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Introduction Kidney transplantation (KTx) is associated with improved blood pressure (BP) levels for kidney transplant recipients (KTRs) without evoking significant changes in donors. However, there is a paucity of studies offering simultaneous detailed evaluation of BP profiles over time in transplant donor–recipient pairs. The aim of the present study was the parallel evaluation of ambulatory BP levels and trajectories in KTRs and their respective living kidney donors in the short and mid-term following KTx. Methods The study enrolled 40 prospective adult KTRs and their 40 respective donors. All participants were evaluated with 24-h ambulatory BP monitoring (Mobil-O-Graph NG device) at three time points: baseline (1 month before KTx), 3 months and 12 months after KTx. Results In KTRs, 3-month 24-h systolic BP (SBP) was marginally reduced and 12-month 24-h SBP significantly reduced compared with baseline [131.9 ± 13.3 versus 126.4 ± 11.9 mmHg (P = .075) and 123.9 ± 10.3 mmHg (P = .009), respectively]. At both the 3- and 12-month time points, 24-h diastolic BP (DBP) was significantly reduced [86.7 ± 11.5 versus 82.2 ± 8.1 mmHg (P = .043) and 80.3 ± 8.5 mmHg (P = .009)]. Similar observations were made for day- and night time SBP and DBP. Repeated-measures analysis of variance (ANOVA) showed a significant gradual decrease over time in mean 24-h SBP [F(1.463, 39.505) = 3.616; P = .049, partial η2 = 0.118] and DBP [F(1.374, 37.089) = 11.34; P = .055, partial η2 = 0.116]. In contrast, in kidney donors, 24-h SBP [118.5 ± 11.6 versus 118.2 ± 12.8 mmHg (P = .626) and 119.2 ± 11.4 mmHg (P = .748)] and DBP did not change at 3 or 12 months compared with baseline; repeated measures ANOVA showed no differences in the mean 24-h SBP and DBP levels over time. The number of antihypertensive agents decreas in KTRs and remained stable in donors. Conclusions KTx reduces ambulatory BP levels and trajectories in KTRs at 3 months and further so at 12 months post-surgery. Kidney donation does not affect the ambulatory BP levels and trajectories of donors at the same intervals.

The present study presents the clinical outcome of SARS-CoV-2 disease in relation to the humoral response in fully vaccinated solid organ transplant (SOT) recipients. Our patient cohort consists of 455 SOT recipients, vaccinated with one of the 2 approved mRNA vaccines. The antibody response was measured 1 month after the second dose, and previously infected patients have been excluded. Of the 449 remaining patients, 15 (3.34%) tested positive, using SARS-CoV-2 polymerase chain reaction. Their mean age was 43.7 ±14.4 years, and median time from transplantation was 7.8 years (1.2-30.2). Eleven patients (73.3%) had been vaccinated with BNT162b2 and 4 (26.7%) with the mRNA1273 vaccine. At the time of infection 9 (60%) patients had a negative (50 AU/mL) antibody titer, and 6 (40%) had a positive one (50 AU/mL). Median antibody titer, 27.4± 14.0 days after the second dose, measured at 13 AU/mL (0-7480 AU/mL). Renal function did not appear to be affected by the disease. Τhe mean estimated glomerular filtration rate at diagnosis was 48 ± 15 mL/min, and when in a 29-day (1-101) median follow-up was 53.9± 20.9 mL/min. Of the 15 patients, 7 had mild symptoms and were not hospitalized, and of the remaining 8 (53.3%) who needed hospitalization 7 had severe disease and 2 of them expired. The study confirms the variable and often severe course of coronavirus 2019 infection in SOT recipients, even after their full vaccination, highlighting the need to vaccinate their close relatives and to accelerate the implementation of the booster dose of vaccine.

Background Hypertension is the most prevalent cardiovascular risk factor in kidney transplant recipients (KTRs). Preliminary data suggest similar ambulatory blood pressure (BP) levels in KTRs and haemodialysis (HD) patients. This is the first study comparing the full ambulatory BP profile and short-term BP variability (BPV) in KTRs versus HD patients. Methods A total of 204 KTRs were matched (2:1 ratio) with 102 HD patients for age and gender. BP levels, BP trajectories and BPV indices over a 24-h ambulatory BP monitoring (ABPM) in KTRs were compared against both the first and second 24-h periods of a standard 48-h ABPM in HD patients. To evaluate the effect of renal replacement treatment and time on ambulatory BP levels, a two-way ANOVA for repeated measurements was performed. Results KTRs had significantly lower systolic blood pressure (SBP) and pulse-pressure (PP) levels compared with HD patients during all periods studied (24-h SBP: KTR: 126.5 ± 12.1 mmHg; HD first 24 h: 132.0 ± 18.1 mmHg; P = 0.006; second 24 h: 134.3 ± 17.7 mmHg; P Conclusions SBP and PP levels and trajectories, and BPV were significantly lower in KTRs compared with age- and gender-matched HD patients during all periods studied. These findings suggest a more favourable ambulatory BP profile in KTRs, in contrast to previous observations.

