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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 2009  |  Volume : 20  |  Issue : 1  |  Page : 77-85
Microvascular and macrovascular complications in diabetic nephropathy patients referred to nephrology clinic


Division of Nephrology, Department of Medicine, King Saud University Riyadh, Saudi Arabia

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   Abstract 

To evaluate the diabetic complications and fate of diabetic nephropathy in Saudi population, we studied 184 diabetic nephropathy (DN) patients who were referred to nephrology clinic of King Khalid University Hospital, Riyadh, Saudi Arabia from January 2003-June 2006. The patients had mean age of 61.9 ± 13.1 years, included 128 (69.6%) males, and were followed up for a mean period of 10.2 ± 1.5 years. The mean duration of diabetes mellitus (DM) was 19.5 ± 5.8 years, and duration of nephropathy was 7.7 ± 3.3 years. Family history of DN was documented in 52 (28.2%) patients. At initial visit, the mean systolic blood pressure was 164 ± 14.5 mmHg, the mean diastolic blood pressure was 97.9 ± 10.4 mmHg. Thirty­seven (20%) patients had normal BMI, 88 (48%) were overweight, while 55 (30%) were obese. Mean creatinine clearance was 51.7 ± 26.3 mL/min, 24 hrs urinary proteins 1.99 ± 2.48 gm/day, HbA1C 9.2 ± 1.8 %, triglyceride 2.1 ± 1.3 mmol/L, and cholesterol 5.17 ± 1.54 mmol/L. Diabetic complications included angiography proven coronary artery disease in 106 (57.6 %) patients, stroke in 21 (11.4%), myocardial infarction (MI) in 27(14.6%), angina in 87 (47.2 %), retinopathy in 82 (44.5%), Blindness in 3 (1.6%), peripheral vascular disease in 121 (65.7%), Neuropathy in 123 (66.8%), hypertension in178 (96.7%), diabetic foot in 25 (13.5%), Amputation in 10 (5.4%), and end-stage renal disease in 70 (38%). Total of 13 (7.05%) patients died in the hospital. Thirty-seven percent of patients developed > 6 concomitant complications. 28% developed 5, 17% developed 4, and the rest developed < 3. DN was relatively refractory to therapy and progressive; 123 (66.8%) patients doubled their serum creatinine in 3.59 ± 2.88 years, 32 (17.3%) maintained stable renal function, 136 (73.6 %) deteriorated, and 12 (6.52%) improved. we conclude that the prevalence of diabetic complications is high among Saudi patients, and many had multiple complications. Baseline creatinine clearance and proteinuria, high systolic blood pressure, advanced age, and longer duration of diabetes were the most significant risk factors for developing complications.

Keywords: Diabetic nephropathy, Diabetic complications, ESRD, Retinopathy, Neuropathy, Diabetic foot, Coronary artery disease

How to cite this article:
Al-Wakeel JS, Hammad D, Al Suwaida A, Mitwalli A H, Memon NA, Sulimani F. Microvascular and macrovascular complications in diabetic nephropathy patients referred to nephrology clinic. Saudi J Kidney Dis Transpl 2009;20:77-85

How to cite this URL:
Al-Wakeel JS, Hammad D, Al Suwaida A, Mitwalli A H, Memon NA, Sulimani F. Microvascular and macrovascular complications in diabetic nephropathy patients referred to nephrology clinic. Saudi J Kidney Dis Transpl [serial online] 2009 [cited 2019 Nov 13];20:77-85. Available from: http://www.sjkdt.org/text.asp?2009/20/1/77/44710

