Home About us Current issue Back issues Submission Instructions Advertise Contact Login   

Search Article 
  
Advanced search 
 
Saudi Journal of Kidney Diseases and Transplantation
Users online: 50 Home Bookmark this page Print this page Email this page Small font sizeDefault font size Increase font size 
 


 
Table of Contents   
RENAL DATA FROM THE ARAB WORLD  
Year : 2013  |  Volume : 24  |  Issue : 2  |  Page : 392-402
Progression of diabetic nephropathy, risk of end-stage renal disease and mortality in patients with type-1 diabetes


1 Department of Nephrology, Medical School, University Mohamed First, Oujda, Morocco
2 Department of Endocrinology, Medical School, University Mohamed First, Oujda, Morocco
3 Department of Medicine, Medical School, University Mohamed First, Oujda, Morocco
4 Medical Emergency Department, Ibn Sina University Hospital; Laboratory of Biostatistics, Clinical and Epidemiological Research, Medical School, University Mohamed V, Rabat, Morocco

Click here for correspondence address and email

Date of Web Publication26-Mar-2013
 

   Abstract 

Numerous studies have shown that diabetic nephropathy (DNP) is associated with an elevated risk of progression toward end-stage renal disease (ESRD) as well as increased cardiovascular mortality. The majority of these studies are from the developed countries. The factors leading to the progression of DNP may not be quite the same in the developing countries. The aim of this study was to evaluate the risk factors of progression toward ESRD and mortality among type-1 diabetes (T1D) patients with DNP in a developing country. This prospective study was conducted enrolling 72 patients with T1D in September 2006, including T1D patients with DNP defined as microalbuminuria, proteinuria, and/or renal failure, and following them up for five years. The mean age was 29.5±7.5 years with a mean duration of diabetes of 17 (11-20) years. At the time of enrollment, 43.1% had arterial hypertension, 69.4% had proliferative retinopathy, 44.4 had clinical neuropathy, 25% lived in rural areas, and 51.4% had macroalbuminuria. Progression toward ESRD was observed in 34.7% of cases. In multivariate analysis, diastolic blood pressure (P = 0.006) and blood hemoglobin (P = 0.003) were identified as the risk factors associated with ESRD. Death occurred in 18.3% of cases, including 92.3% on hemodialysis with a median hemodialysis duration of six (1-60) months. In multivariate analysis, the ESRD was identified as risk factor for death (P <0.001). DNP due to T1D remains a disease involving a heavy burden of morbi-mortality and is difficult to manage in a developing country because of the low socioeconomic level of patients and the lack of reliable epidemiological data.

How to cite this article:
Bentata Y, Haddiya I, Latrech H, Serraj K, Abouqal R. Progression of diabetic nephropathy, risk of end-stage renal disease and mortality in patients with type-1 diabetes. Saudi J Kidney Dis Transpl 2013;24:392-402

How to cite this URL:
Bentata Y, Haddiya I, Latrech H, Serraj K, Abouqal R. Progression of diabetic nephropathy, risk of end-stage renal disease and mortality in patients with type-1 diabetes. Saudi J Kidney Dis Transpl [serial online] 2013 [cited 2014 Sep 2];24:392-402. Available from: http://www.sjkdt.org/text.asp?2013/24/2/392/109617

   Introduction Top


Diabetic nephropathy (DNP) is associated with an increased risk of progression toward end-stage renal disease (ESRD) and cardiovascular mortality. [1],[2],[3],[4] DNP is the major cause of ESRD in many countries around the world and its incidence has increased in the last decades. [3],[5],[6] Approximately 25% of patients with type-1 diabetes (T1D) develop DNP. [7],[8]

Microalbuminuria has been recognized for several years as a powerful predictive marker of DNP. [1],[9],[10] Nevertheless, the presence of microalbuminuria that indicates the early stage of DNP does not explain by itself the progression of DNP toward ESRD. Thus, other factors including poor glycemic and lipid control, arterial hypertension, smoking, as well as genetic and environmental factors have been widely implicated. [11],[12]

Most of these data have been reported from the developed countries. The situation with regard to progression of DNP may not be quite the same in the developing countries, where socioeconomic conditions constitute a real obstacle to patients' medical management. The aim of this study was to evaluate the progression of DNP, identify the risk factors of ESRD progression, and determine the mortality rate in a cohort of T1D patients in a developing country.


