Clinical presentation and outcome prediction of clinical,serological, and histopathological classification schemes in ANCA-associated vasculitis with renal involvement

Several classification schemes have been developed for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), with actual debate focusing on their clinical and prognostic performance. Sixty-two patients with renal biopsy-proven AAV from a single center in Mexico City diagnosed between 2004 and 2013 were analyzed and classified under clinical (granulomatosis with polyangiitis [GPA], microscopic polyangiitis [MPA], renal limited vasculitis [RLV]), serological (proteinase 3 anti-neutrophil cytoplasmic antibodies [PR3-ANCA], myeloperoxidase anti-neutrophil cytoplasmic antibodies [MPO-ANCA], ANCA negative), and histopathological (focal, crescenteric, mixed-type, sclerosing) categories. Clinical presentation parameters were compared at baseline between classification groups, and the predictive value of different classification categories for disease and renal remission, relapse, renal, and patient survival was analyzed. Serological classification predicted relapse rate (PR3-ANCA hazard ratio for relapse 2.93, 1.20–7.17, p?=?0.019). There were no differences in disease or renal remission, renal, or patient survival between clinical and serological categories. Histopathological classification predicted response to therapy, with a poorer renal remission rate for sclerosing group and those with less than 25 % normal glomeruli; in addition, it adequately delimited 24-month glomerular filtration rate (eGFR) evolution, but it did not predict renal nor patient survival. On multivariate models, renal replacement therapy (RRT) requirement (HR 8.07, CI 1.75–37.4, p?=?0.008) and proteinuria (HR 1.49, CI 1.03–2.14, p?=?0.034) at presentation predicted renal survival, while age (HR 1.10, CI 1.01–1.21, p?=?0.041) and infective events during the induction phase (HR 4.72, 1.01–22.1, p?=?0.049) negatively influenced patient survival. At present, ANCA-based serological classification may predict AAV relapses, but neither clinical nor serological categories predict renal or patient survival. Age, renal function and proteinuria at presentation, histopathology, and infectious complications constitute the main outcome predictors and should be considered for individualized management.     

Alternative complement pathway activation in thrombotic microangiopathy associated with lupus nephritis

Clinical Rheumatology - Thrombotic microangiopathy (TMA) in systemic lupus erythematosus is a rare manifestation associated with activation of the complement system. This study aimed to compare...     

Markers of inflammation before and after renal transplantation

BACKGROUND: This study aims to compare serum C-reactive protein (CRP), interleukin (IL-6), and tumor necrosis factor (TNF)-alpha in end-stage renal disease (ESRD) patients before versus after receiving renal transplantation (RT) and versus donors. METHODS: Serum samples from 37 ESRD patients (24 male, age 34+/-13 years) were collected before and after RT; in addition, samples from 31 donors were obtained at transplantation. CRP concentrations were measured using nephelometry, and TNF-alpha and IL-6 were measured by enzyme-linked immunoadsorbent assay. RESULTS: Ninety-two percent of recipients had a living donor, 73% received cyclosporine A, 27% tacrolimus, and 70% induction with daclizumab. Thirteen percent had acute rejection and 16% chronic allograft nephropathy. All inflammation markers decreased 6 months after RT, but only CRP was below baseline values (baseline: 5.0+/-3.5; 6 months: 3.0+/-0; 12 months: 3.2+/-0.7; 18 months: 3.2+/-0.6; donors: 3.6+/-1.5 mg/L; P<0.05), whereas median TNF-alpha (baseline: 0.1 [0.03-0.2]; 6 months: 0 [0-0.1]; 12 months: 0.3 [0.1-2.6]; 18 months: 0.6 [0.1-1.9]; donors: 0 [0-0.1] pg/mL; P<0.05) and IL-6 (baseline: 1.9 [1.2-7.1]; 6 months: 1.2 [0.6-28.3]; 12 months: 2.6 [1.3-3.4]; 18 months: 2.7 [1.7-4.2]; donors: 1.1 [0.6-1.9] pg/mL; P<0.05) significantly increased up to the end of follow-up. Before RT, CRP correlated with age (r 0.45, P=0.006) and albumin (r -0.36, P=0.04). TNF-alpha and IL-6 were correlated before (r 0.34, P=0.04) and after (r 0.55, P=0.02) RT. Inflammation markers were not different in patients who had acute rejection episodes or chronic nephropathy. CONCLUSIONS: Compared with controls, patients displayed an inflammatory phenomenon before receiving RT. Serum CRP decreased significantly after RT, whereas TNFalpha and IL-6 increased.     

