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The renal renin-angiotensin system (RAS) is involved in the development of chronic kidney disease. Here, we investigated whether mice with reduced renal angiotensin I-converting enzyme (ACE−/−) are protected against aristolochic acid nephropathy (AAN). To further elucidate potential molecular mechanisms, we assessed the renal abundances of several major RAS components. AAN was induced using aristolochic acid I (AAI). Glomerular filtration rate (GFR) was determined using inulin clearance and renal protein abundances of renin, angiotensinogen, angiotensin I-converting enzyme (ACE) 2, and Mas receptor (Mas) were determined in ACE−/− and C57BL/6J control mice by Western blot analyses. Renal ACE activity was determined using a colorimetric assay and renal angiotensin (Ang) (1–7) concentration was determined by ELISA. GFR was similar in vehicle-treated mice of both strains. AAI decreased GFR in controls but not in ACE−/− mice. Furthermore, AAI decreased renal ACE activity in controls but not in ACE−/− mice. Vehicle-treated ACE−/− mice had significantly higher renal ACE2 and Mas protein abundances than controls. AAI decreased renal ACE2 protein abundance in both strains. Furthermore, AAI increased renal Mas protein abundance, although the latter effect did not reach statistical significance in the ACE−/− mice. Renal Ang(1–7) concentration was similar in vehicle-treated mice of both strains. AAI increased renal Ang(1–7) concentration in the ACE−/− mice but not in the controls. Mice with reduced renal ACE are protected against AAN. Our data suggest that in the face of renal ACE deficiency, AAI may activate the ACE2/Ang(1–7)/Mas axis, which in turn may deploy its reno-protective effects.
Background
Clinical practice guidelines recommend specialist referral according to different criteria. The aim was to assess recommended and observed referral rate and health care expenditure according to recommendations from:
• Kidney Disease Improving Global Outcomes (KDIGO,2012)
• National Institute for Health and Care Excellence (NICE,2014)
• German Society of Nephrology/German Society of Internal Medicine (DGfN/DGIM,2015)
• German College of General Practitioners and Family Physicians (DEGAM,2019)
• Kidney failure risk equation (NICE,2021)
Methods
Data of the population-based cohort Study of Health in Pomerania were matched with claims data. Proportion of subjects meeting referral criteria and corresponding health care expenditures were calculated and projected to the population of Mecklenburg-Vorpommern.
Results
Data from 1927 subjects were analysed. Overall proportion of subjects meeting referral criteria ranged from 4.9% (DEGAM) to 8.3% (DGfN/DGIM). The majority of patients eligible for referral were ≥ 60 years. In subjects older than 60 years, differences were even more pronounced, and rates ranged from 9.7% (DEGAM) to 16.5% (DGfN/DGIM). Estimated population level costs varied between €1,432,440 (DEGAM) and €2,386,186 (DGfN/DGIM). From 190 patients with eGFR < 60 ml/min, 15 had a risk of end stage renal disease > 5% within the next 5 years.
Conclusions
Applying different referral criteria results in different referral rates and costs. Referral rates exceed actually observed consultation rates. Criteria need to be evaluated in terms of available workforce, resources and regarding over- and underutilization of nephrology services.
Background
Although chronic kidney disease (CKD) is highly prevalent in the general population, little research has been conducted on CKD management in ambulatory care.
Objective was to assess management and quality of care by evaluating CKD coding in ambulatory care, patient diagnosis awareness, frequency of monitoring and whether appropriate patients are referred to nephrology.
Methods
Clinical data from the population-based cohort Study of Health in Pomerania (SHIP-START) were matched with claims data of the Association of Statutory Health Insurance Physicians. Quality of care was evaluated according international and German recommendations.
Results
Data from 1778 participants (56% female, mean age 59 years) were analysed. 10% had eGFR < 60 ml/min/1.73m2 (mean age 74 years), 15% had albuminuria. 21% had CKD as defined by KDIGO. 20% of these were coded and 7% self-reported having CKD. Coding increased with GFR stage (G3a 20%, G3b 61%, G4 75%, G5 100%). Serum creatinine and urinary dip stick testing were billed in the majority of all participants regardless of renal function. Testing frequency partially surpassed recommendations. Nephrology consultation was billed in few cases with stage G3b-G4.
Conclusion
CKD coding increased with stage and was performed reliably in stages ≥ G4, while CKD awareness was low. Adherence to monitoring and referral criteria varied, depending on the applicability of monitoring criteria. For assessing quality of care, consent on monitoring, patient education, referral criteria and coordination of care needs to be established, accounting for patient related factors, including age and comorbidity.
Trial registration
This study was prospectively registered as DRKS00009812 in the German Clinical Trials Register (DRKS).
Background: Mild-to-moderate chronic kidney disease (CKD G3a) is prevalent in older adults. Substantial evidence suggests that individuals with advanced CKD face a high risk for common geriatric conditions, like functional impairment and cognitive decline, whereas the relationships between mild-to-moderate CKD and functional impairment and cognitive decline, but also poor nutritional status and mood disorders, are still unclear. Objective: The aim of this study was to explore associations between mild-to-moderate CKD and impairments in the core domains of geriatric assessment (GA) in a large cohort of community-dwelling older adults. Methods: This was a cross-sectional analysis of 1,476 participants of the Berlin Aging Study II. Study participants were stratified as to presence or absence of CKD G3a (estimated glomerular filtration rate [eGFR] 45-59 mL/min/1.73 m<sup>2</sup> vs. eGFR ≥60 mL/min/1.73 m<sup>2</sup>). GA comprised the following instruments: the Activities of Daily Living Scale (ADL), the Timed up and Go (TUG), the Tinetti test (Tinetti), the Mini-Mental-State Examination (MMSE), the Geriatric Depression Scale (GDS), and the Mini Nutritional Assessment (MNA). We used logistic regression models to estimate multivariable-adjusted associations between CKD G3a and impairments in the respective domains. Results: A total of 282 subjects with mild-to-moderate CKD (CKD G3a) were identified (19.1%). Overall, the prevalence of impairments identified was higher among subjects with compared to without CKD G3a (21 vs. 15.9%, p = 0.043). In multivariable-adjusted models, CKD G3a was consistently associated with increased odds of an impaired gait performance as to the TUG (adjusted odds ratio 2.06, 95% CI 1.04-4.09). In contrast, on average, individuals with and without CKD G3a did not differ as to their results in the MMSE, the ADL, the MNA, and the GDS. Conclusion: GA identified impairments in 21 versus 15.9% of older adults with and without mild-to-moderate CKD, respectively. However, except for an increased likelihood of impaired gait performance (TUG) with mild-to-moderate CKD, we did not find independent associations between mild-to-moderate CKD and geriatric conditions.