Kidney tubule health scores and their associations with incident CKD in women living with HIV.

OBJECTIVES: Individual kidney tubule biomarkers are associated with chronic kidney disease (CKD) risk in people living with HIV (PLWH). Whether a combination of kidney biomarkers can be integrated into informative summary scores for PLWH is unknown. METHODS: We measured eight urine biomarkers of kidney tubule health at two visits over a 3-year period in 647 women living with HIV in the Women's Interagency Health Study. We integrated biomarkers into factor scores using exploratory factor analysis. We evaluated associations between CKD risk factors and factor scores, and used generalized estimating equations to determine associations between factor scores and risk of incident CKD. RESULTS: Factor analysis identified two unique factor scores: a tubule reabsorption score comprising alpha-1-microglobulin, beta-2-microglobulin and trefoil factor-3; and a tubule injury score comprising interleukin-18 and kidney injury molecule-1. We modelled the two factor scores in combination with urine epidermal growth factor (EGF) and urine albumin. Predominantly HIV-related CKD risk factors were independently associated with worsening tubule reabsorption scores and tubule injury scores. During a median follow-up of 7 years, 9.7% (63/647) developed CKD. In multivariable time-updated models that adjusted for other factor scores and biomarkers simultaneously, higher tubule reabsorption scores [risk ratio (RR) = 1.27, 95% confidence interval (CI): 1.01-1.59 per 1 SD higher time-updated score], higher tubule injury scores (RR = 1.36, 95% CI: 1.05-1.76), lower urine EGF (RR = 0.75, 95% CI: 0.64-0.87), and higher urine albumin (RR = 1.20, 95% CI: 1.02-1.40) were jointly associated with risk of incident CKD. CONCLUSIONS: We identified two novel and distinct dimensions of kidney tubule health that appear to quantify informative metrics of CKD risk in PLWH.

The association of adiposity with kidney function decline among HIV-infected adults: findings from the Fat Redistribution and Metabolic Changes in HIV Infection (FRAM) study.

OBJECTIVES: The aim of the study was to investigate the association of adiposity with longitudinal kidney function change in 544 HIV-infected persons in the Study of Fat Redistribution and Metabolic Change in HIV infection (FRAM) cohort over 5 years of follow-up. METHODS: The regional distribution of muscle and adipose tissue was quantified by whole-body magnetic resonance imaging (MRI), and total adiponectin and leptin levels were measured in serum. Kidney function was assessed using the estimated glomerular filtration rate from serum cystatin C (eGFRCys), obtained at baseline and follow-up. Rapid kidney function decline was defined as annual loss of eGFRCys ≥ 3 mL/min/1.73 m(2) , and incident chronic kidney disease (CKD) was defined as eGFRCys <60 mL/min/1.73 m(2) . Multivariate regression analysis was adjusted for age, race, gender, glucose, antihypertensive use, serum albumin, baseline and change in HIV viral load. RESULTS: At baseline, mean age was 43 years, mean eGFRCys was 86 mL/min/1.73 m(2) , and 21% of patients had albuminuria. The mean (± standard deviation) eGFRCys decline was -0.11 ± 4.87 mL/min/1.73 m(2) per year; 23% of participants had rapid kidney function decline, and 10% developed incident CKD. The lowest tertile of visceral adipose tissue and the highest tertile of adiponectin were both marginally associated with annual kidney function decline of -0.5 mL/min/1.73 m(2) each, but these associations were not statistically significant after adjustment. We found no statistically significant associations of MRI-measured regional adiposity or serum adipokines with rapid kidney function decline or incident CKD (all P-values>0.1 in adjusted models). CONCLUSIONS: Contrary to findings in the general population, adiposity did not have a substantial association with longitudinal change in kidney function among HIV-infected persons.

Urinary biomarkers of kidney injury are associated with all-cause mortality in the Women's Interagency HIV Study (WIHS).

