Question

ACUTE RENAL FAILURE

Discuss acute and chronic pyelonephritis, causes and symptoms.

List the drugs that cause kidney damage.

Describe categories of renal failure and their causes.

Describe causes of ATN, and different phases of ATN. Discuss nephrotoxins that cause ATN.

Four phases of ATN

What is intact nephron hypothesis?

Discuss clinical manifestations of chronic kidney disease.

Answer 1

1.Acute pyelonephritis:  Acute pyelonephritis is a sudden and severe kidney infection. It causes the kidneys to swell and may permanently damage them. Pyelonephritis can be life-threatening

• Acute suppurative (pus forming) infection of kidney collecting system as well as renal parenchyma
• Affects infants and young children with congenital lesions, women of childbearing age, men and women age 60+ years (due to nodular hyperplasia of prostate, cystoceles in women, cervical carcinoma, nephrolithiasis)
• Also associated with diabetes or immunocompromise

• Causes: urinary tract infection (UTI), instrumentation, obstruction, pregnancy (4 - 6% have bacteriuria, 20% have symptoms if untreated), vesicoureteral reflux
• Bacterial UTI: due to colonization of distal urethra and introitus by coliform bacteria with adhesins on P-fimbriae (pili), plus upward spread via instrumentation or catheterization; more common in women than men due to short urethra, no anti-bacterial prostatic fluid, hormonal changes, sex-related trauma
• Usually gram negative rods from fecal flora (E. coli, Enterobacter, Klebsiella, Proteus, Streptococcus faecalis) or Staph
• Ascending route most common; also hematogenous spread of bacteria to kidney
• Intrarenal reflux: via open ducts at tips of papillae; most common at poles of kidney where papillae have flat or concave tips; demonstrate via voiding cystourethrogram (seen in 50% of children with UTI)
• Vesicoureteral reflux:due to short intravesical ureter, spinal cord injuries; some UTIs; independent risk factor for renal scar formation after acute pyelonephritis in infants

Signs & Symptoms of Acute Pyelonephritis

• chills.
• fever.
• pain in your back, side, or groin.
• nausea.
• vomiting.
• cloudy, dark, bloody, or foul-smelling urine.
• frequent, painful urination.

Chronic pyelonephritis:

Chronic pyelonephritis is continuing pyogenic infection of the kidney that occurs almost exclusively in patients with major anatomic abnormalities. Symptoms may be absent or may include fever, malaise, and flank pain. Diagnosis is with urinalysis, culture, and imaging tests.

Causes:

Causes include obstructive uropathy, struvite calculi, and, most commonly, vesicoureteral reflux (VUR). Pathologically there is atrophy and calyceal deformity with overlying parenchymal scarring. Chronic pyelonephritis may progress to chronic kidney disease.

Signs and Symptoms:

There is often associated vomiting. Chronic pyelonephritis causes persistent flank or abdominal pain, signs of infection (fever, unintentional weight loss, malaise, decreased appetite), lower urinary tract symptoms and blood in the urine.

2. Drugs that cause kidney damage :

• Pain Medications. Your kidneys could be damaged if you take large amounts of over-the-counter medications, such as aspirin, naproxen and ibuprofen. ...
• Alcohol. ...
• Antibiotics. ...
• Prescription Laxatives. ...
• Contrast Dye (used in some diagnostic tests such as MRIs) ...
• Illegal Drugs. ...

Many medicines can cause acute renal failure . Examples include: Antibiotics , such as aminoglycosides, cephalosporins, amphotericin B, bacitracin, and vancomycin. Blood pressure medicines called ACE inhibitors (such as captopril and ramipril) and angiotensin receptor blockers (such as candesartan and valsartan).

Renal vitamins contain vitamins B1, B2, B6, B12, folic acid, niacin, pantothenic acid, biotin and a small dose of vitamin C. Below is an overview of the fat- and water-soluble vitamins your body cannot do without, and the dietary recommendations for people with CKD.

3. categories of renal failure and their causes

There are five different types of kidney failure:

• Acute prerenal kidney failure. Insufficient blood flow to the kidneys can cause acute prerenal kidney failure. ...
• Acute intrinsic kidney failure. ...
• Chronic prerenal kidney failure. ...
• Chronic intrinsic kidney failure. ...
• Chronic post-renal kidney failure.

The most common causes are:

• high blood pressure.
• chronic glomerulonephritis (kidney damage)
• high blood sugar (diabetes)
• polycystic kidney disease.
• blocked urinary tract.
• kidney infection.

4.

Describe causes of ATN, and different phases of ATN. Discuss nephrotoxins that cause ATN.

Four phases of ATN

Acute tubular necrosis (ATN) is a medical condition involving the death of tubular epithelial cells that form the renal tubules of the kidneys. ATN presents with acute kidney injury (AKI) and is one of the most common causes of AKI. Common causes of ATN include low blood pressure and use of nephrotoxic drugs

Phases of Acute tubular necrosis

• Initiation: This phase usually last hours to days. During this time, glomerular filtration rate (GFR) will decrease caused by a decrease in renal blood flow. ...
• Extension: The GFR continues to decrease or remains low. ...
• Maintenance: Typically lasts 1-2 weeks. ...
• Recovery: Marked by tubular cell repair and regeneration

Causes of Acute tubular necrosis

• Initiation: This phase usually last hours to days. During this time, glomerular filtration rate (GFR) will decrease caused by a decrease in renal blood flow. ...
• Extension: The GFR continues to decrease or remains low. ...
• Maintenance: Typically lasts 1-2 weeks. ...
• Recovery: Marked by tubular cell repair and regeneration.

Nephrotoxic-Induced Acute Tubular Necrosis

The kidney clears and metabolizes many drugs. Some of these drugs behave as exogenous toxins and can cause direct renal tubular injury or crystal-induced acute kidney injury (AKI), leading to acute tubular necrosis. Drugs such as aminoglycoside, amphotericin B, radiocontrast media, sulfa drugs, acyclovir, cisplatin, calcineurin inhibitors (tacrolimus, cyclosporine), mammalian target of rapamycin mTOR inhibitors (everolimus, temsirolimus), foscarnet, ifosfamide, cidofovir, and IV immunoglobulin containing sucrose all can cause acute tubular necrosis.

Heme pigment-containing proteins such as hemoglobin and myoglobin can behave as endotoxins in 3 ways:

1. Causing direct proximal tubular injury, tubular obstruction, or renal vasoconstriction

2. Crystal-induced nephropathy due to high cell turnover such as uric acid, calcium phosphate crystals in the setting of ongoing malignancy treatment

3. Light chains accumulation in multiple myeloma is directly toxic to the renal proximal and distal tubules

Sepsis-Induced Acute Tubular Necrosis

Sepsis also plays a role in causing acute tubular necrosis because of systemic hypotension and renal hypoperfusion. Other mechanisms which are incompletely understood include endotoxemia leading to AKI by renal vasoconstriction, and the release of inflammatory cytokines causing enhanced secretion of reactive oxygen species and leading to renal injury.

5.What is intact nephron hypothesis?

The intact nephron hypothesis (INH) states that impaired renal function results from a reduction in the number of complete (intact) nephrons. Under this model, renal drug clearance is assumed to be a linear function of glomerular filtration while tubular handling is ignored

6.Discuss clinical manifestations of chronic kidney disease.

The most common signs and symptoms of chronic kidney disease include:

• anemia.
• blood in urine.
• dark urine.
• decreased mental alertness.
• decreased urine output.
• edema - swollen feet, hands, and ankles (face if edema is severe)
• fatigue (tiredness)
• hypertension (high blood pressure)