Renal Replacement Therapy (RRT)

Introduction And Indications

• Renal replacement therapy encompasses multiple modalities to support patients with severe kidney dysfunction.
• The primary purpose is the removal of endogenous and exogenous toxins.
• It maintains fluid, electrolyte, and acid-base balance until kidney function recovers or a transplant is performed.
• Dialysis should begin early to prevent life-threatening complications.

Clinical Indications For Dialysis Initiation

Modality Selection And Comparison

• Modality choice is influenced by patient size, hemodynamic stability, and institutional resources.
• The goals of dialysis and the expertise of the dialysis team are critical factors.

Comparison Of Renal Replacement Modalities

Peritoneal Dialysis

Principles And Physiology

• Peritoneal dialysis utilizes the patient’s peritoneal membrane to transport fluid and solutes.
• Excess body water is removed by an osmotic gradient.
• This gradient is typically created by the relatively high dextrose concentration in the dialysis fluid.
• Wastes are removed by diffusion from the peritoneal capillaries into the dialysate.
• The driving forces of solute and water transport are diffusion, osmosis, and convection.
• Ultrafiltration consists of the bulk movement of water and permeable solutes dragged across the peritoneal membrane via convective mass transfer.

Modalities Of Peritoneal Dialysis

Peritoneal Dialysis Catheters And Equipment

• Peritoneal access is achieved via a surgically or percutaneously placed catheter.
• Catheters configurations typically include straight or swan-neck tunnels with pigtail-curled or straight intra-abdominal portions.
• A double-cuff catheter with a downward or lateral subcutaneous tunnel is recommended to reduce peritonitis risk.
• In infants, the exit site should be positioned laterally or downward, distant from the diaper area to prevent contamination.
• An automated cycler provides infusion volumes ranging from 25 to 3500 mL.
• Cyclers are equipped with automated spiking, barcoded bag recognition, and in-line dialysate heating.

Dialysis Solutions

• Conventional solutions possess an acidic pH (5.5), high lactate, and high glucose degradation products (GDPs).
• Prolonged exposure to GDPs contributes to the loss of the mesothelial cell layer, peritoneal fibrosis, and membrane failure.
• Multichamber bags separate glucose at a very low pH from the buffer to prevent the formation of GDPs during sterilization.
• Low-GDP, pH-neutral fluids preserve residual kidney function and peritoneal membrane integrity.
• Icodextrin is a large glucose polymer that provides sustained ultrafiltration during long dwells and is useful for fluid-overloaded patients.

Prescription And Adequacy

• Adequacy cannot be exclusively defined by targets of solute and fluid removal.
• Clinical assessment includes electrolyte balance, anemia control, hydration status, nutrition, and growth.

Adequacy Measurement Parameters

• The minimum delivered total dialysis dose should be at least a Kt/V urea of 1.7 per week for children.
• Weekly creatinine clearance target is suggested to be >45 L/1.73 m2 per week.
• The Peritoneal Equilibration Test (PET) standardizes the assessment of peritoneal membrane transport capacity.
• A 2.5% dextrose dwell is infused, and dialysate to plasma (D/P) creatinine and glucose ratios are measured at 0, 2, and 4 hours.

Peritoneal Transport Categories

• High Transporters: Absorb glucose rapidly, losing the osmotic gradient quickly. Require short dwells (APD/NIPD) to prevent volume overload.
• High-Average Transporters: Have good solute transport and moderate ultrafiltration.
• Low-Average Transporters: Have moderate solute transport and good ultrafiltration.
• Low Transporters: Require long dwell times (CAPD/CCPD) to achieve adequate solute clearance.
• The Mini-PET uses a 3.86% glucose dwell over 1 hour to accurately measure free water transport and sodium sieving through ultrasmall aquaporin-1 pores.

Complications Of Peritoneal Dialysis

Infectious Complications

• Peritonitis is the most frequent cause of hospitalization and a leading contributor to technique failure.
• Diagnosis is confirmed if the PD effluent white blood cell count is greater than 100/mm3 with at least 50% polymorphonuclear neutrophils (PMNs).
• Empiric intraperitoneal antibiotics covering gram-positive and gram-negative organisms must be initiated promptly.
• Exit site and tunnel infections must be diagnosed and treated early to prevent subsequent peritonitis.

