History of Sleep Disorders in Chronic Kidney Disease: First Approach.

OBJECTIVES: In this study, we examined the history of sleep disorders in chronic kidney disease, 60 years after the advent of hemodialysis and renal transplant of genetically nonrelated organs, which have spurred a critical mass of data. MATERIALS AND METHODS: We analyzed selected literature on sleep disorders in chronic kidney disease from 1959 onward. RESULTS: Sleep disturbances are present in the general population. They cause loss of renal function and progressive nephron loss. Insomnia, sleep apnea, restless leg syndrome, and periodic limb movements represent sleep disturbances in chronic kidney disease. These symptoms manifest early in chronic kidney disease and are a rule in patients on dialysis and kidney transplant recipients. Sleep disturbances cause fatigue, excessive daily sleepiness, impaired daytime function, impaired health-related quality of life, increased morbidity, and increased mortality. CONCLUSIONS: Sleep disorders affect most patients with chronic kidney disease. No ascertained pharmacological therapy exists, and even a successful transplant does not totally restore a refreshing sleep. Longer nocturnal hemodialysis is of benefit. Sleep apnea may be cured with continuous positive airway pressure.

[Narrative Medicine can reduce opposition to organ removal for transplantation].

In Italy in 2017 out of 2738 assessments of death, there was a 28.7% of oppositions of family members to the removal of organs post-mortem. This opposition is a serious limitation to the development of transplantation programs. There is a need to increase the number of transplants since transplantation grants the highest quality of life, a longer survival and at a lower cost for the society. We propose the use of Narrative Medicine (MN) to reduce this opposition. "Narrative Medicine - as Charon says - fortifies clinical practice with the narrative competence to recognize, absorb, metabolize, interpret, and be moved by the stories of illness". We have identified eight stories as having a particular echo: 1. That of Nicholas Green, the American child killed on the Salerno-Reggio Calabria highway and whose organs saved seven people. 2. The story of Ylenia, who learned solidarity from transplants. 3. That of Robin JA Eady, Dermatology Professor in London and the second person on dialysis from Scribner in Seattle. 4. The story of the organ donation of Liberato Venditti, a young man who loved life and climbs on a motorcycle. 5. That of the young football player Giuseppe Feola, remembered here by the Napoli player Gonzalo Higuaín. 6. The donation of the organs of Bruno Memoli, Professor of Nephrology in Naples. 7. The reflections of a heart surgeon. 8. The story written by Federico Finozzi about his own transplant. "The stories" - as Greenhalgh writes - "have an ethical dimension. The person who reads or hears such a story incurs a duty to act so. Stories are open and subversive".

Keep moving without hurting: The interaction between physical activity and pain in determining cognitive function at the population level.

BACKGROUND: A number of studies have evaluated the association between cognitive function, pain, and physical activity. To our knowledge, however, no previous studies have evaluated these factors at the population level. AIMS: To evaluate the association between cognitive function in the elderly with pain, physical activity, and the interaction between these variables. Estimates are generated for the United States population. METHODS: We made use of the NHANES database (1999-2002), making adjustments so that our results represent the United States population. Cognitive function was evaluated through the Digit Symbol Substitution Test. Our main predictors were (1) pain, defined as soreness of either the shoulder, neck, lower back and joint, or a severe headache (2) physical activity, measured as the performance while performing tasks at home, physical activity intensity, walking, bicycle riding, and muscle strengthening. RESULTS: Most individual pain sites were not significantly associated with cognitive function, while all physical activity factors were associated with an increase in cognitive function. When evaluating the sample subset of those with cognitive scores lower than the median, a combination of more pain and less physical activity was consistently associated with lower cognitive scores when compared to those performing more physical activity with or without pain. When evaluating individuals with cognitive scores above the median, a similar association pattern was perceived. CONCLUSIONS: Among the population of individuals above the age of 60, higher cognitive levels are associated with more physical activity and less with pain, although both factors might impact cognition. Public policy resources should be commensurate with these findings when targeting cognitive function among the aging population.

Survival is not enough.

