US Pharm. 2016;41(8):HS-12-HS-16.

Healthy kidneys regulate the body’s fluid levels, filter waste and toxins from the blood, release a protein and enzyme that regulates blood pressure (renin), activate vitamin D to maintain healthy bones, release the hormone that directs production of red blood cells (erythropoetin), and keep blood minerals in balance (sodium, phosphorus, potassium). Every 30 minutes, the kidneys filter all the blood in the body, removing waste and excess fluid. Although it is important to have two functional kidneys, it is possible to live with only one. Major risk factors for kidney disease include diabetes, high blood pressure, family history of kidney failure, and age >65 years. Additional risk factors include kidney stones, smoking, obesity, and cardiovascular disease.¹

Since early kidney disease often has no symptoms, it can go undetected until it is very advanced. In its advanced stages, some signs of kidney disease include fatigue; weakness; difficult and painful urination; foamy urine; pink and dark urine (blood in urine); increased need to urinate (especially at night); puffy eyes; swollen face, hands, ankles, and feet; and increased thirst. Early detection and treatment can slow or prevent the progression of kidney disease. In the United States, high blood pressure and diabetes are the two leading causes of kidney disease. In the final stages of kidney disease, also called end-stage renal disease (ESRD), the ultimate treatment is either dialysis or kidney transplantation. The focus of this article is on different forms of dialysis and its vital role in bringing life to patients with renal disease.¹

KIDNEY DISEASE STATISTICS

Acute kidney injury (AKI) is the sudden, temporary, and sometimes fatal loss of kidney function. AKI may lead to a number of complications, including metabolic acidosis, high potassium levels, uremia, changes in body fluid balance, and effects on other organ systems.²

Chronic kidney disease (CKD) is a condition that causes reduced kidney function over a period of time. CKD is present when a patient’s glomerular filtration rate remains <60 mL-min for more than 3 months or when a patient’s urine albumin-to-creatinine ratio is >30 mg of albumin for each gram of creatinine (30 mg/g). The incidence of CKD is increasing most rapidly in people aged >65 years. The incidence of recognized CKD in members of this age group more than doubled between 2000 and 2010. The incidence of recognized CKD among 20- to 64-year-olds is less than 1%.²

ESRD is total and permanent kidney failure. When the kidneys fail, the body retains fluid and harmful wastes. ESRD incidence rates are more than three times higher for African Americans than for Caucasians. After rising from 1980 to 2010, the incidence rates for all races has been stabilized. African American rates rose more quickly than rates for all other races. Since 2001, incidence rates for American Indians have been declining.²

Kidney disease statistics are very important, and in the U.S. these are based on the burden of CKD and ESRD. Having the information, researchers can estimate the future size of the ESRD population and the resulting need for resources such as dialysis and transplant clinics to treat the growing ESRD population.²

Over time, kidney disease statistics show which ethnic and age groups and geographic regions have the highest incidence of kidney disease. This demographic information helps direct targeted programs to the people who need them most. The trend is to measure progress in preventing and treating kidney disease. With the knowledge provided by statistics, researchers and healthcare providers can make great progress in the fight against kidney disease.²

Currently, one in three American adults is at risk for developing kidney disease. Kidney disease is the ninth leading cause of death in the U.S. Every year, kidney disease kills more people than breast or prostate cancer. In 2013, more than 47,000 Americans died from kidney disease. Men with kidney disease are more likely than women to progress to kidney failure. Black Americans are three times more likely to experience kidney failure. Hispanics are one and one-half times more likely to experience kidney failure. Once the kidneys fail, dialysis or a kidney transplant is required.

Currently, more than 659,000 Americans have kidney failure. Of these, 468,000 individuals are on dialysis, and approximately 191,000 live with a functional transplanted kidney. Of more than 120,000 people waiting for lifesaving organ transplants in the U.S., almost 100,000 await kidney transplants this year. Fewer than 17,000 people receive one each year. Persons at risk should have simple blood and urine tests to check if their kidneys are working properly.²

KIDNEY DIALYSIS

The process of removing waste products and excess fluid from the body, when the kidneys are not able to adequately filter the blood, is called dialysis. Dialysis affords patients with kidney failure a chance to live productive lives. The basis of the technique is the diffusion of solute molecules through a semipermeable membrane, normally passing from the side of higher concentration to that of a lower concentration. A semipermeable membrane is one that allows the passage of certain smaller crystalloid molecules, such as glucose and urea, but prevents the passage of larger molecules, such as colloidal plasma proteins and protoplasm.³