Objectives Ambulatory blood pressure (BP) control is worse in men compared with women with chronic kidney disease (CKD) and this may partially explain the faster CKD progression in men. This is the first study investigating possible sex differences in prevalence, control and phenotypes of hypertension in kidney transplant recipients (KTRs) with office-BP and 24-h ambulatory BP monitoring (ABPM). Methods This cross-sectional study included 136 male and 69 female stable KTRs who underwent office-BP measurements and 24-h ABPM. Hypertension thresholds for office and ambulatory BP were defined according to the 2017 ACC/AHA and 2021 KDIGO guidelines for KTRs. Results Age, time from transplantation, eGFR and history of major comorbidities did not differ between groups. Office SBP/DBP levels were insignificantly higher in men than women (130.3 ± 16.3/77.3 ± 9.4 vs. 126.4 ± 17.8/74.9 ± 11.5 mmHg; P = 0.118/0.104) but daytime SBP/DBP was significantly higher in men (128.5 ± 12.1/83.0 ± 8.2 vs. 124.6 ± 11.9/80.3 ± 9.3 mmHg; P = 0.032/P = 0.044). No significant between-group differences were detected for night-time BP. The prevalence of hypertension was similar by office-BP criteria (93.4 vs. 91.3%; P = 0.589), but higher in men than women with ABPM (100 vs. 95.7%; P = 0.014). The use of ACEIs/ARBs and CCBs was more common in men. Office-BP control was similar (43.3 vs. 44.4%, P = 0.882), but 24-h control was significantly lower in men than women (16.9 vs. 30.3%; P = 0.029). White-coat hypertension was similar (5.1 vs. 7.6%; P = 0.493), whereas masked hypertension was insignificantly more prevalent in men than women (35.3 vs. 24.2%; P = 0.113). Conclusion BP levels, hypertension prevalence and control are similar by office criteria but significantly different by ABPM criteria between male and female KTRs. Worse ambulatory BP control in male compared with female KTRs may interfere with renal and cardiovascular outcomes.

Background Hyperkalaemia is a frequent and potentially life-threatening condition in patients with chronic kidney disease (CKD). Even after successful kidney transplantation (KTx), KTx recipients have mild to severe CKD. Moreover, they share comorbid conditions and frequently use medications that predispose to hyperkalaemia. This study aimed to examine the prevalence and factors associated with hyperkalaemia in this population. Methods Over a pre-specified period of 6 months (1 September 2019 to 31 March 2020), we recorded in cross-sectional fashion information on serum potassium (K+) and relevant demographics, comorbidities, medications, laboratory and transplant-associated variables in clinically stable KTx recipients attending the Transplant Outpatient Clinic of our Department. Ηyperkalaemia was classified as follows: serum K+ level >5.0 mEq/L; and further as >5.0 mEq/L with concomitant use of sodium (Na+) polystyrene sulphonate; serum K+ ≥5.2 mEq/L; serum K+ ≥5.5 mEq/L. Univariate and multiple logistic regression analyses were used to identify factors associated with serum K+ >5.0 mEq/L. Results The study population consisted of 582 stable KTx recipients, 369 (63.4%) males, aged 52.4 ± 13.5 years, with estimated glomerular filtration rate (eGFR) of 55.8 ± 20.1 mL/min/1.73 m2 transplanted for >1 year. The prevalence of hyperkalaemia defined as K+ >5.0 mEq/L; >5.0 mEq/L and use of Na+ polystyrene sulphonate; K+ ≥5.2; or K+ ≥5.5 mEq/L, was: 22.7, 22.7, 14.4 and 4.1% (132, 132, 84 and 24 patients), respectively. In multivariate analysis, male gender [odds ratio (OR) = 2.020, 95% confidence interval (CI) 1.264–3.227] and use of renin–angiotensin–aldosterone system (RAAS) blockers (OR = 1.628, 95% CI 1.045–2.536) were independently associated with hyperkalaemia, while higher eGFR (OR = 0.967, 95% CI 0.955–0.979) and use of non-K+-sparing diuretics (OR = 0.140, 95% CI 0.046–0.430) were associated with lower odds of the disorder. Conclusions The prevalence of mild hyperkalaemia in stable KTx recipients is relatively high but that of moderate or severe hyperkalaemia is low. Among a wide range of factors studied, only male gender and RAAS blockade were associated with increased odds of hyperkalaemia, while higher eGFR and diuretics were associated with decreased odds of hyperkalaemia., GRAPHICAL ABSTRACT Graphical Abstract

Background Pneumocystis jiroveci pneumonia (PCP) is a life-threatening pulmonary infection after kidney transplantation (KTx). Its onset in the current era of modern immunosuppression and of routine use of universal PCP prophylaxis seems to differ from its onset in previous decades in terms of late onset with subtle clinical presentation, indicating a need for increased vigilance. Methods We retrospectively studied all KTx recipients from our center who underwent bronchoscopy and bronchoalveolar lavage (BAL) between 2009 and 2018. Of these, all cases with confirmed PCP any time after the first post-KTx year were included in the analysis. Results Among 60 patients with KTx who had undergone bronchoscopy and BAL, 12 cases with late-onset PCP were identified. PCP appeared late at a median of 10.8 (interquartile range, 2.4-15.8) years after transplantation. Patients’ mean age was 59 years, and all were receiving stable low-dose immunosuppression. Most of the patients (67%) had received PCP prophylaxis after KTx. Five out of 12 patients (42%) had concomitant cytomegalovirus (CMV) reactivation at the time of PCP. In almost all cases, clinical presentation was mild. Treatment consisted of trimethoprim-sulfamethoxazole (TMP-SMX) and intravenous corticosteroid administration, and concomitant immunosuppression was temporarily reduced or withdrawn. Outcome was generally good. None of the patients developed respiratory insufficiency or required mechanical ventilation. One patient died as a result of sepsis, and 3 more with preexisting advanced chronic kidney disease subsequently lost their grafts. Conclusion Renal transplant recipients are at risk of late-onset PCP, even at a steady state of low-dose maintenance immunosuppression. Because of its subtle clinical presentation, high suspicion of the disease is warranted. Its early recognition and proper management are essential for a successful outcome.

