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Introduction: High serum gamma-glutamyl transferase (GGT) levels are associated with increased mortality in the general population. However, this association has scarcely been investigated in patients with chronic kidney disease (CKD). This study aims to investigate the clinical characteristics of CKD patients with abnormally elevated serum GGT, and its value for predicting mortality., Material and Methods: Retrospective observational study in a population cohort of adults with stage 4-5 CKD not yet on dialysis. Demographic, clinical, and biochemical parameters of prognostic interest were recorded and used to characterise CKD patients with high levels of GGT (>36 IU/l). Cox proportional hazard regression models were used to analyse the influence of baseline serum GGT and alkaline phosphatase (ALP) levels on mortality for whatever reason., Results: The study group consisted of 909 patients (mean age 65±15 years). Abnormally elevated GGT or ALP levels at baseline were observed in 209 (23%) and 172 (19%) patients, respectively, and concomitant elevations of GGT and ALP in 68 (7%). High GGT levels were associated with higher comorbidity burden, and a biochemical profile characterised by higher serum concentration of uric acid, triglycerides, alanine aminotransferase, ferritin, and C-reactive. During the study period, 365 patients (40%) died (median survival time=74 months). In adjusted Cox regression models, high levels of GGT (hazard ratio [HR]=1.39;CI 95%: 1.09-1.78, P=.009) and ALP (HR=1.31; CI95%: 1.02-1.68, P=.038) were independently associated with mortality., Conclusion: High serum levels of GGT are independent predictors of mortality in CKD patients., (Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Background and Aims: The efficacy of phosphate binders is difficult to be estimated clinically. This study analyzes the changes in serum phosphate and urinary phosphate excretion after the prescription of phosphate binders (PB) in patients with chronic kidney disease stage 4-5 pre-dialysis, and the usefulness of the ratio between total urinary phosphate and protein catabolic rate (Pu/PCR) for estimating the efficacy of PB., Methods: This retrospective observational cohort study included adult chronic kidney disease patients. Biochemical parameters were determined baseline and after 45-60 days on a low phosphate diet plus PB ("binder" subgroup=260 patients) or only with dietary advice ("control" subgroup=79 patients)., Results: Phosphate load (total urinary excretion) per unit of renal function (Pu/GFR) was the best parameter correlated with serum phosphate levels (R 2 =0.61). Mean±SD level of Pu/PCR was 8.2±2.3mg of urinary phosphate per each g of estimated protein intake. After treatment with PB, serum phosphate levels decreased by 11%, urinary phosphate 22%, protein catabolic rate 7%, and Pu/PCR 15%. In the control subgroup, Pu/PCR increased by 20%. Urinary phosphate and urea nitrogen excretion correlated strongly, both baseline and after PB or dietary advice., Conclusions: The proposed parameter Pu/PCR may reflect the rate of intestinal phosphate absorption, and therefore, its variations after PB prescription may be a useful tool for estimating the pharmacological efficacy of these drugs., (Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: The cause of vitamin D deficiency in chronic kidney disease (CKD) is probably multi-factorial; however, the relative importance of each potential determinant is uncertain., Aims: To determine factors associated with serum levels of 25-hydroxy vitamin D (25OHD) and their relative importance in a cohort of pre-dialysis CKD patients., Material and Methods: Incident patients admitted to a CKD outpatient clinic were included. Those who were receiving vitamin D supplements or anticonvulsants were excluded. In addition to demographic and clinical data, information about outdoor physical activity, season of blood collection, prescription of statins, anti-angiotensin drugs and xanthine-oxidase inhibitors were included as potential determinants. Johnson's relative weights analysis was used to estimate the relative importance of each potential determinant and the results were expressed as percentage contribution to multiple R., Results: The study group consisted of 397 patients, 30 of whom were excluded. The mean serum level of 25OHD was 13.7±7.4ng/ml, and 81% of patients had serum levels lower than 20ng/ml. By multiple linear regression and relative weights analyses, the best determinants of low serum 25OHD levels and their relative importance were: higher proteinuria (28.5%), old age (21.4%), low physical activity (19.4%), female gender (19.3%) and low serum bicarbonate levels (11.4%)., Conclusions: Proteinuria and age are the determinants with the highest relative importance for predicting 25OHD levels in CKD patients., (Copyright © 2016. Published by Elsevier España, S.L.U.)