Hemodialysis

The process of removing blood from an artery in a kidney patient, purifying it by a dialysis machine, adding vital substances, and returning it to a vein is called hemodialysis. Hemodialysis is a treatment for kidney failure and removes waste and extra fluid from the blood, using a filter. The filter, called a dialyzer, is a plastic tube filled with millions of hollow fibers. The dialyzer, which functions as an artificial kidney to clean the blood, is a canister connected to the hemodialysis machine.

Hemodialysis removes wastes, extra salts, and water by circulating blood outside the body through an external filter that contains a semipermeable membrane. The blood flows in one direction and the dialysate flows in the opposite. The countercurrent flow of the blood and dialysate maximizes the concentration gradient of solutes between the blood and the dialysate, which helps to remove more urea and creatinine from the blood.³

The hemodialysis machine monitors blood flow and removes waste from the dialyzer. Several months before the first hemodialysis treatment, an access to the bloodstream must be created. Patients may need to stay overnight in the hospital, but many patients have their access created on an outpatient basis. This access provides an efficient way for blood to be carried from the body to the dialyzer and back without causing discomfort.⁴

Vascular Access: A vascular access is very important and makes life-long hemodialysis treatments possible. The access is a surgically enhanced vein used to remove and return blood during hemodialysis. The blood goes through a needle and then travels through a tube that takes it to the dialyzer. A vascular access lets large amounts of blood flow continuously during hemodialysis treatments to filter as much blood as possible per treatment. About a pint of blood flows through the machine every minute. A vascular access should be in place weeks or months before the first hemodialysis treatment.⁵

There are two main types of vascular access for long-term dialysis—arteriovenous (AV) fistula and AV graft. A third type of vascular access is vascular catheter for short-term use.

Arteriovenous Fistula: An AV fistula is the connection, made by a vascular surgeon, of an artery to a vein in the forearm or upper arm. An AV fistula causes extra pressure and allows extra blood to flow into the vein, making it grow large and strong. The larger vein provides easy, reliable access to blood vessels. Untreated veins cannot withstand repeated needle insertions. An AV fistula is recommended over the other access types because of its good blood flow, longer term access, and lower likelihood of becoming infected or causing blood clots.⁵

The vascular access procedure may require an overnight stay in the hospital; however, many patients go home afterward. An AV fistula frequently requires 2 to 3 months to develop, or mature, before the patient can use it for hemodialysis. If an AV fistula does not mature, an AV graft is the second choice for long-lasting vascular access.⁵

Arteriovenous Graft: An AV graft is a looped plastic tube that connects an artery to a vein. A vascular surgeon performs AV graft surgery, much like AV fistula surgery, in an outpatient center or a hospital. A patient can usually use an AV graft 2 to 3 weeks after the surgery. An AV graft is more likely than an AV fistula to have problems with infection and clotting. Repeated blood clots can block the flow of blood through the graft; however, a well-cared-for graft can last several years. AV fistulas and AV grafts both need time to mature before they are ready for use. Giving a vascular access time to mature can help prevent problems with narrow veins, low blood flow, and blood clots.⁵

Venous Catheter: A venous catheter is a tube inserted into a vein in the neck, chest, or leg near the groin, usually only for short-term hemodialysis. The tube splits in two after it exits the body. The two tubes have caps designed to connect to the line that carries blood to the dialyzer and the line that carries blood from the dialyzer back to the body. A person must close the clamps on each line when connecting and disconnecting the catheter from the tubes. If kidney disease has progressed quickly, a patient may not have time for placement of an AV fistula or AV graft before starting hemodialysis treatments.⁵

Venous catheters are not ideal for long-term use. With a venous catheter, a patient may develop a blood clot, an infection, or a scarred vein, causing the vein to narrow; however, if a patient needs to start hemodialysis immediately, a venous catheter will work for several weeks.

