A diagnosis of IC/BPS is one of exclusion, as well as a review of clinical symptoms. The AUA Guidelines recommend starting with a careful patient history, physical examination and laboratory tests to assess and document symptoms of IC, as well as other potential disorders.

The KCl test, also known as the "potassium sensitivity test", is no longer recommended. The test uses a mild potassium solution to evaluate the integrity of the bladder wall. Though the latter is not specific for IC/BPS, it has been determined to be helpful in predicting the use of compounds, such as pentosan polysulphate, which are designed to help repair the GAG layer.

For complicated cases, the use of hydrodistention with cystoscopy may be helpful. Researchers, however, determined that this visual examination of the bladder wall after stretching the bladder was not specific for IC/BPS and that the test, itself, can contribute to the development of small glomerulations (petechial hemorrhages) often found in IC/BPS. Thus, a diagnosis of IC/BPS is one of exclusion, as well as a review of clinical symptoms.

In 2006, the ESSIC society proposed more rigorous and demanding diagnostic methods with specific classification criteria so that it cannot be confused with other, similar conditions. Specifically, they require that a patient must have pain associated with the bladder, accompanied by one other urinary symptom. Thus, a patient with just frequency or urgency would be excluded from a diagnosis. Secondly, they strongly encourage the exclusion of confusable diseases through an extensive and expensive series of tests including (A) a medical history and physical exam, (B) a dipstick urinalysis, various urine cultures, and a serum PSA in men over 40, (C) flowmetry and post-void residual urine volume by ultrasound scanning and (D) cystoscopy. A diagnosis of IC/BPS would be confirmed with a hydrodistention during cystoscopy with biopsy.

They also propose a ranking system based upon the physical findings in the bladder. Patients would receive a numeric and letter based score based upon the severity of their disease as found during the hydrodistention. A score of 1–3 would relate to the severity of the disease and a rating of A–C represents biopsy findings. Thus, a patient with 1A would have very mild symptoms and disease while a patient with 3C would have the worst possible symptoms. Widely recognized scoring systems such as the O'Leary Sant symptom and problem score have emerged to evaluate the severity of IC symptoms such as pain and urinary symptoms.

The symptoms of IC/BPS are often misdiagnosed as a urinary tract infection. However, IC/BPS has not been shown to be caused by a bacterial infection and antibiotics are an ineffective treatment. IC/BPS is commonly misdiagnosed as chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in men, and endometriosis and uterine fibroids (in women).

Diagnosis is made by history and examination.

In immunocompromised patients, pus is present in the urine but often no organism can be cultured. In children, polymerase chain reaction sequencing of urine can detect fragments of the infectious agent.

The procedure differs somewhat for women and men. Laboratory testing of urine samples now can be performed with dipsticks that indicate immune system responses to infection, as well as with microscopic analysis of samples. Normal human urine is sterile. The presence of bacteria or pus in the urine usually indicates infection. The presence of hematuria, or blood in the urine, may indicate acute UTIs, kidney disease, kidney stones, inflammation of the prostate (in men), endometriosis (in women), or cancer of the urinary tract. In some cases, blood in the urine results from athletic training, particularly in runners.

If a kidney stone is suspected (e.g. on the basis of characteristic colicky pain or the presence of a disproportionate amount of blood in the urine), a kidneys, ureters, and bladder x-ray (KUB film) may assist in identifying radioopaque stones. Where available, a noncontrast helical CT scan with 5 millimeter sections is the diagnostic modality of choice in the radiographic evaluation of suspected nephrolithiasis. All stones are detectable on CT scans except very rare stones composed of certain drug residues in the urine. In patients with recurrent ascending urinary tract infections, it may be necessary to exclude an anatomical abnormality, such as vesicoureteral reflux or polycystic kidney disease. Investigations used in this setting include kidney ultrasonography or voiding cystourethrography. CT scan or kidney ultrasonography is useful in the diagnosis of xanthogranulomatous pyelonephritis; serial imaging may be useful for differentiating this condition from kidney cancer.

Ultrasound findings that indicate pyelonephritis are enlargement of the kidney, edema in the renal sinus or parenchyma, bleeding, loss of corticomedullary differentiation, abscess formation, or an areas of poor blood flow on doppler ultrasound. However, ultrasound findings are seen in only 20% to 24% of people with pyelonephritis.

