Q J Med 1999; 92: 443-449
© 1999 Association of Physicians
The care of patients with diabetic nephropathy: audit, feedback, and improvement
From the Richard Bright Renal Unit, Southmead Hospital, Bristol, UK
Received 6 January 1999 and in revised form 7 May 1999
Professor T.G. Feest, Richard Bright Renal Unit, Southmead Hospital, Southmead Road, Bristol BS10 5NB
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Summary |
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Diabetic nephropathy is the commonest cause of end-stage renal failure in the developed world. The quality of care of 152 patients with diabetic nephropathy was assessed at the time of referral to a single nephrologist. The type II diabetics (62%) were older than the type I diabetics (38%) (mean 65 years vs. 48 years). The mean duration of diabetes was 17 years. Significant cardiovascular disease was present in 52%. There was diabetic retinopathy in 84% of the type I diabetics and 53% of the type II diabetics. Overall, 63% had hypertension at referral (St Vincent Declaration criteria), untreated in 25%. ACE inhibitors were not prescribed in 48% when no contraindications to their use were present. Glycosylated haemoglobin was >9.1% in 29%. Twenty were prescribed medications inappropriate to their renal function. Of patients with ischaemic heart disease and serum cholesterol >5.5 mmol/l, 82% were untreated; 82% of patients with secondary hyperparathyroidism were also untreated. At initial referral, many patients' care was sub-optimal. Referral was too late for adequate preparation for renal replacement therapy in 33%. Following a process of education and feedback of the results to referring practitioners, the timing of referral improved. We emphasize the need for closer co-operation between those managing diabetic patients with nephropathy to optimize their care.
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Introduction |
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Despite recent advances in the management of diabetes, diabetic nephropathy is the most frequent cause of end-stage renal failure in patients commencing renal replacement therapy (RRT) in the developed world, e.g. 40% in the USA,1 42% in Germany,2 14% in the UK,3 and 10% in Italy.4 Approximately 20% of patients with type I diabetes will develop nephropathy after 20 years, with a slightly higher cumulative incidence in type II diabetics.5
Type II diabetics comprise an increasing proportion of the diabetics starting RRT, and in many developed countries are in the majority.1,2 Once commenced on RRT, diabetics have an increased morbidity, a hospitalization rate two to three times that of other patients on RRT,4 and a significantly worse survival and outcome. In the USA, 5-year survival of diabetics on RRT is only 28% compared with 37% for other patients, 10-year figures are 12% and 22%, respectively.1 In Italy, the respective 5-year survival figures are 28% and 61%.4
The rate of progression of renal impairment once overt diabetic nephropathy is established varies greatly between patients, but the mean time interval from onset of nephropathy to commencing RRT is 6.5 years for both types of diabetes.6
There is debate whether therapy influences the progression of established diabetic nephropathy, however evidence exists for the effectiveness of blood pressure control,7 treatment with ACE inhibitors,8,9 non-dihydropyridine calcium channel blockers,10 restriction of dietary protein intake,11,12 and treatment of dyslipidaemia.13 Thus, even when diabetic nephropathy is established, patients' care should be optimized to delay the progression of nephropathy, and hence the need for RRT.
The St Vincent Declaration of 1989 was a World Health Organization initiative aimed at improving diabetic care.14 In 1992, the European St Vincent Declaration Action Programme 199215 set down more specific guidelines for the prevention and management of diabetic nephropathy. For overt diabetic nephropathy, these include keeping blood pressure below 140/90 mmHg for patients under 60 years of age, and below 160/90 mmHg in older patients, use of angiotensin-converting enzyme (ACE) inhibitors unless contraindicated, protein restriction to 0.6–0.7 g/kg body weight/day, and referral to a nephrologist once serum creatinine exceeds 200 µmol/l.
This study was undertaken to determine whether, at the time of referral of diabetic patients to this renal clinic, such recommendations were being followed, and whether interventions appropriate to the evidence had been applied.
