Acute kidney failure

Acute kidney failure

GENERAL CONCEPTS

Definition
Acute Renal Failure (ARF) is defined as the decreased capacity of the kidneys to remove waste nitrogen products, established in hours to days. The disposal of waste products is not the only function of these organs, which also play an essential role in regulating the internal environment, keeping the electrolyte balance and blood volume within very narrow margins. Despite some limitations, the plasma creatinine and urea concentrations provide an efficient and rapid estimation of the glomerular filtration rate, although new markers of renal damage are being investigated. The limits to define and classify acute renal failure are very variable according to several authors since their establishment is totally artificial and arbitrary. Under the acronym RIFLE (Figure 1) , corresponding to the English words Risk, Injury, Failure, Prolonged Loss of Kidney Function, and Irreversible End of Renal Function Has sought to unify the diagnostic criteria. This classification, validated in multiple papers, was developed during the 2nd consensus conference of the Adequate Dialysis Quality Initiative (ADKI) held in Vicenza in 2002 (1,2,3,4,5). Subsequently another classification has been designed: AKIN, but so far its application is less implanted [6] . It obviates the criteria of glomerular filtration loss and only maintains elevation of creatinine and decrease in diuresis. Corresponding to the English words Risk, Injury, Failure, Prolonged Loss of Kidney Function and Irreversible End of Renal Function - End has been tried to unify the diagnostic criteria. This classification, validated in multiple papers, was developed during the 2nd consensus conference of the Adequate Dialysis Quality Initiative (ADKI) held in Vicenza in 2002 (1,2,3,4,5). Subsequently another classification has been designed: AKIN, but so far its application is less implanted [6] . It obviates the criteria of glomerular filtration loss and only maintains elevation of creatinine and decrease in diuresis. Corresponding to the English words Risk, Injury, Failure, Prolonged Loss of Kidney Function and Irreversible End of Renal Function - End has been tried to unify the diagnostic criteria. This classification, validated in multiple papers, was developed during the 2nd consensus conference of the Adequate Dialysis Quality Initiative (ADKI) held in Vicenza in 2002 (1,2,3,4,5). Subsequently another classification has been designed: AKIN, but so far its application is less implanted [6] . It obviates the criteria of glomerular filtration loss and only maintains elevation of creatinine and decrease in diuresis. Prolonged loss of renal function (Loss) and irreversible end of renal function (End) has been tried to unify the diagnostic criteria. This classification, validated in multiple papers, was developed during the 2nd consensus conference of the Adequate Dialysis Quality Initiative (ADKI) held in Vicenza in 2002 (1,2,3,4,5). Subsequently another classification has been designed: AKIN, but so far its application is less implanted [6] . It obviates the criteria of glomerular filtration loss and only maintains elevation of creatinine and decrease in diuresis. Prolonged loss of renal function (Loss) and irreversible end of renal function (End) has been tried to unify the diagnostic criteria. This classification, validated in multiple papers, was developed during the 2nd consensus conference of the Adequate Dialysis Quality Initiative (ADKI) held in Vicenza in 2002 (1,2,3,4,5). Subsequently another classification has been designed: AKIN, but so far its application is less implanted [6] . It obviates the criteria of glomerular filtration loss and only maintains elevation of creatinine and decrease in diuresis. Was developed during the 2nd consensus conference of the Adequate Dialysis Quality Initiative (ADKI) held in Vicenza in 2002 (1,2,3,4,5). Subsequently another classification has been designed: AKIN, but so far its application is less implanted [6] . It obviates the criteria of glomerular filtration loss and only maintains elevation of creatinine and decrease in diuresis. Was developed during the 2nd consensus conference of the Adequate Dialysis Quality Initiative (ADKI) held in Vicenza in 2002 (1,2,3,4,5). Subsequently another classification has been designed: AKIN, but so far its application is less implanted [6] . It obviates the criteria of glomerular filtration loss and only maintains elevation of creatinine and decrease in diuresis.

