Search

OBJECTIVES: To evaluate the safety and efficacy of endovascular intervention with angioplasty and stent placement in patients with transplant renal artery stenosis. METHODS: All patients diagnosed with transplant renal artery stenosis and graft dysfunction or resistant systemic hypertension who underwent endovascular treatment with stenting from February 2011 to April 2016 were included in this study. The primary endpoint was clinical success, and the secondary endpoints were technical success, complication rate and stent patency. RESULTS: Twenty-four patients with transplant renal artery stenosis underwent endovascular treatment, and three of them required reinterventions, resulting in a total of 27 procedures. The clinical success rate was 100%. All graft dysfunction patients showed decreased serum creatinine levels and improved estimated glomerular filtration rates and creatinine levels. Patients with high blood pressure also showed improved control of systemic blood pressure and decreased use of antihypertensive drugs. The technical success rate of the procedure was 97%. Primary patency and assisted primary patency rates at one year were 90.5% and 100%, respectively. The mean follow-up time of patients was 794.04 days after angioplasty. CONCLUSION: Angioplasty with stent placement for the treatment of transplant renal artery stenosis is a safe and effective technique with good results in both the short and long term.

This study showed that indoxyl sulfate, an uremic toxin present in the serum of patients with chronic kidney disease, increases oxidative stress and apoptosis in human neutrophils and reduces the production of monocyte chemoattractant protein-1 (MCP-1) by peripheral blood mononuclear cell (PBMC). It is possible that these effects caused by this toxin contribute to vascular injury of the endothelium and decreased response to infectious insults, respectively.

Background. Recent advances in cell therapies have provided potential opportunities for the treatment of chronic kidney diseases (CKDs). We investigated whether human kidney structures could be preformed in vitro for subsequent implantation in vivo to maximize tissue-forming efficiency. Methods. Human renal cells were isolated from unused donor kidneys. Human renal cells were cultured and expanded. Migration was analyzed using growth factors. To form structures, cells were placed in a three-dimensional culture system. Cells were characterized by immunofluorescence, western blots and fluorescence-activated cell sorting using renal cell-specific markers for podocin, proximal and distal tubules and collecting ducts. An albumin uptake assay was used to analyze function. Three-dimensional cultures were implanted into athymic rat kidneys to evaluate survival. Results. Human renal cells were effectively expanded in culture and retained their phenotype, migration ability and albumin uptake functions. Human renal cell in three-dimensional culture-formed tubules, which stained positively for proximal, distal tubule and collecting duct markers, and this was confirmed by western blot. Polarity of the tubular cells was determined by the presence of Ecadherin, N-cadherin and Na-K ATPase. Colocalization of labeled albumin and proximal tubule markers proved functionality and specificity of the newly formed tubules. An in vivo study showed that cells survived in the kidney for up to 6 weeks. Conclusions. These findings demonstrate that human renal cell grown in three-dimensional culture are able to generate kidney structures in vitro. This system may ultimately be developed into an efficient cell-based therapy for patients with CKD.

The role of nitric oxide (NO) in the pathophysiology of lower urinary tract symptoms (LUTS), detrusor overactivity (DO), and overactive bladder symptoms does not seem to be established. As demonstrated in animal models, interference with the NO/cyclic guanosine monophosphate (cGMP)/cGMP-dependent protein kinase (PKG) pathway at any level (NO synthesis, soluble guanylate cyclase, cGMP, PKG) will lead to DO. One important factor influencing the bladder NO/cGMP/PKG pathway is oxidative stress, in which an abnormal level of reactive oxygen species (ROS) causes tissue damage. ROS may be involved in several bladder pathologies known to show LUTS/DO in animal models, including bladder outlet obstruction, ischemia/reperfusion, and inflammation. The role of ROS in the generation of storage LUTS (including overactive bladder), has not been clarified, though it seems to involve the NO/cGMP/PKG pathway and other mechanisms. To gain further insights into this important field of investigation, new animal models are required to define potential targets for future therapeutic interventions.

