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Background Some studies reveal that obesity is associated with a decrease in mortality in haemodialysis (HD) patients. However, few studies have addressed the association between body mass index (BMI) and peritoneal dialysis (PD) patients. Methods We performed this longitudinal, retrospective study to evaluate the impact of obesity on PD patients, using data from the Catalan Registry of Renal Patients from 2002 to 2015 (n = 1573). Obesity was defined as BMI ≥30; low weight: BMI Results Obesity was observed in 20% of patients starting PD. We did not find differences in sex or PD modality, with the obesity group being older (65.9% are ≥55 years versus 59% non-obese, P = 0.003) and presenting more diabetes mellitus and cardiovascular disease (CVD) (47.9% obese versus 25.1% non-obese and 41.7% versus 31.5%, respectively). We did not observe differences in haemoglobin, albumin and Kt/V in obese patients. Regarding peritonitis rate, we did not find any difference between groups, presenting more peritonitis patients on continuous ambulatory peritoneal dialysis and aged ≥65 years [sub-hazard ratio (SHR) = 1.75, P = 0.000 and SHR = 1.56, P = 0.009]. In relation to technique survival, we found higher transfer to HD in the obese group of patients in the univariate analysis, which was not confirmed in the multivariate analysis (SHR = 1.12, P = 0.4), and we did not find differences in mortality rate. In relation to being transplanted, the underweight group, elderly and patients with CVD or diabetic nephropathy presented less probability to undergo kidney transplantation (SHR = 0.65, 0.24, 0.5 and 0.54, P Conclusions Obese and non-obese patients starting on PD had similar outcomes.

Haemodialysis (HD) patients present more morbidity and mortality risk in coronavirus disease 2019 (COVID-19). In patients who may develop severe symptoms, the process called ‘viral sepsis’ seems to be a crucial mechanism. In those cases, the HD procedure provides an excellent tool to explore the benefit of some extracorporeal therapies. We reported the outcome of four HD patients with severe COVID-19 treated with Seraph®100 haemoperfusion (HP) device. Three of the four cases presented a good clinical response after HP. In conclusion, the treatment with Seraph®100 device may be a simultaneous treatment to improve HD patients with severe acute respiratory syndrome coronavirus 2.

Cardiovascular mortality increases with decreasing renal function although the cause is yet unknown. Here, we have investigated whether low chronic inflammation in chronic kidney diseases (CKD) could contribute to increased risk for coronary artery diseases (CAD). Thus, a prospective case&ndash, control study was conducted in patients with CAD and CKD undergoing coronary artery bypass graft surgery with the aim of detecting differences in cardiovascular outcomes, epicardial adipose tissue volume, and inflammatory marker activity associated with renal dysfunction. Expression of membrane CD14 and CD16, inflammatory cytokines and chemokines, mitogen-activated protein (MAP) kinases and hsa-miR-30a-5p were analyzed in peripheral blood mononuclear cells (PBMCs). Epicardial fat volume and tissue inflammation in perivascular adipose tissue and in the aorta were also studied. In the present study, 151 patients were included, 110 with CAD (51 with CKD) and 41 nonCAD controls (15 with CKD). CKD increased the risk of cardiac surgery&ndash, associated acute kidney injury (CSA-AKI) as well as the 30-day mortality after cardiac surgery. Higher counts of CD14++CD16+ monocytes were associated with vascular inflammation, with an increased expression of IL1&beta, and with CKD in CAD patients. Expression of hsa-miR-30a-5p was correlated with hypertension. We conclude that CKD patients show an increased risk of CSA-AKI and mortality after cardiovascular surgery, associated with the expansion of the CD14++CD16+ subset of proinflammatory monocytes and with IL1&beta, expression. We propose that inflammation associated with CKD may contribute to atherosclerosis (ATH) pathogenesis.

