Foot and ankle problems of Aboriginal and non-Aboriginal diabetic patients with end-stage renal disease

BACKGROUND: There is little information available about the profile of lower extremity morbidity in diabetic patients with end-stage renal disease (ESRD) in the Canadian Aboriginal and non-Aboriginal population. METHOD: A retrospective review of medical records in 127 diabetic patients on hemodialysis at a tertiary health care center was performed. Patient interviews and physical examinations were performed in 77 of these patients (36 Aboriginal, 41 non-Aboriginal), and followup evaluation was done in 39 patients at an average of 1 year later. RESULTS: Aboriginal patients were an average of 7 years younger than non-Aboriginal patients. Comorbidities of diabetes and ESRD were frequent. Peripheral neuropathy and inability to occlude the vessels were present in the majority of feet. Lower extremity complications were frequent, including prior foot ulcer in the majority of patients and an amputation in more than one fourth of the patients. Aboriginal patients had a significantly greater frequency of prior foot ulcer, mean number of foot ulcers per patient, amputation, prior osteomyelitis, and Charcot foot than non-Aboriginal patients. Almost all patients were at risk for future foot ulcer, but many patients did not inspect their feet daily. Home care was significantly less frequently available for Aboriginal than non-Aboriginal patients. The majority of patients had inadequate custom or prefabricated shoes and did not wear insoles on the day of examination. Aboriginal patients cited financial cost, insufficient family support, and language barriers as reasons for inadequate foot care and footwear more frequently than non-Aboriginal subjects. A significantly smaller frequency of Aboriginal patients had good knowledge of footwear or diet than non-Aboriginal patients. CONCLUSIONS: Lower extremity complications were significantly more frequent in Aboriginal than non-Aboriginal diabetic patients with ESRD. Financial cost and knowledge deficit were barriers to adequate foot care and footwear. These findings support the need for a formal foot care and footwear program for this high-risk population.     

Renal disease in the Australian Aboriginal population: A pathological study

Summary: End-stage renal failure and clinical evidence of renal disease are more frequent in Australian Aboriginals than in the non-Aboriginal Australian population. to investigate the lesions responsible for this excess a systematic study of renal biopsy findings in a series of Aboriginal patients in South Australia and the Northern Territory was performed and the data on these patients were compared with a consecutive series of renal biopsy findings in non-Aboriginal patients. Histological and morphometric comparison was made between biopsies from 206 Aboriginal and 690 non-Aboriginal patients. the distribution of glomerular lesions was found to differ significantly between the Aboriginal and non-Aboriginal groups: diabetic glomerulosclerosis, idiopathic glomerular enlargement (glomerulomegaly), mesangiocapillary glomeru-lonephritis (MCGN), and non-IgA mesangiopathic glomerulonephritis (GN) were found more frequently in the Aboriginal population, whereas there were fewer than expected examples of thin membrane nephropathy, minimal change disease and membranous GN. Diabetic glomerulosclerosis was significantly more frequent, and the lesions more severe, in Central Australia (where diabetes is more prevalent) and glomerulomegaly was especially common in Bathurst Island. These two conditions accounted for one third of the series and evidence is presented to suggest that a substantial proportion of renal disease in Aboriginals may be the consequence of conversion to a Western life style. of the 206 Aboriginal patients, 23 presented with chronic renal failure, suggesting either late presentation or unusually aggressive renal lesions, and 10 had end-stage renal disease on biopsy.     

Higher rate and earlier peritonitis in Aboriginal patients compared to non-Aboriginal patients with end-stage renal failure maintained on peritoneal dialysis in Australia: analysis of ANZDATA

BACKGROUND: Aboriginal patients maintained on peritoneal dialysis (PD) have a higher rate of technique failure than any other racial group in Australia. Peritonitis accounts for the bulk of these technique failures, but it is uncertain whether the increased risk of peritonitis in Aboriginal patients was independent of associated comorbid conditions, such as diabetes mellitus. METHODS: Using data collected by the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA), peritonitis rates and time to first peritonitis were compared between Aboriginal (n = 238) and non-Aboriginal patients (n = 2924) commencing PD in Australia between 1 April 1999 and 31 March 2003. RESULTS: Aboriginal PD patients were younger, and had a higher incidence of diabetes than their non-Aboriginal counterparts. Mean peritonitis rates were significantly higher among Aboriginal (1.15 episodes/year; 95% confidence interval (CI): 1.03-1.28) than non-Aboriginal patients (0.60 episodes/year; 95% CI: 0.57-0.62, P < 0.05). Using multivariate negative binomial regression, independent predictors of higher peritonitis rates include Aboriginal racial origin (adjusted odds ratio 1.78; 95% CI: 1.45-2.19), obesity, age and absence of a recorded dialysate : plasma creatinine ratio (D/P creatinine) measurement. Aboriginal racial origin was also associated with a shorter median time to first peritonitis (9.9 vs 19.3 months, P < 0.05), which remained statistically significant in a multivariate Cox proportional hazards model (adjusted hazard ratio 1.76; 95% CI: 1.47-2.11, P < 0.05). CONCLUSION: Aboriginal and obese PD patients have a higher rate of peritonitis and a shorter time to first peritonitis, independent of demographic and comorbid factors. Further investigation of the causes of increased peritonitis risk in Aboriginal patients is needed.     