The aim of this study was to investigate whether slow graft function (SGF) after transplantation of deceased-donor kidneys affected the prevalence of anemia or the glomerular filtration rate (GFR). We retrospectively evaluated the records of 534 kidney transplant patients who were classified based on their initial renal function, namely, immediate graft function (IGF), slow graft function (SGF), or delayed graft function (DGF). Among the 534 kidney transplant patients studied, the occurrences of each condition were IGF 104, SGF 133, and DGF 297. Six months after transplantation, a greater percentage of DGF patients were anemic compared with the others (P = .028). However, at 12 months after transplantation, SGF patients showed more anemia than the IGF group. DGF and SGF patients displayed similar GFR values at 18 and 24 months after transplantation. However, IGF patients displayed higher GFRs, even when subjects who experienced acute rejection episodes were censored (P = .004). The incidence of acute rejection episodes was similar among SGF and DGF patients. Patients displaying SGF after deceased-donor transplantation showed a greater tendency to be anemic than those displaying IGF. This study also suggested that SGF patients were at risk for acute rejection episodes and/or significantly reduced kidney function as measured by GFR.

Delayed graft function (DGF) is defined as the necessity for dialysis during the first week after transplantation. This study sought to describe patterns of dialysis prescription and evaluate the impact of dialysis dose in acute rejection. Among 82 patients who received a deceased donor kidney transplant, clinical and laboratory data were evaluated at the moment of dialysis indication. Prescribed and delivered dialysis doses (Kt/V and urea reduction ratio) were analyzed during the first dialysis and the first week (Kt/V) after transplantation. We examined the association between Kt/V and acute rejection. Prescribed Kt/V at the first dialysis session was adequate (2.24 +/- 0.51). However, delivered Kt/V was inadequate (0.75 +/- 0.38). Prescribed and delivered Kt/V during the first week after transplantation were suboptimal, namely, 2.45 +/- 1.52 and 1.56 +/- 0.99, respectively. Dialysis dose had no impact on the occurrence of an acute rejection episode. Among DGF patient, dialysis was prescribed late and a low dose was achieved.

New therapeutic strategies for chronic kidney disease (CKD) are necessary to offset the rising incidence of CKD and donor shortage. Erythropoietin (EPO), a cytokine produced by fibroblast-like cells in the kidney, has recently emerged as a renoprotective factor with anti-inflammatory, antioxidant properties. This study (a) determined whether human renal cultures (human primary kidney cells [hPKC]) can be enriched in EPO-positive cells (hPKC(F+)) by using magnetic-bead sorting; (b) characterized hPKC(F+) following cell separation; and (c) established that intrarenal delivery of enriched hPKC(F+) cells would be more beneficial in treatment of renal injury, inflammation, and oxidative stress than unsorted hPKC cultures in a chronic kidney injury model. Fluorescence-activated cell sorting analysis revealed higher expression of EPO (36%) and CD73 (27%) in hPKC(F+) as compared with hPKC. After induction of renal injury, intrarenal delivery of hPKC(F+) or hPKC significantly reduced serum creatinine, interstitial fibrosis in the medulla, and abundance of CD68-positive cells in the cortex and medulla (p < .05). However, only hPKC(F+) attenuated interstitial fibrosis in the renal cortex and decreased urinary albumin (3.5-fold) and urinary tubular injury marker kidney injury molecule 1 (16-fold). hPKC(F+) also significantly reduced levels of renal cortical monocyte chemotactic protein 1 (1.8-fold) and oxidative DNA marker 8-hydroxy-deoxyguanosine (8-OHdG) (2.4-fold). After 12 weeks, we detected few injected cells, which were localized mostly to the cortical interstitium. Although cell therapy with either hPKC(F+) or hPKC improved renal function, the hPKC(F+) subpopulation provides greater renoprotection, perhaps through attenuation of inflammation and oxidative stress. We conclude that hPKC(F+) may be used as components of cell-based therapies for degenerative kidney diseases.

