Congenital and genetic renal pathology

2021-01-26 12:00 AM

In the dialysis and kidney transplant centres of Europe, the US polycystic kidney accounts for 10% of the causes of end-stage chronic kidney failure.

Outline

Congenital and genetic kidney disease usually manifests itself in young people, some of which are very rare. In this group of diseases are often divided:

Kidney cystic diseases and renal dysplasia.

Inherited tubular diseases.

Kidney diseases of metabolic origin.

Inherited glomerular diseases.

Kidney cyst diseases

This is a group of kidney diseases that have in common the existence of cysts in the kidneys. Include:

Polycystic kidney is inherited in a dominant genotype (Adult polycystic kidney).

Genetically recessive polycystic kidney (Children's polycystic nephrology): uncommon, usually detected immediately after birth or before 10 years old. The prognosis is very bad, rarely able to live until adolescence.

Renal medullary cysts: Including dilatation of the anterior tubular aneurysm and complex of medullary follicular diseases

Polycystic kidney in adults

This is the most common type of kidney cystic disease compared to other types.

Epidemiology:

According to P. Barjon, the rate of adult polycystic kidney disease is about 1/1250 of the population.

In the dialysis and kidney transplant centres of Europe, the US polycystic kidney accounts for 10% of the causes of end-stage chronic kidney failure.

In Vietnam, there are not complete statistics, but in general, the frequency is not large compared to other diseases.

Causes and mechanisms of pathogenesis:

The causes and pathogenesis of polycystic kidneys have so far been poorly understood. It should be recalled that during the embryonic period, kidneys are developed through three successive forms: first Pronephros to Mesonephro and finally Metanephros. The formation and completion of this renal urinary apparatus have a certain genetic code.

Fergusson commented that polycystic kidney disease is inherited equally for both men and women according to the dominant kidney genotype. Dalgard studied a pedigree of 284 patients and families who confirmed the genetics of polycystic kidneys.

Authors Frances A Flinter, Frederic L. Loe, and Satish Kathpalial have demonstrated that adult polycystic kidney disease is inherited in most families via alpha globulin genome complexes and phosphoglycerate kinase genes on the short arm. of multiple chromosomes 16. The frequency of gene expression is 100% at the age of 80 years or older, meaning that in people with inherited polycystic kidney inheritance if surviving 80 years or older, the probability of developing polycystic kidney is 100 %. The cause of the genetic disorder is unknown.

The mechanism of cyst formation is still debated. But it is well known that these cysts form from the components of the nephron especially the manifold and the loop of Henle. Two abnormalities that can explain cyst formation are:

There is damage to the basal membrane of the renal tubules, which dilates the tubules.

Tubular hyperplasia leads to partial obstruction of the tubular lumen.

Anatomy of the disease:

Kidney damage is often both sides. The kidneys increase in size gradually, the weight of a polycystic kidney can weigh from 2000 to 4000g. In the kidneys, there are many cysts, large and small unevenly, with diameters from 0.3 to 0.5 cm.

The kidney cysts contain liquid colourless or straw yellow, dark brown, sometimes with blood when there is haemorrhage in the follicle or in the form of thick colloidal fluid.

Additional renal damage may be associated with polycystic kidneys, including polycystic liver (30%), less frequently, follicles in the spleen, ovary, pancreas ... Vascular damage was also recorded in 10 up to 20% of polycystic kidneys include intracranial aneurysm, aortic aneurysm. Cardiac abnormalities may be associated with mitral prolapse in 1/4 cases, mitral regurgitation, tricuspid valve or aortic valve.

Clinical and subclinical:

Although it is a congenital and genetic disease, polycystic kidney in adults is usually detected at the age of 40 and under. Sometimes detected by accident through ultrasound tests.

Clinical:

The disease has no clinical symptoms for a long time. The reasons for patients to see a doctor for polycystic nephropathy may be: kidney cramps, upset stomach, the patient feels a tumour in the abdomen, haematuria, increased blood pressure, sometimes the patient comes first examination but were symptoms of acute or chronic renal failure. Clinical symptoms when the disease is well established include:

Belly enlarged upset stomach.

Pain in the hip, lower back.

Haematuria: when polycystic kidney disease has stones or trauma, superinfection.

