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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
RENAL DATA FROM THE ARAB WORLD  
Year : 2018  |  Volume : 29  |  Issue : 6  |  Page : 1386-1394
Mortality of diabetic on chronic dialysis in Tunisia


1 Department of Nephrology, Dialysis and Transplantation, La Rabta Hospital, Tunis, Tunisia
2 Department of Nephrology, Kef Hospital, Kef, Tunisia
3 Department of Research Laboratory of Kidney Diseases (LR00SP01), Charles Nicolle Hospital, Tunis, Tunisia

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Date of Submission09-May-2018
Date of Acceptance05-Jul-2018
Date of Web Publication27-Dec-2018
 

   Abstract 

Survival rates of diabetic patients on maintenance hemodialysis (HD) are reported to be poorer in Tunisia than in developed countries. This study aims to specify the epidemio-logical, clinical, and biological characteristics of diabetic disease, chronic kidney disease (CKD), and comorbidities at the initiation of HD and investigate factors associated with mortality during the dialysis period. We retrospectively analyzed the outcome of diabetic patients who were initiated on HD from 2007 to 2012 at the Rabta Hospital of Tunis. During the follow-up period, all morbid events and deaths were recorded. Univariate analysis and multivariate analysis were performed to identify risk factors associated with mortality in our population. The study population included 142 patients. The mean age was 58.7 ± 11.9 years. The sex ratio male/female was 1.4. One hundred and twenty-seven patients were type 2 diabetics (89.4%). Diabetic nephropathy was the main initial nephropathy (87.3%). CKD was diagnosed at Stages 4 or 5 in 95.1% of cases. HD was started in emergency conditions in 68.6% of cases. The one-year and the five-year survival rates were 42% and 17%, respectively. At initiation of HD, low socioeconomic status (P = 0.001), advanced age (P = 0.008), low body mass index (P = 0.04), history of stroke (P = 0.04), peripheral neuropathy (P = 0.02), initial vascular access (P = 0.03), secondary hyperpara-thyroidism (P = 0.03), nephrotic-range proteinuria (P = 0.01), and glycated hemoglobin ≤7% (P = 0.03) were associated with higher mortality rate. During dialysis period, cardiovascular events (P = 0.02), infectious complications (P = 0.04), and secondary hyperparathyroidism (P = 0.04) were significantly more noticeable among deceased patients. Due to poor survival rates of diabetic patients on HD, prevention, early detection, and management of diabetic CKD patients should be the way to go forward.

How to cite this article:
Jebali H, Laifi M, Mami I, Khadhar M, Chirmiti M, Beji S, Rheder R, Smaoui W, Krid M, Hmida F B, Rais L, Fatma L B, Zouaghi M K. Mortality of diabetic on chronic dialysis in Tunisia. Saudi J Kidney Dis Transpl 2018;29:1386-94

How to cite this URL:
Jebali H, Laifi M, Mami I, Khadhar M, Chirmiti M, Beji S, Rheder R, Smaoui W, Krid M, Hmida F B, Rais L, Fatma L B, Zouaghi M K. Mortality of diabetic on chronic dialysis in Tunisia. Saudi J Kidney Dis Transpl [serial online] 2018 [cited 2019 Mar 21];29:1386-94. Available from: http://www.sjkdt.org/text.asp?2018/29/6/1386/248283

   Introduction Top


In the world, the epidemiology of the chronic kidney disease (CKD) is characterized by the epidemic of type 2 diabetes which is responsible or associated with the kidney disease.[1] Diabetes is the most common cause of end-stage renal disease (ESRD) in industrialized countries[2] and its prevalence tends to increase over time.

Observational studies among prevalent hemo-dialysis (HD) patients have identified patient characteristics that are associated with greater mortality risk, including traditional risk factors such as white race, older age, low serum albumin levels, low and elevated serum phosphorus levels, anemia and cardiovascular disease as well as other nontraditional risk factors, including С-reactive protein and interleukin-6 levels.[3],[4] Studies also have supported the importance of early nephrology referral in the predialysis period for reducing mortality after HD initiation.[5],[6],[7]

The increased mortality of diabetics on HD is due to the frequency of cardiovascular and infectious complications and the difficulties related to the vascular access. All these factors account for the relatively poor prognosis of these patients, whose early as well as global survival remains significantly worse than that of nondiabetic patients.[1],[8] Indeed, the 2014 United States Renal Data System reported that only 37.2% of patients with diabetic kidney disease survived five years after initiation of HD.[9]

This group of patients would, therefore, require early management in order to optimize the onset of chronic HD and minimize the considerable financial burden for the public health budget used not only to cover the cost of renal replacement therapy (RRT) but also to take care of different comorbidities.[5]

The aim of this study was to analyze the epidemiological and clinical characteristics and the outcome of patients starting HD for diabetic ESRD and to identify risk factors associated with mortality in our population.


