Prevalence and treatment of cardiovascular disease and traditional risk factors in Australian adults with renal insufficiency

AIM: To evaluate the prevalence and treatment of cardiovascular disease and traditional cardiovascular disease risk factors in Australian adults with renal insufficiency. METHODS: The Australian Diabetes, Obesity and Lifestyle Study was a cross-sectional survey of Australian adults undertaken in 1999-2000. Participants were categorized based on the Cockcroft-Gault estimated glomerular filtration rate in terms of normal renal function (<60 mL/min per 1.73 m(2)) and renal insufficiency (<60 mL/min per 1.73 m(2)). Outcome measures were the prevalence of cardiovascular disease, estimated risk of cardiovascular disease (20% over 10 years) and traditional cardiovascular risk factors, and frequency of pharmacological treatment of traditional cardiovascular risk factors. RESULTS: Among adults with renal insufficiency, cardiovascular disease was present in 29.4 (95% CI: 25.1-33.6) per 100, with an additional 47.9 (95% CI: 44.9-50.9) per 100 having an estimated risk of cardiovascular disease (20% over 10 years). At least one cardiovascular risk factor was present in 90.1%. Hypertension and type 2 diabetes mellitus were three times more frequent, while hyperlipidaemia was nearly twice as frequent in those participants with renal insufficiency. Of those with renal insufficiency, 58.2% with hypertension were treated, with only 14.5% of this group being treated to current recommended target levels of blood pressure, while only 32.5% with hyperlipidaemia were treated, with 7.4% of this group being treated to target lipid levels. CONCLUSION: The present study demonstrates significant scope to reduce the high burden of cardiovascular risk factors in Australian adults with renal insufficiency in the general community, through treatment of traditional risk factors for cardiovascular disease.     

Implications for kidney disease in obese children and adolescents

Increasing attention has been focused on the implications of obesity in adults on the development of kidney disease, but data on the obese pediatric population are lacking. The aim of this study was to investigate whether changes in various renal function indexes/markers, as expressed by the glomerular filtration rate [GFR, as estimated by the Schwartz formula (eGFR)], serum cystatin C (CysC) level, albumin excretion rate (AER), and modifications in nitric oxide (NO; an important modulator of renal function and morphology), urinary isoprostanes (markers of oxidative stress), and blood pressure (BP), can be detected in obese children and adolescents when compared to normal weight controls. Blood and urinary samples were collected to evaluate markers of renal function, serum and urinary NO, and urinary isoprostanes in 107 obese Caucasian subjects and 50 controls. Ambulatory BP monitoring (ABPM) was performed in all cases. Obesity was expressed by the body mass index standard deviation score (SDS-BMI), and insulin resistance by the homeostasis model assessment of insulin resistance (HOMA-IR). CysC and eGFR did not significantly differ between the two groups; AER was increased in obese children. CysC and GFR were related to HOMA-IR, and AER was related to HOMA-IR and SDS-BMI. Obese subjects had reduced NO levels and increased urinary isoprostanes and BP measurements; all three parameters were related to SDS-BMI and insulin resistance. ABPM showed an increased incidence of hypertension and non-dipping in the obese group. Based on our comparison of obese and nonobese children, we conclude that renal involvement is not an early clinically evident manifestation of adiposity in childhood, since no overt changes in eGFR and only a mild albuminuria were detected. A longer exposure to obesity is probably needed before renal function impairment appears.     

The effects of obesity on orthopaedic foot and ankle pathology

BACKGROUND: It is believed that obese individuals may have an increased number of foot and ankle problems. The World Health Organization recommends a standard classification of adult overweight and obesity using the following body mass index (BMI) calculations: a BMI of 25.0 to 29.9 kg per m(2) is defined as overweight; a BMI of 30.0 kg per m(2) or more is defined as obesity. The purpose of this paper was to report a survey of 1411 patients in an orthopaedic foot and ankle practice and compare the incidence of orthopaedic foot and ankle complaints with the BMI. METHOD: One thousand four hundred and eleven adults, including 887(62.4%) women and 535(37.6%) men, were evaluated in this study. The BMI was calculated for each subject using the standards of the World Health Organization. The subjects were divided into two groups: normal and overweight. The normal weight subjects had a BMI of 18.5 to 24.9 (n = 684; 48.1%) and the overweight or obese group had a BMI greater than or equal to 25 (n = 738; 51.9%). RESULTS: In this study, being overweight or obese significantly increased the chances of having tendinitis in general. If the subjects were overweight or obese, there was an increased likelihood, although not significant, of plantar fasciitis and osteoarthritis. If the individuals were of normal weight, there was an increased likelihood of hallux valgus. CONCLUSIONS: Tendinitis, plantar fasciitis, and osteoarthritis usually are secondary to overuse and increased stress on the soft tissues and joints, which may be directly related to increased weight on these structures.     

