RENAL REPLACEMENT THERAPY By:Dr.Amena Fatima

When acute kidney injury (AKI) is severe, resolution can take several days or weeks. During this time, the kidneys cannot maintain homeostasis of fluid, potassium, metabolic acid and waste products because of which life threatening complications frequently develop. In such patients, extracorporeal techniques of blood purification,broadly termed as Renal Replacement therapy (RRT) becomes the life saver.

Techniques of RRT include continuous haemofiltration and its technical variations Intermittent haemodialysis and its variations. Peritoneal dialysis.

All of these techniques rely on the principle of removing unwanted solutes and water through a semipermeable membrane(present in the dialyser). Such membrane is either biological (peritoneum) or artificial (haemodialysis or haemofiltration membranes). Each type of membrane has its own advantages, disadvantages and limitations

principles WATER REMOVAL The removal of unwanted solvent (water) is therapeutically probably as important as the removal of unwanted solute . During RRT, water is removed through a process called ultrafiltration a process which is essentially the same as that performed by the glomerulus.

ultrafiltration It requires a driving pressure to move fluid across a semipermeable membrane because such fluid would normally be kept within the circulation due to oncotic pressure (colloid osmotic pressure). So this pressure (for ultrafiltration) is achieved by :

Generating a transmembrane pressure though pumped blood flow (as in haemofiltration or during intermittent haemodialysis) that is greater than oncotic pressure. Increasing osmolarity of the dialysate (as in peritoneal dialysis.

Solute Removal This is achieved by: Creating an electrochemical gradient across the membrane using a flow-past system with toxin-free dialysate (diffusion) as in intermittent haemodialysis (IHD) and peritoneal dialysis (PD). Creating a transmembrane-pressure-driven ‘solvent drag’, where solutes move together with solvent (convection) across a porous membrane, are discarded together with the solvent and then replaced with toxin-free replacement fluid as in haemofiltration (HF).

Ultrafiltration Conventional hemodialysis blood flow 350-450 ml/min, dialysate flow 500-800 ml/min. In continuous hemodialysis (CVVHD) blood flow is usually set at 100-200 ml/min, dialysate flows at 1000-2000 ml/hr.

The rate of diffusion of a given solute depends on its molecular weight, the porosity of the membrane, the blood flow rate, the dialysate flow rate, the degree of protein binding, and its concentration gradient across the membrane. If standard, low-flux, cellulose-based membranes are used, middle molecules of >500 Daltons molecular weight (MW) cannot be removed. If synthetic high-flux membranes are used (cut-off at 10–20 kiloDaltons (kD) in MW), larger molecules can be removed. With these membranes, convection is superior to diffusion in achieving the clearance of middle molecules.

Indications In the critically ill patient, RRT should be initiated early, prior to the development of complications. The criteria for the initiation of RRT in patients with chronic renal failure are probably inappropriate in the critically ill. A set of modern criteria for the initiation of RRT in the ICU are :

If one criterion is present, RRT should be considered. If two criteria are simultaneously present, RRT is strongly recommended.

Which is the best modality? There is a great deal of controversy as to which modality of RRT is ‘best’ in the ICU, due to the lack of randomised controlled trials comparing different modalities (IHD or CRRT). But modalities of RRT may be judged on the basis of the following criteria: 1. Haemodynamic side-effects 2. Ability to control fluid status 3. Biocompatibility……………contd .

4. Risk of infection 5. Uraemic control 6 4. Risk of infection 5. Uraemic control 6. Avoidance of cerebral oedema 7. Ability to allow full nutritional support 8. Ability to control acidosis 9. Absence of specific side-effects 10. Cost

In relation to the above criteria, CRRT and slow lowefficiency daily dialysis (SLEDD) offer many advantages over PD and conventional IHD (3–4 hours/day for 3–4 times/week).

CONTINUOUS RENAL REPLACEMENT THERAPY If no dialysate is used and effluent is replaced with replacement solutions, the technique is called continuous veno-venous haemofiltration (CVVH) During CVVH, ultrafiltration rates of 2L/h yield urea clearances of approximately 25mL/kg/h in the average 80-kg patient.

In a veno-venous system, dialysate can also be delivered countercurrent to blood flow (continuous venovenous haemodialysis/haemodiafiltration) to achieve either almost pure diffusive clearance or a mixture of diffusive and convective clearance respectively

Slow Continuous Ultra filtration In slow continuous ultra filtration (SCUF), a pump system maintains low blood flow (usually no more than 100 mL per minute) through a hemofilter and generates low rates of ultraltration (typically 100 to 300 mL per hour). This modality provides volume removal but does not alter the chemistry of plasma, since water is removed in proportion to solute. Compared with other CRRT modalities, SCUF is a low intensity nursing procedure. The procedure is often used in settings of severe volume overload with acceptable chemistries. SCUF is often employed as an adjunct to IHD in the hemodynamically stable, volume overloaded patient.

