Hematuria

Article Author:
Muhammad Saleem
Article Editor:
Karim Hamawy
Updated:
11/26/2019 6:03:01 PM
PubMed Link:
Hematuria

Introduction

Hematuria is the presence of blood in the urine. Hematuria can be gross or microscopic. Gross hematuria is visible blood in the urine. Microscopic hematuria refers to the detection of blood on urinalysis or urine microscopy. Hematuria can be intermittent or persistent. Hematuria is defined as the presence of at least 5 red blood cells/HPF in 3 of 3 consecutive centrifuged specimens obtained at least 7 days apart. Hematuria may be asymptomatic or symptomatic and may be associated with other urinary tract abnormalities. Hematuria is often first encountered by the primary care provider.

Etiology

Hematuria is usually caused by a genitourinary disease although systemic diseases can also manifest with blood in the urine. Hematuria is divided into glomerular and non-glomerular hematuria to help in evaluation and management.

Some common glomerular causes are:

  • Alport syndrome
  • Thin basement membrane disease
  • Post-streptococcal glomerulonephritis
  • IgA nephropathy
  • Pauci immune glomerulonephritis
  • Lupus nephritis
  • Membranoproliferative glomerulonephritis
  • Goodpasture syndrome
  • Nephrotic syndrome
  • Polycystic kidney disease

Non-glomerular causes include:

  • Febrile illness
  • Exercise
  • Menstruation
  • Nephrolithiasis
  • Cystitis, urethritis, prostatitis
  • Malignancy: renal cell carcinoma, bladder cancer, prostate cancer
  • Genitourinary mucosal injury by instrumentation
  • Trauma
  • Bleeding tendency: thrombocytopenia, coagulopathy, use of blood thinners, hematological disorders like sickle cell anemia.

Epidemiology

Hematuria is one of the most common presentations in outpatient and Emergency department. Asymptomatic hematuria is thought to be much more prevalent than symptomatic hematuria.[1]

In about 50% of cases, a cause can be identified. When hematuria presents with proteinuria, this usually signals moderate to severe kidney disease.

In infants and young children, hematuria may signal Wilms tumor, whereas post-infectious glomerulonephritis and malignancy are more common in older individuals.

Pathophysiology

Hematuria often occurs as a result of structural alterations due to an injury, infection or a mass. The integrity of the glomerular basement membrane may be damaged by immunological and/or inflammatory processes. Some drugs, calculi, and chemicals may cause erosion of the mucosal surface of the urinary tract, leading to hematuria.

History and Physical

Hematuria can be painful or painless. Patients can have various presentations, most of the time they notice red or dark-colored urine, or passing blood clots.  Associated symptoms include:

  • Flank pain
  • Lower abdominal pain
  • Painful urination
  • Urinary urgency or frequency
  • Fever
  • Active menstruation
  • Passing stone or grits
  • Recent throat or skin infection
  • Joint pains, oral ulcers, rash
  • Hemoptysis
  • Leg swelling
  • Hearing loss
  • Flank mass
  • Constitutional symptoms like weight loss, anorexia, cachexia
  • Back pain 

Patients should be asked about previous such episodes and family history of hematuria. Medical history and recent procedural history is essential in the evaluation. Medications should be carefully reviewed. Ascertain smoking history and use of other recreational drugs.

A complete physical examination can contribute to making a valid differential diagnosis. Important signs to look for are:

  • Febrile
  • Hypertension
  • Periorbital edema
  • Presence of pallor, icterus, oral ulcers or rash
  • Hearing impairment
  • Generalized lymphadenopathy
  • Joints swellings
  • Flank mass
  • Palpable enlarged cystic kidneys
  • Costovertebral angle tenderness
  • Pubic tenderness
  • Urethral discharge or tear
  • Lower extremity edema

A thorough history and focused physical examination can lead to a proper evaluation and subsequent management.

