From secondary to primary prevention of progressive renal disease: The case for screening for albuminuria

From secondary to primary prevention of progressive renal disease: The case for screening for albuminuria. Many subjects nowadays present with end-stage renal failure and its attendant cardiovascular complications without known prior renal damage. In this report we review the evidence available to strongly suggest that the present practice of secondary prevention in those with known prior renal disease should be extended to primary prevention for those subjects in the general population who are at risk for progressive renal failure, but who had never suffered from a primary renal disease. We show that such subjects can be detected by screening for albuminuria. Elevated urinary albumin loss is an indicator not only of poor renal, but also of poor cardiovascular prognosis. In addition to diabetic subjects who are at risk for albuminuria, we also show that hypertensive, obese, and smoking subjects are more susceptible. We suggest that therapies that have been shown to lower albumin excretion, such as ACE inhibitors, angiotensin II receptor antagonists, and statins be started early in such patients to prevent them from developing clinical renal disease and its attendant cardiovascular complications

A method for accurate measurement of GFR in conscious, spontaneously voiding rats

A method for accurate measurement of GFR in conscious, spontaneously voiding rats. Renal function measurement by clearance methods relies on accurately timed urine collection. In small experimental animals, renal function measurement is usually performed under anesthesia and/or with the application of bladder catheters to ensure accurate urine collection. To avoid both anesthesia and the need for bladder catheters we developed a method to measure glomerular filtration rate (GFR) in spontaneously voiding conscious rats. GFR was measured as the urinary clearance of constantly infused 125I-iothalamate. To correct for incomplete bladder emptying, urinary clearance of 125I-iothalamate was multiplied by the ratio of plasma and urinary clearance of simultaneously infused 131I-hippuran, a correction method that has been previously validated in humans. Reproducibility of the technique was evaluated by analysis of the results of four consecutive clearance periods during the day (intra-assay variation) in a group of 17 rats and of two consecutive clearance periods on two or three separate days in a group of 20 rats (inter-assay variation), all with normal renal function. Application of the correction method reduced the intra-assay coefficient of variation (mean ± SD) from 37.4 ± 14.3 to 5.4 ± 2.3% (P < 0.05). The mean inter-assay coefficient of variation fell slightly from 23.4 ± 10.3 to 11.0 ± 7.2% (P < 0.10). In rats with moderately impaired renal function (N = 8) the intra-assay variation fell from 27.9 ± 20.7 to 2.7 ± 1.6% (P < 0.05). Our data show that this correction method is a useful technique to assess renal function in conscious, spontaneously voiding rats

Urinary Albumin Excretion and Its Relation With C-Reactive Protein and the Metabolic Syndrome in the Prediction of Type 2 Diabetes

OBJECTIVE—To investigate urinary albumin excretion (UAE) and its relation with C-reactive protein (CRP) and the metabolic syndrome in the prediction of the development of type 2 diabetes. RESEARCH DESIGN AND METHODS—We used data from the Prevention of Renal and Vascular End Stage Disease (PREVEND) study, an ongoing, community-based, prospective cohort study initiated in 1997 in the Netherlands. The initial cohort consisted of 8,592 subjects. After 4 years, 6,894 subjects participated in a follow-up survey. Subjects with diabetes at baseline or missing data on fasting glucose were excluded, leaving 5,654 subjects for analysis. The development of type 2 diabetes, defined as a fasting glucose ≥7.0 mmol/l and/or the use of antidiabetic medication, was used as the outcome measure. UAE was calculated as the mean UAE from two consecutive 24-h urine collections. Logistic regression models were used, with the development of type 2 diabetes as the dependent variable. RESULTS—Of the 5,654 subjects for whom data were analyzed, 185 (3.3%) developed type 2 diabetes during a mean follow-up period of 4.2 years. UAE, CRP, and the presence of the metabolic syndrome at baseline were significantly associated with the incidence of type 2 diabetes (P &lt; 0.001 for all variables). In a univariate model, the odds ratio (OR) for UAE was 1.59 (95% CI 1.42–1.79). In our full model, adjusted for age, sex, number of criteria of metabolic syndrome, and other known risk factors for the development of type 2 diabetes (including fasting insulin), the association between UAE and type 2 diabetes remained significant (OR 1.53, 95% CI 1.25–1.88, P &lt; 0.001). There was a significant interaction between UAE and CRP (P = 0.002). After CRP was stratified into tertiles, the ORs for the association between baseline UAE and the development of type 2 diabetes were 2.2 (1.47–3.3), 1.33 (0.96–1.84), and 1.04 (0.83–1.31) for the lowest to highest tertiles, respectively. CONCLUSIONS—UAE predicts type 2 diabetes independent of the metabolic syndrome and other known risk markers of development of type 2 diabetes. The predictive value of UAE was modified by the level of CRP

Screen-and-Treat Strategies for Albuminuria to Prevent Cardiovascular and Renal Disease:Cost-Effectiveness of Nationwide and Targeted Interventions Based on Analysis of Cohort Data From the Netherlands

