As a pharmacist, you can play an important role in the management of CKD by making recommendations and suggestions keeping in mind that this condition is one of the key role players in cardiovascular renal metabolic (CVRM) disorder. 

SCREENING 

The detection of early stages diabetic kidney disease creates an opportunity to delay compilations and further kidney failure by appropriate therapeutic interventions and screening of high-risk individuals for kidney damage. 

Diabetic kidney disease is defined by signs of damage or loss of function for more than three months. The following signs are indicative of diabetic kidney disease: 

• Presence of albuminuria/proteinuria 
• Abnormal urine sediments e.g., white, or red blood cells along with 
• Abnormalities seen on imaging or biopsy.¹ 

Levels of protein loss (albuminuria) are graded according to the albumin:creatinine ratio: 

• A1: < 30 mg/g (> 3 mg/mmol) 
• A2: 30-300 mg/g (3-30 mg/mmol) 
• A3: > 300 mg/g (>30 mg/mmol). 

SEMDSA (Society for Endocrinology, Metabolism, and Diabetes of South Africa) guidelines use the albumin: creatinine ratios in mg/mmol and CKD is defined as being at a level of 2 mg/mmol, where 30 mg/g equals approximately 4 mg/mmol.¹ 

Triggers for screening people living with diabetes for kidney disease 

The following high-risk patients should be screened: 

• Patients suffering from hypertension and/or established cardiovascular disease (CVD) 
• Patients who have structural renal tract abnormalities 
• Patients with systemic disease and possible renal involvement 
• Patients with a family history of CKD 
• Patients who are receiving nephrotoxic medicines 
• Patients who have coincidentally found to have haematuria/proteinuria² 
• Elderly patients. 

Frequency of screening for kidney function 

• Bi-annual screening for diabetic patients with existing kidney disease and an eGFR: 30-60 ml/min/1.73 m2 or an albumin:creatinine ratio > 300 mg/g 
• More frequent screening for patients with more advanced CKD is left for the specialist’s discression.³ 

TREATMENT 

Hypertension 

The choice of medicine to be used for hypertension, in newly diagnosed people living with type 2 diabetes, should be chosen in favour to kidney-protective agents of which RAAS (renin-angiotensin-aldosterone system) inhibitors are the first choice (preventing proteinuria, reduce kidney fibrosis, and decline eGFR). This group of agents have also shown benefit in both early and late stages of kidney disease and should as such always be included in the management of CKD. 

Other agents used are the inclusion of: an ACE (angiotensin converting enzyme) inhibitor or an ARB (angiotensin receptor blocker). When there is a reduction in albuminuria of > 30% it has been shown that there is a reduction in adverse renal outcomes as well as CV events. 

When treating CKD, patients should always be titrated to the maximum tolerated dose. 

Blood pressure targets are recommended for 140/90 mmHg in most patients, however KIDGO (Kidney Disease Improving Global Outcomes) guidelines recommend that when a patient also has albuminuria, the target should be set at 130/80 mmHg. 

Lipid treatments for dyslipidaemia 

The recommended target for LDL-cholesterol is < 1.8 mmol/l.  

Suggested treatment with fenofibrate and a statin is indicated in figure 1. 

Figure 1: Lipid management in impaired kidney function for an LDL – cholesterol goal of < 1.8 mmol/l4 

Anti-glycaemic agents 

Patients that have established diabetic kidney disease benefit from effective control of glycaemia. Glycaemic targets should be individualised as patients advance to stages of CKD. This is due to the fact that their risk for hypoglycaemia increases. A suggested HbA1c of 7% is recommended for most patients with early stages of CKD. 

It is important to note that the manner of choosing a specific therapeutic agent is more important than just lowering the HbA1c. 

Metformin 

Metformin is the most commonly used agent for type 2 diabetes – except for stage 4 and 5 CKD for which their use is contraindicated. 

For stage 3 CKD metformin’s dose needs to be reviewed. ADA (American Diabetes Association) recommends that metformin should not be initiated when the eGFR is < 45 ml/min/1.73 m2. 

Sulphonylureas 

First generation sulphonylureas should be avoided in people living with diabetic kidney disease particularly in advanced CKD.  

GLP-1 RAs (glucagon-like peptide-1 receptor agonists) 

GLP-1 RAs, such as liraglutide, dulaglutide, and semaglutide, do not require dose adjustments associated for renal impaired patients. Furthermore, they have shown to reduce albuminuria due to their beneficial effects in diabetic kidney disease, of which their effects are independent of glycaemic control. 

The European Medicines Agency has approved the use of GLP-1 RAs for patients with an eGFR of 15 ml/min/1.73 m3.5 

SGLT2-2 inhibitors 

SGLT-2 (sodium-glucose co-transporter 2) inhibitors have shown to: 

• Reduce tubular reabsorption of glucose 
• Reduce systemic blood pressure 
• Reduce eGFR 
• Reduce glomerular pressure 
• Reduce hyperfiltration (which is the first physiological change in diabetic kidney disease) 
• Reduce albuminuria 
• Reduce oxidative stress > 50% in the diabetic kidney 
• Blunt increases in angiotensin 
• Reduce body weight 
• Reduce pro-inflammatory activity.⁶ 

SGLT-2 inhibitors are not recommended for the management of CKD in SA and clinicians should refer to the package inserts for guidance. 

CKD and concurrent diabetes lead to diabetic kidney disease. The interplay between these conditions forms part of CVRM disorder, and management for each patient should be done in a patient-centred manner. 

REFERENCES 

This article was based on: 

• A MEDTalk presented by Dr. Julian Trokis. MedTalk ZA. Diabetic Kidney Disease. Early detection and treatment. 2022. Available at: https://player.vimeo.com/video/711152088 as well as www.denovomedica.com - accessed: 05 June 2023 

• Aalbers, J. Early intervention in type 2 diabetes to reduce kidney and cardiovascular complications. deNovo Medica, 2022, August, 1-12 

1. Thomas MC, Brownlee M, Susztak K, et al. Diabetic kidney disease. Nat Rev Dis Primers 2015; 1: 15038. DOI: 10.1038/nrdp.2015.38.) 
2. Skolnik NS, Style AJ. Importance of early screening and diagnosis of chronic kidney disease in patients with type 2 diabetes. Diabetes Ther 2021; 12(6): 1613-1630 
3. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care 2021; 44(Supplement 1): S1-S2 
4. KDIGO Clinical practice guideline for lipid management in chronic kidney disease. Kidney Int Supplements 2013; 3(3):259-303) 
5. The 2017 SEMDSA guideline for the management of type 2 diabetes. JEMDSA 2017; 22(Supplement 1): S1-S196. SA clinicians should package inserts for SA guidelines). 
6. Sano M. A new class of drugs for heart failure: SGLT2 inhibitors reduce sympathetic activity. J. Cardiology 2018; 71: 471-476)