it has been well established that patients with end - stage renal disease ( esrd ) undergoing hemodialysis ( hd ) had a higher association of peripheral arterial disease ( pad ) , lower extremity amputation ( lea ) , and foot ulcerations ( fu ) [ 13 ] . such an association could be attributed to a common atherosclerotic cause . moreover ,
diabetic patients with esrd had a 10-fold increased risk of lea in comparison to diabetes patients without renal insufficiency .
several studies have reported increased rates of lea among esrd patients , irrespective of the concomitant presence of diabetes mellitus ( dm ) [ 46 ] .
the mechanism of fu development is multifactorial which depends upon various physiological , mechanical , and treatment factors .
reported significantly higher incidence of foot complications in patients with concomitant esrd and dm in comparison to those who had only dm suggesting a possible relationship between esrd and fu .
in addition , lea and fu are well established complication of diabetic nephropathy [ 8 , 9 ] .
margolis et al .   observed a strong correlation between progressions of chronic kidney disease ( ckd ) with the development of diabetic fu .
game et al .   also demonstrated a close association of fu and amputations in diabetic patients started to undergo dialysis .
performed a meta - analysis to look for the relationship of diabetic fu with cardiovascular disease ( cvd ) and all - cause mortality .
the authors found an increased association of cvd and mortality in diabetic patients with fu in comparison to those without fu .
interestingly , a recent study advocated a higher incidence of risk factors ( pad and peripheral neuropathy ) for fu among hd patients . in qatar , an earlier report from our center identified a high incidence of pad in hd patients .
however , there is a lack of information that describes the risk factors and prognostic implications of fu among hd patients in the arab middle east .
we aim to evaluate this association and its impact on the outcomes over a 5-year period .
we conducted a retrospective analysis of all hemodialysis patients enrolled at the hd unit at hamad general hospital ( hgh ) , qatar , over five years ( 20072012 ) duration .
patients surviving for at least 3 months on the initial hd were included in the study .
hd patients were categorized into two groups according to whether they had foot ulcer ( fu ) or not ( no - fu ) based on physical examination .
the attending physician in the hd unit collected the data regarding the demographics characteristics , clinical evaluation , medical history , and comorbidities . during the follow - up period over 5 years , hd - related procedures such as vascular access ( arteriovenous fistula , arteriovenous grafting , and tunneled catheter ) , renal transplantation , and vascular complication were also reported .
the need for 3 vascular accesses ( due to mechanical obstruction , poor flow , or infection ) had been analyzed .
we speculated that hd patients with fu had poor outcomes compared to no - fu patients .
the study end - points ( major amputation , vascular complications , and mortality ) were also subanalyzed according to the presence or absence of dm and pad .
fu was defined according to the clinical findings as a full thickness skin break below the level of malleoli .
patients were considered to have pad if they had one of the following criteria : abi < 0.9 , history of intermittent claudication , vascular bypass or endovascular intervention for occlusive vascular disease , or amputation due to occlusive vascular disease .
major amputations were defined as amputations proximal to the ankle joint , and minor amputations were defined as those through or distal to the ankle joint .
diabetic nephropathy was diagnosed during patient follow - up in the nephrology out - patient clinic according to the patient chart .
it was defined as presence of macroalbuminuria that is a urinary albumin excretion of more than 300  mg in a 24-hour collection or macroalbuminuria and abnormal renal function as represented by an abnormality in serum creatinine , calculated creatinine clearance , or glomerular filtration rate .
analyses were conducted using the student 's t - test for continuous variables and pearson chi - square (  ) test for categorical variables .
multivariate logistic regression analysis was performed for predictors of development of fu and mortality . adjusted odds ratios ( or ) , 95% ci , and p values
a significant difference was considered when the two - tailed p value was < 0.05 .
data analysis was carried out using the statistical package for social sciences version 18 ( spss inc . ,
the study has been approved by the medical research center , hamad medical corporation , qatar ( irb # 12007/12 ) .
a cohort of 252 hd patients was included in the study , of which 42 had fu ( 17% ) and 210 were without fu .
demographic , clinical characteristics , and risk factors for hd patients with and without fu were shown in table 1 and figure 1 .
patients with fu were 6 years older and had higher incidence of retinopathy ( 67% versus 40.5% ; p = 0.002 ) , polyvascular disease ( 26.2% versus 6.7% ; p = 0.001 ) , angina ( 24% versus 11% ; p = 0.02 ) , pad ( 71% versus 32% ; p = 0.001 ) , and nephropathy ( 79% versus 42% ; p = 0.001 ) compared to no - fu patients .
also , a high percent of patients needed tunneled catheters ( 88% versus 82% ; p = 0.03 ) and aspirin ( 62% versus 45% ; p = 0.04 ) in the fu group , whereas , history of renal transplant ( 14% versus 2.4% ; p = 0.03 ) was observed more in no - fu group .
