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Kidney transplant recipients (KTRs) display higher cardiovascular morbidity and mortality than the general population. Increased short-term blood pressure variability (BPV) is associated with a higher risk of adverse cardiovascular outcomes in chronic kidney disease (CKD). The aim of this study is to investigate sex differences in short-term BPV in KTRs.In total, 136 male and 69 female KTRs with valid 24 h ambulatory blood pressure monitoring were included in this analysis. Systolic and diastolic BPV indices [SD, weighted SD (wSD), coefficient of variation (CV), average real variability (ARV) and variability independent of the mean (VIM)] were calculated with validated formulas for the 24 h, daytime and nighttime periods.Age, time from transplantation surgery and history of major comorbidities did not differ between men and women. During the 24-h period, systolic BPV indices did not differ between men and women (SBP-ARV: 9.4 ± 2.2 vs. 9.9 ± 2.5; P = 0.212). During the daytime period, SBP-CV and SBP-VIM were significantly higher in females compared with male participants (SBP-CV: 9.9 ± 2.4 vs. 11 ± 3.1%; P = 0.022 and SBP-VIM: 12.6 ± 3.0 vs 14.2 ± 3.9; P = 0.008); daytime SBP-SD and SBP-ARV, and all studied indexes during nighttime did not differ between groups. No significant between-group differences in 24 h and daytime diastolic BPV indices were detected. Nighttime DBP-CV was marginally higher in men (12.0 ± 3.6 vs. 11.4 ± 4.0; P = 0.053); the rest nighttime diastolic BPV indices measured were also nonsignificantly higher in men.In conclusion, 24-h systolic and diastolic BPV parameters did not differ between male and female KTRs, but short-term BPV over the respective day- and nighttime periods showed different trends in men and women. Further studies are needed to examine possible differences in long-term BPV in KTRs.

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 The acute and long-term effects of severe acute respiratory syndrome coronavirus 2 infection in individuals with GN are still unclear. To address this relevant issue, we created the International Registry of COVID-19 infection in GN.Methods We collected serial information on kidney-related and -unrelated outcomes from 125 GN patients (63 hospitalized and 62 outpatients) and 83 non-GN hospitalized patients with coronavirus disease 2019 (COVID-19) and a median follow-up period of 6.4 (interquartile range 2.3–9.6) months after diagnosis. We used logistic regression for the analyses of clinical outcomes and linear mixed models for the longitudinal analyses of eGFR. All multiple regression models were adjusted for age, sex, ethnicity, and renin-angiotensin-aldosterone system inhibitor use.Results After adjustment for pre-COVID-19 eGFR and other confounders, mortality and AKI did not differ between GN patients and controls (adjusted odds ratio for AKI=1.28; 95% confidence interval [CI], 0.46 to 3.60; P=0.64). The main predictor of AKI was pre-COVID-19 eGFR (adjusted odds ratio per 1 SD unit decrease in eGFR=3.04; 95% CI, 1.76 to 5.28; PConclusions Pre-COVID-19 eGFR is the main risk factor for AKI regardless of GN diagnosis. However, GN patients are at higher risk of impaired eGFR recovery after COVID-19-associated AKI. These patients (especially those with high baseline proteinuria or a diagnosis of focal segmental glomerulosclerosis or minimal change disease) should be closely monitored not only during the acute phases of COVID-19 but also after its resolution.

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 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.