Survival is not enough is a yearly international event started in 2007 in Naples, Italy, in the week of the World Kidney Day to discuss the needs of renal patients and the quality of life of a category of patients living a machine-dependent life. Renal patients and their associations, philosophers, economists, nephrologists, and health care managers are enrolled to discuss about the possibility to grant the best cures and care without reducing the quality and the quantity of the services the patients need. Various quests have arisen for (1) a new cadre of managers capable of keeping health accounts in balance without cutting expenditure but by reducing waste of resources, (2) the promotion of prevention as the only measure capable of reducing costs in the long run, and (3) the promotion of clinical and translational research. The changes occurring in the health system should be viewed as a window of opportunity, including the advent of the medical-industrial complex firstly described in 1980, an event originating in the United States of America and now spreading worldwide.

Where philosophy meets clinical science.

Nowadays, there is a renewed interest in bone changes in experimental and clinical nephrology. However, the need for understanding the peculiarity of bone can be traced back to the 5th century BC, when Empedocles of Acragas put forward a theory of a world made of air, water, fire, and earth governed by love and hate. By observing the various body tissues, he strove to demonstrate that they consisted of 4 elements assembled with different mathematical ratios (logos). Blood is considered the most perfect tissue, because the ratio between elements is one. Bone is a very unusual tissue because it is made of 2 parts of earth, 2 parts of water, and 4 parts of fire. This kind of reasoning could be considered the first cry in the birth of quantitative chemistry.

The high prevalence of alexithymia in hemodialyzed patients with secondary hyperparathyroidism unsuppressed by medical therapy is cured by parathyroidectomy.

There are scanty data available on alexithymia in patients with end-stage renal disease, which point to an independent association with depression and social support. This study was devised to investigate the prevalence of alexithymia and sleep disorders in patients maintenance hemodialysis with insuppressible secondary hyperparathyroidism, who need parathyroidectomy (PTX), because previous data from our laboratories as well as those of others showed that this patient-group are the worst sleepers among hemodialysis patients with end-stage renal disease. A total of 40 patients needing PTX were enrolled and studied before the surgery. As for the control group, 80 patients on maintenance hemodialysis not needing PTX were enrolled. We measured alexithymia with the Toronto Alexithymia Score (TAS-20), sleep disorders with the Pittsburgh Sleep Quality Index (PSQI), and depression with Beck Depression Inventory (BDI), intact parathyroid hormone (iPTH), calcium, phosphate, use of antihypertensives, systolic and diastolic blood pressure, hemoglobin concentration, and albumin concentration. Patients needing PTX in comparison with those not needing PTX had significantly higher iPTH, calcium, and phosphate; they also had significantly higher systolic and diastolic blood pressure. They were more significantly alexithymic (P < .001), had more severe sleep disorders (P < .001), and were more depressed (P < .043). In multivariate analysis, BDI correlated significantly with iPTH concentration (r = 0.505, P < .001). A reduction of TAS-20 occurred after PTX which correlated with the number of patients on antihypertensive drugs, PSQI, BDI, hemoglobin concentration in the univariate and multivariate analysis. When TAS-20 and PSQI were adjusted for BDI (using analysis of variance) there was still a significant difference of TAS-20 and PSQI between patients needing PTX and not needing PTX (P < .001). This study confirms the high prevalence of sleep disorders in patients with unsuppressed secondary hyperparathyroidism and discloses a high prevalence of Alexithymia which is ameliorated by PTX. However, the correlation of Alexithymia with sleep disorders does not depend on depression.

The nature of water: Greek thought from Homer to Acusilaos.

Greek philosophy finds its roots in the myth of Homer's and Hesiod's poems and especially in Orphism which introduced the concept of a soul separated from the body with an independent principle, psiche (soul), to be rewarded or punished after death. Orphism was an important step in Greek culture. It introduced the divine into man, the soul which does not die with the body and reincarnates. From Orphism started the need of rituals capable of separating the spirit from the body. From Homer to Acusilaos, water was a very important element which connected humans and gods, long before Thales of Miletus defined it the arche.

The nature of water: excerpts from Pythagoras, Xenophanes, Heraclitus and Parmenides.

Water was a prominent substance with Pythagoras, Xenophanes, Heraclitus and Parmenides, who flourished in the years 530-490 bc. The basic Pythagorean elements were earth and fire, and between them there were 2 intermediate entities (water and air), which were instrumental and indispensable components of specific solids. All things are a blend of different elements. For Xenophanes, "All things that come into being and grow are earth and water," "We all originated from earth and water" and "And in certain caves water drips down."For Heraclitus water is an ambivalent substance: "One cannot bathe in the same river on two occasions." "The sea is the safest and the most polluted water, for fish it is healthy and gives life, for men it is unhealthy and causes death." "Fire experiences the death of earth, air experiences that of fire, water experiences the death of air and the earth that of water." Parmenides was a man who sought the truth through reasoning and was, according to Hegel, the founder of Western philosophy. He built a dualist theory of the cosmos based on heat and cold, fire and earth - the former as a cause, the latter as substrate. The former unified, the latter separated. According to Aristotle, Parmenides considered air and water as mixtures of earth and fire.