Non-Infectious Complications

• Elevated intraperitoneal pressure causes hernias, hydrothorax (pleuroperitoneal leak), and gastroesophageal reflux.
• Hydrothorax is confirmed by elevated pleural fluid glucose relative to serum glucose.
• Hypokalemia is the most common electrolyte derangement, especially in infants.
• Encapsulating Peritoneal Sclerosis (EPS) is a life-threatening complication characterized by severe peritoneal fibrosis leading to bowel obstruction.

Intermittent Hemodialysis

Principles And Physiology

• Hemodialysis utilizes an extracorporeal circuit to circulate blood through a hollow fiber dialyzer.
• Diffusion: Movement of solutes across a semipermeable membrane down a concentration gradient. Small molecules like urea move with great ease.
• Convection: Movement of water and dissolved solutes across a semipermeable membrane driven by a hydrostatic pressure gradient.
• Ultrafiltration: The bulk movement of water alone across the dialyzer membrane generated by negative transmembrane pressure.

The Hemodialysis Circuit And Equipment

• The blood circuit consists of an arterial limb moving blood toward the dialyzer and a venous limb returning blood to the patient.
• A rotating roller pump on the arterial limb generates blood flow rates ranging from 10 to 500 mL/min.
• The dialysate circuit uses a proportioning system to mix purified water, an acid concentrate (containing electrolytes), and a base concentrate (bicarbonate).
• Dialysate and blood flow in opposite directions (counter-current flow) through the dialyzer to maximize the diffusion gradient.

Hemodialyzers

• Modern dialyzers contain thousands of hollow capillary fibers made of artificial, biocompatible plastics like polysulfone.
• Membrane surface area should approximate the patient's body surface area.
• The total extracorporeal volume (dialyzer plus tubing) must not exceed 10% of the child's circulating blood volume to prevent hypotension.
• High-flux dialyzers have high permeability, permitting the clearance of middle molecules and high ultrafiltration rates.

Vascular Access

• A functioning vascular access is the Achilles' heel of hemodialysis.

Types Of Vascular Access

AVF Cannulation Techniques

• Rope Ladder Technique: Punctures are rotated along the length of the vessel using sharp needles.
• Buttonhole Technique: Needles are placed in the exact same hole and track every session. Uses blunt needles once the track is established. Decreases the risk of aneurysm formation.
• Area Puncture: Needles are clustered in a single small area. Associated with high risk of aneurysms and stenosis.

Prescription And Adequacy

• Small solute clearance is typically assessed using urea reduction and Kt/V.

Hemodialysis Adequacy Metrics

Complications Of Hemodialysis

Intradialytic Hypotension

• Caused by ultrafiltration exceeding the vascular refilling rate, impaired venoconstriction, and myocardial stunning.
• Management includes temporarily suspending ultrafiltration, administering isotonic fluid boluses, and placing the patient in Trendelenburg.
• Prevention involves cooling the dialysate, sodium profiling, and withholding antihypertensives prior to the session.

Dialysis Disequilibrium Syndrome

• Characterized by neurological changes, severe headache, seizures, and coma.
• Driven by the rapid clearance of urea from the blood, leaving high urea concentrations in the brain.
• This creates an osmotic gradient that draws water into the brain, causing acute cerebral edema.
• Prevented by targeting a lower urea reduction (e.g., 30%) during the initial dialysis sessions.

Other Complications

• Catheter-Associated Bloodstream Infections (CLABSI): Presents with fever, chills, and hemodynamic instability. Managed with broad-spectrum antibiotics (e.g., vancomycin and ceftazidime).
• Intradialytic Cramping: Associated with high ultrafiltration rates and rapid electrolyte shifts.

Hemodiafiltration (HDF)

Principles Of Hemodiafiltration

• Hemodiafiltration (HDF) combines both diffusive and convective solute removal.
• Requires ultrafiltration of 20% or more of the processed blood volume through a high-flux dialyzer.
• Fluid balance is maintained by infusing large volumes of sterile replacement fluid directly into the patient's blood.
• Convection allows for the efficient removal of middle molecules (300-5000 Da) and larger uremic retention solutes (up to 50 kDa) like beta-2 microglobulin.