Acute Renal Failure (ARF) is defined as the decreased capacity of the kidneys to remove waste nitrogen products, established in hours to days. The disposal of waste products is not the only function of these organs, which also play an essential role in regulating the internal environment, keeping the electrolyte balance and blood volume within very narrow margins. Despite some limitations, the plasma creatinine and urea concentrations provide an efficient and rapid estimation of the glomerular filtration rate, although new markers of renal damage are being investigated. The limits to define and classify acute renal failure are very variable according to several authors since its establishment is totally artificial and arbitrary. Under the acronym RIFLE (Figure 1) , corresponding to the English words Risk, Injury, Failure, Prolonged Loss of Kidney Function, and Irreversible End of Renal Function Has sought to unify the diagnostic criteria. This classification, validated in multiple papers, was developed during the 2nd consensus conference of the Adequate Dialysis Quality Initiative (ADKI) held in Vicenza in the year 2.002 [1] [2] [3] [4] [5] . Subsequently another classification has been designed: AKIN, but so far its application is less implanted [6] . It obviates the criteria of glomerular filtration loss and only maintains elevation of creatinine and decrease in diuresis. Corresponding to the English words Risk, Injury, Failure, Prolonged Loss of Kidney Function and Irreversible End of Renal Function - End has been tried to unify the diagnostic criteria. This classification, validated in multiple papers, was developed during the 2nd consensus conference of the Adequate Dialysis Quality Initiative (ADKI) held in Vicenza in the year 2.002 [1] [2] [3] [4] [5] . Subsequently another classification has been designed: AKIN, but so far its application is less implanted [6] . It obviates the criteria of glomerular filtration loss and only maintains elevation of creatinine and decrease in diuresis. Corresponding to the English words Risk, Injury, Failure, Prolonged Loss of Kidney Function and Irreversible End of Renal Function - End has been tried to unify the diagnostic criteria. This classification, validated in multiple papers, was developed during the 2nd consensus conference of the Adequate Dialysis Quality Initiative (ADKI) held in Vicenza in the year 2.002 [1] [2] [3] [4] [5] . Subsequently another classification has been designed: AKIN, but so far its application is less implanted [6] . It obviates the criteria of glomerular filtration loss and only maintains elevation of creatinine and decrease in diuresis. Failure, prolonged loss of renal function (Loss) and irreversible end of renal function- (End) has been tried to unify the diagnostic criteria. This classification, validated in multiple papers, was developed during the 2nd consensus conference of the Adequate Dialysis Quality Initiative (ADKI) held in Vicenza in the year 2.002 [1] [2] [3] [4] [5] . Subsequently another classification has been designed: AKIN, but so far its application is less implanted [6] . It obviates the criteria of glomerular filtration loss and only maintains elevation of creatinine and decrease in diuresis. Failure, prolonged loss of renal function (Loss) and irreversible end of renal function- (End) has been tried to unify the diagnostic criteria. This classification, validated in multiple jobs, was developed during the 2nd consensus conference of the Adequate Dialysis Quality Initiative (ADKI) held in Vicenza in the year 2002 [1] [2] [3] [4] [5] . Subsequently another classification has been designed: AKIN, but so far its application is less implanted [6] . It obviates the criteria of glomerular filtration loss and only maintains elevation of creatinine and decrease in diuresis. Prolonged loss of renal function (Loss) and irreversible end of renal function (End) has been tried to unify the diagnostic criteria. This classification, validated in multiple jobs, was developed during the 2nd consensus conference of the Adequate Dialysis Quality Initiative (ADKI) held in Vicenza in the year 2002 [1] [2] [3] [4] [5] . Subsequently another classification has been designed: AKIN, but so far its application is less implanted [6] . It obviates the criteria of glomerular filtration loss and only maintains elevation of creatinine and decrease in diuresis. Prolonged loss of renal function (Loss) and irreversible end of renal function (End) has been tried to unify the diagnostic criteria. This classification, validated in multiple papers, was developed during the 2nd consensus conference of the Adequate Dialysis Quality Initiative (ADKI) held in Vicenza in the year 2.002 [1] [2] [3] [4] [5] . Subsequently another classification has been designed: AKIN, but so far its implementation is less implanted [6] . It obviates the criteria of glomerular filtration loss and only maintains elevation of creatinine and decrease in diuresis. Was developed during the 2nd consensus conference of the Adequate Dialysis Quality Initiative (ADKI) held in Vicenza in the year 2.002 [1] [2] [3] [4] [5] . Subsequently another classification has been designed: AKIN, but so far its application is less implanted [6] . It obviates the criteria of glomerular filtration loss and only maintains elevation of creatinine and decrease in diuresis. Was developed during the 2nd consensus conference of the Adequate Dialysis Quality Initiative (ADKI) held in Vicenza in the year 2.002 [1] [2] [3] [4] [5] . Subsequently another classification has been designed: AKIN, but so far its application is less implanted [6] . It obviates the criteria of glomerular filtration loss and only maintains elevation of creatinine and decrease in diuresis.

Oliguria and anuria

The normal volume of diuresis moves in a wide range depending on the needs of the organism to regulate blood volume and plasma osmolality primarily. When we urinate less than 400 mL / day we speak of oliguria and an amount less than 100 mL / day is known as anuria.

Pathophysiology / Classification

Pre-renal ARF
In certain clinical situations in which renal perfusion is compromised, there is a pathophysiological response mediated by hormonal reactions and nerve stimuli, which conditions the decrease of urine flow and the elimination of chlorine and sodium by the kidneys. This urine, however, is more concentrated in waste solutes (urea, creatinine, phosphates, ammonium) so it has a high osmolality. The daily need to get rid of solutes that represent approximately 800 milliosmoles is achieved by eliminating very concentrated urine (up to 1,200 mOsm / kg) or very diluted (up to 100 mOsm / kg), depending on whether you want to save water (the hypothalamic osmostat will have triggered the secretion Of vasopressin, which will open channels of water, aquaporin-2,

It is for this reason that if the volume of urine falls below 500 mL in 24 hours, although the kidney functions correctly and concentrates to the maximum of its capacity, it will not be able to eliminate all the substances of waste and will produce a retention of nitrogen products (azotemia ). In this case, we will talk about acute or pre-renal acute renal failure, because the kidney response is developed for compensatory purposes and when the cause is reversed, it returns to normal. Usually, this type of renal failure is associated with oliguria, usually defined as the daily elimination of less than 400 mL of urine (200 mL in 12 hours) or, in a probed patient, less than 20 mL per hour. 