   Materials and Methods Top


This was a prospective study that included all the patients with T1D who presented with DNP in September 2006 and were followed up regularly for five years in specialized nephrology referral center for chronic diseases at Oujda in the eastern region of Morocco. T1D was defined as a diagnosis made before 36 years of age, requiring regular insulin treatment within one year of diagnosis. DNP was defined as the presence of microalbuminuria, macroalbuminuria and/or renal failure after elimination of other etiologies of renal failure. Microalbuminuria was defined as an albumin excretion rate (AER) ranging between 30 and 300 mg/24 h. Macroalbuminuria was defined as an AER exceeding 300 mg/24 h. The urinary assays were performed using the immunological methods. Urinary assays done on admission were repeated on three specimens at three-monthly intervals. Renal failure was defined as creatinine clearance below 60 mL/min estimated by the Modification of Diet in Renal Disease (MDRD) equation. Patients presenting with gestational diabetes, DNP patients with less than one year of nephrological follow-up, patients lost to follow-up and/or having another renal pathology were excluded from the study. Arterial hypertension (AHT) was defined as systolic arterial pressure (SAP) ≥140 mmHg and diastolic arterial pressure (DAP) ≥90 mmHg. Lipid levels were categorized based on The National Cholesterol Education Program and American Heart Association guidelines as follows: high total cholesterol >5.2 mmol/L and high triglycerides >1.7 mmol/L. [13],[14]

The following demographic data were obtained from all patients at the time of enrollment: age, gender, body mass index, duration of diabetes, family history of diabetes, smoking, diabetic retinopathy, diabetic neuropathy, diabetic arteriopathy, and blood pressure.The following biochemical parameters were studied at admission and every year for five years: plasma concentrations of creatinine, urea, glycated hemoglobin (HbA1C), total cholesterol, and triglycerides, as well as hemoglobin, 24-h urinary albumin excretion, and cytobacteriological urine analysis. During the follow-up period, we ensured strict nephrological follow-up (two to four consultations per year depending on the stage of renal disease) and we intensified nephroprotection by initiating treatment based on renin-angiotensin system blockers. We compared different clinical and bio-chemical parameters at the time of enrollment to the study and also during the progression to ESRD and/or the occurrence of death. We also studied the progression of renal parameters in the group of surviving patients who did not develop ESRD.


   Statistical Analysis Top


Quantitative variables were expressed as mean ± SD or as median and interquartile range following their distribution. Qualitative variables were expressed as frequency and percentage. Comparison of quantitative variables between two groups was performed by Student's t-test if the variable showed symmetrical distribution or by Mann-Whitney test if the variable showed asymmetrical distribution. Comparison for repeated measures of albumin excretion was carried out by the Friedman test. Bonferroni's post-hoc test was used to locate the significance. Comparison of qualitative variables between two groups was performed using Chi-square test or Fisher's exact test. Logistic regression was used to identify the risk factors in univariate and multivariate analysis. Results are presented as the odds ratio (OR) and 95% confidence interval (CI). A two-tailed P value of <0.05 was considered significant. Statistical analyses were carried out using SPSS for Windows, version 13.0 (SPSS, Inc., Chicago, IL, USA).


   Results Top


A total of 72 patients (50 males) with T1D were included in the study. Mean age was 29.5 ± 7.5 years (16-45 years). Of these patients, 63.9% had duration of diabetes exceeding 15 years and 84% of the patients had not received regular diabetes care. 85.7% of the patients had never had a nephrological consultation before and 84.7% of the patients had never benefited from specialized nutritional education sessions. Clinical characteristics of T1D patients at admission in the first nephrology consultation are shown in [Table 1].
Table 1: Characteristics of 72 T1D patients with diabetic nephropathy at the time of enrollment.