The effect of obesity on renal transplant outcomes

BACKGROUND: Although obesity has been associated with improved survival on dialysis, its effects on renal transplant outcomes remain unclear. Previous studies have reported conflicting findings and have been limited by the use of outdated patient data, univariate analyses, and liberal transplant selection criteria. The present study aimed to evaluate the effect of obesity on renal transplant outcomes in a rigorously screened population. METHODS: A retrospective analysis was undertaken of all patients transplanted at the Princess Alexandra Hospital from 1 April 1994 to 31 March 2000. Patients were rigorously screened for cardiovascular disease before acceptance for transplantation. The effects of obesity on renal transplant outcomes were assessed by logistic and multivariate Cox regressions. RESULTS: Of the 493 patients transplanted, 59 (12%) were obese (body mass index [BMI] 30 kg/m ). Obese patients were more likely to experience superficial wound breakdown (14% vs. 4%, P<0.01) and complete wound dehiscence (3% vs. 0%, P<0.01). Wound infections also tended to be more frequent in obese recipients (15% vs. 8%, P=0.11). There were no significant differences between the two groups with respect to operative duration, postoperative complications, hospitalization, delayed graft function, or acute rejection episodes. Five-year actuarial survival rates were comparable between the two groups with respect to graft survival (83% vs. 84%, P=NS) and patient survival (91% vs. 91%, P=NS). On multivariate analysis, BMI was an independent risk factor for wound breakdown (odds ratio 1.21, 95% CI 1.09-1.34, P<0.001), but not for other posttransplant complications, hospitalization, graft loss, or patient survival. CONCLUSIONS: The only significant adverse effect of obesity on renal transplant outcomes was an increase in wound complications, which were generally of minor consequence. Provided that adequate care is taken to avoid transplanting patients with significant cardiovascular disease, obese recipients can achieve excellent long-term patient and graft survivals that are on par with their nonobese counterparts. Denying patients access to renal transplantation on the basis of obesity per se does not appear to be justified.     

Weight reduction in renal transplant recipients program: the first successes

INTRODUCTION: Overweight and obesity in kidney graft recipients, both at transplantation and further on, are connected with the development of complications of metabolic syndrome. Hypertension, diabetes, and atherosclerosis are risk factors for chronic allograft nephropathy, shortened graft function, and lower recipient life expectancy. The aim of this study was to present the initial results from a weight reduction in renal transplant recipients program. MATERIAL: Thirty-four overweight and obese kidney transplant recipients were enrolled in the study: 9 overweight (26%), 19 obese (55.8%), and 6 morbidly obese (17.6%). The control group encompassed 418 kidney transplant recipients, in whom fluctuations in body mass and body mass index (BMI) were monitored for 56 months. METHODS: During the first visit, we performed an account of dietary habits and anthropometric measurements. At the second visit following a 6-month interval, patients received dietary guidelines based on an analysis of diet questionnaires. RESULTS: Six months after enrollment, despite not having received dietary guidelines during the first visit, only 27% of study subjects and 80% of controls experienced weight gain. CONCLUSIONS: Patients enrolled in the first step of the weight reduction program had no weight nor BMI increase after 6 months. Recipients having experienced body mass increase constituted only 27% of the study group, whereas increase in body mass occurred in 80% of controls. Reducing body mass accretion in kidney transplant recipients should be the target of preventive measures and nonpharmacological therapeutic interventions conducted by qualified personnel. Greater interest by medical personnel in the issue of body mass increase in recipients may be a strong motivating factor for them to undertake weight loss measures.     

