Sex hormones and the risk of cardiovascular disease and mortality in male and female patients with chronic kidney disease: A systematic review and meta-analysis.

Patients with chronic kidney disease (CKD) commonly experience sex hormone disturbances, which may be associated with the risk of cardiovascular disease (CVD) and mortality. This review aimed to systematically evaluate current findings on the association of sex hormone levels with the risk of CVD events and mortality (CVD and all-cause) in the CKD population. Articles were systematically searched in CINAHL, Cochrane, and PubMed. A total of 1739 articles were independently screened by two reviewers and 17 prospective cohort studies were included. The clinical conditions of the patients were those with non-dialysis CKD [mean/median estimated glomerular filtration rate (eGFR) between 15-51 ml/min/1.73 m2 ] and those on chronic dialysis (mean/median vintage between 6-125 months). The sample size ranged from 111 to 2419 and the mean/median age of subjects ranged from 52 to 72 years. The sex hormones studied were testosterone, estradiol, prolactin, dehydroepiandrosterone sulfate, and relaxin. A random-effects model was used to generate a pooled hazard ratio (HR) to evaluate the association of total testosterone levels with the risk of CVD and all-cause mortality. Most studies examined total testosterone levels (11 out of 17 studies) and studied only male patients (12 out of 17 studies). A lower total testosterone level was associated with a higher risk of CVD mortality [HR 4.37 (95% CI 1.40-13.65)] and all-cause mortality [1.96 (1.35-2.83)] in males with CKD. To conclude, there is a strong need for additional studies examining the association of sex hormones with cardiovascular and mortality risk in female patients with CKD.

Association of Monocyte Count and Monocyte/Lymphocyte Ratio with the Risk of Cardiovascular Outcomes in Patients with CKD.

Background: Emerging evidence suggests an association of higher monocyte count and monocyte/lymphocyte ratio (MLR) with the risk of cardiovascular disease (CVD) in individuals without chronic kidney disease (CKD); however, limited studies have examined if this association translates to the CKD population. This study examined whether monocyte count and MLR are associated with the risk of CVD, CVD death, and all-cause death in patients with nondialysis CKD who participated in the Chronic Renal Insufficiency Cohort observational study. Methods: Baseline monocyte count and MLR were categorized into tertiles and also modeled continuously. Cox proportional hazards models were used to examine the association between monocyte count (primary predictor) and MLR (secondary predictor) at baseline and time to a composite of CVD events, including heart failure, myocardial infarction, ischemic stroke, and peripheral artery disease (primary outcome). Secondary outcomes were time to CVD death and all-cause death. Results: The median follow-up time was 9 years for CVD events and 11.7 years for death. In the fully adjusted model, participants with a higher monocyte count and MLR had a greater risk of CVD events (hazard ratio [HR] per doubling of monocyte count=1.2 [95% CI, 1.1 to 1.31]; HR per doubling of MLR=1.26 [95% CI, 1.16 to 1.36]), CVD death (HR=1.18 [95% CI, 0.99 to 1.41]; HR=1.27 [95% CI, 1.1 to 1.48]), and all-cause death (HR=1.17 [95% CI, 1.06 to 1.3]; HR=1.18 [95% CI, 1.09 to 1.29]). Conclusions: These results suggest that monocyte count and MLR may have the potential to be cost-effective, clinically available indicators of CVD risk in the CKD population.

Shunt Nephritis: An Increasingly Unfamiliar Diagnosis.

BACKGROUND: Shunt nephritis is a rare, reversible immune-complex mediated complication of cerebrospinal fluid (CSF) shunt infection that can progress to end-stage renal disease and even death if diagnosis is delayed. CASE DESCRIPTION: The present case report details the manifestation and clinical course of shunt nephritis in a 50-year-old patient who presented with symptoms of nephrotic syndrome 30 years after ventriculojugular shunt placement. Diagnosis was delayed due to initial negative CSF and blood cultures, but a later CSF culture was positive for Propionibacterium acnes. After treatment with intravenous antibiotics and complete removal of shunt with subsequent replacement with a new ventriculoperitoneal shunt, the nephritic symptoms resolved, but the patient continued to have reduced kidney function consistent with stage IIIa chronic kidney disease. CONCLUSION: This case emphasizes the clinical importance of having a high index of suspicion in patients with a ventricular shunt who present with symptoms consistent with nephritis, even in the setting of negative cultures and delayed presentation.

