Chronic Renal Failure

Definition

• Clinical laboratory syndrome, results from progressive and irreversible destruction of nephrons due to a chronic nephropathy
• Slow onset – months to years
• Incidence – 1000/1 million

Etiology

• CPN, CGN, ADPKD
• Nephropathy caused by DM (developed countries), amyloid, gout, lupus, multiple myeloma
• Essential HTN
• Balkan endemic nephropathy
• Obstructive nephropathy

Pathogenesis

• Irrespective of cause, the eventual impact is severe loss of nephron mass
  • Alteration in function of every organ system
• Structural and functional hypertrophy of surviving nephrons
  • Due to adaptive hyperfiltration, ↑glomerular capillary P
  • Eventually predisposes to sclerosis
• Symptoms of CRF when reduction of nephron mass > 75%

Mechanism of nephron alteration

• Direct lesions – in inflam and vascular diseases
• Indirect, mechanical lesions – ↑cavity pressure in chronic obstructive NPs
• Immunologic lesions – immune complexes in glomeruli and TIS
• Autoimmune

Uremia

• Clinical syn that results from profound loss of renal function
• Named uremia bc it was presumed that abnormalities are due to retention in blood of urea and other end products of metabolism
• Most likely toxins in uremia are by-products of protein and AA metabolism which primarily depend on kidney for excretion
• End products of human metabolism
  • Urea, creatinine
  • End prods of tryptophan, tyrosine, phenylalanine
• Theory for role of uremic toxins
  • Role of homeostatic deviation – J Merrill 1979

Pathophysiology

• Sodium and Water balance
  • Normal plasma osmolality – 275-290 mOsm/L (requires equal water loss + intake)
  • Water loss – urine (1.5L/24h) stool (100ml) skin (500ml)
  • CRF leads to high intracellular Na conc and thus water → overhydration of cells
  • Edema and HTN – restrict fluid intake
• Potassium – Pts are normo/hyperkalemic bc metabolic acidosis induces efflux of K⁺ from cells
• Acid base – Daily acid excretion and buffer prod fall below normal, leads to metabolic acidosis

Pathobiochemy

• Disturbed depuration – endointoxication
• Disturbed water balance – dehydration/overhydration
• Disturbed electrolyte balance
  • Hypo/hypernatremia
  • Hyperkalemia
• Disturbances in acid-alkali regulation – metabolic acidosis causes ↑Ca excretion, leading to bone demineralisation _{(see endocrine dysfunction for explanation)}
• Endocrine dysfunction
  • Low erythropoietin – anemia
  • Loss of nephron → low calcitriol → decrease Ca absorption → hypocalcemia → 2^o hyper PTH → osteodystrophy → breakdown of bone

Clinical presentation

• Always has increase in BUN + creatinine
• May also be assoc with reduced urine output
• In early stage of CRF (GFR 30-50%) – overall renal function is sufficient to keep pt asymptomatic
• SKIN
  • Anemia, ecchymoses/hematoma
  • Pruritis + excoriation – due to Ca deposition and 2^o hyperPTH
  • Poor skin turgor, dry mucous membranes – dehydration
  • Uremic frost – white powder on skin surface
• Metabolic acidosis
  • Profound effects on respiratory, cardiac and nervous system
  • Resp – increase in tidal volume → Kussmaul breathing
• Cardiovascular
  • Congestive HR and/or pulmonary oedema – due to fluid retention and uremia
    • XR – butterfly wing appearance (peripheral vascular congestion)
      • Due to↑ permeability of alveolar cap membrane
  • Pericarditis – due to retained metabolic toxins in uremia
• Hypertension – MC sx of end stage renal failure
  • Only not found if pt has salt-wasting form or is receiving anti-HTN
• GI Syndrome
  • Anorexia, hiccups, N, V – early manifestations of uremia
  • Mucosal ulcerations, peptic ulcer
• Uremic Encephalopathy
  • Inability to concentrate, drowsiness, insomnia
  • Memory loss, cramps, myoclonus, seizures, coma
• Peripheral Neuropathy – Restless leg syndrome
• Endocrine-metabolic disturbances – Renal osteodystrophy – osteomalacia, osteitis, CF
• Normochromic, normocytic anemia

Classification

Diagnosis

• Implies that GFR is known to have been reduced for at least 3-6 months
• Proof of chronicity – bilateral reduction of kidney size by USS
• Other findings of long standing RF – renal osteodystrophy, or sx of uremia
• Lab anomalies – anemia, hyperphosphatemia, hypocalcemia, proteinura (but nonspecific sx)
• Ddx from acute – reduced size of kidneys in CRF

Lab findings

• ↑U+C
• Low UO – oligo (<400ml/day) anuria (<100ml/day)
• ↑K+ – cardiac and muscle problems
• ↑ phosphate – ectopic calcifications
• Hypocalcemia – NM irritability, spasms, cramp
• Proteinuria, hematuria

Treatment

• Etiological treatment – not useful
• Pathogenetic treatment of the 5 functions of the kidney
  • Fluid intake to match the amount of urine output
  • Restrict dietary Na to manage HTN; also restrict K and phosphate rich foods
  • Low protein – to reduce anorexia, N+V in uremia
• Stimulation of renal function – forced diuresis
  • By salt-water isotonic solution combined with high dose furosemide 100-1000mg/day
    • Aim to increase diuresis to 3000ml/day
• Correction of acidosis-induced hyperkalemia
  • With sodium bicarbonate; IV insulin and dextrose
  • Sodium polystyrene sulfonate – most effective to reduce hyperkalemia
• Hyperuricemia – allopurinol 100mg/day if gout develops
• Metabolic acidosis – 20-30mmol/day of sodium bicarbonate (in pts with stable RF)
• Secondary hyperPTH – phosphate binding agents, calcium supplements, vit D
• Anemia – recombinant human epo
  • Epoietin beta (NeoRecomon), Epoetin alfa (Eprex)
• Extra corporeal
  • Dialysis – to decrease severity of disturbances and uremia
    • Indications
      • Severe hyperhydration with untreatable cardiac failure/HTN
      • Uremic pericarditis
      • Severe uremic intoxication from different organs
      • Serum creat >700μmol/l
      • Creat clearance <15ml/min
      • Severe acidosis – pH<7.1
      • Hyperkalemia >7.5mmol/l
  • Transplant