Renal replacement therapy

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renal replacement therapy modalities hemodialysis hemofiltration CRRT diagram

A clinical photograph of a human forearm showing the setup for hemodialysis or continuous venovenous hemofiltration (CVVH). Two large-bore (15-gauge) cannulas are inserted into an arteriovenous (AV) fistula. The tubing is filled with blood, appearing as dark red columns within the translucent flexible plastic. The catheters are secured to the limb using a systematic arrangement of white rectangular gauze pads and medical adhesive tape. One visible connector features a clear Luer lock housing with a blue-coded hub. The tubes run parallel to each other across the arm before looping towards the dialysis machine. This procedural image demonstrates vascular access management and stabilization techniques used in renal replacement therapy. The orientation shows a typical clinical setting for a patient undergoing high-flow extracorporeal blood purification.

This composite educational graphic details a preclinical experimental model for renal replacement therapy using Sprague-Dawley rats. Section A presents a comparative diagram of the Extracorporeal Circulation (ECC) group versus the Hemodialysis (HD) group. The ECC circuit (red lines) involves a carotid-to-femoral shunt driven by an ECC pump. The HD group adds a semipermeable membrane and a counter-current dialysate circuit (green lines) driven by a secondary pump. Section B provides an expanded schematic of the hemodialysis circuit, detailing specific parameters: 2% isoflurane anesthesia, blood flow (Qb) at 1 ml/min, dialysate flow (Qd) at 5 ml/min, and temperature regulation via heater and water bath (36.5°C). Real-time monitoring of Arterial Blood Pressure (ABP) and Glomerular Filtration Rate (GFR) is indicated. Section C includes clinical photographs of the surgical vascular access sites, illustrating the catheterization of the carotid artery for arterial blood output and the femoral vein for return, along with a femoral arterial pressure catheter. This material demonstrates the technical setup for studying renal pathophysiology and dialytic efficacy in a rodent model.

$A multi-panel medical infographic illustrating the relationship between fracture anatomical sites and kidney replacement therapy (KRT) modalities: Hemodialysis (HD), Kidney Transplant (KT), and Peritoneal Dialysis (PD). The central element is a color-coded human skeletal diagram highlighting seven anatomical regions: skull, upper limb, rib/sternum, vertebra, pelvis, hip, and lower limb. The left panel features horizontal stacked bar charts showing the proportion (%) of each KRT modality within specific fracture cohorts, demonstrating that HD patients consistently comprise the vast majority (approx. 88-95%) of patients at every fracture site. The right panel displays clustered horizontal bar graphs showing the frequency (%) of fractures at each site stratified by modality. This data indicates that the HD group has the highest fracture frequency across all sites compared to PD and KT, with the upper and lower limbs being the most frequent sites of injury. This comparison chart serves as a clinical epidemiology resource for understanding bone mineral disorders and fracture risk in end-stage kidney disease (ESKD) populations.$

A multi-panel medical infographic illustrating the relationship between fracture anatomical sites and kidney replacement therapy (KRT) modalities: Hemodialysis (HD), Kidney Transplant (KT), and Peritoneal Dialysis (PD). The central element is a color-coded human skeletal diagram highlighting seven anatomical regions: skull, upper limb, rib/sternum, vertebra, pelvis, hip, and lower limb. The left panel features horizontal stacked bar charts showing the proportion (%) of each KRT modality within specific fracture cohorts, demonstrating that HD patients consistently comprise the vast majority (approx. 88-95%) of patients at every fracture site. The right panel displays clustered horizontal bar graphs showing the frequency (%) of fractures at each site stratified by modality. This data indicates that the HD group has the highest fracture frequency across all sites compared to PD and KT, with the upper and lower limbs being the most frequent sites of injury. This comparison chart serves as a clinical epidemiology resource for understanding bone mineral disorders and fracture risk in end-stage kidney disease (ESKD) populations.

