Mild renal insufficiency is associated with increased cardiovascular mortality: The Hoorn Study

BACKGROUND: Cardiovascular mortality is extremely high in end-stage renal disease. Cardiovascular mortality risk also is increased in selected (high-risk) individuals with mild to moderate impairment of renal function. It is not clear whether a similar association exists in the general population and, if so, through what mechanisms. We investigated the association of renal function with all-cause and cardiovascular mortality in a population-based cohort and explored potential mechanisms underlying any such relationship. METHODS: An age-, sex-, and glucose-tolerance-stratified sample (N = 631) of a population-based cohort aged 50 to 75 years was followed prospectively. After up to 10.2 years of follow-up, 117 subjects had died (50 of cardiovascular causes). At baseline, renal function was estimated by the serum creatinine level, the Cockcroft-Gault formula and Levey's equation. RESULTS: At baseline, the mean age was 64 +/- 7 years, 48% were men, 55% had hypertension, and 27% (by design) had type 2 diabetes. Serum creatinine was 91.7 +/- 19.0 micromol/L; creatinine clearance as estimated by the Cockroft-Gault formula was 72.5 +/- 13.7 mL/min/1.73 m(2), and the glomerular filtration rate (GFR) estimated by Levey's equation was 67.8 +/- 12.1 mL/min/1.73 m(2). Renal function was inversely associated with all-cause and with cardiovascular mortality. Relative risks (95% confidence intervals) were 1.08 (1.04 to 1.13) and 1.11 (1.07 to 1.16) per 5 micromol/L increase of serum creatinine; 1.07 (0.98 to 1.17) and 1.15 (1.01 to 1.31) for each decrease of 5 mL/min/1.73 m(2) creatinine clearance; and 1.15 (1.05 to 1.26) and 1.26 (1.12 to 1.42) for each decrease of 5 mL/min/1.73 m(2) of GFR. These associations remained after adjusting for age, sex, glucose tolerance status, hypertension, prior cardiovascular disease, low-density lipoprotein cholesterol, homocysteine, (micro)albuminuria, von Willebrand factor, soluble vascular adhesion molecule-1 and C-reactive protein. Analyses in diabetic and hypertensive subjects gave similar results. CONCLUSION: Mild to moderate loss of renal function is strongly associated with an increased risk of cardiovascular mortality. The mechanism behind this association is unclear but does not appear to involve common risk factors such as hypertension, diabetes or hyperhomocysteinemia. Estimation of renal function by relatively simple methods therefore may be a valuable tool for cardiovascular risk assessment over and above that provided by conventional risk factors. Our results were obtained in a general middle-aged to elderly population, and thus have broad applicability.     

Renal insufficiency is associated with an increased risk of papillary renal cell carcinoma histology

Purpose

End-stage renal disease (ESRD) and acquired renal cystic disease associated with dialysis are known risk factors of papillary renal cell carcinoma (pRCC); however, it is not known whether renal insufficiency alone is a risk factor for pRCC. Our aim was to test whether renal insufficiency is associated with an increased preponderance of pRCC.

Methods

Retrospective review of institutional database to identify all patients who underwent extirpative renal surgery for renal cell carcinoma (RCC) with complete records from 1992 to 2012. We excluded those patients with preoperative ESRD as defined by GFR < 15 mL/min/1.73 m². The dependent variable was histologic RCC subtype. Independent variables included demographic data, comorbidities, and renal functional data. Multivariate analysis by binary logistic regression was used to determine factors that independently were associated with pRCC development.

Results

A total of 1,226 patients met inclusion criteria, of which 15 % were pRCC. There was a positive association between likelihood of pRCC histology of RCC and increasing preoperative chronic kidney disease (CKD) stage (p = 0.021). Multivariate regression analysis indicated that male gender, race, and declining renal function categorized both by GFR and CKD stage were independently associated with a higher likelihood of pRCC histology as compared to other RCC histology.

