Polyneuropathy is among the most common complications of chronic renal failure. Robson has estimated that neuropathy complicates end-stage renal failure in two-thirds of patients who are about to begin dialysis therapy. Bolton’s figures are much the same; 70 percent of his patients being dialyzed regularly had polyneuropathy and in 30 percent of all his patients, it was moderate or severe in degree. As described originally by Asbury and associates (1963), the neuropathy takes the form of a painless, progressive, symmetrical sensorimotor paralysis of the legs and then of the arms. In some patients, the syndrome begins with burning dysesthesias of the feet or with sensations of creeping, crawling, and itching of the legs and thighs, which tend to be worse at night and are relieved by movement (comparable to “restless legs” syndrome described in Chap. 18). Renal failure that is accompanied by diabetes gives rise to a particularly severe form of polyneuropathy.
The combination of muscle weakness and atrophy, areflexia, sensory loss, and the graduated, distally predominant distribution of the neurologic deficit in the limbs leaves little doubt about the neuropathic nature of the disorder. Usually the neuropathy evolves slowly over many months. Infrequent instances of a more acute sensorimotor polyneuropathy that have been reported occur mainly in diabetic patients receiving peritoneal dialysis as discussed earlier (Ropper, 1993; Asbury et al, 1963). A rare uremic polymyositis with hypophosphatemia has also been described (Layzer). The neuropathy has been observed with all types of chronic kidney diseases. More important to the development of chronic neuropathy than the nature of the renal lesion are the duration and severity of the renal failure and symptomatic uremia.
With long-term hemodialysis, the neuropathic symptoms and signs stabilize but improve in relatively few patients. In fact, rapid hemodialysis may worsen the polyneuropathy (or perhaps its symptoms) temporarily. Peritoneal dialysis appears to be more successful than hemodialysis in improving the neuropathy, but this observation has not been firmly established. Complete recovery, occurring over a period of 6 to 12 months, usually follows successful renal transplantation for reasons given later.
The pathologic findings are those of a nonspecific and noninflammatory axonal degeneration. In rapidly progressive cases, there is a tendency for the large fibers to be more affected; this is evident particularly on electrophysiologic testing that shows slowing of nerve conduction velocities, but there is no conduction block as occurs in other acquired demyelinating polyneuropathies. In all types of uremic polyneuropathies, pathologic changes are most intense in the distal segments of the nerves with the expected chromatolysis of their cell bodies.
The cause of uremic polyneuropathy is unknown. What has been called the “middle molecule” theory is plausible. The end stage of renal failure is associated with the accumulation of toxic substances in the range of 300 to 2,000 kDa molecular weight. Furthermore, the concentration of these substances, which include methyl guanidine and myoinositol, has been shown to correlate with the degree of neurotoxicity (Funck-Brentano et al). These toxins (and the clinical signs of neuropathy) are not greatly reduced by hemodialysis. In contrast, the transplanted kidney effectively eliminates substances of wide-ranging molecular weights, which would account for the almost invariable improvement of neuropathy after transplantation. As is the case with uremic encephalopathy, urea alone given to experimental animals and in controlled studies of humans, does not seem capable of inducing a metabolic neuropathy.