Is the dietary protein restriction achievable in chronic kidney disease? The impact upon quality of life and the dialysis delay

Hippokratia 2011; 15 (Suppl 1): 3-7

E. Koulouridis, I. Koulouridis

Abstract

The possible deleterious effect of meet consumption upon deterioration of renal disease was speculated from Lionel Beale as early as 1869. The first attempt to apply a very low protein diet in humans is attributed to Millard Smith who prescribed a diet consisting of 300 mg protein per day in a volunteer medical student for 24 days. Unfortunately, in early 20th century, prescribing very low protein diets among patients suffering from renal disease complicated with malnutrition and the medical practice of this era turned to the recommendation of high protein diets because it was believed that protein consumption is coupled with the strength of civilized man. In mid sixties Giordano and Giovanetti introduced low protein diets in the treatment of uremic patients but their efforts did not accepted from the medical community. Meanwhile the evolution of haemodialysis, peritoneal dialysis and transplantation as effective methods of treating end stage renal disease guided doctors and patients far from privative diets in the era of plenty. The rapidly increasing number of end stage renal disease patients needed substitution of renal function produced a tremendous increase of financial burden upon public health system expenditure and alternative measures of therapy, prevention and delaying chronic kidney disease searched. Unfortunately MDRD study failed to show convincing results of food protein restriction and blood pressure lowering in ameliorating deterioration of renal function and the majority of physicians turned to the practice of early dialysis in an attempt to avoid malnutrition. Despite the increasing knowledge and the appliance of certain guidelines in treating end stage renal disease patients, the morbidity and mortality remain high among this population. The search toward other possible toxic substances showed that phosphorus consumption with diet is another dangerous element exerting its deleterious effect in deteriorating renal function as well as increasing morbidity and mortality. Recently published epidemiological data suggest a very poor outcome of elderly patients, older than 80 years of age, undergoing substitution of renal function by dialysis or peritoneal dialysis and a lot of skepticism arise concerning the beneficial effect of diet and a rigorous effort of rehabilitation of these patients instead of substitution of renal function by either method.

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Phosphate binders: Sevelamer in the prevention and treatment of hyperphosphataemia in chronic renal failure

Hippokratia 2011; 15 (Suppl 1): 22-26

S. Spaia

Abstract

In chronic kidney disease patients, bone and mineral abnormalities have a major impact on morbidity and mortality. Hyperphosphatemia has been associated with increased mortality and with the development of cardiovascular calcification, an independent predictor of mortality. Sevelamer, or more precisely "sevelamer hydrochloride", is a weakly basic anion-exchange resin in the chloride form that was introduced in 1997 for the treatment of the hyperphosphataemia of patients with end-stage renal failure. Sevelamer sequesters phosphate within the gastrointestinal tract, so prevents its absorption and enhances its faecal excretion. Over the succeeding years, large numbers of patients have been treated with sevelamer, and it has fulfilled expectations in helping to control the hyperphosphataemia of end-stage renal failure. Additionally treatment with sevelamer was accompanied with lower incidence of hypercalcemia, decreased incidence of low PTH levels, a 15-31% decrease of LDL-cholesterol both in dialysis and predialysis patients, decreased C-reactive protein, amelioration of hyperuricemia and low fetuin A, decrease of uremic toxins, suggesting an overall anti-inflammatory effect. In incident dialysis patients, treatment with sevelamer has been associated with better survival, while in prevalent patients a clear benefit could only be demonstrated in older patients and in patients treated for more than 2 years. In dialysis patients, the treatment of hyperphospathemia with calcium based compounds, when compared with sevelamer, is associated with more frequent episodes of hypercalcemia, suppression of intact PTH and with progression of coronary calcifications. In the presence of adynamic bone disease, calcium load has a significantly higher impact on aortic calcifications and stiffening. Sevelamer treatment resulted in no statistically significant changes in bone turnover or mineralization compared with calcium carbonate, but bone formation rate increased and trabecular architecture improved only with sevelamer. In conclusion, the treatment of hyperphosphatemia with sevelamer hydrochloride, a noncalcium and non-metal containing phosphate binder, is associated with a beneficial effect on vascular calcification progression, bone disease and most likely with a survival benefit in some hemodialysis patients populations. Sevelamer carbonate is an improved, buffered form of sevelamer hydrochloride developed for the treatment of hyperphosphataemia in CKD patients. Sevelamer carbonate formulated as a powder for oral suspension presents a novel, patient- friendly alternative to tablet phosphate binders. Safety and efficacy of sevelamer carbonate powder compared with sevelamer hydrochloride tablets in CKD patients are equivalent, with Sevelamer carbonate having fewer side effects from gastrointestinal tract.

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Pregnancy in women with renal disease. Yes or no?