The natural history of renal disease in Australian Aborigines. Part 2. Albuminuria predicts natural death and renal failure.

BACKGROUND: The purpose of this study was to describe the relationship of albuminuria and glomerular filtration rate (GFR) with natural death and renal failure in an Australian Aboriginal community with high rates of renal disease. METHODS: Study subjects were 825 adults (18+ years, mean 33.6 years) or 88% of adults in a remote community who participated in a health screening program offered between 1990 and 1997. The urinary albumin:creatinine ratio (ACR; g/mol) was used as the renal disease marker. Participants were followed for 1.0 to 9.8 years (mean 5.8 years) until renal failure, death, the start of systematic antihypertensive/renal-protective treatment or June 30, 2000. RESULTS: Sixty-five people reached a terminal end point of renal failure or natural death. Sixteen people developed terminal renal failure, all of whom had an ACR of 34+ at baseline exam. There were 49 other natural deaths, which were also strongly correlated with increasing ACR and decreasing GFR over a wide range. This was observed in people without diabetes and in people with normal and elevated blood pressures. It applied to deaths associated with cardiovascular disease and to deaths without an assigned primary or underlying cardiovascular or renal cause. With adjustment for age, the association with death was more robust with ACR than GFR. When compared with people with an ACR <3.4, the hazard ratio (HR; 95% CI) for nonrenal natural death of persons with an ACR 3.4 to 33 was 3.0 (1.1 to 8.4), with an ACR 34 to 99, it was 5.4 (1.8 to 15.9), and with an ACR 100+, it was 6.5 (2.0 to 21). Regression equations predicted that each tenfold increase in the ACR was associated with a 3.7-fold increase in all-cause natural death: a> 400-fold increase in renal deaths, a 4-fold increase in cardiovascular deaths, and a 2.2-fold increase in nonrenal noncardiovascular deaths. Eighty-four percent of all-cause natural death was associated with pathologic albuminuria. CONCLUSION: All renal failure develops out of a background of persistent albuminuria in this population. More important, albuminuria and, inversely, GFR are powerful markers of risk for nonrenal natural death, including, but not restricted to, cardiovascular deaths. Most of the risk for premature death can be assessed by a simple urine test, and interventions that prevent development and progression of albuminuria and loss of GFR should not only prevent renal insufficiency, but powerfully reduce mortality from natural causes as well.     

Effect of obesity on response to cardiovascular drugs in pediatric patients with renal disease

Obesity is associated with an increased concentration of inflammatory mediators, which in turn, in adults, reduces the response to calcium channel blockers (CCBs). We reviewed the medical charts of 263 pediatric nephrology patients with renal conditions, with the aim of studying the effect of obesity on the response to L-type CCBs, angiotensin interrupting agents (ANGIs), or a combination of the two. Forty-eight patients were ultimately enrolled in the study: 25 obese and 23 non-obese patients. The effect of the treatments on lowering the blood pressure was compared in obese versus non-obese patients. The systolic response to CCBs, measured as at least a 10% reduction from the baseline, was significantly lower in the obese (12.5%) patients than in the non-obese (52.9%) ones. The differences in diastolic response (58.8 and 25% for non-obese and obese patients, respectively) did not reach significance. The percentage response to CCBs, however, was significantly less in the obese patients than in the non-obese patients for both systolic and diastolic blood pressure. Corticosteroids also significantly influenced the response to CCBs in terms of diastolic pressure (62.9 and 25% for non-obese and obese patients, respectively). None of the tested covariates, including obesity, was found to significantly influence the response to ANGIs alone or in various combinations with CCBs. In conclusion, obesity and corticosteroid therapy should be considered when initiating antihypertensive drug treatment in children with kidney disease as both may contribute to a reduced efficacy of the antihypertensive therapy.     

