Which pathology may result in acute kidney injury (aki) from a prerenal etiology?

Acute Kidney Injury

Fred F. Ferri MD, FACP, in Ferri's Clinical Advisor 2022, 2022

Diagnosis

Table 3 summarizes useful clinical features, urinary findings, and confirmatory tests in the differential diagnosis of AKI.

Differential Diagnosis

Refer to “Etiology.” Diagnostic tests to distinguish prerenal and renal AKI are described inTable 4. A diagnostic approach to patients with suspected AKI is shown inFig. 1.

Laboratory Tests

Elevated serum creatinine.

Standard estimating equations for glomerular filtration rate (GFR) require steady-state creatinine levels and are not recommended to estimate GFR during AKI.

Elevated blood urea nitrogen (BUN): BUN-to-creatinine ratio is commonly >20:1 in prerenal azotemia, postrenal azotemia, and acute glomerulonephritis.

BUN-to-creatinine ratio is <20:1 in acute interstitial nephritis and ATN.

Hyperkalemia, hyperphosphatemia, and metabolic acidosis are common.

Hypocalcemia and hyponatremia or hypernatremia may occur, depending on etiology.

Urinalysis is the initial diagnostic evaluation. Prerenal and postrenal AKI are typically characterized by a normal urinalysis. Conversely, abnormal findings should prompt further work-up for specific intrinsic causes of AKI that may require intervention. Hematuria and proteinuria imply glomerulonephritis, heavy (>3+) proteinuria is associated leukocyturia may signify AIN. Microscopic examination of urine sediment may facilitate diagnosis: Granular casts in ATN, dysmorphic red blood cells or red blood cell casts in acute glomerulonephritis, and white blood cell casts in AIN.

In oliguric patients, obtain urine sodium and creatinine concentrations for determination of fractional excretion of sodium: FENa = 100% × (UNa × PCr)/(PNa × UCr). FENa <1% is occurs in prerenal AKI and is >1% in intrinsic AKI. FENa may be falsely elevated in patients taking diuretics or falsely low in several intrinsic renal conditions, including acute glomerulonephritis, contrast-induced nephropathy, and rhabdomyolysis.

Fractional excretion of urea (FEUrea) can be used to assess renal dysfunction in AKI. FEUrea is more useful than FENa during diuretic therapy. FEUrea is calculated as follows: FEUrea = 100% × (UUrea × PCr) / (PUrea × UCr). If FEUrea <35% prerenal acute kidney injury is likely, and if FEUrea >50% intrinsic AKI is likely.

Urinary osmolarity range of 250 mOsm/kg H2O to 300 mOsm/kg H2O in ATN (isosthenuria), <400 mOsm/kg H2O in postrenal azotemia, and >500 mOsm/kg H2O in prerenal azotemia and acute glomerulonephritis.

In suspected glomerulonephritis (GN) (e.g., hematuria plus proteinuria), additional serologic testing may be warranted. Abnormal liver function tests and elevated inflammatory markers are nonspecific. Immune complex deposition disorders (e.g., infectious GN, lupus nephritis, cryoglobulinemic vasculitis) are characterized by decreased complement (C3, C4) levels. Specific testing includes antinuclear antibodies (lupus), antineutrophil cytoplasmic antibodies (ANCA-associated vasculitis), antiglomerular basement membrane antibodies (Goodpasture disease), and cryoglobulins. Kidney biopsy is frequently required for diagnostic confirmation.

Creatinine phosphokinase level is indicated if rhabdomyolysis is suspected; positive blood reaction on a urine dipstick with typically few or no red blood cells by microscopy may indicate myoglobinuria from rhabdomyolysis.

Serum free light chain analysis, serum and urine protein electrophoresis, and serum and urine immunofixation electrophoresis for suspected multiple myeloma or other plasma cell dyscrasias. Myeloma can cause AKI via a variety of mechanisms, including tubular precipitation of filtered light chains (cast nephropathy), hypercalcemia, and amyloidosis, among others.

Kidney biopsy may be indicated in patients with intrinsic kidney failure when considering specific therapy. The major indications for kidney biopsy include the following: Differential diagnosis of nephrotic syndrome, distinguishing lupus vasculitis from other vasculitides, distinguishing lupus membranous nephropathy from idiopathic membranous nephropathy, confirmation of hereditary nephropathies based on ultrastructure, diagnosis of rapidly progressive glomerulonephritis, distinguishing AIN from ATN, and separation of primary glomerulonephritides. In addition to establishing a diagnosis, biopsy may determine renal prognosis and guide direction of management. Severe interstitial fibrosis is associated with poor renal outcomes.

