Vitamin K Supplementation to Improve Vascular Stiffness in CKD: The K4Kidneys Randomized Controlled Trial.

BACKGROUND: Vascular calcification, a risk factor for cardiovascular disease, is common among patients with CKD and is an independent contributor to increased vascular stiffness and vascular risk in this patient group. Vitamin K is a cofactor for proteins involved in prevention of vascular calcification. Whether or not vitamin K supplementation could improve arterial stiffness in patients with CKD is unknown. METHODS: To determine if vitamin K supplementation might improve arterial stiffness in patients in CKD, we conducted a parallel-group, double-blind, randomized trial in participants aged 18 or older with CKD stage 3b or 4 (eGFR 15-45 ml/min per 1.73 m2). We randomly assigned participants to receive 400 µg oral vitamin K2 or matching placebo once daily for a year. The primary outcome was the adjusted between-group difference in carotid-femoral pulse wave velocity at 12 months. Secondary outcomes included augmentation index, abdominal aortic calcification, BP, physical function, and blood markers of mineral metabolism and vascular health. We also updated a recently published meta-analysis of trials to include the findings of this study. RESULTS: We included 159 randomized participants in the modified intention-to-treat analysis, with 80 allocated to receive vitamin K and 79 to receive placebo. Mean age was 66 years, 62 (39%) were female, and 87 (55%) had CKD stage 4. We found no differences in pulse wave velocity at 12 months, augmentation index at 12 months, BP, B-type natriuretic peptide, or physical function. The updated meta-analysis showed no effect of vitamin K supplementation on vascular stiffness or vascular calcification measures. CONCLUSIONS: Vitamin K2 supplementation did not improve vascular stiffness or other measures of vascular health in this trial involving individuals with CKD. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Vitamin K therapy to improve vascular health in patients with chronic kidney disease, ISRCTN21444964 (www.isrctn.com).

The aneurysmal arteriovenous fistula - morphological study and assessment of clinical implications. A pilot study.

Aneurysmal dilation of arteriovenous fistulae used for haemodialysis is a recognised complication but its clinical significance is a contentious issue. Our aims were to describe aneurysmal fistulae morphologically and clinically.Sixty patients underwent duplex scanning to measure the maximum diameter and skin thickness of their fistula. Haemodialysis function and bleeding risk were assessed clinically.The 75th percentile of maximum diameter was 2.05 cm. In addition to conventional diameter measurement, we describe a novel volume measurement technique which may be of value. No relationship was found between maximum diameter or volume and function, skin thickness or bleeding.Some studies define aneurysm at 2 cm (75th percentile); however, this definition and other arbitrary definitions lack clinical significance. This work suggests that fistula dilation should be considered together with clinical issues when determining the clinical significance of an aneurysm. Our finding that haemodialysis function, skin thickness and bleeding were not associated with diameter needs further study.

Renal artery stenosis-when to screen, what to stent?

Renal artery stensosis (RAS) continues to be a problem for clinicians, with no clear consensus on how to investigate and assess the clinical significance of stenotic lesions and manage the findings. RAS caused by fibromuscular dysplasia is probably commoner than previously appreciated, should be actively looked for in younger hypertensive patients and can be managed successfully with angioplasty. Atheromatous RAS is associated with increased incidence of cardiovascular events and increased cardiovascular mortality, and is likely to be seen with increasing frequency. Evidence from large clinical trials has led clinicians away from recommending interventional revascularisation towards aggressive medical management. There is now interest in looking more closely at patient selection for intervention, with focus on intervening only in patients with the highest-risk presentations such as flash pulmonary oedema, rapidly declining renal function and severe resistant hypertension. The potential benefits in terms of improving hard cardiovascular outcomes may outweigh the risks of intervention in this group, and further research is needed.

Use of vascular access for haemodialysis in Europe: a report from the ERA-EDTA Registry.

