Vascular and Tubulointerstitial Diseases of the Kidney

This lecture actually did have some more learning outcomes, but I think I might actually just stick to using the diseases as headings.

Vascular Diseases

Vascular diseases of the kidney, as the name implies, are diseases that affect the vasculature of the kidney.

Hypertensive nephrosclerosis

Hypertensive nephrosclerosis is scarring (sclerosis) of the kidney (nephro-) due to hypertension. Hypertensive nephrosclerosis can be either benign or malignant. Benign nephrosclerosis is due to chronic hypertension, defined as a blood pressure greater than 140/90, whereas malignant nephrosclerosis is due to accelerated hypertension (i.e. a rapid spike in blood pressure) or malignant hypertension, defined as a blood pressure greater than 180/110 with acute end-organ damage.

Benign hypertensive nephrosclerosis is the third most common cause of chronic renal failure. Over time, the small arteries and arterioles become thickened and there is damage to the glomeruli and tubules. Benign hypertensive nephrosclerosis may be asymptomatic with proteinuria, but over time it may progress to chronic renal failure. Malignant hypertensive nephrosclerosis is a medical emergency in which the damage is quite severe, and may present as acute renal failure. Under the microscope, there is fibrinoid necrosis of arterioles and hyperplastic arteriolosclerosis.

Renal artery stenosis

Renal artery stenosis is narrowing (stenosis) of the renal artery, which can lead to secondary hypertension. (As you can see, there can be a bit of interplay between the kidneys and hypertension: renal artery stenosis can lead to hypertension, which can lead to hypertensive nephrosclerosis.) Renal artery stenosis is usually due to atherosclerosis in elderly patients, but it can also be due to fibromuscular dysplasia in young women. (Fibromuscular dysplasia involves segmental thickening of arteries, which looks kind of like a string of beads on angiography. So far, the cause of this is unknown.)

One of the problems with renal artery stenosis is that it decreases blood flow to the kidneys, activating the RAAS, which increases vasoconstriction. The vasoconstriction triggered by the RAAS exacerbates the problem, forming a vicious cycle.

Tubulointerstitial Diseases

Tubulointerstitial diseases are diseases that affect the tubules and the interstitium of the kidney. (I love it when names are logical!)

Acute tubular necrosis

Acute tubular necrosis is one of the most common causes of renal failure. Acute tubular necrosis is necrosis of the kidney tubules (again, I'm loving these logical names), which may be due to ischaemia or toxins. There are three main phases of acute tubular necrosis: initiation, maintenance, and recovery. In the initiation phase, there is mild oliguria and a mild increase in serum creatinine. In the maintenance phase, oliguria and the increase in serum creatinine continue. There may also be uraemia. Finally, in the recovery phase, there is a large amount of diuresis (peeing). Because you're losing a lot of fluid pretty rapidly, you're also losing a lot of electrolytes at the same time, which can pose other problems.

Tubulointerstitial nephritis

Tubulointerstitial nephritis is inflammation of the tubules of the kidney. Tubulointerstitial nephritis may be either acute or chronic, with the chronic form being irreversible. There are many causes of tubulointerstitial nephritis but the main one to be aware of is drugs, particularly NSAIDs, proton pump inhibitors, and antibiotics. Unfortunately, drug-related tubulointerstitial nephritis is somewhat hard to predict: we don't really know who will get it and at what dose. It is thought that drugs act as a hapten in order to trigger an immune response (see here for information on what a hapten is).

It is important to distinguish between acute tubulointerstitial nephritis and acute pyelonephritis, as the two conditions may present similarly. (Apparently we will be learning about acute pyelonephritis next week, so stay tuned!) While acute tubulointerstitial nephritis is often drug-related and can be treated by simply removing the drug (and perhaps also giving some steroids), acute pyelonephritis is usually due to an ascending UTI that can be treated with antibiotics.

Chronic pyelonephritis

Chronic pyelonephritis is chronic inflammation of the kidney. It is usually due to either reflex nephropathy (reflux of urine back into the kidney) or obstructive nephropathy (some obstruction to urinary outflow). The kidney surface can have very deep, irregular scars, and under the microscope the inflammation can be so severe that the tubules look almost like the follicles of the thyroid gland. (This is also known as "tubular thyroidisation.")

Myeloma kidney

Myeloma kidney is a result of plasma cell myeloma (a.k.a. multiple myeloma). As the name suggests, plasma cell myeloma is a malignant proliferation of plasma cells (i.e. antibody-producing B cells). Plasma cell myelomas secrete large amounts of the same antibody, and sometimes these antibodies might be abnormal. For instance, the antibodies that are secreted might only consist of light chains. There are a range of complications that can result from myeloma kidney, but for now we'll only focus on two: myeloma cast nephropathy and amyloidosis.

Myeloma cast nephropathy occurs when abnormal light chains precipitate out of solution, forming casts. These casts can clog up the tubules, resulting in acute renal failure. Under immunofluorescence, these light chains will consist of only kappa chains or only lambda light chains (remember, in myeloma, large amounts of the same antibody are being made).

Amyloidosis is characterised by a build-up of amyloid, which consists of abnormally-folded extracellular proteins that resist degradation. Amyloid can be visualised with the Congo red stain. Under the Congo red stain, they stain salmon-pink, and if seen under polarised light while stained, they appear apple-green. In myeloma kidney, amyloidosis occurs due to the light chains in myeloma, and thus this type of amyloid is called AL-amyloid. Amyloid can deposit in a range of places in the kidney, causing a lot of problems.