BACKGROUND AND AIMS To explore the frequency and impact of an autoimmune disease past-medical history (PMH) in the clinical picture and outcomes of patients with ANCA-associated vasculitis (AAV). METHOD This is a retrospective study of patients with biopsy-proven AAV, >16 years old, with detailed information about their PMH. Outcomes of interest included remission, treatment resistance, relapse, end-stage kidney disease (ESKD), and death. RESULTS 215 patients with biopsy-proven AAV and available information regarding their PMH were studied. A total of 65 (30.2%) of them had a history of autoimmune disease prior to PIV diagnosis. The mean age overall was 53.9 years. One hundred and five patients (48.8%) were positive for PR3-ANCA, 101(47.2%) for MPO-ANCA, and 9(4.2%) were negative ANCA. Granulomatosis with polyangiitis was diagnosed in 79 (36.7%), microscopic polyangiitis in 101(47.0%) and renal-limited vasculitis in 35 (16.3%) individuals. Remission rate was similar among patients with and without a PMH of autoimmune disease. Time-to-event analysis indicated that the relapse-free survival was significantly longer in patients with PMH of autoimmune disease (148.2 versus 52.8 months, P-value < .001). After adjusting for covariates, autoimmune disease history was associated with significantly lower risk of relapse {HR 0.31, [95% confidence interval (CI) 0.14–0.69]}, which remained significant in males, patients ≥ 60 years old and those with C/PR3-ANCA, kidney and lung involvement. CONCLUSION Patients with a PMH of autoimmune disease, prior to AAV diagnosis, experienced significantly fewer relapses after achievement of remission, compared with patients without such a history, underlining the importance of individualization of maintenance immunosuppressive therapy, given the different etiopathogenetic settings the disease was developed.

BACKGROUND AND AIMS Hypertension is the most prevalent cardiovascular risk factor in kidney transplant recipients (KTRs). Preliminary data suggest similar ambulatory blood pressure (ΒP) levels in KTRs and hemodialysis (HD) patients. This is the first study evaluating in comparison the full ambulatory BP profile and short-term BP variability (BPV) in KTRs versus HD patients. METHOD Two hundred four KTRs were matched (2:1 ratio) with 102 HD patients for age and gender. BP levels, BP trajectories and BPV indices over a 24-h ambulatory BP monitoring (ABPM) in KTRs were compared against both the first and second 24-h period of a standard 48-h ABPM in HD. To evaluate the effect of renal replacement treatment and time on ambulatory BP levels, two-way-ANOVA for repeated-measurements was performed. RESULTS KTRs had significantly lower SBP and pulse-pressure (PP) levels compared with HD during all periods studied (24-h SBP: KTR: 126.5 ± 12.1 mmHg; HD first 24-h: 132.0 ± 18.1 mmHg, P = 0.006; second 24-h: 134.3 ± 17.7 mmHg, P CONCLUSION SBP and PP levels and trajectories, and BPV were significantly lower in KTRs compared to age- and gender-matched HD patients during all periods studied. These findings suggest a more favorable ambulatory BP profile in KTRs, in contrast with previous observations.

Background and Aims Focal Segmental Glomerulosclerosis (FSGS) recurrence after kidney transplantation (KTx) is relatively frequent and is associated with poor graft survival. The aim of this study was to investigate which management strategies were associated with better outcomes in our cohort of KTx recipients with primary FSGS. Method We retrospectively collected data on patients with primary FSGS who received a KTx between 1993 and 2019. A history of biopsy proven FSGS in native kidneys and new onset of significant proteinuria early post-KTx led to the diagnosis of recurrence, which was confirmed by graft biopsy. Results From 1993 to 2019 we performed 46 KTxs in patients with primary FSGS. We identified 26 episodes of recurrence in 25 patients, 67% of them occurring in males. They were younger at the time of KTx (33.8 vs 41.1 years old, p=0.067) and had progressed to end stage renal disease (ESRD) faster after FSGS diagnosis (61.4 vs 111.2 months, p=0.038), while they were less likely to have received prophylactic plasmapheresis (61.5% vs 90%, p=0.029). 76.7% of recurrences were found early, after a median of 0.5 months (IQR 0.1-1) with a median proteinuria was 8.5 (IQR 4.9-11.9) g/day. All patients with recurrence were treated with plasmapheresis, while 8 (30.7%) additionally received rituximab, 1 (3.8%) abatacept and 4 (15.4%) ACTH. 7 (27%) patients experienced complete and 11 (42.3%) partial remission after a mean time of 3 (±1.79) and 4.4 (±2.25) months respectively. Prognosis was worse for patients who experienced a recurrence. 11 (42.3%) patients lost their graft from FSGS in a median time of 33 (IQR 17.5-43.3) months. Conclusion In this series of patients, primary FSGS recurred frequently after KTx. Prophylacic plasmapheresis was shown efficacious in avoiding FSGS recurrence, while timely diagnosis and plasmapheresis-based regimens induced remission in more than half of the patients.

Background and Aims Cardiovascular disease is highly prevalent in the chronic kidney disease population and associates with higher morbidity and mortality even in young ages. The aim of the present study was to assess data from 24h ambulatory blood pressure monitoring (ABPM) and 24h pulse wave analysis (PWA) in dialyzed children and investigate their association with left ventricular mass as a marker of increased cardiovascular risk. Method Children and adolescents aged 6 to 18 years, on dialysis for more than 12 months, [16 on peritoneal dialysis (PD) and 12 on hemodialysis (HD)], underwent 24h ABPM, 24h PWA, and echocardiography. Results Peripheral and central blood pressures (BPs), mean pulse wave velocity (PWV) and left ventricular mass index (LVMI) were similar between PD and HD patients (figure 1a,b). Among PWA hemodynamic parameters, augmentation index (AIx75), cardiac index (CI), and heart rate were higher in the HD group (p Conclusion HD pediatric patients demonstrate higher AIx75 and CI compared to PD patients even in the absence of LVH. These results suggest distinct patterns of vascular and cardiac functional changes in HD patients that may increase cardiovascular risk beyond LVH.

