IgA Nephropathy Recurrence after Kidney Transplantation: Role of Recipient Age and Human Leukocyte Antigen-B Mismatch.

BACKGROUND: Recurrence of immunoglobulin (Ig)A nephropathy (rIgAN) is a growing cause of kidney allograft dysfunction. This study was aimed at investigating factors associated with rIgAN and the subsequent progression to end-stage renal disease (ESRD). METHODS: Retrospective study including consecutive patients with IgA nephropathy (IgAN) who received a kidney transplant in our center between 1992 and 2016 and had a renal biopsy by clinical indication. The date of detection of chronic kidney disease (CKD) 5 was used as renal outcome. RESULTS: Eighty-six kidney transplants were performed in patients with IgAN, 38 (44%) were from living donors (related n = 26). rIgAN was diagnosed in 23 allografts (27%). Renal function and proteinuria at the end of the follow-up period were worst in the rIgAN patients compared to those without rIgAN (2.2 vs. 1.4 mg/dL, p = 0.014, and 1.16 vs. 0.49 g/day, p = 0.005, respectively). Risk of rIgAN and progression to CKD 5 decreased with patient's age (hazard ratio [HR] 0.95, 95% CI 0.92-0.98, p = 0.002, and HR 0.97, 95% CI 0.83-0.97, p = 0.008 per year, respectively). Patients with rIgAN had a higher risk of progression to CKD 5 (HR 6.7, 95% CI 1.3-35.7, p = 0.025). Full donor-recipient mismatch in the human leukocyte antigen (HLA)-B loci decreased the risk of rIgAN (HR 0.22, 95% CI 0.06-0.76, p = 0.017). CONCLUSIONS: rIgAN was an independent risk factor for ESRD after renal allograft. Younger age increased the risk of rIgAN and CKD 5. Conversely, HLA-B mismatching was a potential protective factor for rIgAN of this glomerular disease.

Early outcomes of kidney transplantation from elderly donors after circulatory death (GEODAS study).

BACKGROUND: Spain has dramatically increased the number of controlled circulatory death donors (cDCD). The initial selection criteria for considering cDCD for kidney transplantation (KT) have been expanded progressively, with practically no limits in donor age during the last years. We aimed to analyze the early clinical outcomes using expanded (> 65 years) cDCD in comparison with standard ones. METHODS: Observational multicenter study including 19 transplant centers in Spain. We performed a systematic inclusion in a central database of every KT from expanded cDCD at each participant unit from January-2012 to January-2017. Surgical procedures and immunosuppressive protocols were based on local practices. Data was analyzed in the central office using logistic and Cox regression or competitive-risk models for multivariate analysis. Median time of follow-up was 18.1 months. RESULTS: 561 KT were performed with kidneys from cDCD, 135 from donors older than 65 years. As expected, recipients from older cDCD were also older (65.8 (SD 8.8) vs 53.7 (SD 11.4) years; p < 0.001) and with higher comorbidity. At 1 year, no differences were found amongst older and younger cDCD KT recipients in terms of serum creatinine (1.6 (SD 0.7) vs 1.5 (SD 0.8) mg/dl; p = 0.29). Non-death censored graft survival was inferior, but death-censored graft survival was not different (95.5 vs 98.2% respectively; p = 0.481). They also presented a trend towards higher delayed graft function (55.4 vs 46.7%; p = 0.09) but a similar rate of primary non-function (3.7 vs 3.1%; p = 0.71), and acute rejection (3.0 vs 6.3%; p = 0.135). In the multivariate analysis, in short follow-up, donor age was not related with worse survival or poor kidney function (eGFR < 30 ml/min). CONCLUSIONS: The use of kidneys from expanded cDCD is increasing for older and comorbid patients. Short-term graft outcomes are similar for expanded and standard cDCD, so they constitute a good-enough source of kidneys to improve the options of KT wait-listed patients.

ANCA serotype and histopathological classification for the prediction of renal outcome in ANCA-associated glomerulonephritis.