Biomarkers of kidney injury have been explored for earlier diagnosis of AKI or to separate intrinsic from prerenal causes. Candidate markers include cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), kidney-injury molecule 1 (KIM-1), liver fatty acid binding protein (LFABP), and the product of tissue inhibitor of metalloproteinase-2 and insulin-like growth-factor binding protein-7 (TIMP2∗IGFBP7), the first biomarker of AKI risk prediction there remains little published experience with this test, and the clinical role remains undefined.

Acute Renal Failure

Robert J. Anderson, in Critical Care Medicine (Third Edition), 2008

BACKGROUND AND DEFINITION

Acute renal failure (ARF) is the sudden development of renal insufficiency that leads to retention of nitrogenous waste (urea nitrogen and creatinine) in the body. Despite consensus regarding this broad definition, there are diverse opinions as to the degree of elevation of serum creatinine sufficient to ascribe a diagnosis of ARF.1–4 These differences in diagnostic criteria, as well as in the populations under study, have led to variances in reported frequency, causes, and outcomes of ARF. In an effort to arrive at a more standard definition of ARF, some recent studies have emphasized the RIFLE criteria.5–8 These criteria refer to various elements in the developmental pathway of ARF including risk (R), injury (I), failure (F), loss (L), and end stage (E) and are based on both the magnitude of rise in the serum creatinine concentration and the urine output. The RIFLE criteria for the diagnosis of ARF are depicted in Table 56-1. Although further validation of the RIFLE criteria is necessary, these criteria can serve as a reasonable starting point for a more uniform approach to the clinical aspects of ARF. Clearly, better criteria for the uniform definition of ARF are necessary.

Although the precise definition of ARF may remain arguable, experts generally agree on several aspects of contemporary ARF. First, ARF occurs with significant frequency, especially in the hospital and in the intensive care unit (ICU) setting.1–9 Second, multiple pathophysiologic pathways and clinical events lead to an identical syndrome of ARF.1–9 Third, timely delineation of the cause of ARF is paramount in designing appropriate therapy.10–13 Fourth, even when modest in degree, ARF is associated with significant morbidity and mortality.10,14,15 Fifth, ARF is one of the few causes of complete organ failure that is potentially totally reversible.1–9 Finally, some studies indicate that a significant percentage of cases of ARF are preventable.10–13 The high frequency of occurrence, multiple causes, associated morbidity and mortality, and potential reversibility demand an organized approach to ARF. In this chapter we review the incidence, pathogenesis, clinical manifestations, management, and outcome of ARF, especially as it relates to critically ill patients. An overview of contemporary ICU-associated ARF is depicted in Table 56-2.

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Prevention and Management of Acute Kidney Injury

Alan S.L. Yu MB, BChir, in Brenner and Rector's The Kidney, 2020

Definition of Acute Kidney Injury

Acute kidney injury (AKI) is a heterogeneous syndrome defined by rapid (hours to days) decline in the glomerular filtration rate (GFR), resulting in the retention of metabolic waste products, including urea and creatinine, and dysregulation of fluid, electrolyte, and acid-base homeostasis.1 Although often considered a discrete syndrome, AKI represents a broad constellation of pathophysiologic processes of varied severity and cause. These include decreases in the GFR as the result of hemodynamic perturbations that disrupt normal renal perfusion without causing parenchymal injury, partial or complete obstruction to urinary flow, and a range of processes with characteristic patterns of glomerular, interstitial, tubular, or vascular parenchymal injury. AKI occurs in a heterogeneous patient population—genetics, age, kidney functional status, accompanying comorbidities—and the cause is often multifactorial.