patients in fu group also had higher percentage of dm ( 83.3% versus 56% ; p = 0.001 ) , major amputation ( 26% versus 1% ; p = 0.001 ) , need for 3 vascular accesses ( 69% versus 47% ; p = 0.01 ) , and coronary artery disease
the two groups were comparable regarding the mean baseline laboratory investigations ( table 2 ) .
similarly , the percentage of dyslipidemia , hypertension , smoking , and cerebral vascular accident ( cva ) was comparable between the two groups ( table 1 ) .
the types of hd vascular accesses such as arteriovenous fistulas , graft , or catheter were comparable in the 2 groups .
overall mortality rate within 3 years was 24.2% among the study cohort and was comparable between the two groups .
development of pad ( 71% versus 32% ; p = 0.001 ) , new foot ulcers ( 47.6% versus 2.4% ; p = 0.001 ) , and need for major amputation ( 16.7% versus 1% ; p = 0.001 ) were significantly higher among fu group as compared to no - fu group . in the following two years ,
significantly more number of patients in fu group developed new pad ( 22% versus 1.4% ; p = 0.001 ) , underwent major amputation ( 22% versus 0% ; p = 0.001 ) , and died ( 70.4% versus 17.5% ; p = 0.001 ) in comparison to no - fu group ( table 1 ) .
the frequency of renal transplant and angina was comparable among both the groups , while cerebral vascular accident ( 3.5% ) was only observed in no - fu group . 

figure 2 shows that dm patients had significantly higher incidence of fu ( 23% versus 7% ; p = 0.001 ) , need for major amputation ( 8.6% versus 0% ; p = 0.003 ) , and mortality ( 65% versus 23% ; p = 0.001 ) than non - dm patients . in dm group ,
figure 3 demonstrates the outcomes in hd patients based on the presence / absence of dm and/or pad .
patients who had pad showed increased incidence of fu ( 41% versus 4% ; p = 0.001 ) , major amputation ( 14% versus 2% ; p = 0.02 ) , and mortality ( 80.5% versus 29% ; p = 0.001 ) than non - pad . on the other hand , among non - dm patients
of these patients , mortality rate was significantly higher among pad group ( 39% versus 13% ; p = 0.007 ) in comparison to non - pad .
univariate analysis ( figure 1 ) shows the mortality rate in patients with fu in both diabetic and nondiabetic patients . on multivariate analysis , after adjusting for dm , hba1c , age , and gender , the presence of pad was the major independent predictor of development of fu in hd patients with an adjusted odd ratio ( aor ) of 16.0 ( 95% confidence interval ( ci ) : 4.4162.18 , p = 0.001 ) followed by duration of hd with aor 1.14 ( 95% ci : 1.0051.299 , p = 0.042 ) .
furthermore , after adjusting for age , sex , and cad , predictors of mortality in hd patients were pad ( aor 4.1 ; 95% ci : 1.948.59 , p = 0.001 ) , fu ( aor 3.6 ; 95% ci : 1.2810.002 , p = 0.01 ) , and dm ( aor 2.7 , 95% ci : 1.235.89 , p = 0.01 ) ( figures 4 and 5 ) .
the present study highlights the frequency and implications of fu in patients undergoing maintenance hd over a 5-year duration .
the mortality rates were higher in patients with fu in both diabetic and nondiabetic patients ; however it was relatively higher in diabetic patients .
moreover , fu was associated with 4-fold increased risk of mortality after adjusting for age , sex , and cad .
presence of pad was associated with 16-fold increased risk of fu in hd after adjustment for age , sex , dm , and duration of hd .
patients in the fu group underwent higher number of repeated hd vascular accesses in comparison to non - fu group .
recent studies have identified an increased risk of fu and lea in ckd patients who did not receive renal replacement therapy [ 10 , 17 ] .
other studies investigated patients of combined dm with esrd and found a higher risk of fu in patients undergoing hd [ 11 , 15 ] .
a swedish study demonstrated a 2.45 times increased risk of lea in esrd patients compared to those without esrd .
similarly , prompers et al .   found the risk of nonhealing of fu to be 2.3-fold higher in esrd than in non - esrd patients .
the correlation between dialysis and foot complications among patients with dm and ckd has been initially described by mcgrath and curran .
they observed 50% mortality rate at one - year follow - up after lea . in our study , the rate of major amputation was significantly higher in fu patients which corroborates with an earlier study showing increased rate of amputation in ckd patients undergoing dialysis ( 57% ) as compared to those without dialysis ( 25% ) .
the relevance of selecting fu in our report is that it is potentially preventable , and its progression generally leads to serious foot complications , major amputation , and mortality . in their long - term follow - up study
( 10 years ) , morbach and coworkers   concluded that patients with diabetic foot had high mortality particularly in the presence of pad or renal failure . in comparison to that study
, our 5-year study showed that fu patients had higher mortality ( 81% versus 70.4% ) although our patients were 6 years younger and less likely to have dm ( 83% versus 100% ) and pad ( 34% versus 55.5% ) .
