Pφ

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.

TP

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.

Dx

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

Pφ

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.

TP

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.

Dx

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.

Pφ

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.

TP

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.

Dx

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.

Pφ

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.

TP

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.

Dx

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.

Pφ

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.

TP

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.

Dx

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.

Pφ

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.

TP

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.

Dx

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.

Pφ

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.

TP

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.

Dx

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.

Pφ

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.

TP

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.

Dx

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.