The termacute kidney injury has largely supplanted the older terminology of acute renal failure (ARF). This change reflects recognition of serious shortcomings with the older terminology. Acute renal failure suggested a dichotomous relationship between normal kidney function and overt organ failure; in contrast, AKI captures the growing body of data associating small to moderate acute and transient decrements in kidney function with serious, adverse outcomes. Although the AKI terminology does emphasize the graded aspect of acute kidney disease, it should be recognized that this terminology is also imperfect. The terminjury can be construed to imply the presence of parenchymal organ damage, which may be absent in a variety of settings associated with an acute decline in kidney function, such as early obstructive disease and prerenal azotemia associated with volume depletion. Although the termacute kidney dysfunction might better characterize the entire spectrum of the syndrome, AKI is the term that has been adopted by consensus and is now increasingly used in the medical literature.2,3 In this chapter, AKI will be used to describe the entire spectrum of the syndrome. Although, in clinical practice, the termacute tubular necrosis (ATN) is often used synonymously with AKI, these terms should not be used interchangeably. Although ATN is the most common form of intrinsic AKI, particularly in critically ill patients, it represents only one of multiple forms of AKI. In addition, there may be a lack of concordance between the clinical syndrome and the classic histopathologic findings of ATN.4,5

Decreased urine output is a cardinal (although not universal) manifestation of AKI, and patients are often classified based on urine flow rates as nonoliguric (urine output >400 mL/day), oliguric (urine output <400 mL/day), or anuric (urine output <100 mL/day).6 Transient oliguria may occur in the absence of significant decrements in kidney function, because increased tubular salt and water reabsorption is a normal physiologic response to volume depletion. In contradistinction, persistent oliguria, despite the presence of adequate intravascular volume, is virtually always a manifestation of AKI, with lower urine volume typically associated with more severe initial renal injury. The categorization of AKI based on urine volume has clinical implications for the development of volume overload, severity of electrolyte disturbances, and overall prognosis. Although oliguric AKI is associated with a higher mortality risk than nonoliguric AKI, therapeutic interventions to augment urine output (see later) have not been shown to improve patient outcomes.7

Biomarkers in Acute and Chronic Kidney Diseases

Alan S.L. Yu MB, BChir, in Brenner and Rector's The Kidney, 2020

Acute Kidney Injury Markers

In the cardiac sciences, the discovery of biomarkers, such as troponins, which reflect early cardiomyocyte damage rather than decreased cardiac function, has enabled the development and implementation of novel therapeutic strategies to reduce coronary insufficiency and associated morbidity and mortality.34,35 By contrast, the delay in diagnosis associated with the use of kidney biomarkers, such as serum creatinine concentration, has impaired the ability of nephrologists to conduct interventional studies in which the intervention can be implemented early in the course of the disease process.36 Although the past decade has seen a revolution in terms of diagnostic criteria for AKI with the RIFLE (risk,injury,failure,loss,end-stage kidney disease) classification37 and the Acute Kidney Injury Network (AKIN) definition of AKI38 being harmonized into the Kidney Disease: Improving Global Outcomes (KDIGO) classification39 (Table 27.3), these criteria remain limited by their reliance on the serum creatinine concentration on some level. More recently, there has been a call to expand these definitions further to potentially include biomarkers, but as of the time of this publication, these new guidelines have yet to be widely accepted.40 These new guidelines and the concept of AKI remain reliant on the serum creatinine level and will continue to serve as a limitation, given creatinine's role as a functional biomarker. The serum creatinine level can increase in cases of prerenal azotemia when there is no tubular injury and can be unchanged under conditions of significant tubular injury, particularly when patients have good underlying kidney function and significant kidney reserve. Nonetheless, these criteria have advanced our understanding of the epidemiology of AKI, and these standardized consensus definitions have allowed for comparisons and aggregation of data from a larger number of papers.41 Biomarkers of AKI can serve several purposes and are no longer thought of as a replacement for the serum creatinine level.Table 27.4 summarizes several of the potential uses of AKI biomarkers.Fig. 27.2 summarizes the kidney-specific location of the AKI biomarkers discussed later.

