WEEK 6 SOAP NOTE

Internal Medicine 33: 49-year-old female with confusion User: YULAK LANDA Email: [email protected] Date: March 31, 2021 2:49AM

Learning Objectives

The student should be able to:

Compare the pathophysiology of major etiologies of acute renal failure including decreased renal perfusion (pre-renal), intrinsic renal disease, and acute renal obstruction (post renal). Calculate fractional excretion of sodium and apply it to distinguish between pre-renal and intrinsic renal disease. Develop appropriate initial management plan for acute renal failure including volume management, dietary recommendations, drug dosage alterations, electrolyte monitoring, and indications for dialysis. Identify risk factors for contrast-induced nephropathy and recommend steps to prevent this complication. Interpret a urinalysis, including microscopic examination for casts, red blood cells, white blood cells, and crystals. Calculate the anion gap and generate a differential diagnosis for metabolic acidosis.

Knowledge

Acute Kidney Injury - Definition & Classification

Definition

Acute kidney injury (AKI) is defined by an abrupt (within 48 hours) decrease in glomerular filtration function with a concomitant elevation in serum creatinine. In this setting, the kidneys are unable to maintain fluid, electrolyte, and acid-base homeostasis. Classification

Development of consensus definitions for acute kidney injury over the past several years have improved physicians' ability to describe acute kidney injury with consistent terminology. This is of benefit for both research and for clinical care prognostication as it has been demonstrated that categories of worsening acute kidney injury are predictive of morbidity including future chronic kidney disease and mortality during the acute kidney injury episode. The first consensus definition was called the RIFLE criteria. Subsequent criteria were developed by the Acute Kidney Injury Network (AKIN). These criteria have been merged and simplified by the Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Acute Kidney Injury. In the KDIGO guidelines acute kidney injury is defined as: 1. An increase in serum creatinine ≥ 0.3 mg/dl within 48 hours - or - 2. Increase in serum creatinine to ≥ 1.5 times baseline, which is known or presumed to have to have occurred within the prior seven days - or - 3. Urine volume < 0.5 ml/kg/hr for six hours In the KDIGO guidelines, acute kidney injury is categorized in to three progressively worsening stages:

Stage Serum creatinine Urine output

1 1.5 - 1.9 times baseline

or ≥ 0.3 mg/dl increase < 0.5ml/kg/hr for 6 - 12 hours

2 2.0 - 2.9 times baseline < 0.5ml/kg/hr for ≥ 12 hours

3

3.0 times baseline

or increase ≥ 4.0 mg/dl

or initiation of renal replacement therapy

or in patients < 18 years, decrease in eGFR < 35 ml/min/1.73m2

< 0.3ml/kg/hr for ≥ 24 hours.

or anuria for ≥ 12 hours

It should be stressed that this definition of acute renal injury is based on the serum creatinine, which is a relatively late biomarker of acute injury. There are presently several promising biomarkers under investigation that may more rapidly identify patients with

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acute renal injury. The ability to more rapidly identify renal injury after an insult will hopefully lead to earlier recognition and more effective treatment.

Pathophysiology and Etiology of Acute Renal Failure

Pathophysiology Etiology

Pre- renal

Tubular and glomerular function are intact.

Decreased renal perfusion due to hypovolemia or hypotension compromises renal function.

Enhanced tubular absorption of both sodium and water increases passive reabsorption of urea.

Hypovolemia from vomiting, diarrhea, poor fluid intake, diuretics, fever, surgical fluid losses

Cardiorenal syndrome: decreased cardiac output with decreased renal perfusion (e.g., congestive heart failure, myocardial infarction)

Systemic vasodilation with decreased renal perfusion (e.g., sepsis, cirrhosis with hepatorenal syndrome, anesthesia)

Renal hypoperfusion could be due to atherosclerosis, fibromuscular dysplasia, or from medications leading to vasoconstriction of the afferent arteriole and impaired glomerular blood flow

Pre-renal kidney injury is the commonest cause of decreased renal function in hospitalized patients.

