Renal Failure

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Continuing Education Activity

The term renal failure denotes inability of the kidneys to perform excretory function leading to retention of nitrogenous waste products from the blood. Acute and chronic renal failure are the two kinds of kidney failure. When a patient needs renal replacement therapy, the condition is called end-stage renal disease (ESRD). This activity reviews the causes, pathophysiology, presentation and diagnosis of renal failure and highlights the role of the interprofessional team in its management.


  • Recall the causes of renal failure.
  • Describe the laboratory features of renal failure.
  • Summarize the treatment options for renal failure.
  • Explore modalities to improve care coordination among interprofessional team members in order to improve outcomes for patients affected by renal failure.


The term renal failure denotes the inability of the kidneys to perform excretory function leading to retention of nitrogenous waste products from the blood. Functions of the kidney are as follows:

  • Electrolyte and volume regulation
  • Excretion of nitrogenous waste
  • Elimination of exogenous molecules, for example, many drugs
  • Synthesis of a variety of hormones, for example, erythropoietin
  • Metabolism of low molecular weight proteins, for example, insulin

Acute and chronic renal failure are the two kinds of kidney failure.

Acute Renal Failure (ARF)

ARF is the syndrome in which glomerular filtration declines abruptly (hours to days) and is usually reversible. According to the KDIGO criteria in 2012, AKI can be diagnosed with any one of the following: (1) creatinine increase of 0.3 mg/dL in 48 hours, (2) creatinine increase to 1.5 times baseline within last 7 days, or (3) urine volume less than 0.5 mL/kg per hour for 6 hours. [1] Recently the term acute kidney injury (AKI) has replaced ARF because AKI denotes the entire clinical spectrum from a mild increase in serum creatinine to overt renal failure. [2]

Chronic Renal Failure (CRF)

CRF or chronic kidney disease (CKD) is defined as a persistent impairment of kidney function, in other words, abnormally elevated serum creatinine for more than 3 months or calculated glomerular filtration rate (GFR) less than 60 ml per minute / 1.73m2. It often involves a progressive loss of kidney function necessitating renal replacement therapy (dialysis or transplantation). When a patient needs renal replacement therapy, the condition is called end-stage renal disease (ESRD). [1]

CKD classified based on grade:

  • Grade 1: GFR greater than 90
  • Grade 2: 60 to 89
  • Grade 3a: 45 to 59
  • Grade 3b: 30 to 44
  • Grade 4: 15 to 29
  • Grade 5: Less than 15

CKD classified based on stage:

  • Stage 1: GFR greater than 90
  • Stage 2: 60 to 89
  • Stage 3: 30 to 59
  • Stage 4: 15 to 29
  • Stage 5: Less than 15


Renal Failure Etiopathogenesis

Acute Renal Failure [3]

  1. Prerenal (approximately 60%): Hypotension, volume contraction (e.g., sepsis, hemorrhage), severe organ failure such as heart failure or liver failure, drugs like non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin receptor blockers (ARB) and angiotensin-converting enzyme inhibitors (ACEI), and cyclosporine
  2. Intrarenal (approximately 35%): Acute tubule necrosis (from prolonged prerenal failure, radiographic contrast material, drugs like aminoglycosides, or nephrotoxic substances), acute interstitial nephritis (drug-induced), connective tissue disorders (vasculitis), arteriolar insults, fat emboli, intrarenal deposition (seen in tumor-lysis syndrome, increased uric acid production and multiple myeloma-Bence-Jones proteins), rhabdomyolysis
  3. Postrenal (approximately 5%): Extrinsic compression (prostatic hypertrophy, carcinoma), intrinsic obstruction (calculus, tumor, clot, stricture), decreased function (neurogenic bladder)

Chronic Renal Failure [4]

  • Diabetes mellitus, especially type 2 diabetes mellitus, is the most frequent cause of ESRD.
  • Hypertension is the second most frequent cause.
  • Glomerulonephritis
  • Polycystic kidney diseases
  • Renal vascular diseases
  • Other known causes, like prolonged obstruction of the urinary tract, nephrolithiasis
  • Vesicoureteral reflux, a condition in which urine to back up into the kidneys
  • Recurrent kidney infections/ pyelonephritis
  • Unknown etiology