Urine and serum biomarkers each have advantages and disadvantages. Serum biomarkers are often not stable and are difficult to measure because of interference with several serum proteins. By contrast, urinary biomarkers are relatively stable and easy to assess; however, their concentrations are greatly influenced by the hydration and volume status of the patient and other conditions that affect urinary volume. To overcome this challenge, urinary biomarker concentrations have often been normalized to urinary creatinine concentrations to eliminate the influence of urinary volume on the assumption that the urinary creatinine excretion rate is constant over time, and that biomarker production or excretion has a linear relationship with the urinary creatinine excretion rate. Bonventre and colleagues have challenged this assumption, especially in AKI settings, when the urine creatinine excretion rate is not constant and changes over time, greatly influencing the normalized value of a putative urinary biomarker after normalization. They have suggested that the most accurate method to quantify biomarkers is the timed collection of urine samples to estimate the renal excretion rate42; however, this approach is not practical for routine clinical care. Endre and colleagues delved into this issue further by demonstrating that the ideal method for quantitating biomarkers of urinary AKI depends on the outcome of interest; absolute biomarker concentrations best diagnosed AKI at the time of intensive care unit (ICU) admission, whereas normalization to urinary creatinine improved the prediction of incipient AKI.43 A potential explanation of the failings of normalization is that it will often amplify the signal. For example, when the glomerular filtration rate (GFR) is reduced in immediate response to a tubular injury, the amount of biomarker produced will increase, and the urinary creatinine level will decrease. The normalized value will therefore increase by a greater amount in the short term than can be explained by the increase in the absolute level of biomarker production. Currently, there is no standardized method of accounting for this issue, with some urinary biomarkers being normalized to urine creatinine and others being reported without normalization.

Acute Renal Failure

In The Most Common Inpatient Problems in Internal Medicine, 2007

1

Acute renal failure (ARF) refers to an abrupt decline in renal function.

2

There is no universally accepted laboratory definition of ARF.

3

Pre‐renal ARF occurs when decreased renal perfusion leads to a reduction in the glomerular filtration rate.

4

Intrinsic ARF occurs when there is injury to the renal glomeruli, tubules, interstitium, or vessels. Acute tubular necrosis is the most common cause of intrinsic ARF.

5

Post‐renal ARF results from obstruction of the urinary collecting system.

6

Most patients with ARF are asymptomatic and are diagnosed based on laboratory data.

7

Initial testing in patients with ARF should include urinalysis and measurement of electrolytes, urine output, serum calcium, phosphate, and magnesium. Depending on the clinical circumstances, other tests may include renal ultrasonography, complete blood count, coagulation panel, urine eosinophils, creatine phosphokinase, and calculation of the fractional excretion of sodium (FENa).

8

The serum creatinine concentration does not accurately reflect the glomerular filtration rate in the nonsteady state of ARF.

9

The blood urea nitrogen‐to‐creatinine ratio is usually >20:1 in prerenal disease.

10

In oliguric patients, FENa < 1% usually suggests prerenal ARF whereas FENa > 2% usually suggests intrinsic renal disease.

11

The approach to renal failure should include determination of (a) chronicity, (b) patient comorbidities, (c) whether there has been a recent vascular intervention, (d) whether the patient has received intravenous contrast or other nephrotoxic medications, and (e) volume status.

12

General management principles of ARF include (a) institution of a “renal” diet, (b) adjusting dosages of all medications metabolized or excreted by the kidneys, (c) discontinuing nephrotoxins or substituting non‐nephrotoxic alternatives (if possible), (d) monitoring fluid status, and (e) monitoring and treating complications of ARF (such as hyperkalemia, hyponatremia, and hyperphosphatemia).

13

Prompt treatment of renal obstruction can lead to complete recovery of renal function. Post‐obstructive diuresis (4–20 L/day), which sometimes occurs following correction of bilateral urinary obstruction, can lead to hypovolemia, hypokalemia, and hypomagnesemia.

14

Diuretics do not reduce mortality or the need for dialysis in ARF patients.

15

Low‐dose intravenous dopamine (1–3 μg/kg/min) does not reduce mortality or promote recovery of renal function in patients with ARF.

