QJM Advance Access originally published online on February 23, 2006
QJM 2006 99(3):153-160; doi:10.1093/qjmed/hcl016
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
The joint diabetic-renal clinic in clinical practice: 10 years of data from a District General Hospital
From the Departments of 1Diabetes and Endocrinology, 2Clinical Audit, and 3Renal Medicine, Cumberland Infirmary, Carlisle, UK
Address correspondence to Dr M. Jayapaul, Floor 4, William Leech Building, School of Clinical Medical Sciences, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH. email: m.k.jayapaul{at}ncl.ac.uk
Received 23 September 2005 and in revised form 22 January 2006
 |
Summary |
|---|
 Top Summary IntroductionMethodsResultsDiscussionReferences |
|---|
Background: Diabetic nephropathy is the leading cause of end-stage renal failure. Untreated, it causes continuous decline in glomerular function, worsening hypertension and a marked increase in cardiovascular risk. Joint diabetic-renal clinics were established to address these factors and prepare patients for renal replacement therapy.
Aim: To determine whether our joint diabetic-renal clinic influenced progression of renal disease, and whether we were able to achieve targets from clinical trials and guidelines in routine practice.
Design: Retrospective review.
Methods: We collected data using clinical notes and electronic records for 130 patients attending the clinic over 10 years.
Results: Our patients had 62% type 2 and 38% type 1 diabetes. Mean duration of diabetes was 24 years for type 1 and 11 years for type 2 diabetes. At referral, 56% had evidence of vascular disease and 45%, proliferative retinopathy. Baseline median creatinine was 124 µmol/l. Significant improvements were made in systolic BP, diastolic BP and cholesterol (p < 0.001), compared to measurements at presentation. We analysed progression of renal disease by linear regression on 45 patients who had follow-up data for 3 years. Rate of decline of GFR was significantly reduced from 1.09 ml/min/month in the first year to 0.39 ml/min/month in the third year, (p < 0.004).
Discussion: Our findings suggest that the rate of deterioration of renal function can be reduced by aggressive management of risk factors. Joint diabetic-renal clinics appear to be useful in achieving targets in routine clinical practice.
|
Introduction |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Diabetic nephropathy (DN) is the leading cause of end-stage renal failure (ESRF) in patients beginning renal replacement therapy (RRT) in the developed world.12 It has been widely accepted that 30% of all diabetic patients develop nephropathy after 30 years of diabetes, but one recent study in type 1 diabetic subjects noted a reduced incidence of 7.8% at 30 years after diagnosis.3 Only a small proportion of these patients reach ESRF, because of premature cardiovascular disease, especially in type 2 diabetes. Untreated diabetic nephropathy is characterized by a progressive decline in glomerular filtration rate (GFR), worsening hypertension and a marked increase in cardiovascular risk.4 Well-controlled blood pressure, treatment of dyslipidaemia and hyperglycaemia, angiotensin-converting enzyme (ACE) inhibition, smoking cessation and reduced dietary protein intake all reduce the rate of progression to ESRF.5–14
Management of these patients with multiple co-morbid factors is challenging in a routine out-patient setting, and hence a multidisciplinary approach has been advocated. The St Vincent's declaration (1992) set down guidelines for the prevention and treatment of diabetic nephropathy,15 and this was followed by the Scottish Intercollegiate Guidelines Network (SIGN) guidelines in 1997 and 2001 (No. 55), and National Institute for Clinical Excellence (NICE) guidelines in 2002.16,17 However, patient education, support and motivation are fundamental to achieving a successful long-term outcome.18 In view of these factors, joint diabetic-renal clinics were set-up in an attempt to reduce the rate of progression to ESRF, with aggressive management of cardiovascular risk and other complications, and prepare patients for renal replacement therapy. Although these clinics help to achieve blood pressure targets, there is little published evidence that they affect the progression of renal disease.