   Patients and Methods Top


Study design

This is a retrospective, descriptive, and analytical study carried out in the Renal Nephrology, Dialysis, and Kidney Transplant Department of the Rabta Hospital, Tunis, during a five-year period from May 12, 2007, to May 25, 2012. The study of the survival of patients was carried out, thanks to a transversal, multicenter study in the public and private HD centers.

During the study period, 650 patients started RRT for ESRD at our dialysis unit. All diabetics over the age of 18 hospitalized in our department who were started on HD were included in the study. Patients treated for documented reversible acute renal failure and those who were initially or later treated with peritoneal dialysis were excluded from the study.

Data collection

The data from our study were collected from the hospital records and outpatient records that preceded the start of HD. The outcome and survival of the patients have been identified from the medical records of public and private dialysis centers.

Three periods were individualized in our study: the period preceding dialysis, the start of the RRT, and the period of chronic HD, with as an end point to the collection of the data December 31, 2015, or the death.

  • Period preceding dialysis: epidemiological characteristics of patients, diabetic disease, comorbidities, and chronic renal disease were noted
  • At the start of the RRT: During this period, the clinical, biological, and radiological parameters and the starting circumstances of RRT were noted
  • Period of chronic HD: During this period, complications related to the vascular access, infectious and cardiovascular complications as well as mineral and bone disorders were recorded.


Definitions:

  • Hypertension is defined as systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg[10]
  • Blood pressure control was judged according to the KDIGO recommendations[10]
  • Diabetes was considered well controlled when glycated hemoglobin (HbAlc) level was ≤7%
  • Stages of CKD were defined from the KDIGO recommendations[11]
  • Secondary hyperparathyroidism is defined as a parathyroid hormone (PTH) level 9 times higher than upper limit of normal in the general population[12]
  • Creatinine clearance was calculated using the modification of diet in renal disease
  • To evaluate comorbidities at the start of HD, the modified Charlson score was applied to patients with chronic renal failure:[13] four grades of increasing comor-bidity were established according to the level of the score:
    • Grade 1: Low comorbidity ≤3
    • Grade 2: Moderate comorbidity: 4–5
    • Grade 3: High comorbidity: 6–7
    • Grade 4: Very high comorbidity ≥8.


The primary outcome was all-cause mortality and the factors associated with early and global mortality. Early mortality was defined as patients who died in the first three months on HD.[7],[14]


   Statistical Analysis Top


The statistical study included a descriptive study, a univariate and multivariate analysis. The data was analyzed using the Statistical Package for the Social Science (SPSS) software version 19.0 (SPSS Inc., Chicago, IL, USA). Comparative analysis was performed using t-test for continuous variables and Chi-square test for quantitative variables. For survival studies, we considered the duration from the date of start of RRT to death or end of the study fixed at the date of December 31, 2015. Cumulative survival rates were calculated according to the actuarial method, and comparison of survival curves was performed using logrank test. The multivariate Cox proportional hazards regression models were used to identify predictors of early and late death from variables influencing survival in univa-riate analysis. For all analysis, results were considered statistically significant if P <0.05.


   Results Top


Among the 142 patients starting RRT for diabetic ESRD, 89.4% had type 2 diabetes and 10.6% had type 1 diabetes. At first dialysis, mean age was 58.7 ±11.9 years and 50% were older than 60 years. Type 2 diabetics were significantly older than type 1 diabetics (P <0.0001). Gender ratio (male:female) was 1.4 (83 men and 59 women). The median follow-up of diabetes at the start of HD was 15.9 years. It was 21.7 years for type 1 diabetes and 15.2 years for type 2 diabetes (P = 0.007).

At the start of HD, 93% of patients (132) had diabetic retinopathy, 97.9% (139) had a symptomatic peripheral neuropathy, 14% (20) had orthostatic hypotension, and 48.6% (69) had digestive disorders such as motor diarrhea and gastroparesis. Autonomic neuropathy was significantly more frequent in type 1 diabetics (P = 0.04). Thirty-six patients (25.4%) had at least one episode of myocardial infarction, 50 (35.2%) had peripheral vascular disease, and 19 (13.4%) had a stroke.

[Table 1] summarized the principal clinical and biological data at the onset of RRT. The discovery of chronic renal failure was made in Stages IV and V of CKD in 95.1% of cases with a mean estimated glomerular filtration rate of 10.2 mL/min. Nephropathy was diagnosed at the time of ESRD in 56.3% of cases.
Table 1: Characteristics of patients at onset of renal replacement therapy.

