Rapid eGFR Decline Research Articles

Selective cyclooxygenase-2 inhibitor use and progression of renal function in patients with chronic kidney disease: a single-center retrospective cohort study.

BackgroundThe use of selective COX-2 (sCOX-2) inhibitors with acute kidney injury, salt water retention, and cardiovascular events have been correlated in subjects with normal kidney function, but sCOX-2 inhibitor use concerning the progression of chronic kidney disease (CKD) remains uncertain.ObjectivesTo determine the progression of renal function and electrolyte abnormalities among CKD patients after using sCOX-2 inhibitors during short- and long-term periods.MethodsThe study employed a retrospective cohort design comprising all types of CKD patients with and without sCOX-2 inhibitors (celecoxib and etoricoxib). Data collected included medical data, estimated glomerular filtration rate (eGFR), and serum electrolytes at 3 and 6 months between January 2009 and January 2014. Subjects attended the outpatient clinic and were then followed up until discontinuation of the drugs at years 1 and 2 until May 2016.ResultsNinety-two CKD patients on sCOX-2 inhibitors and 92 CKD patients without sCOX-2 inhibitors were included. The sCOX-2 inhibitor group showed more decline in eGFR than the control group at 3 and 6 months of follow-up (–8.27±9.75 vs –1.64±6.05 mL/min/1.73 m2, P<0.001 and –12.36±6.48 vs –4.31±5.11 mL/min/1.73 m2, P=0.001, respectively) and at 1 and 2 years of follow-up after subjects discontinued sCOX-2 (–6.84±10.34 vs –1.61±8.93 mL/min/1.73 m2, P=0.004 and –10.26±10.19 vs –5.12±8.61 mL/min/1.73 m2, P=0.005, respectively). In addition, the sCOX-2 inhibitor group had significantly more increased serum potassium during the study follow-up than the control group.ConclusionThe sCOX-2 inhibitors are associated with an increased risk for rapid eGFR decline and hyperkalemia in both the short term and in the long term after sCOX-2 inhibitors were terminated in the setting of a community-based CKD population. For CKD patients, these results suggest that sCOX-2 inhibitors should be closely monitored and chronic exposure to any sCOX-2 inhibitors should be avoided.

Dietary Magnesium and Kidney Function Decline: The Healthy Aging in Neighborhoods of Diversity across the Life Span Study

Background: Prior studies suggest that certain aspects of the diet related to magnesium intake, such as dietary acid load, protein intake and dietary patterns rich in fruits and vegetables, may impact kidney disease risk. We hypothesized that lower dietary magnesium intake would be prospectively associated with more rapid kidney function decline. Methods: Among participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span study with estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m² at baseline (2004-2009), dietary magnesium intake was calculated from two 24-hour dietary recalls. Rapid decline was defined as ≥3% eGFR decline per year. Results: Median (25th-75th percentile) dietary magnesium intake was 116 (96-356) mg/1,000 kcal. Among 1,252 participants, those with lower dietary magnesium intake were younger, and were more likely to be African-American men. A total of 177 participants (14.1%) experienced rapid eGFR decline over a median follow-up of 5 years. Lower dietary magnesium intake was significantly associated with a greater odds of rapid eGFR decline (OR for tertile 1 vs. 3: 2.02, 95% CI 1.05-3.86, p value for trend across tertiles = 0.02) in analyses adjusted for sociodemographics (age, sex, race, education level, health insurance status, poverty status), kidney disease risk factors (smoking status, diabetes, hemoglobin A1c, hypertension, body mass index), baseline eGFR and dietary factors (total energy intake; diet quality; dietary intake of fiber, sodium, calcium, potassium and phosphorus). Conclusions: In this urban population, lower dietary magnesium intake was independently associated with greater odds of rapid kidney function decline.

Dietary Habits and Risk of Kidney Function Decline in an Urban Population.

