A Neptune-mass exoplanet in close orbit around a very low-mass star challenges formation models.

Theories of planet formation predict that low-mass stars should rarely host exoplanets with masses exceeding that of Neptune. We used radial velocity observations to detect a Neptune-mass exoplanet orbiting LHS 3154, a star that is nine times less massive than the Sun. The exoplanet's orbital period is 3.7 days, and its minimum mass is 13.2 Earth masses. We used simulations to show that the high planet-to-star mass ratio (>3.5 × 10-4) is not an expected outcome of either the core accretion or gravitational instability theories of planet formation. In the core-accretion simulations, we show that close-in Neptune-mass planets are only formed if the dust mass of the protoplanetary disk is an order of magnitude greater than typically observed around very low-mass stars.

Clonidine, but not Dexamethasone, Prolongs Ropivacaine-Induced Supraclavicular Brachial Plexus Nerve Block Duration.

BACKGROUND: Ultrasound-guided supraclavicular brachial plexus block (USSB) provides excellent postoperative analgesia after upper extremity surgery. Dexamethasone and clonidine have been added to local anesthetics to enhance and prolong the duration of analgesia. OBJECTIVE: The objective of this randomized prospective study is to evaluate the efficacy of dexamethasone, clonidine, or combination of both as adjuvants to ropivacaine on the duration of USSB for postoperative analgesia. METHODS: Patients receiving USSB for postoperative pain control for upper extremity surgery were randomized to one of four groups; ropivacaine 0.5%, ropivacaine 0.5% with 4 mg dexamethasone, ropivacaine 0.5% with 100 mcg clonidine , or ropivacaine 0.5% with 4 mg dexamethasone and 100 mcg clonidine. Pain scores, sensory and motor function were evaluated at post anesthesia care unit (PACU), discharge and at 24 h postoperatively. RESULTS: The duration of sensory and motor blocks was significantly longer in clonidine groups when compared to ropivacaine alone [Sensorial analgesia: ropivacaine alone 13.4±6, Ropivacaine- Clonidine 17.4±6; Ropivacaine-Dexamethasone-Clonidine 18.8±6.2; Motor blocks: Ropivacaine 12±5, Ropivacaine-Clonidine 16.8±5.2, Ropivacaine-Dexamethasone-Clonidine 18.2±5.7]. In clonidine groups, there was significant prolongation of motor and sensory block when compared to ropivacaine group alone. CONCLUSION: The results demonstrated that clonidine significantly prolongs the duration of ropivacaine effects for the postoperative analgesia in patient underwent upper arm surgeries.

Cortisol and testosterone associations with social network dynamics.

This study integrates behavioral endocrinology and network science to explore links between hormones and social network dynamics. Specifically, we examine how cortisol (C) and testosterone (T) are associated with creation of new friendships and maintenance of existing friendships. A collegiate marching band was used as a model system of a mixed-sex social organization. Participants (n=193; 53% female; M age=19.4years, 62.1% European-American) provided friendship nominations at time 1 and two months later at time 2. At time 1, participants donated saliva before and after rehearsal (later assayed for C and T). Stochastic actor-based models revealed that individuals with higher C levels were less likely to maintain their social relationships and more likely to create new friendships. In contrast, individuals with higher T levels were more likely to maintain friendships and less likely to create new relationships. Findings suggest that individual differences in C and T are associated with the initiation and maintenance of friendships and have several noteworthy theoretical implications.

Kidney allograft fibrosis after transplantation from uncontrolled circulatory death donors.

BACKGROUND: Existing data suggest that increased interstitial fibrosis may occur abnormally in renal transplants from donations after uncontrolled circulatory death (uDCD). METHODS: To evaluate the factors that are associated with the progression of fibrosis and its functional impact on renal grafts, we compared 76 uDCD recipients with 86 recipients of kidney donations after brain death at 1-year after transplantation. Groups were matched for donor age, rank of transplantation, and absence of human leukocyte antigen sensitization. Histology was performed on sequential biopsies in uDCD recipients. Associations between variables were analyzed using linear mixed models and univariate analyses. RESULTS: In the uDCD group, increased fibrosis was detected 3 months after transplantation compared to before implantation. After 1 year, interstitial fibrosis and tubular atrophy score was significantly greater (1.5±0.7 vs. 1.0±0.9; P=0.003) and estimated glomerular filtration rate (49.5±17.4 vs. 60.6±19.1 mL/min/1.73 m2; P=0.0003) was significantly lower in the uDCD group than in the donations after brain death group. No flow duration and donor age were significantly associated with accelerated fibrosis. Interstitial fibrosis and tubular atrophy score, interstitial inflammation score, and estimated glomerular filtration rate were significantly worse in uDCD patients with no flow longer than 10 min. CONCLUSION: Donations after uncontrolled circulatory death grafts show more fibrosis after transplantation. No flow duration is associated with accelerated fibrosis and should be considered during uDCD graft allocation.