moreover , the entire cohort of the present study was undergoing hd ( 100% versus 4% ) .
the association of severe complications in hd patients might be attributed to the cardiovascular risk factors .
several contributing factors have been proposed for the development of fu in patients with esrd and dm .
the important risk factors for the development of diabetic fu involve distal polyneuropathy , microangiopathy , and macroangiopathy . also , cardiovascular autonomic neuropathy is another coexisting complication of dm .
the authors found that pad is independently associated with esrd . according to one of our recent studies ,
pad patients had 4- to 5-fold increased incidence of fu and lea in comparison to non - pad patients . in our study ,
a higher incidence of retinopathy , polyvascular disease , angina , pad , and nephropathy was associated with fu .
studied the risk factors associated with prevalent fu in patients with dm and ckd ( predialysis versus on - dialysis ) .
the authors reported that dialysis therapy and previous fu were the only independent predictors of the development of new fu .
kaminski et al .   reported a high prevalence of risk factors for fu present in patients with esrd either with or without the coexistence of dm .
the authors did not indicate the severity of esrf or whether the patients were on dialysis or not .
.   found that dm , preexisting comorbidities , cvd , hd inadequacy , and lower serum albumin level are the major factors for lea .
consistent with our findings , a recent meta - analysis reported higher association of cvd , dm , and fu . ischemic in comparison to neuropathic ulcers are associated with higher mortality rate . moreover ,
the marked inflammatory response during the process of ulceration has a significant role in the initiation and worsening of the atherosclerosis . in our study , among hd patients without diabetes , only 7% developed fu , despite a high prevalence of pad and cad . 

wolf et al .   reported that the presence of dm in esrf patients increases the risk of lea 10 times in comparison to those who are diabetic without esrf .
moreover , during hd , around 4% of patients require an amputation each year [ 17 , 25 ] .
our subanalysis showed significantly higher incidence of fu , amputation , and mortality in diabetic patients than in non - dm patients .
also , patients with combined dm and pad revealed increased association of fu , amputation , and mortality .
our findings are supported by a large meta - analysis which showed that pad is independently associated with cvd and all - cause mortality .
further , the authors reported an increased risk of all - cause mortality in diabetic patients who developed fu than in diabetics without fu .
it is not possible to specify the extent of infection , neuropathy , ischemia , depth , or extent of tissue loss grade of fu .
another limitation is the additive effect of diabetes on hd patients who developed foot ulcers .
we did not know how many hd patients developed dm during the follow - up . in order to confirm our findings
, large sample - sized studies are needed to establish the implications of fu in hd patients .
abi < 9 was used as a part of the diagnosis of pad which may lead to underestimation of the disease .
previous data showed that as with low abi , high rates of mortality , vascular events , and amputation were reported in patients with high abi or noncompressible vessels . in a large study of patients with dm and cad , singh et al .   reported a high prevalence of arterial stiffness , similar to that seen in older individuals and dialysis patients .
( 2014 ) defined pad as an abi < 0.9 or > 1.4 , these high abi values were observed in patients with diabetes , particularly for those with concomitant ckd . in conclusion , hemodialysis is a significant risk factor for fu which needs special attention .
further , pad is significantly associated with fu , amputation , and mortality in diabetic hd patients .
the increased risk of mortality could be explained by the greater burden of cvd in these patients .
therefore , hd patient needs intensive foot care to avoid complications of the lower limb and warrant progressive modification of cvd risk factors .
 foot ulceration ( fu ) remains a serious concern for patients worldwide . 
 we analyzed the incidence , risk factors , and outcome of fu in hemodialysis ( hd ) patients . 
 a retrospective cohort study was conducted for 252 hd patients who were followed up for 5 years . 
 patients were categorized according to whether they developed fu or not . 
 the fu group ( 17% ) was older and had significantly higher incidence of nephropathy , retinopathy , peripheral ( pad ) , coronary artery disease ( cad ) , and diabetes mellitus ( dm ) as compared to no - fu group . 
 fu group had higher frequency of major amputation ( p = 0.001 ) and hd vascular access ( p = 0.01 ) . 
 patients with combined dm and pad had a 10-fold increased risk of fu in comparison to those who had dm alone . 
 presence of pad was the main independent predictor for development of fu in hd with an adjusted odd ratio ( aor ) of 16.0 ( 95% ci : 4.4162.18 ; p = 0.001 ) . 
 after adjusting for age , sex , and cad , predictors for mortality were pad ( aor 4.3 ) , fu ( aor 3.6 ) , and dm ( aor 2.6 ) . 
 fu is common in hd patients regardless of dm . 
 however , the presence of pad is significantly associated with more fu and mortality in hd . 
 hd patients need intensive foot care and warrant progressive modification of vascular risk factors . 