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Kidney: advanced renal therapies

ISSN 2398-2950


Synonym(s): Hemodialysis, Intermittent hemodialysis, IHD, continuous hemodialysis, continuous renal replacement therapy, CRRT

Introduction

  • Hemodialysis has been developed for the management of acute Kidney: acute renal failure and chronic renal failure Kidney: chronic kidney disease that is refractory to conventional medical therapy.
  • At the moment, there are two modalities of hemodialysis:
    • Intermittent hemodialysis (IHD) and continuous hemodialysis, or continuous renal replacement therapy (CRRT).
  • Intermittent hemodialysis (IHD) is a renal replacement therapy that is defined by short and efficient hemodialysis sessions with the goal of removing endogenous or exogenous toxins from the bloodstream. IHD is indicated in cases of azotemia Azotemia (which needs to be severe or in case there is worsening of the azotemia over time, eg chronic cases will require IHD but not have an acute azotemia), electrolyte abnormalities (hyperkalemia) or severe acidosis Acid base imbalance unresponsive to medical management.
  • Continuous renal replacement therapy (CRRT) is a continuous process and, once treatment begins, therapy continues for days to weeks until renal function returns or the patient is transitioned to intermittent dialysis. The most common indication for CRRT is the treatment of acute kidney injury (AKI) in cases in which renal function is expected to return in the near future or which can be eventually transitioned to IHD.
  • Prolonged intermittent renal replacement therapy (PIRRT) is another modality which allows rapid treatments over 6-18 hours performed intermittently during the week. This method is used for treatment of AKI cases.

Principles of hemodialysis

  • Hemodialysis is a process where blood is removed continuously from the patient and is circulated in an extracorporeal circuit where it passes through a filter composed of thousands of straw-like structures.
  • The main forces used during renal replacement therapy for solute/water removal are diffusion and convection.
  • The magnitude of exchange of fluids and solutes is determined among other factors by the size of the solute, the characteristics of the fluids, blood and dialysate flow, as well as the pore size and structural characteristics of the dialyzer membrane.
  • Diffusion during HD plays a major part as the most powerful force for the exchange of solutes and fluids; there is a more reduced implication of convection and adsoprtion in HD. 
  • During diffusion, solutes move from areas of high to low concentration. Following a concentration gradient, solutes in the blood or dialysate fluid compartment cross the dialysis membrane and enter the opposite fluid compartment.
  • Blood solutes such as BUN, creatinine, and electrolytes diffuse along a concentration gradient across the semipermeable dialyzer membrane away from the blood into the dialysate, which is then discarded. Similarly, solutes in high concentration in the dialysate, such as bicarbonate and selected electrolytes, may diffuse across the dialyzer membrane according to their concentration gradient into the blood.
  • Via diffusion, the rate of solute transfer is determined by the concentration gradient of the solutes, molecular weight and membrane permeability.
  • Diffusion is best at removing molecules with low molecular weight from the blood, including BUN and creatinine, sodium, potassium, phosphorus and magnesium.
  • During convection, water is removed from the blood along with dissolved solutes. Pressure is exerted on the blood circulating in the extracorporeal circuit; this pushes the fluid (ultrafiltrate) and dissolved molecules out of blood through the dialyzer membrane and into the dialysate, which is then discarded.
  • The rate of fluid and solvent transfer via convection is determined by transmembrane hydrostatic pressure between the blood and dialysate and the surface area of the dialysis membrane.
  • Convection, a prevalent force in CRRT but not in IHD, is best at removing molecules with low and middle molecular weight from the blood. Middle molecules include many inflammatory mediators, as well as uremic toxins. The advantage of convection over diffusion is also related to the higher efficiency in fluid removal from the patient compared to the diffusion method.

Intermittent hemodialysis (IHD)

  • Intermittent hemodialysis (IHD) is a renal replacement therapy that is defined by short and efficient hemodialysis sessions with the goal of removing endogenous or exogenous toxins from the bloodstream.
  • Common indications for IHD include:
    • Drug or toxin ingestion (ethylene glycol, metaldehyde, methanol, salicylate, phenobarbital, acetaminophen, theophylline, aminoglycosides). 
    • Acute or acute-on-chronic kidney injury.
    • Chronic kidney disease (CKD).
  • Sessions can be performed once, as is common with toxin ingestion, or can be repeated daily or every other day for several days or longer, as is often done for acute kidney injury (AKI). Sessions can be conducted 2 or 3 times a week in selected cases with CKD. Sessions are traditionally 1 to 6 hours in length, but can be longer, depending on the stability of the patient and efficiency of the session.
  • IHD is designed as a more efficient modality than continuous renal replacement therapy (CRRT), meaning that IHD sessions remove small dialyzable molecules (blood urea nitrogen [BUN], creatinine, phosphorus, electrolytes, and certain drugs and toxins) from the bloodstream more rapidly than CRRT.
  • Between treatments (the interdialysis period), the concentration of these dialyzable molecules may increase over time in the blood due to redistribution from the extravascular space and the persistence of renal dysfunction.

