Uremic neuropathy: Clinical features and new pathophysiological insights

Abstract

Neuropathy is a common complication of end-stage kidney disease (ESKD), typically presenting as a distal symmetrical process with greater lower-limb than upper-limb involvement. The condition is of insidious onset, progressing over months. and has been estimated to be present in 60%-100% of patients on dialysis. Neuropathy generally only develops at glomerular filtration rates of less than 12 ml/min. The most frequent clinical features reflect large-fiber involvement, with paresthesias, reduction in deep tendon reflexes, impaired vibration sense, muscle wasting, and weakness. Nerve conduction studies demonstrate findings consistent with a generalized neuropathy of the axonal type. Patients may also develop autonomic features, with postural hypotension, impaired sweating, diarrhea, constipation, or impotence. The development of uremic neuropathy has been related previously to the retention of neurotoxic molecules in the middle molecular range, although this hypothesis lacked formal proof. Studies utilizing novel axonal excitability techniques have recently shed further light on the pathophysiology of this condition. Nerves of uremic patients have been shown to exist in a chronically depolarized state prior to dialysis, with subsequent improvement and normalization of resting membrane potential after dialysis. The degree of depolarization correlates with serum K(+), suggesting that chronic hyperkalemic depolarization plays an important role in the development of nerve dysfunction in ESKD. These recent findings suggest that maintenance of serum K(+) within normal limits between periods of dialysis, rather than simple avoidance of hyperkalemia, is likely to reduce the incidence and severity of uremic neuropathy.

Alterations of Hepatic Metabolism in Chronic Kidney Disease via D-box-binding Protein Aggravate the Renal Dysfunction

“…Chronic kidney disease (CKD) 3 affects the functions of various organs (1,2) and can cause cardiovascular dysfunction and heart and liver failure (3)(4)(5), thus reducing quality of life. Impaired renal function inhibits the production of various metabolites in the body and aggravates renal fibrosis in CKD.…”

Risk Assessment for Sudden Cardiac Death in Dialysis Patients

“…Dialysis patients with ESRD have several factors that could predispose them to a high risk of ventricular arrhythmias (Table 1). A large number of dialysis patients have diabetes, and thus, autonomic neuropathy as a consequence of both chronic uremia and coexisting diabetes is very common, 7 resulting in alterations in autonomic control with a sustained increase in the sympathetic tone reported to be proarrhythmic. Similarly, hypertension is very common, and uremia leads to secondary hyperparathyroidism, both of which lead to considerable left ventricular hypertrophy (LVH).…”

Recent Advances in the Prevention and Management of Intradialytic Hypotension

“…21 The precise mechanism by which uremia leads to autonomic dysfunction is not known, but chronic hyperkalemic depolarization of nerves may play a contributory role. 22 The most common approach to overcome impaired sympathetic activity has been to administer other vasoconstrictors to increase peripheral vascular resistance. A systematic review of the literature 23 revealed that 2.5 to 10 mg of the selective ␣-1 adrenergic agonist midodrine was proved to be an effective treatment in some patients with frequent intradialytic hypotension.…”