Dialytrauma

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Dialytrauma refers to the set of possible and non-desired complications associated with the use of renal-replacement therapies (RRT). [1]

Contents

Origin

The Dialytrauma Concept was introduced into medical literature in 2008 by a Spanish group of intensivists. [2] The idea was born as a consequence of the publication of the first major trial (known as the ATN Study [3] ) looking at the intensity of renal support in critically ill patients with acute kidney injury (AKI). In this multicenter, randomized, controlled trial, renal support was delivered using different RRT modalities: intermittent hemodialysis, sustained low-efficiency dialysis, or continuous venovenous hemodiafiltration. The main result of this study (including 1,124 patients) was that a fixed “intensive” dose (35 mL/Kg/h) delivered with different RRT modalities, produced the same clinical outcomes than a “less-intensive” dose (20 mL/Kg/h). The authors’ conclusion was that critically ill patients with AKI requiring RRT should be treated with this “less-intensive” dose, given that it will achieve the same results as the “intensive” one. Nevertheless, the rate of complications and adverse events detected was higher in the “intensive” dose arm of this study. As such, the aforementioned Spanish group of intensivists, wrote a letter to the Editor of the same Journal[2] postulating the idea that all those complications (grouped under the term “Dialytrauma”) could have been responsible for the results of the ATN Study. In the same letter to the Editor, and according to what had been previously published by Dr. Schiffl, [4] they hypothesized that a dynamic adjustment of the dose of RRT, would be more physiological due to the dynamic nature of AKI in critical illness. This therapeutic schedule, named “Dynamic Approach”, would reduce the incidence of dialytrauma and, probably, would achieve better clinical outcomes.

Acute kidney injury abrupt loss of kidney function that develops within 48 hours

Acute kidney injury (AKI), previously called acute renal failure (ARF), is an abrupt loss of kidney function that develops within 7 days.

Hemodialysis

Hemodialysis, also spelled haemodialysis, or simply dialysis, is a process of purifying the blood of a person whose kidneys are not working normally. This type of dialysis achieves the extracorporeal removal of waste products such as creatinine and urea and free water from the blood when the kidneys are in a state of kidney failure. Hemodialysis is one of three renal replacement therapies. An alternative method for extracorporeal separation of blood components such as plasma or cells is apheresis.

However, given the lack of level 1 clinical trials on this “Theory of Dynamic Approach”, the authors of the ATN Study branded this idea as being “speculative”. [5] Despite this, a year later Dr. Palevsky (ATN Study’s first author) wrote an Editorial comment [6] on the RENAL Study [7] (the second major trial looking at the intensity of renal support) concluding that the:

Failure to demonstrate improved outcomes with more intensive renal-replacement therapy in critically ill patients […] does not imply that the intensity of renal-replacement therapy does not matter. [...] Furthermore, it should not be forgotten that patient care needs to be individualized – more intensive therapy may be required for the treatment of hyperkalemia, metabolic acidosis, or extreme hypercatabolism – and that the true adequacy of renal-replacement therapy is defined by more than just the clearance of small solutes.
—  Palevsky PM,«Renal Support in Acute Kidney Injury — How Much Is Enough?» (2009)N Engl J Med361(17):1699-1701.

In this way, finally, he seemed to support the Theory of Dynamic Approach, that is: we need to tailor the RRT dose to the clinical scenario of the individual patient.

From then on, both the Dialytrauma Concept and the Theory of Dynamic Approach have been referenced in several publications by impact groups in the field of RRT. [8] [9] [10]

The dialytrauma concept

The potential complications associated with the use of RRT are numerous. [11] But among them all, non-desired mass transference is probably one of the most relevant from a clinical point of view. Due to the non-specific pattern of molecule elimination achieved with RRT (either using diffusion or convection) and with most of blood purification extracorporeal therapies (such as plasmapheresis, CPFA, etc.), they can produce significant clearance of “valuable substances”. This will mean micronutrient depletion, hypophosphatemia, hypokalemia, subtherapeutic doses of antibiotics, etc. The loss of these molecules without appropriate replacement could engender useless, or even harmful a therapy (such as RRT) intended to improve the outcomes of critically ill patients with AKI. But the dialytrauma concept is wider and also encompasses the problems associated with vascular access (mechanical and infectious), dialysis-associated hypotension, hematological complications (blood losses derived from circuit clotting, bleeding associated with the anticoagulation needed to run a RRT, thrombocytopenia, etc.), non-desired heat loss, and increased costs among others.[1]

Plasmapheresis removal, treatment, and return of (components of) blood plasma from blood circulation

Plasmapheresis is the removal, treatment, and return or exchange of blood plasma or components thereof from and to the blood circulation. It is thus an extracorporeal therapy.

