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Background: Patients with chronic kidney disease (CKD) experience high rates of atherosclerotic cardiovascular disease and death that are not fully explained by traditional risk factors. In animal studies, defective cellular cholesterol efflux pathways which are mediated by the ATP binding cassette transporters ABCA1 and ABCG1 are associated with accelerated atherosclerosis. We hypothesized that cholesterol efflux in humans would vary in terms of cellular components, with potential implications for cardiovascular disease., Methods: We recruited 120 CKD patients (eGFR<30mL/min/1.73m 2 ) and 120 control subjects (eGFR ≥60mL/min/1.73m 2 ) in order to measure cholesterol efflux using either patients' HDL and THP-1 macrophages or patients' monocytes and a flow cytometry based cholesterol efflux assay. We also measured cell-surface levels of the common β subunit of the IL-3/GM-CSF receptor (IL-3Rβ) which has been linked to defective cholesterol homeostasis and may promote monocytosis. In addition, we measured plasma inflammatory cytokines and plasma metabolite profiles., Results: There was a strong positive correlation between cell-surface IL-3Rβ levels and monocyte counts in CKD (P<0.001). ABCA1 mRNA was reduced in CKD vs. control monocytes (P<0.05), across various etiologies of CKD. Cholesterol efflux to apolipoprotein A1 was impaired in monocytes from CKD patients with diabetic nephropathy (P<0.05), but we found no evidence for a circulating HDL-mediated defect in cholesterol efflux in CKD. Profiling of plasma metabolites showed that medium-chain acylcarnitines were both independently associated with lower levels of cholesterol transporter mRNA in CKD monocytes at baseline (P<0.05), and with cardiovascular events in CKD patients after median 2.6years of follow-up., Conclusions: Cholesterol efflux in humans varies in terms of cellular components. We report a cellular defect in ABCA1-mediated cholesterol efflux in monocytes from CKD patients with diabetic nephropathy. Unlike several traditional risk factors for atherosclerotic cardiovascular disease, plasma metabolites inversely associated with endogenous cholesterol transporters predicted cardiovascular events in CKD patients. (Funded by the National Institute of Diabetes and Digestive and Kidney DiseasesK23DK097288 and others.)., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Previous studies have shown that treatment with ergocalciferol in patients with CKD stage 3 + 4 is not effective with less than 33% of patients achieving a 25-OH vitamin D target of >30 ng/ml. The aim of this study was to test the response to cholecalciferol in CKD. We attempted to replete 25-OH vitamin D to a target level of 40-60 ng/ml using the response to treatment and PTH suppression as an outcome measure., Methods: This retrospective cohort study identified patients (Stages 2-5 and Transplant) from 2001-2010 who registered at the Chronic Kidney Disease Clinic. Patients received cholecalciferol 10,000 IU capsules weekly as initial therapy. When levels above 40 ng/ml were not achieved, doses were titrated up to a maximum of 50,000 IU weekly. Active vitamin D analogs were also used in some Stage 4-5 CKD patients per practice guidelines. Patients reaching at least one level of 40 ng/mL were designated RESPONDER, and if no level above 40 ng/mL they were designated NON-RESPONDER. Patients were followed for at least 6 months and up to 5 years., Results: 352 patients were included with a mean follow up of 2.4 years. Of the CKD patients, the initial 25-OH vitamin D in the NON-RESPONDER group was lower than the RESPONDER group (18 vs. 23 ng/ml) (p = 0.03). Among all patients, the initial eGFR in the RESPONDER group was significantly higher than the NON-RESPONDER group (36 vs. 30 ml/min/1.73 m2) (p < 0.001). Over time, the eGFR of the RESPONDER group stabilized or increased (p < 0.001). Over time, the eGFR in the NON-RESPONDER group decreased toward a trajectory of ESRD. Proteinuria did not impact the response to 25-OH vitamin D replacement therapy. There were no identifiable variables associated with the response or lack of response to cholecalciferol treatment., Conclusions: CKD patients treated with cholecalciferol experience treatment resistance in raising vitamin D levels to a pre-selected target level. The mechanism of vitamin D resistance remains unknown and is associated with progressive loss of eGFR. Proteinuria modifies but does not account for the vitamin D resistance.

