Your kidneys also regulate red blood cell formation. The kidneys measure oxygen levels in the blood that streams through the glomerular capillaries. When they detect below-normal oxygen levels, the kidneys release the hormone erythropoietin (EPO) into your bloodstream, sending it to the bone marrow. EPO then initiates red blood cell production in the marrow's stem cells. The production of EPO (and consequently the production of your red blood cells) depends directly on your kidneys' ability to measure and respond to changing oxygen levels. It's another example of the finely tuned balancing act constantly being performed by your kidneys.

A frontal section through the kidney reveals an outer region called the renal cortex and an inner region called the medulla (image). The renal columns are connective tissue extensions that radiate downward from the cortex through the medulla to separate the most characteristic features of the medulla, the renal pyramids and renal papillae. The papillae are bundles of collecting ducts that transport urine made by nephrons to the calyces of the kidney for excretion. The renal columns also serve to divide the kidney into 6–8 lobes and provide a supportive framework for vessels that enter and exit the cortex. The pyramids and renal columns taken together constitute the kidney lobes.

The kidneys lie on either side of the spine in the retroperitoneal space between the parietal peritoneum and the posterior abdominal wall, well protected by muscle, fat, and ribs. They are roughly the size of your fist, and the male kidney is typically a bit larger than the female kidney. The kidneys are well vascularized, receiving about 25 percent of the cardiac output at rest.

Overview

The structure of the kidney is divided into two principle regions—the peripheral rim of cortex and the central medulla. The two kidneys receive about 25 percent of cardiac output. They are protected in the retroperitoneal space by the renal fat pad and overlying ribs and muscle. Ureters, blood vessels, lymph vessels, and nerves enter and leave at the renal hilum. The renal arteries arise directly from the aorta, and the renal veins drain directly into the inferior vena cava. Kidney function is derived from the actions of about 1.3 million nephrons per kidney; these are the “functional units.” A capillary bed, the glomerulus, filters blood and the filtrate is captured by Bowman’s capsule. A portal system is formed when the blood flows through a second capillary bed surrounding the proximal and distal convoluted tubules and the loop of Henle. Most water and solutes are recovered by this second capillary bed. This filtrate is processed and finally gathered by collecting ducts that drain into the minor calyces, which merge to form major calyces; the filtrate then proceeds to the renal pelvis and finally the ureters.

The two kidneys are bean-shaped organs located just below the rib cage, one on each side of the spine. Every day, the two kidneys filter about 120 to 150 quarts of blood to produce about 1 to 2 quarts of urine, composed of wastes and extra fluid.

Blood enters the kidneys through arteries that branch inside the kidneys into tiny clusters of looping blood vessels. Each cluster is called a glomerulus, which comes from the Greek word meaning filter. The plural form of the word is glomeruli. There are approximately 1 million glomeruli, or filters, in each kidney. The glomerulus is attached to the opening of a small fluid-collecting tube called a tubule. Blood is filtered in the glomerulus, and extra fluid and wastes pass into the tubule and become urine. Eventually, the urine drains from the kidneys into the bladder through larger tubes called ureters.

Each glomerulus-and-tubule unit is called a nephron. Each kidney is composed of about 1 million nephrons. In healthy nephrons, the glomerular membrane that separates the blood vessel from the tubule allows waste products and extra water to pass into the tubule while keeping blood cells and protein in the bloodstream.

A variety of conditions can cause glomerulonephritis (GN), ranging from infections that affect the kidneys to diseases that affect the whole body, including the kidneys. Sometimes the cause is unknown.

Acute GN (a sudden attack of inflammation) may be caused by infections such as strep throat, impetigo, or bacterial endocarditis. Other infections that may cause GN include HIV, hepatitis B, and hepatitis C. GN may also be caused by immune diseases such as lupus, Goodpasture's syndrome, and IgA nephropathy. Types of vasculitis that may cause the condition include Wegener's granulomatosis and polyarteritis nodosa. Chronic GN sometimes develops after an episode acute glomerulonephritis.

In some cases, GN is caused by an inherited condition. One of these is Alport syndrome (also known as hereditary nephritis). Individuals with Alport syndrome may also have hearing and/or vision loss. Alport syndrome can have different inheritance patterns depending on the disease-causing gene involved.

Blood Pressure Control

Patients with reduced GFR or proteinuria >1 g/d should have all their blood pressure readings below 140/90. This is the recommendation of the most recent Joint National Commission. Patients are encouraged to check their blood pressure at home, ideally at the same time each day (e.g. dinner time or bedtime) and record the results.