Conclusions

Within a large cohort of patients with a diagnosis of RCC, declining renal function was independently associated with an increased likelihood of pRCC histology. This finding and the available molecular evidence indicating protein expression similarity between pRCC and resident stem cells, which appear to be upregulated with kidney damage, suggest a possible causal relationship between renal injury and pRCC.     

Inappropriate left ventricular mass in children and young adults with chronic renal insufficiency

Increased left ventricular (LV) mass (M) in children with chronic renal insufficiency (CRI) might represent an adaptive mechanism to compensate for increased workload. We hypothesized that in children with CRI, pre-dialysis, values of left ventricular mass (LVM) exceed compensatory values for individual cardiac load. Complete anthropometric characteristics, biochemical profile and echocardiograms were obtained for 33 children with CRI, pre-dialysis (age 1–23 years, mean 12.2 ± 5.0 years), and 33 age- and gender-matched healthy controls. LV dimensions, wall thicknesses and volume were measured. Endocardial and midwall shortening, ejection fraction, LVM, LVM index, relative wall thickness, circumferential wall stress and excess LVM (as ratio of observed LVM to value predicted from body size, gender and cardiac workload) were analysed. Patients with CRI showed higher values of LVM index, resulting in higher prevalence of LV hypertrophy (36.3% vs 9%, P < 0.05). The ratio of excess LVM was greater in patients with CRI than in healthy controls (126 ± 19% and 103 ± 13%, respectively, P < 0.001). LV ejection fraction, midwall fractional shortening and stress-corrected midwall shortening were lower in patients with CRI than in controls. We concluded that, in children with CRI, the values of LVM are higher than those needed to sustain individual cardiac load than in healthy controls, a condition associated with LV hypertrophy and reduced systolic performance.     

Human ALOX12, but not ALOX15, is associated with BMD in white men and women.

The Alox15 gene was recently identified as a negative regulator of peak BMD in mice. Polymorphisms in human ALOX12, but not ALOX15, were significantly associated with spine BMD in white men and women, suggesting that ALOX12 may contribute to normal variation in BMD. INTRODUCTION: Osteoporosis is a complex disease with both genetic and environmental risk factors. A major determinant of osteoporosis is peak BMD, which is a highly heritable trait. Recently, the arachidonate 15-lipoxygenase (Alox15) gene was identified as a negative regulator of peak BMD in mice. MATERIALS AND METHODS: To assess the contribution of lipoxygenase genes to normal BMD variation in healthy white men and women, we performed population- and family-based association studies of two arachidonate lipoxygenase genes: ALOX15, which is the human homolog of mouse Alox15, and ALOX12, which is functionally similar to Alox15. Single nucleotide polymorphisms (SNPs) distributed across the two genes were genotyped. BMD was measured at the femoral neck and lumbar spine in 411 men 18-61 years of age and 1291 premenopausal women 20-50 years of age. RESULTS: Moderate evidence of association was found between spine BMD and six SNPs in the ALOX12 gene in both men and women (p = 0.0052-0.050). Furthermore, the most common SNP haplotype in ALOX12 showed evidence of significant association with high spine BMD in men (p = 0.0083), whereas the second most common haplotype was associated with high spine BMD in women (p = 0.0081). CONCLUSIONS: Polymorphisms in the ALOX12 gene may contribute to normal variation in spine BMD.     

Follicle-stimulating hormone is independently associated with lean mass but not BMD in younger postmenopausal women

Purpose

Increased follicle-stimulating hormone (FSH) has been associated with lower bone mineral density (BMD) in animal models and longitudinal studies of women, but a direct effect has not been demonstrated.

Methods

We tested associations between FSH, non-bone body composition measures and BMD in 94 younger (aged 50 to 64 years) postmenopausal women without current use of hormone therapy, adjusting for sex hormone concentrations and clinical risk factors for osteoporosis. Lean mass, fat mass and areal BMD (aBMD) at the spine, femoral neck and total hip were measured using dual energy X-ray absorptiometry (DXA). Volumetric BMD (vBMD) was measured at the distal radius using peripheral quantitative computed tomography (pQCT).