Reduced nephron number and glomerulomegaly in Australian Aborigines: a group at high risk for renal disease and hypertension

Aborigines in remote areas of Australia have much higher rates of renal disease, as well as hypertension and cardiovascular disease, than non-Aboriginal Australians. We compared kidney findings in Aboriginal and non-Aboriginal people in one remote region. Glomerular number and mean glomerular volume were estimated with the disector/fractionator combination in the right kidney of 19 Aborigines and 24 non-Aboriginal people undergoing forensic autopsy for sudden or unexpected death in the Top End of the Northern Territory. Aborigines had 30% fewer glomeruli than non-Aborigines--202,000 fewer glomeruli per kidney, or an estimated 404,000 fewer per person (P=0.036). Their mean glomerular volume was 27% larger (P=0.016). Glomerular number was significantly correlated with adult height, inferring a relationship with birthweight, which, on average, is much lower in Aboriginal than non-Aboriginal people. Aboriginal people with a history of hypertension had 30% fewer glomeruli than those without--250,000 fewer per kidney (P=0.03), or 500,000 fewer per person, and their mean glomerular volume was about 25% larger. The lower nephron number in Aboriginal people is compatible with their susceptibility to renal failure. The additional nephron deficit associated with hypertension is compatible with other reports. Lower nephron numbers are probably due in part to reduced nephron endowment, which is related to a suboptimal intrauterine environment. Compensatory glomerular hypertrophy in people with fewer nephrons, while minimizing loss of total filtering surface area, might be exacerbating nephron loss. Optimization of fetal growth should ultimately reduce the florid epidemic of renal disease, hypertension, and cardiovascular disease.     

Factors that predict site of outflow target artery anastomosis in infrainguinal revascularization

INTRODUCTION: Lower extremity revascularization is indicated for limb salvage and incapacitating leg claudication. Many risk factors (age, hypertension, diabetes, tobacco use, dyslipidemia, etc) have been associated with atherosclerosis and the development of peripheral arterial occlusive disease. However, whether these risk factors or the surgical indication (claudication or limb salvage) influences the extent and location of infrainguinal disease and hence the target artery (distal anastomosis) is unclear. This study examines the risk factors and indication for infrainguinal revascularization with respect to the type of bypass performed. METHODS: Three hundred fifty-two infrainguinal revascularizations in 282 patients were retrospectively reviewed. Patient data, including demographics, cardiovascular risk factors, indications, types of revascularization, and perioperative complications and mortality, were collected. Data were analyzed with t test, chi(2) test, Fisher exact test, and multiple logistic regression. RESULTS: The indication for surgical revascularization was claudication in 70 patients and limb salvage in 282. The likelihood of a popliteal anastomosis (above or below knee) versus a tibial or pedal anastomosis was decreased with increasing age (P =.002) and diabetes (P =.0001), and smoking increased the likelihood (P =.056). However, popliteal bypass also was strongly associated with claudication as the surgical indication (odds ratio [OR], 8.7; P =.0001), and 90% of the claudicant group had undergone popliteal anastomosis. Claudication and popliteal anastomosis were both linked to smoking; 97% of subjects who underwent operation for claudication were smokers compared with 75% of subjects who underwent tibial or pedal anastomosis for limb salvage (P =.001). After adjustment for indication, the likelihood of popliteal anastomosis was still decreased with diabetes (OR, 0.46; P =.002), and age had a borderline significant effect (P =.077). When the analysis was stratified by indication for surgery, the likelihood of popliteal bypass among patients who underwent operation for claudication was not influenced by age, diabetes, or smoking. However, within the subset of patients who underwent operation for limb salvage, the likelihood of any popliteal anastomosis was diminished by diabetes (OR, 0.50; P =.007), age (OR, 0.968 per year; P =.01), and chronic renal insufficiency (OR, 0.476; P =.04). CONCLUSION: Infrainguinal peripheral arterial occlusive disease is not a homogenous disease entity. Claudication and limb salvage are associated with two distinct patterns of vascular disease with different risk factors. Patients who undergo operation for claudication are seen at an earlier age, have a high prevalence of smoking, and have proximal disease and a greater likelihood of a popliteal anastomosis. In contrast, patients for limb salvage are less likely to have a popliteal bypass, favoring a more distal target outflow anastomosis that is strongly influenced by advanced age, diabetes, and chronic renal insufficiency.     

Early chronic kidney disease in Aboriginal and non-Aboriginal Australian children: remoteness,socioeconomic disadvantage or race?