Introduction: Hypertension is the most prominent risk factor in kidney transplant recipients (KTRs). No study so far assessed in parallel the prevalence, control, and phenotypes of blood pressure (BP) or the accuracy of currently recommended office BP diagnostic thresholds in diagnosing elevated ambulatory BP in KTRs. Methods: 205 stable KTRs underwent office BP measurements and 24-h ambulatory BP monitoring (ABPM). Hypertension was defined as follows: (1) office BP ≥140/90 mm Hg or use of antihypertensive agents following the current European Society of Cardiology/European Society of Hypertension (ESC/ESH) guidelines, (2) office BP ≥130/80 mm Hg or use of antihypertensive agents following the current American College of Cardiology/American Heart Association (ACC/AHA) guidelines, (3) ABPM ≥130/80 mm Hg or use of antihypertensive agents, and (4) ABPM ≥125/75 mm Hg or use of antihypertensive agents. Results: Hypertension prevalence by office BP was 88.3% with ESC/ESH and 92.7% with ACC/AHA definitions compared to 94.1 and 98.5% at relevant ABPM thresholds. Control rates among hypertensive patients were 69.6 and 43.7% with office BP compared to 38.3 and 21.3% with ABPM, respectively. Both for prevalence (κ-statistics = 0.52, p < 0.001 and 0.32, and p < 0.001) and control rates (κ-statistics = 0.21, p < 0.001 and 0.22, and p < 0.001, respectively), there was moderate or fair agreement of the 2 techniques. White-coat and masked hypertension were diagnosed in 6.7 and 39.5% of patients at the 140/90 threshold and 5.9 and 31.7% of patients at the 130/80 threshold. An office BP ≥140/90 mm Hg had 35.3% sensitivity and 84.9% specificity for the diagnosis of 24-h BP ≥130/80 mm Hg. An office BP ≥130/80 mm Hg had 59.7% sensitivity and 73.9% specificity for the diagnosis of 24-h BP ≥125/75 mm Hg. Receiver operating curve analyses confirmed this poor diagnostic performance. Conclusions: At both corresponding thresholds studied, ABPM revealed particularly high hypertension prevalence and poor BP control in KTRs. Misclassification of KTRs by office BP is substantial, due to particularly high rates of masked hypertension. The diagnostic accuracy of office BP for identifying elevated ambulatory BP is poor. These findings call for a wider use of ABPM in KTRs.

To explore the frequency and impact of an autoimmune disease past-medical history (PMH) in the clinical picture and outcomes of patients with antineutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis (AAV).This was 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.206 patients with biopsy-proven AAV and available information regarding their PMH were studied. 63(30.6%) of them had a history of autoimmune disease prior to AAV diagnosis. The mean age overall was 54.1 years. One hundred and five patients (51%) were positive for PR3-ANCA, 101 (49%) for MPO-ANCA. Granulomatosis with polyangiitis was diagnosed in 79 (38.3%), microscopic polyangiitis in 97 (47.1%) and renal-limited vasculitis in 30 (14.6%) 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 vs. 61.9 months, p-value0.001). After adjusting for covariates, autoimmune disease history was associated with significantly lower risk of relapse (HR: 0.33, 95% CI: 0.15-0.72), which remained significant in males, patients ≥60 years old and those with C/PR3-ANCA, kidney and lung involvement.Patients with a PMH of autoimmune disease, prior to AAV diagnosis, experienced significantly fewer relapses after achievement of remission, compared to patients without such a history, underlining the importance of individualisation of maintenance immunosuppressive therapy, given the different aetiopathogenetic settings the disease was developed.

Treatment of the plasma cell clone in monoclonal gammopathy of renal significance (MGRS) is necessary in order to reduce toxic immunoglobulin load to the kidneys and salvage renal function. There are limited data on the use of daratumumab in patients with MGRS. We summarize our experience with the use of daratumumab-based therapy in 25 MGRS patients, 12 of whom were previously untreated. The median follow-up of the cohort is 14 months. The best overall haematologic response in evaluable patients was complete response (CR) in five (22%), very good partial response (VGPR) in five (22%) and partial response (PR) in seven (30%) patients for an overall response rate of 74%. Two of five patients in CR and two patients with initially detectable clones, but non-measurable immunoglobulins, had undetectable minimal residual disease (MRD) with next-generation flow cytometry (NGF) after therapy. Haematologic response rate for previously untreated patients was 83% vs. 69% for previously treated and for daratumumab combinations it was 91% vs. 64%, and with CR/VGPR 82% vs. 29%, compared to daratumumab monotherapy. At six months, 12/22 (55%) patients not on dialysis achieved a reduction of proteinuria >30%, of at least 0·5 g/24 h, without an estimated glomerular filtration rate (eGFR) reduction. The toxicity was mild and predictable. In conclusion, daratumumab-based therapy is a new option for patients with MGRS.