Explore the association between following a Dietary Approaches to Stop Hypertension (DASH)-accordant diet and kidney end points among urban adults. Prospective cohort study. Healthy Aging in Neighborhoods of Diversity across the Life Span study. A total of 1,534 urban dwelling participants of the Healthy Aging in Neighborhoods of Diversity across the Life Span study with a baseline estimated glomerular filtration rate (eGFR) ≥60 mL/minute/1.73 m2. DASH diet accordance determined via a score based on nine target nutrients. Rapid kidney function decline (eGFR decline >3 mL/minute/1.73 m2 per year), incident chronic kidney disease (CKD) (follow-up eGFR <60 mL/minute/1.73 m2), and eGFR decline >25%. Participants' mean age was 48 years, and 59% were African-American. Median DASH score was 1.5 (range, 0-8). Over a median of 5 years, 13.4% experienced rapid eGFR decline, including 15.2% among participants not following a DASH-accordant diet (score ≤1) and 12.0% with higher accordance (score >1) (P = .08). Outcomes varied by hypertension status. In multinomial logistic regression models, following adjustment for sociodemographic and clinical factors, including total energy intake, low DASH diet accordance was associated with rapid eGFR decline among participants with hypertension (risk ratio, 1.68; 95% confidence interval: 1.17-2.42) but not among those without hypertension (risk ratio, 0.83; 95% confidence interval: 0.56-1.24; P interaction .001). There was no statistically significant association between DASH diet accordance and incident CKD or eGFR decline >25%. Results were similar when DASH diet accordance was analyzed in tertiles. Among urban adults, low accordance to a DASH-type diet was not associated with incident CKD, but was associated with higher risk of rapid eGFR decline among those with hypertension, yet not among those without hypertension. Further study of dietary patterns as a potential target for improving kidney outcomes among high-risk populations is warranted.

PS 11-79 METABOLIC SYNDROME, INSULIN RESISTANCE IS ASSOCIATED WITH RAPID DECLINE OF KIDNEY FUNCTION AND INCIDENT CHRONIC KIDNEY DISEASE OVER 10 YEARS IN THE KOREAN GENOME AND EPIDEMIOLOGY STUDY (KoGES)

Objective: Although metabolic abnormalities have been considered as important risk factor for chronic kidney disease (CKD), the impact of metabolic syndrome (MetS)/insulin resistance on renal function deterioration is poorly understood. Furthermore, sex differences in this relationship have not been fully evaluated. The aim of this study was to investigate the sex-specific association between MetS and incident CKD/rapid decline of estimated glomerular filtration rate (eGFR) in a 10-year prospective, population-based study of Koreans. Design and Method: Among 10,030 subjects, 6089 (age range 40–69 years) without history of CKD and cardiovascular disease at baseline were analyzed using data generated from rural and urban areas during 2001–2010. They were categorized into two groups on the basis of the presence of MetS at baseline. Incident CKD was defined as eGFR <60 ml/min per 1.73 m2 and rapid decline of eGFR was defined as >3 ml/min per 1.73 m2 /yr. Results: Among 10,030 subjects, 6089 (age range 40–69 years) without history of CKD and cardiovascular disease at baseline were analyzed using data generated from rural and urban areas during 2001–2010. They were categorized into two groups on the basis of the presence of MetS at baseline. Incident CKD was defined as eGFR <60 ml/min per 1.73 m2 and rapid decline of eGFR was defined as >3 ml/min per 1.73 m2 /yr. Conclusions: MetS and insulin resistance were an independent risk factor for incident CKD in relatively healthy Korean population. The MetS-CKD relationship was more prominent in men than in women. Our findings suggest the importance of detection and treatment of MetS and insulin resistance as a strategy to prevent CKD in clinical practice.

Geographic Variation and US County Characteristics Associated With Rapid Kidney Function Decline

IntroductionGeographic variation in the prevalence of chronic kidney disease and incidence of end-stage renal disease has been previously reported. However, the geographic epidemiology of rapid estimated glomerular filtration rate (eGFR) decline has not been examined.MethodsWe built a longitudinal cohort of 2,107,570 US veterans to characterize the spatial epidemiology of and examine the associations between US county characteristics and rapid eGFR decline.ResultsThere were 169,029 (8.02%) with rapid eGFR decline (defined as eGFR slope < –5 ml/min per 1.73 m2/year). The prevalence of rapid eGFR decline adjusted for age, race, gender, diabetes, and hypertension varied by county from 4.10%–6.72% in the lowest prevalence quintile to 8.41%–22.04% in the highest prevalence quintile (P for heterogeneity < 0.001). Examination of adjusted prevalence showed substantial geographic variation in those with and without diabetes and those with and without hypertension (P for heterogeneity < 0.001). Cohort participants had higher odds of rapid eGFR decline when living in counties with unfavorable characteristics in domains including health outcomes (odds ratio [OR] = 1.15; confidence interval [CI] = 1.09–1.22), health behaviors (OR = 1.08; CI = 1.03–1.13), clinical care (OR = 1.11; CI = 1.06–1.16), socioeconomic conditions (OR = 1.15; CI = 1.09–1.22), and physical environment (OR = 1.15; CI = 1.01–1.20); living in counties with high percentage of minorities and immigrants was associated with rapid eGFR decline (OR = 1.25; CI = 1.20–1.31). Spatial analyses suggest the presence of cluster of counties with high prevalence of rapid eGFR decline.DiscussionOur findings show substantial geographic variation in rapid eGFR decline among US veterans; the variation persists in analyses stratified by diabetes and hypertension status; results show associations between US county characteristics in domains capturing health, socioeconomic, environmental, and diversity conditions, and rapid eGFR decline.