Indigenous people suffer substantially more end-stage kidney disease (ESKD), especially Australian Aboriginals. Previous work suggests causal pathways beginning early in life. No studies have shown the prevalence of early markers of chronic kidney disease (CKD) in both Indigenous and non-Indigenous children or the association with environmental health determinants--geographic remoteness and socioeconomic disadvantage. Height, weight, blood pressure, and urinary abnormalities were measured in age- and gender-matched Aboriginal and non-Aboriginal children from elementary schools across diverse areas of New South Wales, Australia. Hematuria was defined as>or=25 red blood cells/microl (>or=1+), proteinuria>or=0.30 g/l (>or=1+), and albuminuria (by albumin:creatinine)>or=3.4 mg/mmol. Remoteness and socioeconomic status were assigned using the Accessibility and Remoteness Index of Australia and Socio-Economic Indexes For Areas. From 2002 to 2004, 2266 children (55% Aboriginal, mean age 8.9 years) were enrolled from 37 elementary schools. Overall prevalence of hematuria was 5.5%, proteinuria 7.3%, and albuminuria 7.3%. Only baseline hematuria was more common in Aboriginal children (7.1 versus 3.6%; P=0.002). At 2-year follow-up, 1.2% of Aboriginal children had persistent hematuria that was no different from non-Aboriginal children (P=0.60). Socioeconomic disadvantage and geographical isolation were neither significant nor consistent risk factors for any marker of CKD. Aboriginal children have no increase in albuminuria, proteinuria, or persistent hematuria, which are more important markers for CKD. This suggests ESKD in Aboriginal people may be preventable during early adult life.     

Reversible cardiac sympathectomy by high thoracic epidural anesthesia improves regional left ventricular function in patients undergoing coronary artery bypass grafting: a randomized trial

HYPOTHESIS: To evaluate the effects of high thoracic epidural anesthesia (TEA) on global and regional myocardial function and on perioperative coronary risk in patients undergoing coronary artery bypass grafting. DESIGN, SETTING, AND PATIENTS: Prospective and randomized clinical trial blinded for the primary outcome measure of 73 patients scheduled for coronary artery bypass grafting who had a left ventricular ejection fraction of 50% or more conducted from February 1, 2000, through August 31, 2000, at University Hospital, Münster, Germany. INTERVENTIONS: Of 73 randomized patients, 37 were control subjects (who received general anesthesia only) and 36 were in the group who received general anesthesia and high TEA. MAIN OUTCOME MEASURES: The primary outcome measure was regional left ventricular function after myocardial revascularization, assessed by transesophageal echocardiography. We further determined the plasma concentrations of cardiac troponin I and atrial and brain natriuretic peptides. Secondary outcome measures were postoperative complications recorded to 14 days and mortality recorded to 720 days. RESULTS: High TEA was effective in all patients of this group, the somatosensory block extended from T1 through T7 vertebrae. Regional left ventricular function was significantly improved (mean [SD] global wall motion index, 0.74 [0.18] vs 0.38 [0.16]; P<.05), and cardiac troponin I concentrations were reduced by 72% (mean [SD], 5.7 [1.5] vs 1.6 [0.7] ng/mL, P<.05) in patients with high TEA. Natriuretic peptide concentrations peaked during reperfusion (atrial natriuretic peptide) and 24 hours after reperfusion (brain natriuretic peptide). High TEA reduced the mean (SD) peak concentrations of atrial natriuretic peptide by 54% (211 [63] vs 98 [33] ng/mL, P =.03) and brain natriuretic peptide by 43% (189 [39] vs 108 [21] ng/mL, P =.01). One of 36 patients who received high TEA and 3 of 37 controls died. CONCLUSIONS: Reversible cardiac sympathectomy by high TEA improves regional left ventricular function and reduces postoperative ischemia after coronary artery bypass grafting. These effects of high TEA may improve the long-term outcome after myocardial revascularization.     

An audit of Keller arthroplasty and metatarsophalangeal joint arthrodesis from national data

Chronic interphalangeal ulcerations of the great toe are a frequent complication in neuropathic diabetic feet. While total contact casting is usually effective as a first-line treatment, some ulcers continue and present substantial management challenges. The objective of this study was to examine the National Hospital Discharge Survey in order to identify links between preexisting medical conditions and lower extremity pathology in patients undergoing a Keller arthroplasty. Those who received a Keller arthroplasty were more likely to have diabetes mellitus (odds ratio [OR] = 4.00, 95% confidence interval [CI]: 3.73-4.30, P = .0001), diabetic neuropathy (OR = 3.80, 95% CI: 3.48-4.15, P = .0001), coronary artery disease (OR = 1.78, 95% CI: 1.57-2.03), or peripheral vascular disease (PVD) (OR = 2.06, 95% CI: 1.49-2.84, P = .0001). Keller arthroplasty patients were less likely to have a foot abscess (OR = 0.44, 95% CI: 0.39-0.50, P = .0001) or hammer toe deformity (OR = 0.60, 95% CI: 0.57-0.63, P = .0001), but more likely to have a foot wound or ulcer (OR = 2.62, 95% CI = 2.44-2.82, P = .0001), bunions (OR = 4.52, 95% CI: 4.26-4.80, P = .0001), and osteomyelitis (OR = 2.65, 95% CI: 2.41-2.92, P = .0001). Hallux limitus or rigidus in a diabetic patient with neuropathy, peripheral vascular disease, and poor healing subjects this patient to a higher risk of ulceration, infection, and amputation. This study shows that this procedure is being performed in the diabetic population with attendant complications.     