Hypertension: seen in 75% of cases.

The large kidney on examination, whose surface is rough, plumped, and large kidneys are often both sides but not proportionate.

There are also unusual clinical signs in combination:

Cyst in the liver: 30%.

Cysts in the spleen, pancreas, ovaries, lungs.

The aortic valve, aortic valve, mitral regurgitation.

Stroke.

Laboratory testing:

Laboratory confirmed the diagnosis:

Kidney ultrasound: is the most effective way to detect polycystic kidney. It is possible to detect cysts less than 0.5cm in diameter. This is a technique that helps to early diagnose polycystic kidney disease.

Computer tomography (CT Scanned): Much more expensive than ultrasound.

Provincial Vascular Contrast Staining (UIV): Can detect enlarged kidney. The calyx is elongated into the "spider leg" shape, sometimes only 1.2 sepals are elongated. The corner of the kidney radio is still sharp when there is chronic inflammation. The big stations were also crowding, narrow and stretched.

Retro peritoneal aspiration scan: Detecting large kidney, uneven kidney face, with many bumpy basal walls. Currently in little use.

Other tests:

Complete blood count: Erythropoietin increased secretion, so anaemia is rarely encountered even in the case of chronic kidney failure.

Urinary protein is usually present but not high.

Urine has red blood cells, white blood cells when complications of haematuria, urinary infection.

Unprepared kidney x-ray: 10% have urinary kidney stones.

Kidney function: Decreased in renal failure.

Diagnosis of polycystic kidney disease in adults:

Situations that lead to a diagnosis:

Location: middle-aged (rarely in the elderly).

Complications of the disease:

Severe lumbar region.

Low back pain.

General haematuria.

Kidney cramping pain.

Cystic infection.

Or discovered by accident:

When examining a system.

When asking about family history.

Occasionally though extrinsic manifestations (eg, liver follicles).

Diagnostic standards:

Diagnosis is based on kidney ultrasound. Kidney ultrasound showed a large kidney on both sides with many cysts on both sides of the kidneys. It should be noted that the sensitivity of the ultrasound to detect cysts depends on the age of the patient with polycystic kidney disease visiting.

According to the author, Ravine recommends diagnostic criteria for polycystic kidneys in the context of a family investigation of a family member with a diagnosis of polycystic kidney.

Table: Diagnosis of polycystic kidney according to Ravine.

Year old

Standard ultrasound

Under 30 years old

At least 2 cysts in the kidney (1 or 2 sides)

From 30 to under 60 years old

At least 2 cysts in each kidney

Over ages 60

At least 4 cysts in each kidney

Differential diagnosis:

Polycystic kidneys in adults are the most common inherited kidney cystic diseases in adults. This disease accounts for about 10% of the causes of end-stage chronic kidney failure in European countries. When making the diagnosis, it is necessary to distinguish from other cystic kidney diseases according to the table below

  

Table: Common kidney cyst diseases.

Kidney cysts

Species

The average age at diagnosis

Age of chronic kidney failure

Frequency

Genetic:

- Polycystic kidney:

+ According to the dominant gene

 + According to recessive genes

Cysts in the renal medullary region

 

 

30-40

0-10

< 30

 

 

> 50

0-10

< 20

 

 

1/1.000

1/40.000

?

Not genetic:

- Single capsule


Kidney sponges

 - Acquired kidney cysts after cyclic dialysis chronic kidney failure

 

Adults


Adults

Dialysis patients

 

No chronic kidney failure

No chronic kidney failure

 

50%

 
?

Cysts in the kidney medulla

Kidney sponges:

Common disease in kidney medullary cyst disease. According to Gardener the ratio could be from

1/500 to 1/2000 population and account for 1/200 patients with urinary tract diseases. In Viet Nam

Nam has not been discovered.

Kidneys are not large, only 30% larger than usual.

The kidney cyst develops by an enlarged tubule and is located in the nipple area or the Malpighi tower region in the kidney medulla. The cyst has both sides but there are also cases with only one. Fluid cyst has a lot of calcium deposition, the most common complications are kidney stones, urinary.