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Renal Toxicology

K.J. Kelly, in Comprehensive Toxicology, 2010

7.07.1.2 Definitions

AKI is a group of syndromes characterized by a sudden and sustained decrease in the excretion of nitrogenous waste products that is not readily reversed by correction of inciting factors and it is associated with histological changes in the kidney. Generally, AKI is diagnosed after a clear increase in serum creatinine over hours or days, often well after a significant decline in glomerular filtration rate (GFR) has occurred. Changes in serum creatinine and urine output can occur in the normal response to intravascular volume depletion and decreased renal blood flow. Thus, changes in serum creatinine and/or urine output do not always define renal pathology, and more specific biomarkers are needed. Studies of AKI have employed changes in creatinine, changes in estimated GFR, urine output, and/or the provision of dialysis to define AKI. In general, there are no uniform criteria for dialysis for studies that used dialysis to define AKI. The heterogeneity of AKI definitions, the diverse patient populations studied, and differences in the severity of renal injury examined have complicated comparisons. More recently, the RIFLE (risk, injury, failure, loss, end-stage renal disease (ESRD)) criteria for AKI were proposed by the Acute Dialysis Quality Initiative (ADQI) group (Bellomo et al. 2004). Definitions and classifications of severity of AKI are given in Table 1. These consensus criteria have proven to be useful and are associated with both mortality and length of hospital stay. In a retrospective study, Hoste and coworkers (2006) reported AKI according to RIFLE criteria in 67% of ICU admissions; AKI class F (failure) was associated with 26.3% mortality, class I (injury) with 11.4% mortality, and class R (risk) with 8.8% mortality (vs 5.5% in the absence of AKI). Given that small changes in renal function affect outcome, the Acute Kidney Injury Network (AKIN) proposed a modification of the RIFLE criteria. These modifications (Mehta et al. 2007) are also given in Table 1. The criterion of increase in creatinine of 0.3 mg dl−1 was proposed in response to data showing that mild declines in renal function are associated with increased mortality (Lassnigg et al. 2008). In addition, AKIN proposed that increases in creatinine occur within 48 h, that criteria be applied after volume status optimization, and that urinary tract obstruction be excluded before the use of anuria to diagnose AKI. As such, the AKIN criteria have been shown to be predictive of mortality (Barrantes, Tian, Vazquez et al. 2008). Interestingly, Zappitelli et al. (2008) reported markedly different estimates of AKI incidence in hospitalized children using different accepted definitions of AKI.

Table 1. Definitions of acute kidney injury (AKI)

RIFLE classification of AKI
Creatinine Urine Output
Risk ↑ Serum creatinine 1.5 fold OR urine output <0.5 ml kg−1 hour−1 for 6 hours
Injury ↑ Serum creatinine 2 fold OR urine output <0.5 ml kg−1 hour−1 for 12 hours
Failure ↑ Serum creatinine 3 fold OR urine output <0.3 ml kg−1 hour−1 for 24 hours or anuria for 12 hours
AKI Network definitiona,b
Stage 1 ↑ serum creatinine 1.5 fold or ≥0.3 mg dl−1 OR urine output <0.5 kg−1 hour−1 > 6 hours
Stage 2 ↑ serum creatinine >2 fold OR urine output <0.5 kg−1 hour−1 > 12 hours
Stage 3 ↑ serum creatinine >3 fold OR urine output <0.3 kg−1 hour−1 for 24 hours or anuria for 12 hours
Or serum creatinine >4 mg dl−1 (with ↑ ≥0.5 mg dl−1)

aIncreases in creatinine within 48 hours.bfor urine output criteria, urinary tract obstructions should be excluded and volume resuscitation administered when applicable.

Azotemia refers to increases in blood urea nitrogen (BUN) and usually indicates decreased clearance of nitrogenous waste products or renal failure. With normal kidney function, however, BUN can increase in the presence of gastrointestinal bleeding, steroid administration, a catabolic state, or the infusion of amino acids (usually in the form of parenteral nutrition) Increases in serum creatinine (independent of renal function) can occur with increased creatinine release from muscle or decreased tubular secretion (i.e., due to cimetidine or trimethaprim). In addition, acetoacetate, cephalosporins, flucytosine, methanol, and isopropyl alcohol can interfere with the standard laboratory (Jaffe) reaction used to determine creatinine.

GFR is the rate at which plasma crosses from glomerular capillaries to the urinary space, and inulin clearance is the standard for estimating GFR or renal excretory function as insulin secretion/reabsorption after filtration is minimal. At this time, renal function is generally estimated from serum creatinine, 24 h creatinine clearance, abbreviated modification of diet in renal disease (MDRD) (Levey et al. 1999), or Cockcroft–Gault equations (Cockcroft and Gault 1976) (Table 2). A significant limitation of these estimates is the assumption of a steady state or stable renal function.

