Inflammatory depression is associated with selective glomerular hypofiltration.

BACKGROUND: Systemic low-grade inflammation may be a pathophysiological mechanism in a subtype of depression. In this study we investigate a novel candidate mechanism of inflammatory depression - Selective Glomerular Hypofiltration Syndromes (SGHS) - which are characterized by a reduced estimated glomerular filtration rate (eGFR) based on cystatin C (cysC) relative to eGFR based on creatinine (crea). SGHS have been associated with increased blood levels of pro-inflammatory markers, but have never been investigated in a sample of depressed individuals. METHOD: The prevalence of SGHS was compared between 313 patients with difficult-to-treat depression and 73 controls. Since there is no single established eGFRcysC/eGFRcrea-ratio cut-off to define SGHS, several cut-offs were investigated in relation to a depression diagnosis, inflammation, and symptom severity. Plasma inflammatory markers tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin (IL)-6, IL-8, and IL-10 were available from 276 depressed patients. We examined mediation effects of IL-6 on the relationship between SGHS and depression. RESULTS: Depressed patients were more likely to have SGHS compared to controls defining SGHS as either eGFRcysC/eGFRcrea-ratio < 0.9 (33.2 % vs 20.5 %, p = 0.035) or < 0.8 (15.7 % vs 5.5 %, p = 0.023). Lower eGFRcysC/eGFRcrea-ratio was associated with higher levels of inflammatory markers in depressed patients. IL-6 partly mediated the relationship between SGHS and depression. CONCLUSION: This is the first study to demonstrate a link between SGHS and inflammatory depression. If replicated in independent and longitudinal cohorts, this may prove to be a relevant pathophysiological mechanism in some cases of depression that could be targeted in future intervention and prevention studies.

Osteosarcopenia: Prevalence and 10-Year Fracture and Mortality Risk - A Longitudinal, Population-Based Study of 75-Year-Old Women.

Osteosarcopenia is the coexistence of low bone mass and sarcopenia. In older women, its prevalence is not well described, and it is unknown if sarcopenia is additive to low bone mass for fracture and mortality risk. The study investigated prevalence of osteosarcopenia and if osteosarcopenia is associated with higher fracture and mortality risk than low bone mass alone in older community-dwelling women. The longitudinal, population-based OPRA Cohort (n = 1044), all aged 75 at inclusion, followed for 10 years. Using WHO and EWGSOP2 definitions for low bone mass (T-score < -1.0 femoral neck) and sarcopenia (knee strength; appendicular lean muscle mass) women were categorized (1) Normal, (2) Low bone mass (LBM), and 3) Osteosarcopenia (probable; confirmed). Risk of hip, major osteoporotic fracture, and mortality were estimated. Osteosarcopeniaconfirmed prevalence increased from age 75 to 80 and 85 from 3.0% (29/970) to 4.9% (32/656) to 9.2% (33/358) but prevalence is potentially 2-4 times higher (11.8%, 13.4%, 20.3%) based on osteosarcopeniaprobable. Having osteosarcopeniaprobable significantly increased 10-year risk of hip fracture (HRadj 2.67 [1.34-5.32]), major osteoporotic fracture (HRadj 2.04 [1.27-3.27]), and mortality (HRadj 1.91 [1.21-3.04]). In contrast, LBM increased osteoporotic fracture risk (HRadj 2.08 [1.46-2.97], but not hip fracture (HRadj 1.62 [0.92-2.85]) or mortality (HRadj 0.94 [0.64-1.38]). Median time-to-hip fracture was 7.6 years (normal), 6.0 years (LBM), and 5.7 years (osteosarcopeniaprobable). Prevalence of confirmed osteosarcopenia is almost 10% at age 85. Probable osteosarcopenia significantly increased risk of hip and major osteoporotic fractures and mortality more so than low bone mass alone.

Muscle mass, creatinine, cystatin C and selective glomerular hypofiltration syndromes.

In this issue of Clinical Kidney Journal, Stehlé and colleagues demonstrate that estimation of glomerular filtration rate (GFR) by use of creatinine and a measure, total lumbar muscle cross-sectional area, reflecting the total muscle mass of an individual, is superior to GFR-estimating equations based upon creatinine and demographic variables. The report by Stehlé et al. demonstrates one solution to the interference of muscle mass in the use of creatinine to estimate GFR. This interference was identified already at the start, in 1959, of using creatinine for estimation of GFR. Different ways of taking the muscle mass into account when creatinine-based estimations of GFR have been used generally include use of controversial race and sex coefficients. A new marker of GFR, cystatin C, introduced in 1979, has been shown to be virtually uninfluenced by muscle mass. In this editorial, the simultaneous use of creatinine and cystatin C to estimate GFR, muscle mass and selective glomerular hypofiltration syndromes is described.

