B/ 69 Developmental abnormalities and cystic disease of the kidney

Question 1

Developmental abnormalities of the kidney

Answer 1

Complete (bilateral) renal agenesis
Unilateral renal agenesis
Hypoplasia
Ectopic kidney
Horseshoe kidney
Abnormal placement of the ureter

Question 2

Complete (bilateral) renal agenesis

Answer 2

Not compatible with life. Oligohydramnios can develop in the second half of the pregnancy as the amniotic fluid is primarily the fetal urine at this point.
These patients will die from pulmonary hyperplasia because the amniotic fluid is needed for the proper maturation of the fetal lungs.

Question 3

Unilateral renal agenesis

Answer 3

More common than bilateral. Remaining kidney undergoes compensatory hypertrophy - usually this compensation is successful and normal kidney function is assured. May, however develop progressive pulmonary sclerosis.

Question 4

Hypoplasia

Answer 4

Failure of the kidney to develop to normal weight. Decreased number of lobes and calyces. Usually unilateral.

Question 5

Ectopic kidney

Answer 5

Most common abnormal position is the pelvic kidney. Usually retains normal function. Tortuous ureters can lead to predisposition to pyelonephritis.

Question 6

Horseshoe kidney

Answer 6

Common congenital disorder. Fusion of the kidneys, usually at the lower pole. Increased risk for kidney obstruction - due to abnormal placement of the ureter, Kidney infections - associated with the vesicoureteral reflux, Kidney stones - deviant orientation of the kidney combined with slow urine flow.

Question 7

General information of cystic disease of the kidney

Answer 7

Heterogenous group of diseases comprising hereditary, developmental but not hereditary, and acquired disorders.

Important to recognize for several reasons:
Common diagnostic problem for clinicians, radiologist and pathologist.
Some forms are major causes of chronic renal failure.
Are occasionally confused with malignancy.

Question 8

Simple cysts

Answer 8

A fluid containing space on the cortical surface. They have no clinical significance. Can be the result of a scar for in the tubular system which compressed a tubular area - leading to dilation of the distal part and accumulation of urine.

Question 9

Dialysis associated cystic kidney disorder

Answer 9

Occur in patients with end stage kidney disease. Chronic kidney failure leads to medullary or cortical ischemia which will cause fibrosis and compression of one or more tubules - again this leads to dilation of the distal part of the tubular system.
The cysts are present in both the medulla and the cortex and they may bleed, causing hematuria.

Question 10

Autosomal dominant (adult) polycystic kidney disease

Answer 10

Multiple cysts on both kidneys. Can ultimately destroy the intervening parenchyma.

Question 11

Pathogenesis of autosomal dominant polycystic kidney disease

Answer 11

Can be due to inheritance of at least two autosomal dominant genes: PKD1 and PKD2.
PKD1: 85-90% of the cases. Codes for Polycystic-1, which is involved in cell-cell and matrix-cell adhesion. Mutation of the leads to alterations in the epithelial tubular calls and to cyst formation.
PKD2: Encodes Polycystin-2. Polycystin-1 and -2 form a complex, therefor a mutation in either one leads to the formation of the disease.
PKD2 have however a slower progression than PKD1.

Question 12

Morphology of autosomal dominant polycystic kidney disease

Answer 12

At the beginning of the disease there are functional nephrons that contain cysts which may arise at any level of the nephron. As the cysts enlarge they compress the parenchyma leading to ischemic atrophy of the intervening renal parenchyma. in the full-blown cases, the kidneys become very large.

Question 13

Clinical course of autosomal dominant polycystic kidney disease

Answer 13

The disease can be asymptomatic until the 4th decade. After this it commonly presents pain, hematuria, hypertension, urinary infection, saccular aneurysm of the circle of willis (Berry aneurism), asymptomatic liver cysts.
Ultimately a fatal disease.

Question 14

Autosomal recessive (childhood) polycystic kidney disease

Answer 14

Genetically differ from the adult type by having autosomal recessive inheritance. The mutated gene is called PKHD1, which codes for a membrane receptor protein called fibrocystin and is located on chromosome 6. The protein may be involved in the function of cilia in the tubular epithelial cells.

Question 15

Morphology of autosomal recessive polycystic kidney disease

Answer 15

Numerous small cysts in the cortex and the medulla give the kidney a sponge-like appearance. the cysts originate from the collecting tubules.
In almost all cases, the cysts can be found in the liver as well.
These patients may die from either renal or hepatic failure. Those who survive infancy develop liver cirrhosis.

Question 16

Medullary cystic disease

Answer 16

This disease has two major types:
Medullary sponge kidney: a relatively common usually harmless condition.
Nephronophthisis-medullary cystic disease complex: almost always associated with renal dysfunction.

Question 17

Nephronophthisis-medullary cystic disease complex

Answer 17

There are 4 variants of this disease based on the time of onset. infantile, juvenile, adolescent and adult. Juvenile is the most common.
Pathogenesis: at least seven gene loci have been associated with this disease complex.
Morphology: Small contracted kidney, with cysts typically located at the portico-medullary junction.

Question 18

Clinical course of nephronophthisis-medullary cystic disease complex

Answer 18

15-20% of the individuals with the juvenile form have extra renal manifestations, which most often appear as retinal abnormalities.
The initial manifestations are usually polyuria and polydipsia due to diminished tubular function.
There is progression to end stage kidney disease in about 5-10 years.
Difficult disease to diagnose due to there being no serological markers and that the cysts are often too small to be seen in radiography.