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

Congenital malformations of the kidneys?

Most are asymptomatic. May cause early renal failure.

- Agenesis

- Hypoplasia

- Ectopic kidney

- Horseshoe kidney

Agenesis?

Lack of one or both kidneys.

Fetus with bilateral kidney agenesis are often terminated or stillborn.

- Tend to have lung hypoplasia as well as bilateral agenesis

Ectopic kidney?

Located outside of the normal position, most often in the pelvic cavity.

- Have failed to ascend during embryonic life

Horseshoe kidney?

Fusion of lower poles of the kidney.

- Leads to kinking of the ureter which predispose it for infections & dilations of the renal pelvis

Autosomal dominant polycystic kidney disease?

Characterized by multiple expanding cysts that affect both kidneys until the whole parenchyma is destroyed.

Pathogenesis - Autosomal dominant polycystic kidney disease?

Disease is mostly caused by defect in the PDK1-gene, found on chromosome 16, which encodes the Polycystin-1 protein, a cell membrane-associated protein.

Polycystin-1 protein - does what in the cell?

- Cell to extracellular matrix adhesion

- Cell to cell adhesion

- Normal tubular epithelial cell proliferation and differentiation

- Localizes the primary cilia to the tubular cells

What are primary cilia?

- Tiny projections that sense the flow of urine through the tubules

- They are not the same as microvilli, which the proximal tubules also have

What does abnormal polycystin-1 cause?

Abnormality of proliferation of tubular cells

- Cells proliferate and form cysts

- Cysts detach from the tubules

- Fluid enters the cysts & inflammatory process are initiated

= Interstitial fibrosis is initiated

What happens if the AD polycystic kidney disease occured in the PDK2 gene?

Not as common as in PDK-1 gene.

- PDK2 codes for polycystin-2, which is also located in the cilia, and leads to the same consequences.

- These patients has a slower rate of disease progression

Clinical features - AD polycystic kidney disease?

- Large cysts throughout the kidney

- Up to 3-4cm

- Filled w/ fluid, no parenchyma within

- Enormous kidneys, weigh up to 4kg

What happens to the rest of the body in ADPKD?

It is a systemic disease

- Cysts will form in other organs, like pancreas, spleen and aneurysm in circle of Willi

- Cysts in the liver tend to be small in this disease, and has little clinical impact

Prognosis of AD polycystic kidney disease?

Asymptomatic until 40-50 years old.

- Develop chronic renal failure

- Abdominal pain, hematuria, hypertension and UTI.

- Cysts can rupture/become infected and form abscesses

Treatment ADPKD?

- Dialysis

- Kidney transplantation

These are treatment needed to survive

Autosomal recessive (childhood) polycystic kidney disease?

- Much rarer than ADPKD, as it is a recessive disease

- Most infants die within first year of life, due to kidney and liver failure w/ ARPKD

Pathogenesis - ARPKD?

Mutations in the PKHD1 gene, which encodes the protein fibrocystin.

- Fibrocystin is a membrane receptor, also found in the cilia of the tubular cells

Morphology - ARPKD?

- Small cysts (1-2mm)

- Located in cortex and medulla, giving kidney a "spongy" look

- Cysts arise from collecting duct

Diagnosing ARPKD?

Is very difficult, as the cysts are very small and the surface of the kidney is smooth.

- There are so many cysts that there is almost no normal parenchyme

What is ARPKD associated with?

- Hepatic cysts

- Congenital hepatic fibrosis

- Portal hypertension

Prognosis ARPKD?

- Infants often die soon after birth, due to kidney and liver failure

- About 30% of affected new-borns die within a week

Multicystic dysplastic kidney?

- Congenital disease

- Presence of multiple cysts of varying size and are separated by abnormal parenchyme

- Usually unilateral

- Forms an abdominal mass that looks like a tumor

Medullary sponge kidney?

Congenital disorder characterized by the accumulation of calcium within abnormally dilated collecting ducts located within the medulla

Simple solitary kidney cysts found during autopsy?

- Not uncommon

- Usually found in cortex, 1-5cm

- Filled w/ clear fluid

- Usually no clinical significance

- Can cause hemorrhage/pain

- May resemble tumor on imaging

Dialysis-related cysts?

May appear in kidneys of patients with end-stage renal failure w/ prolonged dialysis.

- Bleeding & hematuria may occur

- The cysts can progress into cancer

Azotemia?

Elevation of blood urea nitrogen (BUN) & creatinine levels, due to decreased GFR

- Is reversible, if renal function returns to normal and the causative agent is treated.

Reasons for azotemia?

- Prerenal: due to decreased perfusion of the kidney

- Renal: damage to the parenchyma

- Postrenal: due to obstruction of the passage of urine

Uraemia?

When there is azotaemia and other biochemical, metabolic and endocrinological alterations.

- Consequence of chronic renal failure

- Is irreversible

Nephritic syndrome?

Gross hematuria due to damage to the glomeruli.

- RBCs are dysmorphic and not regular

- Proteinuria may also occur

What is nephritic syndrome often a sequel of?

Acute post-streptococcal glomerulonephritis

Most frequent cause of death from kidney disease?

Due to chronic renal failure

- 4 stages exist, depending on the GFR

1. GFR around 50% - decreased renal function

2. GFR around 50-20% - Renal insufficiency

3. GFR around 20-5% - Renal failure

4. GFR <5% - End-stage kidney disease