Intrinsic renal

Dysfunction is due to a primary intrarenal cause (damaged tubules, interstitium, glomeruli or blood vessels).

Injured nephrons are no longer able to maintain homeostasis for electrolytes, acid-base balance and water.

Categorized by primary site of injury:

Tubules: Acute tubular necrosis (ATN) accounts for 85% of intrinsic renal failure.

The leading cause of intrinsic injury in hospitalized patients is sepsis. The next most common cause of ATN is renal ischemia occurring during major heart or vascular surgery.

Toxins also play a major role (aminoglycosides, radiocontrast, myoglobin, hemoglobin, chemotherapy, myeloma light chains, etc.).

Ischemia from prolonged prerenal azotemia will progress to ATN if the prerenal insult cannot be reversed.

Hemorrhagic shock in the setting of bleeding or obstetrical complications may also lead to ATN.

Interstitium: Acute interstitial nephritis accounts for 10% of cases of intrinsic AKI. Most often allergic reaction to a drug. Look for fever, drug rash, eosinophilia, and renal dysfunction. Common causes are fluoroquinolones, sulfa drugs, beta lactams, and NSAIDs. Unlike other drugs, NSAID-induced interstitial nephritis is frequently associated with nephrotic syndrome. Less common causes are infections or autoimmune disease.

Glomeruli: Glomerulonephritis or GN accounts for 5% of cases of intrinsic AKI. These diseases include the the primary and secondary causes of the nephritic syndrome (proliferative lupus, infection related GN, MPGN, IgA nephropathy and the vascular diseases of the glomerular capillary bed). Less commonly, nephrotic diseases can present with AKI .

Vascular lesions: Examples include hypertensive emergency, embolic phenomenon, catastrophic lupus anticoagulant syndrome, scleroderma renal crisis and vasculitides such as granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).

It is important to recognize and diagnose these intrinsic renal causes of AKI as many of them have disease-specific therapies available.

Post- renal

Due to obstruction of the urinary outflow tract that can occur anywhere from the collecting tubules to the urethra.

Both urinary outflow tracts are obstructed or there is obstruction of one tract in a patient with one functional kidney. Anatomically one can think about post-obstructive causes occurring in the following areas:

Tubules: crystals such as uric acid, acyclovir, indinavir or sulfa drugs.

Ureteral: cancer, calculi, clot, sloughed papillary necrosis, lymphadenopathy, retroperitoneal fibrosis

Bladder neck: tumors, calculi, benign prostatic hypertrophy (BPH), prostate cancer, cervical cancer, neurogenic bladder.

Urethral: stricture, tumors, posterior urethral valves in infant males, obstructed in-dwelling catheter

Post-renal renal failure is important to recognize early because the chance of recovery of renal function is inversely related to the duration of the obstruction.

Note: Because hypovolemia and obstruction are so readily treatable, they are considered "can't miss" diagnoses when evaluating

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a patient with acute kidney injury.

Drugs Affecting Glomerular Hemodynamics

Cyclosporine-A, NSAIDs, radiocontrast, and tacrolimus can induce renal dysfunction through vasoconstriction of the afferent arteriole. Angiotensin blockers vasodilate the efferent arteriole , which is generally renal protective by causing a decrease in filtration pressure. However, in a patient with renal artery stenosis with a fixed inflow to the kidney, the addition of an angiotensin blocker (ARB) or angiotensin converting enzyme inhibitor (ACEI) will result in acute kidney injury due to the sudden release of the efferent arteriole vasoconstriction. As a general rule, any creatinine increase beyond 30% should be viewed as AKI prompting the medication to be stopped and an investigation for renal artery stenosis initiated. NSAIDs

NSAIDs have an anti-prostaglandin effect that leads to vasoconstriction of the afferent arteriole and impaired glomerular perfusion. NSAIDs can be particularly harmful in:

older adults patients with underlying renal dysfunction (estimated GFR < 30-50mL/min) patients on diuretics or ACE inhibitors those exposed to IV contrast

Over-the-counter and herbal medicines

It is important to ask every patient with renal dysfunction if they are taking over-the-counter medications such as NSAIDs and even herbal medicines. Two links on herbals and kidney injury: Herbs and the kidney Kidney injury from alternative medicines Note: In addition to vasoconstriction of the afferent arteriole, radiocontrast - induced kidney dysfunction is also related to oxidant injury.