Renal or Intrinsic IRA

However, if the cause that causes renal hypoperfusion is prolonged or very severe, it can trigger hypoxic and oxidative damage in renal tubular cells, with loss of polarity, necrosis and cellular apoptosis, which would lead to a Renal failure established. The portions most susceptible to this damage are the cells of the straight part of the proximal tubule (S3), rich in peroxisomes, and those of the collecting tubule. Once restored adequate renal perfusion, the failure may require days or weeks to recover. This injury is known as acute tubular necrosis (NTA), which, although originally an anatomopathological term, is used with clinical criteria and is based on the exclusion of other causes. On the other hand, intrinsic ARF can be reached by other causes that are not directly renal hypoperfusion, Such as: systemic or local immunological causes, such as vasculitis or acute interstitial immune-allergic drug nephritis; Direct nephrotoxic agents, such as aminoglycosides or iodinated contrast agents; Or vascular problems such as atheroembolic disease, embolisms or thrombosis in the arteries or renal veins. In many cases, there are several mechanisms that lead to renal failure by adding compromises in perfusion and direct renal injury due to toxicity, as can occur in rhabdomyolysis. Intrinsic ARF (with parenchymal damage) may be oliguric, anuric or with preserved diuresis. In the latter case the urine is of "poor quality", little concentrated in nitrogenous products. Such as vasculitis or acute interstitial immune-allergic drug nephritis; Direct nephrotoxic agents, such as aminoglycosides or iodinated contrast agents; Or vascular problems such as atheroembolic disease, embolisms or thrombosis in the arteries or renal veins. In many cases, there are several mechanisms that lead to renal failure by adding compromises in perfusion and direct renal injury due to toxins, as can occur in rhabdomyolysis. Intrinsic ARF (with parenchymal damage) may be oliguric, anuric or with preserved diuresis. In the latter case the urine is of "poor quality", little concentrated in nitrogenous products. Such as vasculitis or acute interstitial immune-allergic drug nephritis; Direct nephrotoxic agents, such as aminoglycosides or iodinated contrast agents; Or vascular problems such as atheroembolic disease, embolisms or thrombosis in the arteries or renal veins. In many cases, there are several mechanisms that lead to renal failure by adding compromises in perfusion and direct renal injury due to toxins, as can occur in rhabdomyolysis. Intrinsic ARF (with parenchymal damage) may be oliguric, anuric or with preserved diuresis. In the latter case the urine is of "poor quality", little concentrated in nitrogenous products. Embolisms or thrombosis in the arteries or renal veins. In many cases, there are several mechanisms that lead to renal failure by adding compromises in perfusion and direct renal injury due to toxins, as can occur in rhabdomyolysis. Intrinsic ARF (with parenchymal damage) may be oliguric, anuric or with preserved diuresis. In the latter case the urine is of "poor quality", little concentrated in nitrogenous products. Embolisms or thrombosis in the arteries or renal veins. In many cases, there are several mechanisms that lead to renal failure by adding compromises in perfusion and direct renal injury due to toxins, as can occur in rhabdomyolysis. Intrinsic ARF (with parenchymal damage) may be oliguric, anuric or with preserved diuresis. In the latter case the urine is of "poor quality", little concentrated in nitrogenous products.

Post-renal or obstructive IRA

Finally, although the kidneys initially perform their filtration, reabsorb and secretion missions, an obstruction to the urinary flow ends up impacting on these functions and may, if bilateral (or unilateral on a single functioning kidney), lead to anuria As the emission of urine less than 100 mL in 24 hours). In this case, there is talk of acute obstructive or post-renal renal failure. The degree of reversibility is high and renal function rapidly returns to its initial values ​​by correcting the cause or simply facilitating urine output (by catheterization, catheterization or nephrostomy).

EPIDEMIOLOGY AND PROGNOSIS
Community-acquired ARI is due in 70% of cases to pre-renal causes and in 17% to obstructive causes. IRA complicates more than 5% of all hospital admissions and appears in up to one-third of patients entering critical units. If we use the RIFLE criteria, the percentage may rise to 20% of all hospitalized patients; Almost always in the context of ischemia, sepsis, drugs and iodinated contrasts. In critical units the cause is often multifactorial and is related to multiorgan failure. Overall, more than half of the cases are due to pre-renal ARF, 40% to renal or parenchymal ARF, and 5% to post-renal ARF. Mortality is highly variable:

If the patient survives, renal function will almost always recover in whole or in part. However, a percentage of cases of severe ARF (10-20%) will continue to require renal replacement therapy at discharge. Some of them recover function to abandon dialysis, although they frequently progress to chronic end stage renal failure (stage 5).

ETIOLOGY

The causes of ARI are summarized in (Table 1) .

DIAGNOSIS
The algorithm of the differential diagnosis of acute renal failure is outlined in   (Figure 2) . The diagnostic steps should follow a systematic logic, comprising a battery that runs from the simplest to the most sophisticated, from the least aggressive to the most bloody and that initially considers the most frequent to reach the rare. In the (Table 2) the 6 steps that are usually used for the correct etiological diagnosis of ARF are listed. On the other hand, it should be remembered that several factors can occur, simultaneously or consecutively, as a result of the evolution of the disease or our intervention.

The Clinic in the Diagnosis of IRA
The correct anamnesis, together with an exhaustive physical examination, will alert us and guide us on a large number of etiologies. It is interesting to know: allergic antecedents and taking of drugs or toxic; Contact with toxic products; Existence of gastroenteritis, heavy drainage, bleeding or signs or symptoms of a third space. Delve into vascular antecedents, such as arteriosclerosis, invasive radiological explorations or with iodinated contrast, cardiac arrhythmia. Also inquire about recent surgery, possible pregnancies or recent obstetric complications, prostate clinic, macroscopic hematuria, renal colic or expulsion of stones or grit. Also investigate data suggesting lymphoproliferative or tumoral processes, recent traumatisms, signs or symptoms of infectious pathology and epidemiological analysis.

It should be remembered that the most frequent cases of ARF will be produced by renal hypo-perfusion (after dehydration due to digestive losses, etc.) and by toxins such as antibiotics (aminoglycosides) and iodinated contrasts. Other drugs less frequently used, such as antimicrobials (amphotericin B, vancomycin, acyclovir and ganciclovir, pentamidine, foscarnet, etc.) or antineoplastic drugs (cisplatin, ifosfamide) produce acute renal failure with high frequency. IRAs produced by anesthetics (enflurane) are uncommon. Carbon tetrachloride (CCl4) poisoning, ethylene glycol or mushrooms, although rare, should be kept in mind as the urgency in diagnosis may be the only hope that the patient's life can be saved.

Hemoptysis, or other bleeding or non-clarified pulmonary condensation data, will direct us to a lung-kidney, infectious or autoimmune etiology (Good Pasture syndrome, SLE, Wegener's granulomatosis or microscopic polyangiitis) or simply to be treated with acute edema Of lung or a neoplastic process. Wegener's granulomatosis presents pulmonary involvement in 90% of cases, microscopic polyangiitis in 50% and Churg Strauss syndrome in 70%, while renal involvement occurs in 80%, 90% and 45% respectively .