Results

FSH was inversely correlated with lean and fat mass, bioavailable estradiol, spine and hip aBMD, and vBMD at the ultradistal radius. In the multivariable analysis, FSH was independently associated with lean mass (β = − 0.099, p = 0.005) after adjustment for age, race, years since menopause, bioavailable estradiol, bioavailable testosterone, LH, PTH, SHBG and urine N-telopeptide. FSH showed no statistically significant association with aBMD at any site or pQCT measures at the distal radius in adjusted models. Race was independently associated with aBMD, and race and urine N-telopeptide were independently associated with bone area and vBMD.

Conclusions

After adjustment for hormonal measures and osteoporosis risk factors, higher concentrations of FSH were independently associated with lower lean mass, but not with BMD. Previously reported correlations between FSH and BMD might have been due to indirect associations via lean mass or weight.     

Delayed graft function is not associated with an increased incidence of renal allograft rejection

Delayed graft function (DGF) is considered as a risk factor for renal allograft rejection, but this association might be confounded by diagnostic biases (e.g., higher biopsy frequency in patients with DGF, inclusion of clinically diagnosed rejection episodes, and limited details on the rejection phenotype). This retrospective study including 329 deceased donor transplantations aimed to clarify a causal relationship between DGF and rejection. DGF occurred in 93/329 recipients (28%), whereas immediate graft function (IGF) in 236/329 recipients (72%). The percentage of patients with ≥1 allograft biopsy within the first year post‐transplant was similar between the DGF and IGF group (96% vs. 94%; p = 0.60). The cumulative one‐yr incidence of biopsy‐proven clinical (35% vs. 34%; p = 0.62) and combined (sub)clinical rejection (58% vs. 60%; p = 0.79) was not different between the two groups. Furthermore, there were no differences regarding rejection phenotypes/severities and time frame of occurrence. By multivariable Cox regression analysis, donor‐specific HLA antibodies, younger recipient age, and immunosuppressive regimens were independent predictors for clinical rejection, while DGF was not. These results in an intermediate sized, but thoroughly investigated patient population challenge the concept that DGF is a risk factor for rejection and highlights the need for additional studies in this regard.     

Hemodialysis-induced left ventricular dysfunction is associated with an increase in ventricular arrhythmias

Conventional hemodialysis results in intradialytic cardiac ischemia in a significant proportion of patients. Segmental myocardial ischemia results in the development of left ventricular regional wall motion abnormalities. Sudden death is the most common cause of mortality in hemodialysis patients. This study looked to examine any association between the development of left ventricular regional wall motion and cardiac arrhythmias. Forty established hemodialysis patients had 24-hour Holter recordings, which commenced immediately before a dialysis session. Frequency of isolated ectopy was classified as a percentage of the total beats on the Holter monitor record. Ventricular arrhythmias were stratified according to the Lown classification. Classes 3 and above were taken as complex ventricular arrhythmias. Patients also underwent baseline and intradialytic echocardiography to assess the development of concurrent regional wall motion abnormalities. Premature ventricular complexes and complex ventricular arrhythmias were both more common during hemodialysis than in the subsequent monitored period. Patients who developed regional wall motion abnormalities (n = 27) had significantly more premature ventricular complexes during hemodialysis than afterward (p < 0.001). Patients with ischemic heart disease and left ventricular hypertrophy both had a higher frequency of premature ventricular complexes during hemodialysis than those without (p < 0.03 and p < 0.02, respectively). Cardiac arrhythmias are common in hemodialysis patients. The frequency of premature ventricular complexes is significantly higher during hemodialysis in patients who develop regional wall motion abnormalities and may be related to factors associated with demand ischemia.     