Prevalence of HLA antibodies and its impact on graft function in a group of kidney transplant recipients: a cross-sectional study

HLA alloantibodies (Abs) are associated with chronic rejection and poorer graft survival. The current study was designed to document the prevalence of HLA Abs in a group of kidney transplant recipients (KTR) and its impact on graft function.Patients and Methods283 KTR transplanted between January 1990 and December 2003 who had a functional graft were invited to participate. 198 KTR were enrolled. HLA class I and II Abs were measured by Luminex-One Lambda. Graft function was assessed by ΔCr and GFR calculated by the Levey formula.ResultsMedian post-kidney transplant (post-KT) follow-up was 51.4 (4.3 to 176.3) months. Forty-four (22.2%) KTR were found to have class I and/or class II Abs. Eleven had both class I and II Abs, ten were positive only for class I, and 23 for class II. Overall, no significant difference was seen in renal function. The ΔCr for Ab positive and Ab negative were −0.24±0.84 and −0.17±0.60 mg/dL (P=0.54), respectively. The GFR for Ab positive and Ab negative were 64.4±26 and 60.2±20 mL/min (P=0.25), respectively. No statistically significant difference was found between HLA Abs and number of HLA mismatches, gender, blood transfusions, pre-KT pregnancies, DGF, history of acute rejection, and chronic allograft nephropathy. Adjusting analysis by transplant year showed no significant difference.ConclusionThe prevalence of HLA antibodies was similar to previous reports. In this cross-sectional study, the presence of HLA antibodies was not related to a negative impact on renal function.     

High frequency of nocturnal hypertension in lupus nephritis: should ABPM be implemented in usual practice?

Clinical Rheumatology - Hypertension management in lupus nephritis (LN) is guided by in-office blood pressure (BP); however, recent studies demonstrate that lupus patients frequently have nocturnal...     

Anti-major histocompatibility complex class I-related chain A antibodies in organ transplantation

Candidate trigger antigens for alloreactive responses have been appearing continuously in the organ transplant scenario. Major histocompatibility complex class I–related chain A (MICA) is a polymorphic gene family, located near the HLA-B locus on chromosome 6, that encode a 62-kd cell surface glycoprotein. Endothelial cells, in addition to many cell lines, express MICA, whereas resting lymphocytes do not, making this polymorphic molecule a target for both cellular and humoral immune responses. Major histocompatibility complex class I–related chain A antigens are able to elicit the synthesis of alloantibodies in transplant recipients. These antibodies have been found in association with irreversible allograft rejection, an increased frequency of acute rejection episodes, and a significantly lower deceased donor graft survival, as well as in the eluates from rejected grafts. This review summarizes currently available information on MICA in the transplant setting. Undoubtedly, the questions that have surfaced surpass in excess the currently available answers.     

Effect of rapamycin on cytokine profile in kidney transplant recipients treated with triple drug therapy

The aim of this study was to explore differences in the cytokine profile among de novo kidney transplant recipients treated with either Rapamycin (Rapa) + cyclosporine (CsA) + prednisone (P) or CsA + azathioprine (Aza) + P.

Patients and methods

Among the 13 adult kidney transplant recipients studied, seven received Rapa + CsA + P while the remaining six received CsA + Aza + P with their living donors serving as controls (n = 13). Spontaneous production of IL-2, IFNγ, IL-10, and TGF-β were measured by ELISA in supernatants from 24-hour cultured unstimulated peripheral blood mononuclear cell (PBMC) at time zero (the day before the transplant), and at 3 and 6 months posttransplant. Cytokines were also measured 1 month after CsA withdrawal in the Rapa + CsA + P group.

