Why Does Vascular Access Dysfunction Occur despite Brachial Artery Blood Flow Being Higher than Preset Blood Flow?

Background: In recent years, many reports have investigated the usefulness of brachial artery blood flow (BAF) measured by ultrasonography as an evaluation index for the vascular access (VA) stenosis of hemodialysis patients. However, the mechanism of VA dysfunction, despite BAF being higher than the preset blood flow, has not been clarified to date. Methods: The relationship between actual blood-removal flow and recirculation rate with decreasing VA flow was examined using a VA flow path model and pure water as a model fluid. The blood-flow rate was set at 180 mL/min, and the set VA flow rate was lowered stepwise from 350 to 50 mL/min. VA flow rate, blood-removal flow rate, and flow waveform measured between two needle-puncture sites were recorded, and then the actual blood-removal flow rate and recirculation rate were calculated. Results: Recirculation was observed at a VA flow rate < 300 mL/min. The recirculation was due to the VA flow rate, which was transiently reduced to the level below the blood-removal flow rate, resulting in backflow. In contrast, no decrease in the actual blood-removal flow rate was observed. Conclusion: It is suggested that the mechanism of the VA dysfunction, despite the BAF being higher than the preset blood-flow rate, was due to the diastolic BAF being lower than the blood-removal flow rate.

Antisense Oligonucleotide: A Potential Therapeutic Intervention for Chronic Kidney Disease

Chronic kidney disease (CKD) is a global public health issue that places an increasing burden on the healthcare systems of both the developed and developing countries. CKD is a progressive and irreversible condition, affecting approximately 10% of the population worldwide. Patients that have progressed to end-stage renal disease (ESRD) require expensive renal replacement therapy, i.e., dialysis or kidney transplantation. Current CKD therapy largely relies on the use of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs). However, these treatments by no means halt the progression of CKD to ESRD. Therefore, the development of new therapies is urgently needed. Antisense oligonucleotide (ASO) has recently attracted considerable interest as a drug development platform. Thus far, eight ASO-based drugs have been granted approval by the US Food and Drug Administration for the treatment of various diseases. Herein, we review the ASOs developed for the identification of CKD-relevant genes and/or the simultaneous development of the ASOs as potential therapeutics towards treating CKD.

Prevalence and Factors Associated with Opioid Prescription in Swiss Chronic Hemodialysis Patients

Pain is a common symptom in patients on chronic hemodialysis (HD) but the prevalence of opioid prescriptions in this population has been poorly studied outside the United States. This study assesses the prevalence of opioid prescription in two Swiss dialysis centers. Prescriptions and clinical characteristics were retrospectively retrieved from the medical records of patients on HD for at least six months, treated at Lausanne University Hospital (academic center, AC), and the private center Clinique Cecil (PC) for the study. A total of 117 patients were included; 29.1% received at least one opioid prescription during the study period. Significantly more patients received an opioid prescription in the AC (39.1%) than in the PC (14.6%, p = 0.004). Univariate logistic regression analysis showed that center (Odds Ratio (OR) 3.76; Confidence Interval (CI) 1.48–9.6; p = 0.006), neuropathic pain (OR 2.99; CI 1.28–6.98; p = 0.011), benzodiazepine prescription (OR 2.72; CI 1.14–6.46; p = 0.024), polyneuropathy (OR 2.71; CI 1.14–6.46; p = 0.024) and amputation (OR 4.23; CI 1.1–16.1; p = 0.034) were associated with opioid prescription. The center was the only independent predictive factor in the multivariate analysis. Our results show that opioids are regularly prescribed to Swiss dialysis patients, although important differences exist between centers. The latter finding might suggest that opioid prescribing is more related to the prescriber than to the patient’s condition, but larger-scale studies are necessary to confirm this.

What Is the Optimal Sodium Concentration in the Dialysate?

Based on our experience in our hemodiafiltration unit we would recommend a personalized isonatremic dialysate bath. We currently prescribe 137 meq (isonatremic) or delta dialysate Na/serum Na less than 2 meq. In addition to the sodium prescribed in the dialysate, for the majority of our patients we do not restrict dietary sodium or water intake. The average sodium intake is 2775 mg per day and blood pressure is maintained without hypertensive medications. We acknowledge that part of the success for achieving dry weight may not be attributable only to the dialysate sodium but is likely the result of a combination of multiple factors such as convection therapy, cooling of dialysate, close monitoring of volume status during sessions with relative blood volume, presence of a nephrologist during all sessions and assessing volume status regularly with lung ultrasound and bioimpedance. In our experience, exercising during hemodialysis has additionally been associated with better hemodynamic status and less intradialytic hypotension. Moreover, we acknowledge there is little evidence to support a gradient dialysate to serum sodium of less than 2 meq and that our approach may not be optimal.

