Hydroxypropyl-ß-cyclodextrin protects from kidney disease in experimental Alport syndrome and focal segmental glomerulosclerosis.

Studies suggest that altered renal lipid metabolism plays a role in the pathogenesis of diabetic kidney disease and that genetic or pharmacological induction of cholesterol efflux protects from the development of diabetic kidney disease and focal segmental glomerulosclerosis (FSGS). Here we tested whether altered lipid metabolism contributes to renal failure in the Col4a3 knockout mouse model for Alport Syndrome. There was an eight-fold increase in the cholesterol content in renal cortexes of mice with Alport Syndrome. This was associated with increased glomerular lipid droplets and cholesterol crystals. Treatment of mice with Alport Syndrome with hydroxypropyl-ß-cyclodextrin (HPßCD) reduced cholesterol content in the kidneys of mice with Alport Syndrome and protected from the development of albuminuria, renal failure, inflammation and tubulointerstitial fibrosis. Cholesterol efflux and trafficking-related genes were primarily affected in mice with Alport Syndrome and were differentially regulated in the kidney cortex and isolated glomeruli. HPßCD also protected from proteinuria and mesangial expansion in a second model of non-metabolic kidney disease, adriamycin-induced nephropathy. Consistent with our experimental findings, microarray analysis confirmed dysregulation of several lipid-related genes in glomeruli isolated from kidney biopsies of patients with primary FSGS enrolled in the NEPTUNE study. Thus, lipid dysmetabolism occurs in non-metabolic glomerular disorders such as Alport Syndrome and FSGS, and HPßCD improves renal function in experimental Alport Syndrome and FSGS.

Health literacy in childhood and youth: a systematic review of definitions and models.

BACKGROUND: Children and young people constitute a core target group for health literacy research and practice: during childhood and youth, fundamental cognitive, physical and emotional development processes take place and health-related behaviours and skills develop. However, there is limited knowledge and academic consensus regarding the abilities and knowledge a child or young person should possess for making sound health decisions. The research presented in this review addresses this gap by providing an overview and synthesis of current understandings of health literacy in childhood and youth. Furthermore, the authors aim to understand to what extent available models capture the unique needs and characteristics of children and young people. METHOD: Six databases were systematically searched with relevant search terms in English and German. Of the n = 1492 publications identified, N = 1021 entered the abstract screening and N = 340 full-texts were screened for eligibility. A total of 30 articles, which defined or conceptualized generic health literacy for a target population of 18 years or younger, were selected for a four-step inductive content analysis. RESULTS: The systematic review of the literature identified 12 definitions and 21 models that have been specifically developed for children and young people. In the literature, health literacy in children and young people is described as comprising variable sets of key dimensions, each appearing as a cluster of related abilities, skills, commitments, and knowledge that enable a person to approach health information competently and effectively and to derive at health-promoting decisions and actions. DISCUSSION: Identified definitions and models are very heterogeneous, depicting health literacy as multidimensional, complex construct. Moreover, health literacy is conceptualized as an action competence, with a strong focus on personal attributes, while also recognising its interrelatedness with social and contextual determinants. Life phase specificities are mainly considered from a cognitive and developmental perspective, leaving children's and young people's specific needs, vulnerabilities, and social structures poorly incorporated within most models. While a critical number of definitions and models were identified for youth or secondary school students, similar findings are lacking for children under the age of ten or within a primary school context.

[,, I would be sad then, because they are all talking about my dad" - The Role of Stigma in Families Affected by Parental Mental Illness]. / " dann würde ich traurig werden, weil alle über meinen Papa reden" ­ Die Rolle des Stigmas in Familien mit psychisch erkranktem Elternteil.

Stigmatization of mental illness is a societal problem, and is also relevant for help-seeking. In a qualitative interview study, the role of stigma in help-seeking was examined from the perspective of parents with mental illness, their children and other relatives. Parents with mental illness assigned an important role to stigma for help-seeking processes. Children rarely made explicit statements about this, but an implicit awareness of stigma can be assumed.

