Dietary protein intake and kidney function decline after myocardial infarction:the Alpha Omega Cohort

BACKGROUND: Post-myocardial infarction (MI) patients have a doubled rate of kidney function decline compared with the general population. We investigated the extent to which high intake of total, animal and plant protein are risk factors for accelerated kidney function decline in older stable post-MI patients. METHODS: We analysed 2255 post-MI patients (aged 60-80 years, 80% men) of the Alpha Omega Cohort. Dietary data were collected with a biomarker-validated 203-item food frequency questionnaire. At baseline and 41 months, we estimated glomerular filtration rate based on the Chronic Kidney Disease Epidemiology Collaboration equations for serum cystatin C [estimated glomerular filtration rate (eGFRcysC)] alone and both creatinine and cystatin C (eGFRcr-cysC). RESULTS: Mean [standard deviation (SD)] baseline eGFRcysC and eGFRcr-cysC were 82 (20) and 79 (19) mL/min/1.73 m2. Of all patients, 16% were current smokers and 19% had diabetes. Mean (SD) total protein intake was 71 (19) g/day, of which two-thirds was animal and one-third plant protein. After multivariable adjustment, including age, sex, total energy intake, smoking, diabetes, systolic blood pressure, renin-angiotensin system blocking drugs and fat intake, each incremental total daily protein intake of 0.1 g/kg ideal body weight was associated with an additional annual eGFRcysC decline of -0.12 (95% confidence interval -0.19 to -0.04) mL/min/1.73 m2, and was similar for animal and plant protein. Patients with a daily total protein intake of ≥1.20 compared with <0.80 g/kg ideal body weight had a 2-fold faster annual eGFRcysC decline of -1.60 versus -0.84 mL/min/1.73 m2. Taking eGFRcr-cysC as outcome showed similar results. Strong linear associations were confirmed by restricted cubic spline analyses. CONCLUSION: A higher protein intake was significantly associated with a more rapid kidney function decline in post-MI patients.</p

Body-fat indicators and kidney function decline in older post-myocardial infarction patients:The Alpha Omega Cohort Study

Background: Obesity increases risk of hypertension and diabetes, the leading causes of end-stage renal disease. The effect of obesity on kidney function decline in stable post-myocardial infarction patients is poorly documented. This relation was investigated in a large cohort of older post-myocardial infarction patients. Design: Data were analysed from 2410 post-myocardial infarction patients in the Alpha Omega Trial, aged 60–80 years receiving optimal pharmacotherapy treatment (79% men, 18% diabetes). Methods: Cystatin C based estimated glomerular filtration rate (eGFRcysC) was calculated at baseline and after 41 months, using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Obesity was defined as body mass index ≥ 30 kg/m2 and high waist circumference as ≥102 and ≥88 cm for men and women. The relation between body mass index, waist circumference and annual eGFRcysC decline was evaluated by linear regression. Results: At baseline, mean (standard deviation) eGFRcysC was 81.5 (19.6) ml/min/1.73 m2, 23% of all patients were obese. After multivariable adjustment, the annual mean (95% confidence interval) eGFRcysC decline in men and women was –1.45 (–1.59 to –1.31) and –0.92 (–1.20 to –0.63) ml/min/1.73 m2, respectively (p = 0.001). Obese versus non-obese patients and patients with high versus normal waist circumference experienced greater annual eGFRcysC decline. Men and women showed an additional annual eGFRcysC decline of –0.35 (–0.56 to –0.14) and –0.21 (–0.55 to 0.14) ml/min/1.73 m2 per 5 kg/m2 body mass index increment (p for interaction 0.3). Conclusions: High compared to normal body mass index or waist circumference were associated with more rapid kidney function decline in older stable post-myocardial infarction patients receiving optimal drug therapy.</p

Publisher Correction: Lower body mass index and mortality in older adults starting dialysis (vol 8, 12858, 2018)

Clinical epidemiolog

Serum Potassium and Risk of Death or Kidney Replacement Therapy in Older People With CKD Stages 4-5: Eight-Year Follow-up

