Human Proenkephalin A 119-159 (penKid) in Extracorporeal Therapies: Ex vivo Sieving Coefficient, Diffusive Clearance, and Hemoadsorption Kinetics.

INTRODUCTION: Enkephalins, endogenous opioid peptides, are involved in the regulation of renal function. One derived molecule, proenkephalin A, also known as penKid, has been demonstrated to be a reliable biomarker for kidney function and its plasma concentration correlates with measured glomerular filtration rate. penKid is used for prediction and diagnosis of AKI and need of renal replacement therapy (RRT). penKid has also been used to predict the successful weaning from RRT in patients with AKI. Whether the concentration of penKid is affected or not by RRT is a controversial point and there are no studies describing the kinetics of the molecule in such conditions. The low molecular weight (4.5 kDa) would imply free removal by the glomerulus and the dialysis membranes. During RRT, this reduction could not be detected in clinical practice due to the complex kinetics involving either low dialytic clearance or increased production in response to impaired kidney function. The aim of this study was to determine the sieving coefficient and the diffusive clearance of the penKid molecule in conditions of in vitro continuous veno-venous hemofiltration (CVVH) and continuous veno-venous hemodialysis (CVVHD), respectively, and also the penKid removal ratio in conditions of in vitro hemoadsorption (HA) using a synthetic microporous resin. METHODS: Blood spiked with a lyophilized penKid peptide solved in 20 mm dipotassium phosphate and 6 mm disodium EDTA [pH 8] to reach target concentrations is used as testing solution. In each experiment, the blood batch was adjusted at a volume of 1,000 mL, maintained at 37°, and continuously stirred. Samples were collected from blood, ultrafiltrate, and spent dialysate at different times during the experiments. Sieving, clearance, and removal ratio were calculated. RESULTS: Significant removal of penKid was observed in CVVH (sieving 1.04 ± 0.27), in CVVHD (clearance 23.08 ± 0.89), and in HA (removal ratio 76.1 ± 1% after 120 min). CONCLUSION: penKid is effectively removed by extracorporeal therapies. In presence of anuria, penKid generation kinetics can be calculated based on extracorporeal removal and volume variation. In steady state conditions, declining values may be the result of an initial renal function recovery and may suggest discontinuation and successful liberation from RRT.

COVID-19-related mortality in kidney transplant and haemodialysis patients: a comparative, prospective registry-based study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has exposed haemodialysis (HD) patients and kidney transplant (KT) recipients to an unprecedented life-threatening infectious disease, raising concerns about kidney replacement therapy (KRT) strategy during the pandemic. This study investigated the association of the type of KRT with COVID-19 severity, adjusting for differences in individual characteristics. METHODS: Data on KT recipients and HD patients diagnosed with COVID-19 between 1 February 2020 and 1 December 2020 were retrieved from the European Renal Association COVID-19 Database. Cox regression models adjusted for age, sex, frailty and comorbidities were used to estimate hazard ratios (HRs) for 28-day mortality risk in all patients and in the subsets that were tested because of symptoms. RESULTS: A total of 1670 patients (496 functional KT and 1174 HD) were included; 16.9% of KT and 23.9% of HD patients died within 28 days of presentation. The unadjusted 28-day mortality risk was 33% lower in KT recipients compared with HD patients {HR 0.67 [95% confidence interval (CI) 0.52-0.85]}. In a fully adjusted model, the risk was 78% higher in KT recipients [HR 1.78 (95% CI 1.22-2.61)] compared with HD patients. This association was similar in patients tested because of symptoms [fully adjusted model HR 2.00 (95% CI 1.31-3.06)]. This risk was dramatically increased during the first post-transplant year. Results were similar for other endpoints (e.g. hospitalization, intensive care unit admission and mortality >28 days) and across subgroups. CONCLUSIONS: KT recipients had a greater risk of a more severe course of COVID-19 compared with HD patients, therefore they require specific infection mitigation strategies.

Neutrophil Gelatinase-Associated Lipocalin Measured on Clinical Laboratory Platforms for the Prediction of Acute Kidney Injury and the Associated Need for Dialysis Therapy: A Systematic Review and Meta-analysis.