Increasing adoption of comparative effectiveness research in community behavioral health: methodology.

Increased efforts in comparative effectiveness research (CER) (comparing various health care intervention and treatment options) are being used to inform health care delivery. While CER research itself is an important step in developing best practices in health care, it is not enough to ensure success. The knowledge must also be successfully disseminated to increase adoption and implementation of practices. To ensure the greatest benefits of successful interventions, it is essential to understand which dissemination strategies are effective and under what conditions. This article provides the background and methodology used in a large-scale, 2-year study aimed at determining how knowledge gained from CER research may be most effectively disseminated to those responsible for delivering behavioral health services. The study takes an important step toward addressing the gaps in dissemination and translation of CER.

Complement-binding anti-HLA antibodies and kidney-allograft survival.

BACKGROUND: Anti-HLA antibodies hamper successful transplantation, and activation of the complement cascade is involved in antibody-mediated rejection. We investigated whether the complement-binding capacity of anti-HLA antibodies plays a role in kidney-allograft failure. METHODS: We enrolled patients who received kidney allografts at two transplantation centers in Paris between January 1, 2005, and January 1, 2011, in a population-based study. Patients were screened for the presence of circulating donor-specific anti-HLA antibodies and their complement-binding capacity. Graft injury phenotype and the time to kidney-allograft loss were assessed. RESULTS: The primary analysis included 1016 patients. Patients with complement-binding donor-specific anti-HLA antibodies after transplantation had the lowest 5-year rate of graft survival (54%), as compared with patients with non-complement-binding donor-specific anti-HLA antibodies (93%) and patients without donor-specific anti-HLA antibodies (94%) (P<0.001 for both comparisons). The presence of complement-binding donor-specific anti-HLA antibodies after transplantation was associated with a risk of graft loss that was more than quadrupled (hazard ratio, 4.78; 95% confidence interval [CI], 2.69 to 8.49) when adjusted for clinical, functional, histologic, and immunologic factors. These antibodies were also associated with an increased rate of antibody-mediated rejection, a more severe graft injury phenotype with more extensive microvascular inflammation, and increased deposition of complement fraction C4d within graft capillaries. Adding complement-binding donor-specific anti-HLA antibodies to a traditional risk model improved the stratification of patients at risk for graft failure (continuous net reclassification improvement, 0.75; 95% CI, 0.54 to 0.97). CONCLUSIONS: Assessment of the complement-binding capacity of donor-specific anti-HLA antibodies appears to be useful in identifying patients at high risk for kidney-allograft loss.

Pathologic classification of antibody-mediated rejection correlates with donor-specific antibodies and endothelial cell activation.

BACKGROUND: Humoral immune responses during heart transplantation may result in antibody-mediated rejection (AMR), which is now taken into account on endomyocardial biopsy (EMB) specimens and ranked according to the pathologic AMR (pAMR) grades of the International Society for Heart and Lung Transplantation classification. This classification might benefit from new immunohistological markers and validation by others biomarkers, namely donor-specific antibodies (DSA). METHODS: From the 293 protocol EMBs performed in 113 patients in our institution during a 1-year period for this prospective study, 280 EMB specimens were available with both histology and immunohistochemistry. C4d and labeling of intravascular cells by cluster of differentiation (CD) 68 were performed on paraffin sections. Available sera (n = 150) concomitant of EMB specimens were tested for the presence of DSA. All of the pAMR+ EMB specimens, along with a set of randomized pAMR0 EMB specimens, were immunolabeled for mammalian target of rapamycin (mTOR) effectors, phosphorylated 70 S6-kinase (p70S6K) and phosphorylated S6 ribosomal protein (pS6RP). RESULTS: AMR was diagnosed in 37 EMB specimens (13.2%): 1 pAMR1(I+), 27 pAMR1(H+), and 9 pAMR2. The proportion of DSA-positive EMB varied according to the pAMR grade, with pAMR0, pAMR1(H+), and pAMR2 EMB presenting 17.6%, 77.3%, and 100% of DSA-positivity, respectively. Among the 30 pAMR+ specimens with available DSA testing and the 30 pAMR0 randomized specimens, mTOR pathway immunohistochemistry showed endothelial cell positivity for p70S6K in 17 pAMR+ EMB specimens (56.7%) and in 1 pAMR0 EMB specimen (3.3%). pS6RP was detected in 8 pAMR+ EMB specimens (26.7%) and in 1 pAMR0 EMB specimen (3.3%). CONCLUSIONS: p70S6K and pS6RP immunohistochemistry afford new markers of AMR on EMB specimens because their expression is correlated with microcirculation inflammation and DSA. The correlation of DSA with pAMR grade suggests that this grading system is valid.