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Methods |
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Included in this study are 152 patients from a total of 162 patients consecutively referred to a single consultant nephrologist for diabetic nephropathy over a 6-year period (1991–1997), from a catchment area including eight diabetic clinics, and general practitioner clinics, serving a population of 1.5 million. Ten patients were excluded from the study, as investigation revealed other predominant renal disease. Diagnosis was on clinical grounds (significant albuminuria>300 mg/day, or random albumin : creatinine ratio>20 g/mmol, and a renal ultrasound scan showing near-equal-sized non-scarred kidneys). Renal biopsy was only performed if there was clinical doubt as to the diagnosis. The absence of diabetic retinopathy on ophthalmoscopy was not of itself considered an indication for renal biopsy.
Patient assessment at referral included a medication and smoking history, evidence of arteriopathy and retinopathy, cardiac assessment, blood pressure, serum creatinine, serum cholesterol, HbA1c, immunoreactive parathyroid hormone (iPTH), calcium and phosphate. All data were entered into computerized case records. The blood pressure measurement used for this analysis was that recorded at the second visit to the renal clinic to avoid the effects of anxiety associated with the initial referral.
Data from the first 100 patients, referred between November 1991 and September 1996, were analysed. The results of this initial analysis were presented to the local GPs, diabetologists and other physicians as part of a continuing programme of dialogue, audit, and education. Recommendations on the appropriate management of nephropathic diabetics, and the optimal timing of referral to nephrologists were also offered. The data from the subsequent 52 patients, referred between October 1996 and July 1998, were later analysed separately as well as with the whole group.
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Results |
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Patient characteristics
Of the 152 patients, 58 (38%) were type I diabetics, and 94 (62%) type II (Table 1
). The mean age was 59 years (range 27–84 years); 48 years (27–84 years) in type I diabetics and 65 years (38–83 years) in type II diabetics. Reviewing sources of referral (Table 2), 56 (96%) type I diabetics, and 61 (64%) type II diabetics were attending a specialist diabetic clinic. In 22 of the 152 patients in whom there was doubt regarding the diagnosis of diabetic nephropathy, this was confirmed by renal biopsy.
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Blood pressure
The blood pressures recorded are summarized in Table 3
. Overall, 63% were hypertensive at referral, and 24% were normotensive but on antihypertensive therapy, giving a total incidence of hypertension in this population of 87%. Many hypertensive patients were not receiving treatment. Of those aged under 60 with a BP>140/90 mmHg (48 patients), 14 (29%) were not receiving treatment, and of the 47 patients aged over 60 whose BP was >160/90 mmHg, 11 (23%) were untreated.
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Use of ACE inhibitors
At referral, 67 patients (44%) were on ACE inhibitors; these had been discontinued prior to referral in nine patients because of complications (marked deterioration of renal function in six, hyperkalaemia in two, intractable cough in one), and had been deliberately avoided in a further three patients because of the presence of severe atherosclerotic disease and risk of renovascular disease.
Vascular disease, retinopathy, and history of smoking
Assessment of the presence of atherosclerotic vascular disease is summarized in Table 4. Of those with retinopathy, 59 (60%) had a positive smoking history, compared with 27 (51%) patients without retinopathy. Table 5 summarizes the results of comparing the relationship of atherosclerotic vascular disease with smoking history. Whilst an association between the two factors appeared to be present, this was not statistically significant. At referral, 30 patients (20%) were current smokers (11 female), and 54 (36%) patients were ex-smokers (13 female). Of those who had stopped smoking before referral, half had stopped after being diagnosed diabetic.