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The median nephrology follow-up before the onset of RRT was 12.2 months. Only 37 patients (26.1%) were referred to a nephrologist before starting HD. Hence, dialysis was started in emergency conditions in 68.6% of cases (96) using a temporary vascular access in 91.2% of cases (125). Referral of patients to a nephrologist before RRT and presence of arteriovenous fistula (AVF) was significantly associated with programmed HD. On the other hand, anemia (P = 0.02) and hypocalcemia (P = 0.05) were more frequent among emergency dialysis patients.

During dialysis period, 45 patients (31.7 %) had presented cardiovascular complications. Myocardial infarction, peripheral vascular disease, stroke, and pericarditis were noted in 13.3% (19), 7.7% (11), 5.6% (8), and 2.8% (4), respectively. Infectious complications were occurred in 38 patients (26.8%), dominated by septicemia, pneumonia, and cutaneous infections noted in 13 (9.1%), 11 (7.7%), and eight (5.6%) patients, respectively.

During the first three months of HD, six patients died with an early mortality rate of 6%. This early mortality rate represented 10.1% of the total number of deaths that occurred during the follow-up period. These deaths were caused by cardiovascular and infectious complications, respectively, in three and two cases. Univariate study revealed that hypocholesterolemia was associated with early mortality in our study.

During the study period, the outcome of only 95 patients (66.9%) could be determined. On December 31, 2015, 59 patients had died. Median survival was 26.5 months and a crude death rate of 62%. Global survival rates were 42% and 17% at one and five years, respectively [Figure 1]. Cardiovascular disease (61%) and infectious complications (25%) were the main causes of death in this cohort [Table 2]. Predictive factors associated with global mortality by univariate study are summarized in [Table 3].
Figure 1: Global mortality.

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Table 2: Causes of death.

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Table 3: Predictors of global mortality.

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Multivariate analysis according to the Cox proportional hazards model was inconclusive due to the redundancy of data and limited number of patients whose evolution was determined.


   Discussion Top


We conducted a retrospective, descriptive, and and analytical study over a period of 5 years of the clinical profile of diabetics at the initiation of RRT and evolutionary modalities in chronic HD. Our study showed the poor prognosis of diabetics on HD in our population.

During the period 2007–2012, 212 diabetic patients were started chronic HD representing 32.6% of all patients within the same period. The prevalence of diabetics with ESRD increased from 10% in 1995 to 15% in 2013 in Tunisia.[15] The rate of diabetics with ESRD in Tunisia is intermediate between that of Western and Arab countries.[2],[3],[4],[16],[17] Indeed, analysis of data from different national and regional dialysis registries demonstrated large differences between many countries according to their life style, prevalence of diabetes, and their policies regarding the acceptance of uremic patients for RRT[1],[2],[3],[7],[16],[18]

The mean duration of known diabetes at the onset of RRT was higher in patients with type 1 diabetes than that of those with type 2 in our study. This delay depends essentially on the quality of management of the diabetic disease, the nephrological follow-up, and the time of adoption of the nephroprotection measures compared to the beginning of the CKD. In our population, the median nephrology follow-up was 12.2 months. Only 26.1% of our patients were referred to a nephrologist before the start of HD against 46.5% in the cohort of Tunis conducted from 1990 to 1996.[18] These results are also lower than what was reported by the majority of authors,[3],[5],[6],[19] but the late reference of diabetics to nephrologists remains a frequent and internationally recognized situation.[2],[20] Comparing Tunisian data with literature, we find that the discovery of the CKD was late in Tunisia.[5],[18],[20],[21],[22] The late reference to the nephrologist of our patients explains the start of emergency HD in 68.6% of cases, more important than that of the Tunis series (30%)[18] and data from the literature showing a significant decrease in the start of emergency dialysis from 80% in the 1980s–1990s to 20% in the 2000s.[3],[5],[20],[23],[24] In our population, temporary vascular access was required in 91.2% of cases, in the range of the Tunis series[18] but higher than those of the data of the literature. According to the 2010 REIN report in France, the first vascular access was a central venous catheter in 54% of patients.[25] The Dialysis Outcomes and Practice Patterns Study (DOPPS) found that central venous catheters accounted for 15%–35% of vascular access in incident patients and 5%–15% in prevalent patients after six months of treatment with increasing recourse to central venous catheters over a decade from 1996 to 2006 (DOPPS I: 8%, DOPPS II: 11%, and DOPPS III: 15%).[26]

The early and overall mortality rates of diabetics are higher than those of nondiabetics both in the general population and in RRT.