Physical examination will begin with the general assessment of the patient, ie, state of consciousness, hydration, skin coloration and distal perfusion, as well as frequency and respiratory ease and temperature. He will continue with the evaluation of his hemodynamic situation, heart rate, blood pressure and venous situation, followed by cardiopulmonary auscultation. The abdominal evaluation will try to determine the size of organs, locate possible painful or inflamed points, rule out peritoneal irritation and estimate intestinal motility. Look for cervical, axillary and inguinal lymph nodes and rule out the existence of complicated hernias. Inspect the limbs for wounds, Bites or stings or punctures that have resulted in the direct entry of toxins or microorganisms or substances that have indirectly caused kidney damage after producing, for example, rhabdomyolysis. Certain skin lesions may appear in allergic (drug nephritis), autoimmune (vasculitis, systemic lupus erythematosus, Schönlein Henoch purpura), infectious diseases (endocarditis, meningitis, etc.) or vascular diseases (livedo reticularis in atheroembolic disease).

At this clinical stage it is equally important not to be content with the diagnosis of ARF. Many times behind this syndrome there is something much more serious, such as severe pancreatitis, cholecystitis, cardiac tamponade, sepsis with multiorgan failure, a complicated myocardial infarction, an emboligenic source, atheroembolic disease, a lymphoproliferative or neoplastic process with Retroperitoneal invasion, multiple myeloma, etc.

Finally, the renal failure that appears in the final stage of many terminal patients deserves special mention, and to emphasize how futile it is to apply diagnostic and therapeutic means beyond the merely palliative.

Basic biochemical
analyzes Basic analyzes
They include the determination in serum or plasma of creatinine, urea or urea nitrogen, mono and divalent ions, pH and gasometry (venous, capillary or arterial depending on the clinical picture). A hematology with a white blood cell count, in addition to a urine test strip. Depending on the clinical manifestations, the creatine phosphokinase (CK), lactodeshidrogenasa (LDH), amylase or transaminases enzymes can also be urgently requested.

Functionality Parameters
They are directed to determine if the kidney is responding pathophysiologically to the inadequate renal perfusion or if there is actually damage in this organ that prevents its correct function. The correct interpretation of these parameters is framed in the scenario of the patient with oliguria that is not under the action of diuretics. In acute renal failure pre-renal mainly translate secondary hyperaldosteronism and stimulation of the antidiuretic hormone or vasopressin (ADH). The first, acting on nonspecific receptors for mineralocorticoids, located in the main cells of the collecting tubule of the distal nephron and the collecting tubule, favors the electrogenic reabsorption of Na + through the sodium epithelial channel (generating a negative electrical potential in The tubular light) and, indirectly, The tubular secretion of H + and K +. The ADH stimulus, acting on its receptors of the collecting tubule cells, favors the exit of water through the aquaporin-2 from the tubular light to the cell and through the acuoporins 3 and 4 from the tubule to the interstice And from here to the circulatory torrent. This results in urine with a low sodium content, relatively potassium content and relatively concentrated (with high osmolality).

The description of the parameters expressing functionality is detailed in (Table 3) . For its calculation we must ask the laboratory, in addition to the parameters mentioned above, a simultaneous determination of urinary ions (Na +, K +, Cl-), urea and creatinine. Osmolality in serum and urine (measured indirectly by the variation in freezing point and its comparison with solutions of known osmolality at different concentrations and expressed in milliosmoles per kilogram) may help us in the categorization of renal failure. Their estimation from the most representative molecules and ions may be simple in serum or plasma but more complicated in urine (see below). If osmolality is not available, the relative density of the urine can give us an orientation. Thus a density greater than 1,018 correlates with a concentrated urine, and that close to 1.010 reveals isosteric urine (of osmolality similar to plasma). Once we reach this point, and if we have reasonably ruled out the existence of pre-renal ARF, we must request an imaging test. Of choice: abdominal ultrasound.

Abdominal ultrasound
Being a bloodless test, relatively inexpensive and even realizable in the patient's own head, it becomes a "gold nugget" in the algorithm of the differential diagnosis of renal failure. The patterns with which we can find are listed in Table 4 and can be seen in Figure 3 (panels a, b and c). In cases of small and hyperechogenic kidneys and of kidneys with large bilateral cysts and decrease Of the renal parenchyma, we will find chronic renal failure in phase of progressive deterioration, or before the exacerbation of previous chronic renal failure.

For dilatation of the excretory route to cause ARF, it must affect both kidneys, the common excretory route or a kidney, provided that it provides most or all of the renal function (the other is aplastic or hypoplastic, ischemic, annulled kidney By an inflammatory or obstructive process, or extirpated by tumor, infectious, vascular or traumatic causes). Although infrequent, renal obstruction can occur without significant system dilation. This has been described in functional monorrenos of many years of evolution and in some elderly patient, and perhaps it is explained by the lack of distensibility of the urinary route. The diminution in the echogenicity of the renal papilas has been described in some nephropathies like in the Immunoallergic interstitial nephritis. However, we consider this sign to be non-specific.

Laboratory tests and other diagnostic
Urinalysis
The different elements that we can find in urine are summarized in (Table 5) . Microscopic analysis of the urine can alert us to the presence of red blood cells. If these are accompanied by significant proteinuria, hematic cylinders and altered morphology (with phase contrast microscopy), this leads us to the glomerular origin of the disease, such as primary or secondary glomerulonephritis to vasculitis, tissue disease Connective or infectious process. The presence of eosinophils in urine (with the corresponding Wright staining after buffering the urine) may support the diagnosis of allergic interstitial nephropathy. However, urine eosinophils can be seen in atheroembolic disease and acute pyelonephritis. The existence of oxalate crystals may lead us, according to the context, to an intoxication by ethylene glycol. The renal cylinders in functional IRA are clear, hyaline, and are produced by the precipitation of the uromucoid of Tamm Horsfall in a concentrated urine, whereas in an NTA they are pigmented, brown and with desquamated epithelial cells. Cylinders may contain red blood cells in proliferative glomerulonephritis and leukocytes in allergic interstitial nephritis.