Predictable outcomes of CRRT 1. Continuous control of fluid status 2. Haemodynamic stability 3. Control of acid–base status 4. Ability to provide protein-rich nutrition while achieving uraemic control 5. Control of electrolyte balance, including phosphate and calcium balance 6. Prevention of swings in intra cerebral water…….contd

7. Minimal risk of infection High level of biocompatibility CONS CRRT mandates the presence of specifically trained nursing and medical staff 24 hours a day. The issues of continuous circuit anticoagulation or the potential risk of bleeding have been of concern. Cost.

CIRCUIT ANTICOAGULATION The flow of blood through an extracorporeal circuit causes activation of the coagulation cascade and promotes clotting of the filter and circuit itself. In order to delay such clotting and achieve acceptable operational lives (approximately 24 hours) for the circuit, anticoagulants are frequently used. However, circuit anticoagulation increases the risk of bleeding

Therefore, the risks and benefits of more or less intense anticoagulation and alternative strategies must be considered.

In the vast majority of patients, low-dose heparin(<500IU/h) is sufficient to achieve adequate (approximately 24 hours) circuit life, is easy and cheap to administer and has almost no effect on the patient’s coagulation tests. In some patients, a higher dose is necessary. In others (pulmonary embolism, myocardial ischaemia) full heparinisation may actually be concomitantly indicated.

Regional citrate anticoagulation is very effective but requires a special dialysate or replacement fluid. Nevertheless, it is safe and effective in patients who do not have liver failure. In patients with liver failure, citrate may accumulate and induce a coagulopathy.

The biochemical signs of citrate accumulation are : an increasing base deficit, an increasing requirement for calcium administration to maintain the target level of calcaemia widening of the total calcium to ionised calcium ratio.

Due to development of commercially available dialysate and replacement fluids to facilitate citrate anticoagulation, And due to new CRRT machine technology the use of citrate anticoagulation is rapidly expanding.

Regional heparin/protamine anticoagulation is also somewhat complex, but simpler than citrate anticoagulation, and may be useful if frequent filter clotting occurs and further anticoagulation of the patient is considered dangerous. Low-molecular-weight heparin is also easy to administer, but more expensive. If enoxaparin is used, its dose should be adjusted for the loss of renal function.

Heparinoids and prostacyclin may be useful if the patient has developed heparin-induced thrombocytopenia. Finally, in perhaps 10–20% of patients anticoagulation of any kind is best avoided because of endogenous coagulopathy or recent surgery or inability to metabolise citrate

Many circuits clot for mechanical reasons (e. g Many circuits clot for mechanical reasons (e.g. inadequate access, unreliable blood flow from double-lumen catheter depending on patient position, kinking of catheter). Particular attention needs to be paid to the adequacy/ ease of flow through the double-lumen catheter.

Responding to frequent filter clotting by simply increasing anticoagulation without making the correct aetiological diagnosis (e.g. checking catheter flow and position, taking a history surrounding the episode of clotting, identifying the site of clotting) is often futile and exposes the patient to unnecessary risk.

Larger catheters (13.5 Fr) in the femoral position or internal jugular position appear to perform more reliably.

INTENSITY OF CRRT The optimal dose (expressed at effective effluent/kg/h)of CRRT has been the subject of controversy for almost a decade. Several studies had initially suggested that higher dose may translate into better outcome But 2 recent RCTs showed no difference with increasing the intensity of RRT indicating that, in current practice, the prescribed dose of RRT should be equivalent to 25–30mL/kg/h.

INTERMITTENT HAEMODIALYSIS Countercurrent dialysate flow is used as in IHD. The major differences are that standard IHD uses high dialysate flows (300–400mL/min), and treatment is applied for short periods of time (3–4 hours), usually every second day.

These differences have important implications. Firstly, volume has to be removed over a short period of time and this may cause hypotension. Repeated hypotensive episodes may delay renal recovery. Secondly, solute removal is episodic. This translates into inferior uraemic control and acid–base control. Limited fluid and uraemic control imposes unnecessary limitations on nutritional support. Furthermore, rapid solute shifts increase brain water content and raise intracranial pressure.