Obesity as defined by waist circumference but not body mass index is associated with higher renal mass complexity

Objectives

Obesity, typically defined as a body mass index (BMI)≥30 kg/m², is an established risk factor for renal cell carcinoma (RCC) but is paradoxically linked to less advanced disease at diagnosis and improved outcomes. However, BMI has inherent flaws, and alternate obesity-defining metrics that emphasize abdominal fat are available. We investigated 3 obesity-defining metrics, to better examine the associations of abdominal fat vs. generalized obesity with renal tumor stage, grade, or R.E.N.A.L. nephrometry score.

Mild renal insufficiency is associated with reduced coronary flow in patients with non-obstructive coronary artery disease

Patients with chronic kidney disease (CKD) have increased risk for cardiovascular events. However, the association between these pathophysiological processes is unclear. Therefore, this study was designed to determine the association between early CKD and coronary microvascular disease in patients with normal or mildly diseased coronary arteries. A total of 605 patients with normal or mildly diseased coronary arteries based on angiography underwent coronary flow reserve (CFR) evaluation using intracoronary adenosine. Patients were divided based on glomerular filtration rate (GFR). CKD was defined as calculated GFR<60 ml/min/1.73 m(2). Patients with normal GFR (> or =60 ml/min/1.73 m(2), n=481) had higher CFR compared to those with CKD (n=124, CFR=3.0+/-0.8 vs 2.6+/-0.6, P<0.001, respectively). Patients with abnormal GFR were more likely to be older and of female gender, with greater prevalence of hypertension. Multiple logistic regression analysis adjusted for the aforementioned risk factors further supported the observed relationship. The current study shows that reduced renal function is associated with attenuated coronary vasodilator capacity in patients without obstructive coronary artery disease. The correlation between low GFR and reduced CFR may suggest parallel alterations in the renal and coronary microcirculation at the early stage of disease. Impairment in both microcirculatory beds may reflect an unmeasured risk factor induced by blunted renal function and add a burden to the increased propensity for cardiovascular events in CKD.     

Hernia repair with polypropylene mesh is not associated with an increased risk of autoimmune disease in adult men

Purpose

Synthetic mesh for herniorrhaphy has been placed under critical observation regarding the potential association of mesh placement and the subsequent development of autoimmune diseases. We sought to evaluate whether there is a link between synthetic polypropylene mesh repairs and the subsequent development of systemic/autoimmune disorders (SAID).

Study design

Adult men undergoing hernia repair with mesh between January 2008 and December 2009 in New York State were identified using International Classification of Diseases, Ninth Revision, Modification procedure codes and Current Procedural Terminology Coding System, Fourth Edition codes. A control cohort of men undergoing colonoscopy was created with whom to compare outcomes.

Results

A total of 29,712 patients underwent hernia repair between January 2008 and December 2009. In the control cohort, 79,265 patients underwent colonoscopy. During the entire follow-up, 475 patients undergoing hernia repair and 1305 patients in the control cohort were diagnosed with autoimmune disease. When patients were matched based on demographics, comorbidities and procedure date, hernia repair was not associated with an increased risk of developing autoimmune disease over the entire follow-up time period. 1.6% of those in the hernia group vs. 1.7% of those in the colonoscopy group developed SAID [risk ratio (95% CI): hernia vs. colonoscopy 0.93(0.79–1.09)]. No association between mesh surgery and increased risks of SAID was found at any of the specified time points (6 months, 1 year, and 2-year follow-up).

Conclusions

Mesh-based hernia repair was not associated with the development of autoimmune diseases compared to those undergoing routine screening colonoscopy.

