DASH-Style Diet Associates with Reduced Risk for Kidney Stones

The impact of the Dietary Approaches to Stop Hypertension (DASH) diet on kidney stone formation is unknown. We prospectively examined the relation between a DASH-style diet and incident kidney stones in the Health Professionals Follow-up Study (n = 45,821 men; 18 yr of follow-up), Nurses'' Health Study I (n = 94,108 older women; 18 yr of follow-up), and Nurses'' Health Study II (n = 101,837 younger women; 14 yr of follow-up). We constructed a DASH score based on eight components: high intake of fruits, vegetables, nuts and legumes, low-fat dairy products, and whole grains and low intake of sodium, sweetened beverages, and red and processed meats. We used Cox hazards regression to adjust for factors that included age, BMI, and fluid intake. Over a combined 50 yr of follow-up, we documented 5645 incident kidney stones. Participants with higher DASH scores had higher intakes of calcium, potassium, magnesium, oxalate, and vitamin C and had lower intakes of sodium. For participants in the highest compared with the lowest quintile of DASH score, the multivariate relative risks for kidney stones were 0.55 (95% CI, 0.46 to 0.65) for men, 0.58 (95% CI, 0.49 to 0.68) for older women, and 0.60 (95% CI, 0.52 to 0.70) for younger women. Higher DASH scores were associated with reduced risk even in participants with lower calcium intake. Exclusion of participants with hypertension did not change the results. In conclusion, consumption of a DASH-style diet is associated with a marked decrease in kidney stone risk.Diet plays a major role in the development of kidney stones, and dietary changes likely have contributed to the substantial increase in nephrolithiasis over the past several decades.^1,2 A wide variety of dietary factors either promote or inhibit the formation of calcium oxalate kidney stones,^1,2 the most common type of stone.³Despite previously observed associations between individual dietary factors and kidney stone risk,² relatively few studies have examined the impact of overall diet or dietary patterns on risk. The identification of an effective stone prevention diet is difficult partly because most diets are isocaloric: if an individual reduces the intake of certain foods, he or she will increase the intake of other foods to maintain constant energy intake.⁴ As a result, consuming less of one dietary factor (such as animal protein⁵) to decrease stone risk may lead to the consumption of other factors (such as sucrose or fructose⁶) that increase risk.The Dietary Approaches to Stop Hypertension (DASH) diet, which is high in fruits and vegetables, moderate in low-fat dairy products, and low in animal protein represents a novel potential means of kidney stone prevention. The consumption of fruits and vegetables increases urinary citrate,⁷ an important inhibitor of calcium stone formation, and a diet with normal to high calcium content but low in animal protein and sodium decreases the risk of calcium oxalate stone recurrence by 51%.⁸ The DASH diet also lowers BP,⁹ which is particularly appealing given the high rates of prevalent and incident hypertension in stone formers.^10–14 Because the DASH diet would be expected to contain higher amounts of oxalate and vitamin C, both of which may increase calcium kidney stone risk,^15,16 the impact of the DASH diet on stone risk is currently unknown.To examine the relation between a DASH-style diet and the risk of incident kidney stones, we conducted prospective studies in three large cohorts: the Health Professionals Follow-up Study (HPFS), the Nurses'' Health Study I (NHS I), and the Nurses'' Health Study II (NHS II). Previously, we identified associations between individual dietary factors and stone risk in each of these study populations.^5,6,15–18 For the first time, we now report the impact of a specific dietary pattern on risk.     

风险指数对急性心肌梗死病人预后的评估

目的探讨风险指数与急性心肌梗死 (AMI)病人早期病情变化及预后评估的相关性。方法对 80例确诊为AMI病人的风险指数进行测评。结果风险指数随年龄增加、心率 (HR)增快、收缩压 (SBP)下降而升高 (P <0 .0 5 ,P <0 .0 1) ,尤其是SBP低于 90mmHg者风险指数明显增大 ;风险指数 >30者住院期间急性左心衰发生率和病死率较≤ 30者显著增加 (均P <0 .0 1)。结论风险指数与AMI病人早期急性左心衰发生率和病死率密切相关 ,是评估AMI病人早期病情变化和预后的有效方法。     

Kidney Function and Histological Damage in Autopsy Subjects with Myocardial Infarction

