| Fact | Explanation |
|---|---|
| Oliguria | Oliguria (Urine output of less than 1 mL/kg/h. ) is an early and ominous sign of AKI. Monitoring the urine output in patients at risk of developing Acute Kidney Injury (AKI) will enable early detection of progression to AKI and prompt management will prevent the occurrence of AKI. [11] |
| Symptoms of dehydration [11] | Excessive thirst, postural dizziness and reduced urine output are symptoms suggestive of volume depletion. |
| Blood loss | Blood loss diminishes renal perfusion and causes pre-renal renal failure. |
| Use of certain drugs | Non-steroidal anti-inflammatory drugs inhibit the cyclo-oxygenase enzyme and reduce the Thromboxane A2 (a vasodilator) concentration. Andiotensin converting enzyme inhibitors (ACEIs) cause dilation of the postglomerular efferent arterioles and reduce the glomerular perfusion pressure. Above drugs reduce the renal perfusion and lead to pre-renal renal failure. [11] Statins causes rhabdomyolysis and “intrinsic renal” renal failure. [15] |
| Exposure to nephro-toxic substances | This is a cause for intrinsic renal renal failure. These substances(ethyl alcohol or ethylene glycol, gentamycin, mercury vapors, lead, cadmium, or other heavy metals ) cause damage to the renal tubular cells. Exposure to radiologic contrast agents is a well-established cause of AKI. [14] |
| Symptoms suggestive of nephritic or nephrotic syndrome | Hematuria, generalized edema and history of hypertension are suggestive of nephritic syndrome as the cause of “intrinsic renal” renal failure. [12] Nephrotic syndrome can cause intravascular hypovolemia and pre-renal renal failure. [13] |
| Symptoms of uremia | Uremic encephalopathy can cause altered level of consciousness. [22] Uremic pericarditis causes retrosternal chest pain which is relieved by bending forwards. [23] |
| Symptoms suggestive of rhabdomyolysis | Muscle pain, recent history of vigorous exercise or muscular trauma, ischemic limb tetanus and seizures can cause rhabdomyolysis. [16,17] |
| Transfusion of incompatible blood | Blood transfusion can induce intravascular hemolysis and hemoglobinuria resulting intrinsic renal failure. [18] |
| Symptoms of ureteric stones | Bilateral ureteric stones causes obstructive nephropathy and post-renal renal failure. [19] Patients will present with flank pain and hematuria. |
| History of atrial fibrillation | Atrial fibrillation is a known cause for thromboembolic occlusion of renal artery, causing pre-renal renal failure. [20] |
| History of liver disease | Hepato-renal syndrome is a known complication of cirrhosis. [21] |
| Risk factors for AKI | Acute severe hypertension is a cause for both acute kidney injury and acute on chronic renal injury. [1] Chronic heart failure [2], diabetes [3], multiple myeloma [4], autoimmune diseases (anti-tubular basement membrane disease, Kawasaki’s disease, Sjogren syndrome, systemic lupus erythematosus, or Wegener’s granulomatosis) [9] and chronic infections (HIV, influenza) are well known causes of AKI. [5,6] Myeloproliferative disorders (chronic myelogenous leukemia, polycythemia vera, essential thrombocythemia) can cause AKI in different ways. Severe hapatosplenomegaly can compress the kidneys and essential thrombocythemia can cause renal artery thrombosis or blood clots can lodge in the ureters causing obstructive nephropathy (post-renal renal failure). [7] Connective tissue disorders can lead to accelerated hypertension and as a consequence of that renal failure develops. [8] Excessive vomiting, diarrhea, fever and low fluid intake are common causes for hypovolemia and pre-renal acute kidney injury. [11] |
| Fact | Explanation |
|---|---|
| Signs of dehydration [1] | These include tachycardia, low pulse volume, postural hypotension, reduced skin turgor, dry mucous membranes and altered mental status. |
| Signs suggestive of connective tissue disorders | Livido reticularis, digital ischemia and palpable purpura are suggestive of systemic vasculitis. Malar rash favors the diagnosis of systemic lupus erythematosis. [2] Keratitis, uveitis, iritis and dry eyes are ophthalmological findings suggestive of autoimmune disorders. [3] Inflammatory ulcerations in the nasal mucosa and pulmonary crepitations are seen in Wegener granulomatosis. [4] |