Rationale &amp; objective: Hypokalemia may accelerate kidney function decline. Both hypo- and hyperkalemia can cause sudden cardiac death. However, little is known about the relationship between serum potassium and death or the occurrence of kidney failure requiring replacement therapy (KRT). We investigated this relationship in older people with chronic kidney disease (CKD) stage 4-5. Study design: Prospective observational cohort study. Setting &amp; participants: We followed 1,714 patients (≥65 years old) from the European Quality (EQUAL) study for 8 years from their first estimated glomerular filtration rate (eGFR)&lt;20mL/min/1.73m2 measurement. Exposure: Serum potassium was measured every 3 to 6 months and categorized as≤3.5,&gt;3.5-≤4.0,&gt;4.0-≤4.5,&gt;4.5-≤5.0 (reference),&gt;5.0-≤5.5, &gt;5.5-≤6.0, and&gt;6.0mmol/L. Outcome: The combined outcome death before KRT or start of KRT. Analytical approach: The association between categorical and continuous time-varying potassium and death or KRT start was examined using Cox proportional hazards and restricted cubic spline analyses, adjusted for age, sex, diabetes, cardiovascular disease, renin-angiotensin-aldosterone system (RAAS) inhibition, eGFR, and subjective global assessment (SGA). Results: At baseline, 66% of participants were men, 42% had diabetes, 47% cardiovascular disease, and 54% used RAAS inhibitors. Their mean age was 76±7 (SD) years, mean eGFR was 17±5 (SD) mL/min/1.73m2, and mean SGA was 6.0±1.0 (SD). Over 8 years, 414 (24%) died before starting KRT, and 595 (35%) started KRT. Adjusted hazard ratios for death or KRT according to the potassium categories were 1.6 (95% CI, 1.1-2.3), 1.4 (95% CI, 1.1-1.7), 1.1 (95% CI, 1.0-1.4), 1 (reference), 1.1 (95% CI, 0.9-1.4), 1.8 (95% CI, 1.4-2.3), and 2.2 (95% CI, 1.5-3.3). Hazard ratios were lowest at a potassium of about 4.9mmol/L. Limitations: Shorter intervals between potassium measurements would have allowed for more precise estimations. Conclusions: We observed a U-shaped relationship between serum potassium and death or KRT start among patients with incident CKD&nbsp;4-5, with a nadir risk at a potassium level of&nbsp;4.9mmol/L. These findings underscore the&nbsp;potential importance of preventing both high and low potassium in patients with CKD 4-5. Plain-language summary: Abnormal potassium blood levels may increase the risk of death or kidney function decline, especially in older people with chronic kidney disease (CKD). We studied 1,714 patients aged≥65 years with advanced CKD from the European Quality (EQUAL) study and followed them for 8 years. We found that both low and high levels of potassium were associated with an increased risk of death or start of kidney replacement therapy, with the lowest risk observed at a potassium level of 4.9 mmol/L. In patients with CKD, the focus is often on preventing high blood potassium. However, this relatively high optimum potassium level stresses the potential importance of also preventing low potassium levels in older patients with advanced CKD

Lower body mass index and mortality in older adults starting dialysis

Lower body mass index (BMI) has consistently been associated with mortality in elderly in the general and chronic disease populations. Remarkably, in older incident dialysis patients no association of BMI with mortality was found. We performed an in-depth analysis and explored possible time-stratified effects of BMI. 908 incident dialysis patients aged >= 65 years of the NECOSAD study were included, and divided into tertiles by baseline BMI (<23.1 ( lower), 23.1-26.0 ( reference), >= 26.0 (higher) kg/ m(2)). Because the hazards changed significantly during follow-up, the effect of BMI was modeled for the short-term (<1 year) and longer-term (>= 1 year after dialysis initiation). During follow-up (median 3.8 years) 567 deaths occurred. Lower BMI was associated with higher short-term mortality risk (adjusted-HR 1.63 [1.14-2.32] P = 0.007), and lower longer-term mortality risk (adjusted-HR 0.81 [0.63- 1.04] P = 0.1). Patients with lower BMI who died during the first year had significantly more comorbidity, and worse self-reported physical functioning compared with those who survived the first year. Thus, lower BMI is associated with increased 1-year mortality, but conditional on surviving the first year, lower BMI yielded a similar or lower mortality risk compared with the reference. Those patients with lower BMI, who had limited comorbidity and better physical functioning, had better survival