Introduction: Chronic musculoskeletal pain (CMP) is a very common symptom in patients with chronic kidney disease (CKD), and is associated with a significant deterioration in quality of life., Aims: To determine the prevalence and clinical characteristics associated with CMP in patients with advanced CKD not on dialysis, and to analyse their relation with other uraemic symptoms and their prognosis significance., Material and Methods: Cross-sectional study to analyse the uraemic symptoms of an unselected cohort of patients with CKD stage 4-5 pre-dialysis. In order to characterise patients with CMP, demographic and anthropometric data were collected, as well as data on comorbidities and kidney function. In addition, inflammatory parameters, uric parameters, bone mineral metabolism including 25-hydroxycholecalciferol (25-OHCC), creatine kinase and drugs of potential interest including allopurinol, statins and erythropoiesis-stimulating agents were recorded., Results: The study group consisted of 1169 patients (mean age 65±15 years, 54% male). A total of 38% of patients complained of CMP, and this symptom was more prevalent in women than in men (49 vs. 28%; P<.0001). Muscle weakness, pruritus, muscle cramps, ecchymosis, insomnia, oedema and dyspnoea were the most common symptoms associated with CMP. There were no significant associations between serum levels of creatine kinase, 25-OHCC, treatment with allopurinol, statins or erythropoiesis-stimulating agents and CMP. The female gender, elderly age, obesity, comorbidity (mainly diabetes, heart failure or COPD), and elevated levels of inflammatory markers (C-reactive protein and non-neutrophilic leukocytes) were the best determinants of CMP. While patients with CMP showed a worse survival rate, a multivariate analysis adjusted for demographic data ruled out the independent association of CMP with mortality., Conclusions: CMP is highly prevalent in patients with advanced CKD and is associated with other common symptoms of chronic uraemia. As with the general population, elderly age, the female gender, obesity and some comorbid conditions are the best determinants of CMP. Increased inflammatory markers commonly observed in patients with CMP may have a relevant role in its pathogenesis., (Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: A relatively high proportion of deaths in dialysis patients occur suddenly and unexpectedly. The incidence of sudden cardiac death (SCD) in non-dialysis advanced chronic kidney disease (CKD) stages has been less well investigated., Objective: This study aims to determine the incidence and predictors of SCD in a cohort of 1078 patients with CKD not yet on dialysis., Methods: Prospective observational cohort study, which included patients with advanced CKD not yet on dialysis (stage 4-5). The association between baseline variables and SCD was assessed using Cox and competing-risk (Fine and Grey) regression models. Demographic, clinical information, medication use, and baseline biochemical parameters of potential interest were included as covariates., Results: During the study period (median follow-up time 12 months), 210 patients died (19%), and SCD occurred in 34 cases (16% of total deaths). All-cause mortality and SCD incidence rates were 113 (95% CI: 99-128), and 18 (95% CI: 13-26) events per 1000 patients/year, respectively. By Cox regression analysis, covariates significantly associated with SCD were: Age, comorbidity index, and treatment with antiplatelet drugs. This latter covariate showed a beneficial effect over the development of SCD. By competing-risk regression, in which the competing event was non-sudden death from any cause, only age and comorbidity index remained significantly associated with SCD., Conclusions: SCD is relatively common in non-dialysis advanced CKD patients. SCD was closely related to age and comorbidity, and some indirect data from this study suggest that unrecognised or undertreated cardiovascular disease may predispose to a higher risk of SCD., (Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Specialised care of patients in advanced stages of chronic kidney disease (CKD) is associated with better survival in dialysis, but it is not known which treatments specifically favour this outcome., Objectives: To analyse normal treatment in advanced stages of CKD and establish which treatments are associated with better survival in dialysis as well as their relationship with causes of death., Material and Method: Cohort, prospective observational study of 591 patients who started dialysis (491 haemodialysis and 100 peritoneal dialysis), who had previously been monitored in the CKD clinic. The treatments analysed were: antihypertensive treatments, statins, antiplatelet drugs, xanthine oxidase inhibitors, correction of metabolic acidosis, treatment with (calcium or non-calcium) phosphate binders, vitamin D (calcitriol or paricalcitol), erythropoietin and the availability of an internal arteriovenous fistula (IAVF). The independent association of each of these treatments with mortality in dialysis was analysed using Cox regression models adjusted for age, sex, pre-dialysis monitoring time, renal function at the start of dialysis, comorbidity, serum albumin and C-reactive protein, and with stratification of the type of dialysis., Results: With a median follow-up period of 28 months, the total number of patients who died was 191 (32%). In the multivariate models, we observed that, in addition to age, the comorbidity index, serum albumin, pre-dialysis treatment with angiotensin-converting-enzyme inhibitors and/or angiotensin receptor blockers, correction of acidosis with sodium bicarbonate and IAVF at the start of haemodialysis were significantly associated with better survival in dialysis. We did not observe differences in causes of death between the different treatments analysed., Conclusion: These results suggest a potential delayed benefit of some treatments in pre-dialysis stages on the outcome of dialysis. Furthermore, beginning dialysis without an IAVF, resulting in the need for intravenous catheters, worsens prognosis in these patients.