Evaluation

Urinalysis is the initial and most useful test to perform. Although urine dipstick is widely available and can be performed quickly, it can give false-positive or false-negative results and warrants urinalysis and urine microscopy to establish the diagnosis. Presence of 3 or more RBCs per High Power Field on urine sediments is defined as microscopic hematuria although there is no "safe" lower limit of hematuria.[2] Urine appearance, pH, the presence of proteins, WBCs, nitrites, leukocyte esterase, crystals, and casts is helpful. A dirty urine specimen with significant WBCs and positive nitrites and leukocyte esterase suggests urinary tract infection and a likely cause of hematuria. The presence of excessive proteins with hematuria favors glomerulonephritis.

Urine microscopy examines urine sediments for RBC morphology, and RBC casts are the single most significant test which can differentiate between glomerular and non-glomerular bleed.[3] Dysmorphic RBCs >25% per High-Power Field is highly specific (>96%) with a high positive predictive value (94.6%) but not much sensitive (20%) for Glomerulonephritis.[4] RBC casts are rare to find but almost diagnostic of Glomerular pathology.

Renal parameters should be obtained to rule out acute kidney injury.

Imaging: Initial imaging could be in the form of an ultrasound of the kidneys, ureters, and bladder. It can assist in diagnosing anatomical causes of hematuria such as a kidney stone or bladder or renal mass. It can also detect renal cysts. Abdominopelvic CT scan with or without contrast is the preferred modality to detect renal stones and other morphological abnormalities of kidneys. MRI abdomen and pelvis is another useful modality if CT scan is contraindicated or not helpful.

Cystoscopy: After ruling out urinary tract infection and having negative imaging of kidneys and ureters to detect any abnormality, cystoscopy by a urologist is the next step in the evaluation of hematuria. It can detect urothelial carcinoma, bladder wall inflammation or mucosal thickening. It can also be therapeutic to remove bladder stones.

Urine Cytology can be performed to detect malignant cells or to detect urothelial carcinoma, but it is not a substitute for a cystoscopy.

Kidney biopsy: The gold standard to diagnose a glomerular cause of hematuria is a kidney biopsy by a nephrologist or interventional radiologist.[5] The presence of dysmorphic RBCs and RBC casts should be followed by a kidney biopsy. As it is an invasive test, it can lead to complications such as life-threatening bleeding, but the frequency of occurrence is low. An adequate renal sample is 2-3 biopsy cores with a sufficient number of glomeruli. Light microscopy, electron microscopy, and immunofluorescence are performed to look at glomerulus structure to diagnose glomerulonephritis and detect a specific type.  

Treatment / Management

Management depends on underlying etiology. For asymptomatic intermittent hematuria with negative imaging, stable renal functions, and absence of proteinuria, observation may be a reasonable approach. Overt hematuria needs prompt management. Hemodynamic stability should be assured first. Any hematological abnormality should be corrected by blood products, transfusions, or medications. In rare instances, interventional radiology guided embolism is required to stop life-threatening bleeding from renal vasculature or for hemorrhagic cystitis refractory to conventional treatments.[6]

Non-Glomerular causes of hematuria:  Acute urinary tract infections are treated with a 7-14 day course of oral or intravenous antibiotics. Nephrolithiasis management is supportive, with controlling pain and administering fluids. Kidney stone size and location could warrant further management.[7] Most stones <0.5 cm pass spontaneously. Larger symptomatic stones may require lithotripsy or nephrostomy. Renal cell carcinoma confined to kidneys would require nephrectomy. Metastatic cancers need staging and further management. Transitional cell carcinoma also needs proper staging and expert opinion for additional treatment.