Pro-Inflammatory Proteins Associated with Frailty and Its Progression-A Longitudinal Study in Community-Dwelling Women.

The complex pathophysiology underlying biological aging creates challenges for identifying biomarkers associated with frailty. This longitudinal, nontargeted proteomics study aimed to identify proteins associated with frailty, particularly the change from nonfrail to frail. The population-based Osteoporosis Prospective Risk Assessment cohort includes women all of whom are 75 years old at inclusion (n = 1044) and reassessed at 80 years (n = 715) and 85 years (n = 382). A deficits in health frailty index (FI) and 92 plasma proteins (Olink CVD-II panel) were available at all ages. The identical age facilitated differentiating chronological and biological aging. Bidirectional analyses, performed cross-sectionally and longitudinally, used regression models controlled for false discovery rate (FDR), across 5- and 10-year time windows and longitudinal mixed models. Frailty outcomes were frailty index, frailty status (frail defined as FI ≥ 0.25), change in frailty index, and change in frailty status, together with protein expression or change in protein expression. Elevated levels of 32 proteins were positively associated with the FI, cross-sectionally at all ages (range: ß-coefficients 0.22-2.06; FDR 0.021-0.024), of which 18 were also associated with frailty status (range: odds ratios 1.40-5.77; FDR 0.022-0.016). Based on the accrued data, eight core proteins (CD4, FGF23, Gal-9, PAR-1, REN, TNFRSF10A TNFRSF11A, and TNFRSF10B) are proposed. A one-unit change in the FI was additively associated with increased protein expression over 5 and 10 years (range: ß-coefficients 0.52-1.59; p < 0.001). Increments in baseline FI consistently associated with a change in protein expression over time (5 years, ß-range 0.05-1.35; 10 years, ß-range 0.51-1.48; all p < 0.001). A one-unit increase in protein expression was also associated with an increased probability of being frail (FI ≥ 0.25) (ß-range: 0.14-0.61). Mirroring the multisystem deterioration that typifies frailty, the proteins and their associated biological pathways reflect pathologies, including the renal system, skeletal homeostasis, and TRAIL-activated apoptotic signaling. The core proteins are compelling candidates for understanding the development and progression of frailty with advancing age, including the intrinsic musculoskeletal component. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

The complexity of kidney disease and diagnosing it - cystatin C, selective glomerular hypofiltration syndromes and proteome regulation.

Estimation of kidney function is often part of daily clinical practice, mostly done by using the endogenous glomerular filtration rate (GFR)-markers creatinine or cystatin C. A recommendation to use both markers in parallel in 2010 has resulted in new knowledge concerning the pathophysiology of kidney disorders by the identification of a new set of kidney disorders, selective glomerular hypofiltration syndromes. These syndromes, connected to strong increases in mortality and morbidity, are characterized by a selective reduction in the glomerular filtration of 5-30 kDa molecules, such as cystatin C, compared to the filtration of small molecules <1 kDa dominating the glomerular filtrate, for example water, urea and creatinine. At least two types of such disorders, shrunken or elongated pore syndrome, are possible according to the pore model for glomerular filtration. Selective glomerular hypofiltration syndromes are prevalent in investigated populations, and patients with these syndromes often display normal measured GFR or creatinine-based GFR-estimates. The syndromes are characterized by proteomic changes promoting the development of atherosclerosis, indicating antibodies and specific receptor-blocking substances as possible new treatment modalities. Presently, the KDIGO guidelines for diagnosing kidney disorders do not recommend cystatin C as a general marker of kidney function and will therefore not allow the identification of a considerable number of patients with selective glomerular hypofiltration syndromes. Furthermore, as cystatin C is uninfluenced by muscle mass, diet or variations in tubular secretion and cystatin C-based GFR-estimation equations do not require controversial race or sex terms, it is obvious that cystatin C should be a part of future KDIGO guidelines.

Can frailty in conjunction with FRAX identify additional women at risk of fracture - a longitudinal cohort study of community dwelling older women.