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Control of diabetes
Assessment of diabetic control by HbA1c was available in 118 patients at referral. In other patients, serum fructosamine levels had been used to assess control. Of the 118 patients, 39 patients (34%) had good control (HbA1c<7.0%), 34 patients (29%) had poor control (HbA1c>9.1%). At referral, 68 patients (45%) were taking oral hypoglycaemic agents, and 32 type II diabetics (34%) were taking insulin. Of the patients taking oral hypoglycaemic agents, 22 were taking Metformin, and 21 Glibenclamide, which were inappropriate prescriptions in 14 (33%) in view of their degree of renal impairment (serum creatinine>300 µmol/l for Metformin, and >700 µmol/l for Glibenclamide).16
Serum cholesterol
The few recommendations which exist for the management of hyperlipidaemia in diabetes recommend that levels >6.2 mmol/l are too high, and that the desired therapeutic goal should be <5.2 mmol/l.17 At referral, only 40 patients (26%) had serum cholesterol <5.2 mmol/l, and 57 (38%) had serum cholesterol >6.2 mmol/l, of whom 82% were untreated. Of the 33 patients with coronary artery disease, 21 (63%) had a serum cholesterol >5.5 mmol/l, the recommended level requiring treatment,18 and this was untreated in 17 (82%). Eighteen patients were receiving treatment for hypercholesterolaemia, eight with statins, and 10 with fibrates. In six patients the prescriptions of fibrates were considered inappropriate for their degree of renal impairment (serum creatinine >300 µmol/l.16
Secondary hyperparathyroidism
The 76 patients whose serum creatinine exceeded 250 µmol/l were assessed to determine whether secondary hyperparathyroidism had been sought and appropriately managed. The criteria used to assess `appropriate' management were those recommended by the Renal Association in 1995.19 Forty-three patients (57%) had evidence of secondary hyperparathyroidism, of whom only eight (18%) were receiving treatment. This pathology had often been overlooked, as over 70% of patients had not had serum iPTH measured prior to referral.
Timing of referral
The St Vincent Declaration recommends nephrology referral when serum creatinine exceeds 200 µmol/l, to enable management of renal failure and adequate preparation for RRT. In this study, 50 (33%) patients were referred when their serum creatinine was >350 µmol/l, and 29 patients (19%) when their serum creatinine was >500 µmol/l. Twenty-five patients (16%) required RRT within 6 months of referral, 13 (9%) within 6 weeks of referral.
There appeared to be a change in referral pattern during the study. The last 52 patients were referred at an earlier stage of their disease as judged by serum creatinine and time to needing RRT (Table 6). The rate of referral also appeared to increase.
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Discussion |
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A number of studies have elucidated the risk factors for progression to end-stage renal failure in diabetic nephropathy.12,20,21 Management strategies have been identified which may slow the rate of deterioration of renal function. Whilst accepting that the desirable targets for such variables as blood pressure and serum cholesterol are not always achievable, this study suggests that possible action is not always taken, and is frequently inadequate.
There has been criticism that the St Vincent recommendations for treatment of hypertension in the elderly are not strict enough. Whilst achieving a pressure of 140/90 or less is difficult in this group, there is no evidence that lowering the pressure to this level is of any less value in the elderly than in younger patients.22,23 Even accepting the relatively liberal St Vincent criteria, at referral 87% of patients were or had been hypertensive, and 63% still had blood pressure higher than recommended. Of those aged under 60 who were hypertensive, 29% were not receiving therapy. These findings are disappointing, as apart from the potential benefits for protecting renal function, diabetics gain more from treatment of hypertension in terms of reducing cardiovascular mortality than non-diabetic hypertensive patients.22,23
The literature on the protective effect of ACE inhibitors in diabetic nephropathy is convincing. Nevertheless 48% of these overtly nephropathic patients were not prescribed ACE inhibitors: most of these were hypertensive and appeared to have no contraindication to their use.
Atherosclerosis, in particular coronary artery disease, is a significant cause of morbidity and mortality in diabetic patients.24 Clinical trials have established that treatment of hypercholesterolaemia reduces the risk of coronary artery disease morbidity and mortality in the setting of both primary25 and secondary26 prevention. Recommendations are that patients with coronary artery disease with serum cholesterol >5.5 mmol/l should be treated.18 Of 33 diabetics with documented coronary heart disease, 21 had a serum cholesterol >5.5 mmol/l, which was untreated in 82%.
In primary prevention, initiation of treatment depends on the number of other risk factors for cardiovascular disease present.27 Studies have shown diabetes to be a strong independent risk factor for cardiovascular disease mortality, even when other established risk factors are absent (hypertension, cigarette smoking, hypercholesterolaemia).24 Thus whether or not hypercholesterolaemia is a causative factor in diabetic nephropathy, treatment of hypercholesterolaemia is important in diabetic patients to reduce the risk of coronary artery disease. Of the 152 patients referred, 111 (73%) had a serum cholesterol >5.2 mmol/l, of whom 25 (23%) had evidence of ischaemic heart disease, and 74 (67%) had two or more risk factors for ischaemic heart disease. Of these latter 99 patients, only 15 were receiving cholesterol-lowering treatment.
