Raloxifene in the Treatment of Osteoporosis in Postmenopausal Women with End-Stage Renal Disease: A Systematic Review and Meta-Analysis.

As a selective estrogen receptor modulator (SERM), raloxifene is used in healthy postmenopausal women to prevent bone loss and reduce fractures. However, the benefit of raloxifene is uncertain in the treatment of osteoporosis among patients with end-stage renal disease (ESRD) or those who require maintenance dialysis. We assessed the safety and efficacy of raloxifene in this particular population. Studies were selected from PubMed, Springer, CNKI (Chinese National Knowledge Infrastructure) and Wanfang Database. Randomized controlled trials (RCTs) and prospective studies with control/placebo groups were included. Five studies were included with a total of 244 participants (121 patients in the raloxifene group and 123 patients in the placebo/control group). The median duration of treatment was 12 months. The incidence rate of side effects of raloxifene was 0/121 (0%). There was a significant improvement of lumbar spine bone mineral density (BMD) levels in the raloxifene group compared with the placebo group (MD: 33.88, 95% CI: 10.93, 56.84, p=0.004). There was no significant difference concerning the improvement of femoral neck BMD (MD: 8.42, 95% CI: -10.21, 27.04, p=0.38), intact parathyroid hormone (iPTH) (MD: -12.62, 95% CI: -35.36, 10.13, p=0.28), calcium (MD: -0.08, 95% CI: -0.61, 0.44, p=0.76), phosphorus (MD: 0.18, 95% CI: -0.12, 0.48, p=0.23) or bone alkaline phosphatase (BAP) (MD: -4.33, 95% CI: -14.44, 5.79, p=0.40). Raloxifene seems to be effective in improving the lumbar spine BMD in postmenopausal women with ESRD. More large RCTs are necessary to evaluate the long-term safety of raloxifene in uremic patients.

Estrogen and estrogen receptors in kidney diseases.

Acute kidney injury (AKI) and chronic kidney disease (CKD) are posing great threats to global health within this century. Studies have suggested that estrogen and estrogen receptors (ERs) play important roles in many physiological processes in the kidney. For instance, they are crucial in maintaining mitochondrial homeostasis and modulating endothelin-1 (ET-1) system in the kidney. Estrogen takes part in the kidney repair and regeneration via its receptors. Estrogen also participates in the regulation of phosphorus homeostasis via its receptors in the proximal tubule. The ERα polymorphisms have been associated with the susceptibilities and outcomes of several renal diseases. As a consequence, the altered or dysregulated estrogen/ERs signaling pathways may contribute to a variety of kidney diseases, including various causes-induced AKI, diabetic kidney disease (DKD), lupus nephritis (LN), IgA nephropathy (IgAN), CKD complications, etc. Experimental and clinical studies have shown that targeting estrogen/ERs signaling pathways might have protective effects against certain renal disorders. However, many unsolved problems still exist in knowledge regarding the roles of estrogen and ERs in distinct kidney diseases. Further research is needed to shed light on this area and to enable the discovery of pathway-specific therapies for kidney diseases.

Diagnostic value of TWEAK for predicting active lupus nephritis in patients with systemic lupus erythematosus: a systematic review and meta-analysis.

PURPOSE: Accumulative studies showed that tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) was up-regulated in the blood and urine from patients diagnosed with lupus nephritis (LN) and that it might be used as a novel biomarker for active LN. This meta-analysis aimed to determine the diagnostic value of TWEAK in active LN. METHODS: We searched the Cochrane Library, Embase, PubMed, Springer, Wanfang and CNKI databases for articles published up to 20 August 2020. The diagnostic capacity of TWEAK for active LN was assessed using pooled sensitivity and specificity, positive and negative likelihood ratios (PLR and NLR), diagnostic odds ratio (DOR), and area under the receiver operating characteristic curve (AUC). Quality assessment and publication bias were also evaluated. STATA 11.0 and Meta-Disc 1.4 were used to perform these analyses. RESULTS: Nine cross-sectional studies were included in this meta-analysis. The overall pooled sensitivity of TWEAK for the diagnosis of active LN was 0.69 (95% CI, 0.63-0.75), and specificity was 0.77 (95% CI, 0.71-0.82). The overall pooled PLR and NLR were 3.31 (95% CI, 2.05-5.35) and 0.38 (95% CI, 0.26-0.55), respectively, with a DOR of 10.89 (95% CI, 6.73-17.63) and AUC (SE) of 0.8276 (0.0289). Deeks' funnel plot revealed that the publication bias was insignificant in the study (p = .32). CONCLUSIONS: Our results suggest that TWEAK might be a potential biomarker for patients with active LN. Future cross-sectional and longitudinal studies are needed to confirm its diagnostic value, as well as to establish more definite cutoff for active LN.