Liew et al. studied patients referred to a joint clinic in a tertiary referral hospital, and found that the time to ESRF was increased by an average of 2 years.19 Joss et al. from the same group studied 170 consecutive patients referred from six different diabetic units, and found that patients who were referred early benefited the most from the clinic, and the rate of decline was slowed from 0.52 ml/min/month in the first year to 0.27 ml/min/month in the third year.20 No longitudinal data have been published on patients attending a joint clinic in a district general hospital, providing secondary care for a single population. Cross-sectional studies and drug trials may be helpful in identifying metabolic defects and effectiveness of new therapeutic interventions, but only longitudinal studies are helpful in understanding the nature and progression of a chronic disease such as diabetic nephropathy.
We studied all patients attending the Joint Diabetic-Renal Clinic in our District General Hospital, in Carlisle, UK, established in 1991. This study has the advantage that most of the patients with diabetic nephropathy in our catchment area were being referred directly to this clinic. In addition, at the outset, most patients were already attending separate diabetic or renal clinics, and so duplicating sometimes quite long journeys from home. We present data retrospectively collected on all patients who attended the Joint Diabetic Renal Clinic for at least two consecutive visits in the last 10 years. Our aim was to determine whether targets from clinical trials and guidelines could be achieved through a joint diabetic renal clinic in a District General Hospital, and whether management of this type influenced progression of diabetic renal disease.
|
Methods |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Data on all patients attending the combined Diabetic-Renal Clinic on at least two consecutive occasions during a 10-year period were collected retrospectively. Patients were referred to the combined clinic from diabetic, renal and general medical clinics, and directly from general practices. The patients were seen by a nephrologist and diabetologist separately during each clinic visit, supported by a diabetic specialist nurse, renal dietician and podiatrist. Patients were seen 3-, 6- or 12-monthly, depending on clinical need. Regularly updated local guidelines based on current evidence were used as targets at the clinic. These were revised regularly in line with published studies, and recommendations were circulated to all General Practitioners, supported by discussion meetings and clinical presentations.
Diabetic nephropathy was defined as the presence of persistent proteinuria with an albumin excretion rate >300 mg/day in a patients with diabetes but no evidence of any other renal disease. Demographic and laboratory data were collected from medical notes and electronic patient records. Data at referral and subsequent 6-month and yearly visits were noted: source of referral, type and duration of diabetes, history of ischaemic heart disease, cerebrovascular disease, peripheral vascular disease, hypercholesterolemia, hypertension, smoking history and presence of retinopathy. Anti-hypertensive, lipid-lowering and glucose-lowering drugs were recorded. Estimated creatinine clearance was calculated using the Cockcroft and Gault formula from serum creatinine measured during or just before the clinic visit.21 The rate of decline in renal function was calculated by linear regression from the slope of the plot of creatinine clearance vs. time, expressed in ml/min/month. A minimum of three readings for each 12-month period was used to draw the slope and hence estimate the rate of decline in renal function. Proteinuria was measured using 24-h urine collections done at home and sent to the local hospital laboratory. Levels of HbA1c, blood pressure, total cholesterol, proteinuria, smoking history, and use of ACE inhibitor drugs were noted at each visit. Blood pressure was measured after 5–10 min sitting, by a physician with a sphygmomanometer. It was rechecked by another physician in the clinic. Results are shown as means and SD or as median and IQR. The significance of difference for various parameters between the groups was determined using the unpaired t test. The paired t test was used to determine the difference in rate of decline with time. A p value <0.05 was taken to indicate a significant difference. All statistical analyses used SPSS (version 11.5).
|
Results |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Between January 1991 and December 2001, 130 patients (76 males, 54 females, mean age 56 years) were referred to the Joint Diabetic-Renal Clinic with diabetic nephropathy. Forty-nine (38%) had type 1 diabetes; the rest had type 2 diabetes (Table 1). General diabetic clinics accounted for 48% of referrals, renal clinics 27%, general medical clinics 6%, and general practitioners 19%.
