Anti-C1q antibodies: a biomarker for diagnosis and management of lupus nephritis. A narrative review

Nephritis is a frequent and severe complication of Systemic Lupus Erythematous (SLE). The clinical course of lupus nephritis (LN) is usually characterized by alternating phases of remission and exacerbation. Flares of LN can lead to deterioration of kidney function, necessitating timely diagnosis and therapy. The presence of autoantibodies against C1q (anti-C1qAb) in the sera of SLE patients has been reported in various studies. Some research suggests that the presence and changes in the titer of anti-C1qAb may be associated with the development of LN, as well as with LN activity and renal flares. However, the exact role of anti-C1qAb in LN remains a subject of debate. Despite variability in the results of published studies, anti-C1qAb hold promise as noninvasive markers for assessing LN activity in SLE patients. Measuring anti-C1qAb levels could aid in diagnosing and managing LN during periods of both inactive disease and renal flares. Nevertheless, larger controlled trials with standardized laboratory assays are necessary to further establish the utility of anti-C1qAb in predicting the reactivation and remission of LN and guiding treatment strategies

Childhood Asthma and Environmental Exposures at Swimming Pools: State of the Science and Research Recommendations

OBJECTIVES: Recent studies have explored the potential for swimming pool disinfection by-products (DBPs), which are respiratory irritants, to cause asthma in young children. Here we describe the state of the science on methods for understanding children's exposure to DBPs and biologics at swimming pools and associations with new-onset childhood asthma and recommend a research agenda to improve our understanding of this issue. DATA SOURCES: A workshop was held in Leuven, Belgium, 21-23 August 2007, to evaluate the literature and to develop a research agenda to better understand children's exposures in the swimming pool environment and their potential associations with new-onset asthma. Participants, including clinicians, epidemiologists, exposure scientists, pool operations experts, and chemists, reviewed the literature, prepared background summaries, and held extensive discussions on the relevant published studies, knowledge of asthma characterization and exposures at swimming pools, and epidemiologic study designs. SYNTHESIS: Childhood swimming and new-onset childhood asthma have clear implications for public health. If attendance at indoor pools increases risk of childhood asthma, then concerns are warranted and action is necessary. If there is no such relationship, these concerns could unnecessarily deter children from indoor swimming and/or compromise water disinfection. CONCLUSIONS: Current evidence of an association between childhood swimming and new-onset asthma is suggestive but not conclusive. Important data gaps need to be filled, particularly in exposure assessment and characterization of asthma in the very young. Participants recommended that additional evaluations using a multidisciplinary approach are needed to determine whether a clear association exists

Delayed Graft Function in Kidney Transplant: Risk Factors, Consequences and Prevention Strategies

Background. Delayed graft function is a frequent complication of kidney transplantation that requires dialysis in the first week posttransplant. Materials and Methods. We searched for the most relevant articles in the National Institutes of Health library of medicine, as well as in transplantation, pharmacologic, and nephrological journals. Results. The main factors that may influence the development of delayed graft function (DGF) are ischemia–reperfusion injury, the source and the quality of the donated kidney, and the clinical management of the recipient. The pathophysiology of ischemia–reperfusion injury is complex and involves kidney hypoxia related to the duration of warm and cold ischemia, as well as the harmful effects of blood reperfusion on tubular epithelial cells and endothelial cells. Ischemia–reperfusion injury is more frequent and severe in kidneys from deceased donors than in those from living donors. Of great importance is the quality and function of the donated kidney. Kidneys from living donors and those with normal function can provide better results. In the peri-operative management of the recipient, great attention should be paid to hemodynamic stability and blood pressure; nephrotoxic medicaments should be avoided. Over time, patients with DGF may present lower graft function and survival compared to transplant recipients without DGF. Maladaptation repair, mitochondrial dysfunction, and acute rejection may explain the worse long-term outcome in patients with DGF. Many different strategies meant to prevent DGF have been evaluated, but only prolonged perfusion of dopamine and hypothermic machine perfusion have proven to be of some benefit. Whenever possible, a preemptive transplant from living donor should be preferred

Cardiovascular Risk after Kidney Transplantation: Causes and Current Approaches to a Relevant Burden