Diet

There is some evidence that restricting protein intake to 0.8 g/kg/d may slow progression of kidney damage. Sodium restriction to 2 g/d will help lower blood pressure and will minimize edema.

Angiotensin Converting Enzyme Inhibitors (ACE Inhibitors)

These medicines have generic names ending in –IL (benazapril, captopril, enalapril, fosinopril lisinopril, moexipril, ramipril, quinapril, trandolopril). The medications have four beneficial effects on the kidney: they lower systemic blood pressure, they reduce pressure within the glomerulus, they reduce proteinuria, and they are anti-fibrotic. Higher doses, up to the FDA recommended maximum, are likely to be more effective. The beneficial effects are potentiated by a low sodium diet and by diuretics.

Common adverse reactions: cough, high serum potassium, low blood pressure, fatigue

Angiotensin Receptor Blockers (ARB)

These medicines have generic names endling in –AN (candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan). These medications have identical beneficial effects on the kidney compared to the ACE inhibitors.

Common adverse reactions: high serum potassium, low blood pressure, fatigue

Glucocorticoids

These medications are related to cortisol, a steroid produced by the body’s adrenal cortex. High doses are used in kidney disease. The mechanism of action is not well understood, but may include the immunosuppressive effect and also direct effects on glomerular cells, including podocytes. Common agents and regimens include the following: oral prednisone daily or alternate days, intravenous pulse methylprednisolone, and oral pulse dexamethasone

Common adverse reactions: nausea, vomiting, abdominal discomfort, edema, headache, mood swings, anxiety, insomnia, high blood glucose, hypertension, acne, skin atrophy

Serious adverse reactions: adrenal suppression, peptic ulcer, osteoporosis, glaucoma, cataract, psychosis

Cyclosporine (Neoral, Sandimmune)

This is an immunsuppressive medication that alters T lymphocyte function. Cyclosporine also may have direct effects on the glomerulus to reduce proteinuria. A typical course lasts 1 year or longer.

Common adverse reactions: hypertension, hair growth, tremor, numbness and tingling, acne, gum hyperplasia, diarrhea, elevated blood glucose, high serum potassium, low serum magnesium, reduced glomerular filtration rate (typically reversible when the dose is reduced)

Serious adverse reactions: seizures, low white blood count, low platelet count, liver injury, kidney fibrosis, diabetes

Tacrolimus (FK506, Prograf)

This medication has almost identical actions to those of cyclosporine. It has a somewhat different adverse event profile compared to cyclosporine: it is more likely to induce diabetes and less likely to cause hirsutism and gum hyperplasia.

Cyclophosphamide (Cytoxan)

This medication has long been used in cancer chemotherapy, at high doses. Much lower doses are used in glomerular disease, and consequently the medication is better tolerated. The effects on kidney disease are believed to be mediated by suppression of both T and B lymphocytes. Typical regimens include oral cylclophosphamide daily for 12 weeks and intravenous pulse cyclophosphamide monthly or quarterly.

Two adverse events deserve special comment, as they can be prevented by appropriate measures:

1. Cyclophosphamide is excreted by the kidney and can damage the bladder cells, causing bloody urine and pain. This can be avoided by drinking extra fluids for at least 4 hours after a dose and emptying the bladder at least hourly for four hours after a dose.
2. Cyclophosphamide can cause sterility in males and females. This does not occur before puberty. The highest risk for sterility is after the age of 30, when fertility is declining. Protective measures include hormone administration for men (testosterone) and women (leuprolide) to temporarily suppress gonadal function.

Common adverse reactions (kidney disease doses): bladder inflammation

Serious adverse reactions (kidney disease doses): sterility, hemorrhagic cystitis, low white blood cell counts, immunosuppression (propensity to viral infections in particular), malignancy (not reported with short course)

Mycophenolate Mofetil (Cellcept)

This agent reduces cell proliferation and acts on both T and B lymphocytes; its mechanism of benefit in glomerular disease is unknown.

Common adverse events: diarrhea, nausea, vomiting, abdominal pain, low white blood cells, headache, tremor, acne, insomnia

Serious adverse events: low white blood cells, low platelets, infection, malignancy, gastrointestinal bleeding

Sirolimus (Rapamycin, Rapamune)

This agent reduces cell proliferation and acts on both T and B lymphocytes; it is also an anti-fibrotic agent.

Common adverse events: high serum cholesterol, high serum triglycerides, diarrhea, constipation, nausea, abdominal pain, anemia, tremor, hypertension

Serious adverse events: infection, malignancy, low white blood cells, low platelets