Nephrolithiasis refers to the presence of crystalline stones (calculi) within the urinary system (kidneys and ureter). Such renal stones are composed of varying amounts of crystalloid and organic matrix. Ureteric stones almost always originate in the kidney but then pass down into the ureter.
Nephrolithiasis is common, with a lifetime prevalence of 10% in men and 5% in women.
The underlying pathophysiological mechanisms responsible for uric acid (UA) nephrolithiasis are: 1) low urine volume; 2) hyperuricosuria; and 3) unduly acidic urine.
A potentially underlying cause of kidney stone formation is an acquired or congenital anatomical structural abnormality. Anatomical abnormalities may favor stone formation, particularly if the abnormality results in urinary stasis in conditions such as pelviureteric junction obstruction or horseshoe kidney.
Crystallization occurs when the concentration of two ions exceeds their saturation point in a solution. The crystals in the supersaturated urine then adhere to the urothelium which may enhance subsequent stone growth, and interstitial stone formation can occur. Just as dilute urine can prevent crystallization of stone-forming salts, dehydration may lead to the development of renal stones.
Renal stones are crystalline mineral depositions that form from microscopic crystals in the loop of Henle, distal tubules, or the collecting duct. Renal stone deposition is usually in response to elevated levels of urinary solutes, such as calcium, uric acid, oxalate, and sodium, as well as decreased levels of stone inhibitors, such as citrate and magnesium. Once crystals are formed, they either pass out with the urine or become retained in the kidney, where they can grow and stones can form. In urine, even when the concentration of calcium oxalate exceeds the normal solubility product, crystallization may not occur because of prevention from urinary inhibitors.
Physical exam: In patients with renal colic, costovertebral angle and ipsilateral flank tenderness may be pronounced. Signs of sepsis, including fever, tachycardia, and hypotension, might indicate an obstructing stone with infection, warranting urgent urological referral.
Lab tests: Initial laboratory tests in all patients with suspected nephrolithiasis are urinalysis, complete blood count (CBC), and serum chemistry to include electrolytes, BUN/creatinine (to assess renal function), calcium, phosphorus, and uric acid. Urinalysis is helpful in confirming a diagnosis of renal stones because microscopic hematuria is present in the majority of patients. However, the absence of hematuria does not exclude nephrolithiasis.
Imaging: If there is suspicion for nephrolithiasis based on the history, physical examination, and laboratory tests, then imaging is indicated. Non-contrast helical CT (NCCT) scan is the preferred imaging modality due to its high sensitivity and specificity. CT accurately determines the presence, size, and location of stones; if it is negative, nephrolithiasis can be ruled out with high degree of accuracy. Patients with indinavir and ritonavir stones from anti-HIV medication may have stones which are radiolucent on CT scan. However, this makes up only a tiny fraction of patients.
According to American Urological Association imaging guidelines for ureteral stones, a low-dose non-contrast CT (<4 mSv ) is preferred for patients with a Body Mass Index (BMI) ≤30 kg/m2, as this limits the potential radiation exposure while maintaining both sensitivity and specificity at 90% or higher. However, low-dose CT is not recommended for those with a BMI >30 kg/m2, owing to lower sensitivity and specificity in these patients.
Most stones are smaller than 5 mm and readily pass without interventions such as lithotripsy, ureteroscopy, or percutaneous nephrolithotomy.
For most patients, pain management is paramount. Randomized controlled trials suggest that parenteral nonsteroidal anti-inflammatory drugs (NSAIDs) are as effective as narcotics for controlling the pain of renal colic.
Diclofenac (Voltaren) has been used in several studies.
To hasten stone passage, some recommend inducing high urine flow with oral intake of at least 2 to 3 L of fluids per 24 hours to ensure a urine output of at least 2 L per day.
Drugs may also help the stone to pass. A study in 210 patients with ureteral stones averaging 6 mm in diameter showed that tamsulosin (Flomax) increased the likelihood of spontaneous stone passage.
A meta-analysis of 693 patients in nine randomized trials concluded that alpha-blockers and calcium channel blockers increased the likelihood of stone passage compared with no treatment.
In a randomized, double-blind study in 86 patients with unilateral ureteral stones, a higher rate of stone passage was reported in patients treated with methylprednisolone (Medrol) 16 mg/day plus nifedipine (Procardia) 40 mg/day than in those given methylprednisolone alone.
The growing advanced chronic kidney disease (CKD) population is a widely recognized global health issue. In CKD, progressive nephron loss causes tubulointerstitial fibrosis and progressive tubular injury.