Mineral Metabolites, Angiotensin II Inhibition and Outcomes in Advanced Chronic Kidney Disease.

BACKGROUND: Evidence suggests that the renin-angiotensin-aldosterone system (RAAS) interacts with the vitamin D-fibroblast growth factor 23-Klotho axis. We investigated whether circulating mineral metabolism markers modify outcomes in response to RAAS inhibition in subjects with advanced chronic kidney disease (CKD). METHODS: In this retrospective cohort study, we analyzed the association of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) use with all-cause mortality and dialysis initiation among 1,753 subjects (1,099 CKD, estimated glomerular filtration rate 18 ± 6 ml/min/1.73 m(2) and 654 end-stage renal disease [ESRD]) from the Homocysteine in Kidney and End Stage Renal Disease (HOST) study. A propensity score analysis accounted for indication bias and Cox regression models adjusted for mineral metabolism markers. RESULTS: Mean follow-up was 3.2 years; 714 (41%) subjects died and 615 (56%) initiated dialysis. In adjusted analyses, all subjects treated with ACEI/ARB had a significantly lower hazard of death (hazards ratio (HR) 0.81, 95% CI 0.70-0.95, p = 0.007). Those with CKD not on dialysis and treated with ACEI/ARB trended toward a lower hazard of dialysis initiation (HR 0.86, 95% CI 0.73-1.01, p = 0.06). The association with mortality did not differ by level of mineral metabolism marker (p for interaction >0.16); however, the relationship with dialysis initiation differed according to the median serum phosphorus level (p for interaction <0.001). CONCLUSIONS: RAAS inhibition was associated with decreased all-cause mortality independent of disordered mineral metabolism among mostly male HOST subjects with advanced CKD and ESRD. However, among those with CKD not requiring dialysis, the renoprotection associated with RAAS inhibition was attenuated by higher serum phosphorus levels. Further studies are needed to confirm this association.

Vitamin D level and risk of community-acquired pneumonia and sepsis.

Previous research has reported reduced serum 25-hydroxyvitamin D (25(OH)D) levels is associated with acute infectious illness. The relationship between vitamin D status, measured prior to acute infectious illness, with risk of community-acquired pneumonia (CAP) and sepsis has not been examined. Community-living individuals hospitalized with CAP or sepsis were age-, sex-, race-, and season-matched with controls. ICD-9 codes identified CAP and sepsis; chest radiograph confirmed CAP. Serum 25(OH)D levels were measured up to 15 months prior to hospitalization. Regression models adjusted for diabetes, renal disease, and peripheral vascular disease evaluated the association of 25(OH)D levels with CAP or sepsis risk. A total of 132 CAP patients and controls were 60 ± 17 years, 71% female, and 86% Caucasian. The 25(OH)D levels <37 nmol/L (adjusted odds ratio (OR) 2.57, 95% CI 1.08-6.08) were strongly associated with increased odds of CAP hospitalization. A total of 422 sepsis patients and controls were 65 ± 14 years, 59% female, and 91% Caucasian. The 25(OH)D levels <37 nmol/L (adjusted OR 1.75, 95% CI 1.11-2.77) were associated with increased odds of sepsis hospitalization. Vitamin D status was inversely associated with risk of CAP and sepsis hospitalization in a community-living adult population. Further clinical trials are needed to evaluate whether vitamin D supplementation can reduce risk of infections, including CAP and sepsis.

Where vaptans do and do not fit in the treatment of hyponatremia.

The treatment of hyponatremia, an exceedingly common electrolyte disorder, has been a subject of controversy for many years. The advent of vasopressin antagonists (vaptans) has added to the treatment arsenal. This review focuses on why hyponatremia should be treated and the role of these antagonists in the treatment. Upon analysis of the available literature, we conclude that there is presently no role for vaptans in acute symptomatic hyponatremia. Although numerous therapeutic approaches are available for chronic symptomatic hyponatremia, vasopressin antagonists provide a simpler treatment option. Vaptans are efficacious in raising serum sodium in long-standing 'asymptomatic' hyponatremia. However, the cost of the only Food and Drug Administration-approved oral agent (tolvaptan) makes its use prohibitive for most patients in this setting.