A DMSA scan is a radionuclide scan that uses dimercaptosuccinic acid in assessing the kidney morphology. It is now the most reliable test for the diagnosis of acute pyelonephritis.

Analysis of the urine may show signs of urinary tract infection. Specifically, the presence of nitrite and white blood cells on a urine test strip in patients with typical symptoms are sufficient for the diagnosis of pyelonephritis, and are an indication for empirical treatment. Blood tests such as a complete blood count may show neutrophilia. Microbiological culture of the urine, with or without blood cultures and antibiotic sensitivity testing are useful for establishing a formal diagnosis, and are considered mandatory.

To make the diagnosis of a urinary tract infection in children, a positive urinary culture is required. Contamination poses a frequent challenge depending on the method of collection used, thus a cutoff of 10 CFU/mL is used for a "clean-catch" mid stream sample, 10 CFU/mL is used for catheter-obtained specimens, and 10 CFU/mL is used for suprapubic aspirations (a sample drawn directly from the bladder with a needle). The use of "urine bags" to collect samples is discouraged by the World Health Organization due to the high rate of contamination when cultured, and catheterization is preferred in those not toilet trained. Some, such as the American Academy of Pediatrics recommends renal ultrasound and voiding cystourethrogram (watching a person's urethra and urinary bladder with real time x-rays while they urinate) in all children less than two years old who have had a urinary tract infection. However, because there is a lack of effective treatment if problems are found, others such as the National Institute for Health and Care Excellence only recommends routine imaging in those less than six months old or who have unusual findings.

In straightforward cases, a diagnosis may be made and treatment given based on symptoms alone without further laboratory confirmation. In complicated or questionable cases, it may be useful to confirm the diagnosis via urinalysis, looking for the presence of urinary nitrites, white blood cells (leukocytes), or leukocyte esterase. Another test, urine microscopy, looks for the presence of red blood cells, white blood cells, or bacteria. Urine culture is deemed positive if it shows a bacterial colony count of greater than or equal to 10 colony-forming units per mL of a typical urinary tract organism. Antibiotic sensitivity can also be tested with these cultures, making them useful in the selection of antibiotic treatment. However, women with negative cultures may still improve with antibiotic treatment. As symptoms can be vague and without reliable tests for urinary tract infections, diagnosis can be difficult in the elderly.

Urinary catheters should be inserted using aseptic technique and sterile equipment (including sterile gloves, drape, sponges, antiseptic and sterile solution), particularly in an acute care setting. Hands should be washed before and after catheter insertion. Overall, catheter use should be minimized in all patients, particularly those at higher risk of CAUTI and mortality (e.g. the elderly or those with impaired immunity).

Unfortunately mesna is ineffective as a treatment once hemorrhagic cystitis has developed. Although rare, once a case of radiation-induced hemorrhagic cystitis is diagnosed there is no empirically-proven treatments to heal this type of condition, which can severely degrade a patient's quality of life and might possibly lead to renal failure with risk of death.

Viral hemorrhagic cystitis in children generally spontaneously resolves within a few days.

The first step in the treatment of HC should be directed toward clot evacuation. Bladder outlet obstruction from clots can lead to urosepsis, bladder rupture, and renal failure. Clot evacuation can be performed by placing a wide-lumen bladder catheter at bedside. The bladder can be irrigated with water or sodium chloride solution. The use of water is preferable because water can help with clot lysis. Care must be taken to not overdistend the bladder and cause a perforation.. Hyperbaric oxygen (HBO2) therapy has been proven to be effective in treating radiation-induced hemorrhagic cystitis.

In chronic bacterial prostatitis there are bacteria in the prostate, but there may be no symptoms or milder symptoms than occur with acute prostatitis. The prostate infection is diagnosed by culturing urine as well as prostate fluid (expressed prostatic secretions or EPS) which are obtained by the doctor performing a rectal exam and putting pressure on the prostate. If no fluid is recovered after this prostatic massage, a post massage urine should also contain any prostatic bacteria.