Hypophosphatemia electrolyte disorder in which there is a low level of phosphate in the blood

Hypophosphatemia is an electrolyte disorder in which there is a low level of phosphate in the blood. Symptoms may include weakness, trouble breathing, and loss of appetite. Complications may include seizures, coma, rhabdomyolysis, or softening of the bones.

Hypokalemia Human disease

Hypokalemia is a low level of potassium (K+) in the blood serum. Mildly low levels do not typically cause symptoms. Symptoms may include feeling tired, leg cramps, weakness, and constipation. It increases the risk of an abnormal heart rhythm, which is often too slow, and can cause cardiac arrest.

The theory of dynamic approach

Critical illness is highly dynamic. As such, critically ill patients needing RRT, depending on the clinical severity (AKI alone, or AKI associated with other organs dysfunction), could require a higher depurative dose of renal support[4]. As a matter of fact, the treatment of a patient with a toxic hyperkalemia, or a severe lactic acidosis due to a metformin intoxication, will need a different (and higher) depurative dose than a patient whose main problem derived from AKI is just anuria. However the two main trials that have studied the intensity of renal support in critically ill patients with AKI[3], [7], allocated them to a higher or lower dose without taking into account the clinical status of each patient. Only in the ATN Study[3] was the modality of RRT changed (from intermittent to extended or continuous) depending on the hemodynamic status of the patient, (patients in shock were managed with extended or continuous modalities), supporting the general idea that intermittent dialysis is not well tolerated by patients with unstable hemodynamic status. Not surprisingly both studies concluded that clinical outcomes were the same whether using a higher or lower intensity of renal support. However, as already mentioned before, they also found a higher incidence of complications (hypothermia, hypokalemia, hypophosphatemia, etc.) in the patients randomized to receive a higher dose. Taking together the results of both studies, it determined that the incidence of both under and overtreatment must have been the same in all groups of patients (whether randomized to receive a higher or lower fixed intensity of renal support, they would have received an improper dose at any time – i.e. if with severe hyperkalemia and allocated to a lower dose, initially undertreated, or if with a normal potassium and assigned to receive a higher dose, overtreated). Trying to conceal this problem, the Theory of Dynamic Approach postulates that we have to adapt the intensity of renal support according to the patient’s clinical situation, transforming in this way a fixed-dose-RRT schedule into a goal-directed-RRT, one to avoid Dialytrauma.[1]

Hyperkalemia elevated level of potassium (K+) in the blood serum.

Hyperkalemia, also spelled hyperkalaemia, is an elevated level of potassium (K+) in the blood serum. Normal potassium levels are between 3.5 and 5.0 mmol/L (3.5 and 5.0 mEq/L) with levels above 5.5 mmol/L defined as hyperkalemia. Typically this results in no symptoms. Occasionally when severe it results in palpitations, muscle pain, muscle weakness, or numbness. An abnormal heart rate can occur which can result in cardiac arrest and death.

Lactic acidosis acquired metabolic disease that has material basis in low pH in body tissues and blood accompanied by the buildup of lactate especially D-lactate

Lactic acidosis is a medical condition characterized by the buildup of lactate in the body, with formation of an excessively low pH in the bloodstream. It is a form of metabolic acidosis, in which excessive acid accumulates due to a problem with the body's oxidative metabolism.

Metformin chemical compound

Metformin, marketed under the trade name Glucophage among others, is the first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome (PCOS). Limited evidence suggests metformin may prevent the cardiovascular disease and cancer complications of diabetes. It is not associated with weight gain. It is taken by mouth.

Related Research Articles

Dialysis Manual removal of toxins from the body

In medicine, dialysis is the process of removing excess water, solutes, and toxins from the blood in people whose kidneys can no longer perform these functions naturally. This is referred to as renal replacement therapy.