Potential Nephrotoxins

Aspirin Aspirin leads to renal hypoperfusion through vasoconstriction of the afferent arteriole. Renal toxicity istypically not seen at standard doses of 81-325mg daily.

Valsartan Valsartan indirectly decreases glomerular filtration pressure and blood flow through vasodilation of theefferent arteriole.

Hydrochlorothiazide Hydrochlorothiazide may rarely cause an allergic interstitial nephritis.

Atorvastatin Atorvastatin is not directly nephrotoxic but in rare cases could lead to rhabdomyolysis, which could inducerenal failure.

Metformin is excreted 100% unmetabolized by the kidneys. It is not nephrotoxic but can lead to lactic acidosis in patients with renal failure or liver disease and should be avoided in these settings.

Relevant Radiological History in the Setting of Acute Kidney Injury

In addition to nephrotoxins, another important historical question is to inquire about radiologic imaging studies using contrast. Contrast nephropathy is a relatively common cause of acute kidney injury, particularly in patients with diabetes. This would be an important clue to look for in a patient presenting with acute kidney injury. Also, if the patient has undergone an invasive angiographic procedure, it would be important to consider cholesterol embolization. Disruption of atherosclerotic plaques can shower cholesterol crystals to the kidneys, inducing an inflammatory response. Unlike contrast-induced nephropathy, in which the creatinine almost always rises within 72 hours, with cholesterol embolization the creatinine does not increase for two to three weeks and may stay elevated. Associated findings are a fine reticular rash (livedo reticularis), low serum complement levels, and eosinophilia.

Key Physical Exam Findings For Acute Kidney Injury

Absence of fever Absence of fever makes infection less likely, though not impossible.

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Normal bowel sounds

The presence of normal bowel sounds points away from a surgical emergency that led to renal failure (decreased in peritonitis, increased in GI bleeding).

Signs of hypovolemia

Hypovolemia is critical to identify in patients with acute kidney injury, as prompt treatment can lead to rapid recovery of renal function. The ability of physical examination to diagnose hypovolemia has not been well studied. The available evidence suggests:

Orthostatic vital signs can help identify patients with hypovolemia. Orthostasis with pulse increase >30 bpm and BP decline of >20mmHg have moderate specificity (75% for HR, 81% for BP) but poor sensitivity (43% for HR, 29% for BP). Orthostatic vital signs are less reliable in patients who are on medications that may affect autonomic response (adrenergic blockers, central alpha agonists, psychotropic medications) or who have underlying autonomic dysregulation from diabetes or other neurological diseases.

Sunken eyes (LR+ 3.4) and dry axilla (LR+ 2.8) are the best predictors of hypovolemia, but their absence does not exclude the diagnosis.

Dry mucous membranes are not very helpful in ruling in the hypovolemia (LR+ 2), but their absence suggest hypovolemia is not present (LR- 0.3).

One study suggests that a combination of findings (for example dry mucous membranes and tongue, sunken eyes, extremity weakness, confusion, nonfluent speech) is highly predictive of hypovolemia.

Skin tenting

Poor skin turgor (skin tenting) refers to the slow return of skin to its normal position after being pinched between the examiner's thumb and forefinger. The protein elastin, which is responsible for the recoil of skin, is markedly affected by moisture content. As little as 3.4% loss in wet weight may prolong the recoil time 40-fold. Elastin deteriorates with age, suggesting that the recoil of skin normally declines with age, although this has never been formally studied.