Indications

  • IHD may be appropriate when medical management fails to achieve a positive outcome in renal diseases.
  • IHD is indicated in cases of significant or rising azotemia Azotemia, electrolyte abnormalities or acidosis Acid base imbalance unresponsive to medical management.
  • IHD is also indicated in cases of oliguria and anuria in the lack of response to appropriate medical management.
  • IHD is commonly used in the management of humans with CKD (Yeun and Depner, 2000), and is an uncommon but available therapy for management of CKD in veterinary patients.
  • Indications for IHD in patients with CKD include reduction of chronic progressive azotemia, hyperkalemia Hyperkalemia and fluid overload, as well as stabilization before renal transplantation.
  • In the future, IHD may become part of the treatment offered for liver failure via liver dialysis, in which a specialized dialyzer membrane acts as an artificial liver.
  • IHD may become part of a routine treatment of patients with systemic inflammatory response syndrome Systemic inflammatory response syndrome (SRIS), sepsis Shock: septic or other severe inflammatory conditions via filtration and removal of inflammatory mediators, although the current evidence for its clinical utility in people is still controversial. Renal replacement therapy is also indicated for fluid overload and congestive heart failure Heart: congestive heart failure unresponsive to diuretic management with removal of excessive fluid via ultrafiltration.
  • Plasmapheresis or plasma exchange is another potential application of renal replacement therapy used to treat selected immune-mediated disorders (eg immune-mediated hemolytic anemia, polyradiculoneuritis or myasthenia gravis) or intoxications.
  • The goal of IHD is to make dramatic changes in a patient’s uremic, acid-base and fluid status over short periods using diffusion; therefore, significant quantities of pure dialysate must be produced onsite. This technique requires a sizeable investment in the purchase and maintenance of specialized water treatment facilities.

Continuous renal replacement therapy (CRRT)

  • CRRT is a more recently developed blood purification modality. It is a continuous process, and once treatment begins, therapy continues until renal function returns or the patient is transitioned to intermittent dialysis (or euthanized if no improvement).
  • CRRT is similar to IHD because patient blood is passed through thousands of straw-like semipermeable membranes contained within a dialyzer; however, whereas IHD is primarily a diffusive therapy, CRRT uses diffusion, convection and, to a lesser extent, absorption.
  • CRRT has several significant advantages compared with IHD:
    • The slow and gradual nature of the technique provides better control of electrolytes and acid-base balance allowing this technique to be employed in critical patients. The continuous operation more closely approximates the functioning of a normal kidney.
    • Use of convection in CRRT provides a significant advantage in the removal of larger molecules compared to diffusion. These larger molecules are closer in size to those that are normally filtered by the kidney.
  • In contrast to IHD, the efficient use of diffusion and convection in CRRT allows for the use of prepackaged sterile fluids and makes CRRT units virtually free of maintenance between treatments.

Indications

  • The most common indication for CRRT is the treatment of acute kidney injury (AKI) in cases in which renal function is expected to return in the near future or for patients who are to be transitioned to IHD.
  • CRRT can be used for patients with AKI secondary to leptospirosis, nephrotoxins such as aminoglycosides, Fanconi syndrome, melamine toxicities and heatstroke Hyperthermia, pre- and postsurgical support of ureteral obstructions Urolithiasis, and tumor lysis syndrome (Acierno, 2011).
  • CRRT can also be used to remove certain drugs and toxins.
  • Recent studies showed that hemodialysis can work wonders in ethylene glycol intoxications in dogs, if initiated early and ethanol 20% administered concurrently.
  • The ability of any extracorporeal therapy to remove a substance depends on the size of the molecule, its volume of distribution, as well as its degree of protein binding (Johnson & Simmons, 2006). A small molecule with a minimal volume of distribution and low protein binding would be most amenable to removal.
  • CRRT has also been used to treat patients with diuretic-resistant congestive heart failure; however, this treatment has not yet been evaluated in companion animals.