All three types of vascular access—AV fistula, AV graft, and venous catheter—can cause problems that require further treatment or surgery. The most common problems include access infection and low blood flow due to blood clotting in the access. Infection and low blood flow happen less frequently in properly formed AV fistulas than in AV grafts and venous catheters.⁵

Peritoneal Dialysis 

This technique is also a kidney dialysis procedure that removes waste, chemicals, and extra water; however, it is performed within the body. This type of dialysis uses the lining of the abdomen, or belly, to filter the patient’s blood. This lining is called the peritoneal membrane and acts as the artificial kidney. A mixture of minerals and sugar dissolved in water (dialysis solution) travels through a dialysis catheter into the belly. The sugar (dextrose) draws waste, chemicals, and extra water from the tiny blood vessels in the peritoneal membrane into the dialysis solution. After several hours, the used solution is drained from the abdomen through the tube, taking the waste from the blood with it. Then the abdomen is refilled with fresh dialysis solution, and this cycle is repeated. This process of draining and refilling is called an exchange.⁶

Continuous Ambulatory Peritoneal Dialysis (CAPD): This technique is a continuous process, requires no machine for treatment, and can be done in any clean, well-lit place. The patient is not attached to a machine, and the exchange happens manually with gravity. The dialysis takes place continuously 24 hours a day, 7 days a week, with dwell time (the time period that the dialysis solution is in the abdomen) lasting 4 to 6 hours. There are about 4 exchanges every day, and each exchange takes about 30 minutes. With CAPD, patients can move around freely and blood is always being cleaned. The dialysis solution passes from a plastic bag through the catheter and into the abdomen, where it stays for several hours with the catheter sealed. Afterward, the dialysis solution containing wastes and toxins is drained into an empty bag for disposal. The patient then refills his or her abdomen with fresh dialysis solution so the cleaning process can begin again.⁶

In many cases, the process of draining the used dialysis solution and replacing it with fresh solution takes about 30 to 40 minutes. Most people change the dialysis solution at least four times a day and sleep with solution in their abdomen at night. With this procedure, it is not necessary to wake up and perform dialysis tasks during the night.⁶

Continuous Cycling Peritoneal Dialysis (CCPD): In this procedure, patients are attached to a machine, called the cycler. The machine accomplishes the exchanges automatically based on preprogrammed settings, and patients are attached to the machine during the night when they are sleeping; automatic exchanges occur over 8 to 10 hours. In the morning, patients begin one exchange with a dwell time that lasts the entire day.⁶

A typical CCPD schedule involves three to five exchanges during the night while the person sleeps. CCPD offers several advantages over CAPD. More daytime freedom with less connect-disconnect per 24 hours and a lower potential for peritonitis. The cycler is an aid to patients who require a helper to complete their exchanges.

Combination of CAPD and CCPD: If a patient weighs 175 lb or if the peritoneum filters wastes slowly, patients may need a combination of CAPD and CCPD to get the right dialysis dose. For example, some people use a cycler at night but also perform one exchange during the day. Others do four exchanges during the day and use a minicycler to perform one or more exchanges during the night. Patients must work with their healthcare team to determine the best schedule for them.⁶

DIALYSIS CONSIDERATION

The biggest impact on lifestyle is whether or not a person has dialysis in a center or does it at home. Treatments in a center need to be scheduled, and the patient must arrive at the appointed time. Dialysis at home provides more flexibility and convenience. Diet is another factor to consider when choosing a treatment modality. For people on dialysis, diet is part of their treatment. Foods containing the minerals phosphorus, potassium, and sodium are usually limited. Because peritoneal dialysis is performed daily, there are fewer dietary and fluid restrictions. Travel is another consideration. While people who choose in-center dialysis are free to travel, they will have to plan ahead and make arrangements to receive dialysis at a center located where they are visiting. For people on peritoneal dialysis, the new cycler machines are smaller and portable, and patients can generally travel with greater ease.