Effect of Omega-3 Fatty Acid Supplementation on Plasma Fibroblast Growth Factor 23 Levels in Post-Myocardial Infarction Patients with Chronic Kidney Disease:The Alpha Omega Trial

Fibroblast growth factor 23 (FGF23) is an independent risk factor for cardiovascular mortality in chronic kidney disease. Omega-3 (n-3) fatty acid consumption has been inversely associated with FGF23 levels and with cardiovascular risk. We examined the effect of marine n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and plant-derived alpha-linolenic acid (ALA) on plasma FGF23 levels in post-myocardial infarction patients with chronic kidney disease. In the randomized double-blind Alpha Omega Trial, 4837 patients with a history of myocardial infarction aged 60–80 years (81% men) were randomized to one of four trial margarines supplemented with a targeted additional intake of 400 mg/day EPA and DHA, 2 g/day ALA, EPA-DHA plus ALA, or placebo for 41 months. In a subcohort of 336 patients with an eGFR &lt; 60 mL/min/1.73 m2 (creatinine-cystatin C-based CKD-EPI formula), plasma C-terminal FGF23 was measured by ELISA at baseline and end of follow-up. We used analysis of covariance to examine treatment effects on FGF23 levels adjusted for baseline FGF23. Patients consumed 19.8 g margarine/day on average, providing an additional amount of 236 mg/day EPA with 158 mg/day DHA, 1.99 g/day ALA or both, in the active intervention groups. Over 79% of patients were treated with antihypertensive and antithrombotic medication and statins. At baseline, plasma FGF23 was 150 (128 to 172) RU/mL (mean (95% CI)). After 41 months, overall FGF23 levels had increased significantly (p &lt; 0.0001) to 212 (183 to 241) RU/mL. Relative to the placebo, the treatment effect of EPA-DHA was indifferent, with a mean change in FGF23 (95% CI) of −17 (−97, 62) RU/mL (p = 0.7). Results were similar for ALA (36 (−42, 115) RU/mL) and combined EPA-DHA and ALA (34 (−44, 113) RU/mL). Multivariable adjustment, pooled analyses, and subgroup analyses yielded similar non-significant results. Long-term supplementation with modest quantities of EPA-DHA or ALA does not reduce plasma FGF23 levels when added to cardiovascular medication in post-myocardial patients with chronic kidney disease

Serum Potassium and Mortality Risk in Hemodialysis Patients: A Cohort Study.

RATIONALE & OBJECTIVE: Both hypo- and hyperkalemia can cause fatal cardiac arrhythmias. Although predialysis serum potassium level is a known modifiable risk factor for death in patients receiving hemodialysis, especially for hypokalemia, this risk may be underestimated. Therefore, we investigated the relationship between predialysis serum potassium level and death in incident hemodialysis patients and whether there is an optimum level. STUDY DESIGN: Prospective multicenter cohort study. SETTING & PARTICIPANTS: 1,117 incident hemodialysis patients (aged >18 years) from the Netherlands Cooperative Study on the Adequacy of Dialysis-2 study were included and followed from their first hemodialysis treatment until death, transplantation, switch to peritoneal dialysis, or a maximum of 10 years. EXPOSURE: Predialysis serum potassium levels were obtained every 6 months and divided into 6 categories: ≤4.0 mmol/L, >4.0 mmol/L to ≤4.5 mmol/L, >4.5 mmol/L to ≤5.0 mmol/L, >5.0 mmol/L to ≤5.5 mmol/L (reference), >5.5 mmol/L to ≤6.0 mmol/L, and >6.0 mmol/L. OUTCOMES: 6-month all-cause mortality. ANALYTICAL APPROACH: Cox proportional hazards and restricted cubic spline analyses with time-dependent predialysis serum potassium levels were used to calculate the adjusted HRs for death. RESULTS: At baseline, the mean age of the patients was 63 years (standard deviation, 14 years), 58% were men, 26% smoked, 24% had diabetes, 32% had cardiovascular disease, the mean serum potassium level was 5.0 mmol/L (standard deviation, 0.8 mmol/L), 7% had a low subjective global assessment score, and the median residual kidney function was 3.5 mL/min/1.73 m2 (IQR, 1.4-4.8 mL/min/1.73 m2). During the 10-year follow-up, 555 (50%) deaths were observed. Multivariable adjusted HRs for death according to the 6 potassium categories were as follows: 1.42 (95% CI, 1.01-1.99), 1.09 (95% CI, 0.82-1.45), 1.21 (95% CI, 0.94-1.56), 1 (reference), 0.95 (95% CI, 0.71-1.28), and 1.32 (95% CI, 0.97-1.81). LIMITATIONS: Shorter intervals between potassium measurements would have allowed for more precise mortality risk estimations. CONCLUSIONS: We found a U-shaped relationship between serum potassium level and death in incident hemodialysis patients. A low predialysis serum potassium level was associated with a 1.4-fold stronger risk of death than the optimal level of approximately 5.1 mmol/L. These results may imply the cautious use of potassium-lowering therapy and a potassium-restricted diet in patients receiving hemodialysis

