This database analysis shows that (1) about every other patient with diabetes is screened for the presence of CKD annually; (2) less than half of patients achieve a target HbA1c of < 7.0 % (or < 53 mmol/mol); recommended use of SGLT-2i and GLP1-RA is well below 10 %; (3) hypertension is controlled in about two-thirds of patients with lower rates depending on age and respective SBP thresholds; RAAS blockers are used in about half of the patients. Taken together there appears to be room for improvement with respect to the renal aspects of diabetes care to prevent kidney-associated morbidity and mortality. It is important to understand guideline compliance because adherence to treatment guidelines is associated with improved clinical outcomes in patients with type 2 diabetes, better glycaemic and blood pressure control, and it has the potential to reduce the risk of developing CKD/ESRD through comprehensive patient assessment [
10,
11].
Chronic Kidney Disease Screening
Renal involvement in diabetes is common and CKD significantly increases the risk of atrial fibrillation in patients with diabetes [
12]. It is essential, therefore, that kidney involvement is detected as early as possible. The ESC/EASD recommendations to screen patients annually for kidney disease using eGFR and UACR has also been recommended by the 2020 American Diabetes Association (ADA) [
4] and the 2013 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline [
13]. The recent 2020 KDIGO guidelines [
14] supports this approach in a more general sense as they recommend multifactorial diabetes management with yearly assessment of urine albumin excretion and eGFR, but refer to primary care and endocrinology society guidelines for further details.
Only about half of the patients with diabetes, irrespective of diabetes type, were screened annually in DIVE/DPV, which appears low. The data are, however, not far off from those of Hagnas et al., [
15] which investigated CKD-screening in Finnish primary healthcare, where 60.2 % of 5,112 patients with type 2 diabetes were regularly screened for both eGFR and albuminuria. An Australian cross-sectional study [
16] found that among 90,550 patients with type 2 diabetes, only 44,394 (49.0 %) were appropriately screened or monitored. Rates in the present study, therefore, are plausible.
There are a number of potential reasons for this low screening rate. First, it may be the result of partial guideline inconsistencies. For example, the 2020 ADA guidelines [
4] recommend only to screen for CKD in type 1 diabetes if diabetes duration is ≥ 5 years. This criterion is not met for at least some of the patients in the current dataset with a median diabetes duration of 11.9 years and an interquartile range of 2.7 to 25.0 years. Secondly, as multiple determinations of urinary albumin (at least two tests out of three need to be positive to arrive at a diagnosis of microalbuminuria) are necessary, the efforts for screening may be perceived to be high. Conversely, albuminuria tests are sometimes regarded as unreliable, especially if only performed once. Thirdly, not every physician’s office is able to collect urinary samples, which may appear unhygienic and, thus, not desirable. As a potential limitation, we did not explore whether a twice-annual monitoring of kidney function is actually performed in patients with advanced disease (urinary albumin > 30 mg/g creatinine and/or eGFR < 60 mL/min/1.73 m
2). Some patients counted as screened in our analysis, would not be classified based on a requirement for two annual investigations as suggested by the ADA.
Finally, only about half of all patients in our database were screened based on both urinary albumin and creatinine. As opposed to the majority of guidelines, a determination of urinary albumin without normalization to creatinine appears to be frequent in clinical practice. This is of concern as a simple urinary dipstick test has a lower sensitivity and higher false-discovery rate compared to UACR-based screening [
17,
18]. It has been previously described that there is no standardised method of collection and measurement of urinary albumin and creatinine and there are concerns about test reliability, intra-individual variability based on body position, activity and temperature [
19,
20].
Blood glucose control and treatment
Only 43.5 % of patients with type 2 diabetes reached the ESC/EASD [
3] recommended HbA1c treatment target of < 7.0 %. Glucose control in type 2 diabetes is generally a matter of debate and a patient-centred approach suggests that individual blood glucose targets should be pursued. Variables that influence the actual HbA1c target are patient age, hypoglycaemic risk, and the comorbidity and co-medication burden of patients. While the 2020 ADA guidelines recommend no specific treatment target [
4], 2020 KDIGO recommends an individualised HbA1c target range between < 6.5 % and < 8.0 % with higher targets tolerated for patients with present/severe macrovascular complications, many comorbidities and high hypoglycaemia risk [
14]. Moreover, KDIGO recommends looser HbA1c targets in patients with severe CKD, which is at odds with the ESC/EASD recommendation [
3]. This is in principal alignment with the recent German recommendations which pursue a corridor of 6.5–7.5 % to prevent CKD with the upper values recommended for patients with macroangiopathy. To prevent progression, an HbA1c value of 7 % or less is requested [
18].