ACE inhibition is renoprotective among obese patients with proteinuria

Obesity may increase the risk for progression of CKD, but the effect of established renoprotective treatments in overweight and obese patients with CKD is unknown. In this post hoc analysis of the Ramipril Efficacy In Nephropathy (REIN) trial, we evaluated whether being overweight or obese influences the incidence rate of renal events and affects the response to ramipril. Of the 337 trial participants with known body mass index (BMI), 105 (31.1%) were overweight and 49 (14.5%) were obese. Among placebo-treated patients, the incidence rate of ESRD was substantially higher in obese patients than overweight patients (24 versus 11 events/100 person-years) or than those with normal BMI (10 events/100 person-years); we observed a similar pattern for the combined endpoint of ESRD or doubling of serum creatinine. Ramipril reduced the rate of renal events in all BMI strata, but the effect was higher among the obese (incidence rate reduction of 86% for ESRD and 79% for the combined endpoint) than the overweight (incidence rate reduction of 45 and 48%, respectively) or those with normal BMI (incidence rate reduction of 42 and 45%, respectively). We confirmed this interaction between BMI and the efficacy of ramipril in analyses that adjusted for potential confounders, and we observed a similar effect modification for 24-hour protein excretion. In summary, obesity predicts a higher incidence of renal events, but treatment with ramipril can essentially abolish this risk excess. Furthermore, the reduction in risk conferred by ramipril is larger among obese than nonobese patients.     

Optimal body mass index that can predict long‐term graft outcome in Asian renal transplant recipients

Aim: There is limited data concerning the impact of recipient body mass index (BMI) on graft outcome in Asian renal transplant recipients. The aim of this study is to identify whether obesity (BMI ≥25 kg/m²) and overweight (BMI ≥23 kg/m²) can predict graft outcome. Methods: This is a single‐centre retrospective study. All patients who received kidney transplantation between 1997 and 2005 were recruited. Patients were categorized according to two different designated BMI cut‐off values. Results: One hundred and thirty‐one patients were recruited with a median follow‐up duration of 73 months. If a BMI cut‐off value of 25 kg/m² was used, 86.3% patients were classified as non‐obese and 13.7% as obese. Obesity was significantly associated with poor renal graft function and decreased patient and graft survival. On the other hand, 34.3% patients were classified as overweight and 65.7% patients as normal if a BMI cut‐off value of 23 kg/m² was used. Overweight was significantly associated with a lower glomerular filtration rate only. Cox regression analysis showed that obesity (odds ratio (OR) = 3.09), acute rejection (OR = 5.68), pre‐transplant diabetes mellitus (OR = 3.21) and age of recipient (OR = 1.06) were all significant independent risk factors associated with graft failure. Conclusion: Recipient BMI ≥25 kg/m² is a significant predictive factor for long‐term renal graft outcome in the Asian population.     

Obesity increases the likelihood of total joint replacement surgery among younger adults

We conducted a retrospective review of medical charts of patients, aged 18 to 59 years old, who underwent either a total knee replacement (TKR) or total hip replacement (THR) from January 2002 to December 2004. Of the 204 study subjects, 52% had a TKR while 48% had a THR. Obesity was significantly associated with the need for a TKR or THR when comparing the study group to adults of similar age in the general population (P< 0.0001). Seventy-two percent (146) of the study group was obese and 21% (42) overweight (BMI 25.0 to 29.9 kg/m(2)) compared to only 26% (596) obese and 34% (732) overweight in the general population. Patients undergoing a TKR were significantly more likely to be obese (BMI>30 kg/m(2)) than those having a THR, 83% (89) compared to 59% (57) (P< .0006). Our findings support those previously observed in the elderly population. Primary and secondary prevention programs aimed at reducing obesity are strongly recommended.     

Screening renal stone formers for distal renal tubular acidosis

A group of 110 consecutive renal stone formers were screened for distal renal tubular acidosis (RTA) using morning fasting urinary pH (mfUpH) levels followed by a short ammonium chloride loading test in patients with levels above 6.0. In 14 patients (12.7%) a renal acidification defect was noted; 13 had incomplete and 1 had complete distal RTA. Distal RTA was found particularly in recurrent stone formers (17%), and especially in those with bilateral stone disease, where a distal renal tubular acidification defect was found in 50%. We have been unable to differentiate primary from secondary RTA in renal stone formers. Regardless of whether the acidification defect is primary or secondary to stone formation, however, all renal stone formers with distal RTA can expect to benefit from prophylactic alkaline therapy and it is recommended that the screening procedure, which is easy to use in daily clinical practice, is applied to all stone formers and not restricted to patients with recurrent stone disease.     