BACKGROUND: Fracture risk assessment is still far from perfect within the geriatric population. The overall aim of this study is to better identify older women at risk for fractures, using a quantitative measure of frailty in conjunction with the web-based Fracture Risk Assessment Tool (FRAX®). METHODS: This study was performed in the Osteoporosis Risk Assessment (OPRA) cohort of n = 1023, 75-year-old women followed for 10-years. A frailty index (FI) of 'deficits in health' was created, and FRAX 10-year probability for major osteoporotic and hip fractures was calculated and bone mineral density measured. Incident fractures were continuously registered for 10-years. Receiver Operating Characteristic (ROC) curves were used to compare FI, FRAX and the combination FI + FRAX as instruments for risk prediction. Discriminative ability was estimated by comparing Area Under the Curve (AUC). In addition, using guidelines from the Swedish Osteoporosis Foundation, a category of low risk women who would not have been recommended for pharmacological treatment (non-treatment group) was identified, categorized by frailty status and for relative risk analysis, hazard ratios (HR) and 95% confidence intervals were calculated using Cox proportional hazard regressions. RESULTS: For hip fracture, FRAX and frailty performed almost equally (HIP AUC 10y: 0.566 vs. 0.567, p = 0.015 and p = 0.013). Next, FI was used in conjunction with FRAX; proving marginally better than either score alone (AUC 10y: 0.584, p = 0.002). Comparable results were observed for osteoporotic fracture. In the non-treatment group (564 women), being frail was associated with higher 10y hip fracture risk (HR 2.01 (1.13-3.57)), although failing to reach statistical significance for osteoporotic fracture (HR 1.40 (0.97-2.01). The utility of measuring frailty was also demonstrated when using T-score as an index of bone density to define fracture risk. Among n = 678 non-osteoporotic women, frailty added to the 10-year fracture risk (Hip; HR 2.22 (1.35-3.71); Osteoporotic fracture; HR 1.57 (1.15-2.14)). CONCLUSIONS: While the addition of frailty to FRAX marginally improved fracture prediction, applying a frailty measurement to a group of 'low risk' women, identified a set of individuals with high actual hip fracture risk that would not be prioritized for pharmacological treatment. Further cost-benefit analysis studies are needed to formally test potential benefit.

Bone health as a co-morbidity of chronic kidney disease.

Chronic kidney disease and osteoporosis commonly co-exist in aged patients. Chronic kidney disease affects bone health because of its effect on mineral metabolism in the syndrome, Chronic Kidney Disease Mineral and Bone Disorder, resulting in an increased risk of fractures. Hip fracture risk may be as much as four-fold higher in the worst affected. Tools to estimate fracture risk such as FRAX® and measuring bone density can be used in patients with chronic kidney disease; however, bone density may underestimate fracture risk in this population as it does not give information on bone quality. While osteoporosis treatment in patients with chronic kidney disease stage 1-3 does not differ from the general population, in the absence of Chronic Kidney Disease Mineral and Bone Disorder, patients with disease stage 4-5 require special consideration. It is, however, of the utmost importance that these patients receive pharmacological treatment because of their high risk of fractures.

Bone Turnover Marker Profiling and Fracture Risk in Older Women: Fracture Risk from Age 75 to 90.

PURPOSE: A major challenge in osteoporosis is to identify individuals at high fracture risk. We investigated six bone turnover markers (BTMs) to determine association with specific fracture types; the time-frame for risk prediction and whether these are influenced by age at assessment. METHODS: Population-based OPRA cohort (n = 1044) was assessed at ages 75, 80, 85 and fractures documented for up to 15 years. Six BTMs were analyzed at each time-point (N-terminal propeptide of type I collagen, PINP; total osteocalcin, OC; bone-specific alkaline phosphatase, BALP; C-terminal telopeptide of type I collagen, CTX; tartrate-resistant acid phosphatase 5b, TRAcP5b; urinary osteocalcin). Hazard ratios (HR) for any, major osteoporotic, vertebral and hip fractures were calculated as short (1, 2, 3 years) and long-term risk (5, 10, 15 years). RESULTS: At 75 year, high CTX levels were associated with an increased risk of all fractures, including major osteoporotic fractures, across most time-frames (HRs ranging: 1.28 to 2.28). PINP was not consistently associated. Urinary osteocalcin was consistently associated with elevated short-term risk (HRs ranging: 1.83-2.72). Other BTMs were directionally in accordance, though not all statistically significant. BTMs were not predictive for hip fractures. Association of all BTMs attenuated over time; at 80 year none were associated with an increased fracture risk. CONCLUSION: CTX, urinary OC and TRAcP5b are predictive for fracture in a 1 to 3 year, perspective, whereas in the long-term or above age 80 years, BTMs appear less valuable. Resorption markers, particularly CTX, were more consistently associated with fracture risk than formation markers in the very elderly.