|
At presentation, 73 (56%) had a history of vascular disease or clinical evidence of this, including ischaemic heart disease, cerebrovascular disease and peripheral vascular disease. Retinopathy was documented in 96 (75%), of whom 74% had background retinopathy and 45% proliferative retinopathy. Of patients with type 1 diabetes, 55% had evidence of proliferative retinopathy compared to 45% of those with type 2 diabetes. No significant relationship between smoking and the presence of retinopathy was found (
2 = 3.78, p = 0.052) (Table 2).
|
Of the 130 patients, 88 were treated with insulin, 34 with oral agents and eight were treated with both insulin and oral agents in combination. Three patients were treated with diet therapy alone. As a part of renal investigations at the clinic, 113 patients (87%) had ultrasound examination of the kidneys, 15 had an intravenous urogram or DTPA (diethylene triamine pentacetic acid) scan and 16 had a percutaneous renal biopsy. Of those 16, 13 had a biopsy diagnosis of diabetic nephropathy; the other three had IgA nephropathy, renal amyloid and focal segmental glomerulosclerosis, respectively.
At presentation, 54% were taking ACE inhibitor drugs, increasing to 64% by the last visit to the clinic. Contraindications for ACE inhibitor therapy were documented in 28/39 patients (72%) not on such therapy (Table 3). Use of other anti-hypertensives is shown in Figure 1. Anti-platelet therapy (aspirin) was taken by 27% of patients. None was receiving any other anti-platelet agent. Hypercholesterolemia was noted in 43% of patients; 81% of these were treated with a statin, 6% with a fibrate and none was on combination therapy.
|
|
Median creatinine at referral was 124 (IQR 92–176) µmol/l (Table 4), and 16% had a referral creatinine >200 µmol/l. Estimated median creatinine clearance was 78.1 ml/min (IQR 51.9–104.3) at presentation. The majority of our patients had a history of hypertension (88%), of whom 83% had a blood pressure of >140/80 mmHg on referral. Overall, 91% of patients were on antihypertensive treatment, and 41% achieved their target blood pressure (140/80) by the end of the study period. On referral, mean systolic blood pressure was 158 mmHg (95%CI 153–163) and mean diastolic pressure 84 mmHg (95%CI 82–86). These levels improved to 141 (95%CI 137–146) and 77 (95%CI 75–79) mmHg, respectively, at the last visit to the clinic (p < 0.001) (Figure 2).
|
|
Mean glycated haemoglobin was 8.4% (95%CI 8.0–8.9) at presentation, and this remained unchanged by the end of the study period at 8.6 (95%CI 8.2–8.9) (p = NS). Mean total cholesterol concentration at presentation improved from 5.9 mmol/l (95%CI 5.6–6.2) to 5.3 mmol/l (95%CI 5.0–5.6) (p < 0.001). Proteinuria
0.5 g/24 h was present in 65% of patients at referral, and 44% of this group had a protein excretion of 
2 g/24 h. The rate of decline in renal function was calculated in 45 patients who had data for a minimum of 3 years, by linear regression from the slope of creatinine clearance vs. time (Figure 3). It was reduced from 1.09 ± 1.34 ml/min/month (mean ± SD) in the first year to 0.39 ± 0.73 ml/min/month in the third year (p < 0.004).
|
During the study period, 41 (32%) patients died. Mean survival from first clinic visit to death was 47.8 months (95%CI 37.6–57.9). Cardiovascular deaths were the major cause, accounting for 64% of deaths, followed by renal failure in 15%. Other causes accounted for the rest. Twenty-one patients started renal replacement therapy.
Univariate ANOVA was used to test relationships between mortality and parameters including age, HbA1c, blood pressure, total cholesterol and proteinuria. High initial total cholesterol (p = 0.012, r2 = 5.3%), high final total cholesterol (p = 0.010, r2 = 7.7%) and age at presentation (p = 0.041, r2 = 3.3%) all predicted mortality.
|
Discussion |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Diabetic nephropathy is the most common single cause of ESRF in the developed world, and the increasing incidence has followed the epidemic of type 2 diabetes and the improved survival of patients with both type 1 and type 2 diabetes. Moreover, patients with diabetic nephropathy are now more readily accepted for renal replacement therapy.4 However, challenges in managing this group of patients include the increasing costs of renal replacement therapy, increased cardiovascular risk and limited availability of organs for transplantation. Primary prevention of diabetic nephropathy would be an ideal solution, but is currently unachievable. It is therefore prudent to identify and manage diabetic nephropathy early, in order to delay or prevent ESRF, and reduce the associated cardiovascular risk.