Absence of signs of volume overload

Absence of signs of volume overload argues against CHF as a cause of possible prerenal hypovolemia.

Absence of palpable bladder

Absence of a palpable bladder makes an obstructive uropathy slightly less likely, although this finding may be less reliable in patients with obesity.

Normal reflexes

Normal reflexes do not help you identify the cause of AKI, but do point against severe derangements in potassium, magnesium, and calcium that could be present in acute kidney injury.

Altered mental status

Altered mental status can lead to hypovolemia by impairing the thirst mechanism.

Hemiparesis Hemiparesis can impair patients' ability to take fluids.

Key Physical Exam Findings in a Patient with Acute Kidney Injury

In a patient with laboratory findings consistent with acute kidney injury, the main question to answer with the exam is: "Does this patient have evidence of volume overload or volume depletion?" Either of these could contribute to pre-renal renal failure by decreasing perfusion to the kidney. Likewise, identifying a distended bladder or elevated post-void residual urine volume is critical because these are signs of obstruction that could be causing post-renal renal failure. Each of these states would be treated very differently, so identifying them would have an impact on which course of therapy is ultimately chosen. It is important to note that although we must look for signs and symptoms of fluid overload, such as jugular venous distension (JVD), the presence of an S3 gallop, crackles, peripheral edema, and ascites -- the sensitivity of these signs individually for making a definitive diagnosis of volume overload is quite low.

Update on Contrast-Induced Nephropathy

Contrast-induced nephropathy (CIN) is defined as an acute decline in renal function within two or three days after the administration of iodinated contrast agent in the absence of another potential cause. Iodinated contrast has been recognized as a potential nephrotoxin for many years. The mechanisms of renal injury likely include both vasoconstriction of the renal vasculature and direct tubular toxicity. In older studies a number of risk factors for CIN were identified including pre-existing renal insufficiency, diabetes, older age,

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hypovolemia, congestive heart failure, cirrhosis, peripheral vascular disease, NSAID use, high dose or repeated loads of contrast and intra-arterial injection. Until recently CIN was attributed to be the third leading cause of AKI in hospitalized patients. However, recent scrutiny of the data has led to a reconsideration of the prevalence and risk of CIN with the use of low osmotic and isosmotic contrast agents in modern use. A number of observational studies including studies employing propensity score matching have found that among hospitalized patients who undergo CT studies, those who receive IV contrast have the same risk of AKI as those who do not receive contrast. A recent meta-analysis examined the data and found no increased risk for AKI, need for renal replacement therapy or mortality for patients who received iodinated contrast for CT imaging versus patients who who underwent CT imaging without contrast. The 2018 American College of Radiology Manual on Contrast Media concludes that CIN is a real but rare condition. They suggest that if a renal function threshold is to be used to avoid use of iodinated contrast a cut of < 30 ml/min/1.73m2 is best supported by the available data. In the case of AKI there is a lack of data but it is prudent to avoid iodinated contrast unless the potential benefits outweigh the risk. If iodinated contrast is indicated and the patient has preexisting renal insufficiency IV hydration with normal saline should be administered. Data does not support the use of N-acetylcysteine to reduce the risk of CIN. As for all patients at risk for AKI, other identifiable risks should be eliminated such as exposure to NSAIDS or other renal toxic medications.

Management

Treatment of Acute Kidney Injury

1. Identify and correct pre-renal and post-renal conditions. 2. Volume management: Accurate monitoring of daily weights and fluid balance is critical. A small fluid challenge is not

unreasonable if your diagnostic studies are inconclusive for a pre-renal etiology. Avoid giving large volumes of fluids to prevent pulmonary edema. Diuretic therapy should be used in patients with clear evidence of volume overload (such as edema, crackles, jugular venous distension, ascites); however, diuretic therapy has not been shown to improve survival or renal recovery rate. The medical literature provides little guidance on vasoactive medications for blood pressure support in the setting of hypotension and acute kidney injury (for example, hypotension in sepsis with ischemic ATN). The use of low dose or so-called "renal-dose" dopamine has not been shown to improve outcomes in critically ill patients with renal failure and should not be used.