Background: Albuminuria is a marker for renal and cardiovascular (CV) risk, allowing early diagnosis of subjects with elevated renal and CV risk. Objective: This study aimed to estimate the cost-effectiveness and budget impact of various population-based screen-and-treat scenarios for elevated albuminuria levels (ie, microalbuminuria) in the Netherlands. Methods: A multistate transition Markov model was developed to simulate the natural course of albuminuria-based disease progression to dialysis and occurrence of CV events. Several population-based strategies directed at screening for elevated albuminuria were evaluated. These strategies depended on urinary albumin concentration (UAC), urinary albumin excretion (UAE), and age. Transition probabilities were derived from the observational community-based Prevention of Renal and Vascular End Stage Disease (PREVEND) cohort study. Health care costs (in year-2008 euros) and life-years gained were calculated over an 8-year period. In the base-case analysis, we analyzed screening for and treatment of microalbuminuria. Screening for microalbuminuria involved prescreening for UAC >= 20 mg/L, followed by a confirmation test for UAE >= 30 mg/d. Other options based on combinations of albuminuria for UAC prescreening (no prescreening, and >= 10, >= 20, >= 100, and >= 200 mg/L) and UAE confirmation test (>= 15, >= 30, and 300 mg/d) for treatment were investigated in scenario analyses. Furthermore, these various strategies based on UAC and UAE values were analyzed in different subgroups based on age (all ages, aged >= 50 years, and aged >= 60 years). Results: The PREVEND study included 8592 Dutch residents aged 28 to 75 years at the time of initial screening. Among a hypothetical cohort of 1000 subjects identified and treated in the base-case analysis, it was estimated (based on PREVEND follow-up data) that, in the screening/treatment and no-screening scenarios, 76 versus 124 CV events occurred, 16 versus 27 CV deaths, and 3 versus 5 dialysis cases, respectively. The per-person difference in net costs for screening was calculated at (sic)926 ((sic)2003 vs (sic)1077), and prevention of CV deaths was estimated to gain 0.0421 discounted life-year per person. Correspondingly, the cost-effectiveness was estimated at (sic)22,000 per life-year gained. In the base-case analysis, probabilistic sensitivity analysis indicated that the likelihood of cost-effectiveness of a screen-and-treat strategy was 54%, 90%, and 95% for a maximum acceptable cost-effectiveness threshold of (sic)20,000, (sic)50,000, and (sic)80,000 per life-year gained, respectively. Higher albuminuria thresholds for screening and start of treatment further improved the cost-effectiveness but reduced the overall health gains achieved. Limiting screening to those subjects aged >= 50 and >= 60 years resulted in more favorable cost-effectiveness compared with population-based screening without age restriction. Conclusions: Our analyses suggest the potentially favorable cost-effectiveness of population-based screen

Addition of AT1 blocker fails to overcome resistance to ACE inhibition in adriamycin nephrosis

Addition of AT1 blocker fails to overcome resistance to ACE inhibition in adriamycin nephrosis.BackgroundAngiotensin-converting enzyme (ACE) inhibitors provide renoprotection, but there is considerable interindividual variability in therapeutic efficacy, with residual proteinuria and progressive renal function loss in many individuals. This requires additional strategies to optimize therapy response, particularly for individuals with a poor response to ACE inhibition. We studied whether co-treatment with an angiotensin II subtype 1 (AT1) receptor antagonist (AII-A) improves the individual antiproteinuric response of maximal ACE inhibition in established adriamycin nephrosis.MethodsRats were instituted on lisinopril (75 mg/L) six weeks after disease induction. After two weeks rats were re-stratified for residual proteinuria to continue this regimen, to a higher dose of lisinopril (150 mg/L) or to co-treatment with the AII-A L 158,809 for another four weeks. Groups on monotherapy AII-A and vehicle served as controls (all groups N = 15).ResultsLisinopril lowered proteinuria by 63% from 741 to 246 g/day (range of percentage change -90 to +2%). Neither increasing the dose of the ACE inhibitor nor addition of AII-A to ACE inhibition improved the antiproteinuric efficacy on a group or individual level: non-responders remained non-responders. All drug categories reduced hard end-points of focal glomerulosclerosis to a similar degree.ConclusionsACE inhibition has variable renal protective efficacy in the adriamycin model. Neither increasing the dose of the ACE inhibitor beyond the optimal level nor co-treatment with AII-A overcome the individual therapy resistance. Thus, in established adriamycin nephrosis, blockade of the renin-angiotensin system at two different levels offers no additional benefit over ACE inhibition alone, either on the group or individual level

High Protein Intake Associates with Cardiovascular Events but not with Loss of Renal Function