Systemic and renal lipids in kidney disease development and progression.

Altered lipid metabolism characterizes proteinuria and chronic kidney diseases. While it is thought that dyslipidemia is a consequence of kidney disease, a large body of clinical and experimental studies support that altered lipid metabolism may contribute to the pathogenesis and progression of kidney disease. In fact, accumulation of renal lipids has been observed in several conditions of genetic and nongenetic origins, linking local fat to the pathogenesis of kidney disease. Statins, which target cholesterol synthesis, have not been proven beneficial to slow the progression of chronic kidney disease. Therefore, other therapeutic strategies to reduce cholesterol accumulation in peripheral organs, such as the kidney, warrant further investigation. Recent advances in the understanding of the biology of high-density lipoprotein (HDL) have revealed that functional HDL, rather than total HDL per se, may protect from both cardiovascular and kidney diseases, strongly supporting a role for altered cholesterol efflux in the pathogenesis of kidney disease. Although the underlying pathophysiological mechanisms responsible for lipid-induced renal damage have yet to be uncovered, several studies suggest novel mechanisms by which cholesterol, free fatty acids, and sphingolipids may affect glomerular and tubular cell function. This review will focus on the clinical and experimental evidence supporting a causative role of lipids in the pathogenesis of proteinuria and kidney disease, with a primary focus on podocytes.

[Subjective Needs of Support in Families with a Mentally Ill Parent ­ A Literature Review]. / Subjektive Hilfebedarfe in Familien mit psychisch erkranktem Elternteil - Eine Literaturübersicht.

Mentally ill parents are often sceptical about professional help for their children although these children face an increased risk to develop a mental disease themselves. To get a better understanding of needs and help-seeking behaviour in those families a systematic literature review was conducted. Four databases (FIS, PsycINFO, PSYNDEX, PubPsych) were scanned for international and national research literature. Out of 18,057 articles 56 were included which report quantitative or qualitative studies taking the children's and parents' perspectives into account. A thematic synthesis was done to categorize the needs. Results concerning the help-seeking behaviour and the influence of demographic variables were extracted and summarized. Our results were limited by the aspect that no evaluation of study quality had been made and influences on the categorizing process by the authors' subjective perceptions are likely. There were a lot of hints regarding the needs of the families, but little report was found about help-seeking behaviour and demographic variables. The "health literacy" concept was discussed as a basis for further research in this area.

Fibroblast growth factor 23 is not associated with and does not induce arterial calcification.

Elevated fibroblast growth factor 23 (FGF23) is associated with cardiovascular disease in patients with chronic kidney disease. As a potential mediating mechanism, FGF23 induces left ventricular hypertrophy; however, its role in arterial calcification is less clear. In order to study this, we quantified coronary artery and thoracic aorta calcium by computed tomography in 1501 patients from the Chronic Renal Insufficiency Cohort (CRIC) study within a median of 376 days (interquartile range 331-420 days) of baseline. Baseline plasma FGF23 was not associated with the prevalence or severity of coronary artery calcium after multivariable adjustment. In contrast, higher serum phosphate levels were associated with prevalence and severity of coronary artery calcium, even after adjustment for FGF23. Neither FGF23 nor serum phosphate were consistently associated with thoracic aorta calcium. We could not detect mRNA expression of FGF23 or its coreceptor, klotho, in human or mouse vascular smooth muscle cells, or normal or calcified mouse aorta. Whereas elevated phosphate concentrations induced calcification in vitro, FGF23 had no effect on phosphate uptake or phosphate-induced calcification regardless of phosphate concentration or even in the presence of soluble klotho. Thus, in contrast to serum phosphate, FGF23 is not associated with arterial calcification and does not promote calcification experimentally. Hence, phosphate and FGF23 promote cardiovascular disease through distinct mechanisms.

FGF23 in chronic kidney disease.