Background Hypocomplementemic urticarial vasculitis syndrome is an infrequent condition characterized by ocular, renal, gastrointestinal and pulmonary involvement with low serum complement levels and autoantibodies. Renal manifestations vary from microscopic hematuria to nephrotic syndrome and acute kidney injury. Accordingly differing histologic patterns have been reported. Case presentation We present the case of a 65 years old woman with a history of chronic uveitis who presented with arthralgias, urticarial rush, nephrotic syndrome, glomerular hematuria and low serum complement. Kidney biopsy revealed an immune-complex membranoproliferative glomerulonephritis. The patient received induction therapy with steroids, cyclophosphamide and hydroxychloroquine followed by rapid clinical improvement and remission of proteinuria. Maintenance treatment consisted of rituximab pulses. Conclusions The majority of hypocomplementemic urticarial vasculitis syndrome cases is idiopathic, although an association to drugs, infections or other autoimmune disorders has been recorded. Given the rarity and heterogeneity of the disease, no standard treatment is established.

Aims Diagnosis of primary membranous nephropathy (PMN) is mainly based on immunofluorescence/immunohistochemistry findings. However, assessment of specific features on optical microscopy can help to estimate the severity of the disease, guide treatment and predict the response. The aim of this study was to identify, classify and grade the precise histological findings in PMN to predict renal function outcome and guide treatment. Methods and results Histological parameters, including focal segmental sclerosis (FSGS), tubular atrophy (TA), interstitial fibrosis (IF) and vascular hyalinosis (VH), were re‐evaluated in 752 patients with PMN. Their predictive value was estimated separately, and also in a combination score (FSTIV) graded from 0 to 4. Finally, the impact of histology was assessed in the response to immunosuppressive treatment. Mean age of patients was 53.3 (15–85) years and most presented with nephrotic syndrome. FSGS was present in 32% and VH in 51% of the patients, while TA and IF were graded as stage ≥1 in 52% and 51.4%, respectively. The follow‐up period was 122.3 (112–376) months. FSGS, TA and IF and VH were associated with impaired renal function at diagnosis (P = 0.02, P 50% eGFR reduction, FSGS (P = 0.001) and TA (P = 0.02). Also, patients presented with FSGS, IF, VH and/or with FSTIV > 1 could benefit from immunosuppression, regardless of clinical presentation. Conclusions The presence and degree of four histological indices, FSGS, VH, TA and IF, assessed separately or in combination, and FSTIV score not only predict renal function outcome after long‐term follow‐up, but can also help in the choice of appropriate treatment. Decisions concerning immunosuppressive treatment can be guided by pathology regardless of clinical findings.

Cardiovascular events are one of the leading causes of mortality in kidney transplant recipients. Hypertension is the most common comorbidity accompanying chronic kidney disease, with prevalence remaining as high as 90% even after kidney transplantation. It is often poorly controlled. Abnormal blood pressure profiles, such as masked or white-coat hypertension, are also extremely common in these patients. The pathophysiology of blood pressure elevation in kidney transplant recipients is complex and includes transplantation-specific risk factors, which are added to the traditional or chronic kidney disease-related factors. Despite these observations, hypertension management has been an under-researched area in kidney transplantation. Thus, relevant evidence derives either from studies in the general population or from small trials in kidney transplant recipients. Based on the relevant guidelines in the general population, lifestyle modifications should probably be applied as the first step of hypertension management in kidney transplant recipients. The optimal pharmacological management of hypertension in kidney transplant recipients is also not clear. Dihydropyridine calcium channel blockers are commonly used as first line agents because of their lack of adverse effects on the kidney, while other antihypertensive drug classes are under-utilised due to fear of the possible haemodynamic consequences on renal function. This review summarizes the existing data on the pathophysiology, diagnosis, prognostic significance and management of hypertension in kidney transplantation.

Monoclonal gammopathies have been associated with a wide spectrum of renal pathologies [1,2]. In symptomatic MM, cast nephropathy is a leading cause of renal dysfunction and acute renal failure [3]...

B-cell clonal expansion has been sporadically described in the blood and/or renal tissue of patients with glomerulonephritides, albeit with unclear pathogenetic role. Herein, using spectratyping analysis, we observed oligoclonal intrarenal B-cell populations in 59% of glomerulonephritis patients with podocyte injury (6/7 with focal segmental glomerulosclerosis, 1/3 minimal change disease, 1/3 idiopathic membranous nephropathy, 3/4 IgA nephropathy, 2/5 membranous lupus nephritis), 20% of glomerulonephritis patients without podocyte involvement (4/13 with mesangial or proliferative lupus nephritis, 0/3 idiopathic membranoproliferative glomerulonephritis, 0/4 pauci-immune vasculitis) and 17% of control patients with renal cancer. In multivariate analysis, oligoclonal B-cells were associated with podocyte injury and the grade of glomerulosclerosis (both p = .009). B-cell oligoclonal expansions were not found in the paired peripheral blood samples. We postulate that B-cell expansion in the kidney results from local stimuli, including antigens expressed on podocytes. Further studies to unravel the role of oligoclonal B-cells in (auto)immune-mediated kidney disease are warranted.

