Alirocumab in a high cardiovascular risk patient on hemodialysis with liver abnormalities.

We present a male diabetic type 2 patient on hemodialysis (HD) with high cardiovascular (CVD) risk and hyperlipidemia. The patient was under cholesterol-lowering therapy with statin and ezetimibe but he was obligated to discontinue due to chronic hepatitis C virus infection. Statins and ezetimibe may exert a potential hepatotoxic effect and for this reason, we attempted to find an alternative treatment to prevent CVD. Given that a potential hepatotoxic effect has not been reported for Abs SPCK9, we administered alirocumab 150 mg every 2 weeks for a total of 8 weeks. Low-density lipoprotein levels have decreased and no side effects have been observed. In conclusion, alirocumab is a safe and efficient alternative therapy approach for HD patients with high CVD risk and liver abnormalities. We suggest that SPCK 9 inhibitors should be considered as a first line treatment for lowering cholesterol in this specific patient group.

Cramps during Hemodialysis: Are They Always Innocent?

Cramps are very common in hemodialysis (HD) patients. A high ultrafiltration rate and volume contraction have been implicated in the pathogenesis, but the underlying mechanism is not yet fully elucidated. We present a male HD patient with cramps during his session, attributed to acute limb ischemia due to thrombosis of a common femoral artery aneurysm (CFAA). The true CFAAs are extremely rare, but the pseudoaneurysms (or false aneurysms) are less uncommon resulting after femoral catheterization for diagnostic and therapeutic procedures. This aneurysm was eccentric in shape which in conjunction with the patient's history of femoral catheterization strongly suggests us to consider it a pseudoaneurysm. Although the patient was operated with the clinical suspicion of arterial embolism due to atrial fibrillation and the subtherapeutic anticoagulation, no embolus was found in the aneurysm. We want to emphasize that the presence of cramps is not always innocent, simply attributed to HD. Rarely, it may result from or mask severe and devastating acute leg ischemia caused by thrombosis of a CFAA. Notably, the thrombosis of a CFAA (true or false) is an extremely rare condition. We suggest all the HD patients with a history of femoral cannulation to undergo a vascular ultrasound in the related femoral artery at least once, to manage and to prevent the complications.

Icodextrin and peritoneal dialysis: advantages and new applications.

The impact of icodextrin (ico) on peritoneal dialysis (PD) extension and patient survival is well established. Predominantly, ico-based solutions were prescribed in high-transporter PD patients. Advantages of the ico-based solutions include increased biocompatibility, avoidance of glucotoxicity, enhanced ultrafiltration failure (UF), sodium removal rates, better metabolic and blood pressure control. Bimodal solutions and twice daily exchanges of ico-based solutions are two newly introduced strategies to avoid glucose exposure and/or enhance UF in PD patients with UF failure. In addition, a simplified schedule of PD using a single nocturnal exchange of ico in patients with refractory congestive heart failure may represent an alternative option to manage fluid removal and azotaemia. The use of a simplified schedule of PD with only two ico exchanges or a single ico exchange is a challenging approach for end-stage renal disease patients with preserved residual function who desire to initiate PD.

Therapeutic alternatives and palliative care for advanced renal disease in the very elderly: a review of the literature.

The overall number of very elderly patients (>79 years of age) requiring renal replacement therapy is rising in the Western societies, with a choice for managing advanced chronic renal disease among hemodialysis, peritoneal dialysis, kidney transplant, conservative, or palliative care. The selection of the most adequate alternatives should be tailored to meet individual needs, considering variables such as patient's choice, clinical status, and social context, analyzed from a geriatric perspective, aiming not only to prolong patient's life expectancy, but also to improve the patient's quality of life. Frailty and sarcopenia are highly prevalent comorbidities found in very elderly population, particularly in the end-stage chronic renal disease population. Both comorbidities have a strong negative impact on health general status, and specific treatment should be provided in conjunction with the selected management for renal replacement, except when a palliative care has been implemented. Moreover, the detected degree of frailty in a renal patient can have an important influence on the decision about which modality of renal replacement treatment will be selected. All these alternatives and considerations are discussed in the present review article.