3. Dietary recommendations: Placing the patient on a renal diet with low potassium, phosphorus, and protein as well as monitoring fluid intake is necessary to maintain fluid and electrolyte balance. If the patient cannot eat, nutritional support is necessary. This strategy is particularly important in the setting of critical illness, because marked visceral and muscle protein wasting can occur. Enteral feeding is preferred over parenteral nutrition.

4. Drug dosage alterations: No drug treatment has been shown to limit the progression or hasten the recovery in the setting of acute kidney injury due to ATN. For all causes of AKI it is important to stop nonsteroidal anti-inflammatory or other nephrotoxic agents (in this case, stop losartan, aspirin, metformin, hydrochlorothiazide and furosemide), avoid nephrotoxic antibiotics (aminoglycosides, amphotericin), and avoid radiocontrast. Renally dose all medications that are given and monitor drug levels where appropriate.

5. Electrolyte monitoring: Watch for hyperkalemia and hyperphosphatemia. Monitor anion gap and acid-base status. In the setting of recovery from ATN (diuretic phase of ATN) electrolyte wasting may occur and potassium supplementation for hypokalemia may be required.

6. Identify and aggressively treat infections: Minimize the use of in-dwelling lines as much as possible. If the patient is anuric, removal of the Foley catheter is appropriate.

7. Watch for increased risk of bleeding: Uremia can lead to abnormal bleeding through a variety of mechanisms, such as dysfunctional vWF. Uremia-related bleeding has specific treatment strategies, including DDAVP.

8. Indications for dialysis: Initiate dialysis before uremic complications develop. 9. Consult Nephrology: Nephrologists are underutilized in these cases, even though studies have shown that

early consultation can improve outcomes. Surprisingly, these better outcomes result simply through meticulous attention to detail regarding supportive care. Nephrologists may also start disease specific therapy such as steroids, immune modulators or plasmapheresis.

Consultation is mandatory in cases when:

the diagnosis is uncertain despite initial diagnostic workup renal replacement therapy or dialysis is likely needed an intrinsic renal cause other than ATN is present

Indications for Acute Dialysis

The mnemonic AEIOU is helpful to remember the indications: Acidemia that does not respond to bicarbonate therapy and other supportive measures. Electrolyte derangements that do not respond to supportive measures (for example hyperkalemia). Ingestion of toxins/medications that are water soluble and easily removed via dialysis. Volume Overload that does not respond to diuretic therapy or causes cardiopulmonary collapse. Clinical evidence of Uremia (persistent mental status changes, uremic pericarditis, etc.). Drugs that can be removed via dialysis

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Toxic alcohols (ethylene glycol, methanol, isopropyl alcohol) Aspirin or salicylates Phenobarbital Lithium Theophylline

Note: The optimal timing and indication for initiation of dialysis in patients with AKI remains uncertain. Currently, there is not a strong consensus on timing of initiation of dialysis in acute kidney failure. As mentioned above, early involvement of a nephrologist has been shown to lead to improved outcomes, however further well designed multi-center clinical trials of early vs late initiation of renal replacement therapy in patients with AKI including both short and long term outcome data are needed.

