Hanneke Joosten

Association of Cognitive Function with Albuminuria and eGFR in the General Population

BACKGROUND AND OBJECTIVES Recent studies found different associations of cognitive function with albuminuria or estimated GFR (eGFR). Most studies were limited to the elderly or did not take both renal variables into account. Therefore, this study analyzed the association of cognitive function with albuminuria and eGFR in community-dwelling persons aged 35 to 82 years. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This was a cross-sectional study comprising 4095 participants of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study. Cognitive function, measured with the Ruff Figural Fluency Test (RFFT), was treated as the dependent variable, and albuminuria and eGFR were treated as independent variables. RESULTS The prevalence of albuminuria <10, 10 to 29, and ≥30 mg/24 h was 54%, 31%, and 15%, respectively. Mean eGFR (± SD) was 79 ± 15 ml/min per 1.73 m(2). Because of interaction between albuminuria and age, analyses were performed per age tertile. After multivariate adjustment, albuminuria ≥ 30 mg/24 h, but not eGFR, was associated with lower RFFT score in the youngest tertile (B -5.3; 95% CI, -0.6 to -9.2; P = 0.05), but not in older tertiles. Moreover, subjects in the youngest tertile with increasing albuminuria (5-15 and >15 mg/24 h) before RFFT measurement had lower mean RFFT scores than subjects with stable albuminuria: mean difference -4.9 (P = 0.3) and -6.7 (P = 0.03), respectively. CONCLUSIONS In this community-based cohort, elevated albuminuria was associated with worse cognitive function in young but not in old persons. There was no association of eGFR with cognitive function.

Fracture treatment by bonesetters in Central-Ghana: Patients explain their choices and experiences

Objective  To understand factors influencing patients’ decisions to choose either fracture treatment by a bonesetter or in the hospital and to explore patients’ experiences with bonesetter treatment.

Optimising drug prescribing and dispensing in subjects at risk for drug errors due to renal impairment: improving drug safety in primary healthcare by low eGFR alerts

Objectives To assess the risk of medication errors in subjects with renal impairment (defined as an estimated glomerular filtration rate (eGFR) ≤40 ml/min/1.73 m2) and the effectiveness of automatic eGFR ≤40-alerts relayed to community pharmacists. Design Clinical survey. Setting The city of Zwolle, The Netherlands, in a primary care setting including 22 community pharmacists and 65 general practitioners. Participants All adults who underwent ambulatory creatine measurements which triggered an eGFR ≤40-alert. Primary and secondary outcome measures The total number of ambulatory subjects with an eGFR ≤40-alert during the study period of 1 year and the number of medication errors related to renal impairment. The type and number of proposed drug adjustments recommended by the community pharmacist and acceptance rate by the prescribing physicians. Classification of all medication errors on their potential to cause an adverse drug event (ADE) and the actual occurrence of ADEs (limited to those identified through hospital record reviews) 1 year after the introduction of the alerts. Results Creatine measurements were performed in 25 929 adults. An eGFR ≤40-alert was indicated for 5.3% (n=1369). This group had a median (IQR) age of 78 (69, 84) years, and in 73% polypharmacy (≥5 drugs) was present. In 15% (n=211) of these subjects, a medication error was detected. The proportion of errors increased with age. Pharmacists recommended 342 medication adjustments, mainly concerning diuretics (22%) and antibiotics (21%). The physicians’ acceptance rate was 66%. Of all the medication errors, 88% were regarded as potential ADEs, with most classified as significant or serious. At follow-up, the ADE risk (n=40) appeared highest when the proposed medication adjustments were not implemented (38% vs 6%). Conclusions The introduction of automatic eGFR-alerts identified a considerable number of subjects who are at risk for ADEs due to renal impairment in an ambulatory setting. The nationwide implementation of this simple protocol could identify many potential ADEs, thereby substantially reducing iatrogenic complications in subjects with impaired renal function.

Reference Data for the Ruff Figural Fluency Test Stratified by Age and Educational Level

The Ruff Figural Fluency Test (RFFT) was developed to avoid the difficulties that were encountered in earlier tests of figural fluency. Although the test characteristics of the RFFT seem to be good and it is a valuable addition to neuropsychological assessments, reference data are still scarce. To this aim, we required 2,404 community dwelling persons in Groningen, the Netherlands to perform the RFFT. All 1,651 persons with a complete RFFT and known educational level formed the reference sample. Their age ranged from 35 to 82 years and their educational level from primary school to university grade. Ninety-six percent of the persons were of Western European descent. All tests were analyzed by two independent examiners and subsequently three measures were calculated: number of unique designs, number of perseverative errors and error ratio. The main finding was that performance on the RFFT was dependent on age and educational level. This was not only observed in older persons but also in young and middle-aged persons. Reference data for the three RFFT measures are presented in groups of five years of age ranging from 35–39 years to 75 years or older.

