12.1 Acute Kidney Injury & Renal Replacement Therapy

12.1 Acute Kidney Injury & Renal Replacement Therapy

Clinical Core: Acute kidney injury (AKI) is a hypercatabolic, pro-inflammatory syndrome characterized by the acute accumulation of nitrogenous waste, fluid overload, and profound electrolyte derangements. Nutrition support must never prioritize blood urea nitrogen (BUN) control over patient protein status. Severe protein restriction ($< 0.6\text{ g/kg/day}$) is obsolete and dangerous in acute illness. Protein prescriptions must match the specific renal replacement modality, scaling from $1.2\text{ to } 1.5\text{ g/kg/day}$ in intermittent hemodialysis up to $2.5\text{ g/kg/day}$ in continuous renal replacement therapy (CRRT) to offset substantial effluent amino acid washout. Furthermore, clinicians must quantify non-nutritional energy from regional citrate anticoagulation ($3.0\text{ kcal/g}$) and dialysate glucose absorption to avoid iatrogenic overfeeding.

Metabolic Alterations & Catabolism in Acute Kidney Injury

Acute kidney injury (AKI) rarely presents as an isolated organ failure in clinical practice; it most commonly emerges in the setting of sepsis, major trauma, cardiopulmonary bypass, or multi-organ dysfunction syndrome (MODS). The metabolic milieu of AKI is distinct from chronic kidney disease (CKD):

1. Profound Proteolysis & Hypercatabolism: Systemic inflammation, metabolic acidosis, insulin resistance, and counter-regulatory hormones (cortisol, glucagon, epinephrine) accelerate skeletal muscle proteolysis. Muscle protein breakdown outpaces protein synthesis, generating excessive circulating amino acids that undergo hepatic deamination into urea.
2. Uremic Toxicity & Insulin Resistance: Elevated circulating uremic toxins impair peripheral glucose uptake, blunt insulin receptor signaling, and disrupt intracellular carbohydrate metabolism. Concurrently, renal gluconeogenesis (which normally accounts for 20% to 40% of endogenous glucose production) is impaired, and renal clearance of exogenous or endogenous insulin is decreased, predisposing patients to unpredictable glycemic swings.
3. Altered Lipid Homeostasis: Impaired renal clearance and downregulation of peripheral lipoprotein lipase reduce triglyceride hydrolysis, resulting in delayed clearance of intravenous lipid emulsions and hypertriglyceridemia.
4. Acid-Base and Solute Disequilibrium: Loss of nephron mass eliminates the primary route for non-volatile acid excretion (titratable acid and ammonium), leading to systemic metabolic acidosis. Metabolic acidosis directly activates the ubiquitin-proteasome pathway and branched-chain ketoacid dehydrogenase, further driving muscle breakdown.

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Nutritional Prescriptions Across Renal Modalities

Nutritional requirements in renal disease are dictated primarily by the degree of metabolic stress and the modality of renal replacement therapy (RRT), rather than by serum BUN or creatinine alone.

+-----------------------------------------------------------------------------------------+
|                        RENAL REPLACEMENT MODALITY & PROTEIN SPECTRUM                    |
+-----------------------------------------------------------------------------------------+
| Modality             | Clinical State           | Protein Target      | Fluid Allowance |
| -------------------- | ------------------------ | ------------------- | --------------- |
| Non-dialyzed AKI     | Non-catabolic / Resolving| 0.8 - 1.0 g/kg/day  | Output + 500 mL |
| Non-dialyzed AKI     | Catabolic / Critical Care| 1.2 - 1.5 g/kg/day  | Strict balance  |
| Intermittent HD (IHD)| Intermittent Dialysis    | 1.2 - 1.5 g/kg/day  | Strict (<1 L/d) |
| CRRT (CVVH/D/HDF)    | Critical Illness / Sepsis| 1.5 - 2.5 g/kg/day  | Liberal / None  |
+-----------------------------------------------------------------------------------------+

