Diabetes is one of the leading causes of chronic kidney disease (CKD), and multiple underlying mechanisms involved in pathogenesis of diabetic nephropathy (DN) have been described. Although various treatments and diagnosis applications are available, DN remains a clinical and economic burden, considering that about 40% of type 2 diabetes patients will develop nephropathy. In the past years, some research found that hypoxia response and hypoxia-inducible factors (HIFs) play critical roles in the pathogenesis of DN. Hypoxia-inducible factors (HIFs) HIF-1, HIF-2, and HIF-3 are the main mediators of metabolic responses to the state of hypoxia, which seems to be the one of the earliest events in the occurrence and progression of diabetic kidney disease (DKD). The abnormal activity of HIFs seems to be of crucial importance in the pathogenesis of diseases, including nephropathies. Studies using transcriptome analysis confirmed by metabolome analysis revealed that HIF stabilizers (HIF-prolyl hydroxylase inhibitors) are novel therapeutic agents used to treat anemia in CKD patients that not only increase endogenous erythropoietin production, but also could act by counteracting the metabolic alterations in incipient diabetic kidney disease and relieve oxidative stress in the renal tissue. In this review, we present the newest data regarding hypoxia response and HIF involvement in the pathogenesis of diabetic nephropathy and new therapeutic insights, starting from improving kidney oxygen homeostasis.
The use of biological therapies may have positive impact on chronic renal disease associated with rheumatoid arthritis. The study evaluates retrospectively renal function in 57 patients with rheumatoid arthritis treated with different types of biological therapy, comparative with 62 RA patients treated conservatively with DMARDs. Patients treated with biological therapies presented a lower mean value for serum creatinine measured both at baseline and after 6 months of treatment, statistically significant compared with the subgroup treated with DMARDs (0.69 ± 0.17 mg/dL vs. 1.18 ± 1.01 mg/dL, p = 0.003). Results for estimated filtration rate were significantly increased in biologically treated cohort (100.36 ± 16.76 mL/min/1.73 m2 vs. 63.49 ± 21.60 mL/min/1.73 m2, p < 0.00001). Rituximab presented a better estimated filtration rate compared with other biological tharapies (eGFR 97.037 mL/min/1.73 m2 vs. 90.933 mL/min/1.73 m2). The positive effect of potent biological anti-inflammatory therapies sustains the need of further exploring the risk of reduced kidney function in immune-mediated diseases, including rheumatoid arthritis.
Background Psoriatic arthritis (PA) is a chronic inflamatory joint diseasewhich combines skin disease (psoriasis) with various joint manifestations (spondylitis, peripheral arthritis, dactilytis and enthesitis) (1). Some authors said that 11% of individuals with psoriasis had PA, but with more severe psoriasis the number rose to 56% (2). There are many composite instruments used for assessment of disease activity, most of them borrowed from another inflammatory disease, particularly rheumatoid arthritis, but none has been firmily established yet (1,3). Disease heterogeneity makes failure use of a single instrument to assess the whole spectrum of clinical feature requiring a separate assessement of the disease manifestation. Objectives To compare different tools and methods for assessing disease activity in patient with PA. Methods A cohort study was performed in our rheumatology department on 33 patients with PA, consecutively included from august 2011 to december 2011. All patients met the CASPAR criteria for PA. The assessment included clinical (tender joint, swollen joint, VAS score, patient global assessment, MASES score) and laboratory variables (ESR,CRP). Also imaging (limb joint X-ray and enthesis ultrasound) and clinical evaluation on skin disease (with PASI score) was made. Moreover, we used a composite index originally developed for reactive arthritis (DAPSA) to express the disease activity. Results The cohort included 18 men and 15 women with mean age 56.55±8.83 years, with family history of psoriasis in about 18.2% of cases. 33.3% had early disease and 27.3% had a disease older than 10 year. Majority of patients (87.9%) following DMARD therapy and 63.6% had erosive disease. Patients with family history of psoriasis had more biological active disease with mean of CRP 6.67±2.65 (p=0.03). Related to disease activity scores, DAPSA score is more increased in polyarticular and decreased when co-exist axial involvement (29.38±17.65 and 15.01±6.10, respectively) (p=0.05). Moreover, DAPSA score had good correlation with clinical indices used in practice (tender joints, swollen joints, VAS score, ESR and CRP), but no correlation with PASI score, entheseal scores (MASEI, MASES) and erosive peripheral disease. PASI score had good correlation only with MASES score (p=0.009, r=0.4). Moreover, MASES score is related with axial involvement (6.71±2.13, p=0.05). Conclusions The DAPSA score reflects the global activity of peripheral joint disease, but when coexist whit axial involvment we need to use suplimentarly indices like MASES and PASI score. References Shoels M et al. Application of the DAREA/DAPSA score for assessmentof disease activity in psoriatic arthritis. Ann Rheum Dis 201 69(8):1441-7 Gladman DD. Psoriatic arthritis Clinical features. In Ritchlin CT, Fitzgerald O. (Eds) Psoriatic arthritis and reactive arthritis. Mosby Elsevier 2007;9-18. De Miguel E et al. Diagnostic accuracy of enthesis ultrasound in the diagnosis of early spondyloarthritis, AnnRheumDis 2011, 70: 434-9 Disclosure of Interest None ...
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