Background and Aims Hyperkalaemia is a frequent and potentially life-threatening condition in patients with CKD. Even after successful kidney transplantation, kidney transplant recipients have mild to severe CKD. Moreover, they share co-morbid conditions and frequently use medications that predispose to hyperkalaemia. This study aimed to examine the prevalence and factors associated with hyperkalaemia in this population. Method Over a pre-specified period of 6 months (September 1st 2019 to March 31st 2020), we recorded in a cross-sectional fashion information on serum potassium and relevant demographics, co-morbidities, medications, laboratory and transplant-associated variables in clinically stable kidney transplant recipients attending the Transplant Outpatient Clinic of our Department. Ηyperkalaemia was classified as follows: serum potassium level >5 mEq/L or >5 with concomitant use of sodium polystyrene sulfonate; ≥5.2; and ≥5.5 mEq/L. Univariate and multiple logistic regression analyses were used to identify factors associated with increased serum potassium >5.0 mEq/L. Results The study population consisted of 582 stable kidney transplant recipients, 369 (63.4%) males, aged 52.4±13.5 years, with eGFR of 55.8±20.1 ml/min/1.73m2 transplanted for more than one year. The prevalence of hyperkalaemia defined as potassium >5, >5 and use of sodium polystyrene sulfonate, ≥ 5.2 or ≥5.5, was 22.7%, 22.7%, 14.4% and 4.1% (132, 132, 84 and 24 patients), respectively. In multivariate analysis, male gender (OR 2.020, 95% CI 1.264-3.227) and use of renin-angiotensin-aldosterone-system blockers (OR 1.628, 95% CI 1.045-2.536), were independently associated with hyperkalaemia, while higher eGFR (OR 0.967, 95% CI 0.955-0.979) and diuretic use (OR 0.140, 95% CI 0.046-0.430) were associated with lower odds of the disorder. Conclusion The prevalence of mild hyperkalaemia in stable kidney transplant recipients is common but that of moderate or severe hyperkalemia is relatively uncommon. Male gender and low eGFR are the most potent factors associated with hyperkalaemia. Among a wide range of factors only male gender, RAAS blockade and low eGFR increased the odds of hyperkalemia.

Since its introduction in 1995, laparoscopic nephrectomy has emerged as the preferred surgical approach for living donor nephrectomy. Given the ubiquity of the surgical procedure and the need for favorable outcomes, as it is an elective operation on otherwise healthy individuals, it is imperative to ensure appropriate preoperative risk stratification and anticipate intraoperative challenges. The aim of the present study was to compare peri-and postoperative outcomes of living kidney donors (LD), who had undergone laparoscopic nephrectomy (LDN), with a control group of those who had undergone open nephrectomy (ODN). Health-related quality of life (QoL) was also assessed using the validated SF-36 questionnaire. Data from 252 LD from a single transplant center from March 2015 to December 2020 were analyzed retrospectively. In total, 117 donors in the LDN and 135 in the ODN groups were assessed. Demographics, type of transplantation, BMI, duration of surgery, length of hospital stay, peri- and postoperative complications, renal function at discharge and QoL were recorded and compared between the two groups using Stata 13.0 software. There was no difference in baseline characteristics, nor in the prevalence of peri-and postoperative complications, with a total complication rate of 16% (mostly minor, Clavien–Dindo grade II) in both groups, while a different pattern of surgical complications was noticed between them. Duration of surgery was significantly longer in the ODN group (median 240 min vs. 160 min in LDN, p &lt, 0.01), warm ischemia time was longer in the LDN group (median 6 min vs.2 min in ODN, p &lt, 0.01) and length of hospital stay shorter in the LDN group (median 3 days vs. 7 days in ODN). Conversion rate from laparoscopic to open surgery was 2.5%. There was a drop in estimated glomerular filtration rate (eGFR) at discharge of 36 mL/min in the LDN and 32 mL/min in the ODN groups, respectively (p = 0.03). No death, readmission or reoperation were recorded. There was a significant difference in favor of LDN group for each one of the eight items of the questionnaire (SF1–SF8). As for the two summary scores, while the total physical component summary (PCS) score was comparable between the two groups (57.87 in the LDN group and 57.07 in the ODN group), the mental component summary (MCS) score was significantly higher (62.14 vs. 45.22, p &lt, 0.001) in the LDN group. This study provides evidence that minimally invasive surgery can be performed safely, with very good short-term outcomes, providing several benefits for the living kidney donor, thereby contributing to expanding the living donor pool, which is essential, especially in countries with deceased-donor organ shortage.