   Introduction Top


Diabetic nephropathy is the leading cause of end stage renal disease (ESRD), [1],[2],[3],[4] diabetic pa­tients with diabetic nephropathy (DN) are at higher risk of fatal and non fatal cardiovascular and other complications. [5],[6],[7],[8] Not only stroke and myocardial infarction but retinopathy and peri­pheral vascular disease have correlation with DN, [9],[10],[11],[12],[13],[14],[15] which has a genetic and racial predis­position, [16],[17],[18] while environmental and bioche­mical factors trigger the genetically prone indi­viduals. Increasing modernization with seden­tary life style and lack of physical activity is favoring increased incidence of obesity, dia­betes and its complications. [19] In a recent report from U.S.A. released in April 2007 the impor­tance of quantification of diabetic complica­tions was emphasized. [20]

In Saudi Arabia, trends of diabetes and dia­betic nephropathy are increasing tremendously. Al Wakeel et al reported diabetic nephropathy to be the leading cause of Chronic renal failure (CRF). [1],[7],[21],[22] The incidence of DN signals a medical catastrophe in dialysis units in ESRD patients whose original kidney disease is DN in addition to consumption of economic re­sources. [22] Management of diabetes is a natio­nal issue, and a reassessment besides urgent action is needed.

Studies on diabetic complications conducted in Saudi Arabia are very few. In 1995, Huraib et al have addressed the pattern of DN in the region. While Al Khader [22] followed 28 diabe­tic nephropathy patients and reported the out­come that 42.8% became dialysis dependent and similar percentage doubled their serum creatinine. There is no recent systematic and detailed report on diabetic complications with reference to DN in Saudi population, and this is the first comprehensive study report from this region.


   Patients and Methods Top


Present study is a cross sectional retrospect­tive study of patients referred to nephrology clinic of King Khalid University Hospital, a tertiary hospital in Riyadh-Saudi Arabia, from Jan 2003-June 2006. Eligible patients screened were clinically diagnosed DN patients accor­ding to World Health Organization (WHO) criteria. [10] There were 184 diabetic nephro­pathy patients included in the study.

Demographics and patients' height and weight were recorded, and body mass index (BMI) was calculated.

Blood investigations included blood glucose, HbA1C, cholesterol, Triglycerides (TG), serum creatinine, creatinine clearance, and24-hour uri­nary protein.

Glomerular filtration rate (GFR) was calcu­lated using Kockroft and Gualt equation:

GFR= (140-Age (yrs) × Weight (kg) × 1.23/Serum Creatinine µmol (for males)

GFR= (140-Age (yrs) × Weight (kg) × 1.02/Serum Creatinine µmol (for females)

Rate of change of GFR was calculated. Renal function was considered to be stable if yearly change of GFR was 1-2.5 mL, and it was con­sidered deteriorated if yearly decrease of GFR was > 2.5 mL. While renal function was consi­dered improved if yearly change of GFR was < 1 mL. Duration of follow-up, age at onset of diabetes, duration of complications, time for doubling of serum creatinine, and ESRD were recorded. Time course of all the above para­meters were followed up carefully.

The target levels definitions were based on the guidelines of the American Diabetic Asso­ciation, European Society of Hypertension, European Society of cardiology, the following recommended target levels were adopted: < 135/85 mmHg for blood pressure,< 7 % for HbA1C, < 1.4 mmol/L of TG, [14] and < 5.2 mmol/ L for cholesterol.


   Statistical Analysis Top


SPSS for Windows Version 11 statistical pa­ckage was used for analysis. ANOVA, Pear­son's Correlation, followed by Regression ana­lysis were performed as required. P value of < 0.05 was considered statistically significant.


   Results Top


Of 184 diabetic nephropathy patients included in the study, 128 (69.6 %) were males patients, and mean age at the enrolment was 61.97 ± 13.1 years, (range, 19-85 years). The mean age for onset of diabetes was 42.4 ± 12.1 years with the (range, 6-68 years) .The mean duration of diabetes was 19.5 ± 5.8 years (range, 6-40 years), the mean follow-up in our hospital was 10.2 ± 1.5 years, and the mean age at the onset of nephropathy was 54.3 ± 12.5 years (range, 15-83 years). The mean duration of nephro­pathy was 7.7 ± 3.3 years (range, 2-14years). Family history of diabetic nephropathy was documented in 52 (39.6%) patients, and there were 6 (3.3%) active smokers in the study patients.

