CKD LAB METHODS, PROGRESSION & RISK FACTORS 1

Abstract

INTRODUCTION AND AIMS: Elderly patients with reduced estimated Glomerular Filtration Rate (eGFR) are now one of the commonest indications for referral to nephrology clinics.The MDRD-4 formula and the new classification of CKD are now being routinely used to screen patients for renal disease in the community. We investigated eGFR values and the prevalence of renal dysfunction in an elderly Scottish population. METHODS: We analysed eGFR (MDRD-4 UK NEQAS) values in 1,043 patients from a population of primary care attenders (age > 64 years). The anonymised eGFR and creatinine results were part of routine blood tests analysed by the biochemistry laboratory for general practitioners. Follow-up bloods were assessed 12 months later. Normal renal function was defined as eGFR > 60 ml/min/1.73m2. Statistical analysis was performed using SPSS software. Patients were stratified into 3 age groups. RESULTS: We investigated 1043 patients, 432 male and 611 female patients, age range 65 to 99 years. The mean eGFR for each age group was: 65 - 74 years, eGFR = 67.2; 75 - 84 years, eGFR = 60.0; and > 84 years, eGFR = 50.7. Multivariate analysis showed a significant association between 10-year increments in age and eGFR (OR 2.3). After 12 months the mean eGFR's for each group were 70.2 (p<0.001), 62.2 (p<0.001) and 51.4 (ns), respectively. eGFR improved in two age groups and was unchanged in the third. There were 464 patients (44.5%) diagnosed with an eGFR < 60 ml/min/1.73m2. From these patients, 255 (24.4%) were classified as Stage 3A and 167 (16.0%) as Stage 3B. There were 42 patients (4.0%) with an eGFR < 30 ml/min/1.73m2. From these patients, 37 (3.5%) had Stage 4 CKD and 5 (0.5%) had Stage 5 CKD. Mean eGFR values in Stage 3A were 52.5 at baseline and 55.5 at 12 months (p<0.001); Stage 3B, 38.2 and 40.7 (p<0.001); Stage 4, 24.8 and 30.8 (p<0.01); Stage 5, 11.8 and 12.9 (ns), respectively. eGFR values improved or were unchanged after 12 months. CONCLUSIONS: Around 45% of our elderly population had eGFR < 60 ml/min/1.73m2 and this was significantly associated with increasing age. The introduction of eGFR reporting has led to a rising number of elderly patients being referred to the renal service for further investigation. The majority (40%) had Stage 3 CKD. Monitoring these elderly patients for 12 months showed no evidence of progressive renal disease. Do these patients have clinically significant treatable disease or are we simply seeing the effect of the normal ageing process? More clinical guidelines for management of CKD in this elderly age group are required. The sub-classification of Stage 3 CKD may assist in appropriate investigations and treatment of elderly patients. INTRODUCTION AND AIMS: Recent studies have shown that adverse pregnancy related outcomes, especially preeclampsia, are associated with an increased risk of kidney disease. The present study has investigated whether a woman's total number of pregnancies is a risk marker for later development of end-stage renal disease (ESRD) and whether number of pregnancies modifies the effect of preeclampsia. METHODS: We linked data from the Medical Birth Registry of Norway, which contains data on all births in Norway since 1967, with data from the Norwegian Renal Registry, which contains data on all patients with ESRD since 1980, to assess associations between the women's total number of pregnancies and the subsequent development of ESRD. We included data from up to three pregnancies for women with a first singleton delivery from 1967 to 1991. RESULTS: The study population included 570,433 women who completed at least one pregnancy; total number of pregnancies for these women were one in 16%, two in 47% and three or more in 37%. Among the included women, 477 developed ESRD after a mean follow-up period of 17{+/-}9 years. Mothers with only one pregnancy had a relative risk (RR) of ESRD of 2.0 (1.6-2.5) as compared to women with two or three pregnancies. This RR was reduced to 1.7 (1.2-2.6) when including only women without adverse pregnancy or birth related outcomes and to 1.5 (0.94-2.3) when including only women without diabetes, hypertension, kidney disease or rheumatic disease before pregnancy who had no adverse pregnancy or birth related outcomes.Women with two or more pregnancies without preeclampsia had the lowest risk of ESRD. Compared to this group, women with only one pregnancy without preeclampsia had a relative risk (RR) of 2.1 (1.7-2.6) and women with only one pregnancy with preeclampsia had a RR of 14 (10-20). Women with two pregnancies or more and preeclampsia in first, second or both pregnancies had RR of 3.2 (2.1-4.8), 6.5 (4.1-10) and 6.2 (2.9-13) as compared to the women with two or more pregnancies without preeclampsia. CONCLUSIONS: Women who have only one pregnancy have increased risk of ESRD. Women with a preeclamptic pregnancy who have a later pregnancy without preeclampsia have a lower risk of ESRD as