The Interaction of Age and Type 2 Diabetes on Executive Function and Memory in Persons Aged 35 Years or Older

It is generally assumed that type 2 diabetes increases the risk of cognitive dysfunction in old age. As type 2 diabetes is frequently diagnosed before the age of 50, diabetes-related cognitive dysfunction may also occur before the age of 50. Therefore, we investigated the association of type 2 diabetes with cognitive function in people aged 35–82 years. In a cross-sectional study comprising 4,135 participants of the Prevention of Renal and Vascular ENd-stage Disease study (52% men; mean age (SD), 55 (12) years) diabetes was defined according to the criteria of the American Diabetes Association. Executive function was measured with the Ruff Figural Fluency Test (RFFT; worst score, 0 points; best score, 175 points), and memory was measured with the Visual Association Test (VAT; worst score, 0 points; best score, 12 points). The association of diabetes with cognitive function was investigated with multiple linear or, if appropriate, logistic regression analysis adjusting for other cardiovascular risk factors and APOE ε4 carriership. Type 2 diabetes was ascertained in 264 individuals (6%). Persons with diabetes had lower RFFT scores than persons without diabetes: mean (SD), 51 (19) vs. 70 (26) points (p<0.001). The difference in RFFT score was largest at age 35–44 years (mean difference 32 points; 95% CI, 15 to 49; p<0.001) and gradually decreased with increasing age. The association of diabetes with RFFT score was not modified by APOE ε4 carriership. Similar results were found for VAT score as outcome measure although these results were only borderline statistically significant (p≤0.10). In conclusion, type 2 diabetes was associated with cognitive dysfunction, especially in young adults. This was independent of other cardiovascular risk factors and APOE ε4 carriership.

The Cockcroft-Gault: A Better Predictor of Renal Function in an Overweight and Obese Diabetic Population

Background: The performance of the Cockcroft-Gault (CG) equation, the Modification of Diet in Renal Disease (MDRD) formula, and the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) was evaluated in body mass index (BMI) categories. Material and Methods: In this retrospective cohort study in diabetic patients, creatinine clearance was measured by collecting 24-hour urines. Renal function was estimated using the CG, MDRD, and CKD-EPI. The performance of the equations was evaluated using correlation, Krippendorff’s coefficient, bias, precision, andaccuracy. Results: The bias of the MDRD and CKD-EPI increased from –13.9 ml/min/1.73 m2 and –14.0 ml/min/1.73 m2 (BMI < 25 kg/m2), respectively, to –31.7 ml/min/1.73 m2 and –29.6 ml/min/1.73 m2 (BMI > 30 kg/m2), respectively. Bias of the CG decreased from –13.4 ml/min (BMI < 25 kg/m2) to –3.2 ml/min (BMI > 30 kg/m2). With an accepted 30% dispersion, CG had the largest accuracy in the overweight and obese group (76.9 and 76.8%, respectively). The MDRD and CKD-EPI had an accuracy of 45.8 and 34.0% (overweight group), respectively,and 51.9 and37.3% (obese group), respectively. Conclusions: All renal function prediction equations are biased when used in overweight or obese diabetic populations with preserved renal function. The CG provides the best estimate of kidney function. The limitations of renal function prediction equations should be kept in mind when making clinical decisions.

An aid to the diagnosis of genetic disorders underlying adult-onset renal failure: a literature review.

Several genetic disorders can present in adult patients with renal insufficiency. Genetic renal disease other than ADPKD accounts for ESRD in 3% of the adult Dutch population. Because of this low prevalence and their clinical heterogeneity most adult nephrologists are less familiar with these disorders. As a guideline to differential diagnosis, we provide an overview of the clinical manifestations and the pathogenesis of the main genetic disorders with chronic renal insufficiency surfacing in adulthood and add an algorithm plus 4 tables. We also indicate where molecular genetics nowadays can be of aid in the diagnostic process. The following disorders are discussed by mode of inheritance: 1) Autosomal dominant: autosomal dominant polycystic kidney disease, nephropathies associated with uromodulin (medullary cystic disease and familial juvenile hyperuricemic nephropathy), renal cysts and diabetes syndrome, nail-patella syndrome, glomerulopathy with fibronectin deposits. 2) Not autosomal dominant: Nephronophthisis, Fabry disease, primary oxalosis, Adenine Phosphoribosyl Transferase deficiency, Alport syndrome, Lecithin-cholesterol acyltransferase deficiency, adult-onset cystinosis.