1. Conservative Management: Non-Dialyzed AKI

• Obsolescence of Low-Protein Diets: Historically, clinicians prescribed low-protein or very-low-protein diets ($0.4\text{ to } 0.6\text{ g/kg/day}$), such as the Giordano-Giovannetti regimen, to delay the initiation of dialysis by suppressing urea generation. In acute critical illness, this practice is obsolete and strictly contraindicated. Protein restriction fails to prevent dialytic intervention, accelerates negative nitrogen balance (losses often reach $-15\text{ to } -25\text{ g/day}$ of nitrogen, representing $100\text{ to } 150\text{ g/day}$ of net lean muscle tissue loss), and significantly increases hospital mortality.
• Modern Protein Targets:
  • Non-catabolic AKI: $0.8\text{ to } 1.0\text{ g/kg/day}$ (e.g., prerenal azotemia or resolving toxic nephropathy without systemic inflammation).
  • Catabolic / Critically Ill AKI: $1.2\text{ to } 1.5\text{ g/kg/day}$. If uremia, hyperkalemia, or volume overload worsens under this regimen, renal replacement therapy should be initiated promptly rather than restricting dietary substrate.
• Energy Requirements: $25\text{ to } 30\text{ kcal/kg/day}$ of actual dry weight or ideal body weight, or measured by indirect calorimetry.
• Electrolytes & Fluid: Potassium, phosphorus, and magnesium must be tailored strictly to serum concentrations and residual urine output. In oliguric patients ($< 400\text{ mL/day}$), strict restriction of potassium ($< 2000\text{ mg/day}$ or $< 1\text{ mEq/kg/day}$) and phosphorus ($< 800\text{ to } 1000\text{ mg/day}$) is required. In the post-oliguric diuretic phase, excessive urinary electrolyte dumping may mandate aggressive replacement.

2. Intermittent Hemodialysis (IHD)

• Modality Profile: Hemodialysis utilizes high countercurrent dialysate flow rates ($500\text{ to } 800\text{ mL/min}$) across a dialyzer membrane for brief durations ($3\text{ to } 4\text{ hours}$), typically 3 to 4 times per week. Diffusion is the primary mechanism of solute clearance.
• Nutrient Clearance: During each 3- to 4-hour hemodialysis treatment, approximately $10\text{ to } 12\text{ g}$ of free amino acids are washed out across the dialyzer membrane into the dialysate effluent. In addition, hemodialysis triggers a transient systemic inflammatory response and transiently increases whole-body proteolysis.
• Protein Prescription: $1.2\text{ to } 1.5\text{ g/kg/day}$ to maintain neutral nitrogen balance and replace treatment-related amino acid losses.
• Interdialytic Fluid & Volume Balance: Because IHD is intermittent, patients accumulate fluid between sessions. Interdialytic weight gain (IDWG) should not exceed $4\%\text{ to } 5\%$ of estimated dry weight (or $< 1.5\text{ to } 2.0\text{ kg}$). Fluid intake is strictly limited to residual 24-hour urine output plus $500\text{ to } 1000\text{ mL}$ for insensible losses. Concentrated enteral formulas ($1.5\text{ to } 2.0\text{ kcal/mL}$) with low electrolyte profiles are standard.

3. Continuous Renal Replacement Therapy (CRRT)

• Modality Profiles: CRRT encompasses continuous veno-venous hemofiltration (CVVH, convective clearance), continuous veno-venous hemodialysis (CVVHD, diffusive clearance), and continuous veno-venous hemodiafiltration (CVVHDF, combined convective and diffusive clearance). Modern intensive care units utilize effluent flow rates of $20\text{ to } 35\text{ mL/kg/hr}$.
• Effluent Amino Acid Clearance: Because CRRT operates continuously 24 hours a day with highly permeable synthetic membranes, small-molecule solutes pass freely. Free amino acids have low molecular weights ($75\text{ to } 204\text{ Da}$) and do not bind significantly to albumin; thus, their sieving coefficient ($S$) approaches $1.0$. Daily amino acid losses into the CRRT effluent range from $10\text{ to } 15\text{ g/day}$, and can exceed $20\text{ g/day}$ during high-volume hemofiltration or severe systemic inflammation. This represents roughly $10\%\text{ to } 15\%$ of the total daily protein intake.
• Protein Targets in CRRT: $1.5\text{ to } 2.5\text{ g/kg/day}$. Nitrogen balance studies indicate that critically ill patients on CRRT require at least $1.5\text{ to } 1.8\text{ g/kg/day}$ merely to prevent severe negative nitrogen balance, while severely hypercatabolic, septic, or trauma patients may require up to $2.0\text{ to } 2.5\text{ g/kg/day}$.
• Fluid & Electrolyte Liberation: Because CRRT provides continuous, hourly ultrafiltration control, it eliminates volume restriction. Clinicians can infuse full-volume nutrition support, medications, and blood products without risking pulmonary edema. Furthermore, CRRT vigorously removes phosphorus, potassium, and magnesium. Hypophosphatemia occurs in $30\%\text{ to } 50\%$ of CRRT patients unless phosphorus is aggressively supplemented enterally, parenterally, or added directly to replacement fluids.

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Non-Nutritional Caloric Contributions in CRRT

A critical competency tested in clinical practice is the identification and mathematical deduction of non-nutritional caloric intake generated by CRRT circuits. Failure to calculate these substrates leads directly to overfeeding, severe azotemia, hepatic steatosis, and respiratory failure.