Background: Renal transplantation is the treatment of choice for chronic kidney disease (CKD) patients, but the shortage of kidneys and the disabling medical conditions these patients suffer from make dialysis essential for most of them. Since dialysis drastically affects the patients’ lifestyle, there are great expectations for the development of wearable artificial kidneys, although their use is currently impeded by major concerns about safety. On the other hand, dialysis patients with hemodynamic instability do not usually tolerate intermittent dialysis therapy because of their inability to adapt to a changing scenario of unforeseen events. Thus, the development of novel wearable dialysis devices and the improvement of clinical tolerance will need contributions from new branches of engineering such as artificial intelligence (AI) and machine learning (ML) for the real-time analysis of equipment alarms, dialysis parameters, and patient-related data with a real-time feedback response. These technologies are endowed with abilities normally associated with human intelligence such as learning, problem solving, human speech understanding, or planning and decision-making. Examples of common applications of AI are visual perception (computer vision), speech recognition, and language translation. In this review, we discuss recent progresses in the area of dialysis and challenges for the use of AI in the development of artificial kidneys. Summary and Key Messages: Emerging technologies derived from AI, ML, electronics, and robotics will offer great opportunities for dialysis therapy, but much innovation is needed before we achieve a smart dialysis machine able to analyze and understand changes in patient homeostasis and to respond appropriately in real time. Great efforts are being made in the fields of tissue engineering and regenerative medicine to provide alternative cell-based approaches for the treatment of renal failure, including bioartificial renal systems and the implantation of bioengineered kidney constructs.

Item does not contain fulltext BACKGROUND: In a previous trial involving patients with early autosomal dominant polycystic kidney disease (ADPKD; estimated creatinine clearance, >/=60 ml per minute), the vasopressin V2-receptor antagonist tolvaptan slowed the growth in total kidney volume and the decline in the estimated glomerular filtration rate (GFR) but also caused more elevations in aminotransferase and bilirubin levels. The efficacy and safety of tolvaptan in patients with later-stage ADPKD are unknown. METHODS: We conducted a phase 3, randomized withdrawal, multicenter, placebo-controlled, double-blind trial. After an 8-week prerandomization period that included sequential placebo and tolvaptan run-in phases, during which each patient's ability to take tolvaptan without dose-limiting side effects was assessed, 1370 patients with ADPKD who were either 18 to 55 years of age with an estimated GFR of 25 to 65 ml per minute per 1.73 m(2) of body-surface area or 56 to 65 years of age with an estimated GFR of 25 to 44 ml per minute per 1.73 m(2) were randomly assigned in a 1:1 ratio to receive tolvaptan or placebo for 12 months. The primary end point was the change in the estimated GFR from baseline to follow-up, with adjustment for the exact duration that each patient participated (interpolated to 1 year). Safety assessments were conducted monthly. RESULTS: The change from baseline in the estimated GFR was -2.34 ml per minute per 1.73 m(2) (95% confidence interval [CI], -2.81 to -1.87) in the tolvaptan group, as compared with -3.61 ml per minute per 1.73 m(2) (95% CI, -4.08 to -3.14) in the placebo group (difference, 1.27 ml per minute per 1.73 m(2); 95% CI, 0.86 to 1.68; P3 times the upper limit of the normal range) occurred in 38 of 681 patients (5.6%) in the tolvaptan group and in 8 of 685 (1.2%) in the placebo group. Elevations in the aminotransferase level were reversible after stopping tolvaptan. No elevations in the bilirubin level of more than twice the upper limit of the normal range were detected. CONCLUSIONS: Tolvaptan resulted in a slower decline than placebo in the estimated GFR over a 1-year period in patients with later-stage ADPKD. (Funded by Otsuka Pharmaceuticals and Otsuka Pharmaceutical Development and Commercialization; REPRISE ClinicalTrials.gov number, NCT02160145 .).