The long-term effects of higher dietary protein intake on cardiovascular and renal outcomes in the general population are not clear. We analyzed data from 8461 individuals who did not have renal disease and participated in two or three subsequent screenings (6.4-yr follow-up) in a prospective, community-based cohort study (Prevention of Renal and Vascular ENd-stage Disease [PREVEND]). We calculated daily protein intake from 24-h urinary urea excretion (Maroni formula) and used Cox proportional hazard models to analyze the associations between protein intake, cardiovascular events, and mortality. We used mixed-effects models to investigate the association between protein intake and change in renal function over time. The mean ± SD daily protein intake was 1.20 ± 0.27 g/kg. Protein intake was significantly associated with cardiovascular events during follow-up. The associations seemed U-shaped; compared with intermediate protein intake, individuals with either higher or lower protein intake had higher event rates. All-cause mortality and noncardiovascular mortality also were significantly associated with protein intake; individuals with low protein intake had the highest event rates. We found no association between baseline protein intake and rate of renal function decline during follow-up. In summary, in the general population, high protein intake does not promote accelerated decline of renal function but does associate with an increased risk for cardiovascular events

Star Clusters in the Nearby Late-Type Galaxy NGC 1311

Ultraviolet, optical and near infrared images of the nearby (D ~ 5.5 Mpc) SBm galaxy NGC 1311, obtained with the Hubble Space Telescope, reveal a small population of 13 candidate star clusters. We identify candidate star clusters based on a combination of their luminosity, extent and spectral energy distribution. The masses of the cluster candidates range from ~1000 up to ~100000 Solar masses, and show a strong positive trend of larger mass with increasing with cluster age. Such a trend follows from the fading and dissolution of old, low-mass clusters, and the lack of any young super star clusters of the sort often formed in strong starbursts. The cluster age distribution is consistent with a bursting mode of cluster formation, with active episodes of age ~10 Myr, ~100 Myr and ~1 Gyr. The ranges of age and mass we probe are consistent with those of the star clusters found in quiescent Local Group dwarf galaxies.Comment: 21 pages, 11 figures, accepted by A

Glomerular and Tubular Damage Markers Are Elevated in Patients With Diabetes

OBJECTIVE: We investigated in a cross-sectional study the levels of serum and urinary damage markers in diabetic patients (n = 94) and nondiabetic control subjects (n = 45) to study the association of glomerular (IgG), proximal tubular (kidney injury molecule [KIM]-1, N-acetyl-β-d-glucosaminidase [NAG], neutrophil gelatinase-associated lipocalin [NGAL], and cystatin C), and distal tubular (heart fatty acid-binding protein [H-FABP]) damage markers with kidney disease severity, as assessed by albuminuria and estimated glomerular filtration rate (eGFR). RESEARCH DESIGN AND METHODS: Damage markers were measured in triplicate in fresh morning urine samples and in plasma. RESULTS: Of the diabetic patients, 41 were normoalbuminuric, 41 were microalbuminuric, and 12 were macroalbuminuric. Urinary NAG (ninefold), NGAL (1.5-fold), and H-FABP (3.5-fold) were significantly elevated in normoalbuminuric diabetic patients compared with nondiabetic control subjects. Urinary concentrations of all markers increased per albuminuria stratum, except KIM-1. All urinary damage markers, except KIM-1, were significantly associated with albuminuria, independent of age, sex, and plasma concentrations of the corresponding biomarker (standard βs between 0.35 and 0.87; all P ≤ 0.001). All urinary damage markers, except KIM-1, were significantly associated with the eGFR in univariate models (standard βs between -0.38 and -0.21; all P < 0.04). After adjusting for age, sex, plasma concentration of the corresponding damage marker, and albuminuria, only the association of H-FABP with eGFR remained significant (standard β -0.26; P = 0.037). CONCLUSIONS: Glomerular and tubular markers are associated with albuminuria, independently of eGFR, suggesting that albuminuria reflects both glomerular and tubulointerstitial damage. Only urinary H-FABP is associated with eGFR independently of albuminuria and, therefore, may be a promising urinary damage marker to assess diabetic kidney disease

Total joint arthroplasty versus trapeziectomy in the treatment of trapeziometacarpal joint arthritis:a randomized controlled trial

The aim of this double anonymized, randomized controlled trial was to determine whether total joint arthroplasty has superior outcomes than trapeziectomy 1 year after surgery for trapeziometacarpal osteoarthritis. A total of 62 women aged 40 years and older, scheduled for surgery for stage II or III osteoarthritis of the trapeziometacarpal joint, were included and randomized to trapeziectomy or total joint arthroplasty. The primary outcome was the total score of the Michigan Hand Outcomes Questionnaire. Secondary outcomes were the Michigan Hand Outcomes Questionnaire subscale scores, Disability of the Arm, Shoulder and Hand Questionnaire, active range of motion, strength, return to work, patient satisfaction and complications. Data were collected at baseline and at 3 and 12 months. At 1 year, we found no superiority of total joint arthroplasty over trapeziectomy regarding the total score of the Michigan Hand Outcomes Questionnaire. The total joint arthroplasty did show a significant advantage in strength and range of motion. Level of evidence: I. </p