The incidence of AKI has been cited as 1% on hospital admission, 2% to 5% during hospitalization, and in as many as 37% of patients treated in intensive care units (ICUs), and in 4% to 15% of patients after cardiovascular surgery. [5] [6] [7]

  • Overall, the incidence of AKI has been estimated to be 209 patients per million population per year, with 36% of patients with AKI requiring renal replacement therapy. [7]
  • The incidence and prevalence of CRF in the United States are uncertain. The third National Health and Nutrition Examination Survey (NHANES III) shows that almost 2 million people in the United States have a serum creatinine level of 2 mg/dl or greater. [8]
  • CRF is known to be more prevalent in men than in women. This gender disparity extends to ESRD.
  • ESRD develops in over 100,000 persons a year in the United States. [7][8]
  • Rates of ESRD vary with race. Both the incidence and prevalence of ESRD are three to four times higher in blacks than in whites. [8]


Renal failure pathophysiology can be described by a sequence of events that happen while during acute insult in the setting of acute renal failure and also gradually over a period in cases of chronic kidney diseases.

Broadly, AKI can be classified into three groups: [9]

  1. The decrease in renal blood flow (prerenal azotemia): Prerenal AKI occurs secondary to either an absolute reduction in extracellular fluid volume or a reduction in circulating volume despite a normal total fluid volume, e.g., in advanced cirrhosis, heart failure, and sepsis. Normally kidney auto-regulatory mechanism maintains intra-capillary pressure during initial phase by causing dilation of afferent arterioles and constriction of efferent arterioles. When prerenal conditions become severe, renal adaptive mechanisms fail to compensate unmasking the fall in GFR and the increase in BUN and creatinine levels.
  2. Intrinsic renal parenchymal diseases (renal azotemia): Intrinsic disorders can be sub-divided into those involving the glomeruli, vasculature, or tubulointerstitium respectively.
  3. Obstruction of urine outflow (postrenal azotemia)

The pathophysiology of CRF is related mainly to specific initiating mechanisms. Over the course of time-adaptive physiology plays a role leading to compensatory hyperfiltration and hypertrophy of remaining viable nephrons. As insult continues, sub sequentially histopathologic changes occur which include distortion of glomerular architecture, abnormal podocyte function, and disruption of filtration leading to sclerosis. [10]

History and Physical

The relevant history and physical examination findings associated with renal failure include:


  • Detailed present medical illness history
  • Medical history such as diabetes mellitus, hypertension
  • A family history of kidney diseases
  • Review of hospital records
  • Previous renal function
  • Medications especially start date, drug levels of nephrotoxic agents, NSAIDs
  • Any use of a contrast agent or any procedure performed

Physical examination

  • Hemodynamics including blood pressure, heart rate, weight
  • Volume status, look for edema, jugular venous distention, lung crackles, and S3 gallop
  • Skin: check for any diffuse rash or uremic frost
  • Look for signs of uremia: asterixis, lethargy, seizures, pericardial friction rub, peripheral neuropathies
  • Abdomen exam: check for bladder distention, note any suprapubic fullness


Patients with renal failure have a variety of different clinical presentations as explained in the history and physical exam section. Many patients are asymptomatic and are incidentally found to have an elevated serum creatinine concentration, abnormal urine studies (such as proteinuria or microscopic hematuria), or abnormal radiologic imaging of the kidneys. The key laboratory and imaging studies to be ordered in patients with renal failure follow.

