Background: Dialysis in older adults with chronic kidney disease (CKD) and comorbidities may not be associated with improved life expectancy compared to conservative management. To inform clinical practice, we performed a systematic review of all available studies examining this hypothesis. Methods: We performed a systematic review of retrospective and prospective cohort studies of older adults with stage-5 CKD who chose dialysis (hemodialysis or peritoneal dialysis) or opted for conservative management (including management of complications of CKD and palliative care). Outcomes of interest included hospitalizations and mortality. Results: Twelve cohort studies (11,515 patients) were identified with most of them focusing on older adults. Patients choosing dialysis were younger compared to those opting for conservative management and were less functionally impaired. Patients opting for conservative management received care in a multidisciplinary setting focusing on palliative care and management of complications of CKD. Patients choosing dialysis and conservative management had a median survival time of 8-67 and 6-30 months, respectively. In a subset of studies of patients 65 years and older with an estimated glomerular filtration rate <15 mL/min/1.73 m2, and where the multivariable analyses included age and comorbidities, by meta-analysis, patients choosing dialysis had a pooled adjusted hazard ratio for mortality of 0.53 (95% CI 0.30-0.91, p = 0.02) relative to those opting for conservative management; however, significant heterogeneity precluded definitive conclusions. Conclusions: When caring for older adults with advanced CKD who are contemplating dialysis therapy vs. conservative management, efforts must focus on promoting patient values and preferences, shared decision-making, and symptom burden alleviation.
More than 50 individuals with activating variants in the receptor tyrosine kinase PDGFRB have been reported, separated based on clinical features into solitary myofibromas, infantile myofibromatosis, Penttinen syndrome with premature aging and osteopenia, Kosaki overgrowth syndrome, and fusiform aneurysms. Despite their descriptions as distinct clinical entities, review of previous reports demonstrates substantial phenotypic overlap. We present a case series of 12 patients with activating variants in PDGFRB and review of the literature. We describe five patients with PDGFRB activating variants whose clinical features overlap multiple diagnostic entities. Seven additional patients from a large family had variable expressivity and lateonset disease, including adult onset features and two individuals with sudden death. Three patients were treated with imatinib and had robust and rapid response,
The incidence of hypocalcemia and bone mineral density (BMD) changes in end-stage renal disease (ESRD) patients on denosumab remains unclear. We performed this meta-analysis to assess the incidence of denosumab-associated hypocalcemia and effects of denosumab on BMD in ESRD patients. A literature search was conducted using MEDLINE, EMBASE, and Cochrane Database from inception through November 2017 to identify studies evaluating incidence of denosumab-associated hypocalcemia and changes in serum calcium, phosphate, alkaline phosphatase (ALP), parathyroid hormone (PTH), and BMD from baseline to post-treatment course of denosumab in ESRD patients. Study results were pooled and analyzed using a random-effect model. The protocol for this meta-analysis is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42017081074). Six observational studies with a total of 84 ESRD patients were enrolled. The pooled estimated incidence of hypocalcemia during denosumab treatment was 42% (95% CI 29-55%, I = 0%). Hypocalcemia occurred approximately 7 to 20 days after the first dose and reached nadir of low calcium levels in the first 2 weeks up to 2 months. However, there were no significant changes in serum calcium or phosphate from baseline to post-treatment course (≥ 3 months after treatment) with mean differences [MDs] of 0.20 mg/dL (95% CI, - 0.30 to 0.69 mg/dL) and - 0.10 mg/dL (95% CI, - 0.70 to 0.49 mg/dL). There were significant reductions in ALP and PTH levels with standardized mean differences (SMDs) of - 0.65 (95% CI - 1.13 to - 0.16) and - 1.89 (95% CI - 3.44 to - 0.34), respectively. There were significant increases in T-scores with MDs of 0.39 (95% CI 0.10 to 0.69) and 0.79 (95% CI 0.60 to 0.98) for lumbar spine and femoral neck, respectively. Our study demonstrates the estimated incidence of denosumab-associated hypocalcemia in dialysis patients of 42%. From baseline to post-treatment course, although there are no differences in serum calcium and phosphate, our findings suggest significant reductions in ALP and PTH and a significant increase in BMD. Currently, denosumab should not be considered as the treatment of choice in ESRD patients until more safety and efficacy data are available.
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