Influence of body size on urinary stone composition in men and women

A larger body size has been shown to be associated with increased excretion of urinary lithogenic solutes, and an increased risk of nephrolithiasis has been reported in overweight patients. However, the type of stones produced in these subjects has not been ascertained. Based on a large series of calculi, we examined the relationship between body size and the composition of stones, in order to assess which type of stone is predominantly favoured by overweight. Among 18,845 consecutive calculi referred to our laboratory, 2,100 came from adults with recorded body height and weight. Excluding calculi from patients with diabetes mellitus, as well as struvite and cystine stones, the study material consisted of 1,931 calcium or uric acid calculi. All calculi were analysed by infrared spectroscopy and categorized according to their main component. Body mass index (BMI) values were stratified as normal BMI (<25 kg/m²), overweight (BMI 25–29.9) or obese (BMI≥30). Overall, 27.1% of male and 19.6% of female stone formers were overweight, and 8.4 and 13.5% were obese, respectively. In males, the proportion of calcium stones was lower in overweight and obese groups than in normal BMI group, whereas the proportion of uric acid stones gradually increased with BMI, from 7.1% in normal BMI to 28.7% in obese subjects (P<0.0001). The same was true in females, with a proportion of uric acid stones rising from 6.1% in normal BMI to 17.1% in obese patients (P=0.003). In addition, the proportion of uric acid stones markedly rose with age in both genders (P<0.0001). The average BMI value was significantly higher in uric acid stone formers aged <60 years than in all other groups, whereas it did not differ from other groups in those aged ≥60 years. Stepwise regression analysis identified BMI and age as significant, independent covariates associated with the risk of uric acid stones. Our data provide evidence that overweight is associated with a high proportion of uric acid stones in patients less than 60 years of age, whereas beyond this limit, advancing age is the main risk factor.     

From secondary to primary prevention of progressive renal disease: the case for screening for albuminuria

Many subjects nowadays present with end-stage renal failure and its attendant cardiovascular complications without known prior renal damage. In this report we review the evidence available to strongly suggest that the present practice of secondary prevention in those with known prior renal disease should be extended to primary prevention for those subjects in the general population who are at risk for progressive renal failure, but who had never suffered from a primary renal disease. We show that such subjects can be detected by screening for albuminuria. Elevated urinary albumin loss is an indicator not only of poor renal, but also of poor cardiovascular prognosis. In addition to diabetic subjects who are at risk for albuminuria, we also show that hypertensive, obese, and smoking subjects are more susceptible. We suggest that therapies that have been shown to lower albumin excretion, such as ACE inhibitors, angiotensin II receptor antagonists, and statins be started early in such patients to prevent them from developing clinical renal disease and its attendant cardiovascular complications.     

Hypercoagulable states in renal transplant candidates: impact of anticoagulation upon incidence of renal allograft thrombosis

INTRODUCTION: Although multiple studies of demographic variables have been associated with allograft thrombosis, these results are not routinely reproducible. Are ESRD patients with hypercoagulable states (HCS) (antithrombin III deficiency, protein S or C deficiency, activated protein C resistance, and anticardiolipin antibodies) at predictably greater risk for allograft thrombosis? METHODS: Between 1996 and 1999, all renal transplant candidates were screened for hypercoagulability risk factors [HRF] (multiple arteriovenous access thromboses, prior deep vein thrombosis, prior allograft thrombosis, collagen vascular disease, multiple miscarriages, diabetes, autoimmune disease, and Fabry's disease). HRF(+) candidates were then tested for HCS status. We administered preemptive posttransplant i.v. Heparin in HCS(+) patients and observed the impact of this intervention upon the incidence of allograft thrombosis. We compared demographic data and incidence of allograft thrombosis in an historic control (346 patients transplanted between June 31, 1992, and March 5, 1996) not tested for HCS and a study cohort (502 patients transplanted between March 6, 1996, and June 31, 1999) prospectively screened for HRF. HRF(+) patients who were HCS(+) in the study cohort received i.v. heparin immediately after transplant and p.o. warfarin as outpatients. RESULTS: Demographic characteristics previously implicated in allograft thrombosis were equivalently distributed in both cohorts with the exceptions that more living-donor transplants (33.1% vs. 15.3%) were performed in study cohort, CIT>24 hr occurred in more control patients (37.3% vs. 22.1%) and more study patients (16.7% vs. 0%) received tacrolimus. Hypercoagulable states were found upon reevaluating five of seven controls (71.4%), who lost prior allografts to thrombosis. Hypercoagulable states were prospectively detected in 10 study patients with hypercoagulability risk factors. Most (9 of 10) study patients receiving anticoagulation have achieved long-term allograft function. Study group allograft thrombosis incidence was reduced (1.59% vs. 4.05%). Hypercoagulable states were demonstrated in most episodes of allograft thrombosis. Control patients who lost prior allografts to thrombosis were anticoagulated after retransplantation and 100% achieved long-term allograft function. CONCLUSIONS: Long-term allograft function has been achieved in 90% of study patients when prophylactically anticoagulating study patients with hypercoagulable states. A 2.6-fold reduction in the expected incidence of allograft thrombosis was observed in anticoagulated patients with hypercoagulable states.     