Glomerular causes of hematuria:  Some hereditary diseases like Alport’s, thin basement membrane disease, and polycystic kidney Disease need monitoring of renal functions, and regular follow up. Post-streptococcal glomerulonephritis requires supportive care. IgA nephropathy treatment depends on degree proteinuria and renal function. Relatively normal creatinine with minimal proteinuria may be managed conservatively. High-risk features including worsening creatinine, persistent proteinuria 1000mg/day, and active disease on renal biopsy are indications to consider immunosuppressive therapy especially steroids.[8] Lupus nephritis is histologically classified into six types to guide treatment. Nephrotic syndrome and other etiologies necessitate an expert opinion for further management.

Differential Diagnosis

  • Hypercalciuria
  • IgA nephropathy
  • Henoch Schonlein Purpura
  • Hemolytic uremic syndrome
  • Post-infectious glomerulonephritis
  • Lupus

Prognosis

Children with isolated hematuria have a good outcome but the presence of proteinuria, hypertension or abnormal renal function usually leads to a guarded prognosis. In adults, hematuria should be taken seriously because it may signal a malignancy.

Postoperative and Rehabilitation Care

A low sodium diet is recommended in patients with hypertension and hematuria

Consultations

Nephrology consultation should be considered if there are dysmorphic RBCs, cellular casts, abnormal renal functions, the presence of proteinuria, or unexplained microscopic hematuria. Urology consult is recommended for management of nephrolithiasis and anatomical abnormalities including renal mass or urinary tract masses.

Enhancing Healthcare Team Outcomes

Hematuria is commonly seen in clinical practice. Because of the vast number of conditions that can cause hematuria, the presentation is best managed by an interprofessional team.

In most cases, initial management will involve a primary care physician or emergency medicine physician. After getting initial workup, referral to a nephrologist or urologist may be indicated. 

Inpatient or outpatient referral decision depends on the severity of presentation, abnormal lab findings, and the presence of risk factors for serious etiology.

Clinicians including the nurse practitioner should inform the parents that hematuria by itself should not prevent the child from undertaking sporting activities, however, the type of activity should be regulated. The pharmacist should educate the patients on some medications that may cause hematuria. However, the pharmacist should consult with the team members before making any recommendation on discontinuation of the drug. 

Because some of the causes of hematuria are caused by malignancies, the key is to communicate with the members of the team so that there is no delay in diagnosis. Educating the patient and communication among the team will result in the best clinical outcomes. [Level 5]


References

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[2] Mariani AJ,Mariani MC,Macchioni C,Stams UK,Hariharan A,Moriera A, The significance of adult hematuria: 1,000 hematuria evaluations including a risk-benefit and cost-effectiveness analysis. The Journal of urology. 1989 Feb     [PubMed PMID: 2492350]
[3] Schramek P,Schuster FX,Georgopoulos M,Porpaczy P,Maier M, Value of urinary erythrocyte morphology in assessment of symptomless microhaematuria. Lancet (London, England). 1989 Dec 2     [PubMed PMID: 2574263]
[4] Hamadah AM,Gharaibeh K,Mara KC,Thompson KA,Lieske JC,Said S,Nasr SH,Leung N, Urinalysis for the diagnosis of glomerulonephritis: role of dysmorphic red blood cells. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2017 Oct 6     [PubMed PMID: 29156008]
[5] Madaio MP, Renal biopsy. Kidney international. 1990 Sep     [PubMed PMID: 2232496]
[6] McIvor J,Williams G,Southcott RD, Control of severe vesical haemorrhage by therapeutic embolisation. Clinical radiology. 1982 Sep     [PubMed PMID: 7116778]
[7] Coll DM,Varanelli MJ,Smith RC, Relationship of spontaneous passage of ureteral calculi to stone size and location as revealed by unenhanced helical CT. AJR. American journal of roentgenology. 2002 Jan     [PubMed PMID: 11756098]
[8] Lv J,Xu D,Perkovic V,Ma X,Johnson DW,Woodward M,Levin A,Zhang H,Wang H, Corticosteroid therapy in IgA nephropathy. Journal of the American Society of Nephrology : JASN. 2012 Jun     [PubMed PMID: 22539830]