Chronic kidney disease (CKD) is a growing public health epidemic that is associated with a markedly increased risk of cardiovascular mortality. Disordered mineral metabolism and particularly, disordered phosphorus metabolism appears to be a contributing factor. Fibroblast growth factor 23 (FGF23) regulates phosphorus and vitamin D metabolism. Its levels increase progressively beginning in early CKD, presumably as a physiological adaptation to maintain normal serum phosphate levels or normal phosphorus balance. FGF23 promotes phosphaturia and decreases production of calcitriol. Recent studies suggest that increased FGF23 is associated with mortality, left ventricular hypertrophy, endothelial dysfunction and progression of CKD. These results were consistently independent of serum phosphate levels. At the very least, FGF23 is emerging as a novel biomarker that may help identify which CKD patients might benefit most from aggressive management of disordered phosphorus metabolism. It is also possible that markedly increased FGF23 levels in CKD could contribute directly to tissue injury in the heart, vessels and kidneys, an exciting question that is sure to be the topic of intense investigation in the near future.

Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease.

Fibroblast growth factor 23 (FGF23) regulates phosphorus metabolism and is a strong predictor of mortality in dialysis patients. FGF23 is thought to be an early biomarker of disordered phosphorus metabolism in the initial stages of chronic kidney disease (CKD). We measured FGF23 in baseline samples from 3879 patients in the Chronic Renal Insufficiency Cohort study, which is a diverse cohort of patients with CKD stage 2-4. Mean serum phosphate and median parathyroid hormone (PTH) levels were in the normal range, but median FGF23 was markedly greater than in healthy populations, and increased significantly with decreasing estimated glomerular filtration rate (eGFR). High levels of FGF23, defined as being above 100 RU/ml, were more common than secondary hyperparathyroidism and hyperphosphatemia in all strata of eGFR. The threshold of eGFR at which the slope of FGF23 increased was significantly higher than the corresponding threshold for PTH based on non-overlapping 95% confidence intervals. Thus, increased FGF23 is a common manifestation of CKD that develops earlier than increased phosphate or PTH. Hence, FGF23 measurements may be a sensitive early biomarker of disordered phosphorus metabolism in patients with CKD and normal serum phosphate levels.

Pregnancy-associated plasma protein-A is an independent short-time predictor of mortality in patients on maintenance haemodialysis.

AIMS: Mortality of maintenance haemodialysis (HD) patients is very high due to polymorbidity, mostly from metabolic and cardiovascular disease. In order to identify patients with high risk for life-threatening complications, reliable prognostic markers would be helpful. Pregnancy-associated plasma protein-A (PAPP-A) has been shown to predict cardiovascular events and death in patients with stable coronary artery disease as well as in acute coronary syndrome in patients with normal renal function. It was the aim of this study to evaluate PAPP-A as a marker for death in patients on maintenance HD. METHODS AND RESULTS: PAPP-A serum levels were measured in 170 patients participating in the monitor! trial, a prospective dynamic dialysis cohort multicenter study in Switzerland. Patients were followed up for a median time of 17 months after measuring PAPP-A, and evaluated for death of any cause. Survivors and non-survivors were compared with regard to baseline PAPP-A concentrations. A multivariate logistic regression analysis for death was performed including PAPP-A, age, sex, number of comorbidities, dialysis vintage, Kt/V, IL-6, C-reactive protein, parathyroid hormone (PTH), Ca x PO(4) product, and total serum cholesterol. A cut-off value for PAPP-A was calculated for discrimination between patients with low and high mortality risk, respectively. A total of 23 deaths occurred during follow-up, equalling an incidence rate of 0.1. Baseline median PAPP-A levels were 40% higher in non-survivors vs. survivors (P = 0.023). In a multivariate analysis, only PAPP-A, age, and Ca x PO(4) product were independent predictors of mortality. A cut-off value of 24 mIU/L discriminates significantly (P = 0.015) between patients at low or high risk for death with a negative predictive value of 91%. CONCLUSION: PAPP-A is a novel and independent short-time predictor of mortality in a maintenance HD population. The pathogenetic relevance of PAPP-A, particularly in the development of cardiovascular disease, remains to be further elucidated.

Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease.

CONTEXT: A high level of the phosphate-regulating hormone fibroblast growth factor 23 (FGF-23) is associated with mortality in patients with end-stage renal disease, but little is known about its relationship with adverse outcomes in the much larger population of patients with earlier stages of chronic kidney disease. OBJECTIVE: To evaluate FGF-23 as a risk factor for adverse outcomes in patients with chronic kidney disease. DESIGN, SETTING, AND PARTICIPANTS: A prospective study of 3879 participants with chronic kidney disease stages 2 through 4 who enrolled in the Chronic Renal Insufficiency Cohort between June 2003 and September 2008. MAIN OUTCOME MEASURES: All-cause mortality and end-stage renal disease. RESULTS: At study enrollment, the mean (SD) estimated glomerular filtration rate (GFR) was 42.8 (13.5) mL/min/1.73 m(2), and the median FGF-23 level was 145.5 RU/mL (interquartile range [IQR], 96-239 reference unit [RU]/mL). During a median follow-up of 3.5 years (IQR, 2.5-4.4 years), 266 participants died (20.3/1000 person-years) and 410 reached end-stage renal disease (33.0/1000 person-years). In adjusted analyses, higher levels of FGF-23 were independently associated with a greater risk of death (hazard ratio [HR], per SD of natural log-transformed FGF-23, 1.5; 95% confidence interval [CI], 1.3-1.7). Mortality risk increased by quartile of FGF-23: the HR was 1.3 (95% CI, 0.8-2.2) for the second quartile, 2.0 (95% CI, 1.2-3.3) for the third quartile, and 3.0 (95% CI, 1.8-5.1) for the fourth quartile. Elevated fibroblast growth factor 23 was independently associated with significantly higher risk of end-stage renal disease among participants with an estimated GFR between 30 and 44 mL/min/1.73 m(2) (HR, 1.3 per SD of FGF-23 natural log-transformed FGF-23; 95% CI, 1.04-1.6) and 45 mL/min/1.73 m(2) or higher (HR, 1.7; 95% CI, 1.1-2.4), but not less than 30 mL/min/1.73 m(2). CONCLUSION: Elevated FGF-23 is an independent risk factor for end-stage renal disease in patients with relatively preserved kidney function and for mortality across the spectrum of chronic kidney disease.

Identification of glomerular and podocyte-specific genes and pathways activated by sera of patients with focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) accounts for about 40% of all nephrotic syndrome cases in adults. The presence of several potential circulating factors has been suggested in patients with primary FSGS and particularly in patients with recurrent disease after transplant. Irrespectively of the nature of the circulating factors, this study was aimed at identifying early glomerular/podocyte-specific pathways that are activated by the sera of patients affected by FSGS. Kidney biopsies were obtained from patients undergoing kidney transplantation due to primary FSGS. Donor kidneys were biopsied pre-reperfusion (PreR) and a subset 1-2 hours after reperfusion of the kidney (PostR). Thirty-one post reperfusion (PostR) and 36 PreR biopsy samples were analyzed by microarray and gene enrichment KEGG pathway analysis. Data were compared to those obtained from patients with incident primary FSGS enrolled in other cohorts as well as with another cohort to correct for pathways activated by ischemia reperfusion. Using an ex-vivo cell-based assay in which human podocytes were cultured in the presence of sera from patients with recurrent and non recurrent FSGS, the molecular signature of podocytes exposed to sera from patients with REC was compared to the one established from patients with NON REC. We demonstrate that inflammatory pathways, including the TNF pathway, are primarily activated immediately after exposure to the sera of patients with primary FSGS, while phagocytotic pathways are activated when proteinuria becomes clinically evident. The TNF pathway activation by one or more circulating factors present in the sera of patients with FSGS supports prior experimental findings from our group demonstrating a causative role of local TNF in podocyte injury in FSGS. Correlation analysis with clinical and histological parameters of disease was performed and further supported a possible role for TNF pathway activation in FSGS. Additionally, we identified a unique set of genes that is specifically activated in podocytes when cultured in the presence of serum of patients with REC FSGS. This clinical translational study supports our prior experimental findings describing a potential role of the TNF pathway in the pathogenesis of FSGS. Validation of these findings in larger cohorts may lay the ground for the implementation of integrated system biology approaches to risk stratify patients affected by FSGS and to identify novel pathways relevant to podocyte injury.

