Commentary: Critical Limb Ischemia and Hemodialysis

What’s wrong in your limb, madam?

Nothing serious, I just have a small ulcer on my fifth toe. It’s because of a new pair of shoes I bought a couple of weeks ago.

This was part of the dialogue I had with a 75-year-old lady last month. The patient was diabetic with end-stage renal disease (ESRD) on hemodialysis for 2 years. Duplex scan showed multilevel lower limb arterial disease with a transcutaneous PO₂ of 12 mm Hg. The lesion on the fifth toe was infected, with deep soft tissue and bone involvement. With no revascularization, these clinical characteristics imply a 100% risk of major limb amputation and a 2-year mortality risk exceeding 40%. ¹

The multicenter study conducted by Shiraki et al ¹ in Japan highlights, once again, how a combination of hemodialysis and critical limb ischemia (CLI) represents a dramatic scenario with very poor life expectancy. When CLI ensues in patients >75 years of age with left ventricular ejection fraction <50%, 2-year mortality may exceed 60%, worse than most cancers. Nevertheless, patients and relatives are often not fully conscious of the risk of short-term major (cardiovascular) adverse events, and awareness of the disease is limited to foot lesions. On one hand, patients and their families, and (often) physicians on the other, do not show apparent apprehension, in striking contrast to a diagnosis of cancer. In the latter situation, patients ask for near-emergent scheduling of any potential diagnostic or therapeutic measures, including staging, chemo- or radiotherapy, and radical surgery, irrespective of side effects.

Conversely, and paradoxically, the underlying poor prognosis for CLI patients may lead to overtreatment or conservative treatment in patients on hemodialysis. Three key elements have to be considered to better understand the reasons for this attitude.

First, chronic renal failure and hemodialysis are associated with diffuse and severe arterial calcifications. The association with multiple risk factors for atherosclerosis, diabetes in particular, may create an extensive plaque burden leading to multilevel peripheral vascular disease from the iliac arteries to the foot vessels. Besides, 90% of lower limb arteries are totally occluded in diabetic patients with CLI and ESRD, ² whereas a high operative risk profile and the extent of calcification tend to dissuade surgeons from complex revascularization. Consequently, the majority of patients are treated with endovascular approaches, despite technically demanding procedures requiring specific skills and expertise, and a dedicated armamentarium of guidewires, microcatheters, low-profile balloons, and debulking systems, all of which are more likely to be present in high-volume centers.

In their Methods section, the authors indicate that consecutive patients who underwent lower limb revascularizations were enrolled in the study. However, no information is provided regarding the number of hemodialysis patients with CLI who were not candidates for any revascularization during the same time frame. In all, 246 patients at 10 institutions were included over a period of 3 years, which returns a mean of only 8.2 patients/year treated by each center. This is likely a result of patient selection and, possibly, a conservative attitude related in turn to low volume itself.

Second, the presence of comorbidities mandates a multidisciplinary approach pivoting on strict collaboration among nephrologists, interventional radiologists, interventional cardiologists, vascular surgeons, cardiac surgeons, diabetologists, anesthesiologists, and orthopedic surgeons. The advantages of a multidisciplinary team regarding improved foot healing and limb salvage rates in patients with CLI have been elucidated in several reports.^3,4 In hemodialysis patients, this is even more relevant in relation to the complexity of foot lesions, delay in foot healing, and comorbidities.^5,6 Most skills are usually available in most centers, but coordination among specialties and, equally important, correct timing of different interventions is often lacking. Metaphorically, top soloists are unlikely to merge in an orchestra, especially in the absence of a conductor.

Third, in view of a very high predicted mortality, efforts in treating CLI patients on hemodialysis may be considered therapeutic obstinacy. Shiraki and coworkers’ message is that 3 simple clinical characteristics may serve to identify a population in whom any form of revascularization may not be prognostically beneficial owing to their high risk of death in under 2 years, as also suggested by the American College of Cardiology/American Heart Association recommendations. ⁷ In other words, are we facing the paradox of denying revascularization to patients with the more severe and extensive atherosclerotic disease?

Hemodialysis is not the sole predictor of poor life expectancy in patients with CLI. More than a decade ago, O’Hare et al ⁸ reported a 50% 1-year mortality for patients with a glomerular filtration rate <30 mL/min/1.73 m² presenting with gangrene. The CRITISCH multicenter registry study, which recently compared different first-line CLI treatment strategies in Germany, ⁹ reported renal insufficiency without dialysis and myocardial infarction within the previous 6 months as the strongest adverse outcome predictors, with more than 6-fold probability of death at 1 year (odds ratio 6.3 and 7.4, respectively), but this cannot be intended as a death sentence and cannot ethically justify an intention-to-retreat. Rather, realizing that about half of hemodialysis patients survive >2 years after a diagnosis of CLI,^1,8,9 revascularization options cannot be denied to a rapidly growing population, nowadays estimated to exceed 2 million worldwide, but more prevalent in Western countries. ¹⁰ The gray zone between “pushing the limit” and overtreatment is the everlasting challenge in medical practice. Because most deaths in CLI patients with renal failure are cardiac related, ¹¹ future attention and research should focus not only on aggressive revascularization but also on cardiovascular screening to identify silent coronary artery or aortic valve disease.