Hematuria (Case 16)

Hematuria (Case 16)

Spirithoula Vasilopoulos MD and Michael Gitman MD

Case: The patient is a 60-year-old male who, during an annual physician visit, was found to have hematuria. His medical history is significant for emphysema from years of smoking, as well as an episode of right-sided nephrolithiasis approximately 1 year ago. At that time he passed the stone spontaneously, and subsequently his urinalysis had been normal. His medications include albuterol and ibuprofen. After hearing of the hematuria, he states that he has never seen any blood in his urine and he certainly does not have any pain. Other than complaints of his chronically poor urinary stream, he feels great. After some discussion, he agrees to complete any evaluation that is necessary.

Differential Diagnosis

Glomerular Hematuria

Nonglomerular Renal Hematuria

Urologic Hematuria

IgA nephropathy

Alport syndrome

Polycystic kidney disease

Chronic tubulointerstitial nephritis (CTIN)


Transitional cell carcinoma (TCC)


Papillary necrosis


Speaking Intelligently

Hematuria is a common clinical problem, occurring in 10% to 20% of adult men and postmenopausal women. It can originate from anywhere within the genitourinary tract including the kidneys, ureters, bladder, and urethra. Its clinical significance varies dramatically from innocuous diseases such as cystitis to a life-altering diagnosis, such as renal failure or malignancy. A thorough history, physical exam, and urine evaluation will help to identify the cause of hematuria and the extent of clinical evaluation that is necessary.


Clinical Thinking

• Determine the context in which the sample was taken. A urinalysis done in the setting of urinary tract infection (UTI), catheter trauma, significant coagulopathy, menstruation, after sexual intercourse, or after vigorous exercise may need to be repeated.

• If the hematuria is evaluated in the appropriate setting, determine whether the red blood cells originated in the kidney or in the lower urinary tract.

• Red blood cells originating in the kidney will be dysmorphic, while red blood cells that originate in the lower urinary tract will retain their usual morphology on visual exam. If the red blood cells originated in the glomerulus, you may see red blood cell casts.

• Hematuria accompanied by proteinuria is often of glomerular origin.

• Categorize the hematuria as gross or microscopic, and glomerular or nonglomerular. Deciding on the origin will help narrow the differential and assist in ordering the appropriate diagnostic tests and referring the patient to the appropriate specialist.


• Determine the degree of hematuria: Is it microscopic or macroscopic? Although macroscopic hematuria can be seen with glomerular diseases, it is much more often a sign of lower urinary tract pathology and is often the initial symptom of genitourinary cancer.

• Look for associated symptoms, which are extremely important. Unintentional weight loss, fevers of unclear origin, or night sweats suggest neoplasm. Colicky flank pain radiating to the groin associated with nausea or vomiting suggests nephrolithiasis. Difficulty initiating urination, poor urinary stream, and nocturia suggest benign prostatic hypertrophy (BPH). Dysuria, frequency, urgency, and suprapubic pain suggest cystitis.

• Ask about recent skin infections or URIs, and the timing of the infections relative to the onset of hematuria. Post-streptococcal glomerulonephritis occurs over a week after an infection, whereas hematuria from IgA nephropathy can be seen concurrent with the URI.

• A family history of males with kidney disease and hearing deficit suggests Alport syndrome, whereas a family history of renal failure and stroke suggests polycystic kidney disease.

• Review cigarette smoking history and toxin exposures. Exposure to aromatic amines, aniline dyes, benzidine, or cyclophosphamide, as well as analgesic abuse, are risk factors for urothelial carcinoma.

Physical Examination

• Hypertension and edema are common in glomerular diseases, but they are not specific findings. Large, polycystic kidneys can often be palpated during the abdominal exam.

• Suprapubic tenderness can be seen with cystitis.

• Costovertebral tenderness can be seen with pyelonephritis or nephrolithiasis.

• Prostatic enlargement and tenderness can be seen with BPH or prostatitis.

Tests for Consideration

Urinalysis can confirm the presence of hematuria and determine if there is concomitant proteinuria. It will show if there is pyuria and bacteriuria, which are often present in the setting of infection.


Urine microscopic examination will show whether there are dysmorphic red blood cells and red blood cell casts, which can be seen with glomerular diseases. WBC casts are often present in patients with interstitial nephritis.


Urine culture confirms the presence of infection and guides antibiotic therapy.


Serum chemistries will determine if the patient has renal dysfunction or metabolic abnormalities such as hypercalcemia or hyperuricemia, which can lead to hematuria.