Prostate specific antigen levels may be elevated, although there is no malignancy. Semen analysis is a useful diagnostic tool. Semen cultures are also performed. Antibiotic sensitivity testing is also done to select the appropriate antibiotic. Other useful markers of infection are seminal elastase and seminal cytokines.

The decision to treat bacteriuria depends on the presence of accompany symptoms and comorbidities.

Testing for bacteriuria is often performed in those with symptoms of a urinary tract infection. Testing is often done in other scenarios as in failure to thrive of a newborn or confusion in the elderly. Screening for bacteriuria is recommended in pregnancy as there is evidence that asymptomatic bacteriuria can lead to low birth weight and preterm delivery.

- Bacteriuria can be detected by urine dipstick test. The urinary nitrite test will be able to detect any nitrate-reducing bacteria in the urine. The leukocyte esterase test detects the presence of leukocytes (white blood cells) in the urine which can be associated with a urinary tract infection.The urine dipstick test is readily available and provides fast results.

- Microscopy can also be used to detect bacteriuria. It is more specific, especially when used with gram staining, but requires more time and equipment.

- The gold standard for detecting bacteriuria is a bacterial culture which identifies the actual organism. This test is more specific but can take several days to obtain a result. As a result, clinicians will often treat a bacteriuria based on the results of the urine dipstick test while waiting for the culture results. The culture will often provide antibiotic sensitivity.

Bacteriuria can be confirmed if a single bacterial species is isolated in a concentration greater than 100,000 colony forming units per millilitre of urine in clean-catch midstream urine specimens (one for men, two consecutive specimens with the same bacterium for women). For urine collected via bladder catheterization in men and women, a single urine specimen with greater than 100,000 colony forming units of a single species per millilitre is considered diagnostic. The threshold is also 100 colony forming units of a single species per millilitre for women displaying UTI symptoms.

Due to the atypical presentation and rarity of the infection, it takes a physician longer to diagnose than more common types of bladder infections. Diagnosis requires a personalized investigation with consideration to risk factors and symptoms (Bobba). Radiology of the abdominal or pubic region has proven to be an important tool in reaching a definitive diagnosis of conditions causing gas in the urinary tract. Computer tomography, or CT scans, are of most help due to their high sensitivity in detecting gas and air bubbles (Gheonea, Bondari). However, radiology is normally not the first tool used to diagnose. Most diagnoses are made by chance after imaging examination (Weerakkody). Sometimes, even when patients don’t show symptoms, their Emphysematous cystitis infection level can be very advanced already (De Baets, Baert). Gas in the bladder wall will often have the appearance of cobblestone or a “beaded necklace” with the use of conventional radiography (Weerakkody). Delayed diagnosis can lead to a severe infection, extension of the uterus, rupturing of the bladder, and death. Emphysematous cystitis has an overall mortality rate of 7%. However, surgery is only considered in severe cases where the disease progresses involving the ureters, kidneys, or adrenal glands. When required, surgery may be extensive. (De Baets, Baert).

There are no definitive diagnostic tests for CP/CPPS. This is a poorly understood disorder, even though it accounts for 90–95% of prostatitis diagnoses. It is found in men of any age, with the peak incidence in men aged 35–45 years. CP/CPPS may be inflammatory (Category Ⅲa) or non-inflammatory (Category Ⅲb), based on levels of pus cells in expressed prostatic secretions (EPS), but these subcategories are of limited use clinically. In the inflammatory form, urine, semen, and other fluids from the prostate contain pus cells (dead white blood cells or WBCs), whereas in the non-inflammatory form no pus cells are present. Recent studies have questioned the distinction between categories Ⅲa and Ⅲb, since both categories show evidence of inflammation if pus cells are ignored and other more subtle signs of inflammation, like cytokines, are measured.

In 2006, Chinese researchers found that men with categories Ⅲa and Ⅲb both had significantly and similarly raised levels of anti-inflammatory cytokine TGFβ1 and pro-inflammatory cytokine IFN-γ in their EPS when compared with controls; therefore measurement of these cytokines could be used to diagnose category Ⅲ prostatitis. A 2010 study found that nerve growth factor could also be used as a biomarker of the condition.