The evolving pandemic of Coronavirus Disease 2019 has posed a substantial health risk worldwide. However, there is a paucity of data regarding the clinical course and the therapeutic management of patients with chronic kidney disease and COVID-19 infection. To date, most evidence has come from renal transplantation, with about 45 patients reported thus far, and the current data from the ERA-EDTA (ERACODA) registry for transplanted patients and patients on Renal Replacement Therapy (RRT); as for those with glomerular diseases, data are lacking. Herein, we report the case of a 62-year-old patient with severe membranoproliferative glomerulonephritis who had been receiving a high burden of immunosuppression until four months before the COVID-19 infection. He developed severe disease with acute respiratory failure requiring mechanical ventilation. After treatment with hydroxychloroquine and azithromycin, despite his low chances, he gradually recovered and survived. To the best of our knowledge, this is one of the few reported patients with glomerulonephritis who had COVID-19 Besides our single case with glomerulonephritis early during the disease outbreak, the very low prevalence of COVID-19 infection in the country’s transplant recipients (0.038%) and dialysis patients (0.24%) reflects the impact of the rapid implementation of social distancing rules as well as of preventive measures for disease control in the hospitals and dialysis units in our country.

Background and Aims Advances in immunosuppressants, used for kidney transplantation (KTx) have significantly improved outcomes in this field. We aimed to compare the long-term results of KTx in recipients with IgAN, as cause of end stage kidney disease (ESKD), with those of patients, with non-glomerular causes of renal failure, during the modern era of immunosuppression for KTx. Method This is a retrospective, case control study, in which were included patients who received a KTx after 2000. Patients were eligible to be included, if they had IgAN in a native kidney biopsy specimen and follow up longer than 1 year after KTx. IgAN patients were compared to a control-group of patients with non-glomerular primary causes of ESKD matched for age, gender, date of KTx and donor source. Graft biopsies were performed by clinical indication. Patients with ABO incompatible KTx, preemptive KTx, re-KTx, PRA>50%, major surgical complications during the 1st post-KTx month or non-compliance were excluded from the analysis of outcome. Primary outcomes of interest included graft function, patient and graft survival at end of follow up. The rate of IgAN recurrence in the graft and its impact in renal function and survival were also recorded. Computed GFR was calculated using the Modification of Diet in Renal Disease formula. Results A total of 102 KTx recipients with biopsy-proven IgAN, were compared to 204 controls with non-glomerular causes of ESKD. The mean age of patients with IgAN was 43.2(±10.15) years and 68(66.7%) were men. The mean time in dialysis was 50.2(±48.7) months and 59(57.8%) of them received a graft from a living donor. The mean cold ischemia time was 17.5(±6.7) hours, while 22(21.6%) of patients experienced delayed graft function. 97.05% of patients received induction therapy with an anti-CD25 inhibitor and 99.3% were maintained with a triple immunosuppressive regimen consisted of a mycophenolate mofetil formulation, a calcineurin inhibitor and glucocorticoids. The mean serum creatinine and eGFR at end of follow up were significantly lower for the IgAN group (p=0.001 and p=0.02 respectfully) with no difference in the frequency of acute rejection. However, graft and patient survival were not different even after controlling for follow up longer than one decade. During a mean follow up time of 120.8(±49.1) months, IgAN recurrence in the graft was documented in 23(22.5%) patients. The mean time to recurrence was 47.8(41.8) months, with a mean serum creatinine 1.83(±0.52) mg/dl and eGFR of 43.45(±18.4) ml/min/1.73m2 at the end of follow up. Within the IgAN group, although graft function was significantly lower in patients with disease recurrence, compared with that of patients without recurrence (p=0.003), graft loss remained not different between these two subgroups (p=0.49). Conclusion In the newer era of immunosuppression, long-term outcomes of KTx in patients with IgAN, as primary disease, appear significantly improved, and although graft function was significantly lower in patients with IgAN at the end of follow up, graft and patient survival was not different, compared to patients with non-glomerular causes of ESKD. Recurrence of IgAN in the graft was documented in 22.5% of patients and was associated with significantly lower eGFR at end of follow up compared to patients without recurrence but it did not impact graft survival in this time period.

Background and Aims Severe kidney involvement represents a frequent clinical scenario for patients with pauci-immune (PI) vasculitis. We aimed to explore the factors, which are associated with prognosis, in short and long term, following administration of appropriate immunosuppressive therapy. Method Patients were included if they had biopsy proven PI glomerulonephritis (GN) with estimated GFR20 ml/min/1.73 m2 with no signs of vasculitis. Histopathological evaluation included arteriosclerosis, % of normal glomeruli, activity index, chronicity index. Results A total of 83 patients, with a mean age of 59.6 (15.05) years were included. There were, 45 males (54.2%). After 3 months, 59 patients (71.1%) had responded to immunosuppressive therapy, 16 (19.3%) were dialysis depended, 5(6.02%) died and 2 were lost in follow up. By the end of the 1st year, 59 patients (71.1%) achieved remission, 16(19.3%) ended up in ESKD and 6(7.4%) died. Factors which were associated with treatment response included MPO-ANCA positivity [odds ratio OR:3.9, 95%CI (1.13-13.37) p=0.03], eGFR>10ml/min/1.73m2 at presentation [OR:2.5, 95% CI(0.86-7.30), p=0.009], normal glomeruli >10% [OR:3.8, 95%CI (1.24-12.1), p=0.02], and chronicity index more than 6 [OR:6.2, 95% CI(1.77-22.4), p=0.004]. Risk factors associated with ESKD included non-response to immunosuppressive therapy [Relative Risk RR:0.05, 95%CI (0.01-0.2) p75 years [RR:3.2, 95% CI (0.9-10.6) p=0.055]. Two of the 6 deaths were disease related. Conclusion A significant proportion of patients with PI-GN, who presented with severe renal dysfunction, responded to immunosuppressive therapy and recovered renal function approximately 3 months after initiation of therapy. The most important risk factors for ESKD were age>75 years