Urine cytology is a screening test for bladder cancer.


Cystoscopy can be used to rule out anatomic bladder or urethral pathology, as well as to search for urothelial malignancies.


Renal biopsy is performed if the hematuria is suspected to be of renal origin; it is performed when a definitive diagnosis is necessary.



A renal sonogram is an excellent screening tool to rule out anatomic abnormalities of the kidney or to diagnose obstruction of the urinary tract. It is noninvasive and does not carry the risk of contrast. When stones are suspected, a CT scan without contrast is the test of choice, while IVP is the test of choice to look for papillary necrosis or for subtle lesions in the urinary tract.

→ Ultrasound of the kidneys, ureters, and bladder can detect structural abnormalities of the urinary tract, obstruction, renal abscesses, and stones.


→ Intravenous pyelogram (IVP) is the test of choice to look for papillary necrosis or subtle lesions in the urinary tract.


→ Abdominal radiography can be used to diagnose calcium-containing renal stones.


→ CT scan of the abdomen and/or pelvis can detect masses or stones within the urinary tract and can evaluate renal parenchyma.


Clinical Entities Medical Knowledge

IgA Nephropathy

IgA nephropathy is caused by the production of abnormal immunoglobulin A molecules that cannot be effectively cleared from the circulation. These IgA complexes deposit in the mesangial portion of the glomeruli and cause an inflammatory reaction that leads to renal damage. It is usually a slowly progressive disease, but more than 25% of those affected will eventually progress to end-stage renal disease.


Patients with IgA nephropathy can present with several different clinical syndromes: recurrent synpharyngitic macroscopic hematuria in the setting of an upper respiratory illness; nephrotic-range proteinuria and microscopic hematuria; acute renal failure due to crescentic glomerulonephritis; or microscopic hematuria and non–nephrotic-range proteinuria with normal or slowly worsening renal function.


The diagnosis is made by renal biopsy showing mesangial deposits of IgA and complement.


The treatment of IgA nephropathy depends on the clinical presentation. Patients with recurrent macroscopic hematuria and normal renal function, and patients with microscopic hematuria and normal renal function, have an excellent prognosis and usually require no treatment. Patients with crescentic glomerulonephritis have a poor prognosis and are treated aggressively with immunosuppressive agents. Patients with nephrotic-range proteinuria are often treated with corticosteroids. Patients with microscopic hematuria and non–nephrotic-range proteinuria with progressive renal failure are treated with antiproteinuric therapy and possibly immunosuppressive medications. See Cecil Essentials 29.

Alport Syndrome

Alport syndrome is a type of hereditary nephritis resulting in renal failure and deafness in some affected individuals. The inheritance in most cases is X-linked, and the majority of cases result from mutations in the gene that codes for the α5 chain of type IV collagen. Since type IV collagen is integral to the basement membrane of the kidney, cochlea, and eye, affected individuals manifest abnormalities of these organs.


Males often present with persistent microscopic hematuria from an early age. As the disease progresses, they often develop proteinuria and hypertension. The majority will go on to develop renal failure and require renal replacement therapy. Many will also develop sensorineural deafness. Females will often have intermittent microscopic hematuria but are much less likely to develop significant renal failure.


The diagnosis is made by observing a typical presentation in a patient with a strong family history of Alport syndrome. On kidney biopsy, electron microscopy shows typical ultrastructural changes in the basement membranes.


There is no specific therapy for Alport syndrome. Hypertension and proteinuria are treated with ACE inhibitors. If a patient develops end-stage renal disease, he or she is started on dialysis or given a renal transplant. See Cecil Essentials 29.

Chronic Tubulointerstitial Nephritis

CTIN results from chronic inflammation of the renal tubules and interstitium. Histologically, the kidney shows interstitial scarring and fibrosis. There are many reported causes of CTIN. Exposure to drugs, including analgesics, and exposure to heavy metals, including lead, have been implicated. Rheumatologic conditions such as SLE and Sjögren syndrome can cause CTIN. Persistent hypokalemia, hypercalcemia, and reflux nephropathy can also cause CTIN.


CTIN is often discovered incidentally during a routine physical exam when laboratory abnormalities are discovered. In the early stages, patients are found to have microscopic hematuria and non–nephrotic-range proteinuria. When the disease is discovered late in its course, patients can present with hypertension and renal failure.