Outcome After Myocardial Revascularization and Renal Transplantation: A 25-Year Single-Institution Experience

BACKGROUND AND OBJECTIVE: Cardiac disease is a common cause of death in renal transplant recipients. This study retrospectively analyzes the results of myocardial revascularization procedures in these patients and makes recommendations for managing coronary atherosclerosis in patients with renal disease who already have a transplanted kidney or who may receive a kidney transplant. METHODS: Patients who had myocardial revascularization (coronary artery bypass grafting [CABG] or percutaneous transluminal coronary angioplasty [PTCA]) and renal transplantation at the authors' institution between 1968 and 1994 were analyzed. Patient, procedural, and institutional variables were used for actuarial analyses of survival, as well as multivariate analyses of risk factors for death. RESULTS: Eighty-three of 2989 renal transplant patients required myocardial revascularization either before or after their transplant, and diabetes mellitus was the cause of renal failure in 42% of these patients. Standard coronary angiography, CABG, and PTCA techniques were used without periprocedural renal allograft loss. Actuarial patient survival was 89%, 77%, and 65% at 1, 3, and 5 years after the last procedure (transplantation or revascularization). Cardiac disease was the most common mode of death. Early-phase risk factors for death by multivariate analysis included hypertension and revascularization before 1989. Late-phase risk factors for death included diabetes mellitus, higher number of pre-CABG myocardial infarctions, renal transplantation before 1984, older age, and unstable angina before CABG. CONCLUSIONS: Myocardial revascularization can be performed with acceptable short- and long-term results in patients with renal disease who have renal transplantation either before or after the revascularization procedure. Diabetes mellitus was a highly prevalent condition among these patients, and cardiac disease was their most common mode of death. PTCA and CABG, as performed at this institution, posed little risk for renal allograft loss. Modification of risk factors for coronary atherosclerosis, rigorous cardiac evaluation of patients at risk for coronary artery disease before renal transplantation, and aggressive use of revascularization procedures to decrease the incidence of myocardial infarction are proposed as ways to prolong the survival of renal transplant patients with ischemic heart disease.     

Is there a role for peritoneal dialysis in remote aboriginal patients with end-stage renal disease in Australia?

SUMMARY:   Peritoneal dialysis (PD) is often the preferred treatment modality of many Aboriginal patients with end-stage renal disease (ESRD) due to their remote locations and the scarcity of remote satellite haemodialysis units. Infectious complications remain an important cause of morbidity in Aboriginal patients maintained on PD in Australia. Analysis of the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA) has revealed that Aboriginal PD patients are more likely to have earlier and a higher rate of peritonitis, higher risk of PD technique failure, and higher mortality compared to non-Aboriginal PD patients independent of other factors. However, the finding of Aboriginality as a risk factor for PD-related complications is at least partly attributable to socioeconomic factors, such as poor housing and hygiene. As PD will remain a necessary first-line therapy in this group of isolated and disadvantaged patients, implementing aggressive preventive strategies and targeting modifiable socioeconomic risk factors may reduce morbidity and preserve their independence and way of life.     

Surgical or endovascular revascularization in patients with critical limb ischemia: influence of diabetes mellitus on clinical outcome

OBJECTIVE: The optimal revascularization strategy in diabetic patients with chronic critical limb ischemia (CLI) is unclear. This study assessed the efficacy of tailored endovascular-first vs surgical-first revascularization stratified for the presence of diabetes. METHODS: This prospective cohort study, with 1-year follow up, was conducted in a tertiary referral center in a consecutive series of 383 patients (45.7% had diabetes) presenting 426 limbs with chronic CLI. Interventions were endovascular (PTA cohort, 207 limbs) or surgical (SURG cohort, 85 limbs) revascularization. Conservatively treated patients without revascularization (NON REVASC cohort, 108 limbs) were used as a reference. The main outcome measures were sustained clinical success, defined as survival without major amputation or repeated target extremity revascularization (TER), and a categoric upward shift in clinical symptoms according to the Rutherford classification. RESULTS: Sustained clinical success of revascularization was significantly better in nondiabetic patients (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.29 to 0.72; P = .001 [SURG cohort]; HR, 0.53; 95% CI, 0.35 to 0.78; P = .002 [PTA cohort]) compared with diabetic patients (HR, 0.78; 95% CI, 0.44 to 1.43, P = .45 [SURG cohort]; HR, 0.83; 95% CI, 0.55 to 1.27, P = .40 [PTA cohort]). Repeated TER significantly improved clinical success, which became equivalent between diabetic and nondiabetic patients (HR, 1.02; 95% CI, 0.7 to 1.4). In multivariate analysis, treatment success was not influenced by mode of initial revascularization, neither in diabetic nor in nondiabetic patients. Cumulative 1-year mortality was 30.4%, with a trend of increased mortality in patients with diabetes (HR, 1.45; 95% CI, 0.98 to 2.17; P = .064). Limb salvage rates were similar in treatment cohorts, also if stratified for diabetes (HR, 1.04; 95% CI, 0.62 to 1.75). CONCLUSION: Diabetic patients with chronic CLI benefit from early revascularization. To achieve this benefit, multiple revascularization procedures may be required, and close surveillance is therefore mandatory. Choice of initial revascularization modality seems not to influence clinical success.     