Association of Skin Autofluorescence Levels With Kidney Function Decline in Patients With Peripheral Artery Disease.

Skin autofluorescence (SAF), a measure of advanced glycation end product accumulation, is associated with kidney function. We investigated the association of SAF with rate of kidney function decline in a cohort of patients with peripheral artery disease. We performed a post hoc analysis of an observational longitudinal cohort study. We included 471 patients with peripheral artery disease, and SAF was measured at baseline. Primary end point was rate of estimated glomerular filtration rate (eGFR) decline. Secondary end points were incidence of eGFR <60 and <45 mL/min/1.73 m(2) and rapid eGFR decline, defined as a decrease in eGFR of >5 mL/min/1.73 m(2)/y. During a median follow-up of 3 years, the mean change in eGFR per year was -1.8±4.4 mL/min/1.73 m(2)/y. No significant difference in rate of eGFR decline was observed per 1 arbitrary unit increase in SAF (-0.1 mL/min/1.73 m(2)/y; 95% confidence interval, -0.7 to 0.5; P=0.8). Analyses of the secondary end points showed that there was an association of SAF with incidence of eGFR <60 and <45 mL/min/1.73 m(2) (hazard ratio, 1.54; 95% confidence interval, 1.13-2.10; P=0.006 and hazard ratio, 1.76; 95% confidence interval, 1.20-2.59; P=0.004, respectively), but after adjustment for age and sex, significance was lost. There was no association of SAF with rapid eGFR decline. In conclusion, in this cohort of patients with peripheral artery disease, elevated SAF was associated with lower baseline eGFR. Although SAF has previously been established as a predictor for cardiovascular disease and mortality, it did not predict the rate of kidney function decline during follow-up in this study.

Dietary Guideline Adherence Index and Kidney Measures intheFramingham Heart Study.

No observational studies have directly considered dietary guidelines when examining the prospective association between dietary intake and kidney measures. Prospective cohort study. We examined participants who attended examinations 7 (1998-2001) and 8 (2005-2008) in the Framingham Offspring Cohort. Individual components of Dietary Guidelines for Americans Adherence Index (DGAI) that reflect adherence to key dietary recommendations based on the 2005 guideline. The primary outcome was incident low estimated glomerular filtration rate (eGFR) at follow-up after exclusion of prevalent low eGFR at baseline. Low eGFR was defined as serum creatinine-based eGFR<60mL/min/1.73m2. Among 1,822 participants (mean age, 59.4 years; 54.6% women), 181 incident cases of low eGFR were identified. After adjustment for potential confounders, compared to optimal adherence to meat and legume recommendations, low adherence was associated with higher odds of incident low eGFR (P for trend= 0.01); ORs in the lowest and intermediate adherence categories were 2.98 (95% CI, 1.13-7.92) and 1.65 (95% CI, 1.02-2.66), respectively. Low adherence to dairy product recommendations was also associated with higher odds of incident low eGFR compared to optimal adherence (P for trend= 0.03); ORs in the lowest and intermediate adherence categories were 1.98 (95% CI, 1.03-3.82) and 1.59 (95% CI, 0.81-3.11), respectively. In addition, low adherence to meat and legume recommendations was associated with rapid eGFR decline (P for trend= 0.01), and low adherence to dairy product recommendations was associated with rapid eGFR decline (P for trend= 0.01) and incident albuminuria (P for trend= 0.03). The DGAI was developed based on the 2005 Dietary Guidelines for Americans. Better adherence to dietary recommendations for both meat and legumes and dairy products was associated with lower risk for developing adverse kidney measures.

Dynamic Changes in Renal Function Are Associated With Major Cardiovascular Events in Patients With Type 2 Diabetes.