Antibody-mediated vascular rejection of kidney allografts: a population-based study.

BACKGROUND: Rejection of allografts has always been the major obstacle to transplantation success. We aimed to improve characterisation of different kidney-allograft rejection phenotypes, identify how each one is associated with anti-HLA antibodies, and investigate their distinct prognoses. METHODS: Patients who underwent ABO-compatible kidney transplantations in Necker Hospital and Saint-Louis Hospital (Paris, France) between Jan 1, 1998, and Dec 31, 2008, were included in our population-based study. We assessed patients who provided biopsy samples for acute allograft rejection, which was defined as the association of deterioration in function and histopathological lesions. The main outcome was kidney allograft loss-ie, return to dialysis. To investigate distinct rejection patterns, we retrospectively assessed rejection episodes with review of graft histology, C4d in allograft biopsies, and donor-specific anti-HLA antibodies. FINDINGS: 2079 patients were included in the main analyses, of whom 302 (15%) had acute biopsy-proven rejection. We identified four distinct patterns of kidney allograft rejection: T cell-mediated vascular rejection (26 patients [9%]), antibody-mediated vascular rejection (64 [21%]), T cell-mediated rejection without vasculitis (139 [46%]), and antibody-mediated rejection without vasculitis (73 [24%]). Risk of graft loss was 9·07 times (95 CI 3·62-19·7) higher in antibody-mediated vascular rejection than in T cell-mediated rejection without vasculitis (p<0·0001), compared with an increase of 2·93 times (1·1-7·9; P=0·0237) in antibody-mediated rejection without vasculitis and no significant rise in T cell-mediated vascular rejection (hazard ratio [HR] 1·5, 95% CI 0·33-7·6; p=0·60). INTERPRETATION: We have identified a type of kidney rejection not presently included in classifications: antibody-mediated vascular rejection. Recognition of this distinct phenotype could lead to the development of new treatment strategies that could salvage many kidney allografts. FUNDING: None.

Prospective assessment of renal histopathological lesions in patients with end-stage liver disease: effects on long-term renal function after liver transplantation.

BACKGROUND & AIMS: The incidence of organic renal lesions in patients with end-stage liver disease is unknown. The goal of this study was to make a prospective evaluation of renal histological lesions in a group of unselected patients awaiting liver transplantation. METHODS: Sixty cirrhotic patients underwent a renal biopsy via the transjugular route. The potential effect of renal lesions on renal function was evaluated five years after transplantation. RESULTS: The yield of biopsies enabling satisfactory analysis was 77%, and no major complications occurred. Proteinuria>0.5 g/day was observed in only 8.7% of these patients, microscopic haematuria in 4.3%, creatinine levels>133 mmol/L (1.5mg/dl) in 10.9%, and Modification of the Diet in Renal Disease (MDRD) clearance<60 ml/min in 13.0%. Twenty-five patients (55.3%) had a morphological diagnosis of renal disease, 15 displayed IgA nephropathy and immunofluorescence testing showed that 12 had specific diabetic linear staining for IgG and albumin, of whom seven had associated histological lesions of diabetic nephropathy. Five years after liver transplantation, renal function had significantly deteriorated more in patients with initial diabetic lesions than in those with normal histology or IgA nephropathy alone. CONCLUSIONS: In patients with end-stage liver disease, IgA nephropathy and diabetic lesions were frequently found despite the absence of renal impairment and/or urinalysis anomalies. Our results strongly suggest that severe renal failure develops preferentially in liver transplant recipients with diabetes or carbohydrate intolerance, and that pre-existing arterial lesions may favour the nephrotoxicity of calcineurin inhibitors. Diabetes prior to transplantation needs to be strictly managed and requires a renal sparing immunosuppressive regimen after transplantation.