BACKGROUND: The phenotype of renal involvement in anti-neutrophil cytoplasmic antibodies (ANCA) vasculitis has a major influence on survival, and histological subgrouping of diagnostic renal biopsies has been proposed to aid in the prediction of renal outcome. We aimed to validate this histological subgrouping and to investigate the additional value of ANCA serotype in the prediction of renal outcome. METHODS: Data were retrospectively collected from the time of diagnosis by systematic review of medical records from 136 patients with renal biopsies recruited to cohorts from the UK and Spain, over 15 years. The end point, renal survival, was the composite of end-stage renal disease (ESRD) or death from any cause. The occurrence of ESRD, Stage 4 Kidney Disease Outcomes Quality Initiative-Chronic Kidney Disease, was assessed separately, in order to establish a severity index risk of chronic kidney disease. RESULTS: Renal survival at 5 years was 96% in the focal, 86% in the crescentic, 81% in the mixed and 61% in the sclerotic subgroups (P = 0.03). Myeloperoxidase (MPO)-ANCA was associated with more severe disease when compared with PR3-ANCA, as demonstrated by a lower frequency of focal and higher frequency of sclerotic subgroups, by more advanced interstitial fibrotic change and by lower glomerular filtration rate at diagnosis and worse renal function at 1 and 2 years. CONCLUSIONS: We have confirmed the predictive value for renal survival of the ANCA vasculitis histology classification in a multi-centre study. We found a worse renal outcome in patients with tubulointerstitial fibrosis and atrophy. MPO-ANCA positive patients had a worse renal prognosis due to more severe glomerular injury. These results contribute to patient stratification in renal vasculitis for therapeutic, epidemiological and basic research.

The acute phase of Trypanosoma cruzi infection is attenuated in 5-lipoxygenase-deficient mice.

In the present work we examine the contribution of 5-lipoxygenase- (5-LO-) derived lipid mediators to immune responses during the acute phase of Trypanosoma cruzi infection in 5-LO gene knockout (5-LO(-/-)) mice and wild-type (WT) mice. Compared with WT mice, the 5-LO(-/-) mice developed less parasitemia/tissue parasitism, less inflammatory cell infiltrates, and a lower mortality. This resistance of 5-LO(-/-) mice correlated with several differences in the immune response to infection, including reduced PGE2 synthesis; sustained capacity of splenocytes to produce high levels of interleukin (IL)-12 early in the infection; enhanced splenocyte production of IL-1ß, IL-6, and IFN-γ; rapid T-cell polarization to secrete high quantities of IFN-γ and low quantities of IL-10; and greater numbers of CD8(+)CD44(high)CD62L(low) memory effector T cells at the end of the acute phase of infection. The high mortality in WT mice was associated with increased production of LTB4/LTC4, T cell bias to produce IFN-γ, high levels of serum nitrite, and marked protein extravasation into the peritoneal cavity, although survival was improved by treatment with a cys-LT receptor 1 antagonist. These data also provide evidence that 5-LO-derived mediators negatively affect host survival during the acute phase of T. cruzi infection.

Invasive lobular carcinoma stable for 4.5 years in a postmenopausal woman user of hormone therapy for 25 years.

We present a case of a 72-year-old woman referred to the breast disorder service due to abnormalities on mammography and breast ultrasound. The patient reported using different hormone therapy (HT) formulations during 25 years and had stopped taking HT for 4 years. Physical examination showed no alterations in the breasts or axilla. Mammography from 2012 detected asymmetry at the 3 o'clock position in the anterior right breast. Ultrasound revealed an irregular, hypoechoic mass with indistinct margins, and posterior acoustic shadowing. A retrospective analysis of mammographies from 2007, 2009 and 2010 showed that a very subtle asymmetry had existed since 2007. Follow-up imaging demonstrated no change in asymmetry during 4.5 years. The patient underwent breast-conserving therapy and sentinel lymph node biopsy. Histopathologic examination demonstrated classic invasive lobular carcinoma. There were no sentinel node metastases. The patient received radiotherapy and endrocrine therapy. This case demonstrates that breast cancer may remain stable and not grow for many years. This aspect should be kept in mind by all professionals dealing with women's healthcare, in particular HT users who may develop breast cancer with a less aggressive behavior. Any suspicious finding on mammography, despite being unchanged for a number of years, must be investigated.

Nutricional intake, maternal outcomes and knowledge on preeclampsia prevention: Was there impact during the COVID-19 pandemic among women with hypertension?