Kidney failure disease where the kidneys fail to adequately filter waste products from the blood

Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys no longer function. It is divided into acute kidney failure and chronic kidney failure. Symptoms may include leg swelling, feeling tired, vomiting, loss of appetite, or confusion. Complications of acute disease may include uremia, high blood potassium, or volume overload. Complications of chronic disease may include heart disease, high blood pressure, or anemia.

Dialysis (biochemistry) process of separating molecules in solution by the difference in their rates of diffusion through a semipermeable membrane, such as dialysis tubing

In biochemistry, dialysis is the process of separating molecules in solution by the difference in their rates of diffusion through a semipermeable membrane, such as dialysis tubing.

Chronic kidney disease progressive loss in kidney function over a period of months or years

Chronic kidney disease (CKD) is a type of kidney disease in which there is gradual loss of kidney function over a period of months or years. Early on there are typically no symptoms. Later, leg swelling, feeling tired, vomiting, loss of appetite, or confusion may develop. Complications may include heart disease, high blood pressure, bone disease, or anemia.

Peritoneal dialysis

Peritoneal dialysis (PD) is a type of dialysis which uses the peritoneum in a person's abdomen as the membrane through which fluid and dissolved substances are exchanged with the blood. It is used to remove excess fluid, correct electrolyte problems, and remove toxins in those with kidney failure. Peritoneal dialysis has better outcomes than hemodialysis during the first couple of years. Other benefits include greater flexibility and better tolerability in those with significant heart disease.

Dialysis tubing

Dialysis tubing, also known as Visking tubing, is an artificial semi-permeable membrane tubing used in separation techniques, that facilitates the flow of tiny molecules in solution based on differential diffusion. In the context of life science research, dialysis tubing is typically used in the sample clean-up and processing of proteins and DNA samples or complex biological samples such as blood or serums. Dialysis tubing is also frequently used as a teaching aid to demonstrate the principles of diffusion, osmosis, Brownian motion and the movement of molecules across a restrictive membrane. For the principles and usage of dialysis in a research setting, see Dialysis (biochemistry).

Home hemodialysis

Home hemodialysis (HHD), is the provision of hemodialysis to purify the blood of a person whose kidneys are not working normally, in their own home.

Liver dialysis is a detoxification treatment for liver failure and has shown promise for patients with hepatorenal syndrome. It is similar to hemodialysis and based on the same principles. Like a bioartificial liver device, it is a form of artificial extracorporeal liver support.

Hepatorenal syndrome Human disease

Hepatorenal syndrome is a life-threatening medical condition that consists of rapid deterioration in kidney function in individuals with cirrhosis or fulminant liver failure. HRS is usually fatal unless a liver transplant is performed, although various treatments, such as dialysis, can prevent advancement of the condition.

In medicine, Kt/V is a number used to quantify hemodialysis and peritoneal dialysis treatment adequacy.

Artificial kidney is often a synonym for hemodialysis, but may also, refer to renal replacement therapies that are in use and/or in development. This article deals with bioengineered kidneys/bioartificial kidneys that are grown from renal cell lines/renal tissue.

Hemofiltration

In medicine, hemofiltration, also haemofiltration, is a renal replacement therapy which is used in the intensive care setting. It is usually used to treat acute kidney injury (AKI), but may be of benefit in multiple organ dysfunction syndrome or sepsis. During hemofiltration, a patient's blood is passed through a set of tubing via a machine to a semipermeable membrane where waste products and water are removed by convection. Replacement fluid is added and the blood is returned to the patient.

Willem Johan Kolff Dutch medical researcher

Willem Johan "Pim" Kolff was a pioneer of hemodialysis as well as in the field of artificial organs. Willem is a member of the Kolff family, an old Dutch patrician family. He made his major discoveries in the field of dialysis for kidney failure during the Second World War. He emigrated in 1950 to the United States, where he obtained US citizenship in 1955, and received a number of awards and widespread recognition for his work.

In nephrology, vascular access steal syndrome is a syndrome caused by ischemia resulting from a vascular access device that was installed to provide access for the inflow and outflow of blood during hemodialysis.