Background. Cardiovascular disease is a frequent complication after kidney transplantation and represents the leading cause of mortality in this population. Material and Methods. We searched for the relevant articles in the National Institutes of Health library of medicine, transplant, cardiologic and nephrological journals. Results. The pathogenesis of cardiovascular disease in kidney transplant is multifactorial. Apart from non-modifiable risk factors, such as age, gender, genetic predisposition and ethnicity, several traditional and non-traditional modifiable risk factors contribute to its development. Traditional factors, such as diabetes, hypertension and dyslipidemia, may be present before and may worsen after transplantation. Immunosuppressants and impaired graft function may strongly influence the exacerbation of these comorbidities. However, in the last years, several studies showed that many other cardiovascular risk factors may be involved in kidney transplantation, including hyperuricemia, inflammation, low klotho and elevated Fibroblast Growth Factor 23 levels, deficient levels of vitamin D, vascular calcifications, anemia and poor physical activity and quality of life. Conclusions. The timely and effective treatment of time-honored and recently discovered modifiable risk factors represent the basis of the prevention of cardiovascular complications in kidney transplantation. Reduction of cardiovascular risk can improve the life expectancy, the quality of life and the allograft function and survival

Old and New Calcineurin Inhibitors in Lupus Nephritis

Calcineurin inhibitors (CNIs) are drugs that inhibit calcineurin, a key phosphatase that dephosphorylates a transcription factor called the nuclear factor of activated T cells (NFAT), allowing its translocation into the nucleus of quiescent T cells. In the nucleus, NFAT activates interleukin 2, which stimulates the proliferation and differentiation of T-cells. CNIs can also stabilize the actin cytoskeleton of podocytes reducing proteinuria. Thanks to these characteristics, CNIs have been often used in the treatment of autoimmune diseases. However, the therapeutic index of CNIs is narrow, and their interactions with other drugs can increase toxicity or reduce efficacy. In lupus nephritis, cyclosporine and tacrolimus have been used both in induction and maintenance therapies. Observational studies and randomized controlled trials showed that both cyclosporine and tacrolimus can increase efficacy. Tolerance is satisfactory if low doses are used and the patient is carefully monitored. More recently, a new CNI, called voclosporin (VCS), has been approved by the Food and Drug Administration for use in lupus nephritis. VCS offers potential advantages over other CNIs. In two large multiethnic trials, VCS was not associated with adverse renal and metabolic events and obtained positive results despite a novel and rapid corticosteroid tapering regime

Kidney Involvement in Systemic Sclerosis

Background: Systemic sclerosis is a chronic multisystem autoimmune disease, characterized by diffuse fibrosis and abnormalities of microcirculation and small arterioles in the skin, joints and visceral organs. Material and Methods: We searched for the relevant articles on systemic sclerosis and kidney involvement in systemic sclerosis in the NIH library of medicine, transplant, rheumatologic and nephrological journals. Results: Half of patients with systemic sclerosis have clinical evidence of kidney involvement. Scleroderma renal crisis represents the most specific and serious renal event associated with this condition. It is characterized by an abrupt onset of moderate to marked hypertension and kidney failure. Early and aggressive treatment is mandatory to prevent irreversible organ damage and death. The advent of ACE-inhibitors revolutionized the management of scleroderma renal crisis. However, the outcomes of this serious complication are still poor, and between 20 to 50% of patients progress to end stage renal disease. Conclusions: Scleroderma renal crisis still represents a serious and life-threatening event. Thus, further studies on its prevention and on new therapeutic strategies should be encouraged

Surveying otter <em>Lutra lutra</em> distribution at the southern limit of its italian range

<strong>Abstract</strong>
 In the last 20 years the otter <em>Lutra lutra</em> has expanded its range in the southern part of the Italian peninsula. Populations at the border of otter range suffer a high risk of extinction and need frequent monitoring. Here we report about a survey carride out by the standard method in the central Calabria region (Sila Massif and surroundings), which currently represents the southern limit of otter distribution. Otter presence has been recorded for 7 out of 31 sites (22.6%), all belonging to the catchment of the River Savuto. A previous record for the River Neto has not been confirmed. A total of 22 spraints has been collected and analysed. Salmonids (<em>Salmo trutta</em>) formed the bulk of otter diet (Vm% = 52.1). Damming and over-fishing could represent the main obstacles to the recolonisation of the area by otters. Habitat management should be addressed to reinforce the existing population and favour its connection to the core of otter range.
 