Table 2. Estimates of renal function

Creatinine Clearance Creatinine clearance = [(urinary creatinine × 24 hour urine volume in mL) × 1440 minutes day1]/(serum creatinine)
Cockcroft–Gault Creatinine clearance = [(140-age) × lean body weight in kg]/(serum creatinine × 72)
Modification of diet in renal disease (MDRD, abbreviated) GFR/1.73 m2 = 186.3 × serum creatinine−1.154 × age−0.203
GFR/1.73 m2 = 186.3 × serum creatinine−1.154 × age−0.203 × 0.742 if female
GFR/1.73 m2 = 186.3 × serum creatinine−1.154 × age−0.203 × 1.21 if black

The relationship between creatinine and GFR is not linear (Figure 1). A normal or near-normal GFR may decrease significantly (i.e., by 50%) before a clear increase in creatinine is observed. As GFR decreases, tubular creatinine secretion may also increase. Conversely, in chronic kidney disease (CKD), a relatively large change in serum creatinine can occur with relatively small changes in GFR.

Which pathology may result in acute kidney injury (aki) from a prerenal etiology?

Figure 1. The nonlinear relationship between renal function and creatinine. A given increase in creatinine (a; within the normal range) can signify a large decline in renal function (glomerular filtration rate) while the same absolute increase in creatinine (b) may represent little change in function with chronic renal failure.

Oliguria generally refers to a urine output of <400 ml day−1, and AKI is frequently characterized by oliguria. Higher urine output in AKI (nonoliguric AKI) may be due to less severe injury (Anderson et al. 1977; Rahman and Conger 1994), and this is generally associated with better prognosis (Allegren et al. 1997). Anuria, a rare condition that usually occurs in shock with severe hypotension, complete bilateral obstruction, or renal cortical necrosis, usually refers to a urine output of <50 ml day−1.

Acute tubular necrosis (ATN) and AKI or ARF are terms often used interchangeably, although ATN refers to the pathological changes observed after acute ischemia or exposure to toxicants such as gentamicin or cisplatin. Although necrosis of proximal tubule epithelial cells is found in animal models of AKI, this finding may not be typical in human disease (Solez et al. 1974). Morphological data in human AKI, however, are limited – biopsies are usually reserved for cases with uncharacteristic features.

Convection refers to the removal of plasma constituents by ‘solvent drag’ with ultrafiltration during RRT. This is the mode of solute clearance in continuous venovenous hemofiltration (CVVH). Diffusion refers to solute removal via movement ‘down’ a concentration gradient (i.e., during dialysis).

RRT generally refers to all forms of dialysis and hemofiltration. These can be categorized into intermittent and continuous therapies. Intermittent hemodialysis is typically performed for 3–4 h per session, 3 times per week, although for AKI it may be performed 6 days per week. In sustained low-efficiency dialysis (SLED) or extended daily dialysis, the duration of dialysis is extended (usually to 6–12 h), permitting a more gradual removal of fluid and solutes and greater hemodynamic stability. The aim of continuous therapies is the provision of solute clearance 24 h per day, although in practice this is rarely achieved. In CVVH, solute removal is by convection, and fluid removed (by ultrafiltration) is replaced (often only partially) with a replacement solution. In continuous venovenous hemodialysis (CVVHD), solute removal is by diffusion; dialysate is delivered across a membrane countercurrent to blood flow; and replacement fluid is generally not used. Continuous venovenous hemodiafiltration (CVVHDF) combines dialysis and hemofiltration so that solutes are removed by both diffusion and convection, and both dialysate and replacement solution are used.

Dialysis ‘dose’ refers to quantification of solute (usually urea) removal, generally in the form Kt/V, where K refers to a constant dependent on the dialysis prescription including membrane characteristics, t to the time, and V to the volume of distribution of the solute in question. Although the removal of BUN may not be representative of the removal of other solutes, the assessment of actual urea clearance is related to outcome in chronic dialysis (Gotch and Sargent 1985; Parker et al. 1994) and possibly AKI (Ricci and Ronco 2008).

The remainder of this chapter will focus on AKI due to intrinsic renal parenchymal injury as a result of exposure to toxicants and/or ischemia.

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Acute Renal Failure

Ajay K. Singh MBBS, FRCP, in Decision Making in Medicine (Third Edition), 2010

Acute renal failure (ARF) is defined as a reduction in renal function manifested by an increase in serum creatinine over a period of hours to days. It is often associated with decreased urine output and a failure to excrete nitrogenous waste products and may lead to fluid and electrolyte imbalances. In the absence of a sustained increase, serum creatinine >0.5 mg/dl is a well-established definition of ARF. The causes of ARF may be prerenal (e.g., hypotension, arterial thrombosis), renal parenchymal (e.g., acute tubular necrosis [ATN], glomerulonephritis, tubulointerstitial nephritis), or postrenal (e.g., acute obstruction).