Sirolimus ameliorates the enhanced expression of metalloproteinases in a rat model of autosomal dominant polycystic kidney disease.

BACKGROUND: Remodelling of matrix and tubular basement membranes (TBM) is a characteristic of polycystic kidney disease. We hypothesized that matrix and TBM degradation by metalloproteinases (MMPs) could promote cyst formation. We therefore investigated the renal expression of MMPs in the Han:SPRD rat model of autosomal dominant polycystic kidney disease (ADPKD) and examined the effect of sirolimus treatment on MMPs. METHODS: 5-week-old male heterozygous (Cy/+) and wild-type normal (+/+) rats were treated with sirolimus (2 mg/kg/day) through drinking water for 3 months. RESULTS: The mRNA and protein levels of MMP-2 and MMP-14 were markedly increased in the kidneys of heterozygous Cy/+ animals compared to wild-type +/+ as shown by RT-PCR and Western blot analyses for MMP-2 and MMP-14, and by zymography for MMP-2. Strong MMP-2 expression was detected by immunoperoxidase staining in cystic epithelial cells that also displayed an altered, thickened TBM. Tissue inhibitor of metalloproteinases-2 (TIMP-2) expression was not changed in Cy/+ kidneys. Sirolimus treatment leads to decreased protein expression of MMP-2 and MMP-14 in Cy/+, whereas MMP-2 and MMP-14 mRNA levels and TIMP-2 protein levels were not affected by sirolimus. CONCLUSION: In summary, in kidneys of the Han:SPRD rat model of ADPKD, there is a marked upregulation of MMP-2 and MMP-14. Sirolimus treatment was associated with a marked improvement of MMP-2 and MMP-14 overexpression, and this correlated also with less matrix and TBM alterations and milder cystic disease.

Conflict management training and nurse-physician collaborative behaviors.

Collaboration between nurses and physicians continues to be elusive although it is a desirable goal for most in health care. This study used a quasi-experimental design to evaluate the outcomes of a conflict resolution (management) training program on nurses' perception of their collaboration with the physicians with whom they work. Results showed no differences between the experimental and control groups following the intervention. Individual readiness and evaluation of the antecedents of collaboration should be determined before implementing such an intervention.

Posttransplant acidosis and associated disorders of mineral metabolism in patients with a renal graft.

BACKGROUND: Persisting disturbances in acid/base homeostasis may have an impact on several metabolic aspects of individuals with a kidney graft, specifically with regard to mineral metabolism and bone. METHODS: We undertook a cross-sectional analysis among 823 unselected patients being transplanted with a functioning renal allograft who had at least one measurement of venous serum bicarbonate available within a 4-year period before May 1, 2005. As a determinate of metabolic acidosis bicarbonate was measured along with serum calcium, phosphate, parathyroid hormone, and other routine serological and epidemiological parameters. Data were assessed according to quartiles of serum bicarbonate and by univariate analysis. A multivariate regression model examined the effects of potential predictors of acidosis. RESULTS: Mean serum bicarbonate was 22.5+/-4 mmol/L, with 58.1% of the examined renal transplant patients having metabolic acidosis as defined by a venous bicarbonate of <24 mmol/L. Bicarbonatemia was highly associated with serum parathyroid hormone, phosphate, and calcium but also with renal graft function (determined as calculated glomerular filtration rate). Multiple stepwise regression analysis revealed age, glomerular filtration rate, parathyroid hormone, and albumin to be the strongest predictors of serum bicarbonate concentration. Therapy with any calcineurin inhibitor was not associated with an increased likelihood of acidosis (odds ratio 1.04), but a significant difference was found between cyclosporine A and tacrolimus, which had an attributed odds ratio for acidosis of 0.6 and 1.8, respectively. CONCLUSIONS: Metabolic acidosis is highly prevalent among an unselected cohort of renal transplant patients. A clear association exists between the severity of acidosis and disturbances of mineral metabolism. Thus, persisting acid/base disorders may accentuate bone disease in a setting with other factors predisposing for posttransplant osteopathy.