Managing these patients within a busy general diabetic or renal clinic is challenging. Intensified multifactorial intervention in patients with type 2 diabetes and microalbuminuria delays progression to nephropathy, retinopathy and autonomic neuropathy.22 Combined diabetic-renal clinics were therefore set up to provide high-quality care and individualized treatment to these patients with multiple risk factors. Our joint clinic was among the first to provide such a service in a busy District General Hospital in the UK, and was aided by the development and use of widely circulated local guidelines, in which General Practitioners were actively involved. The clinic continues to serve a population of approximately 188 000. However, there have been very few publications showing a positive benefit of these multidisciplinary clinics in the management of diabetic nephropathy,19,20,23 and as far as we are aware, no published studies from a District General Hospital providing secondary care for patients with diabetic nephropathy.
The number of patients with type 2 diabetes in our cohort exceeds those with type 1 diabetes. Mean age at presentation in patients with type 1 diabetes was lower when compared with type 2 diabetes, but with a longer duration of diabetes, similar to published data, suggesting that our study group was a representative population.23 The prevalence of retinopathy was high: at least 75% of patients had documented background retinopathy and almost half had proliferative retinopathy. All patients with proliferative retinopathy received laser photocoagulation. Absence of retinopathy was not used as a criterion for renal biopsy in our group of patients. Smoking is an important modifiable risk factor affecting the progression of renal disease, and also has an adverse effect on cardiovascular risk. We were unable to reduce the significant proportion of patients who continued to smoke during the period of follow-up in the clinic. In a recent study, smoking cessation had benefits in addition to blood pressure control and ACE inhibition, in reducing the progression of diabetic nephropathy.13 Patients should be made aware of the benefits of smoking cessation at clinic visits by physicians and nurses, and if possible, offered direct access to smoking cessation clinics.
Reduction of blood pressure is crucial to the management of diabetic nephropathy.5,6 Various guidelines have recommended a target blood pressure of <140/80 mmHg, and a level of <130/80 mmHg has recently been suggested in patients with diabetic nephropathy.4,15,16 Our patients had a high prevalence of hypertension, and most were on anti-hypertensive treatment on referral. Even though most referrals were from specialist diabetic and renal clinics, 83% of subjects had a blood pressure >140/80 mmHg, and only 41% achieved their modest target of 140/80 mmHg at the clinic. These results are consistent with published studies, showing that only a small percentage of patients achieve these targets, despite intensive management.23,24 On the other hand, patients improved their systolic and diastolic blood pressure significantly, compared to their blood pressures on referral. Patients required at least 2–3 anti-hypertensives to achieve their target blood pressure. Large prospective studies including UKPDS25 also showed that patients required multiple drug regimens to reduce blood pressure significantly.
The use of ACE inhibitor drugs improved marginally at the clinic, but contraindications to therapy were well-documented in most patients not taking treatment. Co-existing renal vascular disease was the most common contraindication in almost half of the patients not receiving ACE inhibitor drugs, followed by hyperkalaemia in approximately 20%. This may reflect a reluctance in some clinicians to use ACE inhibitors in the presence of renal insufficiency, more so with a suspicion of renal vascular disease. However, it is important that ACE inhibition in this high-risk group be increased; evidence is accumulating that this offers protection against further deterioration of renal function, independent of blood pressure reduction,26–29 and may also help to reduce cardiovascular risk.30 Aggressive investigation and management of renal vascular disease may be an option to increase the number of subjects on ACE inhibition, rather than relying on a clinical suspicion of renal vascular disease. Dietary advice on restriction of potassium intake from a specialist dietician might be useful.31 Angiotensin II receptor antagonists, with their favourable side-effect profile and once-a-day treatment, might also improve patient compliance.