<table><thead><tr><td></td><td>35. or/1-34 36. exp Renal Replacement Therapy/ 37. (hemodialysis or haemodialysis).tw. 38. (hemofiltration or haemofiltration).tw. 39. (hemodiafiltration or haemodiafiltration).tw. 40. dialysis.tw. 41. (PD or CAPD or CCPD or APD).tw. 42. Kidney Disease/ 43. Chronic Kidney Disease/ 44. Kidney Failure/ 45. Chronic Kidney Failure/ 46. Uremia/ 47. (chronic kidney or chronic renal).tw. 48. (CKF or CKD or CRF or CRD).tw. 49. (end-stage renal or end-stage kidney or endstage renal or endstage kidney).tw. 50. (ESRF or ESKF or ESRD or ESKD).tw. 51. ur?emi$.tw. 52. exp Kidney Transplantation/ 53. or/36-52 54. and/35,53</td></tr></thead><tbody><tr><td>Systematic review topic</td><td>Smoking cessation in patients with CKD and diabetes</td></tr><tr><td>Search strategy – Cochrane Kidney and Transplant Specialised Registry</td><td>Search October 2018 - 2473 studies retrieved; 6 studies relevant to smoking cessation. The February 2020 Search update - 1 study retrieved; not relevant to smoking cessation. The December 2021 search updated retrieved no relevant studies.</td></tr><tr><td>Systematic review topic</td><td>Bariatric surgery in patients with CKD and diabetes</td></tr><tr><td>Search strategy – Cochrane Kidney and Transplant Specialised Registry</td><td>Search October 2018 – 2473 studies retrieved; no relevant studies identified; The February 2020 search update - 4 studies retrieved; no studies included. The December 2021 search update identified 3 relevant records of 1 included study.</td></tr><tr><td>Systematic review topic</td><td>Weight loss interventions in patients with CKD and diabetes</td></tr><tr><td>Search strategy – Cochrane Kidney and Transplant Specialised Registry</td><td>Search October 2018 – 2473 studies retrieved; 155 relevant studies, no studies included. The February 2020 search – 4 studies retrieved; no studies included. The December 2021 search identified 12 relevant records of 10 studies.</td></tr><tr><td>Guideline chapter</td><td>Glycemic monitoring and targets in patients with diabetes and CKD</td></tr><tr><td>Systematic review topic</td><td>Management according to alternative biomarkers</td></tr><tr><td>Search strategy – Cochrane Kidney and Transplant Specialised Registry</td><td>Search October 2018 – 2473 studies retrieved; 21 relevant studies identified. The updated February 2020 – 4 studies retrieved; all studies were excluded; The December 2021 update identified no relevant records</td></tr><tr><td>Systematic review topic</td><td>Management according glucose monitoring (continuous interstitial glucose monitoring (CGM), self-monitoring blood glucose (SMBG)</td></tr><tr><td>Search strategy – Cochrane Kidney and Transplant Specialised Registry</td><td>Search October 2018 – 2473 studies retrieved; 21 relevant studies identified. Updated Search February 2020 – 37 records retrieved; - 0 relevant studies identified; The December 2021 search update identified 1 record of 1 relevant study</td></tr><tr><td>Systematic review topic</td><td>Glycemic targets in patients with CKD</td></tr><tr><td>Search strategy - CENTRAL</td><td>1. MeSH descriptor Diabetes Mellitus, Type 1, this term only 2. MeSH descriptor Diabetes Mellitus, Type 2, this term only 3. MeSH descriptor Diabetes Mellitus, this term only 4. MeSH descriptor Diabetic Nephropathies, this term only 5. ((diabetic or diabetes) and (kidney* or renal or nephritis or glomerulo* or nephropath*)):ti,ab,kw in Clinical Trials 6. (IDDM or NIDDM):ti,ab,kw in Clinical Trials 7. (#1 OR #2 OR #3 OR #4 OR #5 OR #6) 8. MeSH descriptor Insulin explode all trees 9. MeSH descriptor Hypoglycemic Agents explode all trees 10. MeSH descriptor Thiazolidinediones, this term only 11. MeSH descriptor Sulfonylurea Compounds explode all trees 12. MeSH descriptor Dipeptidyl-Peptidase IV Inhibitors, this term only 13. MeSH descriptor Glucagon-Like Peptide 1, this term only 14. MeSH descriptor Sodium-Glucose Transporter 2, this term only 15. (metformin*):ti,ab,kw or (Rosiglitazone*):ti,ab,kw or (Rivoglitazone*):ti,ab,kw or (Pioglitazone*):ti,ab,kw or (Troglitazone*):ti,ab,kw in Clinical Trials</td></tr></tbody></table>

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Renal Replacement Therapy (RRT)

Definition and Overview

Renal replacement therapy (RRT) refers to extracorporeal techniques that temporarily replace some of the usual renal functions - principally salt, water, and solute clearance. The term "renal support therapy" (RST) is sometimes preferred because these modalities do not replicate all renal dynamics (e.g., hormonal functions). In the chronic setting, RRT includes hemodialysis, peritoneal dialysis, and renal transplantation. For acute kidney injury (AKI), these are collectively called kidney replacement therapy (KRT).