Click here to view


After an average follow-up of 3.5 ± 1.5 years, we compared the parameters of patients as two groups according to whether they developed ESRD or not. A statistically significant difference was found concerning the age of onset of diabetes (17 ± 6.5 vs. 12.5 ± 7 years, P = 0.006), duration of diabetes (15 ± 7 vs. 18.5 ± 6 years, P = 0.04), male gender (59.6% vs. 88%, P = 0.01), smoking (21.3% vs. 48%, P = 0.03), diabetic retinopathy (53.2% vs. 100%, P <0.001), diabetic neuropathy (30.4% vs. 75%, P = 0.001), lower extremity arterial disease (11.1% vs. 47.8%, P = 0.002), SAP (125 ± 18 vs. 157 ± 17 mmHg, P <0.001), DAP (72.5 ± 9 vs. 98 ± 10 mmHg, P <0.001), blood hemoglobin (12.2 ± 1.2 vs. 9.1 ± 2.1 g/dL, P <0.001), total triglycerides [0.89 (0.76-1.36) vs. 1.24 (0.85-1.59) mmol/L, P= 0.04], AER [98 (60-460) vs. 1300 (310-3500) mg/24 h, P <0.001], and glomerular filtration rate (GFR) by MDRD [109 (75-139) vs. 13 (9-37) mL/min, P <0.001]. Comparison of clinical and biological parameters at the time of enrollment between the two groups is shown in [Table 2]. Independent factors associated with ESRD were as follows: Diastolic blood pressure (OR = 152.99, 95% CI = 14.69-1593.20, P <0.001) and blood hemoglobin (OR = 1.17, 95% CI = 1.02-1.34, P = 0.01).
Table 2: Comparison of socio-demographic, clinical, and biological parameters at the time of enrollment between patients who developed ESRD with those who did not during follow-up.

Click here to view


We also compared the parameters of two groups of patients according to the occurrence of death. Death was observed in 19.4% of cases. 92.8% of deaths occurred in patients on intermittent hemodialysis with a median duration of dialysis of six (1-30) months. A statistically significant difference was found in the age of onset of diabetes (16 ± 6.5 vs. 11 ± 6 years, P = 0.009), duration of diabetes (16 ± 7 vs. 19.5 ± 3.5 years, P = 0.04), diabetic retinopathy (62.1% vs. 100%, P = 0.004), diabetic neuropathy (40.4% vs. 69.2%, P = 0.05), lower extremity arterial disease (17% vs. 58.3%, P = 0.003), SAP (133 ± 21 vs. 151 ± 15 mmHg, P = 0.004), DAP (78 ± 10 vs. 96 ± 11 mmHg, P <0.001), blood hemoglobin (11.7 ± 1.7 vs. 8.7 ± 2.2 g/dL, P <0.001), AER [180 (64-602) vs. 1200 (165-2750) mg/24 h, P = 0.001], and GFR by MDRD [89 (55-128) vs. 12 (9-33) mL/min, P <0.001). Comparison of clinical and biochemical parameters at the time of enrollment between these two groups is shown in [Table 3]. The independent factor associated with mortality was ESRD (OR = 14.15, 95% CI= 1.70-74.01, P = 0.002). Independent factors associated with ESRD in TD1 patients were as follows: blood hemoglobin (OR = 3.18; 95% CI, 1.47-6.87; P = 0.0003) and diastolic blood pressure (OR = 1.15; 95% CI, 1.04-1.27; P = 0.0006) as demonstrated in [Table 4].
Table 3: Comparison of socio-demographic, clinical, and biological parameters of patients at admission between the dead patients and those survived during follow-up.

Click here to view
Table 4: Risk factors for ESRD in type-1 diabetes patients with diabetic nephropathy.

Click here to view


Regarding the progression of DNP in survivors who did not develop ESRD, there was a statistically significant difference in the AER (mg/24 h) at the time of enrollment with that at two years of follow-up [95 (60-405) vs. 90 (60-220), P = 0.03). Similar difference was found at three years [95 (60-405) vs. 86 (36-190), P = 0.05], four years [95 (60-405) vs. 72 (36-109), P = 0.004], and five years of follow-up [95 (60-405) vs. 102 (35-119), P = 0.006). Progression of AER in survivors without ESRD is shown in [Figure 1].
Figure 1. Progression of albumin excretion rate (AER) in patients who survived without reaching ESRD (n = 45).

Click here to view


There was also a statistically significant difference in the progression of the GFR estimated by MDRD (mL/min) at the time of enrollment and at one year of follow-up [109 (76-141) vs. 108 (75-139), P = 0.004]. Similar finding was also found at two years of follow-up [109 (76-141) vs. 101 (67-131), P <0.001], three years [109 (76-141) vs. 101 (60-121), P = 0.001], four years [109 (76-141) vs. 94 (61-124), P <0.001], and at five years [109 (76-141) vs. 94 (59-123), P <0.001]. Progression of GFR in survivors without ESRD is shown in [Figure 2].
Figure 2. Progression of glomerular filtration rate (GFR) in patients who survived without reaching ESRD (n = 45).

Click here to view


No statistically significant difference was noted concerning the evolution of glycosylated hemoglobin (HbA 1 C) levels, or SAP and DAP at the time of enrollment and at five years of follow-up.