Body Mass Index (kg/m 2 )

At the initial visit, BMI normal (18.5-25) in only 37 (20%) patients 88 (8%) patients were overweight (BMI 25.1-30), 55 (30%) patients were obese (BMI 30.1-40), and only 3 (1.6%) patients were underweight. At the last visit, 2 (1%) patients were underweight, 34 (18.4%) patients remained stable, 80 (43.4%) patients were overweight, while 65 (33%) patients were obese (trend toward more weight gain).

Blood Pressure

At the initial visit, only 2 (1.1%) patients had the recommended systolic blood pressure (SBP) < 135 mmHg, while 182 (98.9%) had elevated SBP including 92 (50%) patients who had SBP between 135-160 mmHg, 82 (44.6%) between 160-190 mmHg, and 6 (3.3%) > 190 mmHg. At the last visit, 76 (41.3%) patients attained the recommended target level of SBP < 135 mmHg, (p= 0.0000), 86 (46.7%) between 135­160 mmHg, 18 (9.8%) between 160-190 mmHg, and 1 (0.5%) > 190 mmHg.

Regarding the diastolic blood pressure (DBP), at the initial visit, 62 (33.7%) patients had the recommended DBP < 85 mmHg, 70 (38%) between 85-90 mmHg, 35 (19%) between 90­100 mmHg, and 14 (7.6%) > 100 mmHg. At the last visit, 142 (77.2 %) patients had DBP < 85 mmHg, p= 0.0000, 33 (17.9%) between 85­90 mmHg, 5 (2.7%) between 90-100 mmHg, and 2 (1.1%) > 100 mmHg.

Prevalence of Health Complications in Diabetic Nephropathy Patients

[Figure 1] and [Table 1] show the prevalence and frequencies of the associated complications in the DN Patients. The most common complica­tion was hypertension (HTN) in 178 (96.7%) patients followed by neuropathy in 124 (67.3%), angiography proven coronary artery disease (CAD) in 106 (57.6%), and peripheral vascular disease (PVD) in 121 (65.7%) patients, and diabetic retinopathy in 82 (44.6%).

Kidney failure was frequent and 70 (38.0%) patients advanced to ESRD, and 13 (7.2%) deaths occurred in the hospital.

The mean time to onset of diabetic com­plications from the diagnosis of diabetes in our study patients was8.9 ± 4.9 years for CAD, 16.4 ± 5.9 years for PVD, 2.52 ± 1.3yrs for retinopathy, 11.7 ± 4.7 years for neuropathy, and 5.4 ± 2.36 years for diabetic foot. In addi­tion, it took 20-25years for amputations after diabetes was diagnosed, 3-22 years for blind­ness, and > 25 years for ESRD.

Prevalence of multiple health complications in DN patients

[Figure 2] shows the frequency of multiple complications in our study patients. Only (1%) of the patients had 1 concomitant complica­tion, 5% had 2, 11% had 3, 17% had 4, 28% had 5, and 37% patients had > 6 and more complications. Reduced Creatinine clearance at base line had impact on the future develop­ment of health complications in DN patients.

In the present study a significant correlation was found between baseline creatinine clea­rance and coronary artery disease (r=-0.15, p = 0.04), neuropathy (r=-.194, p = .01), hyperten­sion (r=-.193, p = 0.01), ESRD (r=-.274, p = 0.005), and Death (r=-.168, p = 0.028),[Table 2].

Changes in the serum creatinine during follow­up

In the present study, there was a constant deterioration of renal function of the patients over time. The mean serum creatinine in­creased from 138 ± 91.0 µmol/L at the base­line to 175 ± 111 µmol/L in 12 months, 218 ± 141 µmol/L in 24 months, 259 ± 165 µmol/L in 3 years, 289 ± 176 µmol/L in 4 years, 361± 245 µmol/L in 5 years, 390 ± 274 µmol/L, in 10 years, 431 ± 300 µmol/L in 15 years, and 441 ± 325 µmol/L at last follow-up.