Venous access and central venous catheters (CVC)

  • Vascular access is the first and most basic requirement of successful extracorporeal renal replacement therapy (ERRT).
  • To allow simultaneous removal and return of blood, a dialysis catheter has 2 lumens. These are dual-lumen catheters - they sit in the cranial vena cava and access is via the jugular vein, which therefore should be preserved in cases potentially requiring RRT.
  • The arterial lumen is usually shorter than the venous return lumen to avoid uptake of blood returning from the dialyzer (access recirculation), which would decrease the efficiency of treatment.
  • The risk of complete occlusion is lessened by having multiple ports (side-holes/end-holes). If the holes are positioned circumferentially around the catheter, even if the vessel wall is drawn against the holes on one side of the catheter, blood flow can continue on the opposite side. If the side holes are small, blood preferentially flows through the tip, making the side holes superfluous. If the side holes are large, they weaken the catheter, and increase the amount of heparin that diffuses out of the catheter between dialysis treatments.
  • Temporary catheters should more precisely be called nontunneled, noncuffed catheters.
  • Depending on the type, a temporary catheter may function for up to 4 weeks.
  • Temporary catheters are designed with a tapering tip to facilitate percutaneous placement and are usually made of polyurethane which allows them to be placed via Seldinger technique Seldinger (over the wire) technique.
  • Long-term hemodialysis catheters are usually made of silicone and have an external cuff which is usually made of Dacron. The catheter is placed with a portion in a subcutaneous pocket, which separates the site where the catheter exits the skin from the site where the catheter enters the vessel by several cm.
  • Another vascular access consists of an arteriovenous (AV) fistula or graft is the preferred access in patients receiving chronic hemodialysis. An artery is surgically anastomosed to a vein with a section of autologous vein or synthetic graft (typically PTFE). Between treatments, no anticoagulant is needed because blood is continually flowing through the graft/fistula. Because it is completely enclosed under the skin, the infection rate is extremely low in comparison to catheters.
  • Propofol Propofol infusion with low doses (an average dose of 3.05mg/kg-1) represents an excellent option for short anesthesia in renal failure cases in which cases sedation is needed for the central venous catheter.

Catheter care and management

  • The extracorporeal renal replacement therapy (ERRT) catheter should be used only for ERRT procedures and handled only by ERRT personnel.
  • At each ERRT treatment, the exit site should be inspected and cleaned with antiseptic solution.
  • When the ERRT catheter is accessed at the beginning and end of each treatment or at any other time, the catheter ports should receive an aseptic scrub for 3 to 5 minutes.
  • The ERRT technician should wear examination gloves and a mask when opening or closing the catheter. When not in use, the catheter is bandaged in place and completely covered.
  • There are two types of catheter lockings that can be safely used for the CVC to avoid clotting and occlusion of the CVC in-between treaments:
    • The first one is represented by undiluted unfractionated heparin solution 1000 IU/ml every 12 h.
    • The second one is represented by unfractionated heparin solution 5000 IU/ml every 24 h.

Complications

  • Complications of IHD include hypotension and hypovolemia; problems with vascular access; and neurologic, respiratory, hematologic, and gastrointestinal complications; and dialysis disequilibrium syndrome (DDS).
  • Hypotension and hypovolemia occur during IHD sessions as a result of ultrafiltration and large extracorporeal blood volumes and can persist during or between sessions as a result of blood loss (from bleeding secondary to uremic ulceration, overheparinization, coagulopathy or blood loss secondary to filter or line clotting in which not all extracorporeal blood volume can be returned to the patient).
  • Treatments for hypotension include decreasing the fluid removal from the patient, administration of crystalloid or colloid therapy, initiation of vasopressor therapy or cessation of the IHD session in severe cases.
  • Respiratory complications include uremic pneumonitis and pulmonary hemorrhage, pleural effusion and pulmonary edema Lung: pulmonary edema, hypoxemia, hypoventilation, and pulmonary thromboembolism (PTE).
  • Hypoxemia Hypoxemia and hypoventilation can be caused by ventilatory failure in the critically ill or neurologically impaired patient; whereas hypoxemia can be caused by diffusion failure as a result of pulmonary hemorrhage Lung: pulmonary hemorrhage, pneumonitis, infectious pneumonia, or edema, or ventilation-perfusion mismatch Ventilation perfusion mismatching caused by PTE.
  • Hematologic complications including anemia Anemia: overview, thrombocytopenia Thrombocytopenia, and leukopenia (also common in patients with IHD).
  • Anemia and thrombocytopenia result from coagulopathy and vasculitis common with systemic inflammatory response syndrome and leukopenia can result from infectious or inflammatory processes.
  • Anemia is also common as a result of frequent blood sampling, loss through the extracorporeal circuit and bleeding, as described earlier.
  • Thrombocytopenia can occur secondary to contact activation with the dialysis membrane, and initiation of the coagulation cascade as a result of disease-specific or iatrogenic coagulopathy, whereas leukopenia can occur transiently as a result of white blood cell interaction with the dialysis membrane.
  • Complications such as nausea, vomiting and inappetence are common in uremic animals Uremia and can also be a complication of dialysis-induced hypotension, DDS, dialysate contaminants and blood transfusion reactions.
  • Clotting is one of the most common complications. Catheters are associated with a high rate of thrombosis. Treatment of thrombosis should be initiated as soon as detected. Bleeding complications are more common with warfarin, and its routine use is not recommended.
  • Infection is the most dangerous catheter complication in patients undergoing hemodialysis and is one of the most common causes of increased morbidity. Catheter-related infections can be minimized by following strict aseptic guidelines when placing and using dialysis catheters and by inspecting the catheter entry site daily while in hospital and before every dialysis treatment.

Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Costea R, Vitalaru B A (2015) Propofol induction anesthesia for central venous catheterization in dogs with renal failure. J Biotechnol 208, S42-S43 ResearchGate.
  • Stanzani G, Jepson R E, Chan D L (2015) Management of acute kidney injury with continuous venovenous haemodiafiltration in a cat. J Feline Med Surg 17 (6), 551-556 PubMed.
  • Acierno M J (2011) Continuous renal replacement therapy in dogs and cats. Vet Clin North Am Small Anim Pract 41 (1), 135-146 PubMed.
  • Bloom C A, Labato M A (2011) Intermittent hemodialysis for small animals. Vet Clin North Am Small Anim Pract 41 (1), 115-133 PubMed.
  • Chalhoub S, Langston C E, Poeppel K (2011) Vascular access for extracorporeal renal replacement therapy in veterinary patients. Vet Clin North Am Small Anim Pract 41 (1), 147-161 PubMed.
  • Claus M A, Jandrey K E, Poppenga R H (2011) Propylene glycol intoxication in a dog. J Vet Emerg Crit Care 21 (6), 679-683 PubMed.
  • Stanley S W, Langston C E (2008) Hemodialysis in a dog with acute renal failure from currant toxicity. Can Vet J 49 (1), 63-66 PubMed.
  • Willms L, Vercaigne L (2008) Does warfarin safely prevent clotting of hemodialysis catheters? a review of efficacy and safety.​ Semin Dial 21 (1), 71-77 PubMed.
  • Clark W R, Ronco C (2004) Continuous renal replacement techniques. Contrib Nephrol 144, 264-277 PubMed.
  • Langston C (2002) Hemodialysis in dogs and cats. Compend 24 (7), 540-549 VetMedResource.
  • Depner T A (2001) Catheter performance. Semin Dial 14 (6), 425-431 PubMed.
  • Elliott D A (2000) Hemodialysis. Clin Tech Small Anim Pract 15 (3), 136-148 PubMed.
  • Bellomo R, Farmer M, Parkin G et al (1995) Severe acute renal failure: A comparison of acute continuous hemodiafiltration and conventional dialytic therapy. Nephron 71 (1), 59-64 PubMed.
  • Clark W R, Mueller B A, Alaka K J et al (1994) A comparison of metabolic control by continuous and intermittent therapies in acute renal failure. J Am Soc Nephrol (7), 1413-1420 PubMed.

Other sources of information

  • Centers for Continuous Renal Replacement Therapy can be found at: Nephrology Knowledge: Veterinary Extracorporeal Renal Replacement Unitswww.queenofthenephron.com.
  • Hemodialivet: www.hemodialivet.ro.
  • Groman R (2010) Apheresis in veterinary medicine: therapy in search of a disease. In: Proceedings of the Advanced Renal Therapies Symposium. pp 26-32.
  • West J B (2008) Respiratory physiology: the essentials. Philadelphia: Lippincott Williams & Wilkins. pp 13-73.
  • Johnson C & Simmons W (2006) Dialysis of drugs. Nephrology Pharmacy Associates, Ann Arbor (MI).
  • Cowgill L D, Francey T (2005) Acute uremia. In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine. 6th edn. St. Louis: Elsevier Saunders. pp 1731-1756.
  • Himmelfarb J, Dember L M, Dixon B S (2005) Vascular access. In: Pereira BJ, Sayegh MH, Blake P, editors. Chronic kidney disease, dialysis, transplantation. 2nd ed. Philadelphia: Elsevier Saunders.  p 341.
  • Cowgill L D, Elliott D A (2000) Hemodialysis. In: DiBartola SP (ed) Fluid therapy in Small Animal Practice. 2nd edn. Philadelphia: WB Saunders. pp 528-547.
  • Yeun J, Depner T (2000) Principles of dialysis. In: Dialysis and Transplantation: A Companion to Brenner & Rectors’ the Kidney, Philadelphia WB Sanders, pp 1-32.