24. Benign and malignant nephrosclerosis and diffuse cortical necrosis. Urolithiasis and obstructive uropathy.

Nephrosclerosis

Nephrosclerosis, or more precisely arterionephrosclerosis refers to thickening and sclerosis of the walls of arteries and arterioles in the kidney. It’s a condition that is related to hypertension. Nephrosclerosis can lead to chronic renal failure. We distinguish two types of nephrosclerosis: the benign type and the malignant type.

Benign nephrosclerosis occurs when there is chronic hypertension. There is a hyaline thickening of the walls of small arteries and arterioles with narrowing of their lumen, called hyaline arteriolosclerosis. The surface of the kidney becomes granular and leathery instead of smooth. The kidneys are atrophic and smaller. The tubules show ischaemic atrophy due to the narrowing of the lumen of arteries and there is interstitial fibrosis.

Nephrosclerosis alone rarely leads to severe kidney damage except in African Americans, who are genetically susceptible to this. In these patients may benign nephrosclerosis progress into chronic renal failure. All patients with benign nephrosclerosis show at least some degree of functional impairment, such as slightly decreased GFR.

Malignant nephrosclerosis occurs when there is malignant hypertension (above 200/120 mmHg). The high pressure damages the walls of small arteries and arterioles and increases their permeability to fibrinogen, causing fibrinoid necrosis of these vessels. Proliferative factors in the plasma enters the vessel wall and causes hyperplasia of the tunica intima, causing hyperplastic arteriolosclerosis.

As the renal perfusion decreases due to arteriolosclerosis is the RAAS activated, which further increases blood pressure. Microthrombi appear in the glomeruli and cause necrotizing glomerulitis.

Untreated malignant nephrosclerosis is an emergency as it can lead to acute kidney failure.

Diffuse cortical necrosis

Diffuse cortical necrosis is a rare cause of acute renal failure due to ischaemic necrosis of the renal cortex. The ischaemia is caused by vascular spasm, microvascular injury or intravascular coagulation (DIC). It’s defined as a necrosis that is sharply limited to the renal cortex. It typically occurs in neonates, pregnancy or postpartum women due to sepsis or pregnancy complications.

Urolithiasis

Urolithiasis is the formation of stones at any level in the urinary collecting system, but most commonly they arise in the kidney (nephrolithiasis). They aren’t an infrequent finding. There is a familial tendency toward stone formation. There are four major types of stone:

• Calcium oxalate stone – 80% of cases
• Struvite (Magnesium ammonium phosphate) stone – 10%
• Uric acid stone – 6%
• Cysteine stone – 1%

All types of stone occur when the urine is supersaturated with the components of the stone. In some cases other factors will contribute to the formation of stones as well, like abnormal pH.

Calcium stones are the most frequent type. They occur when the urine is supersaturated with calcium (hypercalciuria). There are three major causes for this:

• Hypercalcaemia
• Absorptive hypercalciuria – Calcium is absorbed from the gut in excessive amounts
• Renal hypercalciuria – A defect in the renal calcium reabsorption

Struvite stones occur in people with alkaline urine. Alkaline urine is a result of UTIs, especially those caused by bacteria that produce urease, like Proteus and Staphylococci. Struvite stones can sometimes make a “cast” of the renal pelvis, called staghorn calculi.

Uric acid stones occur in people with acidic urine and increased excretion of uric acid. The latter can be idiopathic or in combination with gout or diseases that cause rapid cell turnover, like leukaemia.

Cysteine stones occur in people with genetically determined defects in renal transport of cysteine. Acidic urine also increases the risk for cysteine stones.

Kidney stones are usually small (2-3 mm). They may be present without symptoms, especially if they are in the renal pelvis. Smaller stones may pass into the ureter and get lodged there, causing colicky pain. There is often gross haematuria. The lodged stones can cause ulceration and bleeding, or they can obstruct the outflow of urine. Both cases can be dangerous, and both cases predispose to bacterial infection.

Obstructive uropathy

Obstructive uropathy or urinary tract obstruction is a mechanical or functional block to the outflow of urine. The obstruction may be partial or complete, unilateral or bilateral. It can occur in anywhere in the urinary tract. It can be caused by:

• Inside the kidney
  • Nephrolithiasis
  • Urothelial carcinoma
• Ureter
  • Nephrolithiasis – most common cause in young adults
  • Ureteral stricture – fibrosis after surgery
  • Urothelial carcinoma
  • Pregnancy
  • Extraluminal neoplasia – retroperitoneal, cervical, uterine, colonic
• Bladder
  • Urothelial carcinoma
  • Neurogenic bladder – spinal cord injury with paralysis of the bladder
• Urethra
  • Prostatic enlargement (BPH or cancer) – most common cause in elderly
  • Congenital abnormality of the urethral valves – most common cause in children

An obstruction at or below the level of the ureter will increase the pressure backwards up into the renal pelvis, causing dilation of all parts along the way. It will go like this:

• Hydroureter – dilation of the ureter
• Pyelectasis – dilation of the renal pelvis
• Hydronephrosis

Hydronephrosis refers to dilation of the renal pelvis and calyxes with accompanying atrophy of the renal parenchyme. The increased pressure in the pelvis due to the obstruction causes it to dilate, while the pressure also compresses the renal vasculature and therefor causes ischaemic atrophy. It takes about 3 weeks of complete obstruction or 3 months of incomplete obstruction to cause irreversible damage, so early diagnosis and treatment is important and curative. Hydronephrosis progresses quickly to anuria and renal failure if it is bilateral or if it is unilateral while the unobstructed kidney is already damaged. Hydronephrosis predisposes to pyelonephritis, which may progress into urosepsis.