The impact of donor-specific anti-HLA antibodies on late kidney allograft failure.

Despite improvements in outcomes of renal transplantation, kidney allograft loss remains substantial, and is associated with increased morbidity, mortality and costs. Identifying the pathologic pathways responsible for allograft loss, and the attendant development of therapeutic interventions, will be one of the guiding future objectives of transplant medicine. One of the most important advances of the past decade has been the demonstration of the destructive power of anti-HLA alloantibodies and their association with antibody-mediated rejection (ABMR). Compelling evidence exists to show that donor-specific anti-HLA antibodies (DSAs) are largely responsible for the chronic deterioration of allografts, a condition previously attributed to calcineurin inhibitor toxicity and chronic allograft nephropathy. The emergence of sensitive techniques to detect DSAs, together with advances in the assessment of graft pathology, have expanded the spectrum of what constitutes ABMR. Today, subtler forms of rejection--such as indolent ABMR, C4d-negative ABMR, and transplant arteriopathy--are seen in which DSAs exert a marked pathological effect. In addition, arteriosclerosis, previously thought to be a bystander lesion related to the vicissitudes of aging, is accelerated in ABMR. Advances in our understanding of the pathological significance of DSAs and ABMR show their primacy in the mediation of chronic allograft destruction. Therapies aimed at B cells, plasma cells and antibodies will be important therapeutic options to improve the length and quality of kidney allograft survival.

An introduction to the Safe Schools/Healthy Students Initiative.

The Safe Schools/Healthy Students (SS/HS) Initiative offers a unique opportunity to conduct large-scale, multisite, multilevel program evaluation in the context of a federal environment that places many requirements and constraints on how the grants are conducted and managed. Federal programs stress performance-based outcomes, valid and reliable data, addressing important problems, ensuring efficiency and fiscal responsibility, reducing burden on federal staff and grantees, and developing and disseminating useful solutions and recommendations. MANILA Consulting Group, Inc., (MANILA), in partnership with Battelle Centers for Public Health Research and Evaluation (Battelle) and RMC Research Corporation (RMC), has been conducting the SS/HS national cross-site evaluation, which involves the coordinated efforts of federal Project Officers, local education agencies, technical assistance providers, communication specialists, and national and local evaluators across a diverse set of socioeconomic and cultural contexts. To date, the national cross-site evaluation has provided data indicating that the SS/HS Initiative is, in fact, meeting these goals. Findings revealed that fewer students reported they had experienced violence and fewer students reported they had witnessed violence. Fully 96 percent of school staff said SS/HS had improved school safety. There was a 263 percent increase in the number of students who received school-based mental health services and a 519 percent increase in those receiving community-based mental health services. In addition, more than 80 percent of school staff reported that they saw reductions in alcohol and other drug use among their students. These encouraging results stress the need for ongoing coordination at all levels of the Initiative to continue to ensure safer schools and healthier students. This article provides an overview of the initiative and introduces four articles in this special issue.

Evaluation of a complex, multisite, multilevel grants initiative.

The Safe Schools/Healthy Students (SS/HS) national evaluation seeks to assess both the implementation process and the results of the SS/HS initiative, exploring factors that have contributed to or detracted from grantee success. Each site is required to forge partnerships with representatives from education, mental health, juvenile justice, and law enforcement, coordinating and integrating their efforts and working together to contribute to comparable outcomes (e.g., reduced violence and alcohol and drug use, improved mental health services). The evaluation uses multiple data collection techniques (archival data, surveys, site visits, interviews, and focus groups) from a variety of sources (project directors, community partners, schools, and students) over several years. Certain characteristics of the SS/HS initiative represent unique challenges for the evaluation, including the absence of common metrics for baseline, outcome data, and lack of comparison group. A unifying program theory was required to address these challenges and synthesize the large amounts of qualitative and quantitative information collected. This article stresses the role of program theory in guiding the evaluation.

A clinicopathologic study of thrombotic microangiopathy in IgA nephropathy.