Polymorphonuclear leukocytes (PMNs) from chronic kidney disease (CKD) patients display accelerated apoptosis and dysfunction, which may predispose CKD patients to infections. In this study, we investigated the effect of spermidine and p-cresol on apoptosis and function on PMN from healthy subjects. We measured the effect of spermidine and p-cresol on apoptosis, ROS production unstimulated and stimulated (S. aureus and PMA) and expression of CD95, caspase 3, and CD11b on PMN. After incubation with p-cresol and spermidine, we did not observe any changes in apoptosis, viability or expression of caspase 3 and CD95 in PMN from healthy subjects. PMN incubated for 10 minutes with spermidine demonstrated a significant reduction in spontaneous, S. aureus and PMA-stimulated ROS production. p-cresol induced a decrease in PMA-stimulated ROS production. Spermidine and p-cresol also induced a decrease in the expression of CD11b on PMN. Spermidine and p-cresol decreased the expression of CD11b and oxidative burst of PMN from healthy subjects and had no effect on PMN apoptosis and viability.

In the last two decades, regenerative medicine has shown the potential for “bench-to-bedside” translational research in specific clinical settings. Progress made in cell and stem cell biology, material sciences and tissue engineering enabled researchers to develop cutting-edge technology which has lead to the creation of nonmodular tissue constructs such as skin, bladders, vessels and upper airways. In all cases, autologous cells were seeded on either artificial or natural supporting scaffolds. However, such constructs were implanted without the reconstruction of the vascular supply, and the nutrients and oxygen were supplied by diffusion from adjacent tissues. Engineering of modular organs (namely, organs organized in functioning units referred to as modules and requiring the reconstruction of the vascular supply) is more complex and challenging. Models of functioning hearts and livers have been engineered using “natural tissue” scaffolds and efforts are underway to produce kidneys, pancreata and small intestine. Creation of custom-made bioengineered organs, where the cellular component is exquisitely autologous and have an internal vascular network, will theoretically overcome the two major hurdles in transplantation, namely the shortage of organs and the toxicity deriving from lifelong immuno-suppression. This review describes recent advances in the engineering of several key tissues and organs.

Iron supplementation in hemodialysis patients is fundamental to erythropoiesis, but may cause harmful effects. We measured oxidative stress using labile plasma iron (LPI) after parenteral iron replacement in chronic hemodialysis patients. Intravenous iron saccharate (100 mg) was administered in patients undergoing chronic hemodialysis (N = 20). LPI was measured by an oxidant- sensitive fluorescent probe at the beginning of dialysis session (T0), at 10 min (T1), 20 min (T2), and 30 min (T3) after the infusion of iron and at the subsequent session; P < 0.05 was significant. The LPI values were significantly raised according to the time of administration and were transitory: -0.02 0.20 mmol/L at the beginning of the first session, 0.01 0.26 mmol/L at T0, 0.03 0.23 mmol/L at T1, 0.09 0.28 mmol/L at T2, 0.18 0.52 mmol/L at T3, and -0.02 0.16 mmol/L (P = 0.001 to 0.041) at the beginning of the second session. The LPI level in patients without iron supplementation was -0.06 0.16 mmol/L. Correlations of LPI according to time were T1, T2, and T3 vs. serum iron (P = 0.01, P = 0.007, and P = 0.0025, respectively), and T2 and T3 vs. transferrin saturation (P = 0.001 and P = 0.0003, respectively). LPI generation after intravenous saccharate administration is time-dependent and transitorily detected during hemodialysis. The LPI increment had a positive cor- relation to iron and transferrin saturation. Key Words: Hemodialysis, Intravenous iron, Iron, Labile plasma iron. Anemia is a significant problem in patients under- going chronic hemodialysis treatment in spite of the use of erythropoietin. It is mainly attributed to iron deficiency, which is secondary to decreased iron absorption by the gastrointestinal tract, blood loss into the hemodialysis system or via routine inves- tigations, or to occult gastrointestinal hemorrhage, anticoagulation-related blood loss, and accidental blood loss from arteriovenous fistulas and grafts. On average, maintenance hemodialysis patients are