Renal medullary fibrosis:

It is a type of kidney disease with many cysts on both sides, but the kidney is not enlarged but shrinks, scarring. The clinical symptoms are nocturia, urinary retention, thirst, low urine density due to interstitial nephritis. Decreased kidney concentration is the earliest symptom. Hypertension is uncommon. There are cases with red hair, some cases with retinitis pigmentosa. Subclinical symptoms such as haematuria, proteinuria, masturia, leukaemia, bacteriuria are uncommon. When urinary test disorders are repeated repeatedly, it is important to look for causes other than medullary fibrosis.

The kidney cysts in the renal medullary fibrosis are absent from the renal cortex, have bilateral symmetry and develop from the Henle manifold and loop. Cyst is localized only in the kidney, there is no cystic association in other organs. Approximately 50% of cases have recessive genetic expression. There are cases where there is a dominant genotype. Therefore, there are many variations of the renal medullary cystic fibrosis that many authors have titled as the renal medullary cyst complex to refer to this group of diseases.

Other kidney cystic diseases

Single-cystic kidney:

Cysts are located in the renal cortex, a single cyst or multiple single cysts. The cyst protrudes completely in front of the surface of the kidney. The cyst is usually a baby that contains a clear fluid or straw yellow, the composition resembles a glomerular filtrate. The disease is common in the elderly, so it is easy to confuse polycystic kidneys. However, the disease has little clinical manifestations and is usually detected at random by X-ray and ultrasound of the abdomen for other reasons. When needing a differential diagnosis, it is possible to extract renal cystic fluid. Cancer if there are cancer cells in the fluid or blood.

Congenital polycystic kidney disease:

Congenital polycystic nephropathy belongs to the group of kidney dysplasia, cystic kidneys of all ages, is the result of a disorder of the renal mechanism that causes all, part, or multiple foci of one or both kidneys to turn into one the structure does not belong to any stage of renal formation.

Congenital polycystic kidney disease differs from the polycystic kidney in that it is not inherited and is usually only one. The frequency is not large so there is no document. Found in children in the same family. Beside the follicle, there are clusters of normal kidney organs, incomplete differentiated buffer structure, some renal tubules with atypical epithelium, there are niches with fat, cartilage and hematopoietic organization. Diagnosis detection. Diagnosis is confirmed by renal artery scan. The cystic region is not functional.

Regarding treatment, it is necessary to combine kidney cut when there is bleeding injury, recurrent infection. The prognosis in adults is good, with only one side.

Acquired polycystic kidney:

It is a new condition that has been described in recent years and appears mainly in patients receiving dialysis cycles of more than 3 years. The patient had no history of polycystic kidney and was newly emerging on dialysis.

The cyst can rupture causing sudden bleeding. Cancer can be found. The incidence rate during the dialysis process for many days is 30-50%.

Inherited kidney diseases

This is a group of diseases where there exist abnormalities in the renal tubules that reduce the function of the tubular reuptake or secretion. Common in young ages: infants, children. Include:

Abnormalities of phosphate transport in the kidney

Inherited through chromosomes. The main symptoms are rickets or osteomalacia, decreased blood phosphate and hyper phosphaturia, normal blood calcium, normal or decreased urinary calcium.

Abnormalities in amino acid transport

Includes cystinuria and Hartnup disease.

Cystinuria: Characterized by excretion of many amino acids lysine, arginine, ornithine, cystine but renal tubular reabsorption is normal. It is a recessive genetic disease. Of the above amino acids, the only cystin can be in the crystalline form leading to stones.

Harnup disease: is a disease excretion of many amino acids mono-amino mono carboxyl type (mainly phenylalanine and tryptophane). Inherited by recessive genes. May cause damage to the skin Pellagroid form, neurological manifestations (cerebellar ataxia), memory loss.

Abnormalities of glucose transport, diabetes mellitus

Much urinary tract (5 to 100g / day) but no increase in blood sugar. Normal glucose tolerance test. Progression is usually benign. This is a dominant or recessive genetic disease. Tubular damage is complex including a decrease in proximal tubular glucose transport or a decrease in the transport threshold.

Diabetes pale kidney

A characteristic disorder with loss of sensitivity of tubular cells to the effects of arginine vasopressin (endogenous or exogenous). This disorder may be acquired or inherited in association with the X chromosome.

