POLYCISTIC KIDNEY: causes, symptoms, treatment

Polycystic kidney

What is Polycystic Kidney

There renal polycystosis (or polycystic kidney disease) is a genetic disorder characterized by the development of kidney cysts. Cysts develop in both kidneys (they are therefore bilateral) and alter their normal anatomical structure, thereby also damaging their function. The progression of the disease leads to chronic kidney disease.

Cysts are rounded, fluid-filled formations; they are formed by an altered proliferation of kidney cells. But let's go in order: the functional unit of the kidney (i.e. the characteristic component that allows it to perform its functions) is the nephron. It begins with a structure called renal corpuscle, in which a "ball" of capillaries (il glomerulus), in which arterial blood flows, comes into contact with a concave structure, the Bowman's capsule.

The blood, passing through the glomerulus, is filtered: waste, water, electrolytes and some proteins pass through the walls of the capillaries in the capsule, like through a sieve. A filtrate is thus formed which will flow along the nephron, passing through i tubules and for the duct collector until it reaches the urinary tract. During its journey, the filtrate will be progressively reworked until it becomes urine. The rearrangement consists in the reabsorption and / or secretion of some substances (sodium, calcium, chlorine, etc.) and water by the constituents of the nephron.

We recall the main functions of the kidney:
Depurative: eliminates all metabolic waste (such as uric acid) in the urine which, if accumulated in the blood, would be toxic;
Endocrine: activates vitamin D3, important for good calcium levels, and erythropoietin, which stimulates the production of red blood cells.
Homeostatic: maintains balance levels of electrolytes (sodium, potassium), water and pH (by regulating bicarbonate levels).

In the polycystic kidneys, the alteration involves the cells of the tubules or collecting ducts; the pre-urine flows in them: increasingly important and liquid-rich dilations will form, which will gradually assume a cystic structure. Over time the cysts increase in number and remove more and more functioning nephrons from the kidney, hindering the kidney function in an increasingly serious way.

Types of renal polycystosis

We distinguish two types of polycystic disease:

Autosomal dominant polycystic kidney or ADPKD

Autosomal dominant polycystic kidney or ADPKD: it is the most frequent form and causes more than 5% of chronic renal failure cases and affects adults. Two types are distinguished based on the mutated gene:

  • Type 1: the mutated gene encodes a protein called Polycystin 1 (on chromosome 16). The average life expectancy is around the age of 50.
  • Guy 2: the gene coding for the Polycystin 2 on chromosome 4. Life expectancy is higher than for type 1, about 75 years.

Both polycystins are components of a protein channel located on the primary eyelash, a characteristic structure of renal tubule cells. This channel, allowing the passage of calcium into the tubular cell, activates molecular mechanisms involved in cell proliferation: physiologically, an increased passage of calcium through the channel activates anti-proliferative mechanisms. In addition, the signal that is transmitted from the calcium input affects the expression of some channels. The consequences of the mutation, therefore, are two:

  1. Altered development of the tubules. Despite the increase in intracellular calcium, anti-proliferative mechanisms are not activated, therefore the cells multiply more than they should. Furthermore, instead of multiplying longitudinally with respect to the tubular lumen, they multiply according to a horizontal axis, creating enlarged structures that will then become cysts in all respects.
  2. The over-expression of chlorine channels impairs the function of the tubule (which, remember, is to reabsorb or release solutes in the pre-urine): too much chlorine will be released in the cyst, which in turn will recall water, causing the cysts to swell.
    Patients with dominant disease have an increased risk of developing brain aneurysms, cardiovascular disease, and (in 30% of cases) secondary cysts in the liver, pancreas, spleen and ovary.

Recessive renal polycystosis (or ARPKD or infant polycystic kidney)

Recessive renal polycystosis (or ARPKD or infant polycystic kidney): it is an autosomal recessive disease, therefore rarer (but also much more serious) than polycystic kidney, since it occurs in the fetus during pregnancy, in newborns, in childhood or youth. The mutated gene is that of fibrocystin, a protein that affects the development of the bile ducts (structures into which the liver pours bile) and collecting ducts (the final component of the nephron). Chronic renal failure ensues in intrauterine life, at birth or in childhood. In the perinatal form, children die a few days or weeks after birth if not subjected to mechanical ventilation (it is associated with pulmonary hypoplasia) and dialysis or transplantation.

Normal and polycystic kidney in comparison

Comparison between a normal kidney on the left and a kidney affected by polycystosis on the right.

Causes of polycystic kidney

The origin of these kidney cysts is typically genetic: the dominant form is more frequent; in fact, a patient affected by this form of polycystosis certainly has other relatives affected by the same disease. The recessive form has a lower incidence, both due to the high percentage of infant mortality and because the gene, being recessive, can be present in healthy carriers without giving an obvious disease.

Polycystic kidney symptoms

What are the main symptoms of polycystic kidney? In the initial stages of the dominant form, the course of the disease is asymptomatic.
The symptoms, when present, are attributable to impaired renal function or rupture (rare) of the cysts. However, this occurs in more advanced stages of the disease.

