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.
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.
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.
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.
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.
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.
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.
Microscopic Polyangiitis (MPA) is a systemic pauci-immune necrotizing vasculitis of small-calibre vessels characterized by the absence of granulomas. MPA is an autoimmune disease but its aetiology remains obscure. MPA is associated with presence of antineutrophil cytoplasmatic autoantibodies (ANCAs) but not all patients with MPA have ANCAs. There is strong evidence that not all ANCAs are pathogenetic. It seems that specific epitopes determine ANCAs pathogenicity. Given that MPA is a systemic vasculitis, multiple organs could be affected resulting in a wide spectrum of signs and symptoms. The kidneys and lungs are the most typical organs involved in MPA. Notably, MPA is the major cause of pulmo-renal syndrome. MPA has a poor prognosis if not treated but the use of aggressive immunosuppressive treatment has improved the prognosis and the patient's survival. Rituximab could be considered as an alternative treatment for severe disease, for patients who do not respond adequately to the immunosuppressive treatment and for patients with relapses. However, the long-term safety of Rituximab in MPA is unknown and it should be elucidated by further studies. Interestingly, kidney transplantation is safe and effective and it has a good prognosis in MPA patients with ESRD.
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