AIM: Compare nutritional intake, weight gain, frequency of superimposed pre-eclampsia (SPE) and adequate use/knowledge on preventive interventions for PE, before and during the COVID-19 pandemic among pregnant women with chronic hypertension (CH) METHODS: Prospective cohort of pregnant women with CH. Inclusion between 13 and 25 weeks, with sociodemographic characterization, food frequency questionnaire and 24-hour recall (R24h). Indirect adherence test MEDTAKE was employed to investigate adequate use/understanding of calcium and aspirin. Frequency of SPE, weight gain, food intake, maternal and perinatal outcomes were compared between periods. RESULTS: 58 women were included and 116 R24h considered. Over 80 % used aspirin and calcium for PE prophylaxis. However, less than half understood the meaning of such interventions. There were no differences in sociodemographic characteristics, majority white, 20 to 34 years-old, and multiparous. There were 31 women included before and 27 during the pandemic. Frequency of SPE was respectively 40 % and 44.4 % before and during the pandemic (p = 0.746) and weight gain 8.7Kg before and 7.4Kg during the pandemic. There was no difference in macronutrient intake, average calcium consumption was 444.8 mg before and 402.6 mg during the pandemic; with inadequate use/understanding of preventive interventions for PE. CONCLUSION: The pandemic period did not significantly increase the risk of SPE, without significant increase in weight gain or worsening food quality intake and knowledge on preventive interventions.

Venous thromboembolism with concurrent pulmonary haemorrhage in systemic vasculitis.

BACKGROUND: Pulmonary haemorrhage (PH) is a serious manifestation of systemic vasculitis with high mortality rates yet vasculitis is associated with an increased prevalence of venous thromboembolism (VTE). The concurrent presentation of severe PH and VTE poses a challenge in terms of therapeutic management. METHODS: This is a retrospective case review of the clinical manifestations and response to treatment in vasculitis patients presenting with concurrent pulmonary haemorrhage and VTE (pulmonary embolism and/or deep venous thrombosis). RESULTS: Of 35 patients with severe PH due to systemic vasculitis, 7 (20%) had concurrent VTE. The most common cause was anti-neutrophil cytoplasm antibody-associated vasculitis, followed by anti-glomerular basement membrane disease. Vasculitis responded to conventional therapies and VTE treatment with anticoagulation was uncomplicated in five of six cases. In one case, anticoagulation precipitated the PH and another was not anticoagulated and developed recurrent VTE. All patients survived without further complications after a mean follow-up of 46 months (3-98). CONCLUSIONS: Concurrent VTE occurred in one-fifth of cases with severe PH due to vasculitis. Management of VTE with anticoagulation was effective but led to pulmonary haemorrhage in one patient.

Biocompatible Dialysis Solutions Preserve Peritoneal Mesothelial Cell and Vessel Wall Integrity. A Case-Control Study on Human Biopsies.

UNLABELLED: ♦ INTRODUCTION: Chronic exposure to conventional peritoneal dialysis (PD) solutions has been related to peritoneal function alterations in PD patients, and associated with mesothelial cell loss, submesothelial fibrosis, vasculopathy, and angiogenesis. In vitro and ex vivo analyses, as well as studies with animal models, have demonstrated that biocompatible PD solutions attenuate these morphological alterations. Our aim was to confirm the morphological benefits of biocompatible solutions in PD patients. ♦ METHODS: We analyzed biopsies from 23 patients treated with biocompatible solutions (study group, SG), and compared them with a control group (n = 23) treated with conventional solutions (CG), matched for time on PD. ♦ RESULTS: A total of 56.5% of SG patients showed total or partial preservation of mesothelial cells monolayer, in contrast with 26.1% of patients in CG (p = 0.036). Peritoneal fibrosis was not significantly less frequent in SG patients (47.8% SG vs 69.6% CG; p = 0.13). In patients without previous peritonitis, a significantly lower prevalence of fibrosis was present in SG patients (41.7% SG vs 77.8% CG; p = 0.04). Hyalinizing vasculopathy (HV) was significantly lower in SG (4.3% SG vs 30.4% CG; p = 0.02). Cytokeratin-positive fibroblast-like cells were detected in 10 patients (22%), but the prevalence was not significantly lower in SG. In the univariate regression analysis, the use of biocompatible solutions was associated with mesothelial monolayer integrity (p = 0.04) and an absence of vasculopathy (p = 0.04). ♦ CONCLUSION: The present study demonstrates in vivo in human biopsies that biocompatible solutions are better tolerated by the peritoneum in the medium and long term than conventional solutions.

First report of equine Pegivirus in South America, Brazil.

The human Pegivirus (HPgV, also known as GBV-C virus or hepatitis G virus) is a lymphotropic RNA-virus phylogenetically related to the Hepatitis C virus, which infects approximately 5% of the world's human population. Recently, two novel, presumably hepatotropic, pegiviruses, designated as equine Pegivirus (EPgV) and Theiler's Disease Associated Virus (TDAV), were discovered in horses with clinical and laboratory evidence of hepatic disease. To verify the occurrence of pegiviruses infection in horses from Pará State, northern Brazil, serum samples from 114 horses located in four cities (Acará, Belém, Dom Eliseu and Ananindeua) were submitted for the molecular analysis of EPgV by nested RT-PCR. The results of nucleotide sequencing and phylogenetic analysis of EPgV NS3 and NS5B genomic regions confirmed one positive sample among 114 tested samples (1/114; 0.8%). No evidence of TDAV infection was found, but despite the low prevalence and unknown clinical significance among the studied population, these results represent the first molecular detection of EPgV in horses in South America.

