This thesis investigated the effect of several risk factors on objectively assessed disease progression (renal function decline and time until the start of renal replacement therapy) and... Show moreThis thesis investigated the effect of several risk factors on objectively assessed disease progression (renal function decline and time until the start of renal replacement therapy) and subjectively assessed disease progression (disease-related symptoms and health-related quality of life) in patients with chronic kidney disease on specialized pre-dialysis care. Furthermore, we explored (un)known mechanisms that may determine renal function decline in pre-dialysis patients. The conclusions are: low blood pressure, low proteinuria levels, and low cholesterol levels are associated with a slower objectively assessed disease progression. However, in elderly patients low blood pressure is a marker for an earlier start of renal replacement therapy. Concerning subjectively assessed disease progression, only in young patients treated with anemia-medication, high hemoglobin levels are associated with a better health-relate d quality of life. Furthermore, symptoms increase and health-related quality of life decreases during pre-dialysis care. Therefore, these markers are good candidates for defining the optimal moment to start with dialysis. This thesis also showed that black patients experience a faster renal function decline than white patients. A possible explanation could be the stronger negative consequences of diabetes mellitus in black patients. Finally, at middle-age, renal function is higher in longevity families, revealing possible new genetic mechanisms. Show less
Beukel, T.O. van den; Goeij, M.C.M. de; Dekker, F.W.; Siegert, C.E.H.; Halbesma, N.; PREPARE Study Grp 2013
BACKGROUND To investigate whether high blood pressure accelerates renal function decline in patients with advanced chronic kidney disease (CKD), we studied the association of systolic (SBP) and... Show moreBACKGROUND To investigate whether high blood pressure accelerates renal function decline in patients with advanced chronic kidney disease (CKD), we studied the association of systolic (SBP) and diastolic blood pressure (DBP) with decline in renal function and time until the start of renal replacement therapy (RRT) in patients with CKD stages IV-V on pre-dialysis care. METHODS In the PREPARE-1 cohort 547 incident pre-dialysis patients, referred as part of the usual care to outpatient clinics of eight Dutch hospitals, were included between 1999 and 2001 and followed until the start of RRT, mortality, or end of follow-up (January 1st 2008). Main outcomes were rate of decline in renal function, estimated as the slope of available eGFR measurements, and time until the start of RRT. RESULTS A total of 508 patients, 57% men and median (IQR) age of 63 (50-73) years, were available for analyses. Mean (SD) decline in renal function was 0.35 (0.75) ml/min/1.73 m2/month. Every 10 mmHg increase in SBP or DBP resulted in an accelerated decline in renal function (adjusted additional decline 0.04 (0.02;0.07) and 0.05 (0.00;0.11) ml/min/1.73 m2/month respectively) and an earlier start of RRT (adjusted HR 1.09 (1.04;1.14) and 1.16 (1.05;1.28) respectively). Furthermore, patients with SBP and DBP above the BP target goal of < 130/80 mmHg experienced a faster decline in renal function (adjusted additional decline 0.31 (0.08;0.53) ml/min/1.73 m2/month) and an earlier start of RRT (adjusted HR 2.08 (1.25;3.44)), compared to patients who achieved the target goal (11%). Comparing the decline in renal function and risk of starting RRT between patients with only SBP above the target (≥ 130 mmHg) and patients with both SBP and DBP below the target (< 130/80 mmHg), showed that the results were almost similar as compared to patients with both SBP and DBP above the target (adjusted additional decline 0.31 (0.04;0.58) ml/min/1.73 m2/month and adjusted HR 2.24 (1.26;3.97)). Therefore, it seems that especially having SBP above the target is harmful. CONCLUSIONS In pre-dialysis patients with CKD stages IV-V, having blood pressure (especially SBP) above the target goal for CKD patients (< 130/80 mmHg) was associated with a faster decline in renal function and a later start of RRT. Show less
Huijts, P.E.A.; Dongen, M. van; Goeij, M.C.M. de; Moolenbroek, A.J. van; Blanken, F.; Vreeswijk, M.P.G.; ... ; Devilee, P. 2011
OBJECTIVES To explore measures of metabolic syndrome and glucose metabolism in families with exceptional longevity. DESIGN Case-control study. SETTING A university hospital in Leiden, the... Show moreOBJECTIVES To explore measures of metabolic syndrome and glucose metabolism in families with exceptional longevity. DESIGN Case-control study. SETTING A university hospital in Leiden, the Netherlands. PARTICIPANTS One hundred twenty-one offspring of nonagenarian siblings, who were enriched for familial factors promoting longevity, and 113 of their partners. No subject had diabetes mellitus. MEASUREMENTS Prevalence of metabolic syndrome was determined according to the criteria of the Third Report of the National Cholesterol Education Program. Glucose tolerance was assessed according to a 2-hour oral glucose tolerance test. RESULTS The offspring of nonagenarians siblings had a lower prevalence of metabolic syndrome (P=.03), similar body composition, lower mean fasting blood glucose levels (4.99 vs 5.16 mmol/L; P=.01), lower mean fasting insulin levels (5.81 vs 6.75 mU/L; P=.04), a higher mean homeostasis model assessment of insulin sensitivity (0.78 vs 0.65; P=.02), and a more-favorable glucose tolerance (mean area under the receiver operating characteristic curve for glucose (13.2 vs 14.3; P=.007) than their partners. No significant differences were observed between the offspring and their partners in beta-cell function (insulogenic index 13.6 vs 12.5; P=.38). CONCLUSION Despite similar body composition, the offspring of nonagenarian siblings showed a lower prevalence of metabolic syndrome and better glucose tolerance than their partners, centralizing the role of favorable glucose metabolism in familial longevity. Show less
