by Phyllis Hanlon, Contributing Writer

According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) approximately 14 percent of the general population has chronic kidney disease (CKD); more than 661,000 Americans have kidney failure and 468,000 of these are on dialysis. Furthermore, CKD often occurs along with other medical conditions, earning the name “disease multiplier.”

In addition to the large number of people in the U.S. with kidney disease, doctors have become increasingly interested in how pulmonary hypertension (PH) can negatively impact the kidney, in some cases leading to kidney disease in PH patients. Some of these impacts on the kidney can include increased pressure in the veins, decreases in how much blood the heart pumps, and activation of hormones that increases blood pressure by causing the blood vessels to get tighter. Studies in PAH have shown that impaired kidney function is a predictor of mortality.

Given the unknowns and potential seriousness of these diseases together, a team of researchers conducted a first-of-its-kind meta-analysis (a review of several studies) on this subject to better understand how PH affects patients with CKD as well as end-stage renal disease (ESRD).

Mengyao Tang, M.D., from the Department of Epidemiology at the Harvard T.H. Chan School of Public Health, led the research study, the results of which were published in the July issue of American Journal of Kidney Diseases.

The authors examined 16 studies that included 7,112 people with CKD or ESRD. In these studies, about 1,600 of these people also had PH. They found that having PH placed a person with CKD or ESRD at higher risk of death from heart issues and events related to the heart, such as stroke, acute heart failure, heart attack or peripheral vascular disease (narrowing of the arteries that restricts blood flow to your arms and legs) compared to CKD or ESRD patients without PH.

Dr. Tang and her associates indicated that this risk was greater in ESRD patients receiving dialysis compared to people with CKD at any stage from 1 to 5. They noted that this increased risk of ESRD patients did not depend on whether the patient was receiving hemodialysis or peritoneal dialysis (a treatment that uses the lining of the abdomen and a cleaning solution to cleanse the blood).

Although the authors showed a potential increased risk of death for CKD/ESRD patients who also have PH, they could not clearly determine the underlying reasons for the risk. They surmised that PH could be the result of left-sided heart failure, which can then lead to right-side heart failure, setting up a vicious cycle. The risk also might be associated with fluid overload caused by PH, the authors added. To pinpoint a cause, the authors suggested conducting studies using right-heart catheterization.

The authors specifically discussed the increased risk of ESRD patients receiving dialysis compared to CKD patients. On one hand, the authors noted that this could be explained by a greater severity of PH in patients who require dialysis. The authors also discussed another theory, that creating an arteriovenous fistula (an abnormal connection between an artery and a vein) for hemodialysis could place the patient at risk for PH; however, this remains controversial and is not likely to be the primary answer. Alternatively, a buildup of toxic substances in body fluids as part of the development of CKD or hypersensitivity also might place one at higher risk for the development of PH.

Additionally, the authors pointed out that more research is needed to learn how best to treat PH related to CKD/ESRD. The role and effectiveness of PH-targeted therapies—in addition to supportive therapies such as diuretics, anticoagulants, oxygen therapy, and digoxin—in improving survival in CKD/ESRD patients needs to be studied through clinical trials.

If clinicians can figure out which patients are at higher risk for developing PH, they can develop better management strategies, according to the authors. For example, if a patient displays signs of PH – shortness of breath, fatigue, chest pain, swelling from fluid in the arms or legs – then screening for PH would be appropriate. The authors explained that noninvasive Doppler echocardiography can detect if PH may be present; then patients could follow up with a specialist at a PH center where pulmonary function testing (PFT) and right-sided heart catheterization offer a definitive diagnosis. The authors asserted that this approach could lead to therapy created for the individual patient since there are different classes of PH.