Hyperuricemia and chronic kidney disease: an enigma yet to be solved.

The role of uric acid (UA) on the pathogenesis and progression of chronic kidney disease (CKD) remains controversial. Experimental and clinical studies indicate that UA is associated with several risk factors of CKD including diabetes, hypertension, oxidative stress, and inflammation and hyperuricemia could be considered as a common dominator linking CKD and cardiovascular disease. Notably, the impact of serum UA levels on the survival of CKD, dialysis patients, and renal transplant recipients is also a matter of debate, as there are conflicting results from clinical studies. At present, there is no definite data whether UA is causal, compensatory, coincidental or it is only an epiphenomenon in these patients. In this article, we attempt to review and elucidate the dark side of this old molecule in CKD and renal transplantation.

Prevalence of anemia in patients with type II diabetes and mild to moderate chronic kidney disease and the impact of anti-RAS medications.

Anemia is a common feature of diabetes and chronic kidney disease (CKD) mainly due to erythropoietin (EPO) deficiency and uremic toxicity. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have been established as first-choice medications for the treatment of diabetic nephropathy. However, there are conflicting data regarding their impact on hemoglobin levels in patients with diabetic nephropathy. We evaluated the prevalence of anemia in 101 patients with diabetes mellitus type II and CKD at stage III-IV (group A) compared with 101 non-diabetic patients with similar renal function (group B). Moreover, we evaluated the impact of ACE inhibitors and ARBs on patients' anemia. Anemia was observed in 60 patients in group A and in 47 patients in group B (P < 0.01). Thirty-one (31) patients in group A and 19 patients in group B were receiving exogenous EPO for correction of renal anemia (P <0.05). Mean values of hemoglobin did not show significant differences (12.5 ± 1.8 vs 12.6 ± 1.7 g/dL) between the two groups. Seventy-five patients in group A and 52 patients in group B were receiving ACE inhibitors and/or ARBs (P <0.01), but, after multivariate analysis, we could not detect any association between anemia and the prescription of these medications. Anemia is more common in diabetic patients with CKD stage III-IV than in non-diabetic patients with similar renal function. Our results indicate that ACE inhibitors and ARBs are not a significant cause of anemia for both populations.

Hypomagnesemia, chronic kidney disease and cardiovascular mortality: pronounced association but unproven causation.

Magnesium is as an essential metal implicated in numerous physiological functions of human cells. The kidney plays a crucial role in magnesium homeostasis. In advanced chronic kidney disease, serum magnesium levels are increased. Data from experimental and observational studies suggest that low levels of magnesium are associated with several factors, such as insulin resistance, diabetes, oxidative stress, hypertension, atherosclerosis, and inflammation which are implicated in the progression of chronic kidney disease. Moreover, low levels of magnesium have been correlated with cardiovascular disease and all-cause mortality in end-stage renal disease patients. Hypomagnesemia has also been associated with poorer renal allograft and transplant recipients' outcomes. The causality of these relationships has not been completely elucidated. A thorough review of the current literature indicates that low magnesium levels in dialysis patients may reflect a poorer nutritional status and/or are the result of systemic inflammation. Further studies in chronic kidney disease and dialysis patients are needed in order to clarify the causality of these associations.

The thyroid and the kidney: a complex interplay in health and disease.