Association between albuminuria and proteinuria in the general population: the AusDiab Study.

BACKGROUND: The relationship between urinary albumin and total protein excretion and the appropriateness of one test over the other are unclear due to the paucity of large epidemiological studies of albuminuria and proteinuria. In screening for renal and cardiovascular disease, whether to measure albuminuria, proteinuria or both, is currently an unanswered question. METHODS: Random urine samples from 10,596 (94.2%) participants of the Australian Diabetes, Obesity and Lifestyle Study were tested for albuminuria (urine albumin:creatinine > or =30 mg/g) and proteinuria (urine protein:creatinine > or =0.20 mg/mg). This study was a representative sample of the national non-institutionalized population drawn from 42 randomly selected urban and non-urban areas (census collector districts) across Australia. RESULTS: Among a representative cross-section of the Australian adult population, urine albumin excretion was strongly correlated with total protein excretion, particularly among the elderly, and those with diabetes mellitus, hypertension, obesity and renal impairment (P <0.001). Albuminuria performed well as a screening test for proteinuria: sensitivity 91.7% [95% confidence interval (CI) 87.7-94.5%], specificity 95.3% (95% CI 94.9-95.7%) and negative predictive value 99.8% (95% CI 99.7-99.9%). However, among those with proteinuria, 8% excreted albumin within the normal range. CONCLUSIONS: While albuminuria may be a suitable test for general population screening for renal and cardiovascular disease, it should not replace testing for proteinuria in those with known or suspected renal disease.     

Renal epidemiology. The first clinical and epidemiological programme on renal disease in Bolivia: a model for prevention and early diagnosis of renal diseases in the developing countries

Background. The prevalence and incidence of renal diseases in developing countries are not known. This lack of knowledge is an obstacle to the adoption of preventive measures which may be of great value in a social and economic environment where treatment options for end-stage renal failure are simply not available to the vast majority of the population. Urinalysis, a simple and inexpensive test, remains a cornerstone in the evaluation of the kidney and may also be easily employed in mass screening for renal abnormalities in a developing country. Methods. An educational campaign on renal diseases was conducted in three selected areas of Bolivia. Urine samples were collected and sent to one of 21 participating clinical centers. Fresh urine specimens were screened using a dipstick for chemical analysis and by microscopic urinalysis after centrifugation. In those patients in whom urinary abnormalities were found, further investigations were carried out in order to define the diagnosis; these patients were enrolled in a 3-year follow-up program. Results. Apparently healthy subjects (n=14 082) were referred to the First Clinical and Epidemiological Program of Renal Diseases from rural and metropolitan areas in Bolivia. Urinary abnormalities were detected in 4261 subjects at first screening. The most common form of urinary abnormality was hematuria, which was found in 2010 (47% of positively screened subjects). Other renal abnormalities were leukocyturia (41%) and proteinuria (11%). Confirmatory tests and further clinical studies were then carried out in 1019 people. On a second screening 35% of the subjects had no urinary abnormalities; in the remaining people the following diagnosis were made: asymptomatic urinary tract infection (48.4%), isolated benign hematuria (43.9%), chronic renal failure (1.6%), renal tuberculosis (1.6%). Other diagnosis were: renal stones 1.3%, diabetic nephropathy 1% and polycystic kidney diseases 1.9%. Conclusions. This study helped define for the first time the frequency of asymptomatic renal diseases in Bolivia. It shows that it is possible to screen a large population of patients at relatively low cost, providing the framework for further action that may help in the prevention and timely diagnosis of renal diseases. Keywords: Bolivia; developing countries; epidemiology; renal diseases      

