Renal Replacement Therapy (RRT)

Overview

• Renal replacement therapy (RRT) encompasses treatments intended to substitute for impaired kidney function over an extended period, utilized when kidney dysfunction progresses to the point where homeostasis and survival can no longer be sustained with maximal medical management.
• RRT encompasses dialysis modalities—peritoneal dialysis (PD), intermittent hemodialysis (IHD), and continuous kidney replacement therapies (CKRT)—as well as kidney transplantation, which is the ultimate goal and definitive therapy for children with end-stage kidney disease (ESKD).
• The choice of modality depends on the acuity of the kidney injury, the hemodynamic stability of the patient, the goals of therapy (fluid removal versus rapid toxin clearance), patient size, and institutional resources.

Indications for Renal Replacement Therapy

Acute Kidney Injury (AKI)

• In the setting of AKI, RRT is indicated when medical management fails to control life-threatening complications.
• Persistent, medically refractory hyperkalemia (typically $>6.5$ mEq/L).
• Severe metabolic acidosis (serum bicarbonate $<10-12$ mEq/L) unresponsive to medical management.
• Cumulative fluid overload exceeding 10% of body weight, or clinically significant fluid overload leading to refractory pulmonary edema.
• Profound, symptomatic hyponatremia ($<120$ mEq/L) or hypernatremia.
• Uremia manifesting with clinically significant complications such as uremic encephalopathy, pericarditis, or neuropathy.
• Calcium-phosphorus imbalance manifesting as hypocalcemic tetany.
• Inability to provide adequate nutritional intake or necessary intravenous medications due to the need for severe fluid restriction in an oliguric/anuric patient.
• Non-kidney indications include the rapid removal of toxins in inborn errors of metabolism (e.g., severe hyperammonemia) and the prevention or treatment of severe tumor lysis syndrome.

Chronic Kidney Disease (CKD)

• Initiation of chronic dialysis is generally considered when the estimated glomerular filtration rate (eGFR) falls below 12 mL/min/1.73 m² and is strongly recommended when the eGFR is $<8$ mL/min/1.73 m².
• Clinical well-being heavily influences the initiation timing; RRT is indicated in the presence of intractable fluid overload, treatment-resistant hypertension, persistent gastrointestinal symptoms, uremia, profound growth retardation, or neurological deterioration.

Dialysis Modalities

Peritoneal Dialysis (PD)

• PD utilizes the patient's highly vascularized peritoneal membrane as a semipermeable filtration surface. Dialysis fluid containing a high dextrose concentration is instilled into the peritoneal cavity, driving water transfer (ultrafiltration) and solute exchange via an osmotic and concentration gradient.
• PD is often the initial RRT of choice in neonates and infants because it does not require sophisticated vascular access or equipment, and it can be initiated rapidly using a soft silastic or temporary stiff catheter.
• Chronic PD can be performed manually as continuous ambulatory peritoneal dialysis (CAPD) or at night using an automated cycler (automated peritoneal dialysis, APD or CCPD).
• Advantages: It is an at-home therapy that avoids frequent hospital visits, allowing children to resume schooling and maintain a normal lifestyle. It minimizes hemodynamic instability, provides continuous clearance, and allows for a less restricted diet and fluid intake compared to hemodialysis.
• Disadvantages/Complications: Bacterial peritonitis is the most significant complication, requiring meticulous aseptic technique. Other issues include exit-site infections, catheter malfunction, and variable ultrafiltration dependent on membrane characteristics. PD is also less efficient at rapid solute clearance than hemodialysis.

Intermittent Hemodialysis (IHD)

• IHD involves pumping the patient's blood outside the body through an extracorporeal circuit into a hollow-fiber dialyzer (artificial kidney). Solutes are exchanged via diffusion across a synthetic membrane against a counter-current physiologic dialysate, and fluid is removed via ultrafiltration.
• It requires reliable vascular access, achieved via an arteriovenous fistula (the preferred long-term access), an arteriovenous graft, or a double-lumen central venous catheter (typically in the internal jugular vein).
• Maintenance IHD is generally performed in-center for 3 to 4 hours per session, with a frequency of 3 sessions per week.
• Advantages: IHD is highly efficient and rapid, making it the preferred modality for correcting acute, severe fluid, and electrolyte abnormalities, or for clearing acute drug intoxications.
• Disadvantages/Complications: It requires skilled nursing, highly specialized equipment, and systemic anticoagulation (heparinization). The rapid fluid shifts and high blood flow rates limit its use in hemodynamically unstable patients, frequently causing intradialytic hypotension and predisposing to dialysis disequilibrium syndrome.