BACKGROUND: Although arteriovenous fistulas (AVFs) are actively promoted, their use at the start of haemodialysis (HD) seems to be decreasing worldwide. In this paper, we describe recent trends in incidence and prevalence of vascular access types in Europe from 2005 to 2009 and their relationship with patient characteristics and survival. METHODS: Ten European renal registries participating in the ERA-EDTA Registry provided data on incidence (n = 13,044) and/or prevalence (n = 75,715) of vascular access types. We used logistic regression to assess which factors influence the likelihood to be treated with an AVF rather than another type. RESULTS: The use of AVFs at the start of HD showed a significant decreasing trend from 42% in 2005 to 32% in 2009 (P < 0.0001), while the use of central venous catheters (CVCs) increased from 58 to 68% (P < 0.0001). A similar evolution pattern was observed for the prevalence; use of AVFs decreased from 66 to 62% and use of CVCs increased from 28 to 32%. There was a large international variation in the use of the different vascular access types. Female patients [adjusted odds ratio: 0.84, 95% confidence interval (CI): 0.78-0.90] and those ≥80 years (0.77, 95% CI: 0.67-0.90) were least likely to start HD with an AVF. CONCLUSION: In Europe, there is a decreasing trend in the use of AVFs and an increasing trend in the use of CVCs at the start and after the start of HD. We cannot explain all between-country variations we found, and more research is needed to clarify how healthcare around vascular access is organized in Europe.

Do patients undergoing renal revascularization outside of the ASTRAL trial show any benefit? Results of a single-centre observational study.

INTRODUCTION/OBJECTIVES: Though recent research has concluded that revascularization of atherosclerotic renal artery stenosis has no benefit for most patients, negative findings of the Angioplasty and STent for Renal Artery Lesions (ASTRAL) trial have been criticized in professional fora. Aim of the current study was to determine whether patients undergoing renal revascularization outside of ASTRAL showed any benefit. If so, could we determine a patient group that would benefit from intervention? METHODS: Patients undergoing renal revascularization outside of the ASTRAL trial between 2003 and 2007 at our institution were reviewed. The primary comparison was the rate of decline of renal function based on individual reciprocal creatinine plots for the periods leading up to and following revascularization. Those who showed any improvement in the mean slope were compared to those with a negative or neutral response. RESULTS: One hundred and twenty-seven patients underwent renal revascularization outside of ASTRAL. The majority [79 (62%)] showed some improvement in the rate of change in renal function, though overall this failed to reach statistical significance. Those who responded positively tended to be declining faster prior to intervention; they were less likely to require RRT (6 versus 29%), and if they did, it was significantly later (3.6 versus 0.7 years). Mortality was, however, similar in both groups. Subgroup analysis was undertaken of patients in whom kidney function was rapidly deteriorating prior to revascularization. The rate of change in this group showed a more sizeable improvement (P = 0.05). Nonetheless, a similar proportion of both groups required RRT and there was no evidence of improvement in overall mortality. CONCLUSION: In keeping with ASTRAL's findings, our use of renal revascularization has produced no demonstrable benefit overall. There was a suggestion of benefit in patients with rapidly declining renal function in terms of delaying the need for renal replacement therapy, but improvements in cardiovascular outcomes have yet to be proven.

Long-term effect of lithium maintenance therapy on estimated glomerular filtration rate in patients with affective disorders: a population-based cohort study.