Hippokratia 2011; 15 (Suppl 1): 8-12

K. Edipidis

Abstract

Women with renal disease who conceive and continue pregnancy, are at significant risk for adverse maternal and fetal outcomes. Although advances in antenatal and neonatal care continue to improve these outcomes, the risks remain proportionate to the degree of underlying renal dysfunction. The aim of this article, is to examine the impact of varying degrees of renal insufficiency on pregnancy outcome, in women with chronic renal disease and to provide if possible, useful conclusions whether and when, a woman with Chronic Kidney Disease (CKD), should decide to get pregnant. This article, reviews briefly the normal physiological changes of renal function during pregnancy, and make an attempt to clarify the nature and severity of the risks, in the settings of chronic renal insufficiency and end stage renal disease, including dialysis patients and transplant recipients.

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Is the underutilization of peritoneal dialysis in relation to hemodialysis, as renal replacement therapy, justifiable worldwide? Yes or No

Hippokratia 2011; 15 (Suppl 1): 13-15

E. Grapsa

Abstract

Peritoneal dialysis is the most important home dialysis treatment for end stage renal diseases and needs personal involvement, and support from the family . Peritoneal dialysis presented a number of discouraging technical problems and led to the belief that PD was not an appropriate renal replacement therapy, for patients with end stage renal disease. Despite the improvement of the method its rate remain low (11%) worldwide. The factors affecting the choice of PD are multiple and explain the disparity in the use of peritoneal dialysis in different countries and different parts of the same country. Dialysis costs and reimbursement structures are significant in decisions about the rates and modalities of renal replacement therapy. Late referral and the health care system seems to be very important factors that influence the dialysis modality choice. After the initiation of peritoneal dialysis we can see other factors that influence the survival of the method. The rate of peritonitis and the peritoneum function seems to be important issues.

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The effect of the expenditure increase in the morbidity and the mortality of patients with end stage renal disease: the USA case

Hippokratia 2011; 15 (Suppl 1): 16-21

A. Letsios

Abstract

The worldwide incidence of kidney failure is on the rise and treatment is costly. Kidney failure patients require either a kidney transplant or dialysis to maintain life. This review focuses on the economics of alternative dialysis modalities such as haemodialysis (HD) and peritoneal dialysis (PD). Important economic factors influencing dialysis modality selection include financing, reimbursement and resource availability. Modality selection is also influenced by employment status, with an association between being employed and PD as the modality choice. In the United States, there were 101,688 incident HD patients and 6,506 incident PD patients in 2007. Due to the fact that the worldwide incidence of kidney failure continues to rise placing USA in the second position right after Taiwan, the accumulated experience from USA could be used as a characteristic prototype for the analysis of the economics related with modality choices and their influence in the quality of life and life expectancy of end stage renal disease (ESRD) patients. In the present work we discuss the effect of the expenditure increase in the morbidity and the mortality of patients with end stage renal disease. Data coming from the "USA case" concerning the economic factors which play a vital role in the sequence of events that leads to the choice between different modalities such as HD and PD, will be used as a distinctive example in our study. The relationship between the modality used and employment status is investigated. The cost effectiveness of alternative modalities is reviewed. Examples of statistical models and simulation approaches, studying the increase of the life expectancy in terms of the quality adjusted life years (QALYs) and the incremental cost paid are also presented. Corresponding results originated from different regions of the world are also briefly shown.

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Role of angiotensin converting enzyme inhibitors and angiotensin receptor blockers in hypertension of chronic kidney disease and renoprotection. Study results

Hippokratia 2011; 15 (Suppl 1): 27-32

M. Baltatzi, Ch. Savopoulos, A. Hatzitolios

Abstract

Chronic kidney disease (CKD) is a global health problem associated with considerable morbidity and mortality and despite advances in the treatment of end stage renal disease (ESRD) mechanisms to prevent and delay its progression are still being sought. The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in many of the pathophysiologic changes that lead to progression of renal disease. Traditionally RAAS was considered as an endocrine system and its principal role was to maintain blood pressure (BP). In recent years local RAAS has been described to operate independently from systemic and local angiotensin II (AngII) in the kidney to contribute in hypertension and kidney damage. The benefits of strict BP control in slowing kidney disease progression have been demonstrated in several clinical trials and the question whether specific agents like angiotensin converting enzyme antagonists (ACEIs) and angiotensin receptor blockers (ARBs) provide renoprotective benefits beyond BP lowering is to be answered. Several studies support these agents reduce proteinuria and protect renal function, whereas the opposite is stated by others. According to guidelines, their use is recommended as first line agents in diabetic renal disease and non diabetic renal disease with albuminuria, whereas there is no data to support the same in non diabetic nonalbuminuric renal disease. Dual blockage of RAAS with the combination of ACEIs and ARBs could offer an alternative in strict RAAS blockade, but studies up to now can not prove its safety and the combination is not recommended until ongoing trials will provide new and unarguable results.