Abstract

Objectives: Chronic kidney disease (CKD) is a major risk factor for cardiovascular disease (CVD). We previously reported renal parenchymal damage in autopsy subjects with stroke or abdominal aortic aneurysm. The aim of this study is to evaluate the relationship between renal histology and clinical characteristics of patients with myocardial infarction (MI). Methods: A total of 699 subjects were autopsied at the National Cerebral and Cardiovascular Center Hospital. We retrospectively evaluated all autopsy cases with MI (n = 123). Estimated glomerular filtration rate (eGFR) was calculated using the Japanese formula. Subjects were classified into four groups: 25 subjects with eGFR ≥ 60 mL/min/1.73 m² and no proteinuria (no CKD), 10 subjects with eGFR ≥ 60 and proteinuria (CKD1/2), 65 subjects with 60 > eGFR ≥ 30 (CKD3), and 23 subjects with eGFR < 30 (CKD4/5). Renal parenchymal damage was evaluated using a semi-quantitative histological score (score 0–3) for glomerulosclerosis, interstitial fibrosis, tubular atrophy, arteriolar hyalinosis, and arteriosclerosis of medium-sized artery (maximum score = 15). Results: The mean histological score was significantly higher in patients with CKD3 and CKD4/5 and was associated with age, hypertension, diabetes, kidney function, proteinuria, and other CVD. Conclusions: In patients with MI, renal parenchymal damage and deteriorating kidney function are closely associated.     

APOL1 Variants Associate with Increased Risk of CKD among African Americans

Although case-control studies suggest that African Americans with common coding variants in the APOL1 gene are 5–29 times more likely than those individuals without such variants to have focal segmental glomerulosclerosis, HIV-associated nephropathy, or ESRD, prospective studies have not yet evaluated the impact of these variants on CKD in a community-based sample of African Americans. Here, we studied whether the APOL1 G1 and G2 risk alleles associate with the development of CKD and progression to ESRD by analyzing data from 3067 African Americans in the Atherosclerosis Risk in Communities Study who did not have CKD at baseline. Carrying two risk alleles associated with a 1.49-fold increased risk of CKD (95% CI=1.02 to 2.17) and a 1.88-fold increased risk of ESRD (95% CI=1.20 to 2.93) compared with zero or one risk allele; associations persisted after adjusting for European ancestry. Among participants who developed CKD, those participants with two risk alleles were more likely to progress to ESRD than their counterparts with zero or one risk allele (HR=2.22, 95% CI=1.01 to 4.84). In conclusion, APOL1 risk variants are risk factors for the development of CKD and progression from CKD to ESRD among African Americans in the general population.African Americans suffer disproportionally from the most severe forms of CKD, including ESRD, and progress faster from CKD to ESRD, even after accounting for differences in socioeconomic factors.^1–5 Recent studies show that genetic variants in the MYH9-APOL1 region on chromosome 22 that are common among individuals with African ancestry but rare in Caucasian populations are associated with prevalent ESRD,^6–12 accounting for the excessive risk of kidney disease among African Americans compared with their Caucasian counterparts. In case-control studies, two risk alleles (termed G1 and G2) in the last exon of APOL1, a gene that encodes apolipoprotein-L1, are associated with 5–29 times higher odds of severe kidney disease, such as nondiabetic ESRD, hypertension-attributed ESRD, focal segmental glomerulosclerosis, and HIV-related nephropathy.^8,10,11 However, it is not known whether these variants predict the development of incident CKD or ESRD events and whether the risk of progression from CKD to ESRD in a prospective community-based sample of middle-aged African Americans differs from prior work investigating associations with prevalent kidney disease in case-control studies and cross-sectional analyses of population-based or high-risk cohorts.^8–14 If APOL1 G1 and G2 variants confer higher risk of incident CKD and progression to ESRD in the general population and an effective intervention is identified, then genetic screening could be used to identify high-risk individuals who can be targeted for intervention. Therefore, we sought to determine whether the APOL1 risk alleles are associated with the development of incident CKD and progression to ESRD events in over 3000 African Americans from the Atherosclerosis Risk in Communities (ARIC) Study with a baseline examination in 1987–1989 (visit 1), follow-up examinations in 1990–1992 (visit 2) and 1996–1998 (visit 4), and follow-up for ESRD hospitalizations through 2008. We hypothesized that African Americans carrying two APOL1 risk alleles would have an increased risk of CKD and ESRD progression compared with those individuals carrying zero or one risk allele.     