Patterns of change of serum creatinine at baseline and at last follow-up

A total of 80 (43.5%) patients had serum creatinine < 110 µmol/L, 39 (21.2%) between 110-140 µmol/L, 17 (9.2%) between 141-165 µmol/L, 35 (19%) between 166-220 µmol/L, and 12 (6.5%) > 220 µmol/L. At the last visit 68.5% of patients had their serum creatinine > 220 µmol/L, [Table 3].

Percent of change and doubling of serum creatinine in DN Patients

There were 123 (67 %) patients who doubled serum creatinine after 3.95 ± 2.88 years of follow-up. However, time to doubling was significantly (p=< .05) influenced by certain fac­tors such as initial creatinine clearance (r=0.58, p=0.000), baseline proteinuria (r=- 0.36, p= 0.004), baseline serum creatinine (r=0.334, p= 0.000), age at the onset of diabetes (r=-0.264, p= 0.000), advance age of the patients (r=­0.234, p= 0.001), SBP (r=0.239, p= 0.001), TG (r= 0.171 p= .026), [Table 4].

Time course of creatinine clearance in DN patients

In the present study FN patients showed a continued decline in renal function the crea­tinine clearance (ml/min) deteriorated gradua­lly from 51.7 ± 26.3 at the base line to 41.7 ± 23.2 in 1 year, 33.4 ± 21.5 in 2 years, 26.5 ± 24.3 in 3 years, 26.0 ± 26.2 in 4 years, 25.8 ± 26.2 in 5 years, and further reduced to 20.1 ± 17.1 in 10 years, and 24.8 ± 28.1 at the last follow-up.

Patterns of GFR

There were 19 (10 %) patients who had GFR < 30 mL/min, 78 (43.8%) between 31-60 mL/ min, 41 (23%) between 61-89 mL/min, and 40 (22.4%) > 90 mL/min. A total of 12 (6.5%) patients improved their GFR, 32 (17.7%) re­mained stable, and 134 (72.8%) deteriorated their GFR. A total of 70 (68.6%) patients developed ESRD; 53 (28.8%) males and 17 (9.2%) females.

Baseline health status was detrimental in present study for renal outcome. Baseline crea­tinine clearance (r=0.58, p= 0.000), 24-hour urinary protein (r=-0.36, p= 0.004), Base line serum creatinine (r=-0.334, p= 0.000), age at the onset of diabetes (r=-0.264, p= 0.000), high systolic blood pressure (r=-0.239, p= 0.001), age (r=-0.234, p= 0.001), TG (r= -0.17, p= 0.001) were had a statistically significant correlation with poor renal outcome and ESRD, [Table 5].

24-hour urinary proteins in DN patients

The mean proteinuria in our DN patients (gm/24 hrs) was 1.99 ± 2.5 gm/L (Range 0.02­22.1) at baseline. Protein excretion < 0.5 was found in 55 (29.9%) patients, between 0.5-3 in 90 (48.9%), > 3 in 39 (21.1%). At the last visit, protein excretion of < 0.5 was found in 32 (17.4%) patients, between 0.5-3 in 105 (57.1%), >3 in 47 (25.5%). Thus number of the patients with lower range (< 0.5) of proteinuria were reduced from 55 (29.9%) at baseline to 32 (17.4%) at the last visit, p= 0.04. Similarly, the number of the patients with proteinuria > 3 gm/24hrs increased from 39 (21.1%) at base­line to 47 (25.5%) at the last visit, however, the change was not statistically significant.

Other laboratory investigations

The mean HbA1C was 9.2 ± 1.8 % (Range 5.4-15.9) at base line and 8.93 ± 2.08 % (6.5­12.5) at the last visit.