Less than 10 % of patients with type 2 diabetes received the two treatment options (SGLT-2i and/or GLP1-RAs) recommended for the reduction of renal endpoints by ESC/EASD [
3]. The 2020 ADA guidelines [
4] is slightly more specific than the ESC/EASD guidelines as to the use of SGLT-2i [
3]. It recommends SGLT-2i use in those patients with type 2 diabetes with an eGFR ≥ 30 mL/min/1.73 m
2 and urinary albumin > 30 mg/g creatinine, particularly in those with urinary albumin > 300 mg/g creatinine. KDIGO 2020 recommends SGLT-2i in patients with an eGFR ≥ 30 mL/min/1.73 m
2 on the basis of metformin and GLP-1 RAs or in patients who are unable to tolerate these aforementioned medications [
14]. Actual rates in DIVE/DPV were, however, very low with ~ 9 % and ~ 6 % of the patients with type 2 diabetes receiving SGLT-2i and GLP-1 Ras, respectively. These numbers have to be interpreted in light of their more recent market introduction, limitations by the approved indication (start of treatment until eGFR ≥ 60, stop treatment from eGFR < 45 ml/min/1.73 m
2), the only recent recommendation in guidelines (using the 2020 guidelines as a reference) and the lack of documentation for potential reasons for their non-use.
About 27.2 % of patients with type 1 diabetes in DIVE/DPV reached a target HbA1c < 7.0 and 1.5 % (SGLT-2i)/0.6 % (GLP-1 RAs) received guideline-preferred anti-diabetic drugs as defined by the ESC/EASD [
3]. While HbA1c treatment targets are no less stringent in type 1 than type 2 diabetes, the value of SGLT-2i/GLP-1 RAs in type 1 diabetes is less well documented. In 2019, the European Medicines Agency (EMA) approved a first SGLT-2i and a first dual SGLT-1/-2i to improve glycaemic control, as an adjunctive treatment to insulin in people with type 1 diabetes and a BMI ≥ 27 kg/m
2 [
21]. Of note, these are not approved for patients with type 1 diabetes by the Food and Drug Administration (FDA). No GLP1-RAs are registered for use in type 1 diabetes and neither agency recommends their use in patients with CKD. As such, the low use rate in type 1 diabetes is not surprising, even more so as non-insulin antidiabetic treatment in type 1 diabetes is rare anyway.
Hypertension control and treatment
Blood pressure was controlled for 41.1–68.4 % in patients in DIVE/DPV depending on diabetes type and age for which different targets have been defined [
3]. These findings are supported by another German study, which showed that blood pressure in patients with diabetes is insufficiently managed [
22]. The ESC/EASD guidelines are very specific in recommending SBP to 130 mmHg and < 130 mmHg if tolerated, but not < 120 mmHg in patients between 18 and 65 years and 130–139 mmHg in patients > 65 years. The 2020 ADA and KDIGO [
4,
14] give no specific recommendations as to the target blood pressure pursued, but rather confine their recommendation to the use of RAAS-blocking agents (ACEI or ARB) like the ESC/EASD. We documented ACEi use in 24.0 % (type 1 diabetes) and 39.9 % (type 2 diabetes) in patients with microalbuminuria with higher rates seen in patients with macroalbuminuria/proteinuria (40.9 %/47.7 %) which is below the rates observed for patients with type 2 diabetes in a Finnish study (57.0 %) [
15]. KDIGO also recommends titration of the RAAS-blocker to the highest approved dose that is tolerated. The dose (and the presence of LVH) was not documented in our dataset, which prevents us from judging adequacy of treatment in this respect.
Areas in need of future study or ongoing research
Guidelines conform in demanding regular screening for CKD in patients with diabetes, tight glucose control with the use of SGLT-2i (and GLP-1 RAs), and tight blood pressure control using ACEi/ARBs in those with hypertension and any degree of albuminuria. Inconsistencies are observed when looking at specific recommendations. The degree of translation into clinical practice has room for further improvement, but is somewhat uncertain because of the lack of specific data on the presence of drug contraindications, drug interactions and concomitant disease.
Based on our analysis we believe that (1) partial inconsistency between guidelines with respect to screening and treatment efforts prevents clinical practice to catch up and fully comply with these recommendations. (2) Further research is needed into the use of antidiabetic drugs and their potential benefits in CKD patients with type 2 and potentially even more so in type 1 diabetes. (3) Clear-cut recommendations on the use of antihypertensive and renoprotective drugs is needed. These drugs are widely used irrespective of the presence of albuminuria, but need to be consistently used in those with renal disease. (4) Beneficial drugs are usually not titrated to a maximally tolerated and effective dose resulting in suboptimal effects on renal and overall cardiovascular endpoints. Conversely, over-diagnosis and over-treatment may be deleterious to patients and society from a health and cost perspective and we encourage individual treatment decisions for each patient to maximise the benefits of current (and future) diagnostic and therapeutic treatment options.
Limitations
The main limitation is the retrospective nature of this study, using data from a registry. However, due to the number of patients enrolled in the registry, we can be confident that the data provides a true reflection of diabetes patients in Germany. In addition, the data quality is very much dependent on the information included in the registry by the patient’s prescribing physician. There may be reasons for justified non-compliance to treatment guidelines but this information is not captured in the registry. Finally, this is a single-country study – based on German data – and may not reflect guideline compliance in other countries.