Diabetes is a risk factor associated with all-cause mortality among dialysis patients.[1],[2],[5],[8] Indeed, according to the ANZDATA register and the AUSDIAB cohort, the risk of death is 10.8 times higher in type 2 diabetics in ESRD than in type 2 diabetics without renal failure.[1]

Despite improved overall survival in dialysis, the risk of early mortality remains high, especially in the first few weeks after dialysis begins. Thus, the risk of mortality during the first 90 days is three times the risk of mortality after this period.[7],[14] The early mortality rate varies from 5.6% to 36% depending on the series.[5],[7],[8],[14],[27] It was 18.7% in the Tunis series,[18] while in our study, it was 6%, probably related to the small size of our population. Hypo-cholesterolemia was associated with early death in our study, which has been noted by some authors in their series as well.[28],[29]

The survival of our patients at one year and five years was 42% and 17%, respectively, significantly lower than the data in the literature. In fact, the one-year survival is 80% on average according to the studies[30],[31],[32],[33],[34] while five-year survival varies between 37.2% according to the USRDS[9] and 50% in Europe.[23] Furthermore, the review of the recent literature shows an improvement in survival of diabetics on dialysis. In Finland, the median survival of type 1 diabetics increased from 43.2 months in the 1980s to 96 months in the 2000s, which is found in Australian and New Zealand studies with a significant decrease in adjusted risk of death: 9% per five-year period between 1991 and 2005 for type 2 diabetics.[1] In the United States, the five-year survival of diabetics increased from 25% in 2009 to 37.2% in 2014.[9] In Tunisia, however, the crude death rate of diabetics in HD seems to be increasing over time. This increase in mortality is probably secondary to the aging of diabetics at the initiation of HD, the late reference of our patients to the nephrologist, the prevalence of type 2 diabetics, and the start of renal replacement therapy under emergency conditions in 68.6 % of cases [Table 4].
Table 4: Comparative analysis between current study and Tunis study.

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Cardiovascular mortality is the leading cause of death both in our study (61% of cases) and in the literature. It varies between 40% and 55% and is dominated by the myocardial infarction.[35],[36] Other cardiovascular mortality cases also occurred outside the dialysis units, and hence, their exact cause was not known. Infectious causes were the second leading cause of death in dialysis, both in diabetics and nondiabetics. They are reported in 12% to 25% of cases. 23, 31, 37-39

Advanced age, low socioeconomic level, and comorbidities such as stroke and peripheral neuropathy were associated with mortality in our study. These results have been reported by several authors.[27],[40],[41],[42],[43],[44],[45],[46] Proteinuria likely to directly increase cardiovascular mortality or constitute a marker of certain abnormalities including endothelial dysfunction[47] was a predictor of mortality. Malnutrition is prevalent in 42%–77% of the ESRD population in developing countries, which is strongly associated with increased mortality. Malnutrition is a factor of accelerated atherosclerosis. It is part of the complex malnutrition inflammation atherosclerosis.[48] Thus, several authors adopt the malnutrition inflammation score to predict mortality in dialysis patients.[49],[50] In our study, there was a correlation between low body mass index and low cholesterol and mortality. Secondary hyperparathyroidism was also shown to be a predictor of mortality, thus sharing the findings of some authors regarding the U-shaped relationship between PTH and mortality.[1] The impact of glycemic control on HD mortality remains controversial. The HbA1c level associated with better survival is very variable from one study to another.[31],[52],[53],[54] Even the recommendations for glycemic control in diabetics in HD are extrapolated from data in non-HD and therefore based on opinions and not on evidence.[31] The UK renal association recommends HbA1C between 6.5% and 7.5% to reduce cardiovascular risk.[55] The KDOQI recommendations suggest that strict control of diabetes has no benefit in patients at high risk of hypoglycemia or in whom life expectancy is reduced.[31] The initiation of HD through a permanent vascular access such as AVF was associated with better survival.[56],[57] According to the DOPPS study, the relative risk of death is increased by 32% with catheters compared to AVF.[26]


   Conclusion Top


This study has several limitations. It is a retrospective and monocentric study with a small number of patients and of a short duration. Despite these limitations, this work revealed the increase in mortality of diabetics in HD in Tunisia, unlike data from other countries. Advanced age of patients, late referral to nephrologist, and initiation of HD under emergency conditions in most cases would explain these findings.

Conflict of interest: None declared.

 
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Correspondence Address:
Dr. Hela Jebali
Department of Nephrology, Dialysis and Transplantation, La Rabta Hospital, Tunis
Tunisia
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DOI: 10.4103/1319-2442.248283

PMID: 30588971

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    Abstract
   Introduction
   Patients and Methods
   Statistical Analysis
   Results
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