The mean cholesterol was 5.17 ± 1.5 mmol/L (range 2.2-11.9 mmol/L) at baseline versus 4.22 ± 1.1 mmol/L (1.4-9.9) at the last visit. Hyper­cholesteremia was reported in 152 (82.6%) patients at base line. At the initial visit, there were 102 (55.4%) patients who had cholesterol < 5.2 mmol/L; 70 (38%) patients were on statins. At the last visit, 159 (86.4%) patients had serum cholesterol < 5.2mmol/L; 116 (63%) pa­tients were on statins. There were 25 (13.5%) patients who had serum cholesterol > 5.2 mmol/L at the last visit in comparison with 82 (44.6%) at base line (p= 0.000).

TG were elevated in patients with DN at the initial visit. Only 14 (7.6%) patients had tar­geted recommended TG, 86 (47%) between 1­2 mmol/L, 41 (22%) between 2.01-3 mmol/L, and 43 (23.4%) > 3 mmol/L. The mean TG at the baseline was 2.1 ± 1.33 mmol/L. TG levels improved significantly at the last visit (p< 0 05) At the last visit, 22 (12%) patients had TG < 1 mmol/L, 123 (66.8%) between 1-2 mmol/L, 27 (14.7%) between 2.01-3 mmol/L, and 12 (6.5%) > 3 mmol/L.


   Discussion Top


The present study is by far the biggest com­prehensive overview and recent insight on the diabetic complications present in diabetic nep­hropathy patients. It reveals that the Saudi population has aggressive course of diabetic nephropathy and other health complications than western world. Multiple complications were present in both male and females As many as more than six complications were present in some of the individuals. Similar multiple com­plications were also reported by Mitka et al. [20]

CAD is a quite serious complication that affects a great majority (57.6%) of patients with DN, especially in the older age group. Incidence of CAD is lower in western coun­tries being 25% in patients 45-59 yrs of age in a study from Finland, [23] and 9.1% in USA, [20] than 57.6% in the present study, which may be attributed to DN, high serum creatinine, die­tary preferences favoring dyslipedemia, and sedentary life style.

Diabetic retinopathy was present in 82 (47.8%) in our study and complete loss of vision was found in 3 (1.6%) patients. Prevalence of reti­nopathy among Saudi patients with diabetes was reported previously as 31%. [24] Similar fin­dings were reported by some other studies. [25],[26],[27],[28] another study from Saudi Arabia emphasized that presence of retinopathy could predict other diabetes complications. [28] In 2002, 11.5% pre­valence of retinopathy in was reported in Saudi diabetic patients including both types of diabetes. [29]

The prevalence of neuropathy in the present study was 67.3%, and there was no significant gender difference. A similar high rate of dia­betic neuropathy was reported in western pro­vinces of Saudi Arabia in 2000. [30],[31],[32] Prevalence of painful diabetic neuropathy was 26.4% as reported by Davies et al et al from UK in 2006. [33]

In the present study, problems of lower extre­mities were in 25 (13.6 %) patients. However, there was a trend of improvement in the dia­betic foot disease, and the percentage in the present study was much less than that reported from Saudi Arabia in year 2000(23.5%), [34],[35] and from USA (22.8%). [20]

In the present study the prevalence of HTN (96.7%) was high compared to previous reports in which prevalence of hypertension was 25% [36] and 62.6%. [6]

Susceptibility for diabetic complications varies from one ethnic to another, and also from one individual to another. [16],[17],[18] For instance black Hispanics and Pima Indians are more suscep­tible for diabetic complication than white Ame­ricans. [37] Such differences might be present with other races, necessitating research in diffe­rent races to pool the data for future reforms and special care of high risk groups. The pre­sent study reveals that the Saudi population has progressive and aggressive course of DN, indicating and anticipating a future burden on dialysis units. A similar aggressive course is reported in Pima tribes. [37] The peak incidence of diabetic nephropathy was present between 50 to70 yrs of age. The mean age of the onset of diabetes is early and the majority have dia­betes in their forties.