Continuous Kidney Replacement Therapies (CKRT)

• CKRT encompasses continuous extracorporeal blood purification therapies applied 24 hours/day, primarily in the intensive care setting for critically ill, hemodynamically unstable patients.
• Modalities include continuous venovenous hemofiltration (CVVH - solute clearance primarily by convection), continuous venovenous hemodialysis (CVVHD - solute clearance primarily by diffusion), continuous venovenous hemodiafiltration (CVVHDF), and slow continuous ultrafiltration (SCUF).
• Advantages: CKRT provides precise, slow, and continuous fluid and solute removal, which is exceptionally well-tolerated in patients with hemodynamic instability, sepsis, elevated intracranial pressure, or multiorgan failure. Regional citrate anticoagulation can be utilized to minimize systemic bleeding risks.
• Disadvantages: It requires central venous access, necessitates continuous intensive care nursing, limits patient mobility, and involves highly expensive equipment.
• Hybrid Therapies: Sustained low-efficiency dialysis (SLED) or prolonged intermittent renal replacement therapy (PIRRT) provides treatments over 6-12 hours using traditional HD machines with lowered blood and dialysate flow rates, combining the hemodynamic tolerability of CKRT with the feasibility and reduced cost of IHD.

Comparison of Dialysis Modalities

Kidney Transplantation

• Kidney transplantation is the definitive and desired form of KRT for children with ESKD.
• Transplantation offers significant survival advantages, decreases hospitalization risks, and vastly improves health-related quality of life compared to chronic dialysis. It is the only modality that allows for near-normal catch-up growth and optimal neurocognitive development.
• Pre-emptive transplantation (performed before the initiation of maintenance dialysis) is highly recommended and associated with superior long-term allograft and patient survival.
• The allograft can be sourced from a living-related donor (which offers superior long-term survival) or a deceased donor.
• Pre-transplant Evaluation: Requires comprehensive multidisciplinary assessment including thorough urologic evaluation (to rule out bladder dysfunction requiring augmentation or diversion), cardiovascular screening, evaluation of viral serostatus (CMV, EBV), and comprehensive genetic testing to assess the risk of primary disease recurrence.
• Immunosuppression: Successful transplantation demands lifelong maintenance immunosuppression.
  • Induction therapy utilizes biologic agents (e.g., T-cell depleting rabbit anti-thymocyte globulin or IL-2 receptor antagonists like basiliximab) to prevent early acute rejection.
  • Maintenance therapy typically consists of a combination regimen including a calcineurin inhibitor (tacrolimus or cyclosporine), an anti-proliferative agent (mycophenolate mofetil), and corticosteroids. Corticosteroid-avoidance or early withdrawal protocols are increasingly utilized to optimize pediatric linear growth.
• Complications:
  • Rejection: Can be hyperacute, acute T-cell-mediated (cellular), or acute antibody-mediated (humoral), requiring prompt diagnosis via protocol or indication allograft biopsy.
  • Infections & Malignancy: Chronic immunosuppression predisposes patients to opportunistic viral infections (CMV, BK polyomavirus, EBV) and post-transplant lymphoproliferative disorders (PTLD).
  • Recurrent Disease: Certain primary renal diseases carry a high risk of recurring in the new allograft, leading to premature graft loss. Notable examples include primary focal segmental glomerulosclerosis (FSGS), atypical hemolytic uremic syndrome (aHUS), membranoproliferative glomerulonephritis (MPGN), and primary hyperoxaluria. Recurrent FSGS is treated aggressively with plasma exchange, rituximab, and high-dose calcineurin inhibitors.