Serological tests
The detection of neutrophil anti-cytoplasmic antibodies (ANCA) associated with certain small vessel vasculitis, such as microscopic polyangiitis, Wegener's granulomatosis or Churg-Strauss syndrome may be useful in its diagnosis and evolution and response to treatment. Indirect immunofluorescence of sera with normal neutrophils or by ELISA against specific antigen: The C-ANCA (granular cytoplasmic) pattern is that of immunofluorescence whose antigenic specificity corresponds to proteinase 3 (PR3); While the P-ANCA (perinuclear) pattern corresponds to myeloperoxidase (MPO). The first pattern is positive in 80% of Wegener's granulomatosis, in 30% of microscopic polyangiitis, In 30% of pauci- imune idiopathic extracapillary glomerulonephritis and 35% of Churg-Staruss. While the second pattern is in 50% of microscopic polyangiitis, 50% of extracapillary glomerulonephritis, 35% of Churg-Strauss, and in other autoimmune processes such as rheumatoid arthritis, autoimmune hepatopathy and inflammatory bowel diseases. Antinuclear antibodies, especially anti-DNA, and anti-Scl70 antibodies are analyzed for the evaluation of SLE and scleroderma, respectively. The antiphospholipid syndrome will rarely cause acute renal failure, but an extended thromboplastin time with a history of thrombosis, repeated abortions, or other non-specific alterations will justify the application of anticardiolipin and lupus anticoagulant titles. Glomerular basement antimembrane antibodies to suspected Good-Pasture syndrome will complete the study. Some serological tests in relation to infectious processes such as legionella or leptospirosis, or virus serology, may be requested according to the clinical or epidemiological context of the patient with ARI.

Protein analysis
Plasma electrophoresis and immunofixation and quantification of light chains in urine (search for Bence-Jones proteinuria) will be indicated for renal failure of unclarified cause or for those presenting with hypercalcemia or disproportionate anemia. In some myelomas, especially in light chains, we can not observe monoclonal peak in serum and only appear the light chain in urine, since if it does not circulate polymerized and it does as monomer or as dimer (22 or 44 kDa respectively) Easily crosses the glomerular-capillary filter.

Hematological analysis
A smear of blood can identify the existence of schistocytes, typical of a hemolytic uremic syndrome (HUS), thrombocytopenic purpura (PTT), or malignant arterial hypertension. In these microangiopathic diseases, thrombopenia, anemia (with reticulocytosis and decreased haptoglobin) and elevated serum LDH were observed. In this sense the antecedent of infection by Escherichia coli or Shigella and / or gastroenteritis, pregnancy, family history (mutations related to the complement chain) or the taking of certain immunosuppressive drugs like tacrolimus or mitomicina, will warn us. The existence in peripheral blood or bone marrow of tumor cells in leukemias, lymphomas and multiple myeloma will guide towards these diagnoses.

Microbiological studies
Studies aimed at confirming certain infections such as leptospira, legionella , and enterobacteria (and E. coli serotype if appropriate ); Seroconverted blood cultures in the presence of evident sepsis or more frequent infections such as endocarditis or occult abscess, and viral and culture serological tests according to the concomitant clinical setting.

The osmolar gap
The serum osmolar gap can help us with the suspicion of poisoning with low molecular weight molecules, such as ethylene glycol (present in antifreeze and refrigeration liquids), isopropanol, acetone, ethanol and methanol (burn alcohol). It is determined by establishing the difference between the osmolality measured with an osmometer and the estimated by calculation with the most abundant and low molecular weight molecules that we usually analyze. Osmolality is usually measured either by the variation of the freezing point (the more osmolality will decrease the cryoscopic point) or by the variation in the evaporation pressure. The estimation of the osmolality is calculated as follows:

Osm (mOsm / kg) = 2 [Na (mEq / L)] + [glucose (mMol / L)] + [Urea (mMol / L)]

Osm (mOsm / kg) = 2 [Na (mEq / L)] + [glucose (mg / dL)] / 18 + [Urea (mg / dL)] /

Osm (mOsm / kg) = 2 [Na (mEq / L)] + [glucose (mg / dL)] / 18 + [BUN (mg / dL)] / 2.8

The concentration of Na + is multiplied by 2; Chlorine and sodium are strong ions. Both the non-dissociated NaCl (15% at pH 7.40) and each Cl- ion and each dissociated Na + ion (85%) are considered. That is, for each atom of Na + there will be: 0.15 [NaCl] +0.85 [Na +] + 0.85 [Cl-]. Which results in 1.85 particles (ions plus molecules). As the concentration of a substance in plasma water is equal to its plasma concentration between 1 - Φ (where Φ = 0.0107 * total plasma proteins in g / dL), a protein concentration of 7 g / dL results Following setting: 1.85 • [Na] / 0.925 = 2 • [Na].

C wA = C pA / (1 - Φ)

Where, C wA  is the concentration of a substance "A" in plasma water and C pA is its concentration measured in plasma. The normal value of the osmolality is 280-295 mOsm / kg

If we include ethanol in the formula we would divide its concentration in mg / dL by 4.6 (pm of ethanol 46 Da), that of ethylene glycol by 6.2 (pm 62 Da), that of isopropanol by 6 (pm 60 Da) and That of methanol by 3.2 (pm 32 Da). This allows us, if we do not know the concentration of the toxic, deduct it from the osmolar gap or suspect the involvement of more than one toxic if we do not settle the accounts after having identified one of them.

The fundus examination
The fundus examination will help us to evaluate a possible atheroembolic disease (when visualizing cholesterol emboli), a possible endocarditis or vascular and papilla involvement in an arterial hypertension with suspicion of accelerated or malignant hypertension.