POSSIBLE COMPLICATIONS

The most common problem with peritoneal dialysis is peritonitis, a serious abdominal infection. This infection can occur if the opening where the catheter enters the body becomes infected or if contamination occurs as the catheter is connected or disconnected from the bags. Infection is less common in catheters, which are placed in the chest. Peritonitis requires a course of antibiotic treatment.⁷

To avoid peritonitis, patients must be careful to follow procedures exactly and learn to recognize the early signs of peritonitis, which include fever, unusual color or cloudiness of the used fluid, and redness or pain around the catheter. Patients should report these signs to their doctor or dialysis nurse immediately so that peritonitis can be treated quickly to avoid additional problems.⁷

DIALYSIS OF DRUGS

Drug removal during dialysis could be important for those caring for patients receiving hemodialysis or peritoneal dialysis. The extent of drug dialyzability determines whether supplemental dosing is necessary during or following dialysis. The extent to which a drug is affected by dialysis is determined primarily by several physicochemical characteristics of the drug such as molecular size, protein binding, volume of distribution, water solubility, and plasma clearance. In addition to these, technical aspects of the dialysis procedure also may determine the extent to which a drug is removed by dialysis.

Dialysis is dependent upon the use of a dialytic membrane: either a synthetic membrane in hemodialysis or a naturally occurring one as in peritoneal dialysis. As a general rule, smaller molecular-weight substances will pass through the membrane more easily than larger molecular-weight substances. Another important factor determining drug dialyzability is the concentration gradient of free (unbound) drug across the dialysis membrane. Drugs with a high degree of protein binding will have a low plasma concentration of unbound drugs available for dialysis.⁸ The dialysate used for either hemodialysis or peritoneal dialysis is an aqueous solution. In general, drugs with high water solubility will be dialyzed to a greater extent than those with high lipid solubility. Highly lipid-soluble drugs tend to be distributed throughout tissues, and therefore only a small fraction of the drug is available in plasma and accessible for dialysis.⁸

CONCLUSION

Healthy kidneys regulate the body’s fluid levels and filter waste and toxins from the blood. Every 30 minutes, the kidneys filter all the blood in the body, removing waste and excess fluid. Since kidney disease often has no symptoms, it can go undetected until it is very advanced. Early detection and treatment can slow or prevent the progression of kidney disease. In the U.S., high blood pressure and diabetes are the two leading causes of kidney disease. The ultimate treatment in ESRD is either dialysis or a kidney transplant.

Currently one in three American adults is at risk for developing kidney disease and, ultimately, going under dialysis. Dialysis works on the principles of the diffusion of solutes and ultrafiltration of fluid across a semipermeable membrane. The two main types of dialysis, hemodialysis and peritoneal dialysis, remove wastes and excess water from the blood in different ways and help patients to have a quality life.

Both types of peritoneal dialysis are usually performed by the patient without help from a partner. CAPD is a form of self-treatment that needs no machine. However, with CCPD, patients need a machine to drain and refill their abdomen.

REFERENCES

1. National Kidney Foundation. Kidney disease outcomes quality initiative guidelines. 2006 National Kidney Foundation. www.kidney.org/atoz/content/dialysisinfo.cfm. Accessed May 24, 2016.
2. National Institute of Diabetes and Digestive and Kidney diseases. Kidney disease statistics for the United States. www.niddk.nih.gov/health-information/health-statistics/Pages/kidney-disease-statistics-united-states.aspx#6. Accessed May 24, 2016.
3. Pendse S, Singh A, Zawada E. Initiation of dialysis. In: Handbook of Dialysis. 4th ed. New York, NY: Lippincott, Williams and Wilkins; 2008:14-21.
4. Rosansky S, Glassock R, Clark W. Early start of dialysis: a critical review. Clin J Am Soc Nephrol. 2011;6: 1222-1228.
5. National Institute of Diabetes and Digestive and Kidney Diseases. Vascular access for hemodialysis. www.niddk.nih.gov/health-information/health-topics/kidney-disease/vascular-access-for-hemodialysis/Pages/index.aspx. Accessed May 24, 2016.
6. Ahmad S, Misra M, Hoenich N, Daugirdas J. Hemodialysis Apparatus. In: Handbook of Dialysis. 4th ed. New York, NY: Lippincott, Williams and Wilkins; 2008:59-78.
7. National Institute of Diabetes and Digestive and Kidney Diseases. NIH Pub. No. 07-4578. December 2006. http://kidney.niddk.nih.gov/Kudiseases/pubs/peritonealdose/. Accessed April 28, 2016.
8. Olyaei AJ, DeMattos A, Bennett WM. Principles of drug usage in dialysis patients. In: Nissenson AR, Fine RN, eds. Dialysis Therapy. Philadelphia, PA: Hanley & Belfus; 2002.