Laboratory Tests

  • Urinalysis, dipstick, and microscopy   
  1. Dipstick for blood and protein; microscopy for cells, casts, and crystals
  2. Casts: Pigmented granular/muddy brown casts-ATN; WBC casts-acute interstitial nephritis; RBC casts-glomerulonephritis
  • Urine electrolytes

Fractional excretion of sodium (FENa) = [(UNa x PCr)/ (PNa x UCr)] x 100, where U is urine, P is plasma, Na is sodium, andCr is Creatinine. If FeNa less than 1, then likely prerenal; greater than 2, then likely intrarenal; greater than 4, then likely postrenal

If the patient is on diuretics, use FEurea instead of FENa. Complete blood count, BUN, creatinine (Cr), arterial blood gases (ABGs)

  • Calculate Cr clearance to ensure that medications are dosed appropriately: Cockcroft-Gault equation Cr clearance (mL/min) = (140-age) x (weight in kilograms) x (0.85 if female)/(72 x serum creatinine)

Special Labs

  • Creatinine Kinase (CK)
  • Immunology antibodies based on the clinical scenario


  • Renal ultrasound (US)
  • Doppler-flow kidney US depending upon the clinical scenario
  • An abdominal x-ray (KUB): Rules out renal calculi

More advanced imaging techniques should be considered if initial tests do not reveal etiology:

  • Radionucleotide renal scan, CT scan, and/or MRI
  • Cystoscopy with retrograde pyelogram
  • Kidney biopsy

Treatment / Management

Treatment options for renal failure vary widely and depend on the cause of failure. Broadly options are divided into two groups: treating the cause of renal failure in acute states versus replacing the renal function in acute or chronic situations and chronic conditions. Below is the summary of renal failure treatment.

Acute Renal Failure

  • Mainstay is treating the underlying cause and associated complications
  • In case of oliguria and no volume, overload is noted, a fluid challenge may be appropriate with diligent monitoring for volume overload
  • In the case of hyperkalemia with ECG changes, IV calcium, sodium bicarbonate, and glucose with insulin should be given. These measures drive potassium into cells and can be supplemented with polystyrene sulfonate, which removes potassium from the body. Hemodialysis is also an emergency method of removal.
  • Oliguric patients should have a fluid restriction of 400 mL + the previous day's urine output (unless there are signs of volume depletion or overload).
  • If acidosis: Serum bicarbonate intravenous or per oral, versus emergency/urgent dialysis based on the clinical situation
  • If obstructive etiology present treat accordingly and or if bladder outlet obstruction secondary to prostatic hypertrophy may benefit from Flomax or other selective alpha-blockers

General Measures

  • First things first, always review the drug list.
  • Stop nephrotoxic drugs and renally adjust others. Many supplements not approved by the FDA can be nephrotoxic.
  • Always record ins and outs
  • Monitor daily weights
  • Watch for complications, including hyperkalemia, pulmonary edema, and acidosis-all potential reasons to start dialysis
  • Ensure good cardiac output and subsequent renal blood flow.
  • Pay attention to diet: total caloric intake should be 35 to 50 kcal/kg per day to avoid catabolism. Potassium intake restricted to 40 mEq per day; phosphorus restricted to 800 mg per day. If it becomes high, treat with calcium carbonate or other phosphate binder. Magnesium compounds should be avoided.
  • Treat infections aggressively.

Immediate Dialysis Indications 

  • Severe hyperkalemia
  • Acidosis
  • Volume overload refractory to conservative therapy
  • Uremic pericarditis
  • Encephalopathy
  • Alcohol and drug intoxications

Chronic Renal Failure

  • Optimize control of specific causes of CKD such as diabetes mellitus and hypertension
  • Measure sequentially and plot the rate of decline in GFR in all patients
  • Any acceleration in the rate of decline should prompt a search for superimposed acute or subacute process that may be reversible
  • Rule out extracellular fluid volume depletion, uncontrolled hypertension, urinary tract infection, new obstructive uropathy, exposure to nephrotoxic agents (such as NSAIDs or contrast dye), reactivation or flare of the original disease such as lupus or vasculitis
  • Interventions to slow the progression of CKD
  • Reduce intra-glomerular filtration
  • Reduce proteinuria; effective meds include ACE/ARB
  • Strict glycemic control
  • Prevent and treat complications of CKD
  • Discuss renal replacement therapy with patients appropriately and timely
  • Periodically review medications and avoid nephrotoxic medicines. Dose renally excreted medications appropriately.
  • Patients with CKD should be referred to a nephrologist when eGFR is less than 30 ml per minute, as this provides enough time for adequate preparation for kidney replacement therapy.

