Overview of Glomerular Disease
The glomerulus is the filtering unit of the kidney. It is made up of a tuft of capillaries, whose walls can selectively filter wastes and electrolytes from the blood. Around each glomerulus is a containment sac (Bowman’s membrane) that has an exit into the renal tubule. Thus, the blood is filtered, the filtrate collecting as urine that flows out, ultimately, via urination.
Glomerular disease, a broad term for pathologic abnormalities in the glomeruli, can be inherited genetically or acquired. It can be diffuse, involving most of the glomeruli, or focal, involving <50% of them.
Causes of Glomerular Disease
- Hypovolemia and dehydration: Due to overuse of diuretics, decreased oral intake of fluids, or diarrhea.
- Hypotension: Due to heart failure, causing decreased kidney perfusion.
- Liver disease (portal hypertension).
- Intrinsic renal vascular disease: Including atherosclerosis and the effects of diabetes, affecting both large and small kidney blood vessels.
- Intrinsic glomerular disease: Affecting the glomeruli primarily, or secondarily from drug toxicity or systemic rheumatoid/autoimmune disease.
- Nephritis–red blood cell (RBC): Casts and albuminuria; can be both chronic and acute.
- Nephrosis–proteinuria: Can be both chronic and acute. Excretion of protein in the urine decreases the protein in the blood and can lead to edema or fluid collecting in the abdomen (ascites) or lung spaces (pleural effusion).
- Intrinsic tubular disease: The tubule, which with the glomerulus, makes up the nephron unit, can undergo acute tubular necrosis (ATN), usually due to drug toxicity, cardiac surgery, or severe sepsis; ATN causes significant kidney injury.
- Obstructive nephropathy: Obstruction anywhere in the urinary tract can cause stasis of urine above the obstruction, decreasing glomerular filtration. Stones, prostate surgery, metastatic cancer, or unrecognized surgical damage (suturing the ureter) can cause it.
Signs and Symptoms of Glomerular Disease
- Hematuria: blood in the urine
- Proteinuria: urinary excretion of protein
- Renal insufficiency
- Hypertension: acutely in a person with previously normal blood pressure
- Edema (swelling): bloating, or shortness of breath
- Hypercoagulation: resulting in thrombus formation with risk of thromboembolic events (pulmonary emboli)
- Fever, chills, night sweats
- Heart murmurs: chest pain from pericarditis
- Colitis, pancreatitis
- Peripheral neuropathy
- Arthritis, myalgia
- Infections (Staph, Strep, hepatitis, HIV, syphilis)
How is Glomerular Disease Diagnosed?
Glomerular disease results in one or both of two major presentations:
- Hematuria (blood in the urine)
- Proteinuria/albuminuria (excretion of protein in the urine)
Hematuria is easily identified by dipstick or quantitated by microscopic examination of a urine sample. The finding of red blood cell casts (compressed red blood cell masses that pass out of the tubule intact) indicates glomerulonephritis, an intrinsic glomerular disease. Except for that, the urinalysis is not helpful in identifying specifically the cause of blood in the urine. Hematuria can result from anything, from a stone to cancer.
Protein spillage is identified on a simple dipstick, but that is just the beginning of the diagnostic journey. Protein excreted into the urine can occur from other causes other than glomerular disease, and diagnostic tests are important to differentiate it from the other causes.
- Transient proteinuria: After exercise or exertion. It is temporary, normal, and benign.
- Orthostatic proteinuria: Common in adolescents, this is an unknown mechanism of altered glomerular function affected by standing (upright morning urine collection demonstrating proteinuria) vs. not standing (supine position, as with nighttime urine collection, demonstrating no proteinuria). It is easily identified or ruled out by repeated qualitative testing in both positions.
- Tubular proteinuria: Smaller proteins that are filtered by the glomerulus are normally reabsorbed through the tubules back into the blood. When this process is abnormal, reabsorption does not occur and the protein can end up in the urine.
- Overflow proteinuria: Overproduction of proteins, as in multiple myeloma (white blood cell “plasma cell” cancer) and other leukemias.
- Post-renal proteinuria: Due to inflammation in the urinary tract.
Testing in Glomerular Disease
Qualitative testing: this is useful if a positive dipstick for protein repeats as negative, which would indicate a benign transient proteinuria.
Quantitation: the amount of protein excreted in the urine is helpful in identifying the cause, because when < 1-2 g/day, is usually an isolated and benign phenomenon.
- The standard for quantitation is the 24-hour urine collection: Normal results are <150 mg/day. Because of its accuracy, it is done first, followed by urine protein-to-creatinine ratio spot checks for follow-up.