Water, from Gilgamesh Epic to Nobel Laureate Richard Feynman: a look into polywater and the memory of water.

Water is a complex source of imagination, dreams and rituals, where cultural differences ebb and flow, where a plethora of meanings and interpretations interlink and wash over one another. Water has an ambivalent character as stated in most of the ancient cosmogonies and in the Epic of Gilgamesh. Water's composition was discovered by the London scientist Henry Cavendish in about 1781. Although it is an apparently simple molecule (H2O), it has a highly complex and anomalous character. The anomalous properties of water are those where the behavior of liquid water is quite different from what is found with other liquids. As often stated, life depends indeed on these anomalous properties of water. Notably there are 12 phase, 22 density, 12 material, 11 thermodynamic and 9 physical anomalies. A powerful look into the water molecule was given by Nobel Prize recipient Richard P. Feynman as published in Six easy pieces. A look into the most recent quest for more knowledge about water leads us to the concept of pathological science. The cases of "polywater" and "the memory of water" are indeed paradigmatic episodes of fraudulent research published in journals with high impact factors. In conclusion, men came out of water engineered to handle water, and water greatly affects mythology and philosophy and is a strong presence in the arts and science.

To survive is not enough. Quality of life in CKD--the need for a new generation of health-oriented economists.

CKD is utilized as a paradigm, a chronic disease which allows decades of life conquered with great effort through a machine, a life with many losses and many dependencies. We must understand the patient's needs, which are not related to availability of drugs and machines and hospitals. We cannot provide good medical care with the limited amount of national product devoted to health care. Society is much older than ever before. We need a new cadre of economists working on health care with vision and ability, keeping in mind that there are no resources and there are no expenses which can be cut in medical care nowadays. We have to switch from curative medicine towards prevention, by implementing clinical research, bearing in mind that in the Western world, democracy was granted through the correct allocation of resources. The search for happiness and good quality of life are old concepts born in the Mediterranean area over the centuries, starting with Hesiod and Homer, and sleep and dreams were being investigated centuries before Freud was born.

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.

Sleeping disorders in patients with end-stage renal disease and chronic kidney disease.

About 85% of patients on maintenance hemodialysis have sleep disorders that depend on comorbidities, age, morning dialytic shift, and blood pressure. They are ameliorated by erythropoietin, by transplantation, and by daily and nocturnal dialysis. Some data exist on sleep disorders in CKD patients, and show that lack of a refreshing sleep is present even at early stages of the disease and may affect 82.2% of patients without any relationship to comorbidities.

Depression in chronic kidney disease.

Depression is the most frequent psychiatric problem in patients with chronic renal disease and may predict patient outcome and mortality. Depression is linked to stressful life characterized by many losses and by dependence, which even may lead to suicide. Despite the large number of patients with chronic kidney disease and the economic burden they represent, only a few of these patients receive adequate diagnosis and therapy. Diagnostic and Statistical Manual of Mental Disorders-IV criteria for major depression may help in differentiating symptoms of uremia and depression. Pharmacotherapy is available and antidepressants (tricyclic antidepressants and selective serotonin re-uptake inhibitors) have been used successfully in various studies. Finally, there is a need for further well-designed, longitudinal, survival studies to clarify the relationship better between depression and the different stages of renal dysfunction.

Insomnia and its comorbidities in chronic kidney disease.

Sleep disorders are among the factors that can reduce the quality of life in patients with chronic kidney disease. Chronic kidney disease patients could benefit from an accurate evaluation and treatment of insomnia because this sleep disorder is associated with a high persistence-relapse rate, poor physical health, and mental disease (anxiety, depression) both in terms of comorbidity and antecedent. A multilayer evaluation of insomnia is possible because of valid and reliable instruments (both objective and subjective). Furthermore, a rational etiologic model of insomnia allows better understanding and treatment as a result of effective cognitive-behavioral techniques.