The pattern of renal function decline prior to cardiovascular (CV) events in type 2 diabetes is not well known. Our aim was to describe the association between renal function trajectories and the occurrence of a CV event. We considered patients with type 2 diabetes from the SURDIAGENE (Survie, Diabete de type 2 et Genetique) study (discovery cohort) and the DIABHYCAR (Non-Insulin-Dependent Diabetes, Hypertension, Microalbuminuria or Proteinuria, Cardiovascular Events, and Ramipril) study (replication cohort). Global patterns of estimated glomerular filtration rate (eGFR) (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) and serum creatinine (SCr) prior to a major CV event (MACE) or last update were determined using a linear mixed-effects model and annual individual slopes computed by simple linear regression. In the 1,040 participants of the discovery cohort, establishment of global patterns including 22,227 SCr over 6.3 years of follow-up showed an annual eGFR decline and an annual SCr increase that were significantly greater in patients with MACE compared with patients without (-3.0 and -1.7 mL/min/1.73 m(2)/year and +10.7 and +4.0 μmol/L/year, respectively; P < 0.0001 for both). Median annual individual slopes were also significantly steeper in patients with MACE, and adjusted risk of MACE was 4.11 times higher (3.09-5.45) in patients with rapid decline in eGFR (change less than -5 mL/min/1.73 m(2)/year). Consideration of renal function trajectories provided significant additive information helping to explain the occurrence of MACE for both SCr and eGFR (PIDI < 0.0001 and P = 0.0005, respectively). These results were confirmed in the replication cohort. Renal function decline was associated with a higher risk of MACE. The pattern of renal function decline, beyond baseline kidney function, is an independent factor of CV risk.

Noninvasive Central Systolic Blood Pressure Is More Strongly Related to Kidney Function Decline Than Peripheral Systolic Blood Pressure in a Chinese Community–Based Population

This study aimed to investigate the association of noninvasive central aortic blood pressure with kidney function decline in a Chinese community-based population with normal kidney function at baseline. A total of 3153 Chinese participants from an atherosclerosis cohort were included in our analysis. The primary outcome was renal function decline defined as a drop in estimated glomerular filtration rate (eGFR) category accompanied by a ≥25% drop in eGFR from baseline; or a sustained decline in eGFR of >5 mL/min per 1.73 m(2)/y. The secondary outcomes were rapid eGFR decline (a decline in eGFR of >3 mL/min per 1.73 m(2)/y) and new incidence of chronic kidney disease. Participants were 56.6±8.5 years old, 36.0% were males, and 48.8% had hypertension. Mean (SD) baseline eGFR was 101.2±10.6 mL/min per 1.73 m(2) After a mean 2.35-year follow-up, the incidence of renal function decline, rapid eGFR decline and chronic kidney disease were 7.3%, 19.7%, and 0.7%, respectively. In multivariate logistic-regression analyses, central and peripheral systolic blood pressure (SBP) were both independently associated with all outcomes after adjustment for various confounders. When peripheral SBP was forced into the model with central SBP simultaneously, its significant association with the 3 outcomes all disappeared; however, central SBP was still significantly related with all outcomes even after further adjusting peripheral SBP. In conclusion, central SBP is a stronger predictor compared with peripheral SBP for early kidney function decline in a Chinese community-based population with normal kidney function at baseline.

Pain and Kidney Function Decline and Mortality: A CohortStudyof US Veterans.

Chronic pain is a common condition in the general population. However, large epidemiologic studies examining the role of pain in the deterioration of kidney function, development of chronic kidney disease, and risk for death are lacking. Retrospective cohort study. A nationally representative cohort of 2,360,056 US veterans with baseline estimated glomerular filtration rates (eGFRs)≥ 60mL/min/1.73m(2), followed up from October 2004 to September2006. 4 pain categories were compared: none (score, 0), mild (1-4), moderate (5-6), or severe (≥7). eGFR decline (determined by eGFR slope) and combined incident eGFR<60mL/min/1.73m(2) or all-cause death. We examined the pain management pattern and association of reported pain with (1) rapid eGFR decline and (2) a composite outcome of incident eGFR<60mL/min/1.73m(2) or all-cause death using logistic regression and Cox models adjusted for baseline eGFR, demographics, comorbid conditions, cardiovascular risk factors, and depression. ∼60% of veterans reported pain of any severity during the baseline period. The most commonly prescribed analgesics were opioids. In a dose-response relationship, veterans reporting moderate or severe pain had a higher risk for faster eGFR decline compared with those reporting none (ORs of 1.11 [95% CI, 1.09-1.14] and 1.17 [95% CI, 1.13-1.21] for moderate and severe pain, respectively). In combined analyses, veterans reporting moderate or severe pain both had 30% higher risk of the combined outcome (incident eGFR, 60 mL/min/1.73 m(2) or death) compared with those reporting none (HRs of 1.30 [95% CI, 1.28-1.31] and 1.30 [95% CI, 1.28-1.32] for moderate and severe pain, respectively). Lack of granular data regarding type and location of pain. We observed a high prevalence of pain and analgesic prescription in the US veteran populationwith normal eGFRs. Pain was associated with a higher incidence of eGFRs<60mL/min/1.73m(2), faster kidney function decline, and higher mortality.