Obesity and risk of death or dialysis in younger and older patients on specialized pre-dialysis care

Obesity is associated with increased mortality and accelerated decline in kidney function in the general population. Little is known about the effect of obesity in younger and older pre-dialysis patients. The aim of this study was to assess the extent to which obesity is a risk factor for death or progression to dialysis in younger and older patients on specialized pre-dialysis care.In a multicenter Dutch cohort study, 492 incident pre-dialysis patients (>18y) were included between 2004-2011 and followed until start of dialysis, death or October 2016. We grouped patients into four categories of baseline body mass index (BMI): <20, 20-24 (reference), 25-29, and ≥30 (obesity) kg/m2 and stratified patients into two age categories (<65y or ≥65y).The study population comprised 212 patients younger than 65 years and 280 patients 65 years and older; crude cumulative risk of dialysis and mortality at the end of follow-up were 66% and 4% for patients <65y and 64% and 14%, respectively, for patients ≥65y. Among the <65y patients, the age-sex standardized combined outcome rate was 2.3 times higher in obese than those with normal BMI, corresponding to an excess rate of 35 events/100 patient-years. After multivariable adjustment the hazard ratios (HR) (95% CI) for the combined endpoint by category of increasing BMI were, for patients <65y, 0.92 (0.41-2.09), 1 (reference), 1.76 (1.16-2.68), and 1.81 (1.17-2.81). For patients ≥65y the BMI-specific HRs were 1.73 (0.97-3.08), 1 (reference), 1.25 (0.91-1.71) and 1.30 (0.79-1.90). In the competing risk analysis, taking dialysis as the event of interest and death as a competing event, the BMI-specific multivariable adjusted subdistribution HRs (95% CI) were, for patients <65y, 0.90 (0.38-2.12), 1 (reference), 1.47 (0.96-2.24) and 1.72 (1.15-2.59). For patients ≥65y the BMI-specific SHRs (95% CI) were 1.68 (0.93-3.02), 1 (reference), 1.50 (1.05-2.14) and 1.80 (1.23-2.65).We found that obesity in younger pre-dialysis patients and being underweight in older pre-dialysis patients are risk factors for starting dialysis and for death, compared with those with a normal BMI

The Epidemiology of Diabetic Kidney Disease

Globally, the incidence and prevalence of diabetes mellitus has risen dramatically, owing mainly to the increase in type 2 diabetes mellitus (T2DM). In 2021, 537 million people worldwide (11% of the global population) had diabetes, and this number is expected to increase to 783 million (12%) by 2045. The growing burden of T2DM is secondary to the pandemic of obesity, which in turn has been attributed to increased intake of processed food, reduced physical activity, and increased sedentary behaviour. This so-called western lifestyle is related with the global increase in urbanization and technological development. One of the most frequent and severe long-term complications of diabetes is diabetic kidney disease (DKD), defined as chronic kidney disease in a person with diabetes. Approximately 20&ndash;50% of patients with T2DM will ultimately develop DKD. Worldwide, DKD is the leading cause of chronic kidney disease and end-stage kidney disease, accounting for 50% of cases. In addition, DKD results in high cardiovascular morbidity and mortality, and decreases patients&rsquo; health-related quality of life. In this review we provide an update of the diagnosis, epidemiology, and causes of DKD