Background Cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD). Single nucleotide polymorphisms (SNPs) in ANRIL gene have been associated with higher cardiovascular morbidity and mortality in general population. The main objective was to ascertain whether ANRIL polymorphisms could identify risk of major adverse cardiovascular event (MACE) in patients starting on hemodialysis (HD). Methods This was a prospective observational cohort study. 284 CKD patients starting on HD were included in the study and followed until achievement of the primary end-point (MACE) or end of the study. All patients were genotyped for four ANRIL SNPs (rs10757278, rs4977574, rs10757274 and rs6475606). Kaplan-Meier curves and multivariate Cox survival analyses, together with multiple logistic regression were used to analyze the association between ANRIL SNPs and MACE. Results We found that ANRIL SNP rs10757278 was a representative SNP of a strong linkage disequilibrium block and showed significant genotypic associations with MACE in hemodialysis patients. Homozygous patients for the risk allele (GG) showed 2.17 (1.05–4.49) fold increased risk of MACE during hemodialysis than carriers of the protective allele (AA or AG). Diabetes mellitus was a strong enhancer of this effect. Conclusions Our results indicate that ANRIL polymorphisms may confer risk to development of MACE in incident patients on hemodialysis.

Background: Chronic Kidney Disease (CKD) and inflammation are risk factors for atherosclerotic vascular disease (ASVD). In inflammatory conditions, Nuclear Factor-kappa B (NF-kappa B) is frequently activated and it has been detected in human ASVD. In this work, we investigated if the degree of inflammation and of NF-kappa B activation were increased in the aorta of patients with CKD. Methods: This is a case-control pilot study performed on 30 abdominal aorta samples from 10 human autopsies. Cases were patients with CKD and controls patients with normal glomerular filtration rate (eGFR). Infiltrating mononuclear cells (S100(+), CD3(+), CD40(+), CD40L(+)) and activation of NF-kappa B were identified by immunohistochemistry. Findings: The number of cells in the intima which showed activated nuclear NF-.B correlated with severity of ASVD lesions (r = 0.56, p = 0.003), with numbers of CD3(+) lymphocytes in adventitia (r = 0.50, p = 0.008), with numbers of CD40(+) cells in the intima (r = 0.59, p = 0.002) or in the adventitia (r = 0.45, p = 0.02), and with numbers of CD40L(+) cells in the intima (r = 0.51, p = 0.011). Increased numbers of S100(+) Intimal Dendritic cells (IDCs) were associated with ASVD (p = 0.03) and CKD (p = 0.01). Conclusions: Number of CD3(+) cells, of CD40(+) cells, of CD40L(+) cells and the degree of NF-kappa B activation were increased in ASVD lesions suggesting a role for the adaptive T cell in the development of ASVD lesions. IDCs were associated both with ASVD and CKD suggesting a role of these cells in the pathogenesis of ASVD in CKD.

After transplantation, glomerular volumes increases and large glomerular volume at 4 months is associated with better renal function. The aim is to characterize glomerular adaptation after the fourth month in two serial protocol biopsies and its relationship with subclinical rejection and chronic allograft nephropathy (CAN). Mean glomerular volume (Vg) was estimated according to the Weibel and Gomez method in a 4-month and 1-year serial protocol biopsies in 61 stable grafts. Glomerular enlargement (deltaVg) was calculated as the Vg difference between both biopsies. Banff schema was used to evaluate renal biopsies. Vg increased from 4.4+/-2.4 to 5.7+/-2.6 x 10(6) microm3 (P0.001). Mean deltaVg was 1.0 x 10(6) microm3. Patients with deltaVg1 were considered as patients with impaired glomerular enlargement (n=29). Impaired glomerular enlargement was associated with increased acute index score in the 4-month (1.83+/-1.56 vs 1.06+/-1.48; P0.05) and 1-year protocol biopsies (1.52+/-1.59 vs 0.62+/-1.07; P0.05). Impaired glomerular enlargement was also associated with increased progression of chronic lesions between the 4-month and 1-year biopsy in the glomerular (0.17+/-0.38 vs 0.55+/-0.63; P0.01), tubular (0.38+/-0.56 vs 0.83+/-0.85; P0.01), and interstitial compartment (0.41+/-0.57 vs 0.90+/-0.86; P0.01). The proportion of sclerotic glomeruli between both biopsies increased in patients with impaired glomerular enlargement (1.5+/-3.9 to 5.3+/-10.1, P0.05) while it did not modify in patients with glomerular enlargement (2.1+/-7.3 vs 2.6+/-4.5; P=NS). During the first year, glomeruli enlarge but this adaptation mechanism is impaired in patients with subclinical rejection. Moreover, impaired glomerular enlargement is associated with progression of CAN.