Lower extremity minor amputations: the roles of diabetes mellitus and timing of revascularization

INTRODUCTION: Despite the frequent performance of minor foot amputations in patients with lower extremity vascular disease, little is known regarding the rate of conversion to major amputations and the role of bypass graft timing in relation to amputation. METHODS: Between January 1990 and December 2001, 670 patients underwent 920 minor amputations (interphalangeal, ray, or transmetatarsal) on 747 limbs. RESULTS: Of 670 patients, 468 were men (69.9%), 616 had diabetes mellitus (91.9%), and 137 (19.7%) had a serum creatinine level >2.0 mg/dL, of whom 92 were on dialysis (end-stage renal disease) (11.5%). Ipsilateral revascularization was performed < or =30 days before the initial amputation in 64.9% (485 of 747), whereas 9.8% (73 of 747) had a bypass < or =30 days postamputation. The initial amputation levels were 466 interphalangeal (62.4%), 159 transmetatarsal (21.3%), and 122 ray (16.3%). Operative 30-day mortality was 0.7% (6 of 920). Limb salvage was 89.8% at 1 year and 82.3% at 5 years. Diabetes mellitus had no impact on limb salvage (P = .61). Limb loss predictors included end-stage renal disease (odds ratio [OR], 1.72, 95% confidence interval [CI], 1.12 to 2.83, P < .01) and the need for transmetatarsal amputation as the initial procedure (OR, 1.62; 95% CI, 1.15 to 1.93; P < .01). Patients with revascularizations subsequent to an initial amputation had a significant increase in limb loss (OR, 2.11; 95% CI, 1.39 to 4.21, P < .005). Patient survival was 83.9% at 1 year and 43.5% at 5 years. Neither gender nor diabetes mellitus impacted survival; however, serum creatinine levels >2.0 mg/dL (5 years, 48.8% +/- 2.3% vs 23.9% +/- 4.2%, P < .0001) and the need for a major amputation < or =30 days (3 years, 60.8% +/- 2.1% vs 40.1% +/- 7.8%, P < .01) adversely affected survival. CONCLUSIONS: Although minor amputations can lead to limb preservation in most patients, the performance of a revascularization subsequent to amputation, transmetatarsal as the initial amputation, and end-stage renal disease are poor prognostic indicators. Inferior long-term patient survival is most closely associated with renal insufficiency and conversion to major amputation early after the initial procedure.     

Traumatic spinal cord injuries among Aboriginal and non-Aboriginal populations of Saskatchewan: a prospective outcomes study

BackgroundPeople of Aboriginal (Indigenous) ancestry are more likely to experience traumatic spinal cord injury (TSCI) than other Canadians; however, outcome studies are limited. This study aims to compare Aboriginal and non-Aboriginal populations with acute TSCI with respect to preinjury baseline characteristics, injury severity, treatment, outcomes and length of stay.MethodsThis was a retrospective analysis of participants with a TSCI who were enrolled in the prospective Rick Hansen Spinal Cord Injury Registry (RHSCIR), Saskatoon site (Royal University Hospital), between Feb. 13, 2010, and Dec. 17, 2016. Demographic, injury and management data were assessed to identify any differences between the populations.ResultsOf the 159 patients admitted to Royal University Hospital with an acute TSCI during the study period, 62 provided consent and were included in the study. Of these, 21 self-identified as Aboriginal (33.9%) and 41 as non-Aboriginal (66.1%) on treatment intake forms. Compared with non-Aboriginal participants, Aboriginal participants were younger, had fewer medical comorbidities, had a similar severity of neurologic injury and had similar clinical outcomes. However, the time to discharge to the community was significantly longer for Aboriginal participants (median 104.0 v. 34.0 d, p = 0.016). Although 35% of non-Aboriginal participants were discharged home from the acute care site, no Aboriginal participants were transferred home directly.ConclusionThis study suggests a need for better allocation of resources for transition to the community for Aboriginal people with a TSCI in Saskatchewan. We plan to assess outcomes from TSCI for Aboriginal people across Canada.     

