Starting Dialysis Is Dangerous

How Do We Balance the Risk?

Christopher W McIntyre; Steven J Rosansky

Disclosures

Kidney Int. 2012;82(4):382-387. 

In This Article

Risks of Dialysis

Conventional dialysis treatment has many inherent risks for patients. This appears true in older frailer patients, and in those with minimal comorbidity. Some of these risks are fundamental to the dialytic therapy and some relate to management of the patient during the period of transition from nondialytic to dialytic management of end-stage renal disease. These risks may potentially be mitigated.

The period of dialysis initiation is associated with a particular increase in patient dependency (with similar increment in mortality).[12] In studies looking at longer-term dialysis outcomes, the effects of these risks are not evenly distributed over the entire dialysis vintage, with an excess of mortality condensed into the first 6–12 months of therapy.[4] Survival in the first year of dialysis (in the United States) has decreased despite evidence of overall improvement in dialysis patient survival overall.[13] The window of opportunity for a number of these risks is often in the dialysis preparation period, with a reduced period for specialist care/preparation being associated with increased mortality in the dialytic phase of patient care.[14]

Specific areas of risks that must be considered when initiating dialysis include the following:

Infection and Dialysis Access–related Issues

Risks of all forms of infection are many times higher once the patient is started on dialysis. This relates partially to uremic-induced immuno-incompetence, but also significantly to vascular access in HD patients. Catheter-related infections result either from migration of skin organisms along the catheter into the bloodstream or contamination and colonization of catheter lumens. Biofilm formation (formed from a combination of host and bacterial molecules) on the surface of catheters also has an important role in facilitating colonization and resistance to antibiotic therapy. Patients on dialysis are 100-fold more likely to develop methicillin-resistant Staphylococcus aureus septicemia than the general population and 800-fold more likely than if not dialyzed with a native arteriovenous fistula.[15] Exposure to hospital-acquired infection is often just a component of the myriad of dangers associated with the increased amount of in-patient care, which is often characteristic. Others might include exacerbation of malnutrition, hypostatic pneumonia, falls, and venous thromboembolism risk.

Upper extremity native arteriovenous fistula is the vascular access of choice, supported by the Dialysis Outcome Quality Initiative (K/DOQI) of the National Kidney Foundation. The use of definitive vascular access in HD patients, rather than tunneled central venous catheters, is associated with sustained reduction in mortality.[16] This difference in survival has previously been entirely attributed to differences in access-related sepsis; however, it is being appreciated that arteriovenous fistula formation is associated with a series of structural and functional adaptations that reduce the propensity to demand ischemia and result in a lower-risk cardiovascular milieu (lower central blood pressure, reduced arterial stiffness, and improved ventricular contractile function),[17] and higher vascular access flows are associated with reduced acute recurrent HD-related cardiac injury (myocardial stunning).[18]

Decompensation of Nutrition and Psychosocial Problems

The 6-month interval around the first dialytic treatment may be one of mandated dietary restriction, depression, anxiety, and reduced appetite. These changes result in patients being exquisitely sensitive to worsening malnutrition. Patients newly started on dialysis face the physical and time requirements of their dialysis treatments (e.g., 4 h plus travelling time, 3 days a week for HD, or fluid exchanges 4 times every day for PD). They are also required to adhere to strict dietary restrictions and fluid restrictions despite having to take a median of 19 tablets a day.[19] Dialysis therapy and underlying advanced CKD are associated with lethargy, itching, pain dizziness on HD days, and bloating or gastrointestinal disturbance while on PD.[20] These factors combine to sap patients' confidence and interfere with activity, exercise, and social engagement. Depression and other psychosocial problems are often initiated or aggravated by dialysis start, and are often associated with fundamental reductions in a patient's ability to socialize, or to remain in chosen employment, amplifying these psychological stresses. Clinical depression is highly prevalent, affecting around 25% of patients,[21] and correlates to mortality risk.

Specific Dialysis-related Risks

Cardiovascular Effects Current conventional HD is less capable of exerting significant recurrent systemic circulatory stress that may be important in the development of cardiac disease, as well as perfusion-dependent injury of a wide range of vulnerable vascular beds. These include gut, brain, and potentially the kidney. This predominantly hemodynamic injury can therefore result in a mixed picture of direct perfusion-related injury, local/systemic inflammation, and potentiation of further cycles of injury.[22] Cardiac protection (and potentially other organ systems as well) may be possible by reducing this circulatory stress with modifications such as daily dialysis therapies to limit ultrafiltration requirements.[23]

