Pathophysiological consequences of chronic renal failure

 This chapter tries to satisfy the requirements of Section H1(viii) from the 2017 CICM Primary Syllabus, which expects the exam candidate to "describe the physiological effects of renal dysfunction". It has been asked about in Question 19 from the second paper of 2012, as well as Question 1 from the first Fellowship Exam paper of 2011. The First Part exam question specifically asked about "the changes that occur in the plasma with renal dysfunction". The college comments for this question were characteristically brief and unenlightening, but at the end did mention that "It was expected that some mention of changes in electrolytes (e.g.Na+, K+, Ca2+), HCO3, PO4, hormones (1, 25 vitamin D, erythropoietin), proteins, etc. be included." In short, the question really wanted only biochemistry. In contrast, the Part Two exam question asked for everything, and the college model answer was so good that the author had no choice but to reproduce it below, with minimal modification.

Biochemical changes associated with renal failure, in brief summary, are: 

• Volume changes
  • There is less capacity to reabsorb water 
    • In polyuric phase of ATN, this produces an uncontrolled diuresis
  • Glomerular filtration decreases with chronic renal damage
    • In chronic renal failure, this results in decreased capacity to eliminate water  ("fluid overload")
  • Renal responsiveness to vasopressin and aldosterone decreases
    • The ability to regulate body fluid volume and osmolality is decreased or absent
• Electrolyte changes
  • Hyponatremia can develop as the result of impaired water elimination
  • Hyperkalemia can develop (not enough distal tubular secretion)
  • Hyperphosphataemia develops due to the failure to eliminate phosphate
  • Hypocalcemia can develop initially in response to this
  • Hypercalcemia can develop as a compensatory phenomenon (secondary and tertiary hyperparathyroidism)
• Osmotically active solutes
  • Urea increases, as its clearance is decreased (decreased GFR and fewer nephrons overall)
  • Organic acids and various waste polypeptides are retained because their active secretion mechanisms have failed
• Oncotically active solutes
  • Renal failure can be associated with nephrotic syndrome, which results in the loss of oncotically active protein from the blood stream
• Changes in blood pH
  • Bicarbonate reabsorption capacity becomes less flexible
    • Thus, no further renal compensation for respiratory acid-base disturbances is possible
  • Renal acidification mechanisms are impaired, and thus:
    • Renal compensation for metabolic acidosis (by increased ammonium excretion) is impaired
    • Renal elimination of titratable acids is decreased
  • The net results of this are:
    • A normal anion gap metabolic acidosis (due to the failure of renal acidification mechanisms)
    • A high anion gap metabolic acidosis (due to accumulation of non-volatile acids) 
• Changes associated with renal endocrine function
  • Anaemia due to decreased erythropoietin synthesis
  • Hypocalcemia due to decreased calcitriol (Vitamin D) conversion
  • Thrombocytopenia due to decreased thrombopoietin synthesis
  • Indirect neuroendocrine changes resulting from renal failure include:
    • Renin release, due to decreased renal salt delivery, with the resulting activation of RAAS and increased fluid retention/hypertension
    • The RAAS is thought to play a pathophysiologic role in the progression of chronic renal failure

The best reference for this actually ended up being Wills (1968), which is as ancient as the bedrock, but still relevant for the same reason that kidneys themselves are still relevant (i.e that they and their failure have not changed markedly in the last hundred thousand years).

Overall, the physiological changes associated with renal failure could be summarised as follows:

To this, one might add a note regarding nutrition. A normal or slightly increased daily protein intake may be required to compensate for amino acid losses into the circuit, and for the hypercatabolic state of critical illness. In contrast, intermittent haemodialysis patients tend to benefit from low protein and low sodium diet so as to decrease their urea load.

LITFL take this answer, and build wonderfully upon it. Specifically, they quote an editorial by Szamosfalvi and Yee (2013), which is the single most useful published resource on this topic.

Issues specific to ESRD raised in this article include:

• The central veins draining the access arm with the fistula should be protected from venous
  catheters
• Diet should be potassium- and phosphate-restricted
• An AV fistula should not be accessed for CRRT or SLEDD, because the sessions are long and the risk of needle dislodgement and lifethreatening haemorrhage is thus greatly increased.
• In terms of small solute clearance, there is no need to change the dose of dialysis in critically ill ESRD patients when compared to their regular maintenance dose.
• Hypotonic and hypertonic fluids should be avoided

The all-cause in-ICU mortality of ESRD patients admitted to ICU seems to be over double that of patients without renal failure (11% vs 5%), though it is lower than the mortality of patients with acute renal failure (23%).