Large number of patients presented at the time of start of the study without recommen­ded target levels of blood pressure, cholesterol, TG, serum creatinine, or urinary protein. Du­ring the study, strict medical control of cho­lesterol, triglyceride, and blood pressure were attained in the vast majority, but renal function was refractory to the treatment in DN patients who progressed to ESRD. Time to doubling of serum creatinine was significantly influenced by certain factors such as initial creatinine clearance, base line proteinuria, baseline serum creatinine, age at the onset of diabetes, age of the patient, SBP, and TG. The incidence of ESRD in the present study was 70 (38%) as compared to 27.8% in USA. [20] In another study from the region reported an incidence of 43% ESRD. Only 15 % patients had stable course of DN, indicating an alarming fast progression of DN in Saudi population. [22]

Mortality was low (7.2%) in the present study as compared to other studies, since we have reported only those deaths that occurred in the hospital and did not include the mortality at home.

Finally, the world is facing a huge epidemic of diabetes and its complications consuming health resources and compelling to recognize the problem and galvanize action for the bene­fit of people. In 2007, a report from USA esti­mated the total direct costs spent on diabetes complications as 57 billion US dollars yearly. [20] Heart attack costs $ 14150 per person followed by chronic kidney disease $ 9002 per person, foot problems $ 4687 per person, and eye da­mage $ 1,785 per person. [20] In addition, there are added costs attributed to lost employment, lost productivity, disability and premature death of earning head of the family. [20]

We conclude that DN in Saudi population is aggressive. Patients are having high prevalence of diabetic complications, multiple complica­tions are frequent, and cardiovascular compli­cations are very high. Progression to chronic renal failure and ESRD is fast. Age, male gender, duration of diabetes, baseline HbA1C, systolic blood pressure, and renal function are risk factors for renal outcome and diabetic complications. Frequent screenings in addition to tight glycemic, lipid, and blood pressure control may be helpful. Saudi males are at a higher risk of having retinopathy, diabetic foot, amputation, and CAD, which should be studied further in future.

 
   References Top

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Correspondence Address:
Jamal S Al-Wakeel
Nephrology Unit, Department of Medicine, King Khalid University Hospital, King Saud University, Riyadh
Saudi Arabia
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    Figures

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    Tables

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2 Complications and characteristics of patients referred to a joint diabetes renal clinic in Ireland
Thabit, H. and Besharatian, B. and Conlon, P.J. and Smith, D.
Irish Journal of Medical Science. 2012; 181(4): 549-553
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3 Risk factors of diabetic foot in central Saudi Arabia
Abolfotouh, M.A. and Alfaif, S.A. and Al-Gannas, A.S.
Saudi Medical Journal. 2011; 32(7): 708-713
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4 Relationship between the severity of albuminuria and vibration perception threshold in patients with type 2 diabetics
Shen, J. and Liu, F. and Zeng, H. and Yu, J. and Li, Q. and Zhang, F. and Bao, Y.-Q. and Jia, W.-P.
Fudan University Journal of Medical Sciences. 2011; 38(3): 251-256
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5 Role of endothelin receptor A and NADPH oxidase in vascular abnormalities
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Vascular Health and Risk Management. 2010; 6(1): 787-794
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6 Protective effects of HMG-CoA reducase inhibitor atorvastatin on nephridial tissues of diabetic rats and its related mechanism
Zhao, X.-L. and Xu, W.-W. and Jiang, G.-P. and Liu, X.-I. and Fang, J.
Journal of Xięan Jiaotong University (Medical Sciences). 2010; 31(4): 459-462
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7 Epidemiology of diabetes mellitus and diabetic foot problems in Saudi Arabia
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Avances en Diabetologia. 2010; 26(1): 29-35
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8 Chronic complications of diabetes in Iraq: Experience from Southern Iraq
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    Abstract
    Introduction
    Patients and Methods
    Statistical Analysis
    Results
    Discussion
    References
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