Recommended Prevention & Treatment of Contrast-Induced Nephropathy

The prevention of CIN requires identification of patients at risk. In these individuals the proven treatment options are:

avoidance of high osmolar radiocontrast agents discontinuation of NSAIDs intravenous hydration with 0.9% sodium chloride

A large number of studies have explored potential treatments for the prevention of CIN, but have been challenged by heterogeneity of design and mixed results. The PRESERVE trial, a multinational randomized controlled trial of hydration with normal saline versus sodium bicarbonate and use of oral n-acetylcysteine versus placebo in patients with CKD undergoing intra- arterial angiography published in 2018 was halted early due to a lack of additional benefit beyond hydration with IV normal saline for prevention of death, need for renal replacement therapy, persistent decline in renal function or AKI due to contrast. Hydration with bicarbonate was not found to be superior to normal saline. Thus normal saline can be viewed as the preferred fluid for hydration given the standard availability of this fluid. In addition, this study establishes there is no role for n-acetylcysteine for the prevention of CIN. Further high quality randomized trials of statins are required to fully establish the role of these agents for this indication.

Studies

Recommended Evaluation of Etiology of Renal Failure

Creatine kinase

The creatine kinase level is not unreasonable to check if you are concerned about rhabdomyolysis, this is particularly relevant if the patient has a history of taking a statin.

Lactic acid The serum lactic acid level is important if the patient is taking metformin, you want to ensure that there is no lacticacidosis.

Post-void residual

The post-void residual is an easy bedside method of detecting obstruction from the bladder neck down. After the patient maximally voids, either an ultrasound scan of the bladder to calculate residual volume is obtained or in a more invasive approach, a urinary catheter is inserted. If there is a residual urine volume of >100 mL, this is consistent with obstruction at the level of the bladder neck or lower. If it is <100 mL, this does not exclude an obstruction higher up in the urinary tract.

Renal ultrasound

The renal ultrasound is helpful to assess for urinary obstruction. It is 80-85% sensitive at determining if obstruction is present. It can be falsely negative in early obstruction, severe dehydration, and retroperitoneal fibrosis that will not allow ureteral dilation. Renal ultrasound is also helpful to determine if there is pre-existing renal disease by examining kidney size.

Normal-sized kidneys suggest an acute process. Small atrophic kidneys are seen with chronic kidney disease. An important exception to this rule is diabetic nephropathy as diabetes can cause kidney enlargement even in the setting of chronic disease. Asymmetric kidneys can suggest an underlying renovascular disease.

Spot urine: creatinine ratio

The spot urine : creatinine ratio would be helpful to determine if there is underlying glomerular injury that would lead to urinary protein loss.

Urine chemistries

Urine chemistries can be used to calculate the fractional excretion of sodium (FENa) as shown on the next page. One can also look specifically at Urine Na. Realize that the utility of these measures is compromised in patients taking diuretics or those who have pre-existing chronic kidney disease. In these patients a fractional excretion of urea (FEUrea) may be calculated: FEUrea = 100 x (UUrea x SCr)/(SUrea x UCr). A FEUrea < 35% is consistent with a pre- renal state.

The fractional excretion of sodium can help distinguish prerenal from intrinsic AKI. The FENa should be less than 1% in prerenal AKI, reflecting avid sodium and water reabsorption of intact nephrons. It should be higher than this in intrinsic AKI when damage to the nephrons impairs the ability of the kidney to absorb sodium and water.

The FENa is most accurate in oliguric states because the kidney does not avidly reabsorb sodium and water in non-

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oliguric states. Note also that the administration of diuretics within 12-24 hours of the time of the test may elevate the FENa in the setting of prerenal failure because diuretics impair renal sodium and water reabsorption. Therefore, this test may not be helpful in Mrs. Baxter's case (although she was not taking her medications). However, in a patient not taking diuretics, it would be a very important way to distinguish pre-renal from intrinsic renal failure.

Interpereting FENa

There are several caveats to consider when interpreting the FENa: 1) Some intrinsic renal disease conditions can be associated with a low FENa <1%. In these cases, the urine sediment would be abnormal.