RATIONALE & OBJECTIVE: The usefulness of measures of neutrophil gelatinase-associated lipocalin (NGAL) in urine or plasma obtained on clinical laboratory platforms for predicting acute kidney injury (AKI) and AKI requiring dialysis (AKI-D) has not been fully evaluated. We sought to quantitatively summarize published data to evaluate the value of urinary and plasma NGAL for kidney risk prediction. STUDY DESIGN: Literature-based meta-analysis and individual-study-data meta-analysis of diagnostic studies following PRISMA-IPD guidelines. SETTING & STUDY POPULATIONS: Studies of adults investigating AKI, severe AKI, and AKI-D in the setting of cardiac surgery, intensive care, or emergency department care using either urinary or plasma NGAL measured on clinical laboratory platforms. SELECTION CRITERIA FOR STUDIES: PubMed, Web of Science, Cochrane Library, Scopus, and congress abstracts ever published through February 2020 reporting diagnostic test studies of NGAL measured on clinical laboratory platforms to predict AKI. DATA EXTRACTION: Individual-study-data meta-analysis was accomplished by giving authors data specifications tailored to their studies and requesting standardized patient-level data analysis. ANALYTICAL APPROACH: Individual-study-data meta-analysis used a bivariate time-to-event model for interval-censored data from which discriminative ability (AUC) was characterized. NGAL cutoff concentrations at 95% sensitivity, 95% specificity, and optimal sensitivity and specificity were also estimated. Models incorporated as confounders the clinical setting and use versus nonuse of urine output as a criterion for AKI. A literature-based meta-analysis was also performed for all published studies including those for which the authors were unable to provide individual-study data analyses. RESULTS: We included 52 observational studies involving 13,040 patients. We analyzed 30 data sets for the individual-study-data meta-analysis. For AKI, severe AKI, and AKI-D, numbers of events were 837, 304, and 103 for analyses of urinary NGAL, respectively; these values were 705, 271, and 178 for analyses of plasma NGAL. Discriminative performance was similar in both meta-analyses. Individual-study-data meta-analysis AUCs for urinary NGAL were 0.75 (95% CI, 0.73-0.76) and 0.80 (95% CI, 0.79-0.81) for severe AKI and AKI-D, respectively; for plasma NGAL, the corresponding AUCs were 0.80 (95% CI, 0.79-0.81) and 0.86 (95% CI, 0.84-0.86). Cutoff concentrations at 95% specificity for urinary NGAL were>580ng/mL with 27% sensitivity for severe AKI and>589ng/mL with 24% sensitivity for AKI-D. Corresponding cutoffs for plasma NGAL were>364ng/mL with 44% sensitivity and>546ng/mL with 26% sensitivity, respectively. LIMITATIONS: Practice variability in initiation of dialysis. Imperfect harmonization of data across studies. CONCLUSIONS: Urinary and plasma NGAL concentrations may identify patients at high risk for AKI in clinical research and practice. The cutoff concentrations reported in this study require prospective evaluation.

Arterial Stiffness in the Heart Disease of CKD.

CKD frequently leads to chronic cardiac dysfunction. This complex relationship has been termed as cardiorenal syndrome type 4 or cardio-renal link. Despite numerous studies and reviews focused on the pathophysiology and therapy of this syndrome, the role of arterial stiffness has been frequently overlooked. In this regard, several pathogenic factors, including uremic toxins (i.e., uric acid, phosphates, endothelin-1, advanced glycation end-products, and asymmetric dimethylarginine), can be involved. Their effect on the arterial wall, direct or mediated by chronic inflammation and oxidative stress, results in arterial stiffening and decreased vascular compliance. The increase in aortic stiffness results in increased cardiac workload and reduced coronary artery perfusion pressure that, in turn, may lead to microvascular cardiac ischemia. Conversely, reduced arterial stiffness has been associated with increased survival. Several approaches can be considered to reduce vascular stiffness and improve vascular function in patients with CKD. This review primarily discusses current understanding of the mechanisms concerning uremic toxins, arterial stiffening, and impaired cardiac function, and the therapeutic options to reduce arterial stiffness in patients with CKD.

["Quality" Peritoneal Dialysis].

Evaluation of a peritoneal dialysis (PD) program in a nephrology center involve qualitative and quantitative indicators on clinical outcomes. International guidelines recommend monitoring outcomes of peritoneal catheter implantation, catheter-related infections, peritonitis and purification adequacy. However, none of these parameters can determine the organizational efficiency of a peritoneal dialysis (PD) program. It is desirable that centers with PD programs serving ≤14 patients, once capable of performing the peritoneal equilibration test, either safeguard their expertise or establish collaborations with nephrology units that have well-established PD programs.

