No abstract

Background: Chronic kidney disease (CKD) is characterized by progressive kidney dysfunction accompanied by accumulation of uremic toxins and a potential disequilibrium between the redox status and the generation of prooxidants, resulting in oxidative stress and chronic inflammation which is associated with complications (particularly cardiovascular disease) in this population. We aimed to analyze the concentration of total plasma thiols (indicator of antioxidant capacity) and the protein carbonyl content (a marker of carbonyl stress) in relation to kidney function and inflammation in a group of patients with CKD. Patients and Methods: A group of 68 patients with CKD (stages 2–5; mean age 57 ± 12 years, 46% male, 34% diabetics) and another group of 21 patients who underwent living donor kidney transplantation (mean age 36 ± 17 years, 50% male, 10% diabetics, and 9 ± 2 months after renal transplantation) were included in the study. Total plasma thiol and protein carbonyl levels were determined by the DTNB and DNPH methods, respectively, and were adjusted to the plasma albumin concentrations. Plasma levels of fibrinogen and C-reactive protein (CRP) were measured by routine methods and used as markers of inflammation. Results: Mean glomerular filtration rate (GFR) was 48 ml/min, and there was a positive correlation between GFR and thiol (r = 0.25, p < 0.05) and a negative correlation between GFR and carbonyl (r = –0.26, p < 0.05), fibrinogen (r = –0.45, p < 0.0001) and CRP (r = –0.14, p = ns). Carbonyl strongly correlated with CRP (0.49, p < 0.0001) and fibrinogen (0.30, p < 0.01). There was a significant reduction in plasma carbonyl after renal transplantation (1.4 ± 0.4 nmol/mg albumin), compared with the levels before the procedure (2.0 ± 1.4 nmol/mg albumin, p < 0.05), which parallels an improvement in thiol levels (15 ± 4 vs. 21 ± 5 nmol/mg albumin, p < 0.001). In addition, there was a significant correlation between CRP and carbonyl after the transplantation (r = 0.65; p < 0.005). Conclusion: We observed that patients with CKD present an altered redox status and increased signs of carbonyl stress and inflammatory activity as kidney function deteriorates, which was partially but significantly improved after renal transplantation. These findings indicate the importance of renal function in the complications of CKD related to oxidative stress and inflammation.

After the first two years of renal replacement therapy, transplantation demonstrates lower costs to the system when compared to other modalities evaluated. Based on that, this therapy justifies improvements in government policies in this sector.

During the past few years, it has become increasingly evident that residual renal function (RRF) is an important and independent predictor of poor outcome in patients with chronic kidney disease (CKD). Although the causes of this observation are not fully understood, it appears that the loss of RRF impairs both fluid removal and clearance of solutes, which in turn leads to uremic toxicity and increased morbidity and mortality. There is increasing evidence that patients with CKD develop signs of fluid overload already in the early phases of the disease, and this may be a stimulus for inflammatory activation. Recently, an inflammatory component was identified in uremic atherosclerotic and non-atherosclerotic cardiovascular disease (CVD), which have been consistently associated with poor clinical outcome in patients with CKD. Signs of systemic inflammation occur in parallel to the impairment in renal function, and the pathophysiology is most likely multifactorial, including a decrease in cytokine clearance, advanced glycation end-product accumulation, oxidative stress, and principal fluid overload. Additionally, inflammation seems to be a predictor of accelerated loss of renal function. In this article, we discuss the evidence showing that patients with CKD generally have fluid overload, the mechanisms by which impaired renal function may lead to a chronic inflammatory state, and the available information linking fluid overload to accelerated loss of renal function and CVD through inflammation. Inflammation may lead to the development of complications of CKD, in particular CVD, but on the other hand may also lead to a faster progression of renal disease. Strategies aiming to reduce fluid overload may be useful to reduce cardiovascular morbidity and mortality, but also preserve RRF.

This retrospective multicenter (n = 18) cohort study evaluated the incidence, risk factors, and the impact of delayed graft function (DGF) on 1year kidney transplant (KT) outcomes. Of 3992 deceased donor KT performed in 2014-2015, the incidence of DGF was 54%, ranging from 29.9% to 87.7% among centers. Risk factors ( lower-bound-95%CI OR upper-bound-95% CI ) were male gender ( 1.066 1.249 1.463 ), diabetic kidney disease ( 1.053 1.296 1.595 ), time on dialysis ( 1.005 1.007 1.009 ), retransplantation ( 1.035 1.397 1.885 ), preformed anti-HLA antibodies ( 1.011 1.383 1.892 ), HLA mismatches ( 1.006 1.066 1.130 ), donor age ( 1.011 1.017 1.023 ), donor final serum creatinine (sCr) ( 1.239 1.317 1.399 ), cold ischemia time (CIT) ( 1.031 1.043 1.056), machine perfusion ( 0.401 0.542 0.733 ), and induction therapy with rabbit antithymocyte globulin (rATG) ( 0.658 0.800 0.973 ). Duration of DGF > 4 days was associated with inferior renal function and DGF > 14 days with the higher incidences of acute rejection, graft loss, and death. In conclusion, the incidence and duration of DGF were high and associated with inferior graft outcomes. While late referral and poor donor maintenance account for the high overall incidence of DGF, variability in donor and recipient selection, organ preservation method, and type of induction agent may account for the wide variation observed among transplant centers.