Rhabdomyolysis and myoglobin-related ATN Hemolysis related ATN Contrast nephropathy and ATN ATN occurring in a patient with a sodium avid state (CHF, cirrhosis) Acute glomerulonephritis Vasculitis

2) Early obstruction is associated with a FENa <1%. The FeNa has no role in determining the diagnosis post-obstructive renal failure. 3) Last, FENa can be elevated in any patient on diuretic therapy because diuretics lead to urinary electrolyte wasting. A fractional excretion of urea can be used in this setting as the urinary excretion of urea is not affected by diuretics.

Diagnostic Studies in Acute Kidney Injury

Prerenal ARF Intrinsic Renal Post Renal*

BUN/Cr > 20 10-20 10-20

Urine Sp Grav >1.020 ≈1.010 E > 1.010

L < 1.010

Urine Osm's >350 ≈300 E > 400

L < 400

Urine Na < 20 > 30 E > 20

L < 20

FeNa < 1 > 2 E < 1

L > 3

Ucreat / Pcreat ≥ 40 ≤ 20 E ≥ 40

L ≤ 20

Renal U/S reveals hydronephrosis No No Yes

*Urine diagnostic studies are not very helpful in obstruction or post-renal renal failure E=Early, L=Late

Urine Microscopy Findings in Intrinsic Renal Failure

Cells Casts Other Webpath resources

Acute tubular necrosis (ATN) renal tubular epithelial cells

Granular casts and muddy brown casts None

Example of renal muddy brown casts

Acute glomerulonephritis (AGN)

dysmorphic RBCs, RBCs, WBCs, epithelial cells RBC (WBC can be seen) Protein

Example of dysmorphic RBC in RBC casts

Comparison: normal and

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dysmorphic RBC

Acute interstitial nephritis (AIN) eosinophils, WBCs WBC and hyaline None Example of wbc casts

The following link is an excellent resource for both macroscopic and microscopic urinary findings: http://library.med.utah.edu/WebPath/TUTORIAL/URINE/URINE.html#2

Glomerular vs Nonglomerular Hematuria

Urine microscopy Dipstick

Glomerular hematuria

Red cell casts, red cells of varying sizes and shapes, acanthocytes (some red cells appearing to have buds), or so called dysmorphic red cells.

Urine dipstick will also be positive for protein as the glomerular basement membrane is damaged.

Nonglomerular hematuria All the red cells look the same (monomorphic). Dipstick is negative for protein.

In a symptomatic patient, nonglomerular hematuria may be due to infection, nephrolithiasis, and other causes. In an asymptomatic patient, you have to be concerned about an urothelial malignancy or cancer.

Clinical Reasoning

Differential of Acute Kidney Injury

Pre-renal AKI

Pre-renal AKI is the most common cause of renal failure and accounts for 40-70% of all cases. The presence of orthostasis implies that the patient has lost approximately 20% of their intravascular volume and is suggestive of a pre-renal cause. Supine hypotension and tachycardia in the absence of fever/infection suggest an approximately 40% loss of intravascular volume. A BUN:creatinine ratio > 20 is consistent with a pre-renal cause although the BUN:creatinine ratio can also be elevated for other reasons including a catabolic state (such as that caused by sepsis or glucocorticoid therapy) and gastrointestinal bleeding. Urinalysis can be normal in pre-renal AKI.

Intrinsic AKI

Renal failure develops in 7-15% of inpatients with the most common cause being intrinsic AKI, particularly ATN. In fact, ATN accounts for 55-60% of all hospital acquired AKI. ATN is less common in the outpatient setting; it accounts for only 11% of community acquired AKI.

The top three causes of renal failure in hospitalized patients are ATN due to sepsis, post-operative renal ischemia, and contrast nephropathy.

Intrinsic renal failure can be both non-oliguric or oliguric and patients with intrinsic AKI may be orthostatic.

Urinary casts, cells, and protein are typically seen on urinalysis with intrinsic disease.

Post- renal AKI

Complete anuria is highly suggestive of post-renal AKI or obstruction although complete anuria can also be seen with severe dehydration and aortic dissection through both renal arteries. Note that decreased urine output can be seen with all three types of renal failure.