[Unconventional hemodiafiltration: double-high-flux and push-pull]. / Emodiafiltrazioni inconsuete: ''Double high-flux e Push-Pull Hemodiafiltration''

Growing evidence demonstrates that morbidity and mortality in patients with end-stage renal disease correlate significantly with retention of larger uremic toxins including ß2 microglobulin. Even when hemodialysis is performed, complications such as dialysis-associated amyloidosis are likely to develop. These complications seem to be related to the retention and accumulation of larger uremic substances, only a small amount of which are removed by hemodialysis. On-line hemodiafiltration (OL-HDF) is popular but expensive; double-highflux hemodiafiltration (DHF-HDF) and push-pull hemodiafiltration (PP-HDF), special types of HDF, are very efficient treatments without the need for ultrapure substitution fluid. In DHF-HDF two high-flux dialyzers are connected in series by blood and dialysate lines. In the first dialyzer mixed diffusion convection removes fluid and solutes; in the second dialyzer backfiltration of sterile dialysate occurs, resembling the post-dilution OL-HDF mode. The PP-HDF method alternates rapid convection of body fluids and rapid backfiltration of sterile pyrogen-free dialysate using a high-flux membrane and a double-pump system. These treatments require an elevated blood flow and have the advantage that they use dialysis fluid instead of ultrapure fluid. Several studies have shown an elevated removal rate of middle molecules and reduction of dialysis-related amyloidosis symptoms like back and shoulder pain, restless leg syndrome, and carpal tunnel syndrome.

[Vascular complications following kidney transplant: the role of color-Doppler imaging]. / Le complicanze vascolari del rene trapiantato: il ruolo dell'eco-color-Doppler.

The progressive decline in the incidence of graft rejection has made urological, surgical, parenchymal and vascular complications of kidney transplant more frequent. The latter, although accounting for only 5-10% of all post-transplant complications, are a frequent cause of graft loss. Ultrasonography, both in B-mode and with Doppler ultrasound, is an important diagnostic tool in case of clinical conditions which might impair kidney function. Even though ultrasonography is considered fundamental in the diagnosis of parenchymal and surgical complications of the transplanted kidney, its role is not fully understood in case of vascular complications of the graft. The specificity of Doppler ultrasound is very important in case of stenosis of the transplanted renal artery, pseudoaneurysms, arteriovenous fistulas, and thrombosis with complete or partial artery or vein occlusion. Doppler and color determinations present high diagnostic accuracy, which is higher in case of successive measurements performed during the follow-up of the graft. Modern techniques including contrast-enhanced ultrasound increase the diagnostic power of ultrasonography in case of vascular complications of the transplanted kidney, planted kidney.

["Naked" exit-site for peritoneal dialysis catheters].

Exit site infections (ESI) and peritoneal catheter tunnel infections are strongly associated with peritonitis. Alternative exit-site dressings can include the use of water and soap and the absence of sterile gauze. This article reports our experience with "naked" exit-sites, meaning without any kind of gauze to cover them. From January 2017 to October 2020, we enrolled 38 patients of the Nephrology and Dialysis Unit of the "San Martino" Hospital in Belluno. Nine of these patients had a "naked" exit-site. At the end of the study, no significant differences were found in the percentage of ESI-free patients, in the incidence rate of ESI, in the relative risk of developing ESI and in the incidence rate of peritonitis.

The vascular disease of diabetic kidney disease.

The incidence of cardiovascular disease (CVD) is increased in patients with diabetic kidney disease (DKD). Aortic stiffness is a well-accepted biomarker for cardiovascular (CV) events in all stages of CKD. The worldwide prevalence of diabetes continues to grow, as does the prevalence of DKD. Insulin resistance, hyperglycaemia, hypertension and the metabolic abnormalities of type-2 diabetes are all involved in the pathogenesis of CVD. The effect of these toxins on cardiac and vascular function is amplified by the worsening of renal function and the parallel rise of uraemic toxins. In this narrative review, we analysed why arterial stiffening can be considered a vascular mediator between diabetes and cardiac dysfunction, and we discussed the strong CV and nephroprotective effects of sodium-glucose cotransporter type 2 inhibitors (SGLT2i).

Ultrasonographic Assessment of Atherosclerotic Renal Artery Stenosis in Elderly Patients with Chronic Kidney Disease: An Italian Cohort Study.