+-------------------------------------------------------------------------+
|                  NON-NUTRITIONAL CALORIES IN THE CRRT CIRCUIT           |
+-------------------------------------------------------------------------+
| Substrate Source       | Metabolic Fate           | Caloric Equivalent  |
| ---------------------- | ------------------------ | ------------------- |
| Trisodium Citrate      | Krebs (Citric Acid) Cycle| 3.0 kcal per gram   |
| (Anticoagulation)      | Cleared by liver/muscle  | (0.59 kcal per mmol)|
| ---------------------- | ------------------------ | ------------------- |
| Dextrose Dialysate /   | Systemic uptake via      | 3.4 kcal per gram   |
| Replacement Solutions  | concentration gradient   | monohydrate glucose |
+-------------------------------------------------------------------------+

1. Regional Citrate Anticoagulation (RCA)

To prevent circuit clotting without the systemic bleeding risks of heparin, regional citrate anticoagulation is the preferred standard of care in CRRT:

• Mechanism: Trisodium citrate is infused pre-filter into the arterial line of the circuit. Citrate chelates ionized calcium ($Ca^{2+}$), dropping circuit ionized calcium below $0.35\text{ mmol/L}$, which completely arrests calcium-dependent steps of the coagulation cascade. A post-filter systemic infusion of calcium chloride or calcium gluconate restores physiological systemic ionized calcium ($1.1\text{ to } 1.3\text{ mmol/L}$).
• Systemic Metabolism: Approximately $40\%\text{ to } 60\%$ of the infused citrate-calcium complex is removed across the dialyzer/hemofilter into the effluent. The remaining $40\%\text{ to } 60\%$ enters the patient's systemic circulation, where each molecule of citrate is metabolized in the mitochondria of hepatocytes, renal tubular cells, and skeletal muscle via the citric acid (Krebs) cycle.
• Caloric Value: Oxidation of citrate produces sodium bicarbonate and generates energy:

$\text{Citrate Energy Yield} = 3.0\text{ kcal per gram} \quad (\text{equivalent to } 0.59\text{ kcal per mmol})$

• Clinical Caloric Load: Depending on blood flow rate, hematocrit, and effluent clearance, systemic citrate delivery typically supplies $200\text{ to } 800\text{ kcal/day}$. In high-dose regional anticoagulation protocols, citrate intake may exceed $1000\text{ kcal/day}$.

2. Dextrose Absorption from Dialysate & Replacement Fluids

Commercial CRRT fluids (dialysate and replacement fluids) often contain glucose at concentrations ranging from $100\text{ to } 110\text{ mg/dL}$ ($5.5\text{ to } 6.1\text{ mmol/L}$), and some specialized peritoneal or dialysate fluids contain substantially higher concentrations:

• When the dialysate glucose concentration exceeds the patient's blood glucose concentration, glucose diffuses down its concentration gradient across the membrane into the blood.
• Net daily glucose absorption from CRRT dialysate/replacement solutions typically ranges from $100\text{ to } 500\text{ kcal/day}$.

Mathematical Deduction Protocol

To avoid hypercapnia and hyperglycemia, clinicians must adjust the nutrition regimen:

$\text{Prescribed Nutrition Calories} = \text{Total Target Energy Expenditure} - (\text{Citrate kcal} + \text{Dialysate Glucose kcal} + \text{Propofol/Dextrose Med kcal})$

If a patient's total energy target is $1800\text{ kcal/day}$, and they are receiving $450\text{ kcal/day}$ from citrate anticoagulation and $150\text{ kcal/day}$ from dialysate glucose absorption, the enteral or parenteral nutrition infusion must be formulated to deliver no more than $1200\text{ kcal/day}$, while maintaining the full prescribed amino acid/protein target ($1.5\text{--}2.5\text{ g/kg/day}$).

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Micronutrient Management in Renal Disease

• Oxalosis Risk with Vitamin C: Ascorbic acid is metabolized to oxalate. In renal impairment, excessive vitamin C supplementation ($> 200\text{ mg/day}$) leads to systemic calcium oxalate crystal deposition in renal tubules, myocardium, and vasculature (secondary systemic oxalosis). Dosing should never exceed $100\text{ to } 200\text{ mg/day}$.
• Hypervitaminosis A Risk: Retinol-binding protein (RBP) is normally catabolized by renal proximal tubular cells. In renal failure, RBP accumulates, raising circulating free retinol to toxic levels. Routine vitamin A supplementation should be minimized or omitted in acute and end-stage renal failure.