Introduction. The presence of chronic allograft nephropathy (CAN) in protocol biopsies is negatively associated with graft survival. Although recent studies have indicated that the resistive index (RI) is a predictor of graft failure, it does not correlate with CAN in stable grafts. We therefore studied the relationship between RI and CAN and examined the predictive value of both parameters on graft outcome. Methods. Included were patients transplanted between 1997 and 2002 and who had protocol biopsies and RI determinations. Renal lesions were blindly evaluated according to Banff 97 criteria. Mean glomerular volume, cortical interstitial volume fraction and intimal arterial volume fraction were estimated using a point counting technique. RI was determined before biopsy in at least two different renal locations. The outcome variable was defined as graft failure or a 30% serum creatinine increase between protocol biopsy and last follow-up. Results. Eighty-seven patients were included. RI correlated with recipient age (R ¼ 0.52, P

Protein kinase Emk1/Par1 (GenBank accession no. X97630) has been identified as a regulator of the immune system homeostasis. Since immunological factors are critical for the development of chronic allograft nephropathy (CAN), we reasoned that expression of Par1/Emk1 could be altered in kidney allografts undergoing CAN. In this paper, we have analysed the association among renal allograft lesions and expression of Par1/Emk1, studied by RT-PCR on total RNA from 51 protocol biopsies of transplanted kidneys, five normal kidneys, and five dysfunctional allografts. The most significant result obtained has been the detection of alterations in the normal pattern of alternative splicing of the Par1/Emk1 transcript, alterations that included loss of expression of constitutively expressed isoforms, and the inclusion of a cryptic exon to generate a new Emk1 isoform (Emk1C). Expression of Emk1C was associated with an increase in the extension of the interstitial infiltrate (0.88+/-0.33 in Emk1C([+]) vs. 0.41+/-0.50 in Emk1C([-]); P0.011), and with a trend to display higher interstitial scarring (0.66+/-0.70 vs. 0.29+/-0.52; P=0.09) in protocol biopsies when evaluated according to the Banff schema. Moreover, a higher mean arterial pressure (MAP) was also observed (110+/-11 vs. 99+/-11 mm Hg; P=0.012). From these results we propose that Par1/Emk1 could have a role in the development of CAN in kidney allografts.

Endothelin (ET) is known to play a role in the pathogenesis of warm ischaemic renal damage, however, little is known about its involvement in renal cold ischaemia. This study was designed to investigate the response of ET after kidney cold ischaemia, and to assess the potential protective effect of bosentan, a dual, non-selective ET(A)/ET(B) receptor antagonist, against cold ischaemia reperfusion injury in a rat model of syngeneic renal transplantation.Kidneys from Lewis rats were transplanted, either immediately or after 5 h of cold preservation. After 48 h, contralateral nephrectomy was performed. Rats were organized into three groups: Tr-NoISC, no cold ischaemia; Tr-ISC, 5 h cold ischaemia; and Tr-BOS, 5 h cold ischaemia plus bosentan (100 mg/kg/day, from the day before transplantation until the seventh day post-transplantation). On day 7, plasma and tissue immunoreactive ET (irET), as well as ET mRNA tissue expression, were evaluated. Renal function was measured by means of serum creatinine on days 3, 4, 5 and 7, and by creatinine clearance on day 7. Conventional histology was performed.The ischaemic group had significantly higher plasma irET levels than the non-ischaemic group and significantly lower levels than the bosentan group. Tissue irET levels and ET mRNA expression were similar in the ischaemic and bosentan groups and were higher than in the non-ischaemic group. Throughout the follow-up, serum creatinine was significantly higher in the ischaemic group than in the bosentan group. Moreover, creatinine decreased rapidly in the bosentan group after nephrectomy, whereas it continued to increase for 48 h in the ischaemic group. Kidneys from the ischaemic group showed a higher degree of tubular-cell necrosis and epithelial-cell detachment than kidneys from the bosentan group.We conclude that cold ischaemia and preservation damage induces an increase in renal ET mRNA and irET expression in the reperfusion phase, contributing both to the deterioration of renal function and to tubular necrosis. Bosentan is effective in protecting kidneys from this cold ischaemia reperfusion damage. Non-selective ET(A)/ET(B) receptor antagonists might be potentially useful in clinical renal transplantation.