Peritoneal resting with heparinized lavage reverses peritoneal type I membrane failure. A comparative study of the resting effects on normal membranes.

BACKGROUND: Ultrafiltration failure (UFF) is a serious complication of long-term peritoneal dialysis (PD). Peritoneal rest (PR) has been demonstrated as a valid treatment to reverse the functional changes that occur in UFF. The effects of PR on a normally functioning human peritoneum are unknown but are expected to be neutral. Our hypothesis was that PR positively modifies peritoneal function in patients with UFF, in contrast to the absence of effects when PR is applied under normal conditions. PATIENTS AND METHODS: We studied 84 PR periods, comparing 35 patients with UFF and 49 controls (resting for abdominal surgery with temporary discontinuation of PD). We analyzed peritoneal transport pre-PR and post-PR by calculating the mass transfer coefficients of creatinine (Cr-MTAC), the dialysate/plasma creatinine ratio (D/P Cr) and the ultrafiltration (UF). RESULTS: Baseline data was similar for the 2 groups, although the UFF group had a longer median time in PD (39 [18 - 60] vs 10 [5 - 23] months; p = 0.00001). Peritoneal rest induced a decrease in D/P Cr, Cr-MTAC and an increase in UF capacity in the UFF group (p = 0.0001, p = 0.004 and p = 0.001, respectively), without causing changes in the control group. Peritoneal rest in patients with more than 6 months of UFF was not able to reduce peritoneal solute transport or improve UF capacity. Response to PR did not differ among UFF patients with or without a previous history of peritonitis. Peritoneal rest enabled patients with UFF to continue on PD for a median time of 23 months (range, 13 - 46 months). CONCLUSIONS: Peritoneal rest induces functional changes in patients with UFF but not in those with no functional abnormalities. This demonstrates that PR works only when abnormal but reversible functional conditions are present. However, the effect is highly dependent on how early PR is applied.

A novel and de novo deletion in the OCRL1 gene associated with a severe form of Lowe syndrome.

The oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked disorder. The mutation of the gene OCRL1 localized at Xq26.1, coding for the enzyme phosphatidylinositol (4,5) bisphosphate (PIP2P) 5-phosphatase, is responsible for the phenotypic characteristics of the disease. We report a 22-year-old male with a severe form of OCRL syndrome, diagnosed on the basis of congenital cataracts, severe psychomotor and cognitive deficits, and renal tubular dysfunction without Fanconi syndrome. The patient presented low molecular weight proteinuria, nephrocalcinosis, nephrolithiasis, rickets, and growth retardation and developed progressive renal failure. Genetic analysis showed a novel and de novo deletion of exons 10-13 in the OCRL1 gene.

Encapsulating peritoneal sclerosis in peritoneal dialysis. a review and European initiative for approaching a serious and rare disease.

Encapsulating peritoneal sclerosis (EPS) represents a rare complication in peritoneal dialysis (PD) with high mortality. It is characterised by diffuse peritoneal membrane fibrosis, which develops into encapsulation and manifests as clinical signs and symptoms of intestinal obstruction. Its incidence varies from 0.7%to 3.3%. The most significant risk factor in its development is exposure time to PD solutions, although young age and peritonitis episodes can also contribute. Its aetiopathogeny has not been clearly explained and it is thought that a second hit like peritonitis, hemoperitoneum, surgery, genetic predisposition, etc on an already damaged peritoneal membrane, could also trigger the development of EPS. Some cases appear after transfer to haemodialysis or after transplant. In these cases, the use of calcineurin inhibitors is believed to be related. The presence of clinical symptoms and signs of intestinal obstruction, along with compatible radiological and/or anatomical findings could also confirm the diagnosis. At present there are no clinical or biochemical markers capable of predicting its onset. Therapeutic management comprises the use of immunosuppressors like steroids and tamoxifen, nutritional management and even surgery in advanced cases, all of which provide varying results. This article discusses the diagnosis and treatment of EPS, it encourages the participation in the European Registry and it advocates the need to centralise the management of this medical complication.