How Would You Prescribe the Dialysate Sodium Concentration for Your Patients?

Low sodium dialysate was commonly used in the early year of hemodialysis to enhance diffusive sodium removal beyond its convective removal by ultrafiltration. However, disequilibrium syndrome was common, particularly when dialysis sessions were reduced to 4 h. The recent trend of lowering the DNa from the most common level of 140 mEq/L has been associated with intradialytic hypotension and increased risk of hospitalization and mortality. Higher DNa also has disadvantages, such as higher blood pressure and greater interdialytic weight gain, likely due to increased thirst. My assessment of the evidence leads me to choose DNa at the 140 level for most patients and to avoid DNa below 138. Patients with intradialytic symptoms may benefit from DNa 142 mEq/L, if they can avoid excessive fluid weight gains.

Sodium Dialysate Prescription in a New Dialysis Facility

As the Medical Director of this new dialysis facility, I recommend a fixed sodium dialysate (Nadial) concentration at 138 mEq/L. This relates to my former experience in the Tassin unit in France and the fear of sodium as a powerful uremic toxin. I realize that, according to the Na+ set-point theory, a fixed value of the Nadial may create a plasma–dialysate (P–D) gradient and may favor intradialytic plasma Na+ changes. In cases where this is associated with signs of negative Na+ balance (bad session tolerance/quality of life) or positive Na+ balance (high interdialytic weight gain or high blood pressure), individualization of the Nadial to reduce the P–D gradient and change in plasma Na+ concentration may be useful, even though evidence remains scarce. I look forward to the possibility of using new dialysis machines that allow for the evaluation of sodium balance and tailoring of the sodium diffusion process.

How to Adjust the Sodium Concentration in Dialysate Individually and Practically?

The optimal dialysate sodium concentration for chronic hemodialysis patients remains controversial. Conflicting data from small observational studies and large cohort study data have not convinced nephrologists to choose either a high or low sodium dialysate. Despite a lack of evidence, I would prescribe individualized dialysate sodium concentrations for patients with a risk of hypertension or volume overload, aligning the dialysate sodium concentration with patients’ predialysis serum sodium level. The concentration of dialysate sodium would usually be 0–2 mEq/L below the patient’s serum sodium concentration. I believe that this strategy would help improve hypertension, intradialytic weight gain, cardiac outcomes, and deliver precision medicine.

What Is the Optimal Dialysate Sodium Concentration?

In haemodialysis, sodium and fluid balance (where intake matches loss) is achieved by ultrafiltration and by diffusion between the plasma water and dialysate. If a patient’s sodium intake does not change, any reduction in fluid gain obtained by lowering dialysate sodium concentration will result in less sodium removal by ultrafiltration. The corresponding change in diffusion to achieve balance may mean the benefit of lower fluid gain is offset by morbidity caused by a fall in serum sodium during dialysis. The standard dialysate sodium should minimise harm caused by both high ultrafiltration rates and osmotic disequilibrium. For most units, this is likely to be 138 to 140 mmol/L.

Sodium in Hemodialysis Fluid

The principal aim of dialysis in relation to sodium is that dialysate sodium should not be low enough to cause intradialytic hypotension and cramps, and should not be high enough to cause interdialytic weight gain and hypertension. Dialysis sodium at 138 meq/L is supposed to be neutral and for most patients, this remains the standard sodium level for regular long-term dialysis. In my opinion, sodium should be changed temporarily from this level to 142 meq/L in selected patients only for a few dialysis sessions, where the cause of intradialytic hypotension is not obvious. In patients who regularly go into intradialytic hypotension and whose cause of intradialytic hypotension is unclear or cannot be corrected, sodium profiling should be used for maintenance dialysis. There is no consensus on the level of sodium, although I think 142 meq/L for the initial hour followed by a decrease to 138 meq/L in the last hour is sensible.

Opinion on the (Hemo)dialysate Sodium Prescription: Dialysate Sodium Prescription Should Not Be Considered in Isolation

With advances in hemodialysis technology and the desire to achieve cardiovascular stability during dialysis, prescribed dialysate sodium concentration has gradually increased over the years. Short-term trials suggest low dialysate sodium (<138 mEq/L) is beneficial in reducing interdialytic weight gain, pre- and post-dialysis BP, and predialysis serum sodium; but it increases intradialytic hypotensive episodes. We believe dialysate sodium prescription cannot be considered in isolation. Our approach is to use patient symptoms, meticulous fluid volume management and low temperature dialysate in conjunction with neutral dialysate sodium in managing our dialysis patients. Long-term trials are needed to inform optimum dialysate sodium prescription.