Cardiac arrhythmias and risk of sudden death appear to be the most important final fatal consequence in HD patients. A lengthening of the QT interval corrected for heart rate (QTc) predisposes to torsade de pointes ventricular tachycardia, and although many episodes may be self-terminating torsade can degenerate into ventricular fibrillation. In non-uremic patients, episodes of torsade de pointes often occur because of a combination of factors, including a long QTc in combination with bradycardia or electrolyte abnormalities such as hypokalemia, hypomagnesemia, or hypocalcemia. Several authors have reported an acute increase in both QTc and QTd following dialysis. Although this would support the increase in sudden death temporally related to the dialysis procedure,[24] there are relatively few data showing a direct link between increased QTc or QTd induced by dialysis and either arrhythmia or sudden death. Nakamura et al.[25] compared two groups of 24 dialysis patients separated into those who displayed an increase in QTc post dialysis and those who did not. They reported an increase in cardiac events and cardiac mortality in the group with an increase in QTc post dialysis, but many of the outcomes were not arrhythmias or sudden death.[25] Conversely, two studies have documented the increase in QTc with dialysis but found that there was no resultant increase in arrhythmias.[26,27]

There is also a lack of consensus regarding the mechanisms underlying the acute increase in QTc and QTd with dialysis. It would seem logical that shifts in plasma electrolytes would be the main cause. In essence, the degree of reduction and the absolute end-dialysis plasma concentrations of potassium, calcium, magnesium, and pH have all been linked to lengthening QTc and an increase in arrhythmias, whereas other authors have not found such associations. The longer interdialytic interval in three-times-weekly dialysis schedules and the use of lower dialysate potassium have been linked to increased risk of cardiac arrest in HD patients.

Residual Renal Function The maintenance of residual renal function (RRF) is one of the key factors that has been identified to associate with better survival in HD patients.[28] An accelerated decline in RRF is, however, a characteristic of initiation of conventional three-times-weekly dialysis. This results in both a reduction in urine volume (with exacerbation of long term fluid control and increased ultrafiltration requirements during each HD session) and a reduction in the overall level of clearance of uremic toxins (in particular middle molecule solutes). Previously we have demonstrated that conventional HD has significant intradialytic hemodynamic effects. We hypothesize that the renal circulation is also vulnerable and that the same processes may contribute to new recurrent renal ischemic injury, driving the loss of RRF. This creates a vicious cycle with falling RRF, resulting in increasing interdialytic fluid gains and yet higher ultrafiltration requirements, driving additional injury to vulnerable vascular beds. Dialysis-associated loss of RRF is also associated with an increase in sudden cardiac death.[29]

A detailed discussion of potential therapeutic approaches to help preserve RRF is beyond the scope of this article but might include the following: careful avoidance of dehydration through diuretics or excessive ultrafiltration, consideration of PD in preference to HD, and ensuring the use of only biocompatible dialysis membranes and possibly PD fluids.

One potential approach to mitigate some of the risks associated with dialysis initiation might be to adopt the incremental approach, adding in additional HD time or sessions, or even a planned early use of PD with transition to HD, with subsequent waning of RRF. These approaches, although apparently reasonable, have not been subjected to rigorous study. Early use of even more intermittent short HD runs risks of exacerbated circulatory stress, and potential for further reduction in RRF. Tracking the appropriate stepping up of delivered dialysis dose is also challenging, especially at dialysis initiation with such profound changes in body composition and cardiovascular status. Additional use of PD also has inherent risks of the complications of both therapies, both in terms of access and cumulative metabolic stress. However, PD and HD have been used in a combined approach[30] in patients failing on either initial solo modality or even de novo at the start of renal replacement therapy.[31]

Peritoneal Dialysis versus Hemodialysis Compared with nondialysis patients, both HD and PD patients have an 8-fold increase in cardiovascular risk and non-cardiovascular risks of death. The pathophysiological mechanisms that result in this high death rate are not well understood and may be different in HD versus PD patients. In HD patients, cardiovascular insults appear to be predominately hemodynamic and may involve biocompatibility issues of dialyzers used. PD results in hemodynamic effects, but the response associated with a low ultrafiltration rate is not characteristically hypotensive and does not result in acute cardiac injury.[32] In both dialytic modalities, the changes may be related to fluid type and glucose exposure. Metabolic insults may drive cardiovascular structural and functional pathophysiological processes. Deposition of advanced glycation end products in vascular tissues may result in reduced compliance of arteries and ventricular muscle.[33] Both short-term and longer-term metabolic factors may alter autonomic reactivity. All of these changes may prime patients to experience aberrant regional blood flow to vital organ systems. This principally hemodynamic versus metabolic comparison is superimposed on differing patterns of infection between the modalities and specific risks associated with peritoneal malfunction and failure.

One potential approach to mitigate some of the risks associated with dialysis initiation might be to adopt the incremental approach, adding in additional HD time or sessions, or even a planned early use of PD with transition to HD, with subsequent waning of RRF. These approaches, although apparently reasonable, have not been subjected to rigorous study. Early use of even more intermittent short HD runs risks of exacerbated circulatory stress, and potential for further reduction in RRF. Tracking the appropriate stepping up of delivered dialysis dose is also challenging, especially at dialysis initiation with such profound changes in body composition and cardiovascular status. Additional use of PD also has inherent risks of the complications of both therapies, both in terms of access and cumulative metabolic stress. However, PD and HD have been used in a combined approach in patients failing on either initial solo modality or even de novo at the start of renal replacement therapy.

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