Background. Cyclosporine (CsA) nephrotoxicity can be identified by functional changes and chronic renal damage. CsA-associated renal fibrosis has been related to the overproduction of transforming growth factor (TGF)-β 1 , a fibrogenic cytokine. Mycophenolate mofetil (MMF) may allow CsA dose reduction without increasing the risk of rejection. Methods. We studied the impact of CsA dose reduction in association with MMF on renal function and TGF-β 1 production in 16 long-term renal allograft recipients with suspected CsA nephrotoxicity. Two grams/day of MMF were introduced, and CsA dose was reduced to reach whole-blood levels between 40 and 60 ng/ml within 1 month. CsA dose and levels, renal function parameters, and platelet-poor plasma TGF-β 1 levels were evaluated before and 6 months thereafter. Results. MMF allowed a decrease in both the mean dose of CsA (3.8±1.35 vs. 2.2±0.73 mg/kg/day; P

Background: Patients undergoing conventiona l hemodialysis (C-HD) present a greater immuno-inflam- matory state probably related to uremia, sympathetic nervous system (SNS) activation and /or membrane bioincompat ibility, which could improve with a technique-switch ing to online hemodiafiltration (OL-HD). The antigen-indep endent pathway activation of this modified immunologic state turns dendritic cells (DC) into an accurate cell model to study these patients. The aim of this study is to further evaluate the immune-inflammat ory state of patients in C-HD assessed by DC maturation. Methods: 31 patients were submitted to C-HD and after 4 months switched to the OL-HD technique. Monocytes-derive d DCs from HD patients were cultured in the presence of IL-4/GM-CSF. DC-maturation was evaluated by assessing the maturation phenotype by flow cytometry (FACs). DCs-functiona l capacity to elicit T-cell alloresponse was studied by mixed leuco- cyte reaction. Cytokine release was assessed by FACs and SNS was evaluated measuring renalase levels by ELISA. Results: An up-regulation of maturation markers was observed in C-HD DCs which induced two fold more T cells proliferation than OL-HD DCs. Also, C-HD-mDCs presented with over-produc- tion of pro-inflammatory cytokines (IL-6, IL-1 β , IL-8, IL-10 and TNF- α ) compared with OL- HD-mDC (P < 0·05). Results were correlated with clinical data. When SNS was evaluated, hypotension events and blood pressure were significantly lower and renalase levels were significantly higher after conversion to OL-HD. Diabetes mellitus type 2 patients also found beneficial reduction of mDC when converted to OL-HD compared to non-diabetics. Conclusions: OL-HD could interfere with immuno-inflammatory state in HD patients with an improvement of renalase levels as potential key mediators in the mechanistic pathway of down-regulation of DC maturation