   Discussion Top


About 30%-60% of patients with T1D develop microalbuminuria within the 10-20 years following the onset of diabetes. [15],[16] Chronic Kidney Failure (CKD) generally appears 15-20 years after the onset of microalbuminuria, and ESRD appears in 50% of patients with macroalbuminuria within ten years and in 75% within the following 15years.

Microalbuminuria has been widely recognized since the 1980s as the main predictive factor of DNP in T1D. [1],[10] However, this concept is currently a subject of considerable controversy due to the new observations being reported. In fact, recent studies have observed that microalbuminuria regressed in approximately 50% of cases to normoalbuminuria, [17],[18] while progression toward macroalbuminuria was observed in only 15%-25% of cases. [17],[18],[19],[20] Moreover, in many cases, when microalbuminuria appears, histologic renal lesions are already in place and the process of renal function decline has already begun. These new findings are at the origin of a new concept in the natural progression of DNP in T1D, called early renal function decline (ERFD) which denotes a progressive loss of renal function independent of the progression of urinary excretion of albumin. [21] These two phenomena are certainly independent in terms of progression, but probably share the same pathophysiological mechanism. Thus, whatever the model, microalbuminuria seems to play a fundamental role in the initial development of DNP, while macroalbuminuria is a factor of DNP progression and ESRD evolution. This would be a reason to target decrease in urinary albumin excretion in the treatment of DNP.

According to the classical concept of natural progression of DNP in T1D, ESRD generally occurs beyond 25 years. However, in our study, macroalbuminuria was found in 51.4% of patients at the time of inclusion in the study, with duration of diabetes being 17 ± 6 years, and ESRD occurred in 34.7% with duration diabetes being 18.5 ± 6 years. Thus, the progression of microalbuminuria in itself does not explain the progressive decline of renal function, which suggests the involvement of other factors. Diabetic imbalance and AHT are the two main factors involved in the progression of DNP.

Glycemic imbalance is strongly correlated with the occurrence of ESRD and cardiovascular disease in T1D. In the FinnDiane cohort, HbA1C was elevated in the ESRD group contrary to the non-ESRD group (9.4 ± 1.6% vs. 8.8 ± 1.4%, P <0.05). In this cohort, glycemic control was linearly related to the cumulative incidence of ESRD. [22] In the Joslin cohort, the risk of ESRD increased with increase of baseline HbA1C and the effects of a 1% increase in HgA1C and a doubling of albumin/creatinine ratio (ACR) were approximately equivalent. [23] In addition, glycemic balance remains a difficult goal to achieve in these patients. In our study, we observed glycemic imbalance at admission and throughout follow-up. This may be explained by the poor adherence of patients to their diet and treatment, low socioeconomic level, younger age of patients, and their unawareness of the seriousness of complications.

Hyperglycemia and the duration of exposure to hyperglycemia explain only 11% of the risk of developing microvascular complications in T1D. [24] The remaining risk must be explained by other factors, such as the presence of hypertension, which is known to be especially related to the development and progression of nephropathy. [20],[25] AHT in diabetic patients is strongly correlated with the occurrence of major complications such as retinopathy, nephropathy, and cardiovascular disease. [26],[27],[28] It is an important risk factor for the development and progression of DNP. Analysis of United Kingdom Prospective Diabetes Study (UKPDS) showed that every 10 mmHg reduction in systolic blood pressure is associated with a 13% reduction in the risk of microvascular complications, with the smallest risk among those patients with systolic blood pressure <120 mmHg. [29] This raises the probable need to re-define the blood pressure objectives in diabetic patients with DNP.

Smoking is another risk factor for DNP and its progression. In the FinnDiane cohort, 36% of type-1 diabetics were smokers in the ESRD group versus 43% in the group alive without ESRD (P <0.05). [22] In the Pittsburgh Epidemiology of Diabetes Complications cohort, 53.9% of patients with T1Dwere smokers in the macroalbuminuria group versus 17% in the normoalbuminuric group. [30] Yet, other studies did not bring out this relationship. [23],[31] However, we feel that cessation of tobacco use is to be strongly recommended whatever the stage of DNP.