| Signs suggestive of multiple myeloma | Band keratopathy (calcium deposits are seen in the central cornea) occurs due to hypercalcemia. Suppression of other bone marrow cell lines can cause pallor and petechial marks. [5] |
| Signs suggestive of diabetes mellitus | Evidence of diabetic neuropathy and retinopathy will favor the diagnosis of diabetes as the cause of AKI. [10] |
| Signs suggestive of hypertension | High blood pressure, evidence of hypertensive retinopathy (arteriovenous nicking, silver wiring pattern, papilledema) [9] are helpful signs in detecting acute severe hypertension as the possible cause of AKI. [8] |
| Hearing assessment | Alport syndrome is an autosomal recessive disorder affecting kidneys, eyes and cochlea. Cochlear involvement can cause neurogenic hearing loss. [6] Aminoglycoside toxicity is also another cause for hearing loss and AKI. [7] |
| Examination of the cardiovascular system | Low volume pulse is indicative of intravascular volume depletion. Irregularly irregular pulse is indicative of atrial fibrillation, which causes thromboembolism and pre-renal renal failure. [11] Newly detected murmurs aid in the diagnosis of infective endocarditis which is another causes for thromboembolic occlusion of renal artery. [12] Signs of heart failure are also suggestive of pre-renal renal failure due to renal hypo-perfusion. [13] Measurement of blood pressure will not only favor the diagnosis of severe hypertension but also it has diagnostic value in diagnosing nephritic syndrome as well. |
| Renal angle tenderness | This sign will be positive in nephrolithiasis, papillary necrosis (due to diabetes or non-steroidal anti-inflammatory drug use) [14], renal artery thrombosis and renal vein thrombosis. [15] |
| Signs of bladder outlet obstruction | Distended bladder, and prostatomegaly in males are suggestive of bladder outlet obstruction. [16] |
| Clinical signs of cirrhosis | Jaundice, finger clubbing, palmar erythema, spider naevi, gynecomastia, splenomegaly and ascites are suggestive of cirrhosis. [18] |
| Evidence of acute ischemic limb | Paralysis and anesthesia of the affected limb and pain on squeezing the calf muscles all are suggestive of rhabdomyolysis due to acute limb ischemia. [17] |
| Fact | Explanation |
|---|---|
| Chronic renal failure | Some patients with chronic renal failure may remain undiagnosed and a minor insult to the kidneys can manifest symptoms and signs due to acute on chronic renal failure. |
| Dehydration | Dehydration is one contributory cause for AKI. Other causes of dehydration like excessive vomiting, diarrhea, and iatrogenic causes (inadequate fluid replacement in unconscious patients or patients undergoing surgery) should be considered of. [1] |
| Diabetic ketoacidosis (DKA) | Diabetes is one of the risk factors for the development of AKI. Like some patients with pre-renal AKI, DKA patients can present with polydipsia, altered mental status and fatigue. Other than those symptoms DKA patients tend to have abdominal pain, polyuria, nausea and vomiting. Estimation of random blood sugar value will aid in making the diagnosis. [2] |
| Heart failure | AKI may not be an isolated event but a manifestation of heart failure. Chest X-ray will demonstrate the signs of heart failure like pulmonary edema, Kerley B lines, cardiomegaly, upper lobe diversion and pleural effusions. [3] |
| Hypertension | As for the heart failure AKI can be the presenting complain of severe hypertension. [9] |
| Obstructive uropathy | Benign or malignant prostatic hyperplasia and other possible causes of bladder outlet obstruction should be considered as possible differentials. Urodynamic studies will aid in establishing the diagnosis. [4] |
| Renal calculi | This may be the etiology of AKI. X-ray film of kidney-ureter and bladder (X-ray KUB)will show the presence of calculi. [5] |
| Hemolytic uremic syndrome | This is a combination of microangiopathic haemolytic anaemia, thrombocytopenia and AKI. Commonly seen in children. Full blood count and blood picture will be helpful in diagnosis. [6] |
| Henoch-Schonlein Purpura | This is an IgA-mediated, autoimmune, hypersensitivity vasculitis associated with group A streptococci and Mycoplasma infection cand commonly seen in children. Usual presenting complains are purpuric rash over the lower extremities, abdominal pain, hematuria and arthritis. [7] |