Imaging tests other than ultrasound
In addition to ultrasound, simple chest x-ray, and bone if appropriate, we should consider those tests aimed at ruling out vascular pathology and obstructive uropathy.

For the screening of obstructive uropathy
Mainly aimed to rule out the existence of a urinary obstruction, not detected by the ultrasound, or the topographical location or etiological diagnosis of obstructive uropathy. In this sense, computerized axial tomography, descending pyelography (if a nephrostomy catheter is available), retrograde pyelography and cystography will facilitate this approach. Magnetic uro-resonance (in T2 we clearly see the liquid) is a good choice, since it does not need the administration of any type of contrast medium.

For vascular pathology screening
When renal infarction is suspected, renal arteriography will be the test of choice. If the thrombus or emboli is confirmed, the catheter can be maintained in the renal artery and infused with fibrinolytics locally during the first 24 hours. Phlebography will be indicated on suspicion of renal venous thrombosis. Helical computerized axial tomography, currently with 64-head multi-detectors, can also provide valuable information, without the risks of previous tests. Sometimes Doppler ultrasound can help us decide on the indication of arteriography or phlebography. Isotopic studies can provide diagnostic data of vascular pathology in a bloodless way, but we must consider that we can waste time. It is advisable to be energetic in requesting the complementary test, ensuring that it is performed quickly and reliably with high sensitivity and specificity; Since the therapeutic attitude must be established at an early stage. Renal and abdominal arteriography may reveal small aneurysms in the case of macroscopic classic pan-arteritis.

Renal Biopsy
Renal biopsy is a poor practice today, but it is not without risk. The preferred modality is percutaneous biopsy. It is currently performed with ultrasound control and guided through a guide, firing automatically. All this has achieved a significant reduction of complications with good diagnostic profitability. On special occasions you can opt for surgical biopsy - open air - or even by transjugular biopsy. The latter is reserved for patients with coagulation disorders or when a liver biopsy is to be performed concomitantly. The sample should include bark and marrow fragments, fixing the larger fragment into formaldehyde and including it in paraffin, then staining the sections with hematoxylin eosin, PAS, Silver methenamine from Jones (to highlight basement membranes), Masson's trichrome (which stains blue / green collagen and fibrin red) and Congo red and thioflavin (for amyloid). A fragment (bark) will be frozen for immunofluorescence techniques with immunoglobulins, light chains, complements, fibrinogen and properdin. A third cortical fragment will also be fixed with glutaraldehyde, followed by post-fixation in osmium and inclusion with epoxy resin for ultra-fine cutting and observation with electron microscopy. The biopsy in the patient intubated and connected to respirator may be somewhat more complicated . A technique has been described that includes disconnecting the respirator. In our experience, we believe that with the technique described above and placing the patient in lateral decubitus position, The disconnection of the respirator can be avoided, since the oscillation of the kidney is minimal. Indication of renal biopsy in acute renal failure should not be limited to diagnostic curiosity and should entail therapeutic implications. Recall that in most cases we face acute tubular necrosis. It is therefore indicated when we suspect another etiology (small vessel vasculitis, glomerulonephritis, immunoallergic interstitial nephritis, amyloidosis, etc.). Or when we direct it towards the prognosis by analyzing the degree of affectation - and the histological variant - of a certain systemic disease (v. Sometimes it is indicated before the suspicion of prolonged NTA in the time that does not recover. In the latter case we can find an unexpected diagnosis, With cortical necrosis or with tubular necrosis in resolution. It is not uncommon to see (especially in the context of the critical patient) NTA that they recover after two or even three months of evolution. Longer periods will only exceptionally result in functional recovery. The biopsy is especially indicated in the IRA of the renal transplant patient to establish the difference between NTA, immunosuppressive toxicity and rejection, and in the latter case to classify the cellular or humoral rejection stage, using the Banff classification criteria . Longer periods will only exceptionally result in functional recovery. The biopsy is especially indicated in the IRA of the renal transplant patient to establish the difference between NTA, immunosuppressive toxicity and rejection, and in the latter case to classify the cellular or humoral rejection stage, using the Banff classification criteria . Longer periods will only exceptionally result in functional recovery. The biopsy is especially indicated in the IRA of the renal transplant patient to establish the difference between NTA, immunosuppressive toxicity and rejection, and in the latter case to classify the cellular or humoral rejection stage, using the Banff classification criteria .

New Kidney Damage Markers
In recent years, progress has been made in the detection of renal damage markers that allow: 1) to make an early diagnosis of kidney damage to allow early action; 2) to establish a differential diagnosis between different pathologies; And 3) to establish a prognostic stratification. These markers include molecules that are produced in other cells of the body and which are filtered, such as cystatin C and beta-2 microglobulin, or others that are released by the renal tissue into the blood or urine. Cystatin-C is a protein that is produced by all nucleated cells in the body, which is freely filtered in the kidney and completely resorbed in the proximal tubules. It is best measured by immuno-nephelometry. It does not depend on muscle mass like creatinine and with elevated filtrates correlates better than this with GF. It is not routinely used and may have special interest in cirrhotic patients. In different IRA contexts, molecules such as neutrophil gelatinase-associated lipocalin (NAGL), kidney damage molecule (Kim-1), urinary Interleukin-18 and plasma 6, Netrine-1 in urine, NHE 3 in urine and cytosolic enzymes (GST) in urine, although it is still early to recommend universal use [9] [10] .