compared to women who do not have a later pregnancy. INTRODUCTION AND AIMS: Sparse longitudinal data are available on how diet, which is a potentially important modifiable risk factor, may influence kidney function and microalbuminuria (MA). We hypothesized that nutrients associated with macrovascular cardiovascular disease would also be associated with kidney microvascular disease manifesting as eGFR decline and MA. METHODS: We identified 3348 women participating in the Nurses' Health Study, an established longitudinal cohort study, who had urinary albumin-to-creatinine ratios (ACR) measured in the year 2000; 3282 of these women also had data on eGFR change between 1989 and 2000. This group included 697 women participating in a sub-study of diabetes and kidney function. Cumulative averaged intake of individual nutrients over 14 years were derived from validated semi-quantitative food frequency questionnaires answered in 1984, 1986, 1990, 1994, and 1998. RESULTS: Median age was 67 years, 97% were Caucasian, 54% had HTN, and 23% had diabetes. In this group, 607 (26%) experienced eGFR decline > 25% over 11 years and 205 (6%) had MA (ACR 25 to 355 mcg/mg). Covariates included in adjusted models were age, hypertension, BMI, diabetes, smoking, physical activity (METS/week), and cardiovascular disease for both eGFR decline and MA outcomes; models for MA were also adjusted for eGFR and ACE-I/ARB medication use.Fully adjusted multivariable models revealed that highest quartile of animal fat was independently associated with both eGFR decline (OR 1.31 [1.01, 1.70]) and MA (OR 1.64 [1.05, 2.55]) (Figure 1). Furthermore, the highest quartile of animal protein intake was associated with MA (OR 1.69 [1.02, 2.80]) and the highest quartile of vitamin E intake was inversely associated with eGFR decline (OR 0.70 [0.51, 0.96]). The results did not vary by diabetes status. No significant associations were seen between other types of protein (vegetable, low-fat dairy, high-fat dairy, total dairy, and non-dairy), fat (trans, mono-saturated, polyunsaturated, and vegetable), fiber (total, soluble, and insoluble), anti-oxidant vitamins (vitamins A, C, and beta-carotene), vitamin D, folate, fructose, and potassium and eGFR decline or MA. CONCLUSIONS: Higher dietary intake of animal fat and protein may confer an increased risk for eGFR decline and MA whereas higher intake of vitamin E may reduce risk of eGFR decline.[IMG]/medium/245.gif" ALT="Formula "> INTRODUCTION AND AIMS: Adiponectin is an adipose tissue-derived protein that carries antiatherogenic and anti-inflammatory properties. Increased adiposity, particularly of intra-abdominal fat, has been associated with decreased levels of adiponectin. On the other hand, it has been suggested that adiponectin accumulates as the renal function decreases. The aim of this study was to explore the influence of intra-abdominal fat and renal function on the circulating levels of adiponectin in patients with chronic kidney disease (CKD). METHODS: We prospectively evaluated 98 patients with CKD stages 2 to 5 [glomerular filtration rate (GFR) 36.1{+/-}14.4ml/min, 56.5{+/-}10.4y, 63% male, 31% diabetics, and BMI 27.1{+/-}5.2kg/m2]. Visceral and subcutaneous abdominal fat areas were measured by computed tomography at the L4-L5 level. Total body fat was assessed by dual X-ray energy absorptiometry. Adiponectin concentrations were measured in fasting serum samples by ELISA. GFR estimated by the MDRD equation and proteinuria were used as markers of renal function. RESULTS: Adiponectin correlated inversely with visceral fat (r=-0.49; P<0.001) and GFR (r=-0.45; P<0.001). There was also an inverse association of adiponectin with BMI, HOMA index, triglicerydes, and a positive association with HDL cholesterol and proteinuria. In the multivariate regression analysis, the determinants of adiponectin concentrations were gender (female) ({beta}=3.8; P=0.007), age ({beta}=0.14; P=0.032), visceral fat ({beta}=-0.04; P<0.001) and GFR ({beta}=-0.15; P=0.001) (R2=0.41). After 12 months, a progression of the disease was evidenced by the decrease of GFR (-1.6{+/-}6.3ml/min; P=0.013) and the increase of proteinuria (0.26{+/-}0.78g/day; P=0.002). An accumulation of visceral fat was observed, from 96.7{+/-}72.8cm2 to 111.1{+/-}81.5cm2 (P<0.001), with concomitant reduction of adiponectin concentration, from 27.6{+/-}7.5mg/l to 22.2{+/-}11.6mg/l (P<0.001). Body weight, BMI, total body fat, and subcutaneous abdominal fat remained unchanged. Adjusting for the baseline determinants of adiponectin, changes in visceral fat ({beta}=-0.04; P=0.025) and not changes in GFR or proteinuria were associated with the changes in adiponectin levels during the follow-up (R2=0.21). CONCLUSIONS: Renal function and intra-abdominal fat are independent determinants of adiponectin levels in patients with CKD. However, the prospective evaluation demonstrated that the intra-abdominal fat is the strongest predictor of overtime changes in adiponectin levels. IN