Up to 60% of ICU patients experience AKI; short-term mortality among those who require RRT exceeds 50% (Brenner & Rector's The Kidney).

Mechanisms of Solute Clearance

Mechanism	Principle	Best For
Diffusion	Concentration gradient across a semipermeable membrane	Small molecules (<1 kDa): urea, creatinine, K⁺
Convection	Hydrostatic pressure-driven ultrafiltration (solvent drag)	Water and medium-large molecules up to 50 kDa; fluid overload
Combined	Hemodiafiltration uses both mechanisms	Broad-spectrum clearance

RRT Modalities

1. Intermittent Hemodialysis (IHD)

Diffusive clearance; blood and dialysate flow in opposite directions (countercurrent)
Typically 4-6 hours per session, 3-6 days/week
Increases solute clearance by increasing blood flow rate or dialysate flow rate
Best for hemodynamically stable patients
Subtypes: IHD, isolated ultrafiltration (IUF), daily IHD, extended-duration IHD

2. Continuous RRT (CRRT)

Runs 24 hours/day; best tolerated by hemodynamically unstable patients on vasopressors
CRRT dose: Effluent flow targeted at 25 mL/kg/hour in critically ill AKI (Brenner & Rector)
Venovenous approaches dominate (arteriovenous approaches abandoned due to bleeding risk):
- CVVH - continuous venovenous hemofiltration (convection only)
- CVVHD - continuous venovenous hemodialysis (diffusion only)
- CVVHDF - continuous venovenous hemodiafiltration (both)
- SCUF - slow continuous ultrafiltration (volume removal only)
Preferred in: acute liver failure (reduces risk of cerebral edema/herniation), hemodynamic instability

3. Hybrid / Prolonged Intermittent RRT (PIRRT)

Middle ground between IHD and CRRT
Also called SLED (sustained low-efficiency daily dialysis) or SLEDD
Typically runs 6-18 hours/day, every other day or daily
More gradual volume/solute shifts than IHD; better hemodynamic tolerance
When prescribed daily, closely resembles CRRT in clearance profile

4. Peritoneal Dialysis (PD)

Catheter placed intraperitoneally; dextrose-containing fluid drives osmotic clearance
Risk of peritonitis
Not suitable for recent abdominal surgery; less effective in hypermetabolic critical illness
Important in low- and middle-income countries (LMICs) where other modalities are unavailable
Subtypes: CAPD (continuous ambulatory), CCPD (continuous cycling), APD (automated PD)

Indications for Initiating RRT

Classic / Emergency Indications (AEIOU mnemonic)

Indication	Notes
Acidosis	Severe metabolic acidosis (pH <7.15-7.25) refractory to medical management
Electrolyte disturbance	Hyperkalemia refractory to conservative therapy
Ingestion / overdose	Drug overdose of dialyzable toxins
Overload (fluid)	Refractory pulmonary edema, volume overload unresponsive to diuretics
Uremia	Uremic symptoms (pericarditis, encephalopathy, bleeding); BUN typically >100-140 mg/dL

The AKIKI-2 trial showed delaying RRT until a mandatory indication (acidosis, hyperkalemia, pulmonary edema) or BUN >140 mg/dL was associated with increased mortality (HR 1.60, 95% CI 1.09-2.50), underscoring that waiting too long is harmful (Miller's Anesthesia, 10e).

Timing: Early vs. Late Initiation

This is one of the most debated areas in critical care nephrology:

Early initiation (Stage 2 AKI): One single-center cardiac surgery trial found lower mortality (39.3% vs 54.7%) and higher renal recovery at 90 days with early RRT, but 90% of delayed patients also received RRT eventually, and the difference in time was only 21 hours - so results should be interpreted with caution.
Multiple large RCTs (including IDEAL-ICU, AKIKI, STARRT-AKI trials) found no mortality benefit to early vs. delayed RRT. Importantly, in the IDEAL-ICU trial, 29% of patients in the delayed arm recovered and never needed RRT - highlighting the danger of over-initiating.
Current guidance: Initiate promptly when absolute indications exist; do NOT delay until a mandatory life-threatening indication; do NOT preemptively start RRT in AKI patients who may spontaneously recover.