Renal tubular acidosis

A condition where it is impossible to establish a normal gradient (gradient) between blood and urine (acidosis due to distal tubules) or due to loss of bicarbonate (proximal tubular acidosis).

Fanconi syndrome

This is an abnormal set of proximal tubules, involving amino acids, glucose, phosphates, bicarbonate, unique acid, potassium. Symptoms include dwarfism or osteomalacia, or underdevelopment in children, acidosis. Chemistry, lowering blood potassium.

This syndrome can be secondary to metabolic disorders (Cystinosis disease, Galactose, Fructose tolerance disorder, Glycogens, Wilson's disease) or idiopathic and sometimes family.

Inherited glomerular diseases

Alport syndrome

Including inherited glomerulonephritis accompanied by deafness. A genetic disease inherited by the dominant gene, attached to the X chromosome, sometimes related to the sex (more common in men). Accounting for 5% of the causes of end-stage chronic renal failure by haemodialysis in the US. The disease usually occurs at the age of 6 years (70% of cases), with symptoms of major haematuria, recurrence or as solitary proteinuria or nephrotic syndrome (25%). Between 30 and 50% will be accompanied by deafness.

Fabry syndrome

A genetic pathology associated with the X chromosome, due to deficiency of enzyme alpha-galactosidase to the accumulation of neutral glycosphingolipids. Kidney damage is manifested by proteinuria, microscopic haematuria, often leading to end-stage chronic kidney failure at the age of 50.

Treatment

In the framework of this article, only to introduce treatment and prevention of polycystic kidney disease in adults.

Treatment of polycystic kidney

No specific treatment. Mainly treatment of complications and impact on the risk factors if possible.

Surgically, cystic aspiration and polycystic renal resection are only isolated cases.

In the treatment of polycystic kidneys before chronic renal failure, attention should be paid.

Good control of blood pressure:

Bring the patient's blood pressure below or equal to 130/85 mmHg. Most antihypertensive drugs are effective, but three groups of antihypertensive drugs of choice in polycystic kidney disease are ACE inhibitors, diuretics, beta-blockers. As with other kidney diseases, regular kidney function testing is required when using a class of ACE inhibitors.

Anti-dehydration, electrolyte disturbances:

Be careful when appointing diuretics in the polycystic kidney because it can cause dehydration, vascular collapse, loss of sodium, potassium.

If major haematuria is present, it is necessary to find the cause to eliminate the cause.

Management of urinary kidney stones if any.

Timely treatment of urinary infections, this is an important factor in accelerating the process of kidney failure.

Treatment of dyslipidaemia if any.

Complications of polycystic kidneys leading to end-stage chronic renal failure depend on age and risk factors:

Chronic renal failure due to polycystic kidneys is age-dependent.

Table: Age and likelihood of chronic renal failure in polycystic kidney disease.

Year old

Chronic kidney failure

≤ 40 years old

2%

40 <age ≤ 50

20 -25%

50 <age ≤ 65

40%

Age> 65

50 - 70%

The following factors are known as risk factors for chronic renal failure of polycystic kidney disease:

Early diagnosis.

Male.

PKD1 gene.

Hypertension.

Increased kidney size.

When polycystic kidneys have complications with end-stage renal failure. Renal failure treatment has the following notes:

Peritoneal dialysis should be avoided because polycystic kidneys have very large kidneys that make this technique difficult.

When a kidney transplant requires surgery to remove the polycystic kidney before the transplant store because the polycystic kidney can compress the kidney.

Prevention of polycystic kidney disease

Regarding polycystic kidney disease prevention, the most important thing is early detection, with measures to prolong the patient's life because most patients up to the age of 50 have severe renal failure.

For families who have had polycystic kidney disease. Need to examine and do a mass ultrasound for family members including children and adults. Ultrasound can detect polycystic before clinical manifestations. Intentional combination detection of the polycystic liver is needed because 30% of patients have polycystic liver and kidney.

When detecting polycystic kidneys, it is necessary to promptly monitor and treat complications such as hypertension, kidney stones and especially urinary tract infections.

Practising physicians should pay attention when patients come to the examination with symptoms of haematuria, hypertension, multiple red blood cells, large kidneys, kidney failure ... to detect polycystic kidney disease early.