Plasma Nitrate and Nitrite Kinetics after Single Intake of Beetroot Juice in Adult Patients on Chronic Hemodialysis and in Healthy Volunteers: A Randomized, Single-Blind, Placebo-Controlled, Crossover Study.

Nitric oxide (NO) contributes to maintaining normal cardiovascular and renal function. This bioactive signalling molecule is generally formed enzymatically by NO synthase in the vascular endothelium. NO bioactivity can also be attributed to dietary intake of inorganic nitrate, which is abundant in our diet, especially in green leafy vegetables and beets. Ingested nitrate is reduced to nitrite by oral commensal bacteria and further to NO systemically. Previous studies have shown that dialysis, by means of removing nitrate and nitrite from the body, can reduce NO bioactivity. Hence, dietary intervention approaches aimed to boost the nitrate-nitrite-NO pathway may be of benefit in dialysis patients. The purpose of this study was to examine the kinetics of plasma nitrate and nitrite after a single intake of nitrate-rich concentrated beetroot juice (BJ) in adult hemodialysis (HD) patients and in age-matched healthy volunteers (HV). Eight HD patients and seven HV participated in this single center, randomized, single-blind, placebo-controlled, crossover study. Each participant received a sequential single administration of active BJ (70 mL, 400 mg nitrate) and placebo BJ (70 mL, 0 mg nitrate) in a random order separated by a washout period of seven days. For the kinetic analysis, blood samples were collected at different time-points before and up to 44 h after BJ intake. Compared with placebo, active BJ significantly increased plasma nitrate and nitrite levels both in HD patients and HV. The area under the curve and the maximal concentration of plasma nitrate, but not of nitrite, were significantly higher in HD patients as compared with HV. In both groups, active BJ ingestion did not affect blood pressure or plasma potassium levels. Both BJs were well tolerated in all participants with no adverse events reported. Our data provide useful information in planning dietary nitrate supplementation efficacy studies in patients with reduced NO bioactivity.

"Removal of nitrate and nitrite by hemodialysis in end-stage renal disease and by sustained low-efficiency dialysis in acute kidney injury".

BACKGROUND & PURPOSE: It is well established that end-stage renal disease (ESRD) is associated with increased cardiovascular morbidity and mortality both in the adult and pediatric population. Although the underlying molecular mechanisms are poorly understood, compromised nitric oxide (NO) bioactivity has been suggested as a contributing factor. With this in mind, we investigated the effects of hemodialysis on NO homeostasis and bioactivity in blood. METHODS & RESULTS: Plasma and dialysate samples were obtained before and after hemodialysis sessions from adults (n = 33) and pediatric patients (n = 10) with ESRD on chronic renal replacement therapy, and from critically ill adults with acute kidney injury (n = 12) at their first sustained low-efficiency dialysis session. Levels of nitrate, nitrite, cyclic guanosine monophosphate (cGMP) and amino acids relevant for NO homeostasis were analyzed. We consistently found that nitrate and cGMP levels in plasma were significantly reduced after hemodialysis, whereas post-dialysis nitrite and amino acids coupled to NO synthase activity (i.e., arginine and citrulline) were only significantly reduced in adults with ESRD. The amount of excreted nitrate and nitrite during dialysis were similar to daily endogenous levels that would be expected from endothelial NO synthase activity. CONCLUSIONS: Our results show that hemodialysis significantly reduces circulating levels of nitrate and cGMP, indicating that this medical procedure may impair NO synthesis and potentially NO signaling pathways.

Stent tunnel technique to save thrombosed native hemodialysis fistula with extensive venous aneurysm.

INTRODUCTION AND PURPOSE: The increasing number of patients undergoing hemodialysis and the limited number of access sites have resulted in an increasing number of techniques to maintain vascular access for hemodialysis. Thrombosed arteriovenous (AV) fistulas with large venous aneurysms have poor treatment results, with both endovascular and surgical techniques, leading to a high rate of definitive AV access loss. The purpose of this study was to review the feasibility and initial results of this novel endovascular treatment of thrombosed AV fistulas with large venous aneurysms. MATERIALS AND METHODS: A novel endovascular treatment technique of inserting nitinol auto-expandable uncovered stents stretching through the whole puncture site area, thus creating a tunnel inside the thrombus, was retrospectively analyzed and described. RESULTS: A total of 17 stents were placed in 10 hemodialysis fistulas, with a mean venous coverage length of 17.8 cm. In all the cases, 100% technical success was achieved, with complete restoration of blood flow in all patients. There were no procedure-related complications. The mean follow-up was 167 days (range 60-420 days), with a primary and assisted patency of 80% and 100%, respectively. No multiple trans-stent struts-related complications were observed. Three stent fractures were diagnosed with plain films at the site of puncture without consequence in the venous access permeability. CONCLUSION: The "stent tunnel technique" is a feasible, safe and effective alternative to salvage native hemodialysis access, thus extending the function of the venous access with no signs of stent-related complications and a respectable midterm patency.