| Hyperkalemia | AKI can also cause hyperkalemia. However other possible causes of hyperkalemia like dehydration, syndrome of hyporeninemic hypoaldosteronism and diabetic nephropathy should also be considered. [8] |
| Fact | Explanation |
|---|---|
| Full blood count | Shows evidence of myeloproliferative disorders. Hemoglobin may be low in hemolysis. [1] |
| Blood picture | This is an important investigation in diagnosing hemolytic anemia. Blood picture will show schistocytes in hemolytic uremic syndrome. [2] |
| Urine full report [1] | Macroscopically brown or cola-colored urine indicates either myoglobinuria or hemoglobinuria. Urine protein dipstick will be positive in the presence of above two conditions. |
| Urine micorscopy [1] | Granular, muddy brown casts, oxalate crystals, and presence of tubular cells are seen in tubular necrosis. Calcium oxalate crystal are seen in ethylene glycol poisoning. Dysmorphic red blood cells are suggestive of glomerulonephritis. In pyelonephritis and acute interstitial nephritis white blood cell casts are seen in phase contrast microscopic examination. Presence of eosinophil suggests allergic nephritis or interstitial nephritis. |
| Serum electrolytes | AKI causes hyperkalemia due to poor renal excretion of potassium. [1] |
| Urine electrolytes [1] | Urinary sodium is high and potassium is less. |
| Serum creatinine [1] | Plasma levels are elevated due to diminished renal excretion of creatinine. However it takes some time to develop. In the presence of oliguria fractional excretion of sodium (FENa = (Urinary sodium/Plasma sodium) / (Urinary creatinine /Plasma creatininte) X 100%) will narrow down the possible cause of etiology. FENa is less than 1% in pre-renal causes and more than 1% in acute tubular necrosis. [9] |
| Blood urea nitrogen (BUN) [1] | Elevated in AKI. BUN to creatinine ratio is increased if the urea reabsorption is high, like in hypovolemia and pre-renal renal failure. (More than 20:1 in pre-renal and 10 to 20:1 in intrinsic renal failure.) Fractional excretion of urea ((Urinary urea/Plasma urea) / (Urinary creatinine /Plasma creatininte) X 100%) is also another important calculation. A value less than 35% is in favor of pre-renal cause. The use of estimation of fractional excretion of urea is helpful in patients who are treated with diuretics. [7,8] |
| Investigations to diagnose an autoimmune etiology | Assessment of complement levels and antinuclear antibody (ANA) (favors but not diagnostic of systemic lupus erythematosis). [4] Positive antineutrophil cytoplasmic antibody (ANCA) aids the diagnosis of Wagner’s granulomatosis and other vasculitic disorders. [5] Anti-glomerular basement membrane (anti-GBM) antibody are present in most autoimmune glomerular pathologies. |
| Ultrasound scan of the abdomen | Ultrasound scan can detect possible causes of obstructive uropathy like prostatomegaly. Ultrasound scan combined with Doppler flow can detect renal hypo-perfusion. [13] |
| Radionuclide imaging | These tests can detect renal hypo-perfusion and function of tubular cells. [11] |
| Aortorenal angiography | Angiography can detect renal artery stenosis (a possible cause of severe hypertension) and thrombo-embolic occlusion of the renal arteries. However this also carries a potential risk of contrast induced nephropathy. [12] |
| Renal biopsy | Although not routinely done a biopsy will enable definitive diagnosis of the possible etiology of intrinsic renal failure. [10] |
| Biomarkers | Urinary neutrophil gelatinase-associated lipocalin (NGAL) levels can be checked to detect AKI early. However this is not widely practiced. plasma B-type natriuretic peptide (BNP) is another biomarker. Kidney injury molecule-1 (KIM-1) is a transmembrane protein found in proximal tubular cells and urinary KIM-1 levels are found in increased amounts in tubular necrosis. [3] |
| Fact | Explanation |
|---|---|
| Basic Investigations to assess the fitness | These are been done during the initial assessment of the patient with AKI (See Investigations for Diagnosis) |
| Fact | Explanation |
|---|---|
| Arterial blood gas analysis | Kidneys are main organs involved in acid base homeostasis. Renal failure may lead to acidosis. [1] |