The urinalysis is typically normal in post-renal failure.

A palpable bladder would suggest obstruction.

Urine volume may vary from oliguria or anuria to normal urine output.

A note about urine volume: Oliguria is defined by a urine output of < 400 ml/day. Anuria is defined as < 200 ml/day. Oliguria and anuria may occur with any etiology of AKI.

References

American College of Radiology. ACR Manual on Contrast Media Version 10.3. https://www.acr.org/Clinical-Resources/Contrast-Manual. Accessed April 11, 2019.

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Aycock RD, Westafer LM, Boxen JL, Majlesi N, Schoenfeld EM, Bannuru RR. Acute kidney injury after computed tomography: a meta- analysis. Ann Emerg Med. 2018;71(1):44-53. DOI: 10.1016/j.annemergmed.2017.06.041.

Boccardo P, Remuzzi G, Galbusera M. Platelet dysfunction in renal failure. Semin Thromb Hemost. 2004;30(5):579-89.

Davenport MS, Khalatbari S, Cohan RH, Dillman JR, Myles JD, Ellis JH. Contrast material-induced nephrotoxicity and intravenous low- osmolality iodinated contrast material: risk stratification by using estimated glomerular filtration rate. Radiology. 2013;268(3):719-28. DOI: 10.1148/radiol.13122276.

Hinson JS, Ehmann MR, Fine DM, Fishman EK, Toerper MF, Rothman RE, Klein EY. Risk of acute kidney injury after intravenous contrast media administration. Ann Emerg Med. 2017;69(5):577-586. DOI: 10.1016/j.annemergmed.2016.11.021.

Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Acute Kidney Injury. Kidney International Supplements. 2012;2(2).

Malhotra R, Siew ED. Biomarkers for the early detection and prognosis of acute kidney injury. Clin J Am Soc Nephrol. 2017;12(1):149- 73. DOI: 10.2215/CJN.01300216.

McDonald RJ, McDonald JS, Bida JP, et al. Intravenous contrast material-induced nephropathy: causal or coincident phenomenon? Radiology. 2013;267(1):106-18. DOI: 10.1148/radiol.12121823.

McGee S, Abernethy WB 3rd, Simel DL. The rational clinical examination. Is this patient hypovolemic? JAMA. 1999;281(11):1022-9.

Mehta AN, Emmett JB, Emmett M. GOLD MARK: an anion gap mnemonic for the 21st century. Lancet. 2008;372(9642):892.

Subramaniam RM, Suarez-Cuervo C, Wilson RF, et al. Effectiveness of prevention strategies for contrast–induced nephropathy: a systematic review and meta-analysis. Ann Intern Med. 2016;164(6):406-16. DOI: 10.7326/M15-1456.

Thomas ME, Blaine C, Dawnay A, et al. The definition of acute kidney injury and its use in practice. Kidney Int. 2015;87(1):62-73. DOI: 10.1038/ki.2014.328

Wagner B, Drel V, Gorin Y. Pathophysiology of gadolinium-associated systemic fibrosis. Am J Physiol Renal Physiol. 2016;311(1):F1- F11. DOI: 10.1152/ajprenal.00166.2016.

Weisbord SD, Gallagher M, Jneid H, et al. Outcomes after angiography with sodium bicarbonate and acetylcysteine. N Eng J Med. 2018;378(7):603-14. DOI: 10.1056/NEJMoa1710933.

Wilhelm-Leen E, Montez-Rath ME, Chertow G. Estimating the risk of radiocaontrast-associated nephropathy. J Am Soc Nephrol. 2017;28(2):653-659. DOI: 10.1681/ASN.2016010021.

Zarbock A, Mehta RL. Timing of Kidney Replacement Therapy in Acute Kidney Injury. Clin J Am Soc Nephrol. 2019 Jan 7;14(1):147-149. DOI: 10.2215/CJN.08810718.

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