Although atherosclerotic renal artery stenosis (ARAS) is strictly associated with high cardiovascular risk and mortality, it often may remain unrecognized being clinically silent and frequently masked by co-morbidities especially in elderly patients with coexisting chronic kidney disease (CKD). The present observational study was conducted in elderly CKD-patients with atherosclerosis on other arterial beds. The aims were assessment of (1) ARAS prevalence; (2) best predictor(s) of ARAS, using duplex ultrasound; and (3) cardiovascular and renal outcomes at one-year follow-up. The cohort was represented by 607 consecutive in-patients. Inclusion criteria were age ≥65 years; CKD stages 2−5 not on dialysis; single or multiple atherosclerotic plaque on epiaortic vessels, abdominal aorta, aortic arch, coronary arteries, peripheral arteries that had been previously ascertained by one or more procedures. Duplex ultrasound was used to detect ARAS. Multiple regression analysis and ROS curve were performed to identify the predictors of ARAS. ARAS was found in 53 (44%) out of 120 patients who met the inclusion criteria. In univariate analysis, GFR (b = −0.021; p = 0.02); hemoglobin (b = −0.233; p = 0.02); BMI (b = 0.134; p = 0.036) and atherosclerosis of abdominal aorta and/or peripheral vessels (b = 1.025; p < 0.001) were associated with ARAS. In multivariable analysis, abdominal aorta and/or peripheral atherosclerosis was a significant (p = 0.002) predictor of ARAS. The area under the ROC curve was 0.655 (C.I. = 0.532−0.777; p = 0.019). ARAS is common in older CKD patients with extra-renal atherosclerosis, with the highest prevalence in those with aortic and peripheral atherosclerosis. ARAS may pass by unnoticed in everyday clinical practice.

Regular ultrasound examination of transplanted kidneys allows early diagnosis of renal cell carcinoma and conservative nephron sparing surgery.

INTRODUCTION: The development of malignancies is a relevant long-term complication of organ transplantation. Carcinoma of native kidney accounts for up to 5% of all malignancies found in transplant recipients. Primary clear cell type renal cell carcinoma (RCC) usually arises in the native kidneys. Its occurrence in the renal allograft has been reported infrequently. CASE PRESENTATION: We report a rare case of de novo RCC in a kidney allograft in a 41 years-old woman. Routine ultrasonography denoted a poorly marginated hypoechoic mass at the inferior pole of transplanted organ, confirmed by computed tomography which showed a lesion of 32 mm in diameter with characteristic radiological signs of RCC. The patient underwent nephron sparing surgery (NSS). At histological examination the tumor was T1-T2, N0, M0 with negative margins. At five years after NSS no significant impairment of renal function or recurrence was observed. CONCLUSION: Primary carcinomas of the kidney can be detected after transplantation in the native or transplanted kidney. According to the European Guidelines on the long-term management of kidney transplantation, all recipients should have regular ultrasonography of native and allograft kidneys to screen for cancer, which occurs at a much higher incidence in transplanted patients. NSS is a safe and efficient procedure for the treatment of RCC in renal graft, resulting in the preservation of renal function and in long-term cancer control.

[Diagnosis and therapy of exit-site infection in peritoneal dialysis: an update]. / Aggiornamenti in tema di diagnostica e terapia delle complicanze infettive dell'exit-site in dialisi peritoneale.

Exit-site infection (ESI) is still one of the most important technical complications in peritoneal dialysis because it can lead to peritonitis and catheter loss. Catheter choice does not appear to affect exit-site infection in most cases. Early diagnosis is extremely important in reducing such complications. Ultrasound inspection of the exit site and of the subcutaneous tunnel is one of the best practices to prevent technique failure. Surgical technique, peri- and postoperative protocols and care of the exit site are key points. Medical therapy should be selected based on international guidelines and prompt and timely intervention is the basis of successful therapy. A new treatment for exit-site infection is described and discussed in this paper.

Diagnostic capability of ultrasound in peritoneal catheter malfunction compared to videolaparoscopy.

BACKGROUND: The approach to peritoneal catheter malfunction consists usually in a diagnostic and therapeutic sequence of laxative prescription, abdominal radiography, brushing of the catheter, guide-wire manipulation or fluoroscopy and in the end of a videolaparoscopy (VLS) rescue intervention. Ultrasound (US) is able to find out major causes of peritoneal catheter malfunction, however without a clearly defined diagnostic value. The aim of the study was to validate the diagnostic capability of US in catheter malfunction compared to the diagnostic reference of VLS. METHODS: US scans of the subcutaneous and intraperitoneal segment of the catheter were performed prior to a VLS intervention in 40 adult patients presenting persistent catheter malfunction within a prospective multicentre study. Laxative prescription and brushing of the catheter lumen were undertaken prior to US scan. US diagnosis was compared to the corresponding at VLS, kappa coefficient calculated and the causes of mismatch analysed. RESULTS: In US, causes of persistent malfunction were catheter dislocation combined with omental wrapping in 21 cases, omental wrapping without dislocation in 11 cases, dislocation only in 4 cases, adherences to non-omental structures in 3 cases and entrapment in the lateral inguinal fossa in 1 case. The US diagnosis corresponded to the respective at VLS in 36 of 40 cases, resulting in a kappa coefficient of 0.89 (95% CI: 0.78-1.00). The discrepancies were due to improper visualization of the catheter between omentum and intestinal loops, resulting in an erroneous US diagnosis of omental wrapping. CONCLUSIONS: This study suggests that US might have a pivotal role in the diagnostic approach to peritoneal catheter dysfunction.

