Effective measures for the secondary prevention of chronic renal failure include reducing progression, treating complication, and renal replacement therapy(RRT).

• Protective therapy most effective if initiated early, before Creatinine > 1.5-2.0 mg/dL
  • Treat Hypertension
    • Systemic hypertension–elevated intraglomerular pressure +/or glom hypertrophy.
    • Blood Pressure (BP) control shown in multiple trials to slow progression of renal disease.
    • Goal Blood pressure < 130/80-85; < 125/75 in patients with proteinuria > 1-2 g/d.
    • ACE inhibitors (ACEI) and Angiotensin II receptor blockers (ARB) preferred 1st line agents due to reno-protective effects.^[1]
    • Additional agents as needed, including diuretics if volume overload.
  • Restrict Dietary Protein
    • Controversial – may decrease intraglomerular pressure.
    • Conflicting studies – some show benefit, others do not.
    • No significant adverse effects shown in large trial.
    • Recommendations
      • No restriction (> 0.8 g/kg/d) if GFR 25-55 mL/min.
      • Limit protein to 0.8 g/kg/d if progression or uremic symptoms.
      • Limit to 0.6 g/kg/d if severe renal insufficiency (GFR 13-25 mL/min).
    • Close follow-up by dietician given risk of malnutrition in this population.
  • Control Blood sugar:
    • Tight control (HbA1c < 7.0, [[Fasting blood sugar 70-120) reduces progression in DM I.
    • Unclear if as beneficial in DM II, but potentially helpful.

• Volume Overload
  • Impaired excretion of sodium and water due to decreased GFR +/- AII/aldo activation.
  • Restrict dietary sodium to 1-2 g/d if hypertension or edema.
  • Diuretics
    • Thiazides ineffective if GFR < 25 mL/min (~Creatinine > 2-3).
    • Switch to Loop diuretic as Creatinine rises; may need bid dosing.
    • Addition of thiazide to Loop diuretic can–additional Diuresis.
    • Watch for excessive volume depletion
• Hyperkalemia
  • Potassium usually maintained until GFR < 15-20 mL/min.
  • Increased risk of hyperkalemia with Oliguria, high potassium diet, (ACE inhibitors therapy).
  • Increased risk with many meds: ACEI, NSAIDs, Potassium-sparing diuretics, digoxin, TMP.
  • Increased risk in diabetics with type IV RTA
• Management
  • Low potassium diet (< 60 mEq/d) once GFR < 15 mL/min.
  • Avoidance of salt substitutes (may contain potassium salts).
  • +/- loop diuretic
  • Low dose Kayexelate (5 g with meals) if needed.
• Calcium/phosphate Abnormalities
  • Reduced renal synthesis Calcitriol/Vitamin D–low serum Calcium– Secondary hyperparathyroidism.
  • (Occurs when GFR < 40 mL/min)
  • Reduced GFR–phosphate retention
  • Elevated parathyroid hormone (PTH)–mobilization of Calcium from bone; increased excretion phosphate.
  • Allows maintenance of normal Calcium/phosphate while GFR > 30 mL/min.
  • Causes renal osteodystrophy
  • Once GFR < 25-30 mL/min, hyperphosphatemia occurs
  • Therapy goals = normalize Calcium/Phosphate and maintain parathyroid hormone (PTH)< 200 (2-3x uln).
    • Calcium/Phosphate management should be initiated when Creatinine ~ 2.
    • Calcium x phosphate product should be < 60 to prevent met calcification.
    • Low phosphate diet: < 800 mg/d (challenging)
    • Calcium-based oral phosphate binders: Calcium acetate or Calcium carbonate with meals.
    • Avoid Aluminium-based phosphate binders except for acute therapy of high Calcium x Phosphate products.
      • (Aluminium toxicity = osteomalacia, anemia, encephalopathy)
    • Avoid Calcium citrate (increases gastrointestinal absorption of aluminum)
      • RenaGel = new non-Calcium/Aluminium-containing phosphate binder (cationic polymer).
        • (For patients who cannot tolerate Calcium carbonate or need additional agent)
      • Calcitriol 0.125-0.25 mg/d improves Calcium & Parathyroid hormone levels, decreases bone disease.
        • (Monitor Calcium–reduce dose if hypercalcemic)
• Metabolic Acidosis
  • Occurs when GFR < 25 mL/min due to inability to excrete H+ ions.
  • Underlying cause = impaired renal ammonia production and bicarbonate reabsorption.
  • Risk = bone buffering of acidosis–worsened Osteodystrophy via Calcium/phosphate loss.
  • Increased skeletal muscle breakdown–loss of lean body mass.
  • Therapy goal = bicarbonate > 22 mEq/L via alkali therapy (NaHCO3 0.5-1 mEq/kg/d)
• Anemia
  • Normocytic normochromic anemia due to reduced Erythropoietin production.
  • May be exacerbated by reduced RBC survival, coexistent iron/folate deficiency, etc.
  • Generally occurs when Creatinine > 2-3 mg/dL.
  • If untreated, hematocrit (Hct) usually stabilizes at ~ 25.
  • Therapy recommendations = Erythropoietin if symptomatic anemia or Hemoglobin < 10 g/dL (in pre-dialysis patients).
  • Goal Hematocrit 33-36
  • Must replete iron stores first (oral ferrous sulfate)
  • Initial dose ~ 150 U/kg sc weekly to increase Hematocrit.
  • Maintenance dose ~ 75 U/kg weekly once Hematocrit goal reached.
  • Improves symtoms and may reduce left ventricle (LV) mass (via improvemt of hyperdynamic state).
  • Side effects = increased blood pressure (BP); may need to augment Antihypertensive regimen.

• Indications for Dialysis
  • Malnutrition
  • Creatinine clearance 10-15 mL/min
  • acidosis not responsive to medical therapy
  • Volume overload / CHF
  • Uremic pericarditis
  • Uremic encephalopathy
  • Intractable muscle cramps
  • Anorexia and nausea not attributable to reversible causes such as peptic ulcer disease
  • Protein energy malnutrition
  • Hyperkalemia
  • Extracellular fluid volume overload

Recent studies have shown no benefits of initiating early dialysis with improved patient survival. ^[2]However, advanced preparation for dialysis can help avoid complications like poorly functioning fistula for hemodialysis or malfunctioning peritoneal dialysis catheter, sepsis, bleeding and thrombosis.

• RRT modalities
  • Hemodialysis
  • Peritoneal dialysis
  • Renal transplant
• Access for hemodialysis should be established when GFR < 25 mL/min (estimated Chronic renal failure within 1 year).
• Diabetics tend to require dialysis sooner than non-diabetics because more symptomatic at given GFR.
• Indications for referral to nephrologist
  • Unclear etiology of new or chronic renal insufficiency
• For diagnostic evaluation, e.g. biopsy
• GFR < 50 mL/min: i.e. before vascular access/RRT required