- Urine protein-to-creatinine ratio: Done by deriving a ratio from the dipstick values on a first or second morning-urine sample. A spot sample of protein concentration (mg/dL) is divided by the urine creatinine concentration (mg/dL). It allows an estimate of what the 24-hour urine total protein should be (in grams): normal is < 200; >3500 would be consistent with nephrotic syndrome.
Kidney biopsy is indicated on anyone with more than 3.5 g/day of proteinuria or when there is less proteinuria which is associated with hematuria or cellular casts in a microscopic urinalysis.
Testing Used in Hematuria Unrelated to Glomerular Disease
Since hematuria is simply the presence of red blood cells in the urine, testing should investigate other possible causes:
- X-ray to identify or rule out a stone
- CT or MRI to identify or rule out malignancy
- Urine culture and sensitivity to identify or rule out a urinary tract infection
- Renal ultrasound to identify renal structural (anatomical) problems
- Genetic testing to screen for polycystic kidney disease
How Can I Manage Glomerular Disease?
After ruling out non-glomerular causes of hematuria and/or proteinuria, treatment of glomerular disease is based on controlling its causes or its consequences.
Treatment of the Causes of Glomerular Disease
- Treat hypertension with antihypertensive agents
- Strict glycemic control in diabetics
- Address dyslipidemia aggressively by controlling abnormal cholesterol and triglyceride levels with statin drugs
- Investigate exposure to all medications that might have renal damage as a side effect. Avoid all drugs that are contraindicated in those at risk for kidney disease
- Address metabolic syndrome with weight management, nutritional counseling, and smoking cessation
- Remain vigilant for atherosclerotic and thrombotic complications that could impact kidney perfusion
- Treat autoimmune disease (rheumatoid disorders, lupus, collagen disease) with immunosuppressive agents to suppress the immune system
- Treat infections such as urinary tract infections and strep throat with appropriate antibiotics and in a timely manner
- Eliminate obstructions from stones as quickly as possible
Treatment of the Consequences of Glomerular Disease
- Control of blood pressure with antihypertensive medication
- Diminish protein loss with ACE inhibitors and ARBs
- Diuretics to diminish swelling
- Dietary restrictions on sodium, potassium, and excess protein
- Dialysis or kidney transplant for end-stage renal disease (ESRD)
- Supplementation or dietary/intravenous interventions based on the results of serial, routine blood chemistry tests
Prevention of Glomerular Disease
In some cases, the cause of glomerular disease remains a mystery. It can also be genetic. Either way, these cannot be prevented, so mitigating the disease process itself is the best way to delay the progression that could put one at risk for kidney failure.
As far as the identifiable causes, prevention of these is important, as is prevention of their progression. (This strategy also favorably impacts the glomerular disease from unknown causes).
Prolonged hyperglycemia is toxic to all vasculature, including that of the kidney. Diabetic vasculitis of the glomerular tuft of capillaries can best be prevented by strict glycemic control and maintaining a target hemoglobin A1c level of <7-8%. Diabetic stability also prevents atherosclerotic disease of the large vessels perfusing the kidneys–the renal arteries, and is protective of systemic (body-wide) obstructions to blood flow. Hyperglycemia also makes infections of the urinary tract more likely and more virulent, so good glycemic control helps prevent the scarring of kidney tissue that can occur from infection.
Cardiovascular Disease (CVD)
CVD risks the health of all blood vessels and all of the tissues they reach. With the progression of CVD (atherosclerosis, dyslipidemia, hypertension), the kidney can suffer vascular compromise as can any other organ. Decreased renal perfusion from partial atherosclerotic obstruction will decrease kidney function, and that dysfunction can progress further to injure the kidney permanently. Preventing CVD severity is a valid prevention of kidney disease and an excellent strategy to stop a vicious cycle:
CVD → kidney disease → worsening of hypertension → worsening of kidney disease → worsening of CVD → etc.
Within this vicious cycle are the toxic contributions from diabetes, worsening both CVD and kidney disease simultaneously.
Stone obstructions decrease perfusion of glomeruli to cause glomerular disease. Prompt elimination of the stone via passage, removal, or fragmentation for passage can prevent glomerular damage.
Any infection can become blood-borne, causing the signs and symptoms of sepsis. In the bloodstream, bacteria can reach distant organs, including the kidneys (pyelonephritis); alternately, a rising (vertical) infection from the bladder can reach the kidneys. Promptly treating infections with appropriate antibiotic therapy can prevent glomerular and other kidney damage.
Some medications that are toxic to the kidney and/or liver are unavoidable, such as in life-threatening sepsis when the benefit outweighs the risk or in infections that are resistant to the safer antibiotics. Many infections, however, allow a choice of numerous medications. Equally efficacious drugs that have no anti-renal toxicity can be chosen to avoid risk to the kidneys.