Critical illness and its impact on the Aboriginal people of the top end of the Northern Territory,Australia

The Royal Darwin Hospital (RDH) services a relatively large and geographically remote Aboriginal population who account for 45% of intensive care unit admissions. Critical illness in the Aboriginal population is different from the non-Aboriginal population of the "Top End" of the Northern Territory. The critically ill Aboriginal patient is younger, has more chronic health problems and a higher severity of illness at presentation. The city and the hospital environment are foreign to many Aboriginal patients retrieved from remote communities and this adds to the stress of the critical illness. English is a second, third or fourth language for many Aboriginal people from remote communities and strategies must be put in place to ensure informed consent and effective communication are achieved. Despite the increased severity of illness and complexity, the Royal Darwin Hospital ICU achieves the same survival rates for both Aboriginal and non-Aboriginal patients.     

Defective nitric oxide production and functional renal reserve in patients with type 2 diabetes who have microalbuminuria of African and Asian compared with white origin

Diabetic nephropathy is a leading cause of end-stage renal failure. Its incidence is higher and is increasing in persons of Indo-Asian and African-Caribbean (African-Asian) compared with those of white origin. Nitric oxide deficiency is associated with progressive renal disease. It was hypothesized that differences in the capacity to increase glomerular filtration (functional renal reserve) would exist between these racial groups in relation to nitric oxide availability. Patients with type 2 diabetes of African-Asian (n = 9) and white (n = 9) origin with microalbuminuria were studied under euglycemic conditions. Glomerular filtration, renal plasma flow, and clearance of the stable metabolites of nitric oxide, nitrite, and nitrate were measured before and after a renal vasodilatory stimulus of a mixed amino acid intravenous infusion. There were no significant differences in age, duration of diabetes, and baseline glomerular filtration (57.1 [14.1] versus 55.8 [10.1] yr; P = 0.82, 14.5 [10.2] versus 9.1 [7.0] yr; P = 0.19 and 125.9 [30.9] versus 127.2 [44.6] ml/min per 1.73 m(2); P = 0.94) between the African-Asian and white groups. Functional renal reserve, change in renal plasma flow, and percentage change in nitrate and nitrite clearance was significantly higher in the white compared with the African-Asian group (21.9 [45.7] versus -2.5 [28.2] ml/min per 1.73 m(2); P = 0.043, 155.8 [205.9] versus -90.1 [146.0]; P = 0.03 ml/min per 1.73 m(2) and 26.7 [85.1] versus -44.7 [16.9] %; P = 0.013, respectively). The differences in functional reserve were not confounded after adjustment for diabetes duration (P = 0.034). The data suggest that these patients with type 2 diabetes of African and Asian origin lose functional renal reserve earlier in the evolution of nephropathy than whites. The differences appear to be due to defective nitric oxide production or bioavailability and might explain some of the propensity to develop end-stage renal disease.     

Chlamydia pneumoniae infection and ischemic heart disease in hemodialysis patients

INTRODUCTION: Ischemic heart disease and other atherosclerotic complications are the prominent causes of death among hemodialyzed end-stage renal disease (ESRD) patients and renal transplant recipients. Numerous articles in recent years have raised the possibility of an infective factor, especially Chlamydia pneumoniae, in the development of atherosclerosis and its complications. The aim of this study was to assess the incidence of chronic C pneumoniae infection and its association with ischemic heart disease and atherosclerosis in a population of patients with ESRD awaiting renal transplantation. MATERIAL AND METHODS: The studied group consisted of 164 subjects: 99 ESRD patients (heart disease [HD] group) who were hospitalized for vascular access creation (27), pretransplantation nephrectomy (47), or kidney transplantation (25), and a control group of 65 subjects consisting of 50 healthy blood donors and 15 multiorgan donors. C pneumoniae was detected in vascular wall fragments, kidney biopsy specimens and peripheral blood monocytes using real time polymerase chain reaction (PCR). Serum immunoglobulin IgG and IgA anti-C pneumoniae antibodies were detected using Enzyme-linked immunosorbent assay (ELISA) and a lipid profile (cholesterol, high-density lipoprotein [HDL], low-density lipoprotein [LDL], and triglycerides [TG]) was obtained. Data on cardiovascular disease events, smoking history, diabetes, hypertension, cause, and length of renal failure were collected and analyzed. The existence of atherosclerotic lesions was detected using ultrasound (US) Doppler examination of aortic bifurcation. Chronic C pneumoniae infection was diagnosed on the basis of detection of both IgA and IgG antibodies and/or the detection of C pneumoniae DNA in vascular wall fragments or peripheral blood monocytes. After a follow-up of 32 months, data on cardiovascular events and patient history were collected again. RESULTS: Chronic C pneumoniae infection affected 46.5% (46/99) of HD patients and 9% (6/65) of controls (P < .05). Among HD patients, 26.3% (26/99) had ischemic heart disease (IHD) versus 6% in the control group. Among C pneumoniae-infected HD patients, IHD was more frequent (39.1%) than in noninfected HD patients (15%; P < .05). Within the 32-month observation period of the HD group, cardiac pain was observed in 11 (24%; 11/46) infected patients versus 3 (5.7%; 3/53) patients without C pneumoniae infection (P < .05). Exacerbation of previously diagnosed IHD was observed in 8 (44%; 8/18) cases in the C pneumoniae-infected group versus 0 (0%; 0/8) in the uninfected patients (P < .05). CONCLUSIONS: Chronic C pneumoniae infection affects hemodialysis patients more frequently than healthy subjects. Hemodialysis patients with C pneumoniae infection are at the greater risk of exacerbation of existing IHD.     

