Sleep disorders occur very early in chronic kidney disease.

BACKGROUND: Recent data suggest that sleep disorders may be common in patients with end-stage renal disease (ESRD) and patients with pre-dialytic chronic kidney disease (CKD). The prevalence of sleep disorders in CKD, its association to kidney function and related factors is still unclear. This study aimed to measure the prevalence of sleep disorders in patients with recent diagnosis of CKD and to assess the relation with indices of kidney function, PTH, anemia, blood pressure status, antihypertensive drug(s) and other comorbidities. METHODS: A standardized questionnaire, Sleep Disorders Questionnaire (SDQ) was administered to 124 patients within 4 weeks of first diagnosis of CKD. Blood samples were analyzed to assess kidney function and related variables. Charlson Comorbidity Index was used to index the number of associated diseases. RESULTS: Of these patients 89.5% reported some sleep disorders (subclinical or insomnia). Prevalence of sleep disorders was not associated with age, creatinine plasma concentration, urea, predicted creatinine clearance, uric acid, PTH, blood pressure status, use of antihypertensive drugs, anemia, and comorbidities. Poor sleep is highly prevalent in early CKD patients. Prevalence of sleep disorders in CKD was not associated with factors considered responsible for sleep disorders in maintenance hemodialysis. CONCLUSIONS: The data are in good keeping with findings in narrative studies in ESRD pointing out that the time of diagnosis is a crucial and disrupting moment in the life of patients since they are made aware of significant future personal changes due to a chronic illness.

Parathyroidectomy improves the quality of sleep in maintenance hemodialysis patients with severe hyperparathyroidism.

Sleeping disorders are very common in patients with chronic kidney disease on dialysis (CKD5D) and are an emerging risk factor able to predict mortality. Parathyroid hormone (PTH) although considered a pivotal uremic toxin has rarely been associated with sleep disorders in uremia. In a study from our laboratory PTH concentrations failed to distinguish patients with sleep disorders from those without. In a study performed by Chou et al a 97% prevalence of insomnia was found in patients undergoing hemodialysis requiring parathyroidectomy. Surgery reduced PTH and increased sleeping hours within 3 months. The aim of this study was to study the effects of parathyroidectomy on the sleep disorders of insomniacs on maintenance hemodialysis. The study was performed in 16 insomniac patients on maintenance hemodialysis who successfully underwent surgery with autotransplantation of autologous parathyroid tissue (40 mg) under the skin of the forearm. Patients (5 F and 11 M) were studied from 1 month before surgery to 1 year after. Sleep disorders were assessed by means of a 27-item questionnaire--Sleep Disorder questionnaire (SDQ)--that identified sleeping disorders according to Diagnostic and Statistical Manual of Mental Disorders - IV Edition (DSM-IV) criteria. The Charlson Comorbidity Index (CCI) was also measured along with systolic and diastolic blood pressure, Hb, PTH, Ca, P. A 95.5% prevalence of sleep disorders was found pre operatively. Patients slept 4.90+/-1.2 hours, Ca averaged 10.09+/-0.54 mg/dL, Phosphate 5.5+/-1.93, CCI 9.8+/-1.1, PTH 1498+/-498 ng/mL. After 1 year follow-up 2 out 16 patients had normal sleep, 6 out 16 patients had subclinical sleep disorders and 8 remained insomniacs (p=0.008, Mc Nemar Test for paired data, insomniacs vs. no disturbance + subclinical disorders). Sleeping hours increased up to 6.0+/-1.24 (p<0.05), PTH was normalized, the Charlson Comorbidity Index was reduced (p<0.05) as were plasma calcium and phosphate (p<0.01). The study indicates that insomnia in patients with severe hyperparathyroidism on maintenance hemodialysis is ameliorated by parathyroidectomy.

High prevalence of sleep disorders in hemodialyzed patients requiring parathyroidectomy.

