Fractures in patients with rheumatoid arthritis and end-stage renal disease.

Having rheumatoid arthritis (RA) or end-stage renal disease (ESRD) can lead to fractures. RA independently increases the risk of hip or other femur fracture in dialysis patients. Use of corticosteroids is a potentially modifiable risk factor for fractures among persons with RA and ESRD on dialysis. PURPOSE: Rheumatoid arthritis (RA) and end-stage renal disease (ESRD) both independently increase fracture risk; however, how RA and ESRD interplay to affect fracture risk is unknown. We aim to determine the association of RA with fracture in ESRD and identify risk factors for fracture in patients with RA and ESRD. METHODS: A retrospective cohort study was conducted using the United States Renal Data System (USRDS) to identify ESRD adults with and without a history of RA who initiated dialysis in 2005-2008. International Classification of Diseases, 9th Revision (ICD-9) codes were used to identify fractures following start of dialysis. Risk for incident fracture was compared between those with and without RA. Potential risk factors for fracture among persons with RA and ESRD were analyzed. RESULTS: There were 754 persons with ESRD and RA, of whom 126 (17%) had any incident fracture. In multivariable adjusted final models, among ESRD patients, RA was an independent risk factor for hip/femur fracture (RR 1.28, 95% CI 1.01-1.64). Among persons with RA and ESRD, in final models, only corticosteroid use was a significant risk factor for both any incident (RR 2.00, 95% CI 1.40-2.87) and hip/femur (RR 1.97, 95% CI 1.24-3.11) fracture. Those with higher body mass index had a lower relative risk of hip/femur fracture (RR 0.95, 95% CI 0.91-0.99). CONCLUSION: Among ESRD patients, those with RA have a 28% increased risk for hip or other femur fracture. Use of corticosteroids is a potentially modifiable risk factor for fractures among persons with RA and ESRD.

Incidence and risk factors for HPV-associated cancers in women with end-stage renal disease.

Human papillomavirus (HPV) causes the majority of cervical, anal/rectal, and oropharyngeal cancers in women. End-stage renal disease (ESRD) is also associated with an increased risk of malignancy, but the incidence of and risk factors for HPV-associated cancers in US dialysis patients are not defined. We queried the US Renal Data System for women with HPV-associated cancers and assessed for incidence of cancer diagnosis and association of risk factors. From 2005 to 2011, a total of 1032 female patients with ESRD had 1040 HPV-associated cancer diagnoses. Patients had a mean age of 65 years, were mostly white (63%), and on hemodialysis (92%). Cervical cancer (54%) was the most common, followed by anal/rectal (34%), and oropharyngeal (12%). The incidence of HPV-associated cancers in patients with ESRD increased yearly, with up to a 16-fold increased incidence compared with the general population. Major risk factors associated with the development of any HPV-associated cancer included smoking (adjusted relative risk=1.89), alcohol use (1.87), HIV (2.21), and herpes infection (2.02). Smoking, HIV, and herpes infection were prominent risk factors for cervical cancer. The incidence of HPV-associated cancers in women with ESRD is rising annually and is overall higher than in women of the general population. Tobacco use is a universal risk factor. For cervical cancer, the presence of HIV and herpes are important comorbidities. Recognizing risk factors associated with these cancers may improve diagnosis and facilitate survival. The role of HPV vaccination in at-risk dialysis patients remains to be defined but warrants further study.

Masked Hypotension due to Elevated Venous Pressure in a Patient with Complex Adult Congenital Heart Disease.

An adult with surgically corrected Tetralogy of Fallot presented with profoundly elevated central venous pressure (CVP) and acute renal dysfunction thought secondary to acute on chronic right heart failure. Treatment with dopamine promoted diuresis and a stabilization of renal function. Repeated attempts to wean the patient from dopamine were associated with hypotension and worsening renal failure. Invasive hemodynamic assessment unexpectedly demonstrated high cardiac output with low systemic vascular resistance (SVR). In retrospect, the markedly elevated CVP had concealed the impact of reduced SVR on blood pressure. After reversible causes of low SVR state were excluded, the patient was successfully managed with oral alpha-adrenergic agents. While typically negligible under physiologic conditions, elevated CVP can artificially increase mean arterial pressure. We have coined the term "masked hypotension" to describe this unique pathophysiological phenomenon.

MicroRNA-668 represses MTP18 to preserve mitochondrial dynamics in ischemic acute kidney injury.

The pathogenesis of ischemic diseases remains unclear. Here we demonstrate the induction of microRNA-668 (miR-668) in ischemic acute kidney injury (AKI) in human patients, mice, and renal tubular cells. The induction was HIF-1 dependent, as HIF-1 deficiency in cells and kidney proximal tubules attenuated miR-668 expression. We further identified a functional HIF-1 binding site in the miR-668 gene promoter. Anti-miR-668 increased apoptosis in renal tubular cells and enhanced ischemic AKI in mice, whereas miR-668 mimic was protective. Mechanistically, anti-miR-668 induced mitochondrial fragmentation, whereas miR-668 blocked mitochondrial fragmentation during hypoxia. We analyzed miR-668 target genes through immunoprecipitation of microRNA-induced silencing complexes followed by RNA deep sequencing and identified 124 protein-coding genes as likely targets of miR-668. Among these genes, only mitochondrial protein 18 kDa (MTP18) has been implicated in mitochondrial dynamics. In renal cells and mouse kidneys, miR-668 mimic suppressed MTP18, whereas anti-miR-668 increased MTP18 expression. Luciferase microRNA target reporter assay further verified MTP18 as a direct target of miR-668. In renal tubular cells, knockdown of MTP18 suppressed mitochondrial fragmentation and apoptosis. Together, the results suggest that miR-668 is induced via HIF-1 in ischemic AKI and that, upon induction, miR-668 represses MTP18 to preserve mitochondrial dynamics for renal tubular cell survival and kidney protection.

End-stage renal disease in patients with rheumatoid arthritis.

OBJECTIVES: To determine the frequency of end-stage renal disease (ESRD) in patients with rheumatoid arthritis (RA), the causes of ESRD, and the treatment of RA in the setting of ESRD. METHODS: Cross-sectional study of RA (N = 3754) and non-RA (N = 326,776) patients in the United States Renal Data System (USRDS) during 2011 (N = 330,530). The epidemiology of ESRD in RA was determined and the etiology of ESRD in patients with and without RA was compared. The frequency of patients with RA with at least one filled prescription for prednisone/prednisolone, a DMARD, and/or a biologic in 2011 was determined. RESULTS: The prevalence of RA with ESRD in the USRDS in 2011 was 1.1%. There were significant differences in age, race, sex, and BMI category between the groups (p < 0.01). Diabetes (33.5%) and hypertension (30.6%) were the most common primary causes of ESRD in patients with RA. Amyloidosis, vasculitis, and analgesic nephropathy combined accounted for less than 10% of cases of ESRD. Prednisone was the most commonly filled medication that could be used to treat RA (45.9% of RA patients). Hydroxychloroquine was the most frequently filled DMARD (13.5%); biologics were uncommon (etanercept 2.5%, adalimumab 1.5%; golimumab, infliximab, anakinra, and abatacept <1%). CONCLUSIONS: The co-occurrence of RA with ESRD was 1.1% in the USRDS by 2011. Physicians should be aware of the critical impact of the comorbidities of diabetes and hypertension in causing ESRD in RA patients. Use of DMARDS other than hydroxychloroquine and biologics to treat RA in the setting of ESRD appears to be infrequent. Further prospective studies of treatment strategies for RA in ESRD are needed.