A "snap-shot" visual estimation of health and objectively measured frailty: capturing general health in aging older women.

BACKGROUND: In clinic, a subjective visual estimation of a patient's general health often guides interventions, yet little is known of how this assessment relates to objectively measured frailty. AIMS: To characterize the relationship between these two assessments and explore the implication of discordance. METHODS: The study was performed in the OPRA cohort of 75-year old community-dwelling women (n = 1044). Visual perception of health (VPH) was estimated within 15 s from first sight and stratified into tertiles (poor/intermediate/good health). Frailty was measured using a frailty index (FI) (scored 0.0-1.0) and stratified into tertiles: 'frail' (≥ 0.22), 'pre-frail' (0.13-0-21) and 'non-frail' (≤ 0.12). Association between VPH and FI and with 10-year mortality was evaluated using Kaplan Meier curves and Cox proportional hazard models. RESULTS: VPH and FI correlated, but was strongest in those perceived to be in poor health (rs = 0.424, p < 0.001). Approximately half of these women were also objectively frail (53.7%). Similarly, 50.7% perceived to be in good health were also objectively non-frail. However, for one in ten, perceived health was discordant with measured frailty. Subjective and objective measures were associated with mortality, but VPH lacked discrimination in healthier looking women (p = 0.372) compared to FI (p = 0.002). DISCUSSION: Detecting pre-frailty is important to prevent or slow the transition into a frail state. The frailest can be identified with a visual estimation, but only objective frailty assessments can reliably identity pre-frailty. CONCLUSIONS: A visual estimation of health provides valuable complementary information on health, whereas objective assessment of frailty has a broader applicability for health in aging.

Impaired selective renal filtration captured by eGFRcysC/eGFRcrea ratio is associated with mortality in a population based cohort of older women.

Deranged renal filtration of mid-sized (5-30 kDa) compared to smaller molecules (< 0.9 kDa) results in increased plasma levels of cystatin C (cysC) compared to creatinine resulting in a low eGFRcysC/eGFRcrea ratio. A ratio below 0.6 or 0.7, is termed shrunken pore syndrome (SPS), which in patient based studies is associated with mortality. Reference values for eGFRcysC/eGFRcrea ratio, the prevalence of SPS and the consequence of low eGFRcysC/eGFRcrea ratio in the general, elderly population are unknown. 75-yr old women (n = 849) from the population-based OPRA cohort, followed for 10-years had eGFR calculated with CKD-EPI study equation, and eGFRcysC/eGFRcrea ratio calculated. Mortality risk (HR [95% CI]) was estimated. Women with sarcopenia or on glucocorticoids were excluded. Almost 1 in 10 women (9%) had eGFRcysC/eGFRcrea ratio < 0.6 at age 75 and this did not increase appreciably with age. Women with ratio < 0.6 had higher 10-yr mortality risk compared with ratios > 0.9 (HRadj 1.6 [95% CI 1.1-2.5]). In elderly women eGFRcysC/eGFRcrea ratio < 0.6 is common and associated with increased mortality. Our results confirm patient-based findings, suggesting that identifying individuals with SPS may be clinically relevant to assessing mortality risk in the elderly.

Longitudinal Changes in Kidney Function Estimated from Cystatin C and Its Association with Mortality in Elderly Women.

BACKGROUND/AIMS: Prospective data on age-related changes in kidney function are required, especially since the current Kidney Disease Improving Global Outcomes (KDIGO) definition has been suggested to classify a large number of elderly people with CKD. OBJECTIVE: This study, a complement to our previous Cr-based study in the same cohort, is aimed at evaluating cystatin C (cysC)-based changes in kidney function during aging in older women and analyzing the association between CKD and mortality through 10 years of follow-up. METHODS: cysC was available in 981 women from the Osteoporosis Prospective Risk Assessment (OPRA) cohort, all aged 75 years on entry. Reinvestigations were made after 5 (n = 685) and 10 years (n = 365). Kidney function was estimated (estimated glomerular filtration rate [eGFR]) using Chronic Kidney Disease Epidemiology Collaboration cysC and Caucasian, Asian, Pediatric, and Adult cysC equations and the change in function calculated. Women were staged equivalent to CKD stage 1, 2, 3a, or 3b-5 according to the KDIGO classification. Mortality risk was estimated for 5-year or 10-year follow-up time using Cox proportional hazard analyses (reference category, CKD stages 1 and 2). RESULTS: Mortality risk for women with the worst kidney function (CKD stages 3b-5) increased during both 5-year follow-up times compared to that for women in stages 1 and 2 (age 75-80 years: adjusted Hazard Ratio [HRadj] 3.9, 95% confidence interval [CI] 2.3-6.5; age 80-85 years: HRadj 1.7, 95% CI 1.0-2.7). In contrast, women in stage 3a had increased risk only in the first 5-year follow-up (HRadj 1.7, 95% CI 1.0-3.0, age 75-80 years). Change in kidney function amounted to a loss of 1.9 (±1.4) mL/min/1.73 m2 per year during the 10-year follow-up, and at age 85 years, 4 of every 5 women had an eGFR equivalent to CKD. CONCLUSION: In the future, an age-adapted definition of CKD, lowering the threshold for CKD in the elderly, may be beneficial to avoid overdiagnosis of CKD.