Background Subclinical rejection and interstitial fibrosis and tubular atrophy (IF/TA) in protocol biopsies are associated with outcome. We study the relationship between histologic lesions in early protocol biopsies and histologic diagnoses in late biopsies for cause. Materials and methods Renal transplants with a protocol biopsy performed within the first 6 months posttransplant between 1988 and 2006 were reviewed. Biopsies were evaluated according to Banff criteria, and C4d staining was available in biopsies for cause. Results Of the 517 renal transplants with a protocol biopsy, 109 had a subsequent biopsy for cause which showed the following histological diagnoses: chronic humoral rejection (CHR) (n=44), IF/TA (n=42), recurrence of the primary disease (n=11), de novo glomerulonephritis (n=7), T-cell-mediated rejection (n=4), and polyoma virus nephropathy (n=1). The proportion of retransplants (15.9% vs. 2.3%, P=0.058) and the prevalence of subclinical rejection were higher in patients with CHR than in patients with IF/TA (52.3% vs. 28.6%, P=0.0253). Demographic donor and recipient characteristics and clinical data at the time of protocol biopsy were not different between groups. Logistic regression analysis showed that subclinical rejection (relative risk, 2.52; 95% confidence interval, 1.1-6.3; P=0.047) but not retransplantation (relative risk, 6.7; 95% confidence interval, 0.8-58.8; P=0.085) was associated with CHR. Conclusion Subclinical rejection in early protocol biopsies is associated with late appearance of CHR.

BACKGROUND Detection of markers predicting allograft rejection is important for risk assessment before kidney transplantation, as well as to minimize posttransplantation immunosuppression. METHODS We studied the expression of CD25, HLA-DR, CD134, CD62L, and CD44 by flow cytometry in CD4, CD8, and CD3 cells, from pretransplant blood samples from 91 transplanted patients accounting for 16 episodes of acute renal rejection in the first month after transplantation. RESULTS None of the activation markers showed a significant association to acute rejection. Early rejectors showed less pretransplant CD3CD25 cells than nonrejectors (0.79%±0.50% vs. 1.51%±0.79% of CD3 cells; P=0.001) and a lower CD3CD25/CD3HLA-DR ratio (0.043±0.034 vs. 0.111±0.079; P

Grafts with subclinical rejection associated with interstitial fibrosis and tubular atrophy (SCR+IF/TA) show poorer survival than grafts with subclinical rejection without IF/TA (SCR). Aiming to detect differences among SCR+IF/TA and SCR, we immunophenotyped the inflammatory infiltrate (CD45, CD3, CD20, CD68) and used a low-density array to determine levels of T(H)1 (interleukin IL-2, IL-3, gamma-interferon, tumor necrosis factor-alpha, lymphotoxin-alpha, lymphotoxin-beta, granulocyte-macrophage colony-stimulating factor) and T(H)2 (IL-4, IL-5, IL-6, IL-10, and IL-13) transcripts as well as of IL-2R (as marker for T-cell activation) in 31 protocol biopsies of renal allografts. Here we show that grafts with early IF/TA and SCR can be distinguished from grafts with SCR on the basis of the activation of IL-10 gene expression and of an increased infiltration by B-lymphocytes in a cellular context in which the degree of T-cell activation is similar in both groups of biopsies, as demonstrated by equivalent levels of IL-2R mRNA. These results suggest that the up-regulation of the IL-10 gene expression, as well as an increased proportion of B-lymphocytes in the inflammatory infiltrates, might be useful as markers of early chronic lesions in grafts with SCR.

Chronic allograft nephropathy (CAN) in protocol biopsies is associated with graft loss while the association between subclinical rejection (SCR) and outcome has yielded contradictory results. We analyze the predictive value of SCR and/or CAN in protocol biopsies on death-censored graft survival. Since 1988, a protocol biopsy was done during the first 6 months in stable grafts with serum creatinine