The most important clinical findings are symptoms such as:

  • Palpable kidney mass: the kidney, being almost completely covered by the rib cage, is usually not perceptible on palpation performed by the doctor during the physical examination; however, the formation of the cysts leads to a progressive and significant increase in the size of the organ, so that it becomes appreciable for clinical evaluation.
  • Lower back pain: the patient feels a pain in the lumbar area due to the rupture of the cysts or the formation of stones (in the latter case, the symptoms will have the characteristics of renal colic);
  • Hematuria: bleeding from cysts is associated with blood in the urine. In the most severe forms (gross hematuria) the urine is red.
  • Progressive renal failure: it is the most serious consequence of the formation of cysts.
  • Oliguria (urine production less than 500 ml): the kidney is no longer able to filter normally the blood passing through the glomerulus, therefore less urine will be produced;
  • Edema: or swelling in the sloping areas (eg feet and ankles). It is due to a progressive water retention.
  • Hypertension (normally, by regulating the levels of sodium and water, the kidney contributes to the control of blood pressure);
  • Electrolyte imbalances: altered levels of calcium expose to bone diseases, such as osteoporosis; a potassium imbalance (hypokalemia or hyperkalaemia) can cause cardiac arrhythmias.
  • Hormonal alterations: Active vitamin D deficiency will affect calcium metabolism and erythropoietin deficiency will cause anemia.

Diagnosis of polycystic kidney

  • Clinical and physical examination: a thorough medical examination can lead to suspicion of polycystosis. The patient will complain of any severe hematuria or lower back pain. Sometimes symptoms and signs of chronic kidney disease may already be present at onset (see above);
  • Laboratory tests for kidney function:
    - Increase in BUN and creatinine;
    - Metabolic acidosis;
    - Hyperkalaemia, hypocalcemia and electrolyte imbalances;
    - Anemia and reduction of vitamin D3;
  • Abdominal ultrasound: it is the first choice test for diagnosis. Easily shows the presence of renal cysts (it is important to remember that the finding of a single cyst in the kidney is not indicative of disease, in fact it is necessary that they are multiple and bilateral);
  • MRI of the abdomen: it is more accurate in assessing the number, location and size of cysts and is mainly used to monitor the progression of the disease.
Polycystic kidneys

Photos of polycystic kidneys obtained after an autopsy of a patient suffering from renal polycystosis.

Polycystic kidney therapy 

As already mentioned, the main complication of the polycystic kidney is the development of chronic kidney disease, therefore, treatment focuses on this complication more than on polycystosis itself.

For the control of renal failure and its complications it is first of all important that the patient has some precautions: the diet must be corrected so that high quantities of potassium are not consumed (very concentrated, for example, in kiwis or bananas), drinks or foods that could alter the delicate electrolyte balance and pH that the insufficient kidney would not be able to correct. Furthermore, the stagnation of urine (caused by the anatomical alterations of the kidney cysts) could predispose to the formation of stones, so the diet must also be controlled to avoid this complication.

From a pharmacological point of view, hypertension, anemia and bone diseases will also be monitored by administering diuretics, erythropoietin and vitamin D supplements. As for polycystosis in particular, despite the extensive research to identify drugs capable of acting on the altered intracellular signal during the disease, little can be done to stop or slow down the formation of cysts.

One drug that is giving some results is the Tolvaptan, which inhibits the action of ADH (a hormone that allows the kidney to reabsorb water). In this case it is used because the ADH activates, among other things, molecular mechanisms that in the polycystic kidney are "hyperactive", that is, the proliferative ones: therefore Tolvaptan partially blocks proliferation.

However, the long-term results are still few and far between, so today the main polycystic kidney therapy is replacement therapy, which can be done through:

Extracorporeal dialysis: it is the most common type of dialysis and requires a strong commitment on the part of the patient, who must go to the hospital at a rate usually three days a week to undergo the dialysis, or the "purification" of the blood that the kidney is no longer able to perform.

Peritoneal dialysis: it is a type of dialysis that uses the peritoneum as a filtering barrier, as it is rich in capillaries suitable for this function. The dialysate, i.e. the solution with which the blood comes into contact to purify itself, is inserted directly into the abdomen, which is then emptied after about 4 hours. In some cases, a system is used that allows the maneuver to be carried out in an automated manner. The treatment lasts only one hour, and can also be carried out during the night: in these cases the impact for the patient is very low.

Undergoing dialysis requires additional therapies to replace the hormonal function of the kidney. In fact, dialysis cannot replace the kidney in its endocrine function, but only in its purifying and homeostatic function. They will therefore be assumed: Vitamin D, phosphate chelators, sometimes football, erythropoietin.

Kidney transplant: it is the best therapy since it replaces the kidney in all its functions without any more commitment on the part of the patient. However, like all transplants, there is a long waiting list and compatibility conditions must be met, which is not always easy. Furthermore, the immunosuppressive therapy following the transplant can have serious contraindications, such as infections. In some cases, there may also be rejection of the transplanted kidney.



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