Thrombotic microangiopathy (TMA) occurs in IgA nephropathy, but its clinical significance is not well described. We retrospectively examined a series of 128 patients diagnosed with IgA nephropathy between 2002 and 2008 who had a mean follow-up of 44±27 months. In our series, 53% presented with lesions of TMA, acute or organized, in arteries and/or arterioles. Among patients with TMA, 4% were normotensive, 25% had controlled hypertension, and 71% had uncontrolled hypertension. Of those with uncontrolled hypertension, 26% had malignant hypertension. Histologically, the group with TMA had a significantly greater percentage of sclerotic glomeruli and worse tubulointerstitial fibrosis than those of the group without TMA. However, a significant minority of patients had near-normal histology, with minimal tubular atrophy (20%) and/or <20% interstitial fibrosis (24%). TMA rarely occurred in the absence of significant proteinuria. During follow-up, a doubling of serum creatinine or ESRD occurred in all patients with laboratory evidence of TMA, in 42% of those with morphologic evidence but no laboratory evidence of TMA, and in 11% of those without TMA. In summary, lesions of TMA are frequent in IgA nephropathy and may occur in normotensive patients with near-normal renal histology. Although the pathophysiologic mechanisms involved remain undetermined, the current study rules out severe hypertension or advanced renal disease as sole causes.

Correlates of perceived effectiveness of the Safe Schools/Healthy Students Initiative.

A three-level growth-curve model was applied to estimate perceived impact growth trajectories, using multi-year data from project and school surveys on outcome and program implementation collected from 59 sites and approximately 1165 participating schools in the Safe Schools and Healthy Students Initiative. Primary interest is to determine whether and how project-level and school-level correlates affect schools' perceptions of the Initiative's effectiveness over time when the effects of the pre-grant environmental conditions, grant operations, and near-term outcomes are considered. Coordination and service integration, comprehensive programs and activities for early childhood development, and change in school involvement were found to be significant predictors of school-perceived overall impact when the effect of poverty was considered. Partnership functioning, perceived importance of school resources, and school involvement were found to be significant predictors of school-perceived impact on substance use prevention when the effect of poverty was considered.

A national evaluation of Safe Schools/Healthy Students: outcomes and influences.

The Safe Schools/Healthy Students (SS/HS) Initiative has awarded over $2 billion in grants to more than 350 school districts in partnership with local mental health, law enforcement, and juvenile justice agencies. To estimate the impact of grantee characteristics, grant operations, and near-term outcomes in reducing violence and substance use, promoting mental health, and enhancing school safety, logged odds ratios (LORs) were calculated contrasting Year 3 with Baseline performance from grantee-provided data on seven outcome measures. After comparing grantee performance across outcomes and outcomes across grantees, the LORs were entered as dependent variables in a series of meta-regressions in which grantee characteristics, grant operations, and near-term outcomes were tested after controlling for pre-grant characteristics. Findings indicate that the SS/HS Initiative significantly improved most outcomes, that within-grantee performance varied greatly by outcome, and that random-effects meta-regression appreciably decreased the variance available for modeling. The approach demonstrates that the SS/HS Initiative is effective and that locally collected performance data can be used to estimate grantee success in improving youth outcomes.

Intraoperative end-tidal carbon dioxide concentrations: what is the target?

Recent publications suggest that target end-tidal carbon dioxide concentrations should be higher than values currently considered as acceptable. This paper presents evidence that end-tidal carbon dioxide values higher than concentrations that are currently targeted result in improved patient outcomes and are associated with a reduced incidence of postoperative complications.

A survey of acute pain service structure and function in United States hospitals.

Although the number of U.S. hospitals offering an acute pain service (APS) is increasing, the typical structure remains unknown. This survey was undertaken to describe the structure and function of the APS in U.S. hospitals only. We contacted 200 non-teaching and 101 teaching U.S. hospitals. The person in charge of postoperative pain management completed and returned the survey. Seventy-four percent of responding hospitals had an organized APS. An APS was significantly more formally organized in academic/teaching hospitals when compared to non-teaching hospitals. Pain assessments included "pain at rest" (97%), "pain on activity" (63%), and reassessment after pain therapy intervention (88.8%). Responding hospitals utilized postoperative pain protocols significantly more commonly in teaching hospitals when compared to non-teaching and VA hospitals. Intravenous patient controlled analgesia (IV-PCA) was managed most commonly by surgeons (75%), while epidural analgesia and peripheral nerve block infusions were exclusively managed by anesthesiologists. For improved analgesia, 62% allowed RNs to adjust the IV-PCA settings within set parameters, 43% allowed RN adjustment of epidural infusion rates, and 21% allowed RN adjustment of peripheral nerve catheter local anesthetic infusion rates.

Donor-specific antibodies accelerate arteriosclerosis after kidney transplantation.