     

Urinary angiotensinogen level is increased in renal transplant recipients with masked hypertension and is correlated with left ventricular mass index and albuminuria in these patients

Activation of the local renin‐angiotensin system (RAS) is an independent risk factor for the development of proteinuria and left ventricular hypertrophy (LVH) more commonly seen in masked hypertensives. It has been reported that urinary angiotensinogen (UAGT) level provides a specific index of the intrarenal RAS status. The aim of this study was to evaluate the association between UAGT and left ventricular mass index (LVMI) and urinary albumin‐creatinine ratio (UACR) in renal transplant recipients (RTRs) with masked hypertension (HT). A total of 116 non‐diabetic‐treated hypertensive RTRs were included in this study. The patients were divided into two groups: masked hypertensives and controlled hypertensives. Forty‐two (36.2%) of RTRs had masked HT. Mean UACR and LVMI levels were higher in RTRs with masked HT than in RTRs with controlled HT (P < 0.001). UAGT level was also higher in masked hypertensives compared to controlled hypertensives (P < 0.001). Multivariable regression analysis showed that UAGT was positively correlated with UACR (β = 0.024, P = 0.001) and LVMI (β = 0.082, P = 0.001) in masked hypertensives. Consequently, masked HT was considerably frequent (36.2%) in treated hypertensive RTRs and high UAGT levels accompanied by high albuminuria and LVMI levels were seen in these patients. Overproduction of the UAGT may play a pivotal role in the development of LVH and proteinuria in masked hypertensives.     

Excess body fat is associated with higher risk of vertebral deformities in older women but not in men: a cross-sectional study

Summary  

Thinness is a risk factor for fractures, but the effect of obesity on fracture risk is less clear. We found an association between measures of obesity and prevalence and number of vertebral deformities in women but not in men, in a cross-sectional study of 1,011 participants aged 50–80 years.     

Peripheral arterial disease is not associated with an increased prevalence of intradialytic cramps in patients on maintenance hemodialysis

BACKGROUND/AIMS: Peripheral arterial disease (PAD) has been suggested as a contributing factor to the development of intradialytic muscle cramps in patients on maintenance hemodialysis. METHODS: To test this hypothesis, 122 patients from two dialysis centers were studied. The presence of PAD was determined by measurement of the ankle-brachial index (ABI) in the lower extremities of patients pre- and postdialysis. The experience of intradialytic cramps was assessed using patient history and review of medical records. RESULTS: PAD defined as a predialysis ABI < or =0.90 had an overall prevalence of 16.4% among patients studied. The prevalence of PAD was age-dependent, reaching 37.5% in patients 80-89 years old. Intradialytic muscle cramps were common, with 52.1% of patients reporting cramps within the previous two months, but there was no relationship between cramps during dialysis and PAD (p > 0.05). CONCLUSIONS: PAD was common in hemodialysis patients, but there was no association between the presence of PAD and the prevalence of intradialytic muscle cramps.     

Diabetes is not associated with an increased peri-operative mortality or non-infectious morbidity following lower extremity arterial reconstruction

Background

The aim of this study was to determine if, at a national level, diabetes mellitus is associated with worse perioperative outcomes after open lower extremity arterial reconstruction.

Methods

Using Current Procedural Terminology codes, the National Surgical Quality Improvement Program database was queried to identify diabetic and nondiabetic patients who underwent open lower extremity arterial reconstruction from January 1, 2005, to December 31, 2007. These 2 groups were then compared using bivariate and multivariate analyses.

Results

There was no difference in mortality between the 2 groups (3.3% in diabetics and 3.5% in nondiabetics, P = .618). On multivariate analysis, there was no difference in the incidence of cardiac, pulmonary, or renal complications between the 2 groups. Diabetics, though, were more likely to develop infectious complications postoperatively.

Conclusions

After lower extremity arterial reconstruction, diabetes is not associated with an increased risk for mortality or an increased rate of major postoperative complications. Diabetics, however, have an increased rate of certain perioperative infections.     

Elevated cardiac troponin T is associated with increased left ventricular mass index and predicts mortality in continuous ambulatory peritoneal dialysis patients

Nephrol Dial Transplant