Controversial issues in CKD clinical practice: position statement of the CKD-treatment working group of the Italian Society of Nephrology.

This position paper of the study group "Conservative treatment of Chronic Kidney Disease-CKD" of the Italian Society of Nephrology addresses major practical, unresolved, issues related to the conservative treatment of chronic renal disease. Specifically, controversial topics from everyday clinical nephrology practice which cannot find a clear, definitive answer in the current literature or in nephrology guidelines are discussed. The paper reports the point of view of the study group. Concise and practical advice is given on several common issues: renal biopsy in diabetes; dual blockade of the renin-angiotensin-aldosterone system (RAAS); management of iron deficiency; low protein diet; dietary salt intake; bicarbonate supplementation; treatment of obesity; the choice of conservative therapy vs. dialysis. For each topic synthetic statements, guideline-style, are reported.

Effects of vitamin D on parathyroid hormone and clinical outcomes in peritoneal dialysis: a narrative review.

Vitamin D deficiency is very prevalent in dialysis and peritoneal dialysis (PD) patients show lower levels of cholecalciferol (25(OH)D3) than hemodialysis patients. We conducted a systematic narrative review to assess the effects of vitamin D therapy on control of secondary hyperparathyroidism and clinical outcomes induced by vitamin D pleiotropic effects. Medline database was searched for cohort and intervention studies reporting data on vitamin D (all sterols including synthetic analogs) and peritoneal dialysis without language restriction. Two authors independently extracted data. Twenty-nine observational and eleven interventional studies were identified for inclusion (1,036 subjects). PTH levels decreased in twenty-nine studies, increased in one study and remained stable in ten studies. Thirty-three studies analyzed the oral route for vitamin D administration, ten the intraperitoneal, one the subcutaneous and one the intravenous. A significant decrease of peritonitis risk was observed in two studies. Proteinuria decreased in four studies and remained stable in one study. Peritoneal protein loss decreased in one study and was stable in two studies. Studies on the therapeutic effects of vitamin D in PD are limited and describe small population samples. Moreover, vitamin D compounds do not consistently reduce PTH levels. The administration of active vitamin D in PD may have interesting pleiotropic effects such as decreasing proteinuria and peritoneal protein loss. According to these effects, vitamin D could help to preserve residual renal function and ensure efficient peritoneal membrane dialysance.

Renal anaemia and EPO hyporesponsiveness associated with vitamin D deficiency: the potential role of inflammation.

Resistance to erythropoiesis-stimulating agents (ESAs) has been observed in a considerable proportion of patients with chronic kidney disease (CKD) and it is reportedly associated with adverse outcomes, such as increased cardiovascular morbidity, faster progression to end-stage renal disease (ESRD) and all-cause mortality. The major causes of ESA resistance include chronic inflammation producing suppressive cytokines of early erythroid progenitor proliferation. In addition, pro-inflammatory cytokines stimulate hepcidin synthesis thus reducing iron availability for late erythropoiesis. Recent studies showing an association in deficiencies of the vitamin D axis with low haemoglobin (Hb) levels and ESA resistance suggest a new pathophysiological co-factor of renal anaemia. The administration of either native or active vitamin D has been associated with an improvement of anaemia and reduction in ESA requirements. Notably, these effects are not related to parathyroid hormone (PTH) values and seem to be independent on PTH suppression. Another possible explanation may be that calcitriol directly stimulates erythroid progenitors; however, this proliferative effect by extra-renal activation of 1α-hydroxylase enzyme is only a hypothesis. The majority of studies concerning vitamin D deficiency or supplementation, and degree of renal anaemia, point out the prevalent role of inflammation in the mechanism underlying these associations. Immune cells express the vitamin D receptor (VDR) which in turn is involved in the modulation of innate and adaptive immunity. VDR activation inhibits the expression of inflammatory cytokines in stromal and accessory cells and up-regulates the lymphocytic release of interleukin-10 (IL-10) exerting both anti-inflammatory activity and proliferative effects on erythroid progenitors. In CKD patients, vitamin D deficiency may stimulate immune cells within the bone marrow micro-environment to produce cytokines, inducing impaired erythropoiesis. Immune activation involves the reticuloendothelial system, increasing hepcidin synthesis and functional iron deficiency. Consequences of this inflammatory cascade are erythropoietin (EPO) resistance and anaemia. Given the key role of inflammation in the response to EPO, the therapeutic use of agents with anti-cytokines properties, such as vitamin D and paricalcitol, may provide benefit in the prevention/treatment of ESA hyporesponsiveness.