Relationship between mortality and speed of eGFR decline in the 3months prior to dialysis initiation.

The timing for initiating dialysis in chronic kidney disease is often determined by the clinical symptoms and estimated glomerular filtration rate (eGFR). However, very few studies have examined how the speed of kidney function decline before initiating dialysis relates to mortality after dialysis initiation. Here, we report our examination of the relationship between the speed of eGFR decline in the 3months prior to dialysis initiation and mortality. The study included 1292 new dialysis patients who were registered in the Aichi Cohort Study of Prognosis in Patients Newly Initiated into Dialysis. The subjects were placed in 4 groups based on the speed of eGFR decline in the 3months before initiating dialysis (eGFR at 3months before initiation-eGFR at initiation) <2:≥2,<4:≥4,<6:≥6mL/min/1.73m2. All-cause, cardiovascular, and infection-related mortality rates were compared using Kaplan-Meier curves. A multivariate analysis using the Cox proportional hazard model was used to extract the factors that contributed to all-cause mortality. The group with faster eGFR decline exhibited significantly more heart failure symptoms when dialysis was initiated. Rapid eGFR decline correlated with prognosis (log-rank test: all-cause mortality p<0.001, cardiovascular mortality p<0.001). The speed of eGFR decline was related to elevated all-cause mortality rates [eGFR decline 10mL/min/1.73m2, HR (95% CI)=1.53 (1.12-2.08)]. This study showed that patients with rapid eGFR decline in the 3months before initiating dialysis more often presented with heart failure symptoms when dialysis was initiated and had poorer survival prognoses.

Serum uric acid levels are associated with a high risk of rapid chronic kidney disease progression among patients with type 2 diabetes: a prospective cohort study [Diabetes Distress and Care Registry at Tenri (DDCRT 12)

We assessed the prospective association between baseline serum uric acid (SUA) concentrations and consequent risk of chronic kidney disease (CKD) progression in type 2 diabetes patients. Longitudinal data from a Japanese diabetes registry including 3454 type 2 diabetes patients were obtained. To assess the independent correlations between SUA and rapid CKD progression [i.e., 30% reduction in estimated glomerular filtration rate (eGFR) over 2years], participants were divided into five groups based on SUA levels:<5.0,≥5.0-6.0,≥6.0-7.0,≥7.0-8.0, and≥8.0mg/dl. Cox proportional hazards model adjusted for potential confounders was used for analysis. After 2years, rapid CKD progression was recognized in 169 patients (4.89%) who showed longer duration of type 2 diabetes (15.5 vs. 13.5years, p=0.005); higher systolic blood pressure (142.0 vs. 138.3mmHg, p=0.016), SUA (6.15 vs. 5.32mg/dl, p<0.001), and urinary albumin-creatinine ratio (1127.4 vs. 184.7mg/gCr, p<0.001); and lower diastolic blood pressure (69.7 vs. 72.8mmHg, p=0.003). Multivariate ratios for rapid CKD progression were 1.19 (p=0.371), 1.02 (p=0.937), 1.18 (p=0.625), and 3.04 (p=0.004), respectively, for the first, third, fourth, and fifth serum UA range groups; a second group was used as a reference. Higher SUA levels, independent of possible confounders, were associated with rapid eGFR decline and CKD progression in type 2 diabetes patients. SUA may be a useful biomarker for predicting future risk of rapid diabetic CKD progression.

'To block or not to block'; whether to continue renin-angiotensin-aldosterone system blockade in advanced chronic kidney disease.