OBJECTIVES: Chronic kidney disease (CKD) is common in HIV-infected individuals, and is associated with mortality in both the HIV-infected and general populations. Urinary markers of tubular injury have been associated with future kidney disease risk, but associations with mortality are unknown. METHODS: We evaluated the associations of urinary interleukin-18 (IL-18), liver fatty acid binding protein (L-FABP), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) and the albumin-to-creatinine ratio (ACR) with 10-year, all-cause death in 908 HIV-infected women. Serum cystatin C was used to estimate the glomerular filtration rate (eGFRcys). RESULTS: There were 201 deaths during 9269 person-years of follow-up. After demographic adjustment, compared with the lowest tertile, the highest tertiles of IL-18 [hazard ratio (HR) 2.54; 95% confidence interval (CI) 1.75-3.68], KIM-1 (HR 2.04; 95% CI 1.44-2.89), NGAL (HR 1.50; 95% CI 1.05-2.14) and ACR (HR 1.63; 95% CI 1.13-2.36) were associated with higher mortality. After multivariable adjustment including adjustment for eGFRcys, only the highest tertiles of IL-18 (HR 1.88; 95% CI 1.29-2.74) and ACR (HR 1.46; 95% CI 1.01-2.12) remained independently associated with mortality. Findings for KIM-1 were borderline (HR 1.41; 95% CI 0.99-2.02). We found a J-shaped association between L-FABP and mortality. Compared with persons in the lowest tertile, the HR for the middle tertile of L-FABP was 0.67 (95% CI 0.46-0.98) after adjustment. Associations were stronger when IL-18, ACR and L-FABP were simultaneously included in models. CONCLUSIONS: Among HIV-infected women, some urinary markers of tubular injury are associated with mortality risk, independently of eGFRcys and ACR. These markers represent potential tools with which to identify early kidney injury in persons with HIV infection.

Body mass index as a phenotypic expression of adiposity: quantitative contribution of muscularity in a population-based sample.

OBJECTIVE: Although widely applied as a phenotypic expression of adiposity in population and gene-search studies, body mass index (BMI) is also acknowledged to reflect muscularity even though relevant studies directly measuring skeletal muscle (SM) mass are lacking. The current study aimed to fill this important gap by applying advanced imaging methods to test the hypothesis that, after controlling first for adiposity, SM mass is also a significant determinant of BMI in a population-based sample. DESIGN: Whole-body magnetic resonance imaging scans were completed in Coronary Artery Risk Development in Young Adults study subjects aged 33-45 years. Physical activity (PA) levels, alcohol intake and adequacy of food intake were assessed by standardized questionnaires. SUBJECTS: The study included 58 African-American (AA) and 78 Caucasian (C) men; and 63 AA and 64 C women. MEASUREMENTS: Whole-body adipose tissue (AT) and SM volumes. RESULTS: AT was significantly predicted by not only BMI, but also PA and alcohol intake with total model R (2)'s of 0.68 (P<0.0001) for men and 0.89 (P<0.0001) for women. Men had more SM than AT at all levels of BMI whereas SM predominated in women at lower BMIs (C<26 kg/m(2); AA<28 kg/m(2)). In men, both AT and SM contributed a similar proportion of between-subject variation in BMI. In contrast, in women AT contributed approximately 30% more than SM to the variation in BMI. Developed allometric models indicated SM associations with AT, PA and race after adjusting for height. There was little association of age, lifestyle factors or race with BMI after controlling for both AT and SM. CONCLUSION: Variation in muscularity provides a mechanistic basis for the previously observed nonspecificity of BMI as a phenotypic expression of adiposity. These quantitative observations have important implications when choosing adiposity measures in population and gene-search studies.

The five bromotryptophans.