Differential Diagnosis

  • Acute kidney injury
  • Alport Syndrome
  • Antiglomerular Basement membrane disease
  • chronic glomerulonephritis
  • Diabetic neuropathy
  • Multiple Myeloma
  • Nephrolithiasis
  • Nephrosclerosis


  • Volume overload
  • Hyponatremia
  • Hyperkalemia
  • Acidosis
  • Calcium and phosphate balance
  • Anemia


  1. Consult nephrology in all cases where the patient has a drop in urine output with elevated creatinine.
  2. Urology consultation for obstructive nephropathies
  3. Relief of obstruction with retrograde ureteral catheters or percutaneous nephrostomy
  4. Surgical consults for placement of hemodialysis catheter

Pearls and Other Issues

  • The typical FeNa values for each type of AKI: Pre-renal: Less than 1%; Intrinsic renal greater than 2%; Post-renal: Greater than 4%
  • The typical BUN/creatinine ratios for each type of AKI: Pre-renal greater than 20:1; Intrinsic renal Less than 10:1; Post-renal or normal 10 to 20:1.
  • Patients who get diuretics may have a higher urinary concentration of sodium due to the diuretic, falsely elevating the fractional excretion of sodium. In these patients, use the fractional excretion of urea (FeUrea) instead since it is relatively unaffected by diuretics.
  • Serum creatinine used as a marker of kidney function is affected by muscle mass (lower muscle mass = falsely low serum creatinine).
  • The Modification of Diet in Renal Disease (MDRD) formula includes age, gender, race, BUN, creatinine, and albumin. These are all important factors in measuring kidney function (GFR) and all automatically printed in lab reports.
  • Prevention of AKI begins before hospitalization by obtaining a nephrology consultation appropriately in patients with CKD 3, CKD 4, and CKD 5
  • Adjust doses of medications according to estimated glomerular filtration rate (GFR)
  • Watch for hyperkalemia while taking simultaneous ACEI or ARB/spironolactone in patients with CKD
  • Check for bone mineral disorders in patients with CKD

Enhancing Healthcare Team Outcomes

The management of kidney failure is usually done with an interprofessional team of healthcare professionals dedicated to preserving renal function. Kidney failure has enormous morbidity and mortality, costing the healthcare system billions of dollars each year. Today most hospitals have a kidney failure nurse whose job is to educate patients on the causes, detection, and prevention of kidney failure. The pharmacist also needs to regularly audit patient medications for those that are nephrotoxic. When monitoring patients with kidney failure, the nurse should note the urine output, levels of potassium, blood sugar and creatinine. Control of blood pressure and blood sugars is vital in the prevention of kidney disease. The diabetic nurse should closely monitor the renal function of all diabetics and refer patients to the nephrologist if the renal function is deteriorating. The pharmacist should emphasize the importance of medication compliance for treatment of blood pressure. These patients should have close follow up to ensure that the renal function is not deteriorating. Finally, the patient needs to be given advice on healthy eating, exercise, discontinuing tobacco and abstaining from alcohol. Kidney disease is not well managed can lead to complete renal failure, which requires dialysis.[11][12] (level V) Only through open communication between the team members can the morbidity and mortality of renal failure be lowered.


Recovery from acute renal failure depends on the cause of the disease. If the cause is reversible, the prognosis is good and leans toward a full recovery. Partial recovery of renal function may occur if the injury does not fully resolve. Severe cases of acute renal failure can result in death. 

  1. The prognosis for hospitalized patients with AKI depends largely on the site (ICU or floor).
  2. The mortality rate of patients with AKI on a ventilator is about 80%.
  3. AKI patients are at increased risk for progressing into CKD during their lifetime.
  4. CKD is correlated with high morbidity and mortality. Cardiovascular mortality is 10 to 30 times higher in ESRD patients treated with dialysis compared to those in the general population. [13][14](Level V)

Article Details

Article Author

Sandiya Bindroo

Article Editor:

Hima J. Challa


2/24/2022 4:07:35 PM

PubMed Link:

Renal Failure



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