Association Between Vitamin D, Frailty, and Progression of Frailty in Community-Dwelling Older Women.

CONTEXT: Vitamin D (25OHD) is involved in many physiological functions that decline with age, contributing to frailty and increased risk for negative health outcomes. Whether 25OHD is a long-term risk marker for frailty over a longer time and whether it is consistent with advancing age is unclear. OBJECTIVE: To investigate the association between 25OHD and frailty in older women followed for 10 years. DESIGN AND SETTING: Prospective, population-based, cohort study in Malmö, Sweden. PARTICIPANTS: Community-dwelling women, age 75 years (N = 1044) with reassessments at ages 80 (n = 715) and 85 (n = 382) years. METHODS: Frailty was quantified using a 10-variable frailty index. Women were categorized as 25OHD insufficient (<50 nmol/L) or sufficient (≥50 nmol/L). RESULTS: At ages 75 and 80 years, women with insufficient 25OHD were frailer than women with sufficient 25OHD (0.23 vs 0.18, P < 0.001; and 0.32 vs 0.25, P = 0.001, respectively). At age 80 years, 25OHD insufficiency was associated with subsequent frailty 5 years later (0.41 vs 0.32; P = 0.011). Accelerated progression of frailty was not associated with lower 25OHD levels, and 25OHD level >75 nmol/L was not additionally beneficial with regard to frailty. No association between 25OHD and frailty was observed at age 85 years. Within the frailty index, variables associated with 25OHD were related to muscle strength and function. CONCLUSION: In this study, 25OHD insufficiency was associated with increased frailty in all but the oldest old. This study supports the value of maintaining sufficient 25OHD levels for healthy aging.

Genetic Variants Associated with Circulating Fibroblast Growth Factor 23.

BACKGROUND: Fibroblast growth factor 23 (FGF23), a bone-derived hormone that regulates phosphorus and vitamin D metabolism, contributes to the pathogenesis of mineral and bone disorders in CKD and is an emerging cardiovascular risk factor. Central elements of FGF23 regulation remain incompletely understood; genetic variation may help explain interindividual differences. METHODS: We performed a meta-analysis of genome-wide association studies of circulating FGF23 concentrations among 16,624 participants of European ancestry from seven cohort studies, excluding participants with eGFR<30 ml/min per 1.73 m2 to focus on FGF23 under normal conditions. We evaluated the association of single-nucleotide polymorphisms (SNPs) with natural log-transformed FGF23 concentration, adjusted for age, sex, study site, and principal components of ancestry. A second model additionally adjusted for BMI and eGFR. RESULTS: We discovered 154 SNPs from five independent regions associated with FGF23 concentration. The SNP with the strongest association, rs17216707 (P=3.0×10-24), lies upstream of CYP24A1, which encodes the primary catabolic enzyme for 1,25-dihydroxyvitamin D and 25-hydroxyvitamin D. Each additional copy of the T allele at this locus is associated with 5% higher FGF23 concentration. Another locus strongly associated with variations in FGF23 concentration is rs11741640, within RGS14 and upstream of SLC34A1 (a gene involved in renal phosphate transport). Additional adjustment for BMI and eGFR did not materially alter the magnitude of these associations. Another top locus (within ABO, the ABO blood group transferase gene) was no longer statistically significant at the genome-wide level. CONCLUSIONS: Common genetic variants located near genes involved in vitamin D metabolism and renal phosphate transport are associated with differences in circulating FGF23 concentrations.

Longitudinal Assessment of PTH in Community-Dwelling Older Women-Elevations Are Not Associated With Mortality.