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Secondary hyperparathyroidism and target organs in chronic kidney disease

Hippokratia 2011; 15 (Suppl 1): 33-38

M. Nikodimopoulou, S. Liakos

Abstract

Secondary hyperparathyroidism (SHPT) is a common disorder in patients with chronic kidney disease (CKD) and is characterized by excessive serum parathyroid hormone (PTH) levels, parathyroid hyperplasia and an imbalance in calcium and phosphorus metabolism. Secondary hyperparathyroidism develops early in the course of CKD and becomes more prominent as kidney function declines. PTH is a major uremic toxin and may be responsible for long-term consequences that include renal osteodystrophy, severe vascular calcifications, alterations in cardiovascular structure and function, immune dysfunction, and anemia. These adverse effects may contribute to an increased risk of cardiovascular morbidity and mortality among end-stage renal failure patients.

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Renal anemia: a nephrologist's view

Hippokratia 2011; 15(Suppl 1): 39-43

G. Tsagalis

Abstract

Anemia is a common finding in patients with CKD, with a prevalence that increases gradually as eGFR declines. The prevalence of renal anemia depends on the size of the study and the selection of participants. Diabetic status increases the prevalence of anemia in patients with CKD. Anemia in CKD is due primarily to reduced production of erythropoietin in the kidney and secondarily to shortened red cell survival. Erythropoeitin (EPO) is produced by peritubular cells in the kidneys of the adult and in hepatocytes in the fetus. These cells are sensitive to hypoxia that once sensed leads to an increase in EPO production. EPO circulates in the plasma and induces redcell production in the bone marrow after successful binding to erythroid progenitor cells. Apart from EPO, folate, B12 and iron are needed to assure effective erythropoiesis. Factors that can dysregulate this process include inflammation, uremic toxins, hypothyroidism, hypersplenism and ongoing infection. The investigation of renal anemia requires the assessment of a variety of biological indices. Among them, the complete blood count, the reticulocyte index, B12, folate, ferritin levels and the saturation of transferrin are the most valuable tools in revealing the cause of renal anemia.

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Are we satisfied with the follow-up of hypertensive and chronic kidney disease patients in outpatient clinics?

Hippokratia 2011; 15(Suppl 1): 44-49

M. Peppa, D. Vlahakos

Abstract

Hypertension and chronic kidney disease constitute major health problems as they are associated with increased morbidity and mortality. Large-scale clinical trials, have emphasized the need of a strict blood pressure and early recognition of kidney disease to reduce the complications. However, the rate of hypertension control seems to be low, the prevalence of hypertension and chronic kidney disease steadily increases, indicating a gap in the management of those patients. This is due either to a poor organization of the health care system or a defective patient-physician communication. This review will try to identify possible errors in the management of hypertensive and renal failure patients in outpatient clinics and to propose ways to improve prevention and control of hypertension and chronic kidney diseases in our population.

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Phosphorus metabolism in chronic kidney disease

Hippokratia 2011; 15 (Suppl 1): 50-52

C. Fourtounas

Abstract

The knowledge about the exact mechanisms involved in phosphorus homeostasis and the evolution of secondary hyperparathyroidism in chronic kidney disease (CKD) has improved during the last years. The discovery of Fibroblast Growth Factor 23 (FGF23) has revolutionized our understanding about the links between mineral metabolism, vitamin D and parathyroid hormone (PTH). FGF23 serum levels increase early in CKD before the increase of serum phosphorus or the decrease of vitamin D and there is parathyroid resistance to FGF23 in advanced CKD. Increased levels of serum phosphorus have been related in epidemiological studies with adverse outcomes in patients with CKD, diabetes, coronary artery disease, or even normal adults. In patients with CKD stage 3 or 4, low phosphorus diets have been related with adverse outcomes due to the risk of malnutrition and there are limited data regarding the role of phosphate binders in these patients. Recent studies suggest that increased serum FGF23 levels are associated with mortality, left ventricular hypertrophy and progression of CKD independently of serum phosphorus levels. There is an ongoing debate about the "normal" or "desirable" levels of serum phosphorus in CKD and a new role of FGF23 as a marker of the disturbances of mineral metabolism in CKD is emerging.

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Update of acute kidney injury: intensive care nephrology

Hippokratia 2011; 15(Suppl 1): 53-68

G. Tsagalis

Abstract

Albeit the considerable progress that has been made both in our understanding of the pathophysiology of acute renal failure (ARF) and in its treatment (continuous renal replacement therapies), the morbidity of this complex syndrome remains unacceptably high. The current review focuses on recent developments concerning the definition of ARF, new strategies for the prevention and pharmacological treatment of specific causes of ARF, dialysis treatment in the intensive care setting and provides an update on critical care issues relevant to the clinical nephrologist.

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