We retrospectively evaluated 55 consecutive patients who received at least one dose of lenalidomide for relapsed/refractory AL amyloidosis. Their median age was 63 years; 72% had heart and 75% kidney involvement and 13% were on dialysis; while 20%, 46% and 34% had Mayo stage -1, -2 and -3 disease, respectively. Median time from start of primary therapy to lenalidomide was 15 months (range 2–100) and median number of prior therapies was 1 (range 1–4); 73% of the patients had prior bortezomib and 42% were bortezomib-refractory. On intent to treat, haematologic response rate was 51% (5.5% CRs, 20% VGPRs) and was 56% versus 40% for patients with and without prior bortezomib and 47% versus 62.5% for bortezomib refractory versus non-refractory patients (p = .351). Organ response was achieved by 16% of evaluable patients (22% renal, 7% liver and 3% cardiac); however, 10 (21%) patients progressed to dialysis. Median survival post lenalidomide was 25 months. Bortezomib-refractory patients had worse outcome (median survival of 10.5 versus 25 months for bortezomib-sensitive patients versus not reached for bortezomib-naive patients, p = .011). Median lenalidomide dose was 10 mg and no patient received the 25 mg dose; however, in 60% a dose reduction was required. Median duration of lenalidomide therapy was 7.2 months and 46% discontinued lenalidomide before completion of planned therapy, mainly due to toxicity (26%) or disease progression/no response (13%). We conclude that although lenalidomide is a major salvage option for patients with relapsed/refractory AL amyloidosis, its toxicity in patients with AL amyloidosis is significant and doses should be adjusted for optimal tolerability.

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.

Patients with diabetic kidney disease (DKD) are at very high risk for cardiovascular events. Only part of this increased risk can be attributed to the presence of diabetes mellitus (DM) and to other DM-related comorbidities, including hypertension and obesity. The identification of novel risk factors that underpin the association between DKD and cardiovascular disease (CVD) is essential for risk stratification, for individualization of treatment and for identification of novel treatment targets.In the present review, we summarize the current knowledge regarding the role of emerging cardiovascular risk markers in patients with DKD. Among these biomarkers, fibroblast growth factor-23 and copeptin were studied more extensively and consistently predicted cardiovascular events in this population. Therefore, it might be useful to incorporate them in risk stratification strategies in patients with DKD to identify those who would possibly benefit from more aggressive management of cardiovascular risk factors.

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.

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.

IntroductionManagement of the Primary Membranous Nephropathy (PMN) usually involves administration of immunosuppressives. Cyclophosphamide (Cyclo) and Calcineurin Inhibitors (CNIs) are both widely used but only limited data exist to compare their efficacy in long term follow-up.AimThe aim of the present study was to estimate and compare long term effects of Cyclo and CNIs in patients with PMN.Patients-methodsClinical data, histologic findings and long term outcome were retrospectively studied. The response to treatment and rate of relapse was compared between patients treated with CNIs or Cyclo based immunosuppressive regimens.ResultsTwenty three centers participated in the study, with 752 PMN patients (Mean age 53.4(14-87) yrs, M/F 467/285), followed for 10.1±5.7 years. All patients were initially treated with Renin Angiotensin Aldosterone System inhibitors (RAASi) for at least 6 months. Based on their response and tolerance to initial treatment, patients were divided into 3 groups, group I with spontaneous remission, who had no further treatment, group II, continued on RAASi only, and group III on RAASi+immunosuppression. Immunosuppressive regimes were mainly based on CNIs or Cyclo. Frequent relapses and failure to treatment were more common between patients who had started on CNIs (n = 381) compared to those initially treated with Cyclo (n = 110), relapse rate: 25.2% vs. 6.4%, pConclusionsLong term follow up showed that administration of Cyclo in PMN is followed by better preservation of renal function, increased response rate and less frequent relapses, compared to CNIs.