Treatment targets for total cholesterol levels have been gradually reduced throughout this long study period. Though there are no large randomized studies in this area, a recent meta-analysis found that lipid reduction may preserve glomerular filtration rate and also decrease proteinuria in patients with renal disease.8 It is now widely accepted that dyslipidaemia in chronic renal failure should be aggressively managed with statin therapy, due to the increased cardiovascular risk. Furthermore, for a group of patients with a high risk of atherosclerotic vascular disease, only 27% took aspirin as an anti-platelet agent. We were unable to identify any valid reasons for the low prescription rate of aspirin in this study. Glycaemic control remained unchanged during the study period. On the other hand, HbA1C levels in this group are similar to those in previously published studies, and did not change with declining renal function.20,24
In this observational study, we estimated creatinine clearance using the Cockcroft and Gault equation. We are aware that this method overestimates creatinine clearance,32 but nevertheless, it correlates well with measured creatinine clearance.33 We have assumed that this overestimation will be insignificant because of the longitudinal nature of our study. We used linear regression to calculate the decline in renal function; similar methods have been used for audit purposes by other groups.20 Parving et al. showed that in intensively-treated type 1 subjects with nephropathy, the rate of decline of renal function could be reduced from 0.89 ml/min/month to 0.22 ml/min/month.34 As far as we know, these results have not been reproduced in routine clinical practice in diabetic patients with nephropathy, nor in clinical trials. Joss et al. studied a group of subjects in a joint clinic with early diabetic nephropathy, and showed that the rate of decline could be reduced from 0.52 ml/min/month in the first year to 0.27 ml/min/month in the third year. They suggested that for audit purposes, a joint clinic should aim to achieve a rate of decline of renal function of <0.25 ml/min/month in at least 70% of patients with early nephropathy.20 The rate of decline of GFR in our study was reduced from 1.09 ml/min/month in the first year to 0.39 ml/min/month in the third year. For example, in a patient with a creatinine clearance of 50 ml/min/year, the improvement in the rate of decline in renal function in our study would extend the nephropathy stage, independent of dialysis, from 4 years to 11 years, with all the attendant savings and potential for reduced cardiovascular risk. However, our initial rate decline of GFR was significantly high, and remains unexplained despite moderate control of risk factors. One possibility could be initiation and titration of ACE inhibitors in the first year after referral to the combined clinic. Our analysis could also be vulnerable to sudden changes in serum creatinine, most commonly secondary to incurrent illness. The latter is unlikely to have been a major factor, since most of our readings were done in the clinic setting when patients were well.
One third of our patients died during the 10-year study period. Of these deaths, 64% were due to cardiovascular disease, followed by renal failure and others. Coronary artery disease was the major contributor accounting for most of the cardiovascular deaths. The mean survival in our group of patients who died was only 4 years from their first clinic visit, which is comparable to metastatic tumours of the lung.35 Haffner et al. showed that patients with type 2 diabetes without a history of previous myocardial infarction, carry the same cardiovascular risk as non-diabetic patients with a previous history of myocardial infarction.36 Mild renal insufficiency alone may directly promote atherosclerosis, and this increases with advancing renal failure.37 This increased cardiovascular risk is further aggravated by non-traditional risk factors such as the increased proportion of atherogenic small dense LDL, raised homocysteine and inflammatory markers such as C-reactive protein, which are associated with chronic renal impairment.38,39 Survival on renal replacement therapy appears to be worse for patients with diabetes,40 partly because of the increased cardiovascular disease associated with the end stages of renal disease. The challenge for the future will be improved patient management in the earlier stages of diabetic nephropathy to prevent progression, as well as cardiovascular complications.41
The audit value of this study has allowed us to make improvements to the protocols and guidelines used in our clinic. In summary, management of our patients with diabetic nephropathy in a District General Hospital joint diabetic-renal clinic significantly delayed the rate of decline in renal function and extended the time to renal support, in patients with early diabetic nephropathy. This clinic also helped somewhat to achieve targets in blood pressure control and improve total cholesterol, as suggested by established guidelines in the treatment of diabetic nephropathy, although optimal blood pressure remains difficult to achieve for many patients. This study provides important data regarding the natural history of diabetic nephropathy in a single population attending a district general hospital, which may be valuable for future resource planning and management.