 <strong>Riassunto</strong>
 <strong> Monitoraggio della distribuzione della lontra <em>Lutra lutra</em> al limite meridionale del suo areale italiano.</strong>
 Negli ultimi 20 anni, in Italia meridionale si è verificata un'espansione dell'areale della lontra. Le popolazioni che si trovano al margine dell'areale soffrono un più alto rischio di estinzione e necessitano di un frequente monitoraggio. In questo contesto, si relazione di un'indagine distributiva svolta con il metodo standard nella parte centrale della Calabria (Massiccio della sila e aree circostanti), che attualmente rappresenta il limite meridionale della distribuzione della specie. La presenza della lontra è stata accertata in 7 delle 31 stazioni monitorate (22.6%), tutte appartenenti al bacino idrografico dle fiume Savuto. Una segnalazione prcedente, riguardante il fiume Neto, non è stata confermata. Sono state raccolte e analizzate 22 feci. I salmonidi, rappresentati dalla trota <em>Salmo trutta</em>, costituiscono la frazione predominante della dieta della lontra (Vm% = 52.1). Lo sbarramento dei corsi d'acua e l'eccessivo prelievo ittico potrebbero rappresentare il principale ostacolo alla ricolonizzazione spontanea dell'area da parte della lontra. La gestione ambientale dovrebbe essere finalizzata al rinforzo in termini numerici della popolazione di lontra esistente e a favorire la sua connessione al nucleo centrale dell áreale della specie

Distribution of medium- to large-sized African mammals based on habitat suitability models

The knowledge of the areas inhabited by a species within its distribution range and the connections among patches are critical pieces of information for successful conservation actions. The internal structure of the extent of occurrence (EO) of a species is almost always unknown, even for "well-known" flagship species. We developed a methodology to infer the area of occupancy (AO) within the EO of a species using the limited available data. We present here the results of a three years project funded by European Union to develop high-resolution models of habitat suitability for 281 medium- to large-sized African mammals across the whole continent. The existing literature was reviewed and all data on the geographic distribution and environmental preferences of the selected species were collected. For each species, these data were then expressed in terms of key variables available as GIS layers at a resolution of 1 km(2) over the entire African continent. The AO of each species was obtained merging the information on the ecological needs of the species and the values of ecological variables over the region identified as EO. The habitat suitability models were evaluated through direct field work in four countries (Morocco, Cameroon, Uganda, Botswana) chosen as representatives of the environmental and species diversity of Africa. More than 81% of models had positive true skill statistics (TSS) values, indicating models performing better than random. Rigorous modeling procedures supported by ad-hoc field evaluation allowed the production of high-resolution habitat suitability models useful for conservation applications

Beyond ISN/RPS Lupus Nephritis Classification: Adding Chronicity Index to Clinical Variables Predicts Kidney Survival

Background: A renewed interest for activity and chronicity indices as predictors of lupus nephritis (LN) outcome has emerged. Revised National Institutes of Health activity and chronicity indices have been proposed to classify LN lesions, but they should be validated by future studies. The aims of this study were (1) to detect the histologic features associated with the development of kidney function impairment (KFI), and (2) to identify the best clinical-histologic model to predict KFI at time of kidney biopsy. Methods: Patients with LN who had more than ten glomeruli per kidney biopsy specimen were admitted to the study. Univariate and multivariate logistic regression and Cox proportional hazards models were used to investigate whether activity and chronicity indices could predict KFI development. Results: Among 203 participants with LN followed for 14 years, correlations were found between the activity index, and its components, and clinical-laboratory signs of active LN at baseline. The chronicity index was correlated with serum creatinine. Thus, serum creatinine was significantly and directly correlated with both activity and chronicity indices. In the multivariate analysis, glomerulosclerosis (OR, 3.05; 95% CI, 1.17 to 7.91; P=0.02) and fibrous crescents (OR, 6.84; 95% CI, 3.22 to 14.52; P<0.001) associated with either moderate/severe tubular atrophy (OR, 3.17; 95% CI, 1.04 to 9.64; P=0.04), or with interstitial fibrosis (OR, 2.36; 95% CI, 1.05 to 5.32; P=0.04), predicted KFI. Considering both clinical and histologic features, serum creatinine (OR, 1.68; 95% CI, 1.31 to 2.15; P<0.001), arterial hypertension (OR, 4.64; 95% CI, 1.90 to 11.32; P<0.001), glomerulosclerosis (OR, 2.12; 95% CI, 1.00 to 4.50; P=0.05), and fibrous crescents (OR, 5.18; 95% CI, 2.43 to 11.04; P<0.001) independently predicted KFI. Older age (P<0.001) and longer delay between clinical onset of LN and kidney biopsy (P<0.001) were significantly correlated with baseline chronicity index. Conclusions: The chronicity index and its components, but not the activity index, were significantly associated with an impairment of kidney function. The Cox model showed that serum creatinine, arterial hypertension, chronic glomerular lesions, and delay in kidney biopsy predicted KFI. These data reinforce the importance of timely kidney biopsy in LN