Background: Serum phosphate concentrations usually show great variability in patients with advanced chronic kidney disease (ACKD) not on dialysis. Diuretics treatment can have an influence over the severity of mineral-bone metabolism alterations related to ACKD, but their effect on serum phosphate levels is less known., Objectives: This study aims to determine whether diuretics are independently associated with serum phosphate levels, and to investigate the mechanisms by which diuretics may affect phosphate metabolism., Material and Method: 429 Caucasian patients with CKD not on dialysis were included in this cross-sectional study. In addition to conventional serum biochemical measures, the following parameters of renal phosphate excretion were assessed: 24-hours urinary phosphate excretion, tubular maximum phosphate reabsorption (TmP), and fractional excretion of phosphate (FEP)., Results: 58% of patients were on treatment with diuretics. Patients on diuretics showed significantly higher mean serum phosphate concentration (4.78 ± 1.23 vs. 4.24 ± 1.04 mg/dl; P<.0001), and higher TmP per GFR (2.77 ± 0.72 vs. 2.43 ± 0.78 mg/dl; P<.0001) than those not treated with diuretics. By multivariate linear and logistic regression, significant associations between diuretics and serum phosphate concentrations or hyperphosphataemia remained after adjustment for potential confounding variables. In patients with the highest phosphate load adjusted to kidney function, those treated with diuretics showed significantly lower FEP than those untreated with diuretics., Conclusions: Treatment with diuretics is associated with increased serum phosphate concentrations in patients with ACKD. Diuretics may indirectly interfere with the maximum renal compensatory capacity to excrete phosphate. Diuretics should be considered in the studies linking the relationship between serum phosphate concentrations and cardiovascular alterations in patients with CKD.

Although long-term outcomes also improved, graft loss caused by chronic allograft nephropathy remains an important obstacle. This situation, together with the progressive increase in the number of renal transplant patients, means that the population of transplant patients readmitted to a dialysis program will be progressively greater. The mortality rate in patients starting dialysis after graft loss has been reported as variable, though higher than that observed in patients with a functioning graft and that observed in patients on dialysis treatment. However, it is not known how the management of chronic kidney disease patients in the transplant setting differs from that of patients with native kidney disease with a similar degree of renal dysfunction. Many patients in stages 4T-5T have chronic kidney disease related complications that fall below targets established for nontransplant chronic kidney disease patients. A limited number of studies have evaluated patients returning to dialysis after graft failure and the different guidelines in the setting of transplantation have not analyzed this crucial aspect so important. Parting from this premise, a working group of the Spanish Society of Nephrology in the field of kidney transplantation and dialysis has reviewed in-depth each of the clinical aspects of care of patients with kidney transplant failure coming back to dialysis and drawn up a consensus document in order to optimize the management of this condition.

There's no controlled and prospective studies which show the safest and most effective way to reduce or suspend immunosuppression drugs dosage, and only few groups have published their own protocols. There are reasons to discontinue the immunosuppression therapy; the high incidence of infections is the most important. However, a fast withdrawal is not free of problems, like are residual renal function decline and graft intolerance signs, which could take to nephrectomy, a high risk intervention. Most recommended guidelines for immunosuppression use are: - Antimetabolites immediately cancellation and corticoesteroids slow drop (level C recommendation). - Calcineurin inhibitors could be discontinued but if residual renal function is still significant, it is recommended to maintain a low dosage over three to six months; then, withdrawal may be done slowly (level C recommendation). We have not found information supporting the immunosuppression use beyond six months.

In kidney transplantation patient and graft survival are excellent in short-term and mid-term, although they remain stable in the long-term.The incidence of acute rejection has decreased to 8%-15%.Despite marked progress in understanding immunologic mechanisms involved in transplantation, new tools are required to detect early changes that could affect allograft function allowing us to anticipate histological lesions and providing a more accurate use of immunosuppressive drugs.From an immunologic point of view, efforts should be directed to avoid interstitial fibrosis and tubular atrophy (IF/TA) and to prevent antibody-mediated rejection.The most frequent cause of late graft loss is IF/TA.Improvement in kidney transplant results have been achieved with calcineurin inhibitors -CNI- (cyclosporin and tacrolimus), antiproliferative agents (mycophenolate mofetil and enteric-coated mycophenolic acid) and T-cell depleting antibodies. The combination of tacrolimus + mycophenolate mofetil + steroids has been the gold standard in kidney transplant immunosuppression. An adequate balance in order to maintain the appropriate immune response is essential to the patient to avoid infections or neoplasias as well to prevent rejection.In renal transplant recipients with chronic kidney disease stage 4T in which renal function remains stable,immuno-suppressive drugs can be continued at the usual maintenance doses. As GFR declines, CNI and antiproliferative drugs should be reduced.