|
Acknowledgments |
|---|
We are grateful to Dr Chris Lord, Consultant Chemical Pathologist, and to Dr Akeel Sayeed, Specialist Registrar in Diabetes & Endocrinology, for helpful discussions during the work that led to this study.
|
References |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
1. U.S. Renal Data System. USRDS 2003 Annual Data Report: Atlas of End-Stage Renal Disease in the United States 2003;Bethesda MD National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases.
2. Ansell D and Feest T. The Second Annual Report, The UK Renal Registry 1999;Bristol.
3. Finne P, Reunanen A, Stenman S, Groop PH, Gronhagen-Riska C. Incidence of end-stage renal disease in patients with type 1 diabetes. JAMA 2005; 294:1782–7.
4. American Association. Position statement: Diabetic Nephropathy. Diabetes Care 2004; 27:Suppl. 1, S79–83.[CrossRef][Medline]
5. Mogensen CE. Long-term antihypertensive treatment inhibiting progression of diabetic nephropathy. Br Med J (Clin Res Ed) 1982; 285:685–8.[Medline]
6. Parving HH and Hommel E. High blood pressure is a major factor in progression of diabetic nephropathy. J Diabet Complications 1988; 2:92–5.[CrossRef][Medline]
7. Lam KS, Cheng IK, Janus ED, Pang RW. Cholesterol-lowering therapy may retard the progression of diabetic nephropathy. Diabetologia 1995; 38:604–9.[Web of Science][Medline]
8. Fried LF, Orchard TJ, Kasiske BL. Effect of lipid reduction on the progression of renal disease: a meta-analysis. Kidney Int 2001; 59:260–9.[CrossRef][Web of Science][Medline]
9. The effect of intensive treatment of diabetes on the development, & progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993; 329:977–86.
10. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998; 352:837–53.[CrossRef][Web of Science][Medline]
11. Mathiesen ER, Hommel E, Hansen HP, Smidt UM, Parving HH. Randomised controlled trial of long term efficacy of captopril on preservation of kidney function in normotensive patients with insulin dependent diabetes and microalbuminuria. Br Med J 1999; 319:24–5.
12. Parving HH, Lehnert H, Brochner-Mortensen J, Gomis R, Andersen S, Arner P. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 2001; 345:870–8.
13. Chuahirun T, Simoni J, Hudson C, Seipel T, Khanna A, Harrist RB, et al. Cigarette smoking exacerbates and its cessation ameliorates renal injury in type 2 diabetes. Am J Med Sci 2004; 327:57–67.[Web of Science][Medline]
14. Pedrini MT, Levey AS, Lau J, Chalmers TC, Wang PH. The effect of dietary protein restriction on the progression of diabetic and nondiabetic renal diseases: a meta-analysis. Ann Intern Med 1996; 124:627–32.
15. Diabetes care and research in Europe: the Saint Vincent declaration. Diabet Med 1990; 7:360.[Web of Science][Medline]
16. SIGN. Management of diabetes. Report no. 55 2001; Scottish Intercollegiate Guidelines Network.
17. NICE. Management of type 2 diabetes—renal disease, prevention and early management. Inherited Clinical guideline F 2002;London National Institute for Clinical Excellence.
18. Bergstrom J, Alvestrand A, Bucht H, Gutierrez A. Progression of chronic renal failure in man is retarded with more frequent clinical follow-ups and better blood pressure control. Clin Nephrol 1986; 25:1–6.[Medline]
19. Liew BS, Perry C, Boulton-Jones JM, Simpson K, Paterson K. Diabetic nephropathy: an observational study on patients attending a joint diabetes renal clinic. Q J Med 1997; 90:353–8.
20. Joss N, Paterson KR, Deighan CJ, Simpson K, Boulton-Jones JM. Diabetic nephropathy: how effective is treatment in clinical practice? Q J Med 2002; 95:41–9.
