18. Renal failure, uraemia. Congenital malformations and cystic diseases of the kidney

Page created on March 8, 2019. Last updated on May 5, 2020 at 18:03

Congenital malformations of the kidneys

Most of these malformations are asympomatic. In some cases they may cause early renal failure in infants.

1. Agenesis – lack of one or both kidneys

Foetuses can have bilateral kidney agenesis, but most of these cases are terminated or stillborn. Foetuses with bilateral kidney agenesis tend to have lung hypoplasia as well.

2. Hypoplasia

3. Ectopic kidney

An ectopic kidney is a kidney that have failed to ascend during the embryonic life and remains in the pelvis.

4. Horseshoe kidney

This is honestly the only malformation of the kidney which I still remember from embryology. In most cases the cause is fusion of the lower poles of the kidneys. This malformation also leads to kinking of the ureter which predisposes it for infections and dilatation of the renal pelvis.

Autosomal dominant polycystic kidney disease (AD for adult)

The AD (adult) polycystic kidney disease is characterized by multiple expanding cysts that affect both kidneys until the whole parenchyma is destroyed.

Pathogenesis: The disease is mostly caused by a defect in the PKD1-gene, found on chromosome 16, which encodes the Polycystin-1 protein, a cell membrane-associated protein. This protein does many things, like:

  • Cell to extracellular matrix adhesion
  • Cell to cell adhesion
  • Normal tubular epithelial cell proliferation and differentiation
  • Localizes the primary cilia to the tubular cells
    • Primary cilia are tiny projections that sense the flow of urine through the tubules
    • They’re not the same as microvilli, which the proximal tubules also have

Abnormal polycystin-1 causes abnormality of proliferation and differentiation of tubular cells. These cells proliferate and form cysts which eventually detach from the tubules. The cells secrete fluid into the cyst. An inflammatory response and interstitial fibrosis are initiated.

The mutations may also be in the PKD2 gene, but this is not as common as with PKD1. PKD2 codes for polycystin-2, which is also located in the cilia, and leads to the same consequences. However, patients with mutations in PKD2 have a slower rate of disease progression.

Clinical features: Large cysts occur throughout the kidney. The cysts themselves can be as big as 3-4 cm, filled up with fluid, and no parenchyma can be seen in-between. Patients suffering from this will have enormous kidneys, and they can weight up to 4 kg!

ADPKD is a systemic disease, so cysts will form in other organs as well, like in the pancreas, spleen and as aneurysms in the circle of willis, also known as berry aneurysms. The cysts that occur in the liver in association to this disease are small and have no impact on liver function, unlike in ARPKD.

Prognosis: The patients with ADPKD are asymptomatic until they are 40-50 years old, at which point they develop chronic renal failure. They can experience pain in the abdomen, intermittent gross haematuria, hypertension and urinary infections. Dialysis and kidney transplantation are the treatment needed to survive. The cysts can rupture or become infected and become abscesses.

Autosomal recessive (childhood) polycystic kidney disease

Since it’s recessive it’s much rarer than ADPKD. Most infants with ARPKD die within the first years of life due to kidney and liver failure.

Pathogenesis: This disease results from mutations in the PKHD1 gene which encodes the protein fibrocystin. Fibrocystin is a membrane receptor, also found in the cilia of the tubular epithelial cells.

Morphology: The cysts are very small (1-2 mm) and located in the cortex and the medulla of the kidney, which gives the kidney a “spongy” look. The lining of the cysts reveals that they arise from the collecting tubules. The outer surface of the kidney is smooth. Because the cysts are so small can the condition be hard to diagnose, even with imaging. There are so many cysts that there is almost no normal kidney parenchyme.

ARPKD is also associated with early liver failure due to cysts in the liver.

Prognosis: Infants often die soon after birth due to liver or kidney failure. About 30% of affected new-borns die within one week.

Other causes of kidney cysts

Multicystic dysplastic kidney is a congenital kidney disease. It is characterized by the presence of multiple cysts of varying size that are separated by abnormal parenchyme. It is usually unilateral and forms an abdominal mass that looks like a tumor. It’s most frequently sporadic and not familial.

Medullary sponge kidney is a congenital condition where the collecting tubules are dilated.

Finding simple solitary kidney cysts during autopsy is not uncommon. These cysts are commonly found in the cortex, are 1 – 5 cm in diameter and are filled with clear fluid. They often have no clinical significance, but they may cause haemorrhage or pain. They may also resemble a tumor on imaging.

Dialysis-related cysts may appear in kidneys of patients with end-stage kidney disease who have undergone prolonged dialysis. They may bleed and cause haematuria. The cysts can infrequently progress into cancer.

Clinical manifestations of renal diseases

More about these topics can be studied in pathophysiology 1.

Azotaemia is the condition where there is an elevation of blood urea nitrogen and creatinine levels due to a decreased glomerular filtration rate (GFR). It can be either:

  • Prerenal – due to decreased perfusion of the kidney
  • Renal – due to damage to the parenchyme
  • Postrenal – due to obstruction of the passage of urine

Azotaemia is a reversible condition as renal function always returns to normal when the causative agent is treated.

Uraemia is the condition where there is azotaemia and other biochemical, metabolic and endocrinological alterations. It is a consequence of chronic renal failure, which is irreversible.

Nephritic syndrome is the condition where there is gross haematuria due to damage to the glomeruli. The RBCs are dysmorphic and not regular. Proteinuria may also occur. It’s the classic sequel of acute poststreptococcal glomerulonephritis.

Nephrotic syndrome is the condition where there is gross proteinuria due to damage to the glomeruli. The loss of protein may cause hypoalbuminaemia and oedema.

The most frequent cause of death from kidney disease is due to chronic renal failure. Four stages of chronic renal failure exist, depending on the GFR of the patient:

  • GFR is around 50% of normal – Decreased reserve of renal function
  • GFR is 50 – 20% of normal – Renal insufficiency
  • GFR is 20 – 5% of normal – Renal failure
  • GFR < 5% of normal – End-stage kidney disease

4 thoughts on “18. Renal failure, uraemia. Congenital malformations and cystic diseases of the kidney”

  1. Dear Nick!
    I think you mean microvilli not cilia; since both functions are different and MV are the ones associated with reabsorption!❤️

    1. While you are correct in that I actually thought of the microvilli while writing this topic, it turns out that kidney has both microvilli and primary cilia, and that the gene correctly involves the primary cilia, not the microvilli. I have altered the text to make that more clear. Thanks <3

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