The diagnosis is often made presumptively in patients who give a history of exposures or conditions associated with the development of CTIN and are found to have hematuria and non–nephrotic-range proteinuria. Renal biopsy is often necessary to confirm the diagnosis.


Treatment is often supportive and includes BP control and electrolyte management. Implicated drugs should be stopped, and metabolic and rheumatologic diseases should be treated aggressively. See Cecil Essentials 27, 30.

Polycystic Kidney Disease

There are two major types of autosomal-dominant polycystic kidney disease. Type 1 is the most common and most severe, with approximately 50% of affected individuals requiring dialysis by the age of 60 years; it is linked to an abnormal gene on chromosome 16, named PKD1. Type 2 is less common and less severe, and is linked to an abnormal gene on chromosome 4, named PKD2. PKD1 and PKD2 encode proteins named polycystin-1 and polycystin-2, respectively. These proteins are involved in cell-cell and cell-matrix interactions, and mutations in these genes lead to cyst formation through an as-yet-undefined mechanism.


Patients often present with flank pain resulting from an infected cyst, hemorrhagic cyst, or nephrolithiasis. Other patients present with renal insufficiency and hypertension. Many patients present with extrarenal cystic manifestations; hepatic cysts can be detected in over one half of cases and are more commonly seen in women and elderly patients. Still others present with either gross or microscopic hematuria. Additional manifestations include intracranial aneurysms, which tend to cluster in families.


For patients who are older than 15 years and at risk for the disease, the diagnosis is made by demonstrating multiple cysts on sonography. The number of cysts necessary to make a diagnosis depends on the patient’s age. Genetic testing can be considered for patients with equivocal results on sonography or in patients who are younger than 30 years and need a definite diagnosis.


Aggressive treatment of high BP may slow the progression to renal failure. ACE inhibitors are frequently used to lower BP and control proteinuria, if present. If the patient develops complications of chronic kidney disease such as anemia, acidosis, or bone disease, these manifestations should be treated. If these patients progress to end-stage renal disease, they can either receive a renal transplant or be placed on dialysis. After they are on renal replacement therapy, some patients require nephrectomy for recurrent urinary cyst infection or hemorrhage. See Cecil Essentials 30.

Transitional Cell Carcinoma

TCC is a common malignancy, resulting from neoplastic transformation of transitional cells lining the bladder, ureters, or renal pelvis. Risk factors for the development of TCC include environmental exposure to chemical carcinogens. These carcinogens include tobacco, analgesics, cyclophosphamide, aromatic amines, textile dyes, and chemicals used in rubber and plastic manufacturing. The exposure is theorized to cause chronic irritation and subsequent neoplastic changes.


Patients will typically present with macroscopic or microscopic hematuria. Additionally, patients with TCC involving the upper urinary tract may present with a palpable abdominal mass and renal colic, while patients with TCC involving the bladder may present with dysuria and frequency.


The diagnosis of TCC is often difficult to establish. The difficulty stems from the limited accessibility of the ureters and renal pelvic anatomy, and from the broad differential diagnoses that must be considered in the evaluation of hematuria. Urine cytology is a good screening test, but cystoscopy and biopsy are necessary to confirm the diagnosis of TCC.


Treatment depends on the cancer staging. Superficial lesions are treated with resection with or without intravesical chemotherapy. Deeply invasive tumor is usually treated with cystectomy and urinary diversion. Metastatic disease is often treated with chemotherapy. Many clinical trials are currently ongoing, evaluating the effectiveness of adjuvant chemotherapy. See Cecil Essentials 57.


Risk factors for kidney stones include Caucasian race, male gender, older age, obesity, and a history of polycystic kidney disease, hyperparathyroidism, or RTA. Kidney stones arise when the urine becomes supersaturated with calcium, oxalate, or uric acid, resulting in nidus formation. Ions from supersaturated urine will collect around the nidus to form stones. The most common type of kidney stones is calcium stones, followed by struvite stones, and uric acid stones. Cystine stones are rare. Calcium stones are more likely to form when there is excess calcium or oxalate in the urine, or when there is a deficiency of citrate in the urine. Struvite stones almost always occur in the setting of chronic or recurrent UTIs. Uric acid stones occur in the setting of excess uric acid secondary to malignancies or disorders of uric acid metabolism.


Kidney stones may be asymptomatic and found incidentally on abdominal imaging or in a workup for hematuria. Patients with large stones that cause obstruction or infection present with symptoms. The most common symptom is intense, colicky pain in the back, flank, lower abdomen, groin, and/or genitals. Patients often complain that they cannot find a position to alleviate the pain. Urinalysis usually shows microscopic hematuria.