Glomerular crescents in kidney transplantation are indicative of severe glomerular injury and constitute a hallmark of RPGN. Their concurrence with ABMR has been rarely described only in adult patients. We report a case of 10-year-old boy with compound heterozygous Fin-major Finnish-type congenital nephrotic syndrome, who had received a deceased-donor kidney transplant 5 years before onset of acute kidney injury and nephrotic range proteinuria without hematuria. Kidney allograft biopsy illustrated 6 glomeruli with global sclerosis and 6 with remarkable circumferential or segmental cellular crescents. Negative glomerular immunofluorescence for immune-complex deposits and the absence of serum ANCA eliminated the presence of immune-mediated and ANCA-positive pauci-immune crescentic glomerulonephritis. Diagnosis of ABMR was based on the high levels of HLA class II DSA and the histological evidence of glomerulitis, peritubular capillaritis, and acute tubular injury with positive linear peritubular capillary C4d staining. The patient despite plasmapheresis and enhanced immunosuppressive treatment progressed to end-stage renal disease. We conclude that glomerular crescents may represent a finding of AMBR and possibly a marker of poor allograft prognosis in pediatric patients.

Background Infection by Nocardia species is an uncommon cause of severe clinical syndromes, particularly in immunocompromised patients, and solid-organ transplantation is the most common underlying condition. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) has been described thus far in lung and stem cell transplants with systemic nocardiosis. Case Report We report the first case of SIADH in a female elderly renal transplant recipient diagnosed with systemic nocardiosis 2 years after transplantation. The SIADH was managed appropriately, and her immunosuppressive regimen remained unchanged but was adjusted at a lower level. The systemic Nocardia infection was successfully treated with intravenous administration of trimethoprim-sulfamethoxazole and imipenem for 2 weeks followed by oral trimethoprim-sulfamethoxazole for a total of 12 months. Conclusions The SIADH syndrome is a recognizable complication of Nocardia infection in renal transplant recipients. Prompt identification along with proper management and prolonged antimicrobial treatment are essential to improve patients' outcome.

Objectives Kidney transplant (KTx) recipients with IgAN as primary disease, were compared with recipients with other causes of renal failure, in terms of long-term outcomes. Methods Ninety-nine KTx recipients with end-stage kidney disease (ESKD) due to IgAN, were retrospectively compared to; i/ a matched case-control group of patients with non-glomerular causes of ESKD, and ii/ four control groups with ESKD due to glomerular diseases; 44 patients with primary focal segmental glomerulosclerosis (FSGS), 19 with idiopathic membranous nephropathy (IMN), 22 with lupus nephritis (LN) and 21 with pauci-immune glomerulonephritis (PIGN). Results At end of the observation period, graft function and survival, were similar between KTx recipients with IgAN and all other groups, but the rate of disease recurrence in the graft differed significantly across groups. The rate of IgAN recurrence in the graft was 23.2%, compared to 59.1% (p Conclusion Recipients with IgAN as primary disease, experienced outcomes comparable to those of recipients with other causes of ESKD. The rate of IgAN recurrence in the graft was significantly lower than the rate of FSGS recurrence, but higher than the one recorded in recipients with LN or PIGN. Tacrolimus, as part of the KTx maintenance therapy, was associated with lower rates of IgAN recurrence in the graft, compared to the rate cyclosporine.

Background Natural history, predisposing factors to an unfavourable outcome and the effect of various therapeutic regimens were evaluated in a cohort of 457 patients with immunoglobulin A nephropathy (IgAN) and follow-up of at least 12 months. Methods Patients with normal renal function and proteinuria 2.5 mg/dL and/or severe glomerulosclerosis received no treatment. Patients with normal or impaired renal function and proteinuria >1 g/24 h for >6 months received daily oral prednisolone or a 3-day course of intravenous (IV) methylprednisolone followed by oral prednisolone per os every other day or a combination of prednisolone and azathioprine. The clinical outcome was estimated using the primary endpoints of end-stage renal disease and/or doubling of baseline SCr. Results The overall 10-year renal survival was 90.8%, while end-stage renal disease and doubling of baseline SCr developed in 9.2% and 14.7% of patients, respectively. Risk factors related to the primary endpoints were elevated baseline SCr, arterial hypertension, persistent proteinuria >0.5 g/24 h and severity of tubulointerstial fibrosis. There was no difference in the clinical outcome of patients treated by the two regimens of corticosteroids; nevertheless, remission of proteinuria was more frequent in patients who received IV methylprednisolone (P = 0.000). The combination of prednisolone with azathioprine was not superior to IV methylprednisolone followed by oral prednisolone. Side effects related to immunossuppressive drugs were observed in 12.8% of patients. Conclusion The clinical outcome of patients with IgAN was related to the severity of clinical and histological involvement. The addition of azathioprine to a corticosteroid-based regimen for IgAN does not improve renal outcome.

Glomerular diseases and renal transplantation are the main fields of nephrology in which the immune system plays a prevalent role. Glomerular diseases have traditionally been attributed to auto-immune conditions, whereas allograft rejection has been considered an allo-immune response. However, common immunopathologic mechanisms that include Toll-like receptors, complement and B-cell activation, as well as genetic and infectious factors appear to be involved in the pathogenesis of both entities. Novel therapeutic regimens directed against specific targets of the immune system show promising results in glomerulopathies as well as in renal transplantation.

Glomerular diseases and renal transplantation are the main fields in nephrology in which the immune system plays a prevalent role. They have for long been considered as independent conditions due to the prominent role of autoimmunity in glomerular diseases and of alloimmunity in renal transplantation. Moreover, histologic features differ between glomerular diseases and transplantation: in glomerular diseases, histologic damage involves primarily the glomeruli and secondarily the tubulointerstitium and small vessels, whereas in transplantation, allograft injury comprises primarily the tubulointerstitium and vessels and to a lesser degree the glomeruli. However, recent research has shown that the pathogenetic mechanisms in both conditions share common pathways and that there is cross-reaction between innate and adaptive immunity as well as between auto- and alloimmunity [1].