Vascular access refers to a rapid, direct method of introducing or removing devices or chemicals from the bloodstream. In hemodialysis, vascular access is used to remove the patient's blood so that it can be filtered through the dialyzer. Three primary methods are used to gain access to the blood: an intravenous catheter, an arteriovenous fistula (AV) or a synthetic graft. In the latter two, needles are used to puncture the graft or fistula each time dialysis is performed.

Ultrafiltration (renal) first step of filtration from blood in the kidneys

In renal physiology, ultrafiltration occurs at the barrier between the blood and the filtrate in the glomerular capsule in the kidneys. As in nonbiological examples of ultrafiltration, pressure and concentration gradients lead to a separation through a semipermeable membrane. The Bowman's capsule contains a dense capillary network called the glomerulus. Blood flows into these capillaries through the afferent arterioles and leaves through the efferent arterioles.

Nils Alwall, a Swedish professor, was a pioneer in hemodialysis and the inventor of one of the first practical dialysis machines. Alwall pioneered the technique of ultrafiltration and introduced the principle of hemofiltration. Alwall is referred to as the "father of extracorporeal blood treatment."

Dialysis disequilibrium syndrome (DDS) is the occurrence of neurologic signs and symptoms, attributed to cerebral edema, during or following shortly after intermittent hemodialysis.

Nathan W. Levin is an American physician and founder of the Renal Research Institute, LLC., a research institute dedicated to improving the outcomes of patients with kidney disease, particularly those requiring dialysis. Levin is one of the most prominent and renowned figures in clinical nephrology as well as nephrology research. He has authored multiple book chapters and over 350 peer-reviewed publications, including articles in leading journals such as Nature, the New England Journal of Medicine, and The Lancet.

Cuprophane is a membrane made of cellulose, commonly used for hemodialysis. Cuprophane is a synthetic non-biocompatible membrane. It has been associated with hemodialysis-associated amyloidosis.

References

  1. ↑ Maynar Moliner J, Honore PM, Sánchez-Izquierdo Riera JA, Herrera Gutiérrez M, Spapen HD. Handling continuous renal replacement therapy-related adverse effects in intensive care unit patients: the dialytrauma concept. Blood Purif. 2012;34(2):177-185.
  2. ↑ Maynar-Moliner J, Sánchez-Izquierdo-Riera JA, Herrera-Gutierrez M: Renal support in critically ill patients with acute kidney injury. N Engl J Med 2008(18); 359: 1960–1961.
  3. ↑ Palevsky PM, Zhang JH, O’Connor TZ, Chertow GM, Crowley ST, Choudury D et al for the VA/NIH Acute Renal Trial Network. Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med 2008;359(1):7-20.
  4. ↑ Schiffl H Daily haemodialysis in acute renal failure. Old wine in a new bottle? Minerva Urol Nefrol. 2004 Sep;56(3):265-277.
  5. ↑ Palevsky PM, et al. Renal support in critically ill patients with acute kidney injury. N Engl J Med 2008; 359(18):1961-1962.
  6. ↑ Palevsky PM. Renal Support in Acute Kidney Injury — How Much Is Enough? N Engl J Med 2009; 361(17):1699-1701.
  7. ↑ RENAL Replacement Therapy Study Investigators, Bellomo R, Cass A, Cole L, Finfer S, Gallagher M, Lo S, McArthur C, McGuinness S, Myburgh J, Norton R, Scheinkestel C, Su S: Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med 2009, 361:1627-1638.
  8. ↑ Helmut Schiffl. The dark side of high-intensity renal replacement therapy of acute kidney injury in critically ill patients. Int Urol Nephrol (2010) 42: 435–440.
  9. ↑ Vesconi S, Cruz D, Fumagalli R, Kindgen-Milles D, Monti G, Marinho A, Mariano F, Formica M, Marchesi M, Rene R, Livigni S, Ronco C Delivered dose of renal replacement therapy and mortality in critically ill patients with acute kidney injury. Crit Care 2009; 13:R57.
  10. ↑ Bouchard J, Macedo E, Mehta RL. Dosing of Renal Replacement Therapy in Acute Kidney Injury: lessons learned from clinical trials. Am J Kidney Dis 2010; 55: 570-579.
  11. ↑ Finkel KW, Podoll AS. Complications of Continuous Renal Replacement Therapy. Semin Dial 2009 22 (2): 155-159.


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