Limited costimulatory molecule expression on renal tubular epithelial cells impairs T cell activation.

BACKGROUND/AIMS: MHC molecules are upregulated on renal proximal tubular epithelial cells (TEC) under inflammatory conditions. This allows TEC to act as 'non-professional' antigen-presenting cells (APC). The aim of this study was to compare the costimulatory molecule expression pattern and the T cell activation capacity between renal TEC and professional APC, e.g. bone marrow-derived dendritic cells (BM-DC). METHODS: Flow cytometry analysis was used to study the costimulatory molecule surface expression on TEC or BM-DC. Ovalbumin-specific CD4 and CD8 T cell activation induced by TEC or BM-DC was compared, in terms of T cell proliferation, cytokine production and CTL activity. RESULTS: TEC did not constitutively express significant amounts of costimulatory molecules. Stimulation of TEC with IFN-beta or IFN-gamma, but not other tested cytokines, enhanced the expression of PD-L1, ICOS-L and CD40. Compared to BM-DC, TEC only induced suboptimal T cell activation. Blockade of PD-L1 on both APC strongly increased T cell activity. Furthermore, high PD-L1-expressing TEC were more resistant to the cytolysis by CTL. CONCLUSION: The low costimulatory molecule expression may explain the suboptimal T cell activation by TEC. The IFN-upregulated negative costimulatory molecule PD-L1 on TEC may play a protective role to limit tissue injury during renal parenchymal immune responses.

Everolimus retards cyst growth and preserves kidney function in a rodent model for polycystic kidney disease.

BACKGROUND/AIMS: Rapamycin inhibits cyst growth in polycystic kidney disease by targeting the mammalian target of rapamycin (mTOR). To determine if this is a class effect of the mTOR inhibitors, we examined the effect of everolimus, the analogue of rapamycin, on disease progression in the Han:SPRD rat model of polycystic kidney disease. METHODS: Four-week-old male heterozygous cystic (Cy/+) and wild-type normal (+/+) Han:SPRD rats were administered everolimus or vehicle (3 mg/kg/day) by gavage for 5 weeks. Kidney function and whole-blood trough levels of everolimus were monitored. After treatment kidney weight and cyst volume density were assessed. Tubule epithelial cell proliferation was assessed by BrdU staining. RESULTS: Everolimus trough levels between 5 and 7 microg/l were sufficient to significantly reduce kidney and cyst volume density by approximately 50 and 40%, respectively. The steady decrease of kidney function in Cy/+ rats was reduced by 30% compared with vehicle-treated Cy/+ rats. Everolimus treatment markedly reduced the number of 5-bromo-2-deoxyuridine-labeled nuclei in cyst epithelia. Body weight gain and kidney function were impaired in everolimus-treated wild-type rats. CONCLUSION: Moderate dosage of everolimus inhibits cystogenesis in Han:SPRD rats. The inhibitory effect of everolimus appears to represent a class effect of mTOR inhibitors.

What are the family needs when a parent has mental health problems? Evidence from a systematic literature review.