Risk of treatment of peripheral arterial disease is related to inflammation-sensitive plasma proteins: a prospective cohort study

BACKGROUND: Studies in patients with peripheral arterial disease (PAD) have reported an association between inflammatory markers and severity of disease or worsening of symptoms. However, few have studied the prognostic significance of inflammatory markers in asymptomatic subjects, measured many years before the onset of symptomatic PAD requiring treatment (trPAD). MATERIAL AND METHODS: Five inflammation-sensitive plasma proteins (ISPs), including fibrinogen, alpha 1-antitrypsin, haptoglobin, ceruloplasmin, and orosomucoid, were determined in 5619 healthy men (mean age, 46.8 +/- 3.7 years) without walking-induced calf pain. Data for men who subsequently underwent a revascularization procedure because of trPAD (intermittent claudication or critical ischemia) were retrieved from hospital-based registers. Future trPAD was studied in relation to the number of ISPs in the top quartile at the baseline examination. RESULTS: Seventy men (1.2%) underwent revascularization because of trPAD at a mean of 16.5 years after the baseline examination. The proportion with future trPAD was 0.4%, 1.0%, 1.5%, and 3.2%, respectively, for men with 0, 1, 2, and 3 or more ISPs in the top quartile (trend, P < .0001). After adjustment for age, screening year, systolic blood pressure, blood pressure medication, cholesterol concentration, diabetes, smoking, and tobacco consumption the corresponding odds ratios (95% confidence interval [CI]) were 1.00 (reference), 1.5 (CI, 0.7-3.6), 1.9 (CI, 0.8-4.6), and 2.9 (CI, 1.3-6.4), respectively, in these groups (trend, P = .003). CONCLUSION: Elevated ISPs, measured 16 years earlier in apparently healthy men without walking-induced calf pain, were associated with increased risk for development of PAD requiring revascularization.     

Charcot Reconstruction: Outcomes in Patients With and Without Diabetes

The objective of this study is to compare risk adjusted matched cohorts of Charcot neuroarthropathy patients who underwent osseous reconstruction with and without diabetes. The 2 groups were matched based on age, body mass index, hypertension, history of end-stage renal disease, and peripheral arterial disease. Bivariate analysis was performed for preoperative infection, location of Charcot breakdown, and post reconstruction outcomes, in patients with a minimum of 1 year follow-up period. Through bivariate analysis, presence of preoperative ulceration (p = .0499) was found to be statistically more likely in the patients with diabetes; whereas, delayed osseous union (p = .0050) and return to ambulation (p ≤ .0001) was statistically more likely in patients without diabetes. The nondiabetic Charcot patients were 17.6 folds more likely to return to ambulation (odds ratio [OR] 17.6 [95% confidence interval {CI} {3.5-87.6}]), and 16.4 folds more likely to have delayed union (OR 16.4 [95% CI {1.9-139.6)]). Subanalysis compared well-controlled diabetic and nondiabetic Charcot neuroarthropathy patients for same factors. Multivariate analysis, in the subanalysis, found return to ambulation was 15.1 times likely to occur in the nondiabetic CN cohort (OR 15.1 [95% CI 1.3-175.8]) compared to the well-controlled diabetic CN cohort.     

Refinement of survival prediction in patients undergoing lower extremity bypass surgery: stratification by chronic kidney disease classification