Qualitative and quantitative lipid abnormalities are often present in subjects with T1D and are related to glycemic control. [32] In T1D, increased serum triglycerides and total cholesterol were associated with micro- and macro-albuminuria. [33] A rise in total blood cholesterol is also a risk factor for GFR decrease in T1D patients with macroalbuminuria. [34] Recent studies have shown that the use of statins improved the pre-ESRD mortality rate and the incidence of ESRD. [35],[36] In FinnDiane cohort, blood cholesterol was strongly associated with the incidence of ESRD and pre-ESRD mortality. [22] However, in Joslin clinic cohort, poor glycemic control was not associated with the occurrence of ESRD. [23]

Body mass has been identified as a DNP risk factor in several studies. In FinnDiane cohort, body mass was also a predictor of cumulative incidence of ESRD. [22] On the other hand, in Joslin clinic cohort, body mass was not identified as an ESRD risk factor in T1D patients with macroalbuminuria. [23] However, the mean body mass reported in the various studies is relatively high in type 1 diabetic patients with DNP and can reach up to 27 kg/m 2 . [22],[23] In our study, however, the mean body mass remained low (around 22 kg/m 2 ).This is related to genetic and environmental factors and/or the low socioeconomic level of our population.

With regard to ethnicity, the prevalence of DNP varies according to ethnicity; it is higher in African-Americans, Asians, and Native Americans than in Caucasians. [37] No studies have been published concerning the relationship between genetics, ethnicity, and the pre-disposition to the progression of DNP in our population. The profile of our population probably does not correspond closely to those of the populations in the studies cited.

ESRD risk remains high among T1D patients despite the reinforcement provided by antihypertensive and renal protection treatments. The risk of ESRD per 100 person-years was 5.8 in the Joslin cohort and 5.1 in the FinnDiane cohort, which corresponded in the two studies to a mortality rate of 40%and 35%, respectively. [22],[23] Muhlhausser et al also found 34.8% of ESRD in diabetic patients with macroalbuminuria. [38] In Pittsburgh cohort (EDC), ESRD occurred in 24% of T1D patients with macroalbuminuria. [30] In Steno cohort, the risk of ESRD was only 17%. [39] In our study, 33.8% of T1D patients developed ESRD. This rate, which corresponds to findings in the literature, is rather surprising, since in our context, previous strict medical follow-up was almost absent and there was much difficulty in achieving optimal glycemic and blood pressure control, related to the low socioeconomic level of our population.

About 19.4% of patients had ESRD at the time of entry to the study, which attests to the great delay in diagnosis and management of DNP in T1D. 18.6% (11 cases) of patients developed ESRD during follow-up, but those patients had already presented a low GFR and a high AER. In contrast, patients who did not develop ESRD had a normal GFR [109 (76-141) mL/min)] and a relatively low AER [95 (60-405) mg/24 h] at the time of entry, despite the absence of optimal glycemic and blood pressure control at admission and throughout the follow-up. This implies that the values of GFR and AER on the time of entry are important predictive factors for the progression from DNP to ESRD.

Mortality in T1D remains high in ESRD patients, mainly among those in ESRD requiring dialysis. In Joslin clinic cohort, 42% mortality was found in ESRD patients under dialysis and 70% mortality in ESRD patients without dialysis, and the ten-year cumulative mortality after the onset of ESRD was 56.6%. [23] In this cohort, 69% of deaths were attributable to cardiovascular disease. Mortality was 31% and 29.1%, respectively, in T1D patients with ESRD requiring dialysis in FinnDiane cohort and Muhlhauser et al's study. [22],[38] In our study, death occurred in 52% of T1D patients with ESRD requiring dialysis, and the median duration of dialysis was only six [1],60 months.

Socioeconomic status has been identified as an important predictor for prognosis in T1D in several studies. [40],[41] To a great extent, our results can also be attributed to the low socio-economic level of our patients, as shown by the lack of health care coverage in 90.2%. This low socioeconomic level hinders patients' access to health care and treatments.

In Joslin clinic cohort, mortality rate was only 1% in type-1 diabetic patients in ESRD who had benefited from preemptive kidney transplant. In our study, no patient received a kidney transplant. This was due to the lack of health care coverage and not because of the unfeasibility of performing the double-kidney and pancreas transplant in Morocco. Renal and pancreatic transplantation performed preemptively remains the best treatment for type-1 diabetic patients in ESRD.

The exact pathogenesis of DNP is complex and not completely understood. This makes the medical management of DNP difficult and requires a multidisciplinary approach targeting control of all the factors that influence its progression. Optimal glycemic control by insulin therapy remains an essential objective in the management of patients with T1D. Renin-angiotensin system blockers and statins are widely prescribed and recommended for these patients even with subnormal arterial pressure and lipid profile. In addition, they permit the regression of microalbuminuria toward normoalbuminuria in T1D. [42],[43] Our first objective concerning our cohort of patients with T1D was to establish a strict medical follow-up system so as to optimize the medical treatment based on renin-angiotensin system blockers and statins and intensify glycemic and blood pressure control, in view of improving the renal and general prognosis of these patients.