Long-term consequences of glomerular enlargement after transplantation are not well understood. The aim is to evaluate the relationship between glomerular volume (Vg) estimated in protocol biopsies, graft function and graft survival. Vg and Banff chronic damage score were evaluated in protocol biopsies at 4 months. Creatinine clearance (CrCl) was estimated by the Cockroft-Gault formula. Vg estimated in 144 patients was 4.8 +/- 2.0 x 10(6)mu(3). It was associated with donor age (r = 0.23, p0.01), recipient body mass index (r = 0.17, p = 0.04), delayed graft function (Vg = 5.9 +/- 2.3 vs. 4.6 +/- 1.9 x 10(6)mu(3), p0.01) and CrCl (r = 0.17, p = 0.04). The best cutoff of Vg, Banff chronic damage score and CrCl was determined by Cox regression analysis, being 5.0 x 10(6)mu(3) for Vg (relative risk (RR): 2.4, 95% confidence interval (CI): 1.03-5.6),2 for chronic damage score (RR: 3.4, 95% CI: 1.03-8.9) and 60 mL/min for CrCl (RR: 3.5, 95% CI: 1.04-11.9). These variables were independent predictors of death-censored graft survival. According to Vg and CrCl, four groups of patients were defined. Patients with small glomeruli and high CrCl had a 95% graft survival while patients with large glomeruli and low CrCl had a 45% graft survival at 15 years (p0.01). Large glomerular volume, high Banff chronic score and poor early renal function in stable grafts are independently associated with death-censored graft survival.

Genotype DD of the angiotensin-converting enzyme (ACE) is not associated with an increased incidence of native renal diseases, although it could modulate progression to renal failure in patients who already display chronic lesions. Because its role in renal allograft degeneration is not well characterized, whether ACE genotype was associated with the prevalence of chronic allograft nephropathy (CAN) was studied, in a group of protocol biopsies from 180 patients, or with the incidence of CAN in 152 patients with at least two sequential biopsies. As a control group, ACE genotype was also studied in 41 donors and 72 healthy subjects. For analyzing the influence of ACE genotype in graft survival, patients were grouped into six categories (II-normal biopsy, ID-normal, DD-normal, II-CAN, ID-CAN and DD-CAN). Finally, relative renal ACE mRNA levels were measured in 67 cases by real-time PCR using the delta threshold cycle method. ACE-DD genotype was more frequent in patients who received a transplant than in control subjects (43.3% versus 30.1%, P = 0.026), but prevalence (DD = 42.7% versus non-DD = 42.2%) or incidence (DD = 24.6% versus non-DD = 29.9%) of CAN was not different regarding recipient ACE genotype. Furthermore, patients with the ACE-DD genotype and CAN had the poorest graft survival (II-normal = 100%, ID-normal = 91%, DD-normal = 84%, II-CAN = 100%, ID-CAN = 66%, and DD-CAN = 36%; P = 0.034) and higher ACE mRNA levels than non-DD and CAN (DD = -3.36 +/- 2.35 versus non-DD = -5.65 +/- 1.72-fold in ACE copies; P = 0.012). It is concluded that ACE-DD genotype is not associated with an increased prevalence or incidence of CAN but is actually associated with higher ACE mRNA levels and poorer graft survival in patients who already display CAN.

Aim: To evaluate the utility of intimal thickness and interstitial width as a primary efficacy variable in the design of clinical trials aimed to modify the natural history of chronic allograft nephropathy. Methods: A donor and a 4-month protocol biopsy were evaluated in 40 stable grafts according to the Banff schema. In 27 patients, a second protocol biopsy was done at 1 yr. Arterial intimal volume fraction (Vvintima/artery) and cortical interstitial volume fraction (Vvinterstitium/cortex) were estimated with a point counting technique. Results: Chronic Banff scores increased during follow-up, while acute scores reached its peak at 4 months. Vvintima/artery and Vvinterstitium/cortex significantly increased at 4 months, but not at 1 yr. Vvintima/artery at 4 months correlated with donor Vvintima/artery (r = 0.57, p