Thyroid hormones may directly affect the kidney and altered kidney function may also contribute to thyroid disorders. The renal manifestations of thyroid disorders are based on hemodynamic alterations or/and to direct effects of thyroid hormones. The renin-angiotensin system plays a crucial role in the cross-talk between the thyroid and the kidney. Hypothyroidism may be accompanied by an increase of serum creatinine and reduction of glomerular filtration rate (GFR), whereas hyperthyroidism may increase GFR. Treatment of thyroid disorders may lead to normalization of GFR. Primary and subclinical hypothyroidism and low triiodothyronine (T3) syndrome are common features in patients with chronic kidney disease (CKD). In addition low levels of thyroid hormones may predict a higher risk of cardiovascular and overall mortality in patients with end-stage renal disease. The causal nature of this correlation remains uncertain. In this review, special emphasis is given to the thyroid pathophysiology, its impact on kidney function and CKD and the interpretation of laboratorial findings of thyroid dysfunction in CKD.

Role of testosterone in the pathogenesis, progression, prognosis and comorbidity of men with chronic kidney disease.

Testosterone deficiency and hypogonadism are common conditions in men with chronic kidney disease (CKD). A disturbed hypothalamic-pituitary-gonadal axis due to CKD is thought to contribute to androgen deficiency. Data from experimental studies support the hypothesis that exogenous administration of testosterone may induce the activation of the renin-angiotensin system (RAS), the production of endothelin and the regulation of anti- or/and proinflammatory cytokines involved in the pathogenesis of hypertension and kidney damage. On the other hand, low testosterone levels in male patients with CKD are paradoxically associated with a higher risk of morbidity and mortality, possibly explained by anemia, osteoporosis and cardiovascular disease. In this article, we present an overview of clinical and experimental studies of the impact of testosterone on the progression and prognosis of male patients with CKD; even today, this remains a controversial issue.

Bimodal solutions or twice-daily icodextrin to enhance ultrafiltration in peritoneal dialysis patients.

The efficacy and safety of icodextrin has been well established. In this paper, we will discuss the pharmacokinetics and biocompatibility of icodextrin and its clinical effect on fluid management in peritoneal dialysis patients. Novel strategies for its prescription for peritoneal dialysis patients with inadequate ultrafiltration are reviewed.

Beneficial effects of nocturnal hemodialysis in a hemodynamically unstable patient with AL-amyloidosis.

We present a patient with primary systemic AL-amyloidosis, who stabilized hemodynamically on nocturnal hemodialysis (NHD). The NHD allowed a significant reduction in ultrafiltration rates which likely underlies the procedural tolerability. It also provided an increase in urea clearance, better control of serum phosphorus levels without the use of any binders, and normalization of blood pressure despite the discontinuation of all antihypertensive agents. Given the autonomic derangements associated with AL-amyloidosis pathophysiology and the clinical benefits of NHD on hemodynamic stability, the use of intensive hemodialysis may be considered for the management of patients with unstable hemodynamic profiles.

Diagnosis and management of chronic kidney disease in the elderly: a field of ongoing debate.

Chronic kidney disease (CKD) is rather common in elderly adults who comprise the fastest growing subset of patients with end-stage renal disease (ESRD). At present, there are no specific guidelines and recommendations regarding early identification and management of elderly with CKD and the current CKD classification system may overestimate its exact prevalence. Screening strategies based either in a more accurate formula of estimation of GFR alone, or preferably in combination with proteinuria are urgently needed in order to raise awareness and to promote early diagnosis of CKD in the elderly. The number of elderly dialysis patients is also increasing and may lead to severe socio-economic problems worldwide. Both hemodialysis and peritoneal dialysis can sustain life, but present various disadvantages. There is a trend for home based dialysis therapies but the results are based on a small number of patients. Recent reports indicate that dialysis may not provide a clear benefit over non-dialysis regarding survival and quality of life issues, especially in the presence of extensive comorbidities. Current practices around the world regarding access to dialysis in the elderly are rather controversial, reflecting each country's health policies and ethical patterns. Although advanced age should not be considered as an absolute contraindication for kidney transplantation, it is not frequently offered in elderly ESRD patients due to the shortage of renal grafts. Global judgment of all physical and mental/psychological issues and full informed consent regarding possible complications are mandatory before listing elderly ESRD patients for kidney transplantation. As scientific evidence is rather scarce, there is an urgent need for prospective studies and an individualized approach for the diagnosis and treatment of the elderly CKD patients, in order to optimize care and improve quality of life in this special population.