After five years of evaluation, we are relatively satisfied with the results, since our rates of ESRD and mortality in patients with T1D are relatively similar to those in the literature. Also, having not developed ESRD and having survived, patients maintained stable GFR and AER at five years of evolution in relation to these rates at admission. However, several questions remain unanswered, such as the role of ethnicity, genetics, and environment in the physiopathology of DNP in our population. We hope to find answers through solid and validated studies over the course of coming years.

The limits of this study are the small size of the sample (72 patients) and the absence of a national and/or at least a regional register of type-1 diabetic patients. On the other hand, the low socioeconomic level of patients with T1D and the absence of health care coverage means that patients do not benefit in an optimal manner from the same therapeutic strategies.

T1D is a frequent pathology that involves a heavy burden of morbimortality. Blindness due to retinopathy, ESRD requiring dialysis resulting from the nephropathy, and mortality related to cardiovascular disease mean that T1D must be considered a serious pathology with very significant human and economic consequences. DNP is even more difficult to manage in developing countries, where patients are referred to nephrologists at a late stage of their disease. In this context, early detection of DNP is an important step in the treatment of these patients and the improvement of their prognosis.

Conflict of Interest

The authors declare that there is no conflict of interest associated with this manuscript.

 
   References Top

1.Mogensen CE, Christensen CK. Predicting diabetic nephropathy in insulin dependent patients. N Eng J Med 1984;311:89-93.  Back to cited text no. 1
[PUBMED]    
2.Krolewski AS, Kosinski EJ, Warram JH, et al. Magnitude and determinants of coronary artery disease in juvenile-onset insulin dependent diabetes mellitus. Am J Cardiol 1987;59:750-5.  Back to cited text no. 2
[PUBMED]    
3.Bruno RM, Gross JL. Prognostic factors in Brazilian diabetic patients starting dialysis: A 3.6-year follow-up study. J Diabetes Complications 2000;14:266-71.  Back to cited text no. 3
[PUBMED]    
4.Valmadrid CT, Klein R, Moss SE, Klein BE. The risk of cardiovascular disease mortality associated with microalbuminuria and gross proteinuria in persons with older-onset diabetes mellitus. Arch Intern Med 2000;160: 1093-100.  Back to cited text no. 4
[PUBMED]    
5.Collins AJ, Kasiske B, Herzog C, et al. Excerpts from the United States Renal Data System 2004 annual data report: Atlas of end-stage renal disease in the United States. Am J Kidney Dis 2005;45:A5-7.  Back to cited text no. 5
[PUBMED]    
6.USRDS TUSRDS. Annual Data Report. Bethesda: The National Institutes of Diabetes and Digestive and Kidney Diseases; 2005.  Back to cited text no. 6
    
7.Andersen AR, Christiansen JS, Andersen JK, Kreiner S, Deckert T. Diabetic nephropathy in type 1 (insulin-dependent) diabetes: An epidemiological study. Diabetologia 1983;25:496-501.  Back to cited text no. 7
[PUBMED]    
8.Krolewski AS, Warram JH, Christlieb AR, Busick EJ, Kahn CR. The changing natural history of nephropathy in type 1 diabetes. Am J Med 1987;78:785-94.  Back to cited text no. 8
    
9.Viberti GC, Hill RD, Jarrett RJ, Argyropoulos A, Mahmud U, Keen H. Microalbuminuria as a predictor of clinical nephropathy in insulin- dependent diabetes mellitus. Lancet 1982;1: 1430-2.  Back to cited text no. 9
[PUBMED]    
10.Mogensen CE. Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med 1984;310:356-60.  Back to cited text no. 10
[PUBMED]    
11.Jones CA, Krolewski AS, Rogus J, Xue JL, Collins A, Warram JH. Epidemic of end-stage renal disease in people with diabetes in the United States population: Do we know the cause? Kidney Int 2005;67:1684-91.  Back to cited text no. 11
[PUBMED]    
12.Parving HH. Diabetic nephropathy: Prevention and treatment. Kidney Int 2001;60:2041-55.  Back to cited text no. 12
[PUBMED]    
13.National Cholesterol Education Program (NCEP). Highlights of the report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents. Pediatrics 1992;89:495-501.   Back to cited text no. 13
    