When the history suggests kidney stones, the diagnosis is made through imaging tests. Potential tests include abdominal radiography, ultrasound, IVP, retrograde pyelogram, and noncontrast spiral CT scan. Currently, noncontrast spiral CT scan is the test of choice. When a stone is obtained, its composition should be determined by stone analysis. Patients with recurrent stones should have a 24-hour urine stone risk profile performed. This evaluation can detect metabolic abnormalities of calcium, citrate, oxalate, and uric acid that make stone formation more likely.


Treatment depends on the type and size of the kidney stone. Options include conservative management with hydration and pain control, extracorporeal shock wave lithotripsy (ESWL), and surgical removal. Prevention of stone formation includes high fluid and low sodium intake in all affected individuals. Additional therapy depends on the type of stone and associated metabolic abnormality but may include thiazide diuretics for individuals with hypercalciuria, dietary modification for individuals with hyperoxaluria, and urine alkalization and allopurinol for patients with uric acid stones. Complicated cases require nephrology and urology referrals. See Cecil Essentials 30.


Cystitis is caused when microorganisms that are capable of infecting bladder cells such as Escherichia coli, Staphylococcus saphrophyticus, Proteus mirabilis, Enterococcus spp., or Klebsiella spp. gain access to the bladder. Most commonly this occurs when microorganisms of the rectal and vaginal flora gain access to the bladder by first entering the distal urethra. Less commonly, cystitis can occur after urethral instrumentation. In men, isolated infectious cystitis is quite uncommon. When it does occur, it is often seen in the setting of anatomic or functional urinary tract obstruction.


Patients with cystitis present with dysuria, which is often associated with frequency and urgency. The location of the pain is typically suprapubic. The presence of fever, nausea, vomiting, or flank pain suggests pyelonephritis. Urinalysis will typically show microscopic hematuria, WBCs, and bacteriuria.


The diagnostic approach to cystitis depends on the clinical scenario. To make a proper diagnosis a clinician must first categorize the cystitis. Uncomplicated cystitis occurs in young, healthy women. Complicated cystitis occurs in patients who are male, elderly, pregnant, diabetic, immunocompromised, after instrumentation, or in the presence of urolithiasis, urinary tract malignancy, foreign body, or functional or structural urinary tract abnormalities. The diagnosis of cystitis in a young, healthy woman can initially be a clinical one. A female with dysuria, frequency, and urgency can be presumptively diagnosed and treated for uncomplicated cystitis. On the other hand, patients with complicated cystitis should undergo formal diagnosis with urinalysis, culture, and sensitivity testing. The degree of pyuria and bacteriuria required to make a diagnosis of UTI will differ depending upon the clinical scenario.


Cystitis is treated with antimicrobial agents. In uncomplicated cystitis in young, healthy females, empirical treatment with trimethoprim-sulfamethoxazole or a fluoroquinolone (e.g., ciprofloxacin) for a short 3-day course is acceptable. A clinician should be aware of geographic antimicrobial resistance patterns in his or her area. Treatment of cystitis in patients other than young, healthy females should be case-specific and guided by the urine culture and sensitivity. See Cecil Essentials 105.

Papillary Necrosis

Papillary necrosis results from ischemia to the renal medulla. The papillae, which are located in the medulla, are vulnerable to ischemic injury due to their limited blood supply and the surrounding hypertonic environment. Conditions associated with papillary necrosis include analgesic use, diabetes mellitus, sickle cell disease, and UTIs.


Affected individuals often present with hematuria, which can be microscopic or macroscopic, and dysuria. If the sloughed papillae cause obstruction, patients can present with renal colic. Patients with multiple sloughed papillae or solitary kidneys can present with acute renal failure. When there is an associated infection, patients will have fever and leukocytosis.


The most sensitive test to diagnose papillary necrosis is an IVP. This test will show irregular calyces with central contrast defects representing the necrosed papillae. Sloughed papillae can cause filling defects in the ureters.


Treatment is supportive. If patients are hypotensive, they should be given IV fluids. If the hematuria is significant, patients may need to be transfused. Offending analgesics should be stopped. UTIs must be treated with antibiotics. If the sloughed papillae are obstructing the ureters, they may have to be removed by interventional means.


Oct 3, 2016 | Posted by in MANUAL THERAPIST | Comments Off on Hematuria (Case 16)

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