| Serum electrolytes [2] | Recovery of renal function is indicated by normalizing serum electrolyte concentrations. |
| Serum creatinine [2] | As for serum electrolytes serum creatinine also provides a way of monitoring recovery of the renal function. |
| Blood urea [2] | Return of the elevated values to normal indicates recovery from the acute insult to the kidneys. |
| ECG [2] | Detects cardiac complications of hyperkalemia. |
| Chest X-ray | Diagnose heart failure and fluid overload. |
| Fact | Explanation |
|---|---|
| Serum creatinine | This is used in staging the severity of AKI according to the Acute Kidney Injury Network (AKIN) classification. Serum creatinine of 26.5 μmol/L (0.3 mg/dL) or more is categorized as stage 1. If creatinine is more than 200 μmol/L it is categorized as stage 2 and if it is more than or similar to 353.6 μmol/L, it is stage 3. [1] Although not routinely done serum creatinine can be estimated to screen for AKI. [2] |
| Fact | Explanation |
|---|---|
| Health education | Patients can be advised to prevent the recurrence of AKI due to potentially reversible causes (dehydration, ingestion of nephrotoxic drugs). Good glycemic control will halt the progression of diabetic nephropathy. [5] |
| Stop nephrotoxic drugs | If the patient is on any nephrotoxic drugs it should be stopped or changed to once daily regime. Ethylene glycol or methanol poisoning is treated with alcohol drip or with fomepizole (Antizol). [4] |
| Salt restriction [8] | In oliguric renal failure salt restriction will minimize the risk of fluid retention. |
| Fluid restriction | This is also applicable in oliguric renal failure in preventing fluid overload. [7] |
| Protein restriction | Dietary protein intake of 0.6 g per kg per day is usually adequate and rest of the energy requirement should be met with carbohydrates. [4] |
| Maintaining the homeostasis of sodium and potassium [4] | During the oliguric phase serum levels of sodium and potassium tend to be high which decreases rapidly during the polyuric phase at the recovery. Restriction is necessary during the oliguric phase and replacement might be necessary during the polyuric phase. If serum potassium levels fall below 6 mEq/L (6 mmol/L) dietary restriction of potassium and potassium binding resins can be used for treatment. Severe hyperkalemia refractory to medical management may need renal replacement therapy. [4] |
| Maintenance of acid-base homeostasis | Severe metabolic acidosis (pH below 7.2) is treated with sodium bicarbonate. If refractory, renal replacement therapy is indicated. [4] |
| Prevention of contrast-induced nephropathy | Adequate hydration (intravenous saline 1 mL/kg/h is administered from 12 hours before the procedure which is continued till 12 hours after the procedure), administration of isotonic NaHCO3 solution before and after the procedure for at risk patients and oral N –acetylcysteine (1200 mg every 12 hours) will be useful in prevention of contrast-induced nephropathy. [2] |
| Treatment of bladder outlet obstruction | The cause of bladder outlet obstruction should be treated in order to improve the renal function. [1] |
| Treatment of hypertension | Uncontrolled hypertension lead to hypertensive nephropathy and chronic renal failure. Pharmacological treatment will control blood pressure and delay or minimize the progression to hypertensive nephropathy. [3] |
| Treatment of heart failure | Diuretics and angiotensin converting enzyme inhibitors are used as the baseline treatment. In acute heart failure dopamine and other inotropics are used. [3] |
| Management of hepato-renal syndrome | Vasoconstrictors are the mainstay of treatment. Intravenous terlipressin (0.5 2 mg/4–6h) is used in treatment. [6] |
| Fact | Explanation |
|---|---|
| Replacement of fluid deficit | If renal hypoperfusion is found to be the possible etiology of AKI fluid replacement will restore the normal renal perfusion. |
| Renal vasodilators | Dopamine (1-5 mcg/kg/min) will improve the renal perfusion. [1] |
| Renal replacement therapy | Patient may require renal replacement therapy in the form of peritoneal dialysis or preferably hemodialysis. Common indications for the renal replacement therapy are severe pulmonary edema, hyperkalemia refractory to medical management, uremic pericarditis, uremic encephalopathy and severe acid base disturbances. [1] |