Modes Of Hemodiafiltration

Advantages And Outcomes

• HDF provides superior clearance of inflammatory cytokines, reducing oxidative stress and systemic inflammation.
• Associated with vastly improved hemodynamic stability, resulting in fewer episodes of intradialytic hypotension.
• Pediatric studies (like the 3H study) demonstrate improved nutrition, accelerated catch-up growth, and regression of left ventricular hypertrophy.
• Patients report fewer post-dialysis symptoms such as headaches, dizziness, and cramping, with significantly shorter recovery times.

Continuous Kidney Replacement Therapy (CKRT / CRRT)

Principles Of Continuous Therapies

• Continuous therapies substitute for impaired kidney function over 24 hours a day.
• They are specifically indicated for critically ill, hemodynamically unstable patients, or those with severe fluid overload and multi-organ failure.
• Extracorporeal circuits with miniaturized systems and accurate volumetric controls are utilized to safely treat small infants.

Modalities Of Continuous Kidney Replacement Therapy

Slow Low Efficiency Dialysis (SLED) / PIRRT

• SLED, also known as Prolonged Intermittent Renal Replacement Therapy (PIRRT), is a hybrid therapy combining advantages of CRRT and standard HD.
• Therapy is delivered daily over an extended period (typically 6 to 12 hours) using conventional hemodialysis machines.
• Uses drastically reduced blood and dialysate flow rates compared to standard HD.
• SLED achieves excellent fluid volume targets with high hemodynamic stability while minimizing the prohibitive costs and technical complexities associated with CRRT.

Specialized Equipment For Infants And Neonates

• Standard adult CRRT machines require large extracorporeal volumes (59-100 mL) which vastly exceed 10% of a neonate's blood volume, mandating hazardous blood-priming.
• Miniaturized devices have revolutionized neonatal acute dialysis:
• CARPEDIEM (Cardio-Renal Pediatric Dialysis Emergency Machine): A dedicated, pump-driven machine using extremely small double-lumen catheters. Designed for infants weighing 2.5 to 10 kg, featuring priming volumes as low as 27-30 mL.
• NIDUS (Newcastle Infant Dialysis and Ultrafiltration System): A syringe-driven system utilizing a single-lumen line for babies 800 g to 8 kg. Features an extracorporeal volume of less than 10 mL, entirely eliminating the need for blood priming.
• Aquadex FlexFlow System: An ultrafiltration device adapted to provide CVVH and SCUF for infants, utilizing a minimal priming volume of 33 mL.

Anticoagulation Strategies

• Regional Citrate Anticoagulation (RCA): The preferred method for CRRT. Citrate is infused pre-filter, binding ionized calcium and inhibiting the clotting cascade exclusively within the circuit. Calcium is infused systemically into a separate central line to restore physiological levels in the patient.
• Citrate Lock: A metabolic complication of RCA where hepatic citrate clearance fails, leading to citrate accumulation. Diagnosed by a rising total calcium to ionized calcium ratio (>2.5) and worsening metabolic acidosis.
• Systemic Heparin: Achieved by continuous infusion pre-filter. Requires monitoring of partial thromboplastin time (PTT). Carries a significant risk of systemic bleeding and heparin-induced thrombocytopenia.

Drug Clearance In Renal Replacement Therapy

• The physicochemical properties of a drug—such as molecular size, protein binding, and volume of distribution—determine its dialyzability.
• High-flux dialyzers efficiently remove molecules up to 40,000 Daltons; for example, vancomycin (1,450 Da) is extensively cleared.
• Drugs with a large volume of distribution (>0.8 L/kg) or high plasma protein binding (>80%) are minimally removed by dialysis.
• CRRT Clearance Modalities: Convective clearance methods remove larger and protein-bound drugs more efficiently than diffusive methods. In terms of drug clearance: CVVHF > CVVHDF > CVVHD.
• PD Dosing: Drug clearance is far less efficient in PD than in HD. Medications appropriately dosed for HD may become supratherapeutic in PD patients. KDIGO suggests adapting PD dosing from recommendations for an eGFR < 15 mL/min.
• IHD Dosing: Supplemental drug doses are routinely required following intermittent hemodialysis sessions to replace the fraction cleared during therapy. Therapeutic drug monitoring is mandatory for narrow-index medications like aminoglycosides.