For CP/CPPS patients, analysis of urine and expressed prostatic secretions for leukocytes is debatable, especially due to the fact that the differentiation between patients with inflammatory and non-inflammatory subgroups of CP/CPPS is not useful. Serum PSA tests, routine imaging of the prostate, and tests for Chlamydia trachomatis and Ureaplasma provide no benefit for the patient.

Extraprostatic abdominal/pelvic tenderness is present in >50% of patients with chronic pelvic pain syndrome but only 7% of controls.

Healthy men have slightly more bacteria in their semen than men with CPPS. The high prevalence of WBCs and positive bacterial cultures in the asymptomatic control population raises questions about the clinical usefulness of the standard 4-glass test as a diagnostic tool in men with CP/CPPS. The use of the four-glass test by American urologists is now rare, with only 4% using it regularly.

Men with CP/CPPS are more likely than the general population to suffer from Chronic Fatigue Syndrome (CFS), and Irritable Bowel Syndrome (IBS).

Experimental tests that could be useful in the future include tests to measure semen and prostate fluid cytokine levels. Various studies have shown increases in markers for inflammation such as elevated levels of cytokines, myeloperoxidase, and chemokines.

Some conditions have similar symptoms to chronic prostatitis: Bladder neck hypertrophy and urethral stricture may both cause similar symptoms through urinary reflux ("inter alia"), and can be excluded through flexible cytoscopy and urodynamic tests.

Biochemical blood tests determine the amount of typical markers of renal function in the blood serum, for instance serum urea and serum creatinine. Biochemistry can also be used to determine serum electrolytes. Special biochemical tests (arterial blood gas) can determine the amount of dissolved gases in the blood, indicating if pH imbalances are acute or chronic.

Urinalysis is a test that studies urine for abnormal substances such as protein or signs of infection.

- A Full Ward Test, also known as dipstick urinalysis, involves the dipping of a biochemically active test strip into the urine specimen to determine levels of tell-tale chemicals in the urine.

- Urinalysis can also involve MC&S microscopy, culture and sensitivity

Urodynamic tests evaluate the storage of urine in the bladder and the flow of urine from the bladder through the urethra. It may be performed in cases of incontinence or neurological problems affecting the urinary tract.

Ultrasound is commonly performed to investigate problems of the kidney and/or urinary tract.

Radiology:

- KUB is plain radiography of the urinary system, e.g. to identify kidney stones.

- An intravenous pyelogram studies the shape of the urinary system.

- CAT scans and MRI can also be useful in localising urinary tract pathology.

- A voiding cystogram is a functional study where contrast "dye" is injected through a catheter into the bladder. Under x-ray the radiologist asks the patient to void (usually young children) and will watch the contrast exiting the body on the x-ray monitor. This examines the child's bladder and lower urinary tract. Typically looking for vesicoureteral reflux, involving urine backflow up into the kidneys.

Antibiotic therapy has to overcome the blood/prostate barrier that prevents many antibiotics from reaching levels that are higher than minimum inhibitory concentration. A blood-prostate barrier restricts cell and molecular movement across the rat ventral prostate epithelium. Treatment requires prolonged courses (4–8 weeks) of antibiotics that penetrate the prostate well. The fluoroquinolones, tetracyclines and macrolides have the best penetration. There have been contradictory findings regarding the penetrability of nitrofurantoin , quinolones (ciprofloxacin, levofloxacin), sulfas (Bactrim, Septra), doxycycline and macrolides (erythromycin, clarithromycin). This is particularly true for gram-positive infections.

In a review of multiple studies, Levofloxacin (Levaquin) was found to reach prostatic fluid concentrations 5.5 times higher than Ciprofloxacin, indicating a greater ability to penetrate the prostate.

Persistent infections may be helped in 80% of patients by the use of alpha blockers (tamsulosin (Flomax), alfuzosin), or long term low dose antibiotic therapy. Recurrent infections may be caused by inefficient urination (benign prostatic hypertrophy, neurogenic bladder), prostatic stones or a structural abnormality that acts as a reservoir for infection.

In theory, the ability of some strains of bacteria to form biofilms might be one factor amongst others to facilitate development of chronic bacterial prostatitis.