The limitations of applying ‘standard’ IHD to the treatment of ARF have led to the development of new approaches (so-called ‘hybrid techniques’) such as SLEDD.

Sustained Low Efficiency Dialysis Hybrid therapies apply the CRRT principle of low solute clearance over an extended, but not continuous, period of time. Sustained low effciency dialysis (SLED) is better tolerated hemodynamically than IHD and can be performed with either standard hemodialysis machines or with CRRT equipment.

Lower blood flow (100 to 200 mL per minute) and dialysate flow (100 mL per minute) rates achieve adequate diffusive solute clearance and convective volume removal over a typical 8- to 12-hour session. SLED done with standard hemodialysis machines expands the clinical utility of these devices.

PERITONEAL DIALYSIS This technique is now uncommonly used in the treatment of adult ARF in developed countries. However, it may be an adequate technique in developing countries or in children where the peritoneal membrane has a greater relative surface Alternatives are considered too expensive, too invasive, or are not available.

Typically access is by the insertion of an intraperitoneal catheter. Glucose-rich dialysate is then inserted into the peritoneal cavity and acts as the ‘dialysate’. After a given ‘dwell time’ it is removed and discarded with the extra fluid and toxins that have moved from the blood vessels of the peritoneum to the dialysate fluid.

PD can be performed as a series of manual dialysate exchanges done during the day (chronic ambulatory peritoneal dialysis or CAPD) or through automated exchanges utilizing a PD machine (cycler) typically done at night (continuous cycled peritoneal dialysis or CCPD). For CAPD, dialysate is changed every 4 to 6 hours with a longer overnight “dwell.” For CCPD, the exchanges are typically done every 2 to 3 hours through the night, and the abdomen is often left empty or with only a small volume of dialysate (sometimes called a “cushion” ) during the day.

PD is much less effcient than IHD but is better tolerated hemodynamically, since solute and fluid shifts occur gradually. In the ICU setting, PD is generally reserved for ESRD patients who are already maintained on this modality. PD is generally not used for AKI because of technical difficulty in establishing dialysis access as well as the low ef ciency of solute clearance.

cons 1. Limited and sometimes inadequate solute clearance 2. High risk of peritonitis 3. Unpredictable hyperglycemia 4. Fluid leaks 5. Protein loss 6. Interference with diaphragm function.

So….. The shift toward CRRT is driven by a number of important practical as well some theoretical advantages for CRRT over IHD: ■ CRRT induces less hypotension and is better tolerated by the patient with unstable hemodynamics. ■ CRRT permits removal of large fluid volumes without inducing or exacerbating hypotension. ■ Since CRRT induces less hypotension, it may promote renal recovery from AKI ■ CRRT provides greater solute clearance than alternate day IHD. ■ Since CRRT minimizes/limits hypotension and disequilibrium, it may better preserve cerebral perfusion in acute brain injury and in hepatic failure. ■ The convective clearance of CRRT, particularly CVVH, may remove harmful immunomodulatory substances in sepsis.

Recommendations Of CRRT over IHD for the management of AKI in the following clinical settings: ■ Hypotension requiring pressor support ■ Massive volume overload with high obligate fluid intake ■ Highly catabolic patients who have failed to reduce BUN less than 80 mg per dL over three IHD sessions ■ AKI in the setting of severe liver failure

Technical recommendations: ■ We favor pump-driven venovenous systems over arteriovenous systems. ■ We practice CVVH because of its simplicity and theoretic advantage of clearing middle molecules and harmful immunomodulatory cytokines. There is no evidence that CVVH is associated with better outcomes than CVVHD or CVVHDF. Regardless of the CRRT modality, the prescribed effluent volume should be 20 to 25 mL per kg per hour.

Discontinuation of Therapy Recovery of renal function is traditionally defined by the reversal of oliguria and progressive decline in serum creatinine. Increased urine volume may not be apparent in the nonoliguric patient. If the CRRT patient is intensively treated, the serum creatinine may be normal, making it impossible to detect a spontaneous decline. We define recovery of renal function according to the criteria used in the ATN study : ■ Urine volume exceeding 30 mL per hour (720 mL per day) ■ 6-hour timed urine collection to compute creatinine clearance: Ccreat = Ucreat × volume/ Pcreat ÷ 360 < 12 mL per minute -----continue CRRT 12–20 mL per minute -------individualize ongoing CRRT 20 mL per minute ---------discontinue CRRT

COMPLICATIONS OF RRT Infection Electrolyte and Acid–Base Disorders Access Thrombosis Hypotension

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