PROBLEM: Little evidence exists showing how a given high-risk group of children born to parents with poor mental health seek help and how care may be improved in order to better reach and support their families. METHODS: A systematic literature review was undertaken to identify the needs and help-seeking behaviors of children and their parents. Through an analysis of both quantitative and qualitative studies, published in German- and English-speaking research literature, the needs of children and parents were identified and categorized. Findings concerning their help-seeking behavior and the influence of demographic variables on needs and help-seeking behaviors were also described. FINDINGS: In the primary studies, the most identified parental needs were "the need for being a good parent"; "worries about the child's well-being"; and "the need for practical help." For children, the categories identified included "the need for knowledge"; "worries about parent's well-being"; and "the need for normality." However, information about help-seeking behaviors and influences of demographic factors was fairly limited in the literature. CONCLUSIONS: In families with parental mental health problems, it seems especially important to take a family-focused approach. The individual needs of children (and their families) should shape the planning of treatment and nursing care.

Addressing global health through the marriage of public health and medicine: developing the University of Washington department of global health.

Widespread interest in global health issues is a common characteristic of students and faculty in schools of public health and schools of medicine. Building on strong university-based and community-based programs in global health, the University of Washington has created a unique Department of Global Health that is housed jointly in its School of Public Health and Community Medicine and its School of Medicine. The creation of this department has generated significant enthusiasm throughout the university and the Seattle community as a new paradigm for addressing global health education, research, and service. Placing the new Department of Global Health in two university schools and finding the appropriate niche for the department among the university's many global health initiatives presented challenges, as well as opportunities. This article describes the goals of the department, the process by which it was created, and what it expects to accomplish.

Prediction of Individual Response to Electroconvulsive Therapy via Machine Learning on Structural Magnetic Resonance Imaging Data.

IMPORTANCE: Electroconvulsive therapy (ECT) is one of the most effective treatments for severe depression. However, biomarkers that accurately predict a response to ECT remain unidentified. OBJECTIVE: To investigate whether certain factors identified by structural magnetic resonance imaging (MRI) techniques are able to predict ECT response. DESIGN, SETTING, AND PARTICIPANTS: In this nonrandomized prospective study, gray matter structure was assessed twice at approximately 6 weeks apart using 3-T MRI and voxel-based morphometry. Patients were recruited through the inpatient service of the Department of Psychiatry, University of Muenster, from March 11, 2010, to March 27, 2015. Two patient groups with acute major depressive disorder were included. One group received an ECT series in addition to antidepressants (n = 24); a comparison sample was treated solely with antidepressants (n = 23). Both groups were compared with a sample of healthy control participants (n = 21). MAIN OUTCOMES AND MEASURES: Binary pattern classification was used to predict ECT response by structural MRI that was performed before treatment. In addition, univariate analysis was conducted to predict reduction of the Hamilton Depression Rating Scale score by pretreatment gray matter volumes and to investigate ECT-related structural changes. RESULTS: One participant in the ECT sample was excluded from the analysis, leaving 67 participants (27 men and 40 women; mean [SD] age, 43.7 [10.6] years). The binary pattern classification yielded a successful prediction of ECT response, with accuracy rates of 78.3% (18 of 23 patients in the ECT sample) and sensitivity rates of 100% (13 of 13 who responded to ECT). Furthermore, a support vector regression yielded a significant prediction of relative reduction in the Hamilton Depression Rating Scale score. The principal findings of the univariate model indicated a positive association between pretreatment subgenual cingulate volume and individual ECT response (Montreal Neurological Institute [MNI] coordinates x = 8, y = 21, z = -18; Z score, 4.00; P < .001; peak voxel r = 0.73). Furthermore, the analysis of treatment effects revealed a increase in hippocampal volume in the ECT sample (MNI coordinates x = -28, y = -9, z = -18; Z score, 7.81; P < .001) that was missing in the medication-only sample. CONCLUSIONS AND RELEVANCE: A relatively small degree of structural impairment in the subgenual cingulate cortex before therapy seems to be associated with successful treatment with ECT. In the future, neuroimaging techniques could prove to be promising tools for predicting the individual therapeutic effectiveness of ECT.