TREATMENT
The treatment as a whole is reviewed in the Acute Renal Failure Action Guides promoted by the Spanish Society of Nephrology and directed by FJ Gainza and F Liaño [11]

Medical treatment
The first link in the treatment of ARI is to act on the cause. In pre-renal failure due to dehydration, crystalloids (saline saline 0.9% or 0.45% hypotonic or lactated Ringer) or hematocrit concentrate should be given in severe bleeding. It is important to frequently analyze blood ions and pH, with special attention to potassium. In heavy hydration it is recommended to monitor the central venous pressure (a good target being 8 mm Hg = 10 cm H2O). In cases of sepsis, vigorous hydration together with vasoactive drugs (preferably noradrenaline) to maintain a mean arterial pressure [(TAS + 2TAD) / 3] greater than 60 mm Hg, adding adequate antibiotic therapy and drainage when indicated, Will be the most effective tools to avoid multiorgan failure and very high mortality. In the hepatorenal failure the paracentesis to decrease the intra-abdominal pressure, together with the administration of albumin and terlipressin present the best results. In refractory cases, the placement of an intrahepatic Portosystemic Transjugular shunt (TIP) may be indicated. In the parenchymal ARF IAR, a number of treatments have been tried, with greater or lesser success in animals, that in humans have not been advantageous: Endothelin antagonists, atrial natriuretic peptide, dopamine, calcium antagonists, loop diuretics, antibodies, etc. In autoimmune diseases (vasculitis, pauci-immune extracapillary glomerulonephritis, LES) the use of immunosuppressants (glucocorticoids and cyclophosphamide) is indicated. In immunoallergic nephritis by drugs the use of steroids seems to shorten the evolution and to diminish the residual fibrosis that can remain after yielding the inflammatory activity.

Obstructive or post-renal ARF should be performed by the urologist (with or without radiologic help) to resolve or alleviate obstruction with urethral catheterization, ureteral catheterization, nephrostomy, lithotomy, or whatever. It is advisable to monitor the volumetric and electrolytic state following the unobstruction, since in the case of marked azotemia an osmotic polyuria usually leads to dehydration and hypokalemia. Other times a tubulointerstitial damage has occurred which can cause water and / or salt to be lost in an inconvenient manner.

Renal replacement
therapy Indications for initiation of substitution therapy
There are situations in which extracorporeal clearance is clearly indicated: for the management of fluids (oliguria / anuria, need for high intake - nutrition or other situations of hydrosaline overload or pulmonary edema); The correction of electrolytic and pH problems (hyperkalemia: [K]> 6.5 mEq / L, sodium alterations, severe metabolic acidosis: pH <7.2); And / or treatment of clinical alterations secondary to uremia (myopathy, encephalopathy or pericarditis). However, although it is evident that the aforementioned problems require a determined action to correct them, there are several retrospective and non-randomized studies in the literature that point to the possibility that an early onset of extracorporeal depuration may have an effect Positive about the evolution of the IRA,

Technical Variants of Renal Renal Treatment
Peritoneal Dialysis (PD)

PD, although very simple, has encountered the obstacle of increasing intra-abdominal pressure, thus compromising respiratory function. This modality is contraindicated in the presence of previous abdominal surgery and in many cases is insufficient to control the volume or the metabolic situation of the critical patient. It has therefore been relegated to the management of IRA in pediatrics (hemolytic uremic syndrome, etc.) and in countries without economic resources or in development.

Intermittent Hemodialysis (HDI)

HDI decades ago used a dialysis fluid (bath) whose buffer precursor was acetate, so hemodynamic instability in the severe patient was almost guaranteed. Today, the use of bicarbonate buffer has been widespread. The HDI machines have conductivity regulators, allowing the conductivity to be increased to 14.5-15 mS / cm to raise the Na + concentration and thus improve the hemodynamic tolerability of the patient. Moderately lowering the temperature of the dialysis bath (35.5 ° C) also makes it possible to improve stability by promoting vascular refilling. Modern monitors allow convective techniques, including the generation of replacement liquid of sufficient quality in line. An advance of the most modern monitors is the possibility of measuring the dose of dialysis (Kt and Kt / VUREA) by incorporating the calculation of ionic dialysance and calculating the variations of blood volume by variations in the hematocrit. Nowadays there are portable water treatment units (filtration + decalcification + dechlorosis + reverse osmosis) that can be approached at the foot of bed in any place that only has potable water and drainage.

Continuous purification techniques (TDC)

History and generalities

The first continuous technique to emerge was continuous arteriovenous hemofiltration (HFAVC), which did not require a blood pump, when circulating through a hemodialyzer of a membrane of high permeability to water. The blood ran in a similar way as it does for our tissues. The clearance was based on uncontrolled spontaneous ultrafiltration. This modality of treatment was a revolution, but it had two important problems: 1) the ultrafiltrate depended on the average arterial pressure of the patient and when this was insufficient (hypotension) the treatment was not effective; 2) purification was based on convention (shadowing our glomeruli) but there are no tubules to recover - from the filtrate - the valuable, We must replace part of what was ultrafiltraba with fluids as physiological as possible. Lactated Ringer has been a useful alternative for almost a decade.

The second step was the use of pumps to maintain a vein-to-vein circuit. Initially, isolated pumps were used, but some of the HDI equipment was soon used, from which the hydraulic systems that were not interested here were depleted. Taking advantage of any of your alarms and security systems, such as pressure meters, blood leak detectors or air intake to the circuit. Replacement of the ultrafiltrate continued to be a problem, leading to delays and a multitude of errors, so that the episodes of hemodynamic instability (the problem we theoretically tried to avoid with its use) were frequent. Slow dialysis was used as an option, and continuous veno-venous hemofiltration (HFVVC) was supplemented with continuous veno-venous hemodiafiltration (HDFVVC).

The substitutive renal treatment of ARF in the critical units (ICU) should not differ from that which is applied in the medical units and yet, given their special vulnerability, these patients present a low tolerance to extracorporeal treatment treatments. Hemodynamic instability has traditionally been a serious stumbling block because of the poor tolerance to rapid volume and internal medium modifications that characterize an HDI session. At times, the only alternative for treatment was PD. However, the extension of CDDs in the 1980s and 1990s has totally changed the scenario, not only from the technical point of view, but also on the indications, the moment of onset or even the person performing the indication and control Of the treatment.

