress in high-flow arteries, but superoxide scavenging did not prevent hypertrophy. Both Tempol and the absence of endothelial NO synthase prevented the rise in diameter in high-flow vessels. Extracellular signal–regulated kinase 1/2 activation in high-flow arteries was prevented by perindopril and candesartan and not by hydralazine. Extracellular signal–regulated kinase 1/2 inhibition in vivo (U0126) prevented hypertrophy in high-flow arteries. Thus, a chronic rise in blood flow in resistance arteries induces a diameter enlargement involving NO and superoxide, whereas hypertrophy was associated with extracellular signal–regulated kinase 1/2 activation by angiotensin II.

A case of sulphasalazine-induced DRESS syndrome with delayed acute interstitial nephritis

Drug rash with eosinophilia and systemic symptoms (DRESS syndrome) is a rare and severe drug-induced hypersensitivity syndrome characterized by haematological abnormalities (hypereosinophilia and/or mononucleosis) and multiorgan involvement. Renal failure has been rarely described. We report the case of a 77-year-old female with sulphasalazine-induced DRESS syndrome who improved rapidly on corticosteroid treatment. After prednisone withdrawal, the patient developed renal failure that necessitated a session of haemodialysis. A kidney biopsy showed acute tubulointerstitial nephritis with an intense lymphocytic infiltrate and tubular necrosis. Kidney function normalized after a further 2 weeks of corticosteroid treatment. This is the first histologically proven case of acute tubulointerstitial nephritis in the setting of sulphasalazine-induced DRESS syndrome.

Involvement of angiotensin II in the remodeling induced by a chronic decrease in blood flow in rat mesenteric resistance arteries

Blood flow reduction induces inward remodeling of resistance arteries (RAs). This remodeling occurs in ischemic diseases, diabetes and hypertension. Nonetheless, the effect of flow reduction per se, independent of the effect of pressure or metabolic influences, is not well understood in RA. As angiotensin II is involved in the response to flow in RA, we hypothesized that angiotensin II may also be involved in the remodeling induced by a chronic flow reduction. We analyzed the effect of angiotensin I-converting enzyme inhibition (perindopril) and angiotensin II type 1 receptor blockade (candesartan) on inward remodeling induced by blood flow reduction in vivo in rat mesenteric RAs (low flow (LF) arteries). After 1 week, diameter reduction in LF arteries was associated with reduced endothelium-dependent relaxation and lower levels of eNOS expression. Superoxide production and extracellular signal-regulated kinases 1/2 (ERK1/2 phosphorylation were higher in LF than in normal flow arteries. Nevertheless, the absence of eNOS or superoxide level reduction (tempol or apocynin) did not prevent LF remodeling. Perindopril and candesartan prevented inward remodeling in LF arteries. Contractility to angiotensin II was reduced in LF vessels by perindopril, candesartan and the ERK1/2 blocker PD98059. ERK1/2 activation (ratio phospho-ERK/ERK) was higher in LF arteries, and this activation was prevented by perindopril and candesartan. ERK1/2 inhibition in vivo (U0126) prevented LF-induced diameter reduction. Thus, inward remodeling because of blood flow reduction in mesenteric RA depends on unopposed angiotensin II-induced contraction and ERK1/2 activation, independent of superoxide production. These findings might be of importance in the treatment of vascular disorders.

Therapeutic plasma exchange in chronic dysimmune peripheral neuropathies: A 10-year retrospective study

Therapeutic plasma exchange (TPE) can be proposed in the treatment of chronic dysimmune peripheral neuropathies (CDPN). Actual guidelines are however based on few studies, and indications and protocols still remain to be clarified. We conducted a 10‐year retrospective study in order to assess the effectiveness and tolerance of TPE in CDPN.

An Unusual Cause of Abdominal Pain: Lupus Enteritis

0002-9343/

Bunches of grapes in renal polyarteritis nodosa

-see front matter 2016 Elsevier Inc. All rights reserved. is nonspecific, and main symptoms include focal or diffuse abdominal pain, vomiting, diarrhea, and fever. Even if there is no pathognomonic imaging feature of lupus enteritis, computed tomography may be suggestive. Typical computed tomography features that have been reported are bowel wall thickening over 3 mm (“target sign”) with abnormal bowel-wall contrast enhancement, dilatation of intestinal segments, and engorgement of mesenteric vessels (“comb sign”).

Addition of Plasma Exchange to Glucocorticosteroids for the Treatment of Severe Henoch-Schönlein Purpura in Adults: A Case Series

A 26-year-old woman presented to a local community hospital with fever and abdominal pain. Clinical examination showed mild abdominal and bilateral lumbar tenderness. Blood analysis showed C-reactive protein of 401 mg/l, leukocyte count of 15,340/mm3, and serum creatinine of 71 μmol/l. Chest radiograph and abdominal ultrasound were normal. She was diagnosed with pyelonephritis despite negative urinalysis and was discharged. Soon after, her condition worsened with 5 kg weight loss, myalgia, and arthralgia. Two months later, she was readmitted with severe left flank pain. Contrast-enhanced abdominal computed tomography (CT) showed a large subcapsular hematoma surrounding the left kidney (Figure 1). Multiple bilateral intrarenal aneurysms of variable diameter (1–14 mm) were detected during the arterial phase (Figure 1) with the appearance of bunch of grapes. Multiple bilateral wedge-shaped low-attenuation involving cortex and medulla suggesting kidney infarcts were also detected (Supplementary Figure 1 online). Urinalyses showed microscopic hematuria and proteinuria of 0.9 g/24 h. Comprehensive autoimmune including Anti-neutrophil cytoplasmic antibodies (ANCA) research and viral screenings were negatives.