[Home hemodialysis: multicenter observational study].

Home dialysis is a primary objective of Italian Ministry of Health. As stated in the National Chronicity Plan and the Address Document for Chronic Renal Disease, it is mostly home hemodialysis and peritoneal dialysis to be carried out in the patient's home. Home hemodialysis has already been used in the past and today has found new technologies and new applications. The patient's autonomy and the need for a caregiver during the sessions are still the main limiting factors. In this multicenter observational study, 7 patients were enrolled for 24 months. They underwent six weekly hemodialysis sessions of 180' each; periodic medical examinations and blood tests were performed (3, 6, 12, 18 and 24 months). After 3-6 months of home hemodialysis there was already an improvement in the control of calcium-phosphorus metabolism (improvement in phosphorus values, (p <0.01), a reduction in parathyroid hormone (p <0.01)); in the number of phosphorus binders used (p <0.02); in blood pressure control (with a reduction in the number of hypotensive drugs p <0.02). Home hemodialysis, although applicable to a small percentage of patients (10-15%), has improved blood pressure control, calcium-phosphorus metabolism and anemia, reducing the need for rhEPO.

Role of Contrast-Enhanced Ultrasound (CEUS) in Native Kidney Pathology: Limits and Fields of Action.

Gray scale ultrasound has an important diagnostic role in native kidney disease. Low cost, absence of ionizing radiation and nephrotoxicity, short performance time, and repeatability even at the bedside, are the major advantages of this technique. The introduction of contrast enhancement ultrasound (CEUS) in daily clinical practice has significantly reduced the use of contrast enhancement computed tomography (CECT) and contrast enhancement magnetic resonance (CEMR), especially in patients with renal disease. Although there are many situations in which CECT and CEMRI are primarily indicated, their use may be limited by the administration of the contrast medium, which may involve a risk of renal function impairment, especially in the elderly, and in patients with acute kidney injury (AKI) and moderate to severe chronic kidney disease (CKD). In these cases, CEUS can be a valid diagnostic choice. To date, numerous publications have highlighted the role of CEUS in the study of parenchymal micro-vascularization and renal pathology by full integration with second level imaging methods (CECT and CEMRI) both in patients with normal renal function and with diseased kidneys. The aim of this review is to offer an updated overview of the limitations and potential applications of CEUS in native kidney disease.

[The COVID-19 pandemic and hemodialysis: a multicentric experience].

The SARS-CoV-2 pandemic has forced a reshaping of economic, productive, commercial and healthcare systems. The last one had the dual mandate to limit intra-hospital infections and strengthen its ability to deal with the ongoing emergency. In this paper we report the experience gained by the staff of the Nephrology and Dialysis Unit of the AULSS7 Pedemontana (Vicenza - Veneto region) and the organizational model pursued during the first wave of the pandemic.

[Vascular dysfunction in Cardiorenal Syndrome type 4].

The Cardiorenal Syndrome type 4 (CRS-4) defines a pathological condition in which a primary chronic kidney disease (CKD) leads to a chronic impairment of cardiac function. The pathophysiology of CRS-4 and the role of arterial stiffness remain only in part understood. Several uremic toxins, such as uric acid, phosphates, advanced glycation end-products, asymmetric dimethylarginine, and endothelin-1, are also vascular toxins. Their effect on the arterial wall may be direct or mediated by chronic inflammation and oxidative stress. Uremic toxins lead to endothelial dysfunction, intima-media thickening and arterial stiffening. In patients with CRS-4, the increased aortic stiffness results in an increase of cardiac workload and left ventricular hypertrophy whereas the loss of elasticity results in decreased coronary artery perfusion pressure during diastole and increased risk of myocardial infarction. Since the reduction of arterial stiffness is associated with an increased survival in patients with CKD, the understanding of the mechanisms that lead to arterial stiffening in patients with CRS4 may be useful to select potential approaches to improve their outcome. In this review we aim at discussing current understanding of the pathways that link uremic toxins, arterial stiffening and impaired cardiac function in patients with CRS-4.