14.Kavey RE, Daniels SR, Lauer RM, Atkins DL, Hayman LL, Taubert K; American Heart Association. American Heart Association guidelines for primary prevention of atherosclerotic cardiovascular disease beginning in childhood. J Pediatr 2003;142:368-72.  Back to cited text no. 14
[PUBMED]    
15.Orchard TJ, Dorman JS, Maser RE, et al. Prevalence of complications in IDDM by sex and duration. Pittsburgh Epidemiology of Diabetes Complications Study II. Diabetes 1990; 39:1116-24.  Back to cited text no. 15
[PUBMED]    
16.Hovind P, Tarnow L, Rossing P, et al. Predictors for the development of micro albuminuria and macroalbuminuria in patients with type 1 diabetes: inception cohort study. BMJ 2004;328:1105.  Back to cited text no. 16
[PUBMED]    
17.Perkins BA, Ficociello LH, Silva KH, et al. Regression of microalbuminuria in type 1 diabetes. N Engl J Med 2003;348:2285-93.  Back to cited text no. 17
[PUBMED]    
18.Giorgino F, Laviola L, Cavallo Perin P, et al. Factors associated with progression to macroalbuminuria in microalbuminuric Type 1 diabetic patients: The EURODIAB Prospective Complications Study. Diabetologia 2004;47: 1020-8.   Back to cited text no. 18
[PUBMED]    
19.Amin R, Widmer B, Prevost AT, et al. Risk of microalbuminuria and progression to macroalbuminuria in a cohort with childhood onset type 1 diabetes: Prospective observational study. BMJ 2008;336:697-701.  Back to cited text no. 19
[PUBMED]    
20.Raile K, Galler A, Hofer S, et al. Diabetic nephropathy in 27,805 children, adolescents, and adults with type 1 diabetes: Effect of diabetes duration, A1C, hypertension, dyslipidemia, diabetes onset, and sex. Diabetes Care 2007;30:2523-8.  Back to cited text no. 20
[PUBMED]    
21.Perkins BA, Krolewski AS. Early Nephropathy in type 1 diabetes: the importance of early renal function decline. Curr Opin Nephrol Hypertens 2009;18:233-40.  Back to cited text no. 21
[PUBMED]    
22.Forsblom C, Harjutsalo V, Thorn LM, et al. Competing-Risk Analysis of ESRD and Death among patients with type 1 diabetes and macro albuminuria. J Am Soc Nephrol 2011;22:537-44.  Back to cited text no. 22
[PUBMED]    
23.Rosolowsky ET, Skupien J, Smiles AM, et al. Risk for ESRD in type 1 Diabetes remains High despite renoprotection. J Am Soc Nephrol 2011;22:545-53.  Back to cited text no. 23
[PUBMED]    
24.Lachin JM, Genuth S, Nathan DM, Zinman B, Rutledge BN. The effect of glycemic exposure on the risk of microvascular complications in the diabetes control and complications trial: Revisited. Diabetes 2008;57:995-1001.  Back to cited text no. 24
    
25.Lurbe E, Redon J, Kesani A, et al. Increase in nocturnal blood pressure and progression to microalbuminuria in type 1 diabetes. N Engl J Med 2002;347:797-805.  Back to cited text no. 25
[PUBMED]    
26.Roy MS, Affouf M. Six-year progression of retinopathy and associated risk factors in African American patients with type 1 diabetes mellitus: The New Jersey 725. Arch Ophthalmol 2006;124:1297-306.  Back to cited text no. 26
[PUBMED]    
27.Roy MS. Proteinuria in African Americans with type 1 diabetes. J Diabetes Complications 2004;18:69-77.   Back to cited text no. 27
[PUBMED]    
28.Roy MS, Peng B, Roy A. Risk factors for coronary disease and stroke in previously hospitalized African-Americans with type 1 diabetes: A 6 year follow up. Diabet Med 2007;24:1361-8.  Back to cited text no. 28
[PUBMED]    
29.Adler AI, Stratton IM, Neil HA, et al: Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): Prospective observational study. BMJ 2000;321:412-9.  Back to cited text no. 29
    