The five regioisomeric bromotryptophans (BrTrps) play an important role in the life of sponges and lower marine invertebrates. These bromo-amino acids, which are formed by post-translational modifications, are not found in nature in their free state, but rather are involved in more complex structures. Any of the BrTrps can be part of a peptide, a cyclic peptide, an indole alkaloid, an ergot alkaloid, a macrocycle and others. The present review covers the synthesis, physical and spectroscopic properties of the five BrTrps. It also describes the many exiting pharmacological and biological activities played by the BrTrps and by various secondary metabolites containing brominated tryptophan moieties. Of special interest are cyclic peptides containing the 2-BrTrp unit, which were isolated from marine sponges e.g. konbamide, orbiculamide A, the various keramamides, jaspamide eusynstyelamide and more. Important families of non-cyclic peptides containing the 6-BrTrp, include the styelins, the conotoxins, the cathelicidins and several constrained macrocyclic peptides. Many marine secondary BrTrp-containing, non-peptidic metabolites also display a remarkable spectrum of bioactivities, which can be harnessed for therapeutic and other purposes. Examples are: barettin, bromotryptanthrin, tetraacetyl clionamide, cyclocinamide A, clavicipitic acid, various brominated beta-carbolines. In this review we have presented the various synthetic routes leading to the preparation of the five BrTrps and many of its derivatives. Also, we have introduced the reader to many synthetic routes leading to BrTrp-containing non-peptidic natural products. Although the functional role of the various compounds in the human body is only poorly understood, its effects were extensively studied. Almost all of these compounds exhibit important therapeutic properties e.g. antifungal, antimicrobial, antihelmintic, insecticidal ichthyotoxic and anticancer activity. In the present review attempts have been made to provide synopsis, synthesis and symbiosis of chemical and biological actions, which may provide future guidance and facilitate further research in this area.

[Terminal decline--a problematic construct? A study of persons in their 80's and 90's]. / Terminal Decline--ein problematisches Konstrukt? Eine Studie bei Personen im 8. und 9. Lebensjahrzehnt.

Within the research of intellectual functioning in aged people the hypothesis of terminal decline is quite common. This paper is stressing the question of the global validity of terminal decline. It will be shown that terminal decline has to be discussed within the frame work of changes in the processes of aging.

[Terminal care--a burden for professional and familial caregivers?]. / Sterbebegleitung--eine Last für professionelle und familiäre Helfer?

Within a framework of the results of thanatological research the main concerns of caring for the dying are worked out. It is shown that the personal besides education and training on the job needs a sort of permanent supervision in that field of work. Nevertheless caring for the dying will be a burden as long as the society neglects and ignores the needs of dying people. This is also true for the members of the family, friends and other nonprofessional people, who engage themselves in the care for the dying.

Reflections on cultural influences on aging and old-age suicide in Germany.

The limited attention paid to old-age suicide in Germany is likely related to society's lack of interest in the specific problems of old people. This is despite the fact that over half of all German suicides are committed by persons 65 and older. In reviewing what is known about elderly suicide based on retrospective studies, I submit that suicide in later life is not always based on pathologic mental processes. There may be a number of risk factors unique to elderly suicides, in addition to depressive disorders that involve broader cultural issues among the many motives likely present in any one suicide. Today's emphasis on individualized values may lead to a feeling of meaninglessness in the suicidal elderly. The uncertainty and fear of the inability to influence their own dying a certain weariness of life are also likely unique risk factors for the elderly. Thus the reasons or motives for a suicide may be best considered by understanding the entire life situation and the biographical aspects of the person. Prevention of elderly suicides requires a number of approaches ranging from social assistance and improved training of care providers to more acceptance and valuing of older persons by society.

[Consistency and variability of intellectual and psychomotor abilities in aged people (author's transl)]. / Konstanz und Veränderung in der psychischen Leistungsfähigkeit.

Several methods of statistical analyses, featuring as well group specific changes and intra-individual changes, in an investigation of intelligence, psychomotor abilities of 121 aged men and women over a period of 7 years, lead to results that there are many different aspects of consistancy and change. An attempt is made to discuss these results in the framework of differential and developmental psychological aspects.

[Preparing for old age. Biographic perspectives]. / Vorbereitung auf das Alter - eine biographische Perspektive.

Some biographical perspectives within the frame of preretirement education are lined out. Elements of learning ability, knowledge and motivation are discussed and some strategies for practise are developed.

[Adjustment and adaptation]. / Anpassung und Adaptation.

As in many other scientific disciplines, in gerontology adaptation is a central term. Yet it is not being used in a standardized way. This article describes the concepts and theoretical approaches which can be identified in Social Gerontology, together with their functions and the results of research.