[Therapeutic options to reduce arterial stiffness in chronic kidney disease].

Chronic kidney disease is associated with an increased cardiovascular risk. Several uremic toxins are also vascular toxins and may contribute to the increase of the cardiovascular risk through the development of aortic stiffening. In this process, oxidative stress and endothelial dysfunction play an important role. Considering that aortic stiffness is a known cardiovascular risk factor and a vascular biomarker involved in the development of chronic cardiac dysfunction, and that the reduction of aortic stiffness is associated with an improved survival of patients with end-stage kidney disease, we aim at reviewing the therapeutic options to reduce aortic stiffness and potentially the cardiovascular risk.

Machines for continuous renal replacement therapy.

A significant number of advancements have taken place since the beginning of continuous renal replacement therapy (CRRT). In particular, high volume hemofiltration and high permeability hemofiltration have been successful extensions of the technique. The additional and combined use of sorbent has also been tested successfully. Specific machines have now been designed to permit safe and reliable performance of the therapy. These new devices are equipped with a friendly user interface that allows for easy performance and monitoring. The apparent complexity of the circuit is made simple by a self-loading circuit or a cartridge which includes the filter and the blood and dialysate lines. Priming is performed automatically by the machine and pre- or postdilution (reinfusion of substitution fluid before or after the filter) can easily be performed by changing the position of the reinfusion line. These new machines permit all CRRT methodologies to be performed by programming the flows and the total amounts of fluid to be exchanged or circulated as a countercurrent dialysate at the beginning of the session. Progress has been made not only in technology in this area but also on our understanding of the pathophysiology of acute renal failure. New biomaterials and new devices are now available with new frontiers are on the horizon. We might, however, speculate that although improvements have been made, a lot remains to be done. There is no doubt that technology has progressed enormously in critical care nephrology and that more progress will come in the near future. The goal, and likely outcome, is an improvement in the morbidity and mortality of the most severely ill patients.

Oxidative stress and 'monocyte reprogramming' after kidney transplant: a longitudinal study.

Uremia has been implicated in increased oxidative stress (OS) and decreased monocyte HLA-DR expression in chronic kidney disease (CKD) patients. Thus, one would expect normalization of these parameters after successful kidney transplant (KTx). Our aim was to describe patterns of OS and HLA-DR expression after KTx and to explore the effect of renal function and different immunosuppression regimens. 30 KTx patients (20 male; 48 +/- 11 years) were enrolled and compared with 20 healthy controls. We measured advanced oxidation protein products (AOPP) and the percentage of monocytes expressing HLA-DR (%DR+) before (preKTx) and after KTx (on days 2, 30, 90, 180 and after 1 year). Compared to controls, patients had a higher preKTx AOPP (152.6 vs. 69.3 micromol/l; p < 0.001). AOPP decreased at 48 h after KTx, achieving values similar to controls. Thereafter, it increased again and remained significantly higher compared to controls, returning to preKTx levels at 90 days. Prior to KTx there was a trend for lower %DR+ in KTx patients compared to controls (96 vs. 98%; NS). Following KTx, patients had a lower %DR+ in the 1st month; then it gradually returned to preKTx levels during the 1st year; at no time did it reach a value similar to controls. Cyclosporine (CyA)-treated patients had a significantly higher AOPP (161.5 vs. 99.5 micromol/l; p = 0.03) and a lower %DR+ (91.7 vs. 96.4; p < 0.05) at 30 days than patients on tacrolimus (FK). Patients on mycophenolate mofetil (MMF) showed a low AOPP (106.9 vs. 168.1 micromol/l; p = 0.05) and a high %DR+ (96.7 vs. 88.2%; p = 0.001) than those on everolimus. After 3 months, CyA-treated patients had a non-significant increase in AOPP levels, whereas those on FK showed a decrease (p < 0.05) as did those treated with MMF (p < 0.05). Successful KTx reduced but did not normalize AOPP, suggesting ongoing OS, perhaps due to persistent mild renal dysfunction and the effects of immunosuppression. HLA-DR expression remained low after KTx, which may be a possible contributing factor to infectious complications after transplantation. Immunosuppressive agents appear to have diverse effects on OS and HLA-DR expression.