OBJECTIVE: Although there has been contrasting evidence for a causative role of parathyroid hormone (PTH) in sleep disorders in patients on maintenance hemodialysis, a recent study disclosed the possibility that this role might exist at least in patients requiring parathyroidectomy because of failure of medical therapy. The present study was devised to assess a possible difference in sleep disorders of patients on hemodialysis needing parathyroidectomy and those in whom medical therapy controlled hyperparathyroidism. DESIGN AND PATIENTS: To this end, a group of 22 patients requiring parathyroidectomy were studied by means of a sleep questionnaire, along with a group of 44 patients matched for age, gender, body weight, and duration of dialytic treatment. RESULTS: Patients requiring parathyroidectomy slept fewer hours (P < .001), had a higher prevalence of sleep disorders (P < .001), and were more often insomniac (P < .001). CONCLUSIONS: This study indicates that patients on hemodialysis requiring parathyroidectomy for intractable hyperparathyroidism comprise a good model for investigating the causative role of PTH on disordered sleep, and that these patients have very poor sleep. These data support recent findings on the prevalence of sleep disorders in dialyzed patients with insuppressible hyperparathyroidism.

High prevalence of sleep disorders at the time of CKD diagnosis.

OBJECTIVE: Sleep disorders are very common in adult and children on maintenance hemodialysis and are not cured by renal transplantation. SETTING/DESIGN: Studies in our laboratory of patients with a mean plasma creatinine concentration of 2 mg/dL, studied within 2 months of chronic kidney disease (CKD) diagnosis, have detected a high prevalence of sleep disorders that could not be explained by using the factors prevalent in hemodialysis patients. MAIN OUTCOME MEASURES: To understand if the intrusiveness of the disease is a cause for the high prevalence of sleep disorders in early CKD, we have assessed, by means of a questionnaire, sleep disorders within 1 month from the diagnosis of renal dysfunction. RESULTS: A total of 100 CKD patients with a mean estimated creatinine clearance of 59.1 +/- 26.7 mL/min were studied. The prevalence of sleep disorders was 89%. CONCLUSION: We believe this high prevalence might represent the effects of disease's intrusiveness and difficulty in coping with the disease.

Possible mechanisms of homocysteine toxicity.

Hyperhomocysteinemia is a risk factor for cardiovascular disease in the general population. In chronic renal failure (CRF), plasma homocysteine levels rise when the glomerular filtration rate (GFR) is reduced 50%, and in uremia the majority of patients are hyperhomocysteinemic. The purpose of this study was to review possible mechanisms of homocysteine toxicity. Homocysteine, a sulfur amino acid found in blood in micromolar concentrations, can have toxic effects through a handful of general possible mechanisms. These mechanisms include oxidative stress (through the production of reactive oxygen species), binding to nitric oxide, production of homocysteinylated/acylated proteins, and accumulation of its precursor, S-adenosyl-homocysteine, a potent inhibitor of transmethylation reactions. Methyltransferase inhibition actually occurs in CRF and in uremia, and can have several functional consequences.

Homocysteine in uremia.

Hyperhomocysteinemia is an independent cardiovascular risk factor that possibly accounts for about one of 5 cardiovascular deaths. It is conceivable that the importance of hyperhomocysteinemia will increase when other risk factors, such as hypertension or hypercholesterolemia, will become less prevalent in the general population. In chronic renal failure (CRF), high plasma homocysteine levels are a common finding and in uremia almost the rule. However, a small subset of patients remains normohomocysteinemic. The cause of hyperhomocysteinemia in CRF, whether it lies in an impaired renal or extrarenal metabolism or through uremic retention toxins, is still under intensive scrutiny. As for the consequences of high homocysteine levels in the general population and in patients with CRF, these are many-fold and linked to the mechanism of homocysteine toxic action. In fact, homocysteine can be harmful to cells because (1) it evokes oxidative stress (through the production of reactive oxygen species), (2) binds to nitric oxide, (3) produces homocysteinylated proteins, or (4) leads to the accumulation of its precursor, S-adenosylhomocysteine, a potent inhibitor of biological transmethylations. Macromolecule hypomethylation is a common feature in CRF and uremia with possible functional consequences. Nutritional or pharmacologic interventions have been proposed in the treatment of hyperhomocysteinemia, while the results of large clinical trials designed to assess if lowering homocysteine levels is effective in reducing cardiovascular risk, are pending.