Background. Although colonic injury is a well-known complication of mycophenolic acid (MPA), the involvement of the upper gastrointestinal tract is less extensively documented. We present the occurrence of celiac-like duodenopathy manifested as a severe diarrhea syndrome in 2 renal transplant recipients on enteric-coated mycophenolate sodium. Methods. The patients belong to a setting of 16 renal transplant recipients under MPA suffering from chronic diarrhea in the absence of MPA-related colitis. Results. Both patients had a history of persistent diarrhea with significant weight loss. Colonic mucosa was unremarkable, whereas duodenal biopsies revealed celiac-like changes with increased epithelial cell apoptosis. Clinical symptoms completely resolved, and follow-up biopsies demonstrated normalization of histology after enteric-coated mycophenolate sodium withdrawal and switching to azathioprine. Conclusions. Celiac-like enteropathy seems to represent a rare side effect of MPA-associated immunosuppressive therapy and should be taken into account in the differential diagnosis of diarrhea in transplant recipients treated with MPA particularly in the absence of MPA-related colitis. As macroscopic lesions are usually missing, blind duodenal biopsies are necessary to establish the diagnosis.

Patients returning to dialysis after kidney transplant failure represent approximately 5%-15% of the population starting hemodialysis. These patients exhibit a high risk of morbidity and mortality attributed mainly to the exposure to immunosuppressive medications and to a uremic environment. The purpose of this paper was to review data regarding survival after renal allograft failure and the optimal management of patients before returning to dialysis. Moreover, issues surrounding nephrectomy after renal allograft failure, the tapering of immunosuppression and the possibility of retransplantation are examined, because they seem to be crucial for patient survival and the quality of life.

Background Long-term allograft survival is a major challenge in kidney transplantation. This study sought to estimate the evolution of renal function in patients receiving different immunosuppressive regimens based on everolimus (EVR). Methods Ninety-nine renal allograft recipients were included in a 12-month open-label, noninterventional, prospective, single-center study. Patients were divided into 2 groups, de novo and late conversion to EVR. Results Group A included 40 patients under calcineurin inhibitor (CNI) plus EVR. Median time posttransplantation was 33.06 months (interquartile range 18.25 to 42.85). Mean estimated glomerular filtration rate (eGFR) the first month posttransplantation (using Modification of Diet in Renal Disease formula) was 54.89 ± 19.08 mL/min, and mean proteinuria was 0.54 ± 0.38 g/24 h. At the end of follow up, mean eGFR and mean proteinuria significantly improved (65.49 ± 20.79 mL/min; P = .011 and 0.157 ± 0.089 g/24 h; P = .002, respectively). Group B consisted of 59 patients; 49 of them initially received mycophenolic acid (MPA) plus CNI, and 10 had been on azathioprine plus CNI. Initial immunosuppression was switched to MPA plus EVR in 49 patients, CNI plus EVR in 4 patients, and EVR in 6 patients, in a median time of 37 months (interquartile range 14.75 to 112.5) posttransplantation. Main indications for conversion were malignancies and biopsy-proven chronic allograft injury. Mean eGFR 1 month posttransplantation and at the time of conversion were 50.79 ± 17.83 mL/min and 57.39 ± 19.17 mL/min, respectively (P = .014). After conversion, mean eGFR increased (66 ± 24.89 mL/min; P = .006). Mean proteinuria was 0.509 ± 0.530 g/24 h the first posttransplantation month, and it remained stable at 0.415 ± 0.431 g/24 h until study completion. Two acute rejection episodes occurred. At the end of follow-up, patient and death-censored graft survival were 97% and 100%, respectively. Conclusions In kidney transplant recipients, EVR either de novo or after conversion with or without CNI is a safe and effective treatment that preserves renal function.

The treatment of lupus nephritis still represents a therapeutic challenge for the clinician. Besides early recognition, appropriate guiding by the histologic classification at presentation as well as at relapsing disease, is essential. The most severe proliferative and mixed forms require aggressive induction therapy. Nevertheless, recent but established by RCTs advances, as low dose iv cyclophosphamide, lower doses of cor-ticosteroids and mychophenolate acid (MPA) allow us to achieve remission induction with lower toxicity without any cost in terms of efficacy. For maintenance, azathioprine and mycophenolate acid with concomitant low dose steroids have shown both good results with a slight superiority of mycophenolate acid. Emerging therapies as B cell targeting-either by depleting agents as the anti-CD 20 mAb Rituximab, or by modulating agents as the anti-Bliss Belimumab, further contribute to the effort to minimize toxicity. This review mainly focuses on the recent efforts to treat the most aggressive form of lupus nephritis effectively with the minimal possible toxicity.

B cells play a central role in the pathogenesis of many autoimmune diseases. Selective targeting can be achieved with the use of the monoclonal antibody rituximab. In addition to being a drug for non-Hodgkin's lymphoma, rituximab is also an FDA-approved treatment for refractory rheumatoid arthritis and, since recently, ANCA vasculitis. It has shown efficacy in many autoimmune diseases. This review will discuss current evidence and the rationale of the use of rituximab in glomerular diseases, including randomized controlled trials. The focus will be on the use of rituximab in idiopathic membranous nephropathy, systemic lupus erythematosus and ANCA-associated vasculitis. The emerging role of rituximab in renal transplantation, where it seems to be important for the desensitization protocols for highly sensitized patients as well as for the preconditioning of ABO-incompatible recipients and the treatment of antibody-mediated rejection, will also be addressed.