Donor ABCB1 Variant Associates with Increased Risk for Kidney Allograft Failure

The impact of variation within genes responsible for the disposition and metabolism of calcineurin inhibitors (CNIs) on clinical outcomes in kidney transplantation is not well understood. Furthermore, the potential influence of donor, rather than recipient, genotypes on clinical endpoints is unknown. Here, we investigated the associations between donor and recipient gene variants with outcome among 4471 white, CNI-treated kidney transplant recipients. We tested for 52 single-nucleotide polymorphisms (SNPs) across five genes: CYP3A4, CYP3A5, ABCB1 (MDR1; encoding P-glycoprotein), NR1I2 (encoding the pregnane X receptor), and PPIA (encoding cyclophilin). In a discovery cohort of 811 patients from Birmingham, United Kingdom, kidney donor CC genotype at C3435T (rs1045642) within ABCB1, a variant known to alter protein expression, was associated with an increased risk for long-term graft failure compared with non-CC genotype (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.20–2.40; P=0.003). No other donor or recipient SNPs were associated with graft survival or mortality. We validated this association in 675 donors from Belfast, United Kingdom (HR, 1.68; 95% CI, 1.21–2.32; P=0.002), and in 2985 donors from the Collaborative Transplant Study (HR, 1.84; 95% CI, 1.08–3.13; P=0.006). In conclusion, these data suggest that an ABCB1 variant known to alter protein expression represents an attractive candidate for future study and risk stratification in kidney transplantation.Calcineurin inhibitors (CNIs) remain principal components of most immunosuppression regimens in kidney transplantation. CNI dose adjustments based on CNI blood levels is the traditional approach to drug administration; however, this is an imperfect approach because CNIs have a narrow therapeutic index and high pharmacokinetic variability.¹ The unpredictable response to CNI drug dosing has been attributed to interindividual differences in expression of drug-metabolizing enzymes and transporters. Important components of this CNI disposition “axis” are the nuclear pregnane X receptor (PXR, encoded by the nuclear receptor subfamily 1, group I, member 2 [NR1I2] gene), which is proposed to be a “master regulator” of hepatic drug handling; cytochrome P450 (CYP) enzymes 3A4 and 3A5; the drug transporter P-glycoprotein (P-gp, encoded by the ATP-binding cassette, sub-family B, member 1 [ABCB1] gene, also known as the multidrug resistance 1 [MDR-1] gene); and cyclophilin A (Cyp, encoded by the peptidylprolyl isomerase A [PPIA] gene), the target of cyclosporine.^2–6Although data are inconsistent, there is evidence that single-nucleotide polymorphisms (SNPs) within these genes are associated with variation in cyclosporine and tacrolimus pharmacokinetics.^7–9 Preliminary and unreplicated reports also suggest that recipient genotype for ABCB1 is associated with delayed graft function¹⁰ and acute rejection,^11,12 and recipient CYP3A5 genotype is associated with mortality.¹³ However, with the exception of this report by Kreutz and colleagues,¹³ no studies have addressed the relationship between recipient genotype and the important “hard” clinical endpoints of renal transplantation (i.e., allograft failure or mortality), with limitations stemming from small sample sizes and short follow-up.¹⁴In contrast to studies of recipient genotype, far less information is available on the relationship between SNPs within genes of the kidney transplant donor and subsequent outcome. Although reduced expression of CYP3A5 and P-gp within the transplanted kidney have been associated with CNI toxicity,^15,16 only two small published studies to date have addressed the relationship between donor SNPs and clinical outcomes in cyclosporine-treated patients. These provide some evidence for an association between genetic variation in donor ABCB1 and acute cyclosporine nephrotoxicity¹⁷ and allograft failure.¹⁸ Both studies focused on the C3435T polymorphism within the ABCB1 gene, an exonic SNP whereby the TT genotype is associated with reduced P-gp expression.¹⁹The purpose of this study was to assess the relationship of both donor and recipient genotype with kidney allograft survival and recipient mortality. The study was not restricted to the limited number of SNPs previously studied but rather involved a comprehensive survey of common sequence variation in the target genes involved in CNI disposition. This was accomplished by interrogating the International HapMap resource²⁰ and selecting 52 tagging SNPs to capture the majority of common variation within five candidate genes. Preliminary positive findings from an initial discovery cohort were examined in two further independent populations, incorporating a total of 4471 renal transplant recipients followed for up to 20 years.     

Risk Factors in Surgical Patients with Verified Preoperative Myocardial Infarction

A series of 89 surgical patients (111 operations) with preoperative myocardial infarction (MI) was analysed for factors predisposing to the development of a postoperative reinfarction. Six of them suffered postoperative MI, and three of these patients died. In the statistical analysis the following risk factors emerged: age over 60 years, anaemia, hypertension, and the fact that the previous MI had been posterior. Abdominal operations were more dangerous concerning reinfarction than other operations. In the other series of 11 deceased patients with postoperative reinfarction collected from the autopsy material, about the same risk factors were found. The most important factor seemed to be hypotension, which complicated the surgery. All 11 patients had arrhythmias in their preoperative electrocardiogram. Previously treated heart failure was present in five of these patients. Postoperative symptoms analysed in the first series suggest that if a patient with preoperative MI has arrhythmias, hypotension, dyspnoea, diffuse unlocalized pain or chest pain after sugery, he is very likely to have a reinfarction.