OBJECTIVE: End-stage renal disease (ESRD) imparts a significant survival disadvantage to individuals undergoing lower extremity revascularization; however, the influence of lesser degrees of renal impairment remains unclear. This study examined the prognostic significance of the chronic kidney disease (CKD) classification on survival, limb salvage, and graft patency in patients undergoing lower extremity arterial reconstruction. METHODS: A prospective registry was evaluated for consecutive patients between January 31, 1995, and December 21, 2004, undergoing first-time, lower extremity vein bypass surgery. Glomerular filtration rate (GFR) was estimated with the Modification of Diet in Renal Disease equation using each patient's preoperative creatinine concentration. CKD categories were taken from current National Kidney Foundation Kidney Disease Outcomes Quality Initiative staging criteria. RESULTS: The cohort included 456 subjects, with a mean (+/- SD) age of 68.1 +/- 10.8 years. There were 274 men (60%) and 378 Caucasians (82.5%). Comorbidities included diabetes mellitus in 270 (59.0%), hypertension in 333 (72.7%), coronary artery disease in 242 (52.8%), and dyslipidemia in 203 (44.5%). The surgical indication was critical limb ischemia in 384 (83.8%). Among the variables examined, diabetes and critical ischemia as the indication for bypass were significantly skewed toward higher CKD classifications (P < .001). The 5-year survival rates by CKD class were, CKD 1 and 2, 57%; CKD 3, 46%; CKD 4, 23%; and CKD 5, 9.5%. On univariate analysis, age, coronary artery disease, diabetes mellitus, hypertension, critical ischemia, and CKD were significant predictors of mortality. After adjustment, however, only age (hazard ratio [HR], 1.05, 95% confidence interval [CI], 1.03 to 1.06) and CKD stages 4 (HR, 4.23; 95% CI, 2.04 to 8.75) and 5 (HR, 3.27; 95% CI, 1.96 to 5.45) retained significance. Subjects within the CKD 5 classification were more likely to have a major amputation (P = .018) compared with all other CKD classes. Notably, no relationship was detected between CKD category and graft patency. CONCLUSION: CKD staging adequately differentiates survival curves and risk for major amputation among patients with renal impairment who are undergoing lower extremity bypass surgery. This may help in clinical decision analysis as well as in the refinement of stratification in future clinical trial design where survival is an end point.     

Preservation of renal function with surgical revascularization in patients with atherosclerotic renovascular disease

OBJECTIVE: Clinical and anatomic factors predictive of a favorable response to renal revascularization performed for renal function salvage remain poorly defined. To clarify decision making in such patients we reviewed a contemporary experience of surgical renal artery revascularization (RAR) performed primarily for preservation of renal function. METHODS: Between June 1990 and March 2001 (ensuring 1 year minimum follow-up), 96 patients with renal insufficiency (serum creatinine [Cr] concentration >or=1.5 mg/dL) and hypertension underwent RAR for preservation of renal function. Study end points included early and late renal function response, progression to dialysis dependence, and long-term survival. Variables potentially associated with these end points were assessed with univariate analysis, Cox regression analysis, and logistic regression analysis, and survival was assessed with the Kaplan-Meier method. RESULTS: Perioperative failure of RAR occurred in 3 patients (3%), with perioperative mortality in 4 patients (4.1%); thus 92 patients were available for long-term follow-up (mean, 39 months). Mean patient age was 70 +/- 9 years with a mean baseline Cr of 2.6 mg/dL (range, 1.5-7.8 mg/dL). Operative management consisted of aortorenal bypass in 38% of patients, extraanatomic bypass in 38% of patients, and endarterectomy in 24% of patients; 32% of patients required combined aortic revascularization and RAR, and 27% underwent bilateral RAR. At hospital discharge renal function had improved (20% decrement in Cr) in 41 (43%) patients, including 7 patients who were removed from dialysis; remained unchanged in 40 (41%) patients; and declined (20% increase in Cr) in 15 (16%) patients. At last follow-up renal function was either improved or unchanged in 72% of patients. Predictors of a favorable response to RAR at last follow-up included stable Cr at hospital discharge (odds ratio [OR], 7.1; 95% confidence interval [CI], 2.5-21.8; P =.0004) and decreased Cr at hospital discharge (OR, 16; 95% CI, 1.6-307.8; P <.0001); bilateral renal artery repair (OR, 3.1; 95% CI, 0.9-10.6; P =.07) approached clinical significance. Predictors of worsened excretory function at last follow-up included decline of renal function at hospital discharge (OR, 28.9; 95% CI, 5.0-165.4; P =.0002), intervention to treat unilateral renal artery stenosis (OR, 3.8; 95% CI, 0.8-16.6; P =.05), and level of baseline Cr (OR, 3.0; 95% CI, 1.0-4.0; P =.04). Progression to dialysis occurred in 16 (17%) patients. Dialysis-free survival at 5 years was 50%, and overall actuarial survival at 5 years was 59%. Predictors of progression to dialysis during follow-up included treatment of complete renal artery occlusion (OR, 6.2; 95% CI, 1.3-29.5; P =.02), early failure of RAR (OR, 3.1; 95% CI, 0.7-14.2; P =.04) and baseline Cr (OR, 2.9; 95% CI, 1.3-6.1; P =.006). CONCLUSION: Long-term clinical success in the preservation of renal function, noted in 70% of patients, can be predicted by the initial response to RAR and by anatomic factors, in particular, bilateral repair. While extreme (mean Cr >or=3.2 mg/dL) renal dysfunction generally is predictive of poor long-term outcome, a subset of patients will experience favorable results, even to the extent of rescue from dialysis. These results may facilitate clinical decision making in the application of RAR for renal function salvage.