The present study examined the long-term consequences of warm renal ischemia (WRI) with or without renal ablation. Male Sprague-Dawley rats (250–300 g) were subjected to 60 min of complete WRI by pedicle clamping and then followed for 52 wk. Animals were organized into four groups: rats in which both kidneys were subjected to warm ischemia (2WIK); rats with left WRI and right nephrectomy (1WIK); uninephrectomized rats with a left nonischemic kidney (1NK); and sham-operated rats (2NK). Additional animals were studied at 24 h, 7 days, and 16 and 32 wk. In the first week after WRI, rats from the 2WIK and 1WIK groups displayed a similar degree of acute renal damage. After recovering from acute renal failure, 1WIK rats developed progressive and severe proteinuria, whereas it was mild in the 2WIK group, as well as in the 1NK and 2NK groups. Only animals from the 1WIK group developed severe chronic renal failure, glomerulosclerosis, interstitial fibrosis, and upregulation of transforming growth factor-β1(TGF-β1) gene, which was associated with increased TGF-β1protein expression in tubular epithelial cells, arterioles, and in areas of mononuclear interstitial cell infiltrate. On the contrary, long-term renal TGF-β1expression, function, and histology were similar in 2WIK and 2NK rats. The present study shows that prolonged bilateral WRI, when both kidneys are retained in place, induces very mild long-term renal lesions as opposed to the severe renal scarring observed when WRI is combined with contralateral nephrectomy.

Renal ischemia—reperfusion injury is a complex sequence of events that leads to organ lesion. Ischemia depletes cells of energetic adenosine nucleotides, altering the membrane ionic ATP-dependent pumps which favours the entry of calcium, sodium and water to the cytoplasma. The catabolism of adenine nucleotides results in an accumulation of hypoxanthine. The supply of molecule oxygen during blood reperfusion generates oxygen free radicals which are highly reactive for lipidic cellular membranes in the same sites in which they are produced. The increase in intracellular calcium is thought to activate membrane phospholipase A2 which leads to the activation of arachidonic acid cascade and the generation of platelet activating factor. As a result, polimorphonuclear cells interact with endothelial cells. This interaction is regulated by selectins, platelet activating factor and integrins. Polymorphonuclear cells become activated and produce oxygen free radicals via the respiratory burst, and proteases. The altered endothelium in ischemia-reperfusion injury results in an imbalance of the ratio between endothelin and nitric oxide that entails a vasoconstrictory state which impairs renal function [1, 2]. Thus, ischemia-reperfusion injury may be considered an inflammatory and vasomotor phenomenon. In renal transplantation, ischemia-reperfusion injury hampers organ function recovery. The absence of immediate renal allograft function is usually known as delayed graft function (DGF), and commonly defined as the need for dialysis during the first week of transplantation.

Reliability of chronic allograft nephropathy diagnosis in sequential protocol biopsies.BackgroundChronic allograft nephropathy (CAN) progresses rapidly during the first few months and slowly thereafter. Although the presence of CAN in protocol renal biopsies is a predictor of outcome, the reliability of this diagnosis according to Banff criteria has not been characterized.MethodsRenal lesions were evaluated according to the Banff criteria in sequential protocol biopsies performed at 4 and 14 months in 310 biopsies obtained from 155 patients.ResultsCAN progressed from 40 to 53% (P = 0.001) while serum creatinine remained stable (146 ± 44 vs. 147 ± 48 μmol/L, P = NS). Graft survival in patients with and without CAN in the first biopsy was 74 versus 91% (P < 0.05), and in the second biopsy 75 versus 94% (P < 0.05). In 54 patients (35%) no CAN was present in both biopsies, 39 (25%) showed progression to CAN, 19 (12%) showed regression of CAN, and 43 (28%) showed CAN in both biopsies. Graft survival was: 100%, 81.6%, 82.6% and 69.4%, respectively (P < 0.01). Assuming that CAN does not regress and sampling error is normally distributed, we estimated that 25% of biopsies cannot be properly classified.ConclusionsThe increase in the incidence of CAN between the 4th and 14th month is lower than the proportion of misclassified biopsies. Thus, monitoring the progression of CAN by means of two sequential biopsies at 4 and 14 months is inaccurate. We suggest that progression of scarring be monitored by means of a donor and a protocol biopsy performed during the first year evaluated with a quantitative approach.