In patients with advanced and declining kidney function, multiple interventions including modality education and vascular access planning are required, ideally prior to the development of end stage kidney disease (ESKD). Most patients with CKD however do not progress to ESKD. Thus assessment of risk of ESKD is necessary for counseling of patients and adequate advanced care planning.
Under physiological condition, intrarenal vascular distribution is heterogeneous, and the medulla is relatively hypoxic. Inflammation, systemic or intrarenal, not only can abolish the microvascular response to its regulators, but also induces an array of tubular toxins, including reactive oxygen species, leading to tubular injury, nephron dropout, and onset of CKD. Positive acid balance, electrolyte alterations, and intestinal dysbiosis can perpetuate CKD progression.
In the early stages, there usually are no symptoms. As the disease worsens, symptoms may include:
• Changes in how often you need to urinate
• A feeling of tiredness or drowsiness
• Loss of appetite
• Swelling of hands and feet
• A feeling of itchiness
• Feeling of nausea or vomiting
• Muscle cramps
• Darkening of the skin
Often, kidney diseases are discovered through routine testing of blood or urine. According to the National Kidney Foundation, 3 tests are recommended for testing for kidney disease:
• Measuring blood pressure. Blood pressure levels are not only a factor in causing kidney disease, but may also indicate the presence of kidney disease.
• Testing urine for the presence of albumin or other proteins.
• Measuring serum creatinine to provide for a calculation of glomerular filtration rate (GFR).
• In addition, measuring the level of urea nitrogen in the blood can also be useful.
If these tests come back with an indication of kidney disease, your health care provider may order additional testing. These may include imaging tests, such as ultrasound, magnetic resonance imaging (MRI), and computerized tomography (CT) scans. If the healthcare provider needs additional information, he or she may order a kidney biopsy. This procedure means that a needle is used to retrieve a piece of kidney tissue in an operation using local anesthesia.
There is no cure for chronic kidney disease, but steps may be taken in early CKD to preserve a higher level of kidney function for a longer period of time. People who have reduced kidney function should:
• Make and keep regular doctor visits; a nephrologist (kidney specialist) might be recommended.
• Keep their blood sugar under control (for diabetics).
• Avoid taking painkillers and other medications that may make kidney disease worse.
• Keep blood pressure levels under control.
• Consult a dietitian regarding useful changes in diet. This may include limiting protein intake, reducing blood cholesterol levels, and limiting sodium (salt) and potassium intake.
• Stop smoking.
• Treat anemia if present.
For patients with established CKD and/or diabetes with albuminuria, the updated hypertension guidelines have recommended a blood pressure (BP) goal < 130/80 mmHg. Blood pressure levels above 130/80 mmHg in CKD patients require lifestyle modifications and multiple antihypertensive medications.
According to recent guidelines, angiotensin-converting enzyme (ACE) inhibitors should be the drugs of first choice. Angiotensin II receptor blockers (ARBs) should be used if the ACE inhibitor is not tolerated. Non-dihydropyridine calcium-channel blockers (CCBs) consistently reduce albuminuria and slow the decline in kidney function. Dihydropyridine CCBs should not be used as monotherapy in proteinuric CKD patients but always in combination with a RAAS blocker. Diuretics are commonly used and represent the cornerstone in the management of CKD patients.
Because there is no cure for CKD, people who are in the later stages of the disease must consider options. Complete kidney failure, left untreated, will result in death. Options for patients in the end stages of CKD include dialysis and kidney transplantation.
Kidney failure, also called end-stage renal disease (ESRD), is the last stage of chronic kidney disease. The most common causes of kidney failure are diabetes and high blood pressure. Sometimes, though, kidney failure happens quickly due to an unforeseen cause.
When the kidneys lose function suddenly (within hours or days), it’s called acute kidney failure (or acute kidney injury). This type of kidney failure is often temporary. Common causes of acute kidney failure can include:
• Autoimmune kidney diseases
• Certain medications
• Severe dehydration
• A urinary tract obstruction
• Uncontrolled systemic disease like heart or liver disease
The biggest causes of kidney failure from chronic kidney disease are:
• Diabetes: Unmanaged diabetes can lead to uncontrolled blood sugar levels. Consistently high blood sugar can damage the body’s organs, including the kidneys.
• High blood pressure: High blood pressure (hypertension) means blood travels through your body’s blood vessels with increased force. Over time, untreated high blood pressure levels can damage the kidneys’ tissue.