21. Cockcroft DW and Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16:31–41.[Web of Science][Medline]
22. Gaede P, Vedel P, Parving HH, Pedersen O. Intensified multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: the Steno type 2 randomised study. Lancet 1999; 353:617–22.[CrossRef][Web of Science][Medline]
23. Feest TG, Dunn EJ, Burton CJ. Can intensive treatment alter the progress of established diabetic nephropathy to end-stage renal failure? Q J Med 1999; 92:275–82.
24. Dunn EJ, Burton CJ, Feest TG. The care of patients with diabetic nephropathy: audit, feedback, and improvement. Q J Med 1999; 92:443–9.
25. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. Br Med J 1998; 317:703–13.
26. Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001; 345:851–60.
27. Bakris GL, Weir MR, Shanifar S, Zhang Z, Douglas J, van Dijk DJ, et al. Effects of Blood Pressure Level on Progression of Diabetic Nephropathy: Results From the RENAAL Study. Arch Intern Med 2003; 163:1555–65.
28. Rossing K, Jacobsen P, Pietraszek L, Parving HH. Renoprotective effects of adding angiotensin II receptor blocker to maximal recommended doses of ACE inhibitor in diabetic nephropathy: a randomized double-blind crossover trial. Diabetes Care 2003; 26:2268–74.
29. Mogensen CE, Neldam S, Tikkanen I, Oren S, Viskoper R, Watts RW, et al. Randomised controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the candesartan and lisinopril microalbuminuria (CALM) study. Br Med J 2000; 321:1440–4.
30. Mann JF, Gerstein HC, Pogue J, Bosch J, Yusuf S. Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: the HOPE randomized trial. Ann Intern Med 2001; 134:629–36.
31. Ahuja TS, Freeman D Jr, Mahnken JD, Agraharkar M, Siddiqui M, Memon A. Predictors of the development of hyperkalemia in patients using angiotensin-converting enzyme inhibitors. Am J Nephrol 2000; 20:268–72.[CrossRef][Web of Science][Medline]
32. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999; 130:461–70.
33. Rolin HA 3rd, Hall PM, Wei R. Inaccuracy of estimated creatinine clearance for prediction of iothalamate glomerular filtration rate. Am J Kidney Dis 1984; 4:48–54.[Web of Science][Medline]
34. Parving HH, Andersen AR, Smidt UM, Hommel E, Mathiesen ER, Svendsen PA. Effect of antihypertensive treatment on kidney function in diabetic nephropathy. Br Med J (Clin Res Ed) 1987; 294:1443–7.[Medline]
35. Adebonojo SA, Bowser AN, Moritz DM, Corcoran PC. Impact of Revised Stage Classification of Lung Cancer on Survival: A Military Experience. Chest 1999; 115:1507–13.[Medline]
36. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from Coronary Heart Disease in Subjects with Type 2 Diabetes and in Nondiabetic Subjects with and without Prior Myocardial Infarction. N Engl J Med 1998; 339:229–34.
37. Hall WD. Abnormalities of kidney function as a cause and a consequence of cardiovascular disease. Am J Med Sci 1999; 317:176–82.[CrossRef][Web of Science][Medline]
38. Rajman I, Harper L, McPake D, Kendall MJ, Wheeler DC. Low-density lipoprotein subfraction profiles in chronic renal failure. Nephrol Dial Transplant 1998; 13:2281–7.
39. Arnadottir M, Hultberg B, Nilsson-Ehle P, Thysell H. The effect of reduced glomerular filtration rate on plasma total homocysteine concentration. Scand J Clin Lab Invest 1996; 56:41–6.[Web of Science][Medline]
40. Foley RN, Parfrey PS, Sarnak MJ. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis 1998; 32:Suppl. 3, S112–19.[Web of Science][Medline]
41. Ritz E, Rychlik I, Locatelli F, Halimi S. End-stage renal failure in type 2 diabetes: A medical catastrophe of worldwide dimensions. Am J Kidney Dis 1999; 34:795–808.[Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||