Background. Despite improvements in immunosuppressive therapy, infections remain a complication of renal transplantation that is associated with increased morbidity and graft rejection. The aim of this study was to evaluate the relationship between initial renal function after deceased donor transplantation and viral infections. Methods. We included patients 18 years and older who received a deceased donor transplantation between January 1995 and December 2004. They were divided into 2 groups: cases from 1994 to 1999, versus from 2000 to 2004. Initial renal function was classified as immediate (IGF), slow (SGF), or delayed (DGF). Infections were classified according to Centers for Disease Control and prevention standards. Results. Among 534 patients, SGF and DGF patients who underwent immunosuppression between 2000 and 2004 show a higher infection rate than IGF patients (P = .005). SGF patients showed a higher incidence of tissue-invasive cytomegalovirus disease (P < .001). Second episodes of viral infections were more common among all patients in this period. However, DGF patients were more susceptible to second episodes of viral infection. In the first group, OKT3 use (P = .013) and donor age (P = .012) were the major risk factors associated with viral infections whereas in the second group, thymoglobulin use (P = .002), acute rejection episode (P = .003), and anemia (P = .044) were the risk factors for viral infection. Conclusion. Initial renal function after deceased donor transplantation was correlated with viral infection. DGF patients had a higher risk for second infection episodes. SGF patients had a higher risk for tissue-invasive cytomegalovirus infection.

End stage renal failure is a devastating condition that involves multiple organ systems in affected individuals. Although management strategies, such as dialysis, are able to prolong survival, renal transplantation is the only definitive treatment that can restore complete kidney function. However, transplantation is limited by several factors, such as critical donor shortage, complications due to chronic immunosuppressive therapy and rejection. Recent advances in cell technologies have facilitated the development of cell-based approaches for kidney tissue regeneration. The kidney exhibits a complex cellular composition, which makes bioengineering renal tissue a challenging task. Isolation and expansion of specific types of renal cells, such as erythropoietin-producing cells, may be a good approach for selective cell therapy. In addition, different cell sources, improved growth environments, novel differentiation factors and the use of synthetic or natural biomaterials have led to exciting regenerative medicine strategies that may be used to restore renal function. Although these approaches hold promise, implementation of these technologies in the clinic is still distant. This chapter reviews current regenerative medicine and tissue engineering strategies that may be used to develop innovative alternatives to improve, restore or replace renal function.

A severe disadvantage of administration of recombinant human erythropoietin to hemodialysis patients has been reported. A significant correlation has been shown with hemoglobin values determined online by use of the blood volume monitor (BVM) and by laboratory measurement. Online hemoglobin and hematocrit were measured by use of the BVM during hemodialysis session. Data were analyzed by t test and statistical significance was defined as a P of0.05. Increases in the mean values of hemoglobin and hematocrit from 11.6 +/- 1.9 to 13.9 +/- 2.4 g/dL (17.4 +/- 7.1%, P = 0.02) and from 34.4 +/- 6.8 to 42 +/- 8.3% (20.6 +/- 8.8%, P = 0.022), respectively, were observed from the beginning to the end of dialysis. We hypothesize that a new strategy for adjusting erythropoietin dose may be based on hemoglobin and hematocrit values evaluated at the end of hemodialysis, when patients are no longer hypervolemic. Inadvertent high levels of hemoglobin could be one explanation why patients present higher rates of cardiovascular and access-related events, especially when monitored online by use of the BVM to achieve the dry weight.

Objective To establish whether the mutation in the Immp2L gene induces renal fibrosis and whether aging exacerbates renal morphology in mice. Methods Female mutant mice with mutation in the inner mitochondrial membrane peptidase 2-like protein at 3 and 18 months of age were used. Renal fibrosis was analyzed using classic fibrosis score, Masson’s trichrome staining, and analysis of profibrotic markers using real time polymerase chain reaction (superoxide dismutase 1, metalloproteinase-9, erythropoietin, transforming growth factor beta), and immunostaining (fibroblasts and Type IV collagen). Oxidative stress markers were determined by immunohistochemistry. The number of renal apoptotic cells was determined. Renal function was estimated by serum creatinine. Results Young mutant mice had significantly more glomerulosclerosis than age-matched mice (p=0.034). Mutant mice had more tubular casts (p=0.025), collagen deposition (p=0.019), and collagen type IV expression (p