Other causes of chronic kidney disease include:
• Polycystic kidney disease, a hereditary condition where cysts grow inside the kidneys.
• Glomerular diseases, such as glomerulonephritis, which affect how well the kidneys can filter waste.
• Lupus and other autoimmune diseases that can affect multiple body systems.
Dialysis: This treatment helps the body filter the blood.
In hemodialysis, a machine regularly cleans the blood. People often receive this kidney failure treatment at a hospital or dialysis clinic, 3 or 4 days each week.
Peritoneal dialysis cleans the blood in a slightly different way using a dialysis solution and a catheter. Sometimes, people can do their treatment at home.
Urinary tract infections are caused by microorganisms—usually bacteria—that enter the urethra and bladder, causing inflammation and infection. The infection can involve the urethra (urethritis), bladder, (cystitis), or kidneys (pyelonephritis). Cystitis is the most common type of urinary tract infection. More than 90 percent of cystitis cases are caused by E. coli, a bacterium normally found in the intestines.
Urinary tract infections are very common, occurring in 1 out of 5 women sometime in their lifetime. 1 to 2% of children develop urinary tract infections.
• Pain in the flank (side), abdomen or pelvic area
• Pressure in the lower pelvis
• The need to urinate at night
• Abnormal urine color (cloudy urine)
• Blood in the urine
• Strong or foul-smelling urine
• Urinalysis to examine the urine for red blood cells, white blood cells and bacteria (The number of white and red blood cells can indicate an infection.)
• Urine culture to determine the type of bacteria in the urine. This is important to help determine the appropriate treatment.
The gold standard for the diagnosis of a urinary tract infection is the detection of the pathogen in the presence of clinical symptoms. The pathogen is detected and identified by urine culture (using midstream urine).
This also allows an estimate of the level of the bacteriuria. However, the minimum level of bacteriuria demonstrating an infection of the urinary tract has not been defined in scientific literature or standardized by microbiological laboratories. Many laboratories define 105 colony forming units (CFU)/mL urine as the threshold.
However, this threshold misses many relevant infections. There are therefore other recommendations that recommend the diagnosis of UTI from a count of 103 CFU/mL, depending on the types of bacteria detected.
UTI with a low bacterial count is most reliably detected with the below algorithm:
• Burning sensation or discomfort when passing urine
• Detection of leukocytes
• Any detection of nitrite.
The diagnostic criterion is then the presence of at least two test criteria (sensitivity 80%, specificity 54%). Additional urine microscopy only slightly improves the probability of detection.
The guideline recommendations for the antibiotic treatment of infections of the urinary tract are often not implemented in practice. National and international recommendations warn against the broad and uncritical use of fluoroquinolones for uncomplicated infections.
The group of antibiotic medicines known as fluoroquinolones — such as ciprofloxacin (Cipro), levofloxacin (Levaquin) and others — isn’t commonly recommended for simple UTIs, as the risks of these medicines generally outweigh the benefits for treating uncomplicated UTIs. In some cases, such as a complicated UTI or kidney infection, the physician might prescribe a fluoroquinolone medicine if no other treatment options exist.
For an uncomplicated UTI that occurs when you’re otherwise healthy, your doctor may recommend a shorter course of treatment, such as taking an antibiotic for one to three days.
There are special recommendations for complicated UTI, as greater diagnostic accuracy and different therapeutic strategies are necessary.
For all therapy-resistant and complicated infections of the urinary tract, an attempt should generally be made to perform a urine culture to detect the causative organisms and their antimicrobial susceptibility.
Absolute diagnostic reliability and maximally specific therapy would only be achieved if the gold standard—urine culture—was always used. This approach would require considerable additional effort, but would be capable of greatly reducing the rate of antibiotic prescriptions. On the other hand, this would delay specific antibiotic therapy. One current demand is for immediate empirical therapy, together with preparation of a urine culture at the same time.
Erectile dysfunction (ED) is the inability to get and keep an erection firm enough for sexual intercourse. Estimates suggest that one of every 10 men will suffer from ED at some point during his lifetime. It is important to understand that in most cases, ED is a symptom of another, underlying problem. ED is not considered normal at any age, and may be associated with other problems that interfere with sexual intercourse, such as lack of desire and problems with orgasm and ejaculation.
Although more common in older men, over half of all ED cases are the result of physical issues such as obesity, smoking and diabetes; emotional issues including stress, anxiety and depression; or a combination of both. However, compelling evidence suggests ED is also a warning sign of other underlying and more serious medical conditions, like cardiovascular disease, and may precede a cardiovascular event by up to five years.