In patients with chronic kidney disease (CKD), proteinuria and high blood pressure predict cardiovascular morbidity, mortality and progression to end-stage kidney disease (ESKD) [1–3]. A large evidence base now supports the use of blockers of the renin–angiotensin–aldosterone system (RAAS) to lower blood pressure, reduce proteinuria and retard the progressive loss of renal function in this population [4–7]. Evidence for renoprotection, and the associated individual and economic benefits, is particularly strong in patients with diabetes and diabetic nephropathy, and has been endorsed in guidelines including the 2012 ‘KDIGO Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease’, which recommend the use of RAAS inhibitors as first-line treatment in all adult CKD patients with blood pressure >130/80 and albuminuria >30 mg/24-h [8, 9]. However, few patients with advanced CKD were included in the trials on which the guidelines were based [10], raising concerns about the generalizability of recommendations across the spectrum of CKD. Of note, the European Renal Best Practice position statement on the 2012 KDIGO hypertension guidelines specifically questions the continuous use of RAAS blocking drugs into advanced (stage 4 and 5) CKD [11]. Studies showing an accelerated disease progression in patients with advanced CKD, treated with ACE inhibitors (ACEi) and ARBs [12, 13], have added to these concerns, as has an observational study from the UK which showed substantial and sustained improvement in estimated glomerular filtration rate (eGFR) following withdrawal of RAAS blockade in 52 elderly patients with CKD stage 4–5 [14]. Furthermore, rapidly declining eGFR may be an independent predictor of cardiovascular events and mortality [15, 16] in CKD, lending support to the view that the continued use of ACEi and ARBs in CKD stage 4 and 5 may be harmful. In practice, ACEi and ARB therapy may be discontinued in advanced CKD, most commonly due to the development of hyperkalaemia, or following a rapid decline in eGFR; and often in the setting of dehydration or an intercurrent illness, and in the elderly [10]. Drug withdrawal was a frequent event in the pivotal trials of ACEi and ARBs in CKD. In The Reduction of Endpoints in NIDDM with Angiotensin II Antagonist Losartan (RENAAL) Study, 46.5% of patients in the treatment arm discontinued losartan [4]. A recent retrospective cohort study of 3039 patients initiated on an ACEi included 165 patients with serum creatinine ≥177 μmol/L (2 mg/dL) before treatment. In this group, 11.5% discontinued the drug within the first 3 months, and only 30% were still on the ACEi after 1 year [17]. It is unclear whether stopping therapy may have additional, potentially adverse, effects due to exposure of patients to an activated RAAS, and the effects of unopposed angiotensin II on arterioles, including glomerular efferent arterioles, resulting in an increased systemic and glomerular hypertension [18]. In animal experiments, the natriuretic and blood pressure lowering effects of ACE inhibitionmay last for weeks after withdrawal [19]. Whether long-term suppression, or post-withdrawal activation, of the RAAS has effects on inflammation, cell proliferation, endothelial function, cardiac hypertrophy/remodelling or renal fibrosis in humans [18] is not known. Thus, there is considerable uncertainty about the use, and effects, of blockade of the RAAS, and specifically the possible benefits or adverse consequences of withdrawal of ACEi and ARBs, in patients with CKD stage 4 and 5. To address this uncertainty, Bhandari et al. [20] describe the protocol of the ongoing, multicentre, open-labelled, randomized controlled ‘STOP-ACEi’ trial. This study will include 410 patients with progressive CKD stage 4 and 5 (not requiring renal replacement therapy), treated with an ACEi, an ARB or

Prognostic value of endocapillary hypercellularity in IgA nephropathy patients with no immunosuppression.

Interpretation of retrospective clinicopathological studies of IgA nephropathy (IgAN) has been confounded by immunosuppression bias. In published validation studies of the Oxford Classification of IgAN, an average of 33% of patients received non-randomised steroid and/or cytotoxic therapy. In order to determine the true impact of proliferative lesions on the natural history of IgAN, analysis of patient cohorts that have received no immunosuppression is required. We performed a retrospective single centre study of patients with IgAN managed without immunosuppressive therapy. Biopsies were scored according to the Oxford Classification. The primary outcomes were renal survival or a rapid loss of renal function defined as a decline in eGFR of>5ml/min/year. 237 patients with IgAN were identified with a mean follow-up of 82months. 200 had biopsies available for review, of which 156 were adequate for scoring using the Oxford Classification. 9/156 patients (5.8%) received some immunosuppressive therapy, mostly for unrelated conditions: these were excluded. In multivariate COX regression, including histological and clinical data, the only independent predictors of time to ESRD were baseline eGFR (HR 0.96 per ml/min increase, p=0.018), baseline proteinuria (HR 1.36 per doubling, p=0.004) and endocapillary hypercellularity (HR 4.75 for E1 compared to E0, p<0.001). Independent predictors of a rapid decline in eGFR were proteinuria (OR 1.45 per doubling, p=0.006), endocapillary hypercellularity (OR 3.41 for E1 compared to E0, p=0.025) and tubular atrophy/interstitial fibrosis (OR 8.77 for T2 compared to T0, p=0.006). In a cohort of IgAN patients receiving no immunosuppression, endocapillary proliferation and tubular atrophy/interstitial fibrosis are independent predictors of rate of loss of renal function. The lack of predictive value of E score in other clinicopathological studies is most likely a result of immunosuppression-associated bias. Our findings provide evidence to support immunosuppressive treatment of endocapillary-pattern IgAN.