Escherichia coli extract and cranberry have a potentially preventive effect on the development of chronic bacterial prostatitis, while combining antibiotics with saw palmetto, lactobacillus sporogens and arbutin may lead to better treatment outcomes.

Bacteriophages hold promise as another potential treatment for chronic bacterial prostatatis.

The addition of prostate massage to courses of antibiotics was previously proposed as being beneficial and prostate massage may mechanically break up the biofilm and enhance the drainage of the prostate gland. However, in more recent trials, this was not shown to improve outcome compared to antibiotics alone.

In a small minority of cases of urethral syndrome, treatment with antibiotics is effective, which indicates that in some cases it may be caused by bacterial infection which does not show up in either urinalysis or urine culture. For chronic urethral syndrome, a long term, low-dose antibiotic treatment is given on a continuous basis or after intercourse each time if intercourse appears to trigger symptoms.

As low oestrogen may also be considered a source for urethral syndrome, hormone replacement therapy, and oral contraceptive pill (birth-control pills) containing oestrogen are also used to treat the symptoms of this condition in women.

Diagnosis is made by patient history of passing air or a sputtering urine stream. CT scans may show air in the urinary bladder or bladder walls.

Treatment involves avoiding the trigger if that can be determined.

In addition to traditional IC therapies, diet modification remains a core self care strategy as foods that are irritating to the bladder dramatically worsen the symptoms that patients may experience. Foods high in acid and/or caffeine (such as all coffees, regular teas, green teas, sodas, diet sodas, artificial sweeteners and most fruit juices) should be avoided. The daily goal of patients should be to soothe rather than irritate the bladder wall.

Bacteria and yeast, including those naturally occurring as part of the human microbiome, can travel along urinary catheters and cause an infection in the bladder, kidneys, and other organs connected to the urinary tract.

CAUTI can lead to complications such as prostatitis, epididymitis, and orchitis in men, and cystitis, pyelonephritis, gram-negative bacteremia, endocarditis, vertebral osteomyelitis, septic arthritis, endophthalmitis, and meningitis in all patients. Complications associated with CAUTI cause discomfort to the patient, prolonged hospital stay, and increased cost and mortality. It has been estimated that more than 13,000 deaths are associated with UTIs annually. Estimated > 560,000 nosocomial UTIs annually.

Even when caught early, aggressive treatment is required (Bobba). Antibiotics are proven to cure Emphysematous cystitis over time and reduce the amount of gas inside the bladder wall. Prognosis is poor if antibiotics are not used to treat the patient. Additional treatment consists of urinary drainage and good control of blood glucose. The treatment of underlying comorbid diseases, such as diabetes, is extremely important because they can intensify the infection (Gheonea, Bondari). Hyperbaric oxygen is an effective treatment, and has cured some cases in as little as 48 hours. Although it is unclear as to how gas formation occurs in emphysematous cystitis, it’s dependant on whether or not the patient has contributing diseases (Mccabe). Gas formation in diabetic patients diagnosed with Emphysematous cystitis has been determined to occur due to the production of carbon dioxide as a result of the fermentation of the high concentrations of glucose. Gas formation in nondiabetic patients is most likely due the breaking down of urinary lactulose and tissue proteins. Inflammation caused by infection increases pressure and decreases circulation, which provides the perfect environment for bacteria to produce gas (Sereno).

Eosinophilic cystitis is a rare condition where eosinophiles are present in the bladder wall. Signs and symptoms are similar to a bladder infection. Its cause is not entirely clear; however, may be linked to food allergies, infections, and medications among others.

Glomerulation refers to bladder hemorrhages which are thought to be associated with some types of interstitial cystitis (IC).

The presence of glomerulations, also known as petechial hemorrhages, in the bladder suggests that the bladder wall has been damaged, irritated and/or inflamed. In fact, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Diagnostic Criteria for IC, developed in 1987, required the presence of glomerulations or Hunner's Ulcers to make a firm diagnosis of IC and is still used, today, to determine patient eligibility for some clinical trials. Research conducted by Waxman, however, determined that the hydrodistention procedure itself may have created these tiny broken blood vessels. Thus, a diagnosis of IC is now based upon other, less invasive methods, such as the PUF questionnaire.