Colchicine is a lipophilic alkaloid drug, which exhibits ant-inflammatory and anti-fibrotic properties. Cardinal mechanisms of action of colchicine are the disruption of the microtubule system and the inhibition of neutrophil adhesion and recruitment. Colchicine is indicated in the prevention and treatment of gouty arthritis and familial Mediterranean fever. In this review, we summarize current and potentially future pharmacologic activities of colchicine in various renal disease entities along with pharmacokinetic and pharmacodynamic properties. Additionally, we will refer to main interactions of colchicine with medications used in renal medicine, as well as dosing recommendations in patients with reduced glomerular filtration rate.

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.

Data regarding the prognosis of resistant hypertension (RHTN) with respect to its severity is limited. We investigated the cardiovascular risk of severe RHTN in a prospective observational study. A cohort of 1700 hypertensive patient with treated uncontrolled HTN was followed for a mean period of 3.6 ± 1.8 years. At baseline, standard clinical and laboratory workup was performed, including testing for secondary causes of RHT where applicable. Three groups were identified depending on presence of RHTN (office-based uncontrolled HTN under at least three drugs including a diuretic) and levels of office systolic blood pressure (BP): 1187 patients (70%) without RHTN, 313 (18%) with not-severe RHTN (systolic BP

A staging system for patients with renal AL amyloidosis, based on eGFR (50 ml/min/1.73 m

SummaryIn patients with ANCA-associated vasculitis (AAV), CD25 expression is increased on circulating T cells. Although in animal experiments the role of CD4+ CD25+ T-regulatory-cells (Treg) in protection against autoimmunity is well established, the role of these cells in AAV is unknown. To investigate the hypothesis that an increased expression of CD25 on T cells is related to persistent T cell activation and not to disturbances in Treg cells in AAV (34 patients, six of them after renal transplantation), we investigated CD25 expression in different subpopulations of CD4+ cells and FOXP3 mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR). In addition, T cell proliferation and cytokine secretion after stimulation with anti-CD3 and anti-CD28 and intracellular cytokine production after stimulation with phorbol myristate acetate (PMA)-ionomycin was determined. Controls were non-vasculitic renal transplant patients (n = 9) and healthy controls (HC) (n = 13). In AAV the total number of lymphocytes, CD4+ lymphocytes and the percentage of naive T cells are lower than in HC and RTX. An increased percentage of CD25+ cells was found in AAV and AAV/RTX, irrespective of disease activity, but not in HC or RTX. This was confined to the naive (CD4+ CD45RBhigh) population only. FOXP3 mRNA expression in CD4+ T cells did not differ between AAV patients and healthy controls. In vitro T cell proliferation was enhanced in AAV patients compared to HC (P

SummaryWhile most of our understanding of immune dysfunction in dialysis patients involves alterations in CD28–CD80/86 signalling, nothing is known of CD46-mediated co-stimulation of T cells in these patients. Because C3b/C4b bind to CD46 and complement activation occurs during haemodialysis (HD), we addressed whether CD46-mediated T cell activation is altered in HD (n = 9), peritoneal dialysis (PD) (n = 10) and predialysis patients (n = 8) compared to healthy controls (HC) (n = 8). T cell surface markers, T cell proliferation and interleukin (IL)-10 production were studied in CD4+T cells. In addition, CD46 splice-variants and IL-10 promoter gene polymorphisms were studied by reverse transcription (RT) or amplification refractory mutation system-polymerase chain reaction (ARMS-PCR), respectively. In all uraemic patients, irrespective of the stage of renal insufficiency or dialysis modality, a significant increase in the percentage of CD25 positivity in naive CD4+T cells was found (64% ± 21%versus 23% ± 18%, P < 0·001). Lymphocytes of HD patients proliferated in greater numbers and produced more IL-10 after co-stimulation with anti-CD46 than after co-stimulation with anti-CD28. This was also found in CD4+T cells of PD patients, albeit to a lesser extent. In contrast, with T cells of predialysis patients and of HC, co-stimulation via CD28 was more efficient. The observed alterations in T cell proliferation and IL-10 production were associated neither with CD46 splice variants nor with IL-10 promoter gene polymorphisms. Lymphocytes of HD patients show an increased response on CD46 co-stimulation. These data suggest that ongoing complement activation in HD patients may lead to alterations in acquired immunity.