CONTEXT: In older women, the magnitude of elevated parathyroid hormone (PTH) and its consequence is unclear. OBJECTIVE: To describe normal PTH profiles over time and the association with mortality. DESIGN AND PARTICIPANTS: There were 1044 community-dwelling women in the Malmö Osteoporosis Prospective Risk Assessment cohort (OPRA) who attended baseline (age 75 years). Follow-ups were attended by 715 (age 80 years) and 382 (age 85 years). MAIN OUTCOME MEASURES: PTH, estimated glomerular filtration rate (eGFR), 25-hydroxyvitamin D (25OHD) and mortality. RESULTS: At age 75 years, PTH levels for most (n = 877, 88%) were within the normal reference range (NRR) (i.e., <6.9 pmol/L). Longitudinally, between ages 75 and 80 years, PTH increased in 60% of all women (n = 390) but increases of up to 50% above baseline values (64%; n=250) still resulted in PTH levels within the NRR. These women had lower 25OHD levels (74 vs 83 nmol/L, P = 0.001). Only when increases were >50% was PTH elevated beyond the NRR (mean 7.1 ± 3.3). Here, a pronounced decline in eGFR (56 vs 61 mL/min/1.73 m2, P = 0.002) was found, despite no further changes in 25OHD. Extending the observational period until age 85 years gave similar results. Baseline PTH levels above NRR were associated with mortality (hazard ratio, 1.4; 95% confidence interval (CI), 1.1-1.8; P = 0.007), although not after adjustment for covariates (P = 0.082). CONCLUSIONS: Most women remained within normal PTH ranges despite large increases of up to 50%. PTH elevated above normal is not independently associated with mortality; impaired kidney function and low 25OHD status may be more prognostic in the very old.

[Leguminous plant causes poisoning with anticholinergic syndrome]. / Baljväxt orsakar förgiftning med antikolinergt syndrom.

In this case report we illustrate how incorrectly prepared and cooked seeds from white lupin - a common snack among people from parts of the Mediterranean and Middle East - caused an anticholinergic syndrome in a previously healthy man. The symptoms subsided without treatment and the patient was discharged from the hospital in good health. Anticholinergic syndrome results from inhibition of the parasympatic nervous system. The symptoms commonly include dry mouth, confusion, hallucinations, fever, tachycardia, and urine retention. The syndrome may most frequently be provoked by overdose of drugs such as prometazin, hyoscyamin, and biperidin or by ingestion of plants such as belladonna, datura and henbane. The aim of this report is to increase clinicians' awareness of white lupin's anticholinergic effects.

Declining Estimated Glomerular Filtration Rate and Its Association with Mortality and Comorbidity Over 10 Years in Elderly Women.

BACKGROUND/AIMS: Renal function deteriorates with age, but a few studies have addressed this longitudinally in elderly women. Our objective was, using 5 estimated glomerular filtration rates (eGFR)-equations, to evaluate changes in renal function and association with adverse outcomes for a decade in 75-year-old women. METHODS: Plasma creatinine was measured at ages 75 (n = 1,011), 78 (n = 827), 80 (n = 689) and 85 (n = 363). Glomerular filtration rates were estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI); Modification of Diet in Renal Disease (MDRD); revised Lund-Malmö (LM-rev); Berlin Initiative Study 1 (BIS1) and Cockcroft-Gault/body surface area (CG/BSA) equations. Mortality and comorbidity were investigated in women with chronic kidney disease (CKD) stage 3A and 3B-5. RESULTS: Approximately, 95% of women had eGFR indicating CKD stage 2-3 and progression towards stage 3 was continuous. The women lost 22% of their eGFR during follow-up and loss accelerated between 80 and 85. Mean loss per decade was 16.6 ml/min/1.73 m(2). Women in CKD stage 3B-5 had an adjusted hazard ratio for death of 3.5 (95% CI 2.1-5.8) compared to stage 1-2 during follow-up and increased risk of diabetes, heart failure and hypertension. The CG/BSA, BIS1 and LM-rev equations continuously predicted lower eGFR than the MDRD and CKD-EPI equations. CONCLUSION: eGFR in women aged 75-85 ranges from 30 to 89 ml/min/1.73 m(2) (stage 2-3). Decline was 16.6 ml/min/1.73 m(2) per decade; accelerated with age and appeared nonlinear. Women with CKD 3B-5 demonstrate an over 3-fold risk of death. eGFR <45 ml/min/1.73 m(2) was associated with mortality, confirming the new KDIGO classification 3A and 3B, as clinically applicable in the elderly.