Although early NICE guidelines recommended renal referral based on serum creatinine >150μmol/l, it is now well recognised that eGFR provides a more reliable measure of renal function. In study 1, all patients had eGFR <60ml/min/1.73m2
equating to CKD class III. eGFR is calculated using the modification of diet in renal disease equation using serum creatinine, age, gender and ethnicity13
. For a given creatinine, GFR will be lower in those patients who are older, white and female. Of note only 20 of our 74 patients were female which probably reflects the exclusion of many women with significant renal disease but a serum creatinine <150μmol/l. Serum creatinine alone is an insensitive measure of renal function with a rise in creatinine to just above the normal range reflecting the loss of more than one-half of the total glomerular filtration rate. Using a serum creatinine >150μmol/l identified less than half of patients with significant nephropathy.
Comparable with our results, a recent study of renal disease in diabetic patients showed that the sensitivity of abnormal serum creatinine levels in identifying eGFR <60 ml/min/1.73 m2
was 45.3%, albuminuria 51.2% and either an abnormal serum creatinine or albuminuria 82.4%15
. Therefore inclusion criteria based solely on creatinine will miss a significant number of patients with early nephropathy. We identified 74 patient with a creatinine > 150μmol/l. Given the prevalence of diabetic nephropathy as 13.9% of the local diabetic population we would have expected to have identified at least 256 patients with nephropathy3
. This is defined as microalbuminuria. Clearly the use of creatinine alone will miss a significant number of patients. However for the clinic to be manageable a more stringent criterion would be needed. It is well established that microalbuminuria is predictive of disease progression in diabetic nephropathy and indeed that progression accelerates with development of macroalbuminuria11
. We therefore looked at patients with ACR > 30mg/mmol (macroalbuminuria). Including such patients with early modifiable nephropathy alongside our initial group with creatinine > 150μmol/l increased our patient group by more than double from 74 to 197.
In performing these studies, we identified 17 patients (23%) with creatinine >150μmol/l who were also normoalbuminuric. This result confirms the lack of specificity of elevated creatinine in identifying diabetic nephropathy. It has been reported that about 20% of patients with diabetes have reduced GFR but normal ACR16
. These patients are typically women with a shorter duration of diabetes, a low prevalence of retinopathy, a non-smoking history and a higher haemoglobin and HDL level. It is difficult to identify an underlying cause of renal impairment in these patients. However they typically have a low risk of CKD progression or death16
. In some cases the kidney disease may relate to hypertension or ischaemic nephropathy secondary to renal artery stenosis. In contrast to the benefits of ACEI/ARB therapy in diabetic nephropathy, treatment in patients with significant renal artery stenosis is associated with an over 30% rise in serum creatinine which is reversible on stopping the drug17
. The prevalence of renal artery stenosis detected by MRA in patients with type 2 diabetes is 17%18
. Although not all structural defects are associated with clinically significant disease, this highlights the need to screen for kidney disease in diabetic patients using a combination of both creatinine (or eGFR) and ACR.
Now that eGFR is being used more commonly, this, combined with estimation of urinary albumin, will be a useful means of identifying patients with early nephropathy for inclusion in a specialist diabetic clinic. All of the patients in study 1 were in CKD class III and one possibility is to include all patients with this stage of kidney disease in specialist diabetes renal clinics. On screening of general practice populations without diabetes, approximately 5% of patients have CKD stage III-V with 97% of these patients in CKD class III14
. However in a group of patients with diabetes, this percentage will be much higher. Indeed in one study, 27.5% of patients with diabetes have clinically significant CKD, as defined by an eGFR <60 ml/min/1.73 m2,15
. This study included patients from both primary and secondary care. At our centre, to include up to one third of our diabetic population in a specialist renal clinic, may exceed the capacity of service provision and therefore we plan to screen initially using creatinine and ACR.
As discussed above patients with diabetic nephropathy have significantly increased cardiovascular risk and therefore attention to cardiac risk factors is an essential part of their care. Only 65% of our patients met recommended audit standards for blood pressure in our general diabetes clinic. This could be improved with increased focus on blood pressure control at a subspecialty clinic. To achieve blood pressure control our patients required an average of 3 antihypertensive agents. Good blood pressure control often needs 2 or more agents. In a study comparing intensive and conventional blood pressure management, the UKPDS group found that 29% of patients in the intensive group required 3 or more agents to achieve targeted blood pressure control19
. displays the number of antihypertensives used for patients with both controlled and uncontrolled blood pressure. Of note 9 patients with uncontrolled blood pressure were taking 0–2 agents and thus were not being treated aggressively enough. This highlights the need for strict blood pressure control through introduction and titration of new agents if necessary. Cholesterol was well controlled in our study with good use of statin therapy.
It was more difficult to attain audit standards for HbA1C with just 45% achieving HbA1c of <7.5%. However the mean HbA1c in our study was 7.8±1.5% which is similar to mean HbA1c after longterm follow up (8–10years) in other studies such as Steno-2 and UKPDS20,21
This study demonstrates a need to improve our focus on cardiovascular risk reduction in this high risk group of diabetic patients. This can be achieved through ongoing education of medical staff and early and appropriate use of antihypertensives, statins and antiplatelets. Rather than refer many patients to a specialised nephrology service we feel that the skills within a diabetes centre should also allow us to intensify and improve glycaemic control and delay progression of renal disease. We feel that this can best be achieved with a subspecialty clinic.
Other guidelines are also in place for patients with CKD stage III-V9
. In addition to the measures outlined above, patients with established kidney disease require further monitoring, investigation and management. It is recommended that all patients with CKD stage III should have annual measurement of haemoglobin, calcium and phosphate. Those patients who are anaemic may benefit from treatment with iron and or erythropoietin. In addition, patients at this stage are at risk of renal bone disease. Therefore parathyroid hormone should be checked and if elevated (with an associated low vitamin D level), treatment with vitamin D should be initiated. It is also recommended that patients are referred for a renal ultrasound scan if they describe lower urinary tract symptoms, have refractory hypertension or an unexpected progressive fall in eGFR. Patients should also be immunised for influenza and pneumococcus.
Before this study these measures were not included as part of our diabetic clinic. Thus patients not attending a nephrologist were not routinely screened for these complications of renal disease. As they attend our diabetic clinic on at least a biannual basis, this care can be included as part of their routine review at a specialist diabetic renal clinic.