281 research outputs found
Canakinumab as rescue therapy in familial Mediterranean fever refractory to conventional treatment
No full textMirella Alpa, Dario Roccatello Centro di Ricerche di Immunopatologia e Documentazione su Malattie Rare (CMID), Struttura Complessa Direzione Universitaria di Immunologia Clinica, Università di Torino e Ospedale G Bosco, Torino, ItalyAbstract: Familial Mediterranean fever is an autosomal recessive autoinflammatory disorder mainly affecting Mediterranean populations, which is associated with mutations of the MEFV gene that encodes pyrin. Functional studies suggest that pyrin is implicated in the maturation and secretion of interleukin-1 (IL-1). The IL-1 receptor antagonist or anti-IL-1 monoclonal antibody may therefore represent a rational approach for the treatment of the rare patients who are refractory to conventional therapy. We report the case of a young female affected by familial Mediterranean fever who proved to be resistant to colchicine and was successfully treated with canakinumab.Keyword: interleukin-1, colchicine, familial Mediterranean fever, anti-IL-1 treatment, biologic agent
EFFECTS OF CALCITRIOL ON THE BIOGENESIS OF A LYSOSOMAL PROTEASE IN MONOCYTES FROM PATIENTS WITH RENAL-FAILURE
No full text
A multidrug, antiproteinuric approach to alport syndrome : a ten-year cohort study
No full textBACKGROUND/AIMS:
Combined ACE inhibitor, angiotensin-receptor-blocker, non-dihydropyridine calcium-channel-blocker, and statin therapy (Remission Clinic) reduced proteinuria and halted progression in non-diabetic nephropathies, but their efficacy in Alport syndrome (AS) nephropathy is unknown.
METHODS:
From February 2004 to September 2007, we included nine albuminuric AS adults with creatinine clearance >20 ml/min/1.73 m(2) in a single-center, open-label, prospective, off-on-off academic study. After the 1-month wash-out from RAS inhibition (Run-in), patients entered the 4-month, add-on, treatment period with benazepril (10-20 mg/day), valsartan (80-160 mg/day), diltiazem (60-120 mg/day), and fluvastatin (40-80 mg/day) followed by the 1-month wash-out (Recovery). The primary outcome was albuminuria at month 4. After recovery, patients were kept on the Remission Clinic protocol and followed until July 2014 (Extension).
RESULTS:
The median (IQR) albuminuria progressively declined from 657.7 (292.7-1,089.6) μg/min at baseline to 71.4 (21.7-504.9) μg/min at treatment end (p = 0.009) and raised to 404.3 (167.9-446.8) μg/min after recovery. Albumin and IgG fractional clearances significantly (p ≤ 0.005) decreased from 66.9 (53.6-80.8) to 9.4 (4.6-26.0) and from 5.1 (3.0-8.4) to 1.1 (0.6-3.2), and then recovered toward baseline. Blood pressure and lipids significantly decreased on treatment, without changes in inulin-measured GFR or para-aminohippuric-measured RPF. After recovery, one patient refused to enter the extension, one with severe renal insufficiency at baseline reached ESRD, and seven retained normal serum creatinine until the end of the study. At the final visit, three were microalbuminuric and one was normoalbuminuric. Treatment was well tolerated.
CONCLUSION:
The Remission Clinic approach safely ameliorated albuminuria, blood pressure, lipids, and glomerular selectivity in AS patients and halted long-term progression in those without renal insufficiency to start with
Systemic AA amyloidosis as a unique manifestation of a combined mutation of TNFRSF1A and MEFV genes
No full textWe report the case of a 22-year-old Caucasian woman presenting with a new-onset nephrotic syndrome with normal renal function during the 35th week of pregnancy. AA (secondary) amyloidosis was further diagnosed at the renal biopsy. Extensive genetic testing revealed that the patient was heterozygous for both TNFRSF1A p.R92Q and MEFV p.M694I mutations leading to an autoinflammatory syndrome characterized by amyloid deposition as the sole manifestation
Differentiating between UCTD and early-stage SLE: from definitions to clinical approach
No full textSystemic lupus erythematosus (SLE) is an autoimmune disease with heterogeneous clinical manifestations that can potentially affect every organ and system. SLE is usually identified on the basis of clinical or serological manifestations; however, some individuals can present with signs and symptoms that are consistent with SLE but are not sufficient for a definite diagnosis. Disease in these individuals can either progress over time to definite SLE or remain stable, in which case their disease is often described as intermediate, possible or probable SLE. Alternatively, such individuals might have undifferentiated connective tissue disease (UCTD). Being able to differentiate between those with stable UCTD and those with SLE at an early stage is important to avoid irreversible target-organ damage from occurring. This Review provides insight into existing and evolving perceptions of the early stages of SLE, including clinical and mechanistic considerations, as well as potential paths towards early identification and intervention. Further research into the earliest phases of SLE will be important for the development of targeted diagnostic approaches and biomarkers for the identification of individuals with early disease who are likely to progress to definite SLE
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