Fernando L. Soldano, Antonio Molina Rojas and Gustavo Lavenia

Chronic kidney failure is the result of irreversible loss of functioning nephrons. The natural history of many nephropathies produces a situation of progressive chronic renal failure (CRF), which usually evolves in variable periods of time, on average, not less than 10 years, to end-stage chronic renal failure (ESRD). Therapeutic measures such as, intake of a diet appropriate to the degree of metabolic alteration present in each evolutionary stage of the disease and the use of medications (hypotensive, antiproteinuric drugs, lipid-lowering drugs), delay the progression of the disease and allow addressing the replacement techniques of kidney function, later and in the best possible conditions.

Not all kidney disease has the same rate of progression to end-stage failure. Glomerular nephropathies usually evolve with a progressive, practically linear, deterioration of renal function, but the times in which the final stages are reached are very different, depending on the type of glomerulonephritis in question. In general, interstitial nephropathies have a slower evolution. Of the hereditary kidney diseases, the most common is polycystic kidney disease. The same after a time, sometimes prolonged, of preservation of renal function, it begins to decline with a course little modifiable. Conversely,

Evolutionary stages of CRI:

Chronic kidney failure presents four evolutionary stages, which logically requires that the therapeutic measures be very different at all times.

When the glomerular filtration rate is greater than 50% of normal ( Stage I ), the patient has lost an important part of his functional reserve, maintains biochemical normality and does not present symptoms of renal failure; The symptoms in this first stage correspond to that of the diseases that cause kidney damage, which are very different from each other and the treatment must be appropriate for each one.

In Stage II , with glomerular filtration rates lower than 50%, precisely at the moment when the most commonly used markers to detect kidney failure (creatinine and blood urea) begin to rise, the first clinical symptoms of kidney failure appear. (polyuria and anemia) and it is time to establish conservative treatment, diet and medication management, investigate if there is any deficit that explains the anemia and start the prevention of the osteodystrophy that CRF produces in more advanced stages.

In Stage III there are usually biochemical manifestations, although they may be nuanced by a correct treatment recommended in the previous phase, and patients usually have symptoms directly attributable to the deficit of the multiple functions, purifying and endocrine, that the kidney performs.

In Stage IV , with renal function below 10% of normal, the symptoms are marked, conservative measures, even taken to their extreme extremes, are not enough and substitute therapies for renal function (dialysis or transplantation) should be indicated. .

Clinic of the patient with CRF (signs and symptoms)

Mineral and water metabolism: in the evolution of the stages, the ability to concentrate initially and dilute the urine in the final phase is lost, altering the adaptive homeostatic mechanisms. Therefore, when faced with excessive salt intake, sodium is retained, aggravating Arterial Hypertension with edema and signs of heart failure. Serum urea levels rise, giving digestive symptoms (nausea, vomiting) that can cause volume depletion, aggravating symptoms. The clearance of Free Water is lost in parallel with the fall of glomerular filtration. In advanced stages, a load of 2 to 3 liters can produce hyponatremia due to dilution and symptoms of water intoxication (neurological signs such as confusion, drowsiness, seizures and coma) that may improve with the correction of the metabolic disorder. Potassium,

Its level can increase before this value, under the following conditions:

A-increased catabolism and acidosis,

B-by intercurrent processes (hypoaldosteronism),

C-contributions (diet, potassium salts of penicillin, transfusions),

D-drugs (potassium-sparing diuretics, ACE inhibitors and ARBs, antiprostaglandins).

Clinically its slight elevation, usually presents weakness, drowsiness and fatigue, in severe pictures flaccid paralysis, Respiratory Insufficiency due to alteration of respiratory muscles, arrhythmias and even cardiac arrest due to Ventricular Fibrillation.

Hydrogen Ion : below 50 ml of GFR, its excretion decreases in direct relation to glomerular filtration. However, for acidemia to occur, the filtration is usually less than 20 ml / min. The first compensatory mechanism is the reabsorption of CO3H, generating more ammonium and buffer substances in the form of phosphate. When acidosis finally occurs, it is because 10 to 20 mEq of hydrogen ions are retained daily due to deficient or insufficient ammonium production. Take into account that, in children, it results in skeletal alterations due to the use of calcium phosphates in the bone, as a buffer.

Calcium, Phosphorus and Magnesium : altered in CRF, with a defect in the elimination of phosphorus and magnesium and in the intestinal absorption of calcium. Hypocalcemia occurs because the kidney cannot hydroxylate 25-hydroxycholecalciferol to 1.25-hydroxycholecalciferol. Phosphates and magnesium are retained when the filtrate drops more than 25 ml / min. Calcium malabsorption produces hypocalcemia that is added to hyperphosphatemia to stimulate the synthesis of parathyroid hormone (PTH), the latter is further exaggerated, due to the deficiency of active vitamin D that makes the skeleton resistant to the hormone. Secondary hyperparathyroidism leads to osteitis fibrosa cystica, hyperphosphatemia, soft tissue calcifications, and osteosclerosis; and vitamin D deficiency to osteomalacia.