Impacto de la glomerulopatía post trasplante en la sobrevida del injerto renal / Post-transplant glomerulopathy impact in renal graft survival

Introducción: las glomerulopatías primarias son causa de enfermedad renal crónica en receptores de trasplante renal (30%-50%), siendo un determinante importante en la sobrevida del injerto. Recientes estudios revelan que la recurrencia fue la tercer causa más frecuente de pérdida delinjerto a 10 años de seguimiento postrasplante. Objetivo: Analizar el impacto de las glomerulopatía postrasplante como predictor de pérdida del injerto. Material y métodos: Entre enero de 1990 y abril del 2013 se realizaron 849 biopsias renales en 375 pacientes trasplantados, diagnosticándose 50 casos de glomerulopatía. Se comparó dicha población con un grupo histórico de receptores de trasplante renal entre 2000 al 2011, sin glomerulopatía. Se analizó la sobrevida del injerto renal en ambas poblaciones. Resultados: Se diagnosticaron 50 glomerulopatías post trasplante en 47 pacientes. No encontramos diferencias estadísticamente significativas entre este grupo y el grupo histórico en: edad del receptor; sexo del donante; tipo del donante; n¿²mero de miss match; tiempo de isquemia del órgano; tasa de rechazo agudo; retardo de la función del injerto; ni en la mortalidad del receptor. Si hallamos diferencias significativa en sexo masculino, 88 vs 55% (p< 0.05). La tasa de pérdida del injerto renal fue significativamente más frecuente entre los pacientes que presentaron enfermedad glomerular 38 vs 8% (p< 0.01). Conclusión: En nuestra población, la aparición de glomerulopatía post trasplante se asoció a una disminución de la sobrevida del injerto observándose una mayor tasa de pérdida en la glomerulopatía membranoproliferativa.

Introduction: primary glomerulopathy is cause of renal chronic disease in renal transplant recipients (30%-50%), being an important determinant in graft survival. Recent studies reveal that recurrence was the third most frequent cause of graft lost after 10 years post-transplant monitoring process. Objective: To analyze posttransplant glomerulopathy impact as a graft lost predictor. Methods: Between January 1990 and April 2013, 849 renal biopsies were carried out on 375 transplanted patients, 50 glomerulopathy cases were diagnosed. This population was compared with an historical renal transplant recipients group between 2000 to 2011, without glomerulopathy. Renal graft survival was analyzed in both populations. Results: 50 post-transplant glomerulopathies were diagnosed in 47 patients. We did not find statistically significant differences between this group and the historical one concerning recipient age, donor sex, donor type, miss match number, organ ischaemia time, acute rejection rate, delayed graft function, and neither in the recipient mortality. We did find significant differences in male sex, 88% vs 55% (p< 0.05). Renal graft lost rate was significantly more frequent among patients presenting glomerular disease 38 vs 8 % (p< 0.01). Conclusion: In our population, post transplant glomerulopathy was associated to graft survival reduction and a higher membranoproliferative glomerulopathy lost rate was observed.

Factors determining a low dose of haemodialysis as measured by ionic dialysance in critical patients with acute kidney injury.

BACKGROUND: Estimating the dialysis dose is a requirement commonly used to assess the quality of renal replacement therapy (RRT) in patients with chronic kidney disease (CKD). In patients with acute kidney injury (AKI), this value is not always evaluated and it has been estimated that the prescribed dose is seldom obtained. Reports addressing this issue in AKI individuals are scarce and most have not included an adequate number of patients or treatments, nor were patients treated with extended therapies. Kt values obtained by the ionic dialysance method have been validated for the evaluation of the dialysis dose and it has also been shown that, compared with Kt/V, this is the most sensitive strategy for revealing inadequate dialysis treatment in critically ill AKI individuals. The main aim of this study was to assess the difference between the prescribed and the administered dialysis dose in critically ill AKI patients, and to evaluate what factors determine this gap using Kt values assessed through ionic dialisance. MATERIAL AND METHOD: Data from 394 sessions of renal replacement therapy in 105 adult haemodialysis (HD) patients with oliguric acute kidney injury and admitted to ICU were included in this analysis. RRT was carried out with Fresenius 4008E dialysis machines equipped with on-line clearance monitoring (OCM® Fresenius), which use non-invasive techniques to monitor the effective ionic dialysance, equivalent to urea clearance. The baseline characteristics of the study population as well as the prescription and outcome of RRT were analysed. These variables were included in a multivariate model in which the dependent variable was the failure to obtain the threshold dose (TD). RESULTS: The main baseline characteristics of the study population/treatments were: age 66 ± 15 years, 37% female, most frequent cause of AKI: sepsis (70%). Low BP and/or vasoactive drug requirement (71%), mechanical ventilation (70%) and average individual severity index: 0.7 ± 0.26. Two hundred and one intermittent HD (IHD) and 193 extended HD (EHD) sessions were performed; the most frequently used temporary vascular access was the femoral vein catheter (79%). Prescribed Kt was 53.5 ± 14L and 21% of prescriptions fell below the TD. Sixty-one percent of treatments did not fulfill the TD (31 ± 8L) compared with 56 ± 12L obtained in the subgroup that achieved the target. Compared to IHD, EHD provided a significantly larger Kt (46 ± 16L vs 33L ± 9L). Univariate analysis showed that inadequate compliance was associated with age (>65y), male gender, intra-dialytic hypotension, low Qb, catheter line reversal, and IHD. The same variables with the exception of age and gender were independently associated in the multivariate analysis. CONCLUSIONS: The dialysis dose obtained was significantly lower than that prescribed. EHD achieved values closer to the prescribed KT and significantly higher than in IHD. Ionic Kt measurement facilitates monitoring and allows HD treatments to be extended based upon a previously established TD. Besides the chosen strategy to dispense the dose of dialysis, a well-functioning vascular access allowing for optimal blood flow and other approaches aimed at avoiding hemodynamic instability during RRT are the most important factors to achieve TD, mainly in elderly male patients. The dialysis dose should be prescribed and monitored for all critically ill AKI patients.