Proteome analysis of skeletal muscle from obese and morbidly obese women

Obesity-related diseases such as the metabolic syndrome and type 2 diabetes originate, in part, from the progressive metabolic deterioration of skeletal muscle. A preliminary proteomic survey of rectus abdominus muscle detected a statistically significant increase in adenylate kinase (AK)1, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and aldolase A in obese/overweight and morbidly obese women relative to lean control subjects. AK1 is essential for the maintenance of cellular energy charge, and GAPDH and aldolase A are well known glycolytic enzymes. We found that muscle AK1 protein and enzymatic activity increased 2.9 and 90%, respectively, in obese women and 9.25 and 100%, respectively, in morbidly obese women. The total enzymatic activity of creatine kinase, which also regulates energy metabolism in muscle, was shown to increase 30% in obese/overweight women only. We propose that increased protein and enzymatic activity of AK1 is representative of a compensatory glycolytic drift to counteract reduced muscle mitochondrial function with the progression of obesity. This hypothesis is supported by increased abundance of the glycolytic enzymes GAPDH and aldolase A in obese and morbidly obese muscle. In summary, proteome analysis of muscle has helped us better describe the molecular etiology of obesity-related disease.     

Weight gain after renal transplantation is a risk factor for patient and graft outcome

BACKGROUND: The present study aimed to evaluate the effect of weight gain after transplantation on patient and graft outcome. METHODS: Patients receiving kidney transplants between April 1986 and April 2001 were divided according to their body mass index (BMI) at 6 months after transplantation into group I, BMI less than 25 (normal weight); group II, BMI greater than or equal to 25 and less than 30 (overweight); and group III, BMI greater than or equal to 30 (obese) after exclusion of pediatric patients (aged < or =18 years), second transplant recipients, those with a history of cardiovascular disease, and those with a BMI less than 25 and greater than 18.5 kg/m2. Six hundred fifty kidney transplant recipients were selected for this retrospective study. RESULTS: There was a statistically significant increase in the incidence of posttransplant hypertension, diabetes mellitus, and ischemic heart disease in the obese group. The incidence and frequency of acute rejection episodes were similar in the three groups. A trend toward decreased graft and patient survival, which reached significance at 5 years and 10 years, was observed in the obese group. CONCLUSIONS: BMI has a strong association with outcomes after renal transplantation independent of most of the known risk factors for patient and graft survival.     

Homocysteine as a predictive biomarker in early diagnosis of renal failure susceptibility and prognostic diagnosis for end stages renal disease

Glomerular filtration rate and/or creatinine are not accurate methods for renal failure prediction. This study tested homocysteine (Hcy) as a predictive and prognostic marker for end stage renal disease (ESRD). In total, 176 subjects were recruited and divided into: healthy normal group (108 subjects); mild-to-moderate impaired renal function group (21 patients); severe impaired renal function group (7 patients); and chronic renal failure group (40 patients) who were on regular hemodialysis. Blood samples were collected, and serum was separated for analysis of total Hcy, creatinine, high sensitive C-reactive protein (CRP), serum albumin, and calcium. Data showed that Hcy level was significantly increased from normal-to-mild impairment then significantly decreases from mild impairment until the patient reaches severe impairment while showing significant elevation in the last stage of chronic renal disease. Creatinine level was increased in all stages of kidney impairment in comparison with control. CRP level was showing significant elevation in the last stage. A significant decrease in both albumin and calcium was occurred in all stages of renal impairment. We conclude Hcy in combination with CRP, creatinine, albumin, and calcium can be used as a prognostic marker for ESRD and an early diagnostic marker for the risk of renal failure.