Delusional parasitosis: a rare cause of pruritus in hemodialysis patients.

Uremic pruritus is a common symptom in patients undergoing hemodialysis (HD) or peritoneal dialysis, but its exact pathogenesis remains rather unclear. However, severe or "intractable" pruritus may be the manifestation of another underlying disease or disorder other than uremia. Delusional parasitosis, or Ekbom syndrome, is a rare psychiatric disorder characterized by the false conviction of being infested with parasites, and it can be primary, or secondary to several medical and psychiatric disorders. We report 2 elderly HD patients who presented one after another, with delusional parasitosis. At some point in time, the delusional beliefs of the first patient were adopted by the second patient who was waiting to start his HD session on the same bed and HD machine, on a subsequent shift. They were both diagnosed with Ekbom syndrome and described as having monosymptomatic hypochondriac delusion. They were both prescribed antipsychotic medications. During follow-up they admitted feeling better than before; however, they remained concerned about the "insects/parasites."

Encapsulating peritoneal sclerosis: a single-center experience and review of the literature.

Encapsulating peritoneal sclerosis (EPS) is a serious and often fatal complication of long-term PD with severe malnutrition and poor prognosis. It causes progressive obstruction and encapsulation of the bowel. This retrospective study reviews our experience and that reviewed in the literature concerning EPS. It refers to a total of 1966 patients treated with chronic PD between 1974 and 2008. Twenty one of them (1.1%) developed EPS, with the incidence increasing with the duration of PD. Mean age of our patients with EPS was 43, ranging from 18 to 71 years, 8 were men and 13 women with a mean body mass index (BMI) of 21.6 kg/m(2). Only one patient had Type II diabetes, 15 patients had glomerular disease, and six of these 15 had an autoimmune disease such as Wegener's granulomatosis and SLE. Thirteen patients developed EPS while on PD, 7 within 2 years after transfer to HD, and only one after renal transplantation. However, 7 patients had a previous renal transplant before returning to PD and subsequently developing EPS. Interestingly, we did not observe more episodes of EPS after transplantation. In the patients who developed EPS, the peritonitis rate over the period of observation was 1/15.6 pt-months and was due to Staphylococcus aureus, coagulase-negative staphylococcus, Pseudomonas and fungi. A history of peritonitis was not a prerequisite for developing EPS, since one patient had no episodes of peritonitis and 4 had just one previous episode. Fifteen patients presented with peritonitis within 4 months before the diagnosis of EPS with particularly virulent micro-organisms such as S. aureus, Candida, Pseudomonas, Corynebacterium, and Peptostreptococcus. Eleven patients were treated with hypertonic dextrose solutions (4.25 g/dl of dextrose) and seven with icodextrin, indirectly suggesting problems with ultrafiltration. Nine of 21 patients were on beta-blockers. The diagnosis of EPS was made either surgically or radiologically with signs of small bowel obstruction in combination with severe malnutrition. Eleven of our patients (52%) had evidence of small bowel obstruction and 14 patients required total parenteral nutrition (TPN). Tamoxifen (10-20 mg daily) was started in 6 patients, 4 of whom are alive and 2 deceased 3 and 5 years after EPS was diagnosed. Of the 12 patients who were not given tamoxifen, 2 are alive and 10 died. No side effects of tamoxifen were reported. Only 7 of our patients (33%) died during the first year after the diagnosis of EPS. Currently, 4 patients are on HD and 3 have had a renal transplant. Six patients of the fourteen who underwent surgery (42.8%) died within the first 6 months after operation and five died after an average of 6.6 years, mostly due to cardiovascular causes, three are still alive. As EPS becomes more prevalent with longer duration of PD, large multicenter prospective studies are needed to establish its incidence and identify risk factors, therapeutic approach, and prognosis.