In biopsies of renal allografts, arteriosclerosis is often more severe than expected based on the age of the donor, even without a history of rejection vasculitis. To determine whether preformed donor-specific antibodies (DSAs) may contribute to the severity of arteriosclerosis, we examined protocol biopsies from patients with (n=40) or without (n=59) DSA after excluding those with any evidence of vasculitis. Among DSA-positive patients, arteriosclerosis significantly progressed between month 3 and month 12 after transplant (mean Banff cv score 0.65 ± 0.11 to 1.12 ± 0.10, P=0.014); in contrast, among DSA-negative patients, we did not detect a statistically significant progression during the same timeframe (mean Banff cv score 0.65 ± 0.11 to 0.81 ± 0.10, P=not significant). Available biopsies at later time points supported a rate of progression of arteriosclerosis in DSA-negative patients that was approximately one third that in DSA-positive patients. Accelerated arteriosclerosis was significantly associated with peritubular capillary leukocytic infiltration, glomerulitis, subclinical antibody-mediated rejection, and interstitial inflammation. In conclusion, these data support the hypothesis that donor-specific antibodies dramatically accelerate post-transplant progression of arteriosclerosis.

Focal segmental glomerulosclerosis plays a major role in the progression of IgA nephropathy. I. Immunohistochemical studies.

IgA nephropathy (IgAN) often shows lesions morphologically identical with those of focal segmental glomerulosclerosis (FSGS). In order to determine the possible role of FSGS in IgAN lesions, we measured glomerular capsular adhesions, often the first step toward FSGS, in biopsies from 127 patients with IgAN, 100 with lupus nephritis, and 26 with primary FSGS. Capsular adhesions with no lesions in the underlying tuft, consistent with podocyte abnormality or loss, were found regularly in FSGS and IgAN, but infrequently in lupus. Fifteen biopsies of patients with IgAN were studied immunohistochemically using markers for podocytes, Bowman's parietal epithelial cells, proliferating cells, and macrophages. Cytokeratins CK-8 and C2562 differentiated normal podocytes (negative) from parietal epithelial cells (variably positive). There was focal loss of the podocyte markers synaptopodin, glomerular epithelial protein 1 (GLEPP-1), nephrin, and vascular endothelial growth factor (VEGF), particularly at sites of capsular adhesions in otherwise histologically normal glomeruli. Cells displaying the parietal epithelial cell markers PAX2 (paired box gene 2) and the cytokeratins were also positive for the proliferating cell marker, proliferating cell nuclear antigen. These cells gathered at sites of adhesion, and in response to active lesions in the tuft, grew inward along the adhesion onto the tuft, forming a monolayer positive for parietal markers and the podocyte marker Wilms tumor protein-1 (WT-1). These cells deposited a layer of collagen over the sclerosing tuft. Thus, all biopsies of patients with IgAN had changes basically identical to those classically described in FSGS. Hence, our study strongly suggests that podocytopathy of a type similar to that in primary FSGS occurs frequently in IgAN.

Focal segmental glomerulosclerosis plays a major role in the progression of IgA nephropathy. II. Light microscopic and clinical studies.

It is well known that lesions morphologically identical with focal segmental glomerulosclerosis (FSGS) may appear in IgA nephropathy (IgAN). Capsular adhesions without underlying abnormalities in the tuft, often the first sign of FSGS, are frequent in IgAN. In this retrospective study, a new cohort of 128 adult patients with IgAN was used to validate the new Oxford classification system of IgAN, and shown to have highly significant associations with clinical and outcome parameters. We then used these patients to determine the extent to which IgAN could be accounted for in terms of FSGS. Some form of lesion consistent with FSGS, notably hyalinosis and collapsing glomerulopathy, was found in 101 of these patients. No glomerular lesions were found in 16 patients, and 11 had mild lesions not definable as FSGS. Those with FSGS had significantly worse renal survival at 80 months than those without. Comparison of pure forms of FSGS (excluding collapsing glomerulopathy) with cases of FSGS having other glomerular lesions (mesangial hyperplasia, endocapillary hypercellularity, glomerular necroses, extracapillary proliferation) revealed that those with FSGS and other superimposed lesions did significantly worse than cases of pure FSGS at 80 months following diagnosis. Importantly, patients with pure FSGS had relatively poor survival even without other superimposed glomerular abnormalities. Thus, the majority of cases of IgAN can be interpreted as representing one or another variant of FSGS. Hence, interpreting IgAN in terms of FSGS emphasizes the role that podocyte lesions may play in the pathogenesis and progression of this disease.