About 50% of newly diagnosed mutilple myeloma (MM) patients (NDMM) have some degree of renal impairment (RI) at presentation, up to 20% have severe acute kidney injury (AKI) and ~1–5% may require extrarenal dialysis, whereas severe RI is associated with high risk of early death and other complications.1, 2 Immediate effective anti-myeloma therapy and vigorous supportive care are the cornerstones of management.2, 3 However, there are limited data focusing specifically on the management and outcomes of MM patients requiring dialysis as a consequence of MM, mostly including small numbers of patients on dialysis.4, 5, 6, 7, 8 Moreover, the use of high cut-off hemodialysis to rapidly reduce the load of nephrotoxic light chains may provide some additional benefit in patients requiring dialysis when treated with bortezomib-based therapies, but the reported results of two randomized studies are controversial.9, 10 Thus, we analyzed the outcomes of 52 consecutive NDMM with RI requiring dialysis, which were managed and treated in a single center, to provide data on response to therapy, dialysis discontinuation and survival in unselected patients, outside the context of clinical trials.

Inflammation has been established as an important determinant of cardiovascular disease progression. Currently, clinical examination, laboratory and imaging tests are invaluable for the diagnosis, prognosis and disease monitoring. Novel inflammatory biomarkers are also used to better restratify patients in risk groups but their potential to guide treatment decisions and management of patients has not been extensively evaluated. Therefore, in this review article we present the most recent data concerning the use of inflammatory biomarkers in cardiovascular therapeutics.

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.

Systemic Castleman's disease is a lymphoproliferative disorder with various clinical presentations and incompletely understood aetiology. The authors report on a rare case of the plasma cell variant of Castleman's disease associated with autoimmune haemolytic anaemia and autoimmune thrombocytopenia (Evan's syndrome) and complicated by mixed nephrotic-nephritic syndrome and acute renal failure due to an underlying glomerulopathy with microscopic and immunofluorescence findings suggestive of membranoproliferative glomerulonephritis (MPGN) type I. Immunocomplexed glomerulonephritis is rare in Castleman's disease, while, to the best of our knowledge, constellation of all these autoimmune phenomena is reported for the first time suggesting that apart from the putative role of VEGF and IL-6 in the pathogenesis of the disease, a more generalised immunological disturbance occurs, probably through autoantibodies induced by active polyclonal B cells raised from Castleman's disease tumour.

Summary15-Deoxyspergualin (DSG) is an alternative treatment modality for Wegener's granulomatosis (WG) patients refractory to conventional treatment. Nevertheless, it is unclear how DSG modulates disease activity in these patients. This study was conducted to investigate which parameters of adaptive and acquired immunity were influenced during two subsequent cycles of DSG treatment. Emphasis was put upon T cell and monocyte activation, neutrophil function and surface expression of proteinase-3 (PR-3). Anti-CD3/anti-CD28 and interleukin (IL)-15/IL-7-mediated T cell proliferation were assessed by fluorescence activated cell sorter (FACS) analysis using carboxyfluorescein succinimidyl ester (CSFE) labelling. Interferon (IFN)-γ and IL-10 production were determined in the supernatants of these cultures by enzyme-linked immunosorbent assay. Monocyte activation was assessed in lipopolysaccharide (LPS)-stimulated whole blood, using tumour necrosis factor (TNF)-α as read-out. Neutrophil function was determined by measuring oxidative burst, chemotaxis and phagocytosis. T cell activation markers and PR3 expression were measured by FACS. All parameters were determined directly before and after each DSG cycle. Anti-CD3/anti-CD28-mediated T cell proliferation was reduced directly after DSG treatment. Directly before a subsequent cycle of DSG was started, T cell proliferation was increased. Similar findings were observed for IFN-γ and IL-10 production by T cells. DSG did not influence IL-15/IL-7-mediated T cell proliferation. LPS-mediated TNF-α production was also impaired directly after DSG treatment. No influence on T cell activation markers, neutrophil function and surface PR-3 expression was observed in peripheral blood of these patients. Our data demonstrate that DSG influences T cell and monocyte activation in a reversible fashion. Although DSG causes neutropenia in these patients, it does not influence neutrophil function.

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.