TDC monitors

The modern monitors allow any therapeutic modality, they have gravimetric volume control, pressures (input, filter, return and effluent) and homologated alarms (air, foam, blood leakage, pressure fork and blood coagulation risk alert in the circuit). All this together with software that makes them friendly to the professionals who handle them. Together they have at least 4 peristaltic pumps and one of piston (for heparin as anticoagulant); In addition, the most modern incorporate another to be able to use citrates as anticoagulant. AQUARIUS (Baxter-Edwards), MULTIFILTRATE (Fresenius) and PRISMA FLEX (Hospal-Gambro) are among the most widely used in our country. Thanks to these advances, The use of TDC has shifted critical units to HDI and relegated the DP to an almost anecdotal role. This reality is reflected in the large international multicenter study published by Uchino et al which shows that ICU patients with ARF were treated in 80% of cases with BDD, in 17% with HDI and so Only 3% with PD.

Subsequently, a set of therapeutic modalities have been described, alongside CDT and intermittent, such as mixed techniques, which in the literature can be identified as low efficiency and sustained dialysis ( SLED ); Extended daily dialysis ( EDD ) and also as continuous slow dialysis ( SCD ).

Selecting Debug Therapy
HDI is capable of eliminating small molecules (such as urea, creatinine or gentamicin) through dialysis based on the principle of diffusion, explained by Adolf Fick 's first law and the Einstein-Stokes formula for Brownian diffusion. The TDCs, mainly represented by hemofiltration (HFVVC), are also capable of eliminating medium-sized molecules (several thousand molecular weight) by means of a process of entrainment with the ultrafiltrate produced by a set of pressures (convection) through the membrane Of the hemofilter. We can combine dialysis and filtration by adding diffusion in hemodiafiltration (HDFVVC) as shown in Figure 4 , thereby increasing the removal of small molecules.

Although these modalities can eliminate some substances by adsorption, there are other more specific techniques to enhance this physical mechanism, such as the hemoadsorption of endotoxins through a cartridge with polymyxin or plasma-filtration with adsorption (CPFA), purification mode in which The patient plasma obtained by plasma-filtration is passed through a cartridge of hydrophobic resins.

There are several indications and theoretical bases for thinking that continuous techniques are better tolerated than those intermittent from the biochemical and hemodynamic point of view and that, in addition, also improve the patient's survival rate. Some studies have found a similar survival between DDC and HDI [12] [13] , but the former may be advantageous in more severe patients if we consider: a) their greater capacity to eliminate large volumes without altering the patient's hemodynamic stability, (B) the fact that the stipulated total dose is more easily available; C) that its application is less demanding in terms of technology and d) finally that, by adding convention as a purification mechanism, we provide elimination of molecules of medium size, Among which are some mediators of the systemic inflammatory response. In this scenario, mixed techniques ( SLEDD or SCD ) stand out as the most promising solution since they combine the best of continuous and intermittent techniques, although at the moment there are no studies that address the comparison of these variants.

Depuration and survival rates
Another fundamental aspect of scientific progress has been to define the minimum dose of treatment to reduce the high mortality rate of patients with multiorgan failure. In the classic work of Ronco et al [14] , the "magic number" of convection of 35 mL • kg-1 • h-1 was established. Here, survival was analyzed 14 days after hemofiltration was completed, using polysulfone membrane and post-dilution (post-dilution) liquid lavage with lactate and a survival of 41% at 57 and 58% at 20 , 35 and 45 mL • kg-1 • h-1, respectively. However, in this study, there were few septic patients (between 11 and 14%, by randomized groups) and the analysis in this subgroup of patients was not statistically or clinically significant. In the study by Saudan et al [15] an increase in survival was demonstrated when diffusion (HDFVVC) was added to a normal (non-high volume) ultrafiltration dose, concluding that survival improves not only with convection but with The clearance dose of small molecules. The North American Multicenter Study (ATN)[16] has not been able to demonstrate advantages with higher doses (20 vs. 35 mL • kg-1 • h-1 in continuous or HDI 3 sessions per week vs. 6 sessions), although it has already been answered by different groups, including By the Spanish group, who recommend a dynamic approach that adjusts the dose at each moment of the evolutionary situation of the patient. More recently the Australian and New Zealand study (RENAL) [17] in which the 60-day and 90-day survival is identical if a standard dose (25 mL • kg-1 • h-1) is applied to a dose Intensive (40 mL • kg-1 • h-1) In this sense, We also highlight the elegant work of Helmut Schiffl et al where daily HDI improved survival at two weeks (72%) compared to that applied in a classic scheme every other day (54%). In the first, the clearance dose adjusted for time and volume of distribution of urea (Kt / V) practically doubled to the conventional standard. Also, if we opt for HDI, it seems that more intensive dialysis with higher sodium concentration, higher Kt / V and applied more frequently can give good results [18] . A 40L Kt for women and 45L for men is recommended. It seems that more intensive dialysis, with higher sodium concentration, higher Kt / V and applied more frequently can give good results [18] . A 40L Kt for women and 45L for men is recommended. It seems that more intensive dialysis, with higher sodium concentration, higher Kt / V and applied more frequently can give good results [18] . A 40L Kt for women and 45L for men is recommended.

Problems of application and complications of use
To guarantee a good performance of these techniques, a good vascular access is necessary. Adequate anticoagulant therapy is required and is individualized for each patient. In particular, it allows, as far as possible, to keep the filter, extracorporeal lines and catheters without clots, avoiding a systemic anticoagulation that may favor bleeding. The most commonly used alternative is sodium heparin at low doses [5] [10 U per kg of body weight per hour], but we must learn to handle other alternatives such as prostacyclin [19] and citrates.

Another crucial aspect in ensuring the proper functioning of the technique and the absence of problems is the adequate training of the personnel responsible for its care; We must consider that on many occasions it will be the nursing staff of the ICU (without previous training in renal purification techniques) who supports this function and, under these conditions, a suitable training program must be considered.