It is disappointing that 21 (14%) were receiving drugs inappropriate for their degree of renal dysfunction (9 metformin, 5 glibenclamide, 6 fibrates). In four cases, a fibrate was contributing to significant symptoms, which resolved when the drug was stopped.
The optimal timing for referral of nephropathic patients, stated in the St Vincent Declaration, is when serum creatinine exceeds 200 µmol/l. We assessed referrals as being acceptable in patients whose serum creatinine was below 350 µmol/l; 50 referrals (33%) did not meet this standard.
The timing of referral of any patient with renal impairment to nephrologists is important, because of its impact on their subsequent management. Early referral enables patient assessment, and the institution of a management plan with specific aims. These include interventions to attempt to slow the rate of decline of renal function and delay the need for dialysis, and management of the consequences of renal impairment to optimize patients' health (including assessment of nutritional status and dietary advice, correction of calcium/phosphate disorders, treatment of acidosis, investigation and treatment of anaemia, and adjustment of drugs and drug dosages appropriate to the degree of residual renal function). Preparation for RRT involves emotional support, education, hepatitis B vaccination, choice of appropriate treatment modality, and construction of dialysis access. This takes at least 6 months. Late referral of patients with chronic renal failure has been shown to be associated with a higher morbidity and mortality.28
Before referral, no patient was receiving specialist renal dietetic advice. Secondary hyperparathyroidism was present in 57%, was treated in only 18%, and had not been tested for in 70% of patients. Within 6 months of referral, 25 patients (16%) required RRT, 13 (9%) within 6 weeks of referral. Such late referrals must be avoidable in a group of patients who were all under regular medical follow-up for their diabetes.
These results show that, as in Germany,29 the care of diabetic patients with renal disease is far from optimal, and that referral to a nephrologist occurs too late in many cases. To optimize the care of these patients and delay the need for dialysis, closer co-operation is needed between those managing the early stages of diabetic nephropathy, i.e. primary care physicians and diabetologists, and nephrologists. The change in referral pattern following presentation of the early data to local referring physicians shows that with closer co-operation between generalists and specialists it is possible to improve the care of those with diabetic nephropathy. This study illustrates the need for, and the benefits of, undertaking clinical audit.
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References |
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TopSummaryIntroductionMethodsResultsDiscussionReferences |
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1. United States Renal Data System. USRDS 1997 Annual Data Report. Bethesda, MD, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, April 1997.
2.
Lippert J, Ritz E, Schwarzbeck A, Schneider P. The rising tide of ESRF from diabetic nephropathy type II—and epidemiological analysis. Nephrol Dial Transplant 1995; 10:462–7.
3.
Roderick PJ, Ferris G, Feest TG. The provision of renal replacement therapy for adults in England and Wales: recent trends and future directions.Q J Med 1998; 91:581–7.
4.
Marcelli D, Spotti D, Conte F, Limido A, Malberti F, Locatelli F. Prognosis of diabetic patients on dialysis: analysis of Lombardy Registry data. Nephrol Dial Transplant 1995; 10:1895–901.
5.
Hasslacher C, Ritz E, Wahl P, Michael C. Similar risks of nephropathy in patients with Type I or Type II Diabetes Mellitus. Nephrol Dial Transplant 1989; 4:859–63.
6.
Biesenbach G, Janko O, Zazgornik J. Similar rate of progression in the predialysis phase of Type I and Type II Diabetes Mellitus. Nephrol Dial Transplant 1994; 9:1097–102.
7. Parving HH, Jacobsen P, Rossing K, Smidt UM, Hommel E, Rossing P. Benefits of long term antihypertensive treatment on the prognosis in Diabetic Nephropathy. Kidney Int 1996; 49:1779–82.
8. Bjorck S, Nyberg G, Mulec H, Granerus G, Herlitz H, Aurell M. Beneficial effects of angiotensin converting enzyme inhibition on renal function in patients with diabetic nephropathy. Br Med J 1986; 293:471–4.
9.
Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin converting enzyme inhibitors on diabetic nephropathy. N Engl J Med 1993; 329:1456–62.
