69. Chronic renal failure. Causes, characteristics and progression

Last updated on May 25, 2019 at 19:19

Chronic renal failure

Chronic renal failure (CRF) is a condition where there is a gradual, unstoppable and progressive loss of nephrons. The loss is irreversible and can’t be cured, however the progression can be slowed. As soon as a significant number of nephrons are lost will the remaining nephrons also take damage, for reasons we will se below. Chronic renal failure is therefore caused by diseases that reduce the number of functioning nephrons, and as soon as that has happened is the ball already rolling and the loss of further nephrons is inevitable.

It can be caused by primary damage to the kidney (in 20% of cases) or due to secondary damage to the kidney due to some other disease (80% of cases).

Primary renal damage:

  • Chronic glomerulonephritis
  • Interstitial nephritis
  • Pyelonephritis
  • Cysts
  • Nephrolithiasis
  • Urinary tract infection
  • Drug side effects

Secondary renal damage due to diseases like:

  • Diabetes mellitus (30% of all cases)
  • Hypertension (20% of all cases)
  • Autoimmune diseases (especially SLE)
  • Heart failure
  • Cirrhosis
  • Gout
  • Hypercalcaemia

Four mechanisms or principles are important in understanding chronic renal failure:

  • The intact nephron principle states that a nephron functions only when all parts of it are morphologically intact. So a nephron does not work if some tubular function or some glomerular function is lost. However, that doesn’t necessarily mean that the function of all morphologically intact neurons is normal.
  • Hyperfiltration is the principle where, in cases where the number of functioning nephrons decreases, will the remaining intact nephrons increase their filtration to compensate (SNGFR increases). This allows continued normal clearance of the plasma. This increased SNGFR isn’t good for the nephrons in the long-term as they’ll sustain damage for it. However the increased SNGFR is necessary to excrete enough urea and creatinine so that they don’t build up in the plasma.
  • The magnification phenomenon has already been discussed, and is basically the same as tubular adaptation. It states that when the number of functional nephrons decreases will the remaining nephrons increase their salt excretion so that the total salt excretion of the kidney is approximately normal, despite the lower number of functioning nephrons.
  • The retention of certain substances cause damaging secondary changes. Recall from topic 64 that when total GFR is decreased can’t the tubules do anything to get rid of urea and creatinine in the blood, because there’s no tubular adaptation. This causes accumulation of uraemic toxins, which damage other stuff.
Phases of chronic renal failure

Chronic renal failure has five phases (starting from zero):

Phase Functioning nephron amount (out of normal 2 million total for both kidneys) GFR (in mL/min) Symptoms
Null phase > 50% > 90 Nothing yet
Phase I 50 – 25% 89 – 60 Azotaemia. SNGFR is so high that hyposthenuric polyuria occurs.
Phase II 30 – 20% 59 – 30 Hyposthenuria is now so severe that the kidneys can’t adapt properly to water or salt excess. Polyuria is now less severe, as there are so few functioning nephrons that even increased SNGFR can’t compensate
Phase III 20 – 5% 29 – 15 Oliguria occurs. Hyposthenuria is even more severe.
Phase IV (End-stage renal failure (ESRF) < 5% < 15 Worse oliguria/anuria. Asthenuria. Dialysis or transplant needed.
Factors that promote the progression of chronic renal failure

Certain factors increase the rate of progression of chronic renal failure (CRF):

Systemic hypertension does this, especially if the mean arterial pressure exceeds the range of autoregulation for the RBF (above 160 mmHg). This increases the GFR, which progressively damage the glomeruli.

Intraglomerular coagulation for any reason progresses CRF. Endothelial damage and hypercoagulable states must therefore be prevented.

Metastatic calcification of the kidney may occur due to the high PTH levels often seen in CRF.

Hyperlipidaemia, especially LDL, can bind to GAGs in the basement membrane and decrease the negative charge, which increases the permeability of the glomerulus which further damages it.

High dietary protein intake does three things:

  • Increases the protein filtration. As more protein is filtered will more protein be reabsorbed in the proximal tubule. When protein reabsorption is increased will sodium reabsorption also be increased. When less sodium reaches the macula densa will tubero-glomerular feedback (TGF) cause increase filtration
  • Increases the intraglomerular pressure due to (presumably?) binding water, which causes the volume of blood that enters the glomeruli to be increased. This enhances coagulation.
  • Increases inflammation, because increased protein filtration activates mesangial cells which produce pro-inflammatory cytokines.
  • Enhances fibrosis. Inflammation of the glomeruli enhances parenchymal fibrosis
Things we can do to slow down the progression of CRF

These things mostly work by inhibiting the processes outlined above:

  • Controlling blood pressure. 130/80 mmHg should be the maximum.
  • Low protein diet
  • Reduction of hyperlipidaemia, by changes diet and use of statins (HMG-CoA reductase inhibitors)
  • Glycaemic control to reduce endothelial injury. HbA1c should be below 8%
  • Smoking cessation
Chronic renal failure’s effect on non-excretory renal functions

When nephrons stop functioning and die will the kidney as a whole be affected. Renal parenchyme will be lost, where most of the non-excretory functions lie.

Renoparenchymal hypertension occurs due to deficiency of the renal depressor system and in the late stages will there also be increased blood volume due to increased sodium retention. This further progresses the renal damage (see above) and also progresses other diseases, like left ventricular failure, ischaemic heart disease and atherosclerosis, which may have been important in causing the CRF in the first place.

Anaemia occurs due to multiple mechanisms. Iron and protein deficiency, lack of EPO production and uraemic toxicity of the bone marrow are important.

Bone deformities occur. The increased phosphate and PTH causes calcium to mobilize from the bones, however the kidney loses calcium faster than it can be reabsorbed from the bones, so serum calcium is low anyway. The vitamin D-producing ability of the kidney is also deficient.

Previous page:
68. Non-excretory kidney functions and their abnormalities

Next page:
70. Metabolic disorders and organ dysfunctions in uraemia

2 thoughts on “69. Chronic renal failure. Causes, characteristics and progression”

    1. I certainly don’t know exactly how hyperkalemia contributes to uraemic encephalopathy, and I’m not sure anyone does. Uraemic encephalopathy is a complex phenomenon, and hyperkalemia alone definitely can’t cause it. You can read more about it in topic 71

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