BACKGROUND: For more than 40 years, the long-term effect of lithium maintenance therapy on renal function has been debated. We aimed to assess the effect of lithium maintenance therapy on estimated glomerular filtration rate (eFGR) in patients with affective disorders, and explore predictors for a decrease in eGFR. METHODS: This population-based cohort study included adult patients (18-65 years of age at baseline) in Tayside (Scotland, UK) who had recently started on lithium maintenance treatment between Jan 1, 2000, and Dec 31, 2011 (retrospectively assigned to the lithium group) or those with exposure to other first-line drugs used in the treatment of affective disorders (quetiapine, olanzapine, and semisodium valproate) during the same period (retrospectively assigned to the comparator group). Patients had to have at least 6 months of (incidence) exposure to lithium or any of the comparator drugs, at least two eGFR values available in the observation period (one at baseline and at least one after ≥6 months post baseline). We excluded patients with previous exposure to lithium or one of the comparator drugs, those with a previous diagnosis of schizophrenia or other psychotic disorder, those with glomerular disease, tubulo-interstitial disease, or chronic kidney disease stages 4-5 at baseline, and those who had undergone renal transplant before exposure. Maximum follow-up was 12 years. Data were provided by the University of Dundee Health Informatics Centre, who have access to health-related population-based datasets containing data for every patient registered with a regional family doctor. Each patient has a unique ten-digit identifier, the Community Health Index, enabling us to link laboratory tests, dispensed community prescriptions, Scottish Morbidity Records, and mortality records to the patient. All data were anonymised according to Health Informatics Centre standard operating procedures. The primary outcome was the change per year in the eGFR, adjusted for age, sex, and baseline eGFR, and analysed by random coefficient models. FINDINGS: 1120 patients (305 exposed to lithium and 815 to comparator drugs) qualified for inclusion, providing 13 963 eGFR values over 12 years. The mean duration of exposure to lithium was 55 months (SD 42; range 6-144). Mean annual decline in eGFR (adjusted for age, sex, and baseline eGFR) was 1·3 mL/min per 1·73 m(2) (SE 0·2) in the lithium group, which did not differ significantly to that in the comparator group (0·9 mL/min/1·73 m(2) [SE 0·15]). After adjustment for additional confounders, the monthly decline in eGFR attributable to lithium exposure amounted to 0·02 mL/min per 1·73 m(2) (SE 0·02, p=0·30). As a post-hoc secondary outcome, we estimated the annual decline in eGFR for the lithium group to be 1·0 mL/min per 1·73 m(2) (SE 0·2), which again did not differ significantly to that in the comparator group (0·4 mL/min/1·73 m(2) [SE 0·2]. Modelling identified significant predictors for eGFR decline as age, baseline eGFR, comorbidities, co-prescriptions of nephrotoxic drugs, and episodes of lithium toxicity; however, duration of exposure to lithium and mean serum lithium level were not significant predictors for eGFR decline. INTERPRETATION: Our analysis suggests no effect of stable lithium maintenance therapy (lithium levels in therapeutic range) on the rate of change in eGFR over time. Our results therefore contradict the idea that long-term lithium therapy is associated with nephrotoxicity in the absence of episodes of acute intoxication and that duration of therapy and cumulative dose are the major determinants of toxicity. FUNDING: None.

Vascular access using the superficial femoral vein.

PURPOSE: The superficial femoral vein (SFV) provides an alternative autologous conduit for fistula formation in patients who might otherwise require a prosthetic graft for hemodialysis (HD) access. The purpose of this study was to assess the results of this technique. METHODS: Patients who underwent formation of a SFV fistula were identified from a prospectively maintained database. Casenotes were reviewed for details of the operation, complications, subsequent interventions, and to determine whether the fistula was used for vascular access. RESULTS: Fifteen patients (seven males, eight females; median age 53, range 28-72 yrs) were identified. Patients had a median of four (range 2-9) previous fistulae. In three patients, the mobilized SFV was transferred to the upper limb while 12 patients had lower limb fistulae. Twelve patients (80%) used their SFV fistula for HD. Eleven patients developed a wound complication (infection, dehiscence, hematoma or bleeding), with four patients returning to theater for formal exploration and three requiring application of a vacuum dressing. Two patients developed post-operative lower limb ischemia. Two patients died during a median follow-up time of 7 (range 1-27) months. CONCLUSION: In selected patients who have exhausted conventional routes for vascular access the SFV fistula can be used for the maintenance of HD. There is, however, significant associated morbidity and repeated intervention is often required.

Primary cutting balloon angioplasty for treatment of venous stenoses in native hemodialysis fistulas: long-term results from three centers.

AIM: To evaluate the technical success and patency rates following primary cutting balloon angioplasty for venous stenoses in native dialysis fistulas. METHODS: Forty-one patients (26 men, 15 women; age range 26-82 years, average age 59 years) underwent 50 (repeat procedures in 9 patients) primary cutting balloon (PCB) angioplasty procedures in three institutions by three primary operators. The indication was primary stenosis in 21 patients, recurrent lesions in 15, and immature fistulas in 5. A PCB was used alone in 17 cases, but was followed by a larger standard balloon in 33 cases. Follow-up included ultrasound, flow analysis and urea reduction ratio, and ranged from 2 to 30 months (mean 14 months). RESULTS: The technical success rate was 98%. All procedures were relatively painless. Two PCBs burst and 4 leaked, but without causing any morbidity. Nineteen fistulas were still working at last follow-up. Primary patency rates at 6, 12, and 24 months using Kaplan-Meier analysis were 88%, 73%, and 34%, respectively, and the primary assisted patencies were 90%, 75%, and 50%, respectively. CONCLUSION: PCB angioplasty has high technical success and low complication rates. The long-term patency rates are favorable for PCB angioplasty and compare favorably with other series.