Background: We examined the extent and severity of radiographic periodontal bone loss in patients with different stages of chronic kidney disease (CKD) and explored a potential dose-response relationship between bone loss and CKD-related biomarkers., Methods: Panoramic radiographs were obtained from 129 CKD patients (78 males and 51 females; mean age: 63.5 years, range: 24 to 91 years), including 63 patients undergoing dialysis for an average of 3.3 years (range: 0.5 to 14 years). Glomerular filtration rate (GFR), dialysis dose, and levels of serum biomarkers were obtained through a hospital database. Interproximal bone loss was assessed as a percentage of root length., Results: Twenty-nine participants were edentulous (23.8% of those on dialysis versus 21.2% of those with residual kidney function; χ(2) test, P = 0.724). The extent of bone loss was higher among dialysis patients (analysis of variance [ANOVA], P = 0.007), but no clear dose-response association between CKD stage and extent was evident. GFR, dialysis dose, and levels of serum biomarkers did not differ between edentulous and dentate individuals, and only serum albumin was lower in patients with extensive bone loss (ANOVA, P = 0.030). After adjusting for dialysis status, the severity of bone loss was positively associated with glucose levels (multiple regression, P = 0.019) and white blood cell count (P = 0.032), whereas the number of teeth present was positively associated with plasma phosphorus (P = 0.008) and negatively with glucose levels (P = 0.011)., Conclusion: Despite a higher extent of bone loss in dialysis patients, the lack of a dose-response association between bone loss and CKD stage or the levels of CKD-related serum biomarkers underscores the complex relationship between the two conditions.

We performed a prospective study to examine the epidemiology and microbiology of peritonitis complicating acute intermittent peritoneal dialysis (IPD) performed in an in-hospital setting for the management of acute and chronic renal failure and to see the effect of a closed-drainage system on altering the frequency and cause of peritonitis. Over a 15-month period, 79 patients were treated with acute IPD for a total of 136 treatments each ranging in length from 2 to 40 days (median, 4 days). The majority of cases had acute renal failure (ARF; 65%) and were treated in intensive care units (ICUs; 74%) with serious comorbid conditions (60%). About half were treated with a two-bag, ventable (open)-drainage system with unprotected spikes, and the other half were treated with a single-bag, spike-protected, closed-drainage system. There were 27 cases of peritonitis for a rate of 4.5 cases/100 patient-days at risk. About half were gram-positive infections; the remainder were gram-negative or mixed (25%) or Candida sp (25%). The use of a closed-drainage system reduced the incidence of system-related peritonitis from 3.6 to 1.5 cases/100 patient-days. There was a high rate of peritonitis in the first 48 hours of treatment, which fell to a low stable rate thereafter and remained so for up to 15 days of continuous IPD. The use of a closed-drainage system eliminated the early (< 48 hours) high rate of peritonitis and maintained a low constant rate of peritonitis throughout treatment. There was an association of ARF and severe comorbid disease with more virulent organisms (gram-negative, mixed, and Candida sp), which, in turn, were both associated with antecedent broad-spectrum antibiotic therapy. Random positive surveillance cultures showed a frequency distribution similar to that of peritonitis cases over the duration of treatment, but with less virulent organisms. Peritonitis in acute IPD occurs when large or repeated inocula of organisms from the prevailing flora overwhelm the peritoneal immune clearance mechanisms. Prolonged courses of broad-spectrum antibiotic therapy provide no protection, but shift the resulting infecting flora toward more virulent pathogens. A closed-drainage system provides one method to reduce the frequency of peritoneal contamination.

The data concerning annual usage in a general hospital and the frequency of resistant bacterial strains, isolated from patients with urinary tract's infection from 1975 to 1977 were collected and statistically processed. It was noticed that the year by year variation of resistance were mainly confined to E. coli and P. mirabilis. Increasing resistance with time was found for E. coli with Co-trimoxazole, P. mirabilis with Cephaloridin and Gentamicin, Proteus indole-positive with Rifampicin. Reducing resistance with time was found for E. coli with Colistin and Rifampicin, and Klebsiella-Enterobacter with Rifampicin. Trende with usage were found for E. coli and Klebsiella-Enterobacter with Rifampicin (decreasing) and P. mirabilis with Cephalorin (increasing). Naturally, none of the above trends imply cause and effect.