Management of chronic kidney disease in type 2 diabetes: screening, diagnosis and treatment goals, and recommendations

Figures & data

Table 1. Categories used to describe albuminuria

Current term	Previous term	UACR value
Normal or mildly increased	-	<30 mg/g
Moderately increased	Micro-albuminuria	30–300 mg/g
Severely increased	Macro-albuminuria	>300 mg/g

UACR, urinary albumin-to-creatinine ratio

Figure 1. Association of UACR and eGFR with cardiovascular mortality [19]. Adjusted for each other (UACR or eGFR), age, gender, race, CVD history, systolic blood pressure, diabetes, smoking, and total cholesterol. Circles represent statistically significant, and triangles represent not significant.

Reprinted from The Lancet, 375(9731), Matsushita K, et al. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Pages 2073–81, Copyright (2010), with permission from Elsevier CVD, cardiovascular disease; eGFR, estimated glomerular filtration rate; HR, hazard ratio; UACR, urinary albumin-to-creatinine ratio.

Figure 2. Guideline recommendations for the assessment of UACR and eGFR. ^a Calculated from serum creatinine (CKD-EPI); ^b With random spot urine sample; ^c Early morning urine sample is preferred.

CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; eGFR, estimated glomerular filtration rate; UACR, urinary albumin-to-creatinine ratio.

Figure 3. KDIGO guide to frequency of monitoring by GFR and albuminuria category [12]. Grid reflects the risk of progression by intensity of coloring (green: low risk [if no other markers of kidney disease, no CKD]; yellow: moderately increased risk; Orange: high risk; red/deep red, very high risk). The numbers in the boxes are a guide to the frequency of monitoring (number of times per year).

Reprinted from KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney International Supplements. 2013; 3 [1]: 1–163 with permission from Elsevier CKD, chronic kidney disease; GFR, glomerular filtration rate; KDIGO, Kidney Disease Improving Global Outcomes.

Table 2. Summary of risk mitigation strategies for SGLT2is, GLP-1 RAs, and MRAs in DKD

Adverse event	Potential mitigating strategies
SGLT-2i
Genital mycotic infections	Stress hygiene – keeping genital area clean and dry
Volume depletion	Proactive dose reduction of diuretics in patients at risk of hypovolemia Hold SGLT-2i during illness (nausea, vomiting, diarrhea) Implement sick day protocol
DKA	Educate patients on early recognition ‘STOP DKA’ protocol (stop SGLT-2i, test for ketones, maintain fluid and carbohydrate intake, use maintenance and supplemental insulin)
Amputation	Encourage foot self-examinations; examinations by HCP at each visit
Hypoglycemia	Adjustment of background antihyperglycemic agents, as appropriate
GLP-1 RA
Nausea/vomiting/diarrhea	Patient education on tolerability and symptom recognition Start at lowest dose and titrate slowly
Hypoglycemia	Adjustment of background antihyperglycemic agents, as appropriate
MRAs
Hyperkalemia	Monitoring of serum potassium prior to initiation and during treatment, and use of potassium binders, as appropriate

DKA, diabetic ketoacidosis; DKD, diabetic kidney disease; GLP-1 RA, glucagon-like peptide 1 receptor agonist; HCP, health care provider; MRA, mineralocorticoid receptor agonist; SGLT-2i, sodium-glucose cotransporter-2 inhibitor

Figure 4. Optimal treatment recommendations for CKD associated with T2D. ^a Referring clinicians may wish to discuss with their nephrology service depending on local arrangements regarding monitoring or referring. KDIGO guidelines provide direction on when to consider referral to a nephrologist based on eGFR and UACR levels (Figure 5); ^b For people with normal to mildly increased albuminuria (UACR <30 mg/g and eGFR >60 mL/min/1.73 m²), no immediate treatment to reduce CKD progression is required, but such individuals should be rescreened within a year, and guideline-directed therapy should be optimized to prevent micro and macrovascular complications. Refer to ADA guidelines to improve glycemic control and lipid levels, maintain healthy body weight, and optimize blood pressure; ^c ACEi or ARB therapy should be maintained even if eGFR is reduced.

ACEi, angiotensin-converting enzyme inhibitor; ADA, American Diabetes Association; ARB, angiotensin II receptor blocker; CV, cardiovascular; eGFR, estimated glomerular filtration rate; FDA, Food and Drug Administration; HF, heart failure; KDIGO, Kidney Disease: Improving Global Outcomes; MI, myocardial infarction; PAD, peripheral artery disease; SGLT-2i, sodium-glucose cotransporter-2 inhibitor; T2D, type 2 diabetes; UACR, urinary albumin-to-creatinine ratio

Figure 5. KDIGO referral decision making by eGFR and albuminuria [12]. *Referring clinicians may wish to discuss with their nephrology service depending on local arrangements regarding monitoring or referring.

Reprinted from KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney International Supplements. 2013; 3 [1]: 1–163 with permission from Elsevier GFR, glomerular filtration rate; KDIGO, Kidney Disease Improving Global Outcomes.

Table 3. Current KDIGO criteria of nephrology referral in CKD [12]

Criteria

AKI with abrupt sustained decrease in eGFR eGFR <30 mL/min/1.73 m^2 Consistent finding of significant albuminuria (UACR ≥300 mg/g/24 hours, approximately equal to PCR ≥500 mg/g or PER ≥500 mg/24 hours Rapidly worsening kidney function Urinary red cell casts, RBC >20 per high-power field and sustained and not readily explained CKD and hypertension refractory to treatment with 4 or more antihypertensive agents Persistent abnormalities of serum potassium level Recurrent or extensive nephrolithiasis Hereditary kidney disease

AKI, acute kidney injury; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; PER, protein excretion rate; PCR, protein: creatinine ratio; RBC, red blood cells; UACR, urinary albumin: creatinine ratio

Chronic Kidney Disease Prognosis C , Matsushita K , van der Velde M , Astor BC , et al. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet. 2010;375(9731):2073–2081.

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Kidney Disease Improving Global Outcomes . KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3:1–163.

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Rangaswami J , Bhalla V , de Boer IH , et al. Cardiorenal protection with the newer antidiabetic agents in patients with diabetes and chronic kidney disease: a scientific statement from the american heart association. Circulation. 2020;142(17):e265–e86.

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