Almost all forms of primary as well as secondary glomerulonephritides may recur after renal transplantation. Recurrence of the original disease is now the third most common cause of late allograft loss. Nevertheless, in most cases it is difficult to assess the true impact of primary disease recurrence in the allograft; histological recurrence with mild features does not necessarily implicate clinically severe disease. Moreover it is often difficult to distinguish recurrent from de novo disease as in membranous glomerulopathy. Because recurrence occurs late, histological lesions of recurrent glomerulonephritis may be unmasked by chronic damage from other causes such as chronic rejection. Beside the difficulties to interpret renal histology due to the variety of allograft lesions, there are no well-established options to prevent clinically severe disease recurrence nor the therapeutic approaches to the problem. The purpose of this review was mainly to underline that almost all primary and secondary glomerulonephritides represent a contraindication to transplantation. For the majority of patients with end-stage renal disease due to glomerulonephritis, transplantation still represents the treatment of choice.

Neurological complications after renal transplantation constitute an important cause of morbidity and mortality. Their differential diagnosis is difficult and essential for subsequent patient's management. Valproate-induced hyperammonemic encephalopathy is an uncommon but serious effect of valproate treatment. Here, we describe the case of a 15-year-old girl who was on a long-term therapy with valproate due to epilepsy and revealed impaired consciousness with hyperammonemia 12 days after renal transplantation. After withdraw of valproate, patients' symptoms resolved within 24 h. Clinicians should increase their awareness for potential complication of valproate, especially in transplanted patients.

To investigate the long-term results of ABO-incompatible (ABOi) kidney transplantation in a single center in Greece.Thirty consecutive ABOi kidney transplantations were performed from June 2005 to December 2013. All patients received rituximab one month prior to transplantation. Immunoadsorption therapy was performed for the removal of anti-A/B IgG antibodies until the titer was ≤ 1:16. Additional apheresis sessions were performed post-operatively. Intravenous immunoglobulin and oral immunosuppression consisting of tacrolimus (TAC) in combination with either everolimus or mycophenolate acid was administered. We compared the long term results of our ABOi group to those of a matched group of 30 ABO compatible (ABOc) living kidney recipients with similar baseline characteristics. The ABOc recipients received an immunosuppressive regimen consisting of TAC and mycophenolate acid. All patients in both groups received induction therapy with Basiliximab or Daclizumab, whereas corticosteroids were instituted on the day of surgery. During the follow-up period, indication biopsies were performed and interpreted by an experienced nephropathologist. The parameters we analyzed included the following: Donor/recipient age, gender, blood type, human leukocyte antigen mismatches, panel reactive antibodies, primary cause of renal failure, mean time on dialysis, immunosuppressive regimen, patient survival, graft outcome, incidence of rejections, surgical and infectious complications.The mean follow-up period was 6 years (range 1 to 9 years). A mean of 5.0 ± 3.0 (range 0-14) pre-transplant immunoadsorptions were required in order to reach the target titer. Patient survival in ABOi group in comparison to ABOc group at 1, 3, 5 and 8 years did not differ significantly (100% vs 100%, 96% vs 100%, 92% vs 100% and 92% vs 100%, P = ns). Additionally, graft survival was similar in the two groups at the same time points (100% vs 100%, 96% vs 96%, 92% vs 96% and 81% vs 92%, P = ns). The mean serum creatinine and the estimated glomerular filtration rate by the modification of diet in renal disease formula at 1, 3, 5 and 8 years did not differ significantly between ABOi and ABOc group. None of the patients in the ABOi group developed acute or chronic antibody-mediated rejection evidenced by histological signs. Four patients (13.3%) in the ABOi group and 3 (10%) in the ABOc group experienced acute cellular rejection, which was treated successfully in all cases. Bacterial and viral infections were also similar between the two groups.ABOi kidney transplantation is a safe and effective alternative that enables kidney transplantation in countries with unacceptably long deceased-donor waiting lists.

Although in antineutrophil cytoplasmic autoantibodies (ANCA)-associated systemic vasculitis (AASV) patients, activation of T-cells has been described, persistence of these alterations has not been well characterized. This study was conducted to define persistent T-cell activation (PTA) in AASV patients and to assess whether this correlates with disease activity, disease severity, age or therapy.The expression of CD4, CD45RO, CD25, CD26, CD28, CCR7 and HLA-DR was examined longitudinally in 38 consecutive AASV patients. Clinical parameters were compared by univariate and multiple analysis and Kaplan-Meier curves for relapse-free survival were calculated.PTA could be defined as either of two activation phenotypes, i.e. a low percentage of CD4+ CD45RO- T-cells or a high percentage of CD25 in the naïve CD4+ population (n = 26), since only these phenotypes were stable over time and were not associated with active disease. In patients with PTA, major organ involvement was significantly more often found than in patients without PTA. Moreover, the cumulative cyclophosphamide dose (26.86 vs 8.53 P0.01) was significantly increased in these patients, suggesting that PTA was associated with disease severity. In general, patients with PTA were older than those without (62.92 +/- 9.4 years vs 48.42 +/- 16.9 years respectively, P0.01). PTA was independent of disease duration. Interestingly, patients with a low percentage of CD4+CD45RO- T-cells were significantly more often diagnosed as microscopic polyangiitis (P0.01).We identified two independent phenotypes of T-cell activation in AASV patients. These phenotypes are persistent and do not reflect disease activity. PTA predominantly occurs in patients with severe disease. This might explain the higher cumulative cyclophosphamide dose found in these patients.