Measurement of fasting serum glucose, lipid profile, and morning total testosterone should be considered mandatory in all newly presenting patients. Patients attending their primary care physician with chronic cardiovascular disease should be asked about erectile problems.
Evaluation and Diagnosis
• Men presenting with symptoms of ED should undergo a thorough medical, sexual, and psychosocial history; a physical examination; and selective laboratory testing.
• For the man with ED, validated questionnaires are recommended to assess the severity of ED, to measure treatment effectiveness, and to guide future management.
• Men should be counseled that ED is a risk marker for underlying cardiovascular disease (CVD) and other health conditions that may warrant evaluation and treatment.
• In men with ED, morning serum total testosterone levels should be measured.
• For some men with ED, specialized testing and evaluation may be necessary to guide treatment.
Selecting optimal care for each patient can be an intricate process that requires physicians to help patients choose options consistent with the individual’s own values or beliefs, and with the goal of restoring their sexual function.
Current therapeutics for ED consist of oral medications, intracavernosal injections, vacuum erection devices, and penile implants. While such options may manage the disease state, none of these modalities, however, restore function.
The American Urological Association (AUA) has issued the guidelines 2018 for men treated for ED:
• For men being treated for ED, referral to a mental health professional should be considered to promote treatment adherence, reduce performance anxiety, and integrate treatments into a sexual relationship.
• Clinicians should advise men with ED who have comorbidities known to negatively affect erectile function that lifestyle modifications, including changes in diet and increased physical activity, improve overall health and may improve erectile function.
• Men with ED should be informed regarding the treatment option of an FDA-approved oral phosphodiesterase type 5 inhibitor (PDE5i), including discussion of benefits and risks/burdens, unless contraindicated.
• When men are prescribed an oral PDE5i for the treatment of ED, instructions should be provided to maximize benefit/efficacy.
• For men who are prescribed PDE5i, the dose should be titrated to provide optimal efficacy.
• Men who desire preservation of erectile function after treatment for prostate cancer by radical prostatectomy (RP) or radiotherapy (RT) should be informed that early use of PDE5i post-treatment may not improve spontaneous, unassisted erectile function.
• Men with ED and testosterone deficiency (TD) who are considering ED treatment with a PDE5i should be informed that PDE5i may be more effective if combined with testosterone therapy.
• Men with ED should be informed regarding the treatment option of a vacuum erection device (VED), including discussion of the benefits and risks/burdens.
• Men with ED should be informed regarding the treatment option of intraurethral (IU) alprostadil, including discussion of the benefits and risks/burdens.
• For men with ED who are considering the use of IU alprostadil, an in-office test should be performed.
• Men with ED should be informed regarding the treatment option of intracavernosal injections (ICI), including discussion of the benefits and risks/burdens.
• For men with ED who are considering ICI therapy, an in-office injection test should be performed.
• Men with ED should be informed regarding the treatment option of penile prosthesis implantation, including discussion of the benefits and risks/burdens.
• Men with ED who have decided on penile implantation surgery should be counseled regarding post-operative expectations.
• Penile prosthetic surgery should not be performed in the presence of systemic, cutaneous, or urinary tract infection.
• For young men with ED and focal pelvic/penile arterial occlusion and without documented generalized vascular disease or veno-occlusive dysfunction, penile arterial reconstruction may be considered.
• For men with ED, penile venous surgery is not recommended.
• For men with ED, low-intensity extracorporeal shock wave therapy (ESWT) should be considered investigational.
• For men with ED, intracavernosal stem cell therapy should be considered investigational.
• For men with ED, platelet-rich plasma (PRP) therapy should be considered experimental.
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- Matz EL et al. Stem Cell Therapy for Erectile Dysfunction. Sex Med Rev. 2018 pii: S2050-0521(18)30014-3. doi: 10.1016/j.sxmr.2017.12.008.
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- Mayo Clinic. Erectile Dysfunction. Available at: https://www.mayoclinic.org/diseases-conditions/erectile-dysfunction/symptoms-causes/syc-20355776
- American Urological Association. AUA Releases New Clinical Guideline for Diagnosis and Treatment of Erectile Dysfunction. Available at: https://www.prnewswire.com/news-releases/aua-releases-new-clinical-guideline-for-diagnosis-and-treatment-of-erectile-dysfunction-300644289.html
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