Renal Pathology Overview (AKI & CKI)

Renal Pathology Overview (AKI & CKI)

Renal Review

The kidneys filter the blood to remove wastes and balance fluid, electrolytes, minerals, and acids and bases in the body.
The kidneys are also responsible for production of renin and erythropoietin, and activation of Vitamin D.
Impairment of these functions can lead to systemic problems, even death.
The kidneys are retroperitoneal organs in the posterior abdominal wall, just below the ribcage.
Kidney, with outer cortex and inner medulla, which comprises the renal pyramids.
The pyramids contain millions of nephrons, which filter the blood to create urine – nephrons are the functional units of the kidney.
Urine exits the renal pyramids and enters the renal sinus, which is drained by the ureter – from here, urine travels to the urinary bladder in the pelvis.
The renal artery and its branches deliver 25% of cardiac output to the kidneys for filtering.
The nephron:

The renal corpuscle is where the afferent arteriole, glomerulus (capillary network), and efferent arteriole enter and exit the nephron.
Within the renal corpuscle, blood is filtered in the glomerulus, a network of capillaries, to form ultrafiltrate.
The ultrafiltrate travels through the nephron tubule as tubular fluid; the fluid and remaining solutes exit the collecting duct as urine, destined for the ureter and urinary bladder.

Acute Kidney Injury

Acute kidney injury is diagnosed when patients have increased creatinine and decreased urine volume (specifically: an increase in creatinine (Cr) higher than 0.3 mg/dl (26.5 umol/L) in 48 hours, a rise of creatine greater than 1.5 times the baseline ((occurring within the last seven days)), and a decrease of urine volume of equal to or lesser than 0.5 ml/kg/h (2012 Kidney Disease: Improving Global Outcomes)).
Be aware that acute kidney injury was formerly called acute kidney failure; this new terminology includes, but is not limited to, kidney failure.
“Azotemia” is increased blood urea nitrogen (BUN), creatinine, and other nitrogenous waste products in the blood (azot = nitrogen, emia = blood), which occurs as a result of reduced renal filtering in both acute and chronic kidney injury.
Causes of acute kidney injury (AKI) are categorized as prerenal, intrinsic/intrarenal, and postrenal.
Pre-renal causes are those that alter renal hemodynamics: when renal blood flow decreases, so does the glomerular filtration rate. As a result, less fluid and solutes are filtered from the blood.

With the reduction in GFR, urine sodium levels in prerenal AKI patients are lower than normal, less than 20 mEq/L, and fractional excretion of sodium is less than 1%.
Upon fluid administration, patients with pre-renal AKI will show reduction in serum creatinine.
Any event that alters systemic circulation or renal perfusion can impact GFR, including intravascular volume depletion, bilateral renal stenosis, heart failure, use of ACE inhibitors or Angiotensin II receptor blockers (ARBs), and hypotension.
In healthy individuals, GFR is maintained by autoregulatory mechanisms, but these can become overwhelmed.

Intrinsic/intrarenal acute kidney injury can be further divided based on the renal structures primarily involved:

Vascular causes of AKI include vasculitis, malignant hypertension, and thrombotic thrombocytopenia purpura (TTP) and hemolytic uremic syndrome (HUS).
Glomerular damage can be further divided based on which solutes erroneously pass through the membrane:
Nephrotic syndrome occurs when proteins leak out of the capillaries and into the ultrafiltrate; this occurs in focal segmental glomerulosclerosis, membranous nephropathy, and minimal change disease.

Nephrotic syndrome (aka nephrosis) is characterized by a group of signs/symptoms resulting from the loss of protein in the urine: proteinuria, hypoalbuminemia, edema, hyperlipidemia, with puffy eyelids and edema, foamy urine, fatigue, and loss of appetite.

Nephritic syndrome occurs when blood cells leak into the ultrafiltrate, and is associated with infection associated glomerulonephritis, IgA nephropathy, and anti-glomerular basement membrane antibody disease.

Signs and symptoms of nephritic syndrome include hematuria, hypertension, edema, and oliguria, with red blood cells and their casts and WBC in urine; proteinuria is not uncommon, but to a lesser degree than in nephrotic syndrome.

Tubular damage is usually caused by acute tubular necrosis (ATN), which is the most common cause of AKI overall (especially in hospitalized patients); it is associated with high morbidity and mortality.

Acute tubular necrosis is characterized by patchy injury to the nephron tubule, often caused by ischemia (so etiologies of pre-renal AKI can also cause acute tubular necrosis) or toxic substances (medicines, hemoglobin/myoglobin, lead, etc.). Renal tubular cell damage and death impair tubular function, and the debris that obstructs tubules with backflow leads to reduced GFR. Urine analysis shows muddy brown casts, and tubular cells. Lastly, acute interstitial nephritis (AIN) is usually caused by medicines, esp. antibiotics and NSAIDs; it is also caused by autoimmune disorders and infections. Notable signs and symptoms include skin rash, fever, and eosinophilia, with white blood cells and their casts in urine. Indicate that intrinsic/intrarenal causes of AKI are associated with elevated urine sodium, higher than 40 mEq/L, and fractional excretion of sodium greater than 2 percent.

Post-renal AKI is the result of obstruction, including:

Congenital anomalies (i.e., renal dysplasia),
Tumors (i.e., prostate tumors that compress and obstruct urine flow),
Kidney stones (which can comprise calcium, ammonium magnesium, phosphate, uric acid, or cystine),
Infections that cause swelling or other means of compression.
Bladder outlet obstruction is the most common cause of post-renal AKI; urine trapped in the bladder, with potential to backflow into the ureters, causes increased pressure in the renal system and results in lowered GFR.
Note that unilateral renal obstruction is less often associated with AKI because the non-obstructed structure can typically compensate.

Chronic kidney injury

Formerly called chronic renal failure

Occurs when GFR is chronically impaired (less than 60 ml/min/1.73 mt2 lasting for 3+ months) due to gradual, progressive loss of renal functioning; as a result, toxins accumulate to dangerous levels.
Top causes of chronic kidney injury:

Diabetes
Primary glomerulonephritis
Hypertension (secondary glomerulonephritis)
Autosomal dominant polycystic kidney disease

Uremia, which can occur in acute kidney injury but is more common in chronic injury, is azotemia that leads to a cluster of signs/symptoms in various body systems, including the cardiac and nervous systems.
End-stage renal disease is established when GFR is less than 5% of normal; this is the terminal stage of uremia.

Renal failure

Excess retention of nitrogenous waste products and electrolyte disturbances, which results in a variety of signs and symptoms we can remember with the mnemonic

MAD HUNGER: Metabolic acidosis Dyslipidemia Hyperkalemia Uremia Na+ and H2O retention (with resulting heart failure, pulmonary edema, and hypertension), Growth retardation and developmental delay Erythropoietin deficiency (anemia) Renal osteodystrophy

For references, please see full tutorial.

Renal Pathology Overview (AKI & CKI)

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