Cardiovascular system : Hypertension due to hydrosaline retention is the most observed alteration, associated with retinopathy and ventricular hypertrophy (LVH). The myocardial dysfunction suffered by these patients is due not only to high blood pressure, but also to electrolyte disorders, uremia, and the hyperdynamic load caused by anemia. The arteriosclerotic complications are frequent (coronary and cerebral), it can also be found pericarditis with mild heart failure, or with pericardial effusion and tamponade.

 Gastrointestinal system : the most frequent clinical findings are detailed in the following table.

 Neurological Disorders :

Patients with advanced renal failure very frequently present neurological disorders that affect the central and / or peripheral nervous system and that can manifest with very different clinical pictures.

Peripheral nervous system involvement:

Uremic polyneuropathy: it is characterized by being distal, symmetric and with mixed involvement (sensory and motor); sensory symptoms often precede motor symptoms.

Physical examination may demonstrate loss of reflexes, the achilles more early than the patellar, loss of sensation in the form of "media" and pain to touch, vibrations or pressure. It is an axonal degeneration that leads to segmental demyelination. The etiology of uremic polyneuropathy is not fully understood. The most sensitive test for diagnosis is the electrophysiological study ELECTOMIOGRAPHY (EMG).

Uremic mononeuropathy: The high incidence of polyneuropathies in advanced renal failure predisposes to the development of mononeuropathies, being typical the involvement of the median nerve, carpal tunnel syndrome and other affectations.

Central nervous system involvement:

The central nervous system (CNS) can be affected by factors similar to those that occur in other types of patients without kidney failure and by causes properly related to their uremic pathology. Given the lowering of the seizure threshold in this type of patient, almost all the noxas that affect the CNS can cause seizures.

Uremic encephalopathy is dependent on the degree and speed of the onset of renal failure, the symptoms can vary from irritability and confusion to seizures, coma and death. Anorexia, nausea, insomnia, restlessness, decreased attention, tremor, and asterixis are usually the earliest symptoms. Symptoms usually go away easily, within days or weeks, after starting dialysis.

Metabolic and Endocrine System: the alterations found are a product of the high circulating levels of polypeptide hormones, a consequence of their increased synthesis (due to tissue resistance to their effects) and of less renal degradation. Insulin resistance and lower renal catabolism raise circulating levels of this hormone, despite this there is an alteration in the cellular uptake of glucose. Diabetic glucose tolerance curve is found, insulin resistance decreases TGC clearance and increases hepatic VLDL synthesis. They commonly present with sexual dysfunction due to anxiety, depression and alteration of the hypothalamic-gonadal axis. They may have hyperprolactinemia with gynecomastia in men and galactorrhea in women. Patients are euthyroid, however,

Blood: CKD in advanced stages, present anemia (normocytic-normochromic), caused by a) decrease in erythropoietin synthesis B) decrease in the half-life of erythrocytes c) tendency to hemorrhage due to platelet factor III deficiency, added with a slow and constant consumption of clotting factors, there is also a decrease in factor XIII and an increase in factor Von-Willebrand. The effect on platelets causes petechiae and visceral hemorrhages.

In summary, significant damage to the renal parenchyma causes a deficit in erythropoietin production and, although the sensor mechanism for hypoxia in cells responsible for erythropoietin synthesis is apparently intact, levels of this hormone are well below the needs to maintain a normal erythropoiesis.

Study methodology

Detection : Much of this information comes from a very good medical history, anamnesis and physical examination, the degree of CRI is determined by the Creatinine Clearance or an equivalent determination (Cocroft formula or MDRD).

Diagnosis of the syndrome: A good clinical tolerance to high urea and creatinine values ​​suggests chronicity, but the most reliable data is to know the previous biochemical values. It is important to determine the decrease in kidney size or renal atrophy by ultrasound, to primarily verify the existence of two kidneys, measure them and rule out urinary obstruction (hydronephrosis). However, in some causes such as Diabetes (DBT), amyloidosis and polycystic kidney disease, patients have normal or enlarged kidneys. It is important to clarify that normal kidney size is directly related to the body surface area, and if they are affected by some pathologies, as stated above. If they are small (below 9 cm, according to body surface) they indicate chronicity and irreversibility,

The Echo-Doppler is useful in experienced hands, as the first diagnostic step of unilateral or bilateral renal artery stenosis. Confirmatory studies, such as arteriography (performed with non-ionic contrasts, to avoid toxicity) or the current gold-standard, angioresonance or CO2 angiography, which obviate contrast toxicity, are necessary. In the latter case, as it is an invasive arterial procedure, it increases the risk of atheroembolic disease in patients with peripheral arterial disease. In general, the etiology is clinically evident, renal biopsy is rarely useful in the end stage, and in an atrophic kidney it will not provide clear data. If it is done only in early stages, it can be done, but its indication should be evaluated according to risk-benefit.