A.

The patient with ARF usually presents with abnormal laboratory values, decreased urine output, or both. A thorough history and physical examination are critical in evaluation. Key issues are as follows: (1) ascertaining a history suggestive of bladder outflow obstruction (e.g., secondary to prostatism, such as nocturia, hesitation, and frequency of urination; assessment of any exposures to toxins or nephrotoxic medications, such as exposure to lead or ingestion of NSAIDs; and any systemic symptomatology suggesting an autoimmune etiology, such as arthralgias, arthritis, skin rash); (2) family history of diabetes or kidney disease; and (3) a physical examination focused on assessment of extracellular volume (edema, dry mucous membranes, hypertension, orthostatic hypotension, skin turgor) and detection of systemic process, such as an infection or an autoimmune process.

B.

The evaluation of a fresh-voided urine sample for dipstick and microscopy of the urine sediment is essential. The presence of hematuria, proteinuria, or pyuria is important in diagnosis. Careful evaluation of the urinary sediment is key. In a patient with ATN, the presence of tubular cells, amorphous debris representing necrotic cells, and deeply pigmented coarsely granular (“muddy brown”) casts are typical. In glomerulonephritis, the presence of red cells, particularly dysmorphic red cells, and red cell casts are characteristic. In acute tubulointerstitial nephritis, the presence of white cells, tubular epithelial cells, and white cell and/or tubular cell casts is typical. Laboratory testing should also include measurement of urine osmolality; sodium, protein, and creatinine in the urine; and serum osmolality, sodium, glucose, anion gap, albumin, total protein, calcium, BUN, and creatinine. In the workup of a patient suspected of having glomerulonephritis, serologic testing, including measurement of complement fractions, and assays for ANA, antineutrophil cytoplasmic antibody (ANCA), and antiglomerular antibody (anti-GBM) should be considered. Early evaluation with a renal ultrasound (US) is essential to exclude urinary obstruction. Severe cases of ATN and some forms of rapid progressive glomerulonephritis (RPGN; e.g., anti-GBM disease) may require a renal biopsy for diagnosis.

C.

Prerenal renal failure can result from any condition that leads to decreased renal perfusion, such as intravascular volume depletion (e.g., hemorrhage, GI losses, excessive sweating, third space losses), decreased effective volume (e.g., congestive heart failure), increased renal vascular resistance (e.g., NSAIDs, hepatorenal syndrome), vasoconstrictor drugs (e.g., cyclosporine, radiocontrast), or decreased intraglomerular pressure (e.g., angiotensin-converting enzyme inhibitors). As proximal tubule function is preserved, the urine osmolality (UOsm) is typically >500 mOsm/kg, urine sodium (UNa) is <20 mEq/L, and the fractional excretion of sodium (FeNa) is <1%. In patients receiving diuretics, a fractional excretion of urea of <35% has been found to be more useful. Prerenal azotemia is reversible within 24–72 hours of correction of the hypoperfused state; however, prolonged hypoperfusion may lead to ischemic ATN, which has a more protracted course to recovery (see later). An otherwise bland urine sediment or hematuria with nondysmorphic RBCs calls for evaluation with imaging studies to exclude obstruction.

D.

ATN may result from ischemia, exogenous toxins and nephrotoxic drugs (e.g., aminoglycosides, cisplatin, radiocontrast), or endogenous toxins (hemoglobin, myoglobin, uric acid). Urinary oxalate crystals and an osmolar gap point toward ethylene glycol as the etiology, whereas predominance of uric acid crystals should evoke dedicated laboratory studies for gout and other states with high cell turnover such as hematologic malignancies and tumor lysis syndrome. A dipstick positive for hemoglobin in the absence of RBCs in the urine sediment is indicative of myoglobin or hemoglobin in the urine. Serum studies for creatine kinase (CK), haptoglobin, and the clinical context help to make the diagnosis of rhabdomyolysis. A clinically important issue is the differentiation of prerenal azotemia and ischemic ATN that together underlies 75% of cases with acute kidney injury. ATN is characterized by loss of renal tubule epithelial cell function; therefore, urine osmolality is typically <350 mOsm/kg, urine sodium is >40 mEq/L, and FeNa is >1%. In some nonoliguric forms of ATN, such as after radiocontrast or rhabdomyolysis, the FeNa can initially be <1%. Treatment for ATN is supportive; thus far, no therapeutic intervention has been shown to accelerate recovery from ATN, reduce mortality, or improve the length of stay in the hospital. Renal replacement therapy should be provided in a timely fashion when required by volume status or electrolyte imbalances.

