Nephropathy - Long Term Complications of Diabetes

NEPHROPATHY

Nephropathy, or renal disease secondary to diabetic microvascu-lar changes in the kidney, is a common complication of diabetes. People with diabetes account for nearly half of new cases of end-stage renal disease (ESRD) each year and about a quarter of those requiring dialysis or transplantation each year in the United States. About 20% to 30% of people with type 1 or type 2 diabetes de-velop nephropathy, but fewer of those with type 2 diabetes progress to ESRD. Native American, Hispanic, and African-American persons with type 2 diabetes are at greater risk for ESRD than non-Hispanic whites (ADA, Diabetic Nephropathy, 2003).

Patients with type 1 diabetes frequently show initial signs of renal disease after 10 to 15 years, whereas patients with type 2 diabetes develop renal disease within 10 years of the diagnosis of diabetes. Many patients with type 2 diabetes have had diabetes for many years before it was diagnosed and treated. Therefore, they have evidence of nephropathy at the time of diagnosis.

There is no reliable method to predict whether a person will develop renal disease. The DCCT results showed that intensive treatment of diabetes with a goal of achieving a hemoglobin A_1C level as close to the nondiabetic range as possible reduced the oc-currence of early signs of nephropathy, such as microalbuminuria by 39%, and albuminuria by 54%. Similarly, the UKPDS study demonstrated a reduced incidence of overt nephropathy in type 2 diabetes with control of blood glucose levels (ADA, Diabetic Nephropathy, 2003).

Soon after the onset of diabetes, and especially if the blood glucose levels are elevated, the kidney’s filtration mechanism is stressed, allowing blood proteins to leak into the urine. As a re-sult, the pressure in the blood vessels of the kidney increases. It is thought that the elevated pressure serves as the stimulus for the development of nephropathy. Various medications and diets are being tested to prevent these complications.

Clinical Manifestations

Most of the signs and symptoms of renal dysfunction in the pa-tient with diabetes are similar to those seen in patients without diabetes. Also, as renal failure progresses, the catabolism (breakdown) of both exogenous and endogenous insulin de-creases, and frequent hypoglycemic episodes may result. Insulin needs change as a result of changes in the catabolism of insulin, and also as a result of changes in diet related to the treatment of nephropathy. The stress of renal disease affects self-esteem, fam-ily relationships, marital relations, and virtually all aspects of daily life. As renal function decreases, the patient commonly has multiple-system failure (eg, declining visual acuity, impotence, foot ulcerations, heart failure, and nocturnal diarrhea).

Assessment and Diagnostic Findings

One of the most important blood proteins that leaks into the urine is albumin. Small amounts may leak undetected for years. Of patients with microalbuminuria, clinical nephropathy even-tually develops in more than 85%. However, if microalbumin-uria is not present, nephropathy develops in fewer than 5%. Early microalbuminuria may also be discovered in a 24-hour urine sample. The urine should be checked annually for microalbu-minuria. If the microalbuminuria level exceeds 30 mg/24 hours on two consecutive tests, treatment is indicated.

When a urine dipstick test reads consistently positive for sig-nificant amounts of albumin, serum creatinine and BUN levels are obtained. At this point in the development of renal disease, diagnostic testing for cardiac or other systemic problems may also be required. Some of the tests involve injection of special dyes that are not easily cleared by the damaged kidney, so the value of the diagnostic test must be weighed against the potential risks.

Hypertension often develops in patients (both diabetic and nondiabetic) who are in the early stages of renal disease. How-ever, essential hypertension occurs in up to 50% of all individu-als with diabetes (for unknown reasons). Thus, it should not be assumed that someone with diabetes who has hypertension also has renal disease; other diagnostic criteria must also be present.

Medical Management

In addition to achieving and maintaining near-normal blood glu-cose levels, management for all patients with diabetes should in-clude careful attention to the following:

·      Control of hypertension (the use of angiotensin-converting enzyme [ACE] inhibitors, such as captopril, because control of hypertension may also decrease or delay the onset of early proteinuria)

·       Prevention or vigorous treatment of urinary tract infections

·       Avoidance of nephrotoxic substances

·       Adjustment of medications as renal function changes

·       Low-sodium diet

·       Low-protein diet

If the patient has already developed microalbuminuria and its level exceeds 30 mg/24 hours on two consecutive tests, an ACEinhibitor should be prescribed. ACE inhibitors lower blood pres-sure and reduce microalbuminuria and therefore protect the kid-ney. Alternatively, angiotensin-receptor blocking (ARB) agents may be prescribed. This preventive strategy should be part of the standard of care for the person with diabetes. Carefully designed low-protein diets also appear to reverse early leakage of small amounts of protein from the kidney (ADA, Clinical Practice Recommendations, 2003; ADA, Diabetic Nephropathy, 2003).

In chronic or end-stage renal failure, two types of treatment are available: dialysis (hemodialysis or peritoneal dialysis) and transplantation from a relative or a cadaver. Hemodialysis for the patient with diabetes is similar to that for patients without the disease. Because hemodialysis creates additional stress on patients with cardiovascular disease, it may not be ap-propriate for certain patients. In addition, it is extremely intru-sive into a patient’s life.

Continuous ambulatory peritoneal dialysis is being used by an increasing number of patients with diabetes, mainly because of the independence it allows patients. In addition, insulin can be mixed into the dialysate, which may result in better blood glucose control and end the need for insulin injections. However, these patients may require more insulin because the dialysate contains glucose. Major risks of peritoneal dialysis are infection and peri-tonitis. The mortality rate for diabetic patients undergoing dial-ysis is higher than that in patients without diabetes undergoing dialysis and is closely related to the severity of cardiovascular problems.

Renal disease is frequently accompanied by advancing reti-nopathy that may require laser treatments and surgery. Severe hypertension also worsens eye disease because of the additional stress it places on the blood vessels. Patients being treated with hemodialysis who require eye surgery may be changed to peri-toneal dialysis and have their hypertension aggressively controlled for several weeks before surgery. The rationale for this change is that hemodialysis requires anticoagulants that can increase the risk of bleeding after the surgery, and peritoneal dialysis mini-mizes pressure changes in the eyes.

The success rate for kidney transplantation in patients with diabetes has improved. In medical centers performing large num-bers of transplants, the chances are 75% to 80% that the trans-planted kidney will continue to function in the patient with diabetes for at least 5 years. Like the original kidneys, transplanted kidneys in patients with diabetes can eventually be damaged if blood glucose levels are consistently high after the transplanta-tion. Therefore, monitoring blood glucose levels frequently and adjusting insulin levels in diabetic patients with transplanted kidneys are essential for long-term success. Pancreas transplants are sometimes attempted when a kidney transplant is performed. Pancreatic transplants have not been successful enough to be performed alone because of the risks associated with immuno-suppression.