Choice of Modality

Clinical Situation	Preferred Modality
Hemodynamically stable	IHD or PIRRT/SLED
Hemodynamically unstable (on vasopressors)	CRRT
Acute liver failure	CRRT (reduces cerebral edema risk)
Recent abdominal surgery	IHD or CRRT (avoid PD)
LMIC settings with limited resources	Peritoneal dialysis
Volume removal only	SCUF

No large RCT has demonstrated superiority of any single modality regarding mortality or renal recovery (Current Surgical Therapy, 14e; Miller's Anesthesia).

Anticoagulation in CRRT

Anticoagulation is needed to prevent filter clotting:

Regional citrate anticoagulation (RCA) - preferred; citrate chelates ionized calcium in the circuit; calcium is replaced post-filter systemically
Systemic heparin - effective but increases bleeding risk; relevant concern in postoperative patients
Regional heparin with protamine reversal - alternative but less used
RCTs comparing citrate vs. heparin show citrate has at least equivalent efficacy with fewer bleeding complications

Intensity / Dose of RRT

Higher ultrafiltration doses in CRRT studies (e.g., ATN trial at 20 vs 35 mL/kg/hr; RENAL trial at 25 vs 40 mL/kg/hr) showed no mortality benefit with higher intensity
Target: Effluent flow of 25 mL/kg/hour for CRRT in ICU patients
Increased dose has even shown some untoward effects in some trials
Prescribed dose is often not the delivered dose - circuit downtime means actual delivered dose is lower

Vascular Access

Double-lumen, large-bore central venous catheter (dialysis catheter / Mahurkar / Vascath)
Preferred sites: right internal jugular > femoral > left internal jugular > subclavian
Subclavian avoided when possible due to risk of subclavian vein stenosis (compromises future AV fistula)
For chronic HD: arteriovenous fistula (AVF) is preferred over AV graft or tunneled catheter

Drug Dosing in RRT

Drug clearance is altered by RRT - careful review is mandatory:

Small, water-soluble, low-protein-bound drugs are most cleared by dialysis
Vancomycin, aminoglycosides, many antibiotics require dose adjustment
Lipid-soluble, highly protein-bound drugs (e.g., most benzodiazepines) are poorly dialyzed
Dosing must be tailored to the specific RRT modality in use (IHD vs CRRT have very different clearance profiles)

RRT in Chronic Kidney Disease / ESRD

Dialysis generally initiated when GFR <10 mL/min (earlier in diabetics if volume-dependent hypertension or hyperkalemia is uncontrollable)
80% of ESRD patients receive dialysis; ~5:1 ratio of hemodialysis to peritoneal dialysis (Goldman-Cecil Medicine)
~25% of renal transplants in the US are performed in diabetic patients
Transplantation is the preferred long-term modality - superior survival vs. all dialysis modalities:
- 5-year survival: 96% (transplant) vs. 83% (PD) vs. 81% (HD) - Brenner & Rector
- Transplanted children have adjusted relative risk of death = 0.26 vs. those remaining on dialysis

Complications of Chronic Dialysis

Complication	Notes
Cardiovascular disease	Most common cause of death in dialysis patients
Dialysis-related amyloidosis	β₂-microglobulin deposition; carpal tunnel, joint pain
Arteriovenous access failure	Thrombosis, stenosis, infection
Intradialytic hypotension	Rapid fluid/solute shifts; risk of prolonging AKI
Peritonitis (PD)	Major complication; gram-positive organisms most common
Hyperphosphatemia / renal osteodystrophy	Secondary hyperparathyroidism
Anemia	EPO deficiency; treated with erythropoiesis-stimulating agents

Outcomes After AKI Requiring RRT

AKI mortality averages ~23%; Medicare 90-day mortality post-discharge reaches 35% for AKI patients
Most common cause of death is cardiovascular
Risk of CKD progression, renal malignancy, hypertension, and stroke all increased
Recovery defined: early (<7 days post-AKI), late (7-90 days); failure to recover at 90 days = CKD
All AKI patients should have rapid post-discharge nephrology follow-up (Current Surgical Therapy, 14e)

Key References:

Brenner and Rector's The Kidney, 2-Volume Set - ICU RRT chapter
Current Surgical Therapy, 14e - Renal Support Therapy
Miller's Anesthesia, 10e - Perioperative RRT
Goldman-Cecil Medicine - Diabetic nephropathy and ESRD management
Harrison's Principles of Internal Medicine, 22e - Renal indications in critical illness

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