Longitudinal Study of Performance on the Ruff Figural Fluency Test in Persons Aged 35 Years or Older

The Ruff Figural Fluency Test (RFFT) is a cognitive test to measure executive function. Longitudinal studies have shown that repeated testing improves performance on the RFFT. Such a practice effect may hinder the interpretation of test results in a clinical setting. Therefore, we investigated the longitudinal performance on the RFFT in persons aged 35–82 years. Performance on the RFFT was measured three times over an average follow-up period of six years in 2,515 participants of the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) study in Groningen, the Netherlands: 53% men; mean age (SD), 53 (10) years. The effect of consecutive measurements on performance on the RFFT was investigated with linear multilevel regression models that also included age, gender, educational level and the interaction term consecutive measurement number x age as independent variables. It was found that the mean (SD) number of unique designs on the RFFT increased from 73 (26) at the first measurement to 79 (27) at the second measurement and to 83 (26) at the third measurement (p<0.001). However, the increase per consecutive measurement number was negatively associated with age and decreased with 0.23 per one-year increment of age (p<0.001). The increase per consecutive measurement number was not dependent on educational level. Similar results were found for the median (IQR) number of perseverative errors which showed a small but statistically significant increase with repeating testing: 7 (3–13) at the first measurement, 7 (4–14) at the second measurement and 8 (4–15) at the third measurement (p trend = 0.002). In conclusion, the performance on the RFFT improved by repeating the test over an average follow-up period of three to six years. This practice effect was the largest in young adults and not dependent on educational level.

eGFR and creatinine clearance in relation to metabolic changes in an unselected patient population

BACKGROUND It is widely assumed that moderate to severe renal failure (creatinine clearance <60 ml/min; or an MDRD-4 (Modification of Diet in Renal Disease equation) <60 ml/min/1.73 m(2)) is associated with metabolic changes, often needing further assessment and treatment. We investigated whether such abnormalities are already present at earlier stages of kidney disease, as assessed by 24-hour urine sampling and MDRD-4 calculation. METHODS A select, retrospective cohort study was conducted. Creatinine clearance was measured by collecting 24-hour urines. The individual eGFRs were calculated with the MDRD-4 formula and patients were then divided by renal function category (<15, 15-30, 30-45, 45-60, 60-90, >90 ml/min(/1.73 m(2))). Per clearance category the number of people with anaemia, hypokalaemia, uraemia and hyperphosphataemia was evaluated. RESULTS The median creatinine clearance rate was 67.3 ml/min (quartiles: 42.9-95.8) versus a median MDRD-4-eGFR of 51.6 ml/min/1.73 m(2) (35.8-67.7). Anaemia, hyperkalaemia, hypocalcaemia, and uraemia were found to be present at higher levels of creatinine clearance rate and eGFR than previously reported (p<0.0005). This increased prevalence was more pronounced in elderly subjects, particularly with respect to anaemia (OR 2.71 and 2.02 for MDRD-4 and creatinine clearance respectively, p<0.0005). The same holds for the proportion with uraemia (OR 1.85, p<0.0005) and hypocalcaemia (OR 1.97, p=0.011) for MDRD-4. CONCLUSION Metabolic changes in an in- and outpatient hospital population are present at earlier stages than was stated in recent guidelines, especially when creatinine clearance levels are used as indicators. This might have implications for testing and treatment of patients with suspected kidney disease and/or loss of renal function.

Statin Use and Cognitive Function : Population-Based Observational Study with Long-Term Follow-Up

We aimed to evaluate the association between statin use and cognitive function. Cognitive function was measured with the Ruff Figural Fluency Test (RFFT; worst score, 0; best score, 175 points) and the Visual Association Test (VAT; low performance, 0–10; high performance, 11–12 points) in an observational study that included 4,095 community-dwelling participants aged 35–82 years. Data on statin use were obtained from a computerized pharmacy database. Analysis were done for the total cohort and subsamples matched on cardiovascular risk (N = 1232) or propensity score for statin use (N = 3609). We found that a total of 904 participants (10%) used a statin. Statin users were older than non-users: mean age (SD) 61 (10) vs. 52 (11) years (p<0.001). The median duration of statin use was 3.8 (interquartile range, 1.6–4.5) years. Unadjusted, statin users had worse cognitive performance than non-users. The mean RFFT score (SD) in statin users and non-users was 58 (23) and 72 (26) points, respectively (p<0.001). VAT performance was high in 261 (29%) statin users and 1351 (43%) non-users (p<0.001). However, multiple regression analysis did not show a significant association of RFFT score with statin use (B, −0.82; 95%CI, −2.77 to 1.14; p = 0.41) nor with statin solubility, statin dose or duration of statin use. Statin users with high doses or long-term use had similar cognitive performance as non-users. This was found in persons with low as well as high cardiovascular risk, and in younger as well as older subjects. Also, the mean RFFT score per quintile of propensity score for statin use was comparable for statin users and non-users. Similar results were found for the VAT score as outcome measure. In conclusion, statin use was not associated with cognitive function. This was independent of statin dose or duration of statin use.