Estimated GFR and Subsequent Higher Left Ventricular Mass in Young and Middle-Aged Adults With Normal Kidney Function: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Left ventricular hypertrophy is common and is associated with cardiovascular events and death among patients with known chronic kidney disease. However, the link between reduced glomerular filtration rate (GFR) and left ventricular mass index (LVMI) remains poorly explored among young and middle-aged adults with preserved kidney function. In this study, we examined the association of cystatin C-based estimated GFR (eGFRcys) and rapid decline in eGFR with subsequent LVMI. Observational study. We included 2,410 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort with eGFRcys > 60mL/min/1.73m(2) at year 15 and who had an echocardiogram obtained at year25. eGFRcys at year 15 and rapid decline in eGFRcys (defined as >3% per year over 5 years from years 15 to 20). LVMI measured at year25. We adjusted for age, sex, race, diabetes, body mass index, low- and high-density lipoprotein cholesterol levels, cumulative systolic blood pressure, and albuminuria. Mean age was 40±4 (SD) years, 58% were women, and 43% were black. After 10 years of follow-up, mean LVMI was 39.6±13.4g/m(2.7). Compared with eGFRcys > 90mL/min/1.73m(2) (n= 2,228), eGFRcys of 60 to 75mL/min/1.73m(2) (n= 29) was associated with 5.63 (95% CI, 0.90-10.36) g/m(2.7) greater LVMI (P= 0.02), but there was no association of eGFRcys of 76 to 90mL/min/1.73m(2) (n= 153) with LVMI after adjustment for confounders. Rapid decline in eGFRcys was associated with higher LVMI compared with participants without a rapid eGFRcys decline (β coefficient, 1.48; 95% CI, 0.11-2.83; P= 0.03) after adjustment for confounders. There were a limited number of participants with eGFRcys of 60 to 90mL/min/1.73m(2). Among young and middle-aged adults with preserved kidney function, eGFRcys of 60 to 75mL/min/1.73m(2) and rapid decline in eGFRcys were significantly associated with subsequently higher LVMI. Further studies are needed to understand the mechanisms that contribute to elevated LVMI in this range of eGFRcys.

Impact of the Triglycerides to High-Density Lipoprotein Cholesterol Ratio on the Incidence and Progression of CKD: A Longitudinal Study in a Large Japanese Population

The impact of the triglycerides to high-density lipoprotein cholesterol (TG:HDL-C) ratio on chronic kidney disease (CKD) is unclear. Longitudinal cohort study. 124,700 participants aged 39 to 74 years in the Japanese Specific Health Check and Guidance System, including 50,392 men, 74,308 women, 102,900 without CKD, and 21,800 with CKD. Quartiles of TG:HDL-C ratio. Changes in estimated glomerular filtration rate (eGFR) and urinary protein excretion during the 2-year study period. Incident CKD in participants without CKD, and progression of CKD in participants with CKD. In the entire study population, higher quartile of TG:HDL-C ratio at baseline was significantly associated with greater decline in eGFR and increase in urinary protein excretion during the 2-year study period, even after adjustment for confounding factors. A higher ratio was associated with higher risk of incident CKD in participants without CKD and higher risk of rapid decline in eGFR and increase in urinary protein excretion in participants with CKD. Higher TG:HDL-C ratio was more strongly associated with decline in eGFR (P for interaction= 0.002) and with incident CKD (P for interaction = 0.05) in participants with diabetes than without diabetes. Short observation period and single measurement of all variables. A higher TG:HDL-C ratio affects the decline in eGFR and incidence and progression of CKD in the Japanese population.

Time-dependent risk factors associated with the decline of estimated GFR in CKD patients.

BackgroundTargeting the modifiable risk factors may help halt the progression of CKD, thus risk factor analysis is better performed using the parameters in the follow-up. This study aimed to examine the time-dependent risk factors for CKD progression using time-averaged values and to investigate the characteristics of rapid progression group.MethodsThis is a retrospective cohort study enrolling 770 patients of CKD stage 3–4. Time-dependent parameters were calculated as time-averaged values by a trapezoidal rule. % decline of estimated GFR (eGFR) per year from entry was divided to three groups: <10 % (stable), 10–25 % (moderate progression), and ≥25 % (rapid progression). Multivariate regression analyses were employed for the baseline and the time-averaged datasets.ResultseGFR decline was 2.83 ± 4.04 mL/min/1.73 m2/year (8.8 ± 12.9 %) in male and 1.66 ± 3.23 mL/min/1.73 m2/year (5.4 ± 11.0 %) in female (p < 0.001). % decline of eGFR was associated with male, proteinuria, phosphorus, and systolic blood pressure as risk factors and with age, albumin, and hemoglobin as protective factors using either dataset. Baseline eGFR and diabetic nephropathy appeared in the baseline dataset, while uric acid appeared in the time-averaged dataset. The rapid progression group was associated with proteinuria, phosphorus, albumin, and hemoglobin in the follow-up.ConclusionThese results suggest that time-averaged values provide insightful clinical guide in targeting the risk factors. Rapid decline of eGFR is strongly associated with hyperphosphatemia, proteinuria, and anemia indicating that these risk factors should be intervened in the follow-up of CKD.