E.

Dysuria, flank pain, and fever may be associated with an ascending pyelonephritis. Antibiotics are given according to urine and blood culture results. Urinary tract infections in single kidneys (native or transplanted) are particularly prone to decrease renal function. Drug-induced allergic interstitial nephritis (AIN) resulting from a broad variety of medications may be associated with eosinophilia, fever, and skin rash. However, <10% of patients with AIN present with all three symptoms. Any suspected agent should be discontinued. A renal biopsy is recommended to confirm the diagnosis prior to initiating steroid therapy and to exclude other causes of interstitial nephritis such as the tubulointerstitial nephritis and uveitis (TINU) syndrome or sarcoidosis.

F.

Serologic evaluation is usually indicated to diagnose cases of ARF with hematuria, proteinuria, and a sediment that contains dysmorphic RBCs and/or RBC casts. Measurement of a spot urine protein and creatinine is helpful in the differential diagnosis. A urine protein:creatinine ratio >3.5 indicates nephrotic-range proteinuria. If, in addition, the patient has edema and there is a low serum albumin (<3 mg/dl), the patient fits the definition of nephritic syndrome. In this scenario, a renal biopsy can be helpful in establishing the precise diagnosis. In a patient with hypertension and a urine sample that reveals hematuria, proteinuria, and the presence of dysmorphic cells and/or red cell casts, acute nephritis is the most likely diagnosis. A careful clinical evaluation looking for systemic abnormalities and a full serologic evaluation are necessary. Serologic evaluation includes, depending on history and examination, complement levels, ASLO-titer, ANA, ANCA, anti-GBM, hepatitis B and C serologies, cryoglobulins, and syphilis serology. In many instances, a renal biopsy is needed for diagnosis. If signs of systemic vasculitis or pulmonary involvement are present, early intervention with immunosuppressive therapy (IV steroids, cyclophosphamide, plasmapheresis) may be indicated before the results of serologic evaluations are available.

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Acute Kidney Injury

Joseph V. Bonventre M.D., Ph.D., Venkata Sabbisetti Ph.D., in Chronic Kidney Disease, Dialysis, and Transplantation (Third Edition), 2010

Abstract

The diagnosis of acute kidney injury (AKI) has relied on serum creatinine and urine output, two biomarkers that are insensitive and nonspecific especially early in the course of the syndrome. Additionally, creatinine and urine output are functional markers and not markers of injury. The lack of sensitive and specific injury biomarkers has greatly impeded the early diagnosis of AKI and limited the ability to predict outcome of the syndrome. Furthermore, the absence of early biomarkers has impaired the ability of investigators to design clinical trials to adequately evaluate the potential therapeutic efficacy of agents that might improve outcomes of AKI. A large number of biomarkers of kidney injury have been suggested and yet, for various reasons, none has been routinely accepted in animal or clinical studies. We review the rationale for biomarker development and the status of some of the more promising biomarkers, and provide reasons why the clinical use of these markers will transform the way that we diagnose AKI. Biomarkers of kidney injury also will enable the development of more efficient strategies to evaluate new therapeutic approaches to this common clinical condition, which continues to be associated with high morbidity and mortality.

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URL: https://www.sciencedirect.com/science/article/pii/B9781437709872000480

What is the most common cause of Prerenal AKI?

Causes of prerenal acute kidney injury include: Severe blood loss and low blood pressure related to major cardiac or abdominal surgery, severe infection (sepsis), or injury.

What is the pathology of AKI?

The pathophysiology of AKI involves a complex interplay among vascular, tubular, and inflammatory factors followed by a repair process that can either restore epithelial differentiation and function to normal or result in fibrotic chronic kidney disease.

Which potential cause of kidney failure is Prerenal?

Prerenal azotemia is the most common form of kidney failure in hospitalized people. Any condition that reduces blood flow to the kidney may cause it, including: Burns. Conditions that allow fluid to escape from the bloodstream.

What are the 3 causes of AKI?

What causes acute kidney injury? There are three major reasons why your kidneys might be injured: lack of blood flow to the kidneys, blockage in urine flow that causes infections, or direct kidney damage by infections, medications, toxins, or autoimmune conditions.