30.Costacou T, Ellis D, Fried L, Orchard TJ. Sequence of progression of albuminuria and decreased GFR in persons with type 1 diabetes: A cohort study. Am J Kidney Dis 2007;50:721-32.  Back to cited text no. 30
[PUBMED]    
31.Hovind P, Rossing P, Tarnow L, Parving HH. Smoking and progression of diabetic nephropathy in type 1 diabetes. Diabetes Care 2003; 26:911-6.  Back to cited text no. 31
[PUBMED]    
32.Durrington PN. Diabetic dyslipidaemia. Baillieres Best Pract Res Clin Endocrinol Metab 1999; 13:265-78.  Back to cited text no. 32
[PUBMED]    
33.Chaturvedi N, Fuller JH, Taskinen MR. Differing associations of lipid and lipoprotein disturbances with the macrovascular and microvascular complications of type 1 diabetes. Diabetes Care 2001;24:2071-7.  Back to cited text no. 33
    
34.Mulec H, Johnsen SA, Wiklund O, Bjorck S. Cholesterol: A renal risk factor in diabetic nephropathy? Am J Kidney Dis 1993;22:196-201.  Back to cited text no. 34
    
35.Kearney PM, Blackwell L, Collins R, et al. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: A meta-analysis. Lancet 2008; 371:117-25.  Back to cited text no. 35
[PUBMED]    
36.Colhoun HM, Betteridge DJ, Durrington PN, et al. Effects of atorvastatin on kidney outcomes and cardiovascular disease in with diabetes: An analysis from the Collaborative Atorvastatin Diabetes Study (CARDS). Am J Kidney Dis 2009;54:810-9.  Back to cited text no. 36
[PUBMED]    
37.U.S. Renal Data System, USRDS 2003 Annual Data Report: Atlas of End-Stage Renal Disease in the United States, National Institute of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2003.  Back to cited text no. 37
    
38.Muhlhauser I, Overmann H, Bender R, Jorgens V, Berger M. Predictors of mortality and end stage diabetic complications in patients with type 1 diabetes mellitus on intensified insulin therapy. Diabet Med 2000;17:727-34.  Back to cited text no. 38
    
39.Jorsal A, Tarnow L, Flyvbjerg A, Parving HH, Rossing P, Rasmussen LM. Plasma osteoprotegerin levels predict cardiovascular and all-cause mortality and deterioration of kidney function in type 1 diabetic patients with nephropathy. Diabetologia 2008;51:2100-7.  Back to cited text no. 39
[PUBMED]    
40.Buhlhauser I, Overmann H, Bender R, et al. Social statut and the quality of care for adult people with type 1 diabetes mellitus- a population based study. Diabetologia 1998;41:-1139-50.  Back to cited text no. 40
    
41.Robinson N, Lyod CE, Stevens LK. Social deprivation and mortality in adults with diabetes mellitus. Diabet Med 1998;15:205-12.   Back to cited text no. 41
    
42.Randomised placebo-controlled trial of lisinopril in normotensive patients with insulin-dependent diabetes and normoalbuminuria or microalbuminuria. The EUCLID Study Group. Lancet 1997;349:1787-92.  Back to cited text no. 42
[PUBMED]    
43.Douglas K, O'Malley PG, Jackson JL. Metaanalysis: The effects of statins on albuminuria. Ann Intern Med 2006;145:117-24.  Back to cited text no. 43
[PUBMED]    

Top
Correspondence Address:
Yassamine Bentata
Department of Nephrology, Medical School, University Mohamed First Oujda, Oujda
Morocco
Login to access the Email id


DOI: 10.4103/1319-2442.109617

PMID: 23538374

Get Permissions



    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]

This article has been cited by
1 Is regenerative medicine a new hope for kidney replacement?
Maciej Nowacki,Tomasz Kloskowski,Marta Pokrywczynska,Lukasz Nazarewski,Arkadiusz Jundzill,Katarzyna Pietkun,Dominik Tyloch,Marta Rasmus,Karolina Warda,Samy L. Habib,Tomasz Drewa
Journal of Artificial Organs. 2014; 17(2): 123
[Pubmed]
2 Microalbuminuria and glycated hemoglobin in children with type 1 diabetes mellitus
Magdy A. Omar,Moustafa M. Rezk,Ahmed A. El-Kafoury,Marwa S. Kandil
Alexandria Journal of Medicine. 2014;
[Pubmed]



 

Top
   
 
 
    Similar in PUBMED
    Search Pubmed for
    Search in Google Scholar for
    Email Alert *
    Add to My List *
* Registration required (free)  
 


 
    Abstract
   Introduction
    Materials and Me...
   Statistical Analysis
   Results
   Discussion
    References
    Article Figures
    Article Tables
 

 Article Access Statistics
    Viewed1057    
    Printed20    
    Emailed0    
    PDF Downloaded307    
    Comments [Add]    
    Cited by others 2    

Recommend this journal