10. Bakris GL, Copley JB, Vicknair N, Sadler R, Leurgons S. Calcium channel blockers versus other antihypertensive therapies on the progression of NIDDM associated nephropathy. Kidney Int 1996; 50:1641–50.[Web of Science][Medline]
11. Kasiske BL, Lakatua JD, Ma JZ, Louis TA. A meta-analysis of the effects of dietary protein restriction on the rate of decline in renal function. Am J Kidney Dis 1998; 31:954–61.[Web of Science][Medline]
12.
Pedrini MT, Levey AS, Lau J, Chalmers TC, Wang PH. The effect of dietary protein restriction on the progression of diabetic and non-diabetic renal diseases: a meta-analysis. Ann Intern Med 1996; 124:627–32.
13. Krolewski AS, Warram JH, Christlieb AR. Hypercholesterolaemia—A determinant of renal function loss and deaths in IDDM and nephropathy. Kidney Int 1994; 45:s125–s131.
14. Diabetes Mellitus in Europe: a problem at all ages in all Countries. A model for prevention and self care. Ital Diabetol 1990; 10(Suppl.).
15. Krans HMJ, Porta M, Keen H, eds. Guidelines for the prevention of renal failure. In: Diabetes care and research in Europe: the St Vincent Declaration action programme. WHO Regional Office for Europe, 1992:29–32.
16. British National Formulary. British Medical Association and Royal Pharmaceutical Society of Great Britain, 1998 (Number 35 March).
17. American Diabetes Association. American Diabetes Association consensus statement: role of cardiovascular risk factors in prevention and treatment of microvascular disease in diabetes. Diabetes Care 1989; 12:573–9.[Web of Science][Medline]
18.
Oliver MF, Pyorala K, Shepherd J. Management of hyperlipidaemia. Eur Heart J 1997; 18:371–5.
19. The Renal Association. Treatment of adult patients with renal failure: recommended standards and audit measures. London, Publications Unit of the Royal College of Physicians, 1995.
20. Yokoyama H, Tomonaga P, Hirayama M, Ishii A, Takeda M, Babazano T, et al. Predictors of the progression of diabetic nephropathy and the beneficial effect of angiotensin converting enzyme inhibitors in NIDDM patients. Diabetologia 1997; 40:405–11.[Web of Science][Medline]
21. Breyer JA, Bain RP, Evans JK, Nahman NS, Lewis EJ, Cooper M, et al. The Collaborative Study Group. Predictors of progression of renal insufficiency in patients with insulin dependent diabetes and overt diabetic nephropathy. Kidney Int 1996; 50:1651–8.[Web of Science][Medline]
22.
Kostis JB, Davis BR, Cutler J, Grimm RH Jr, Berge KG, Cohen JD, et al. Prevention of heart failure by antihypertensive drug treatment in older persons with isolated systolic hypertension. SHEP Cooperative Research Group. JAMA 1997; 278:212–21.
23. Hansson L, Zanchetti A, Carruthers SG, Dahlof B, Elmfeldt D, Julius S, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet 1998; 351:1755–62.[Web of Science][Medline]
24. Stamler J, Vaccaro O, Neaton JD, Wentworth D. Diabetes, other risk factors and 12 year cardiovascular mortality in multiple risk factor intervention trial. Diabetes Care 1993; 16:434–44.[Abstract]
25.
Shepherd J, Cobbe SM, Ford I. Prevention of Coronary heart disease with pravastatin in men with hypercholesterolaemia. N Engl J Med 1995; 333:1301–7.
26. Scandinavian Simvastatin Survival Study Group. Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Survival Study (4S). Lancet 1994; 344:1383–9.[Web of Science][Medline]
27.
Pyorala K, De Baker G, Graham I, Poole-Wilson P, Wood D. Prevention of coronary heart disease in clinical practice. Recommendations of the task force of the European Society of Cardiology, European Atherosclerosis Society and European Society of Hypertension. Eur Heart J 1994; 15:1300–31.
28.
Jungers P, Zingraff J, Albouze G, Chauveau P, Page T, Hannedouche T, et al. Late referral to maintenance dialysis: detrimental consequences. Nephrol Dial Transplant 1993; 8:1089–93.
29.
Pommer W, Bressel F, Chen F, Molzahn M. There is room for improvement of preterminal care in diabetic patients with ESRF—The epidemiological evidence in Germany. Nephrol Dial Transplant 1997; 12:1318–31.
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