Results

From time zero to the end of the study, IL-2, IFNγ, and IL-10 were present at low or undetectable levels in all three groups. TGF-β tended to increase in supernatants from patients under Rapa + CsA + P at 6 months posttransplant and at 1 month after CsA withdrawal without correlation to Rapa blood levels. TGF-β remained stable throughout the study period for patients included in the CsA + Aza + P group. There was no difference in this cytokine level between these study groups at any given time.

Conclusions

This study showed no differences in the spontaneous cytokine profiles evaluated in patients treated with both therapeutic schemes.     

Association of the metabolic syndrome and long-term renal function in kidney donors

Background

Metabolic syndrome (MetS) may represent risk factor for long-term renal function of kidneys from living donors. The aim of this study was to evaluate the impact of MetS on renal function in donors.

Methods

Data regarding the presence or absence of MetS and renal function, as assessed by estimated glomerular filtration rate (eGFR) were obtained from 140 kidney donors before nephrectomy (BN) and at follow-up (AF). Donors were divided into those with (group 1; n =28) versus without MetS (group 2; n = 112).

Results

Comparing the groups, we observed a significantly greater reduction in eGFR among the group with MetS BN versus AF 27.5% (19.3-33.0) versus 21.4% (9.6-34.1 P = .02) respectively using a Cox regression model, including age, gender, serum uric acid, body mass index (BMI), and basal eGFR, MetS BN (hazard ratio = 2.2; 95% confidence interval [CI], 1.21-4.01; p = .01) was an independent factor associated with a greater risk of a-eGFR <70 mL/min/1.73 m² at follow-up (P < .001). Additionally, age (hazard ratio = 1.03%; 95% CI, 1.01-1.06; P < .001), and female gender (hazard ratio = 1.86; 95% CI, 1.03-3.36; P = .03) were associated with a greater decrease in eGFR. Individuals with MetS BN showed a GFR <70 mL/min/1.73 m² at significantly shorter follow-up time (5.6 ± 0.8 years) versus persons without MetS (12.8 ± 1.0 years; P = .001)

Conclusion

Kidney donors with MetS BN experiment a significantly greater decrease in eGFR at follow-up.     

Infiltrating cellular pattern in kidney graft biopsies translates into forkhead box protein 3 up-regulation and p16INK4α senescence protein down-regulation in patients treated with belatacept compared to cyclosporin A

Renal allograft survival is related directly to cell senescence. In the transplantation scenario many cellular events - participating as immunological and non-immunological factors - could contribute to accelerate this biological process, responsible for the ultimate fate of the graft. Mechanisms concerned in tolerance versus rejection are paramount in this outcome. For this reason, immunosuppressive treatment constitutes an extremely important decision to prevent organ dysfunction and, finally, graft loss. This study was conducted to document the proportion of CD4(+) /interleukin (IL)-17A(+) -, CD16(+) /indoleamine 2, 3-dioxygenase (IDO(+) )-, forkhead box protein P3 (FoxP3(+))-expressing cells, senescent cells (p16(INK) (4α)) and the percentage of interstitial fibrosis (IF) in graft biopsies of kidney transplant recipients participating in the BENEFIT (Bristol-Myers Squibb IM103008) study. CD4(+) /IL-17A(+) , CD16(+) /IDO(+), FoxP3(+) and p16(INK) (4α+) cells were evaluated by immunohistochemistry, and the percentage of IF by morphometry on graft biopsies obtained at time 0 (pre-implantation) and at 12 months post-transplant. Senescent cells and CD4(+) /IL-17A(+) cells were increased among graft biopsies in subjects receiving cyclosporin A (CsA) compared to those under belatacept treatment. Meanwhile, CD16(+) /IDO(+) and FoxP3(+) -expressing cells were lower in biopsies from CsA treatment compared to patients treated with Belatacept. Histological morphometric analyses disclosed more IF in 12-month CsA-treated patients in comparison to pre-implantation biopsy findings. Summing up, renal biopsies from patients receiving belatacept showed greater amounts of FoxP3(+) cells and lower amounts of CD4(+) /IL-17A(+) and senescent cells compared to patients under CsA treatment. Along with these findings, an increase in IF in annual CsA-treated-patients biopsies compared to pre-implantation and belatacept-treated patients were observed.