[Estimating length of stay of geriatric rehabilitation patients]. / Zur Abschätzung der Verweildauer bei geriatrischen Rehabilitationspatienten.

The aim of the study was to identify the most influential predictors of length of stay (LOS) among data, which are usually available on admission in geriatric rehabilitation units, such as diagnosis, functional limitations, age, gender, or marital status. Datasets of 6740 consecutive patients of a geriatric rehabilitation clinic have been retained for the analysis. As the density distribution of the LOS was grouped in intervals of 0-4, 4-6, 6-8 and 8 weeks and more, separate multivariate logistic regression models have been tested for the four intervals of LOS as well as for each of the four intervals separately. Some functional limitations on admission are significantly associated with longer LOS: limitations in dressing are associated with LOS of 6-8 weeks (OR = 1.47; CI = 1.32-1.65), and limitations in using the toilet are associated with LOS of 8 weeks and more (OR = 3.50; CI = 2.98-4.10). Shorter LOS of 0 to 4 weeks are significantly predicted by being respectively married (OR = 1.52; CI = 1.37-1.68), 75 years old and alder (OR = 1.29; CI = 1.16-1.43) or having a femur fracture (OR = 1.45; CI = 1.22-1.73). Single ADL-limitations such as in using the toilet or in dressing have a high predictivity of the LOS. Married patients and older patients are discharged earlier. Social characteristics like those subsumated under age or marital status seem to play a more important role as expected in determining the LOS in geriatric rehabilitation patients.

[Status of the elderly among gypsies]. / Zur Situation alter Menschen bei Zigeunern.

An overview of the relevant literature shows that on one side the chronological age is important in the frame of the social position of an old man or woman in a gypsy society, but much more important is the individual itself and its social situation. Only by reaching a very old age no old gypsy can reach an important position in his society.

[Crises in old age. Trial with a multivariant analysis of adjustment strategies in crises]. / Krisen im Alter. Ein Versuch einer multivariaten Analyse von Bewältigungsstrategien in Krisen.

After a short review of some relevant theories focusing mainly on their developmental aspects, an own model is proposed. This is statistically analysed by means of the LISREL-algorithm, which is applied to data concerning crises behavior in a problematic housing situation, and which were gained from the Bonn-Longitudinal Study of Aging. From the psychological point of view, especially those findings seem to be important which imply that an active and problem-oriented coping strategy is often joined but not overruled by a passive and problem-disoriented one, whereas, if a problem-disoriented strategy predominates, this interferes with any rather active solution strategies turning up. Moreover, the situational stress is perceived more intensive under active rather than under passive strategies and--additionally--health and (test-)intelligence turned out to interact with other variables in a specific way: high intelligence covaries with low scores on perceived stress and passive coping styles, while stressed health rather correlates with passive strategies and a raised subjective load.

[Structural problems to open the universities for older adults (author's transl)]. / Die strukturellen Voraussetzungen für die Offnung der Universitäten für ältere Erwachsene.

On the basis of a comprehensive selection of problems the group decided to discuss two problems intensively: What are the legal and institutional conditions for continuing university studies in later years, and what are the characteristic contributions of universities, in terms of research, curricula and education?

Research on aging in behavioral sciences in the Federal Republic of Germany.

The paper reports on cross-sectional and longitudinal studies on psychological, sociological, as well as physical aspects of aging completed or going on in the Federal Republic of Germany. Most of these studies are referring to community aged and point to the complex conditions of consistency and change in cognitive functioning and personality adjustment during the middle and later years. They stress the high degree of interindividual variability of the aging process and ask for a differential instead of a normative gerontology.

[Initial results of a comparative study of the life style of the elderly in homes in Spain and Germany]. / Erste Ergebnisse einer Vergleichsstudie zur Lebenssituation alter Menschen in Heimen in Spanien und Deutschland.

Within the framework of a pilot study 100 inhabitants of homes for the aged in Spain and in Germany were asked for aspects of their life-situation. The results are described under different views of the social and cultural living conditions in both countries, and analyzed for studies comparing Spain and Germany to be planned in the future.