Lifestyle Factors and Indices of Kidney Function in the Framingham Heart Study

Background and Objectives: Lifestyle characteristics are modifiable factors that could be targeted as part of chronic kidney disease (CKD) prevention. We sought to determine the association of lifestyle characteristics with incident estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m² and rapid eGFR decline in older adults in the United States. Methods: Prospective cohort study of Framingham Offspring participants with baseline eGFR <60 ml/min/1.73 m² (n = 1,802) who attended the seventh (1998-2001; baseline) and eighth (2005-2008; follow-up) examinations (mean age = 59 years, 54.8% women). Predictors included measures of diet quality, physical activity, alcohol intake, and current smoking status assessed during baseline. Outcomes were based on creatinine-based eGFR at baseline and follow-up and included incident eGFR <60 ml/min/1.73 m² (at follow-up) and rapid eGFR decline (annual eGFR decrease ≥3 ml/min/1.73 m²). Results: Over an average follow-up of 6.6 years, 9.5% (n = 171) of participants developed incident eGFR <60. A trend was observed across quartiles of diet quality, with higher levels of diet quality associated with a decreased odds ratio (OR) of incident eGFR <60 (p trend = 0.045). Higher diet quality was associated with decreased odds of rapid eGFR decline (p trend = 0.03) and was attenuated with additional adjustment (p trend = 0.07). In sensitivity analysis for rapid eGFR decline using a secondary definition (annual eGFR decrease ≥3 and incident eGFR <60), diet associations remained significant with additional adjustment (p trend = 0.04). No associations were observed with physical activity, smoking status, or alcohol intake with incident eGFR <60 or rapid eGFR decline (all p > 0.19). Conclusions: Higher diet quality may be associated with a decreased risk of incident eGFR <60 ml/min/1.73 m², and rapid eGFR decline. Whether adherence to a healthy diet can prevent reduction in kidney function warrants further study.

Relationship between low Ankle-Brachial Index and rapid renal function decline in patients with atrial fibrillation: a prospective multicentre cohort study

ObjectiveTo investigate the relationship between Ankle-Brachial Index (ABI) and renal function progression in patients with atrial fibrillation (AF).DesignObservational prospective multicentre cohort study.SettingAtherothrombosis Center of I Clinica Medica of ‘Sapienza’ University...

Serum 25-hydroxyvitamin D level and kidney function decline in a Swiss general adult population.

Molecular evidence suggests that levels of vitamin D are associated with kidney function loss. Still, population-based studies are limited and few have considered the potential confounding effect of baseline kidney function. This study evaluated the association of serum 25-hydroxyvitamin D with change in eGFR, rapid eGFR decline, and incidence of CKD and albuminuria. Baseline (2003-2006) and 5.5-year follow-up data from a Swiss adult general population were used to evaluate the association of serum 25-hydroxyvitamin D with change in eGFR, rapid eGFR decline (annual loss >3 ml/min per 1.73 m(2)), and incidence of CKD and albuminuria. Serum 25-hydroxyvitamin D was measured at baseline using liquid chromatography-tandem mass spectrometry. eGFR and albuminuria were collected at baseline and follow-up. Multivariate linear and logistic regression models were used considering potential confounding factors. Among the 4280 people included in the analysis, the mean±SD annual eGFR change was -0.57±1.78 ml/min per 1.73 m(2), and 287 (6.7%) participants presented rapid eGFR decline. Before adjustment for baseline eGFR, baseline 25-hydroxyvitamin D level was associated with both mean annual eGFR change and risk of rapid eGFR decline, independently of baseline albuminuria. Once adjusted for baseline eGFR, associations were no longer significant. For every 10 ng/ml higher baseline 25-hydroxyvitamin D, the adjusted mean annual eGFR change was -0.005 ml/min per 1.73 m(2) (95% confidence interval, -0.063 to 0.053; P=0.87) and the risk of rapid eGFR decline was null (odds ratio, 0.93; 95% confidence interval, 0.79 to 1.08; P=0.33). Baseline 25-hydroxyvitamin D level was not associated with incidence of CKD or albuminuria. The association of 25-hydroxyvitamin D with eGFR decline is confounded by baseline eGFR. Sufficient 25-hydroxyvitamin D levels do not seem to protect from eGFR decline independently from baseline eGFR.