The 2023 KDIGO CKD Guidelines Are Coming, Browse The Update Points Of Drug Treatment in This Article!

On June 16, 2023, at the 60th European Renal Association Congress (ERA), experts from KDIGO announced the upcoming news and some important contents of the 2023 KDIGO Chronic Kidney Disease (CKD) Guidelines.

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Prof. Magdalena Madero from Mexico is a former international editor of AJKD, a former member of the KDIGO executive committee, and vice-president of the International Society of Nephrology for Latin America and the Caribbean. At this meeting, she introduced in detail the latest update of this guideline on CKD treatment, including methods to delay the progression of kidney disease and control complications. Using a specific case example, she demonstrates the practical application of these updates.

The SPRINT study published on NEJM in 2021 showed that in CKD patients without diabetes, intensive blood pressure reduction was more able to reduce the risk of death compared with standard blood pressure reduction, with a hazard ratio (HR) of 0.73 (95% CI, 0.63~0.86, Figure 1).

Figure 1 The effect of standard blood pressure reduction vs intensive blood pressure reduction on the risk of death in CKD patients

However, analysis of the secondary endpoints of the SPRINT study showed that intensive blood pressure lowering did reduce cardiovascular disease (HR = 0.81; 95% CI, 0.63-1.05) and all-cause mortality (HR = 0.72; 95% CI, 0.53-0.99), but did not improve composite renal endpoints, such as eGFR decreased by more than 50% or end-stage renal disease (ESRD; HR = 0.90; 95% CI, 0.44-1.83). It is worth noting that intensive antihypertensive therapy cannot delay the progression of renal disease in CKD patients with diabetes.

This KDIGO guide has the following 2 updates for SGLT-2i:

Clinical recommendation 1: Use SGLT-2i to treat adult CKD patients with eGFR≥20ml/min/1.73㎡, UACR≥200mg/g, and heart failure (1A).

Clinical recommendation 2: Use SGLT-2i to treat adult CKD patients with eGFR ≥ 20-45 ml/min/1.73㎡ and UACR < 200 mg/g (2B).

In general, many studies and Meta-analysis have shown that SGLT-2i has a positive effect on delaying the progression of kidney disease, protecting cardiovascular function, and preventing the occurrence of heart failure in CKD patients.

The management of CKD in this guideline is similar to the management of diabetic nephropathy published in 2022. SGLT-2i and renin-angiotensin inhibitors (RAASI) are the cornerstone and first-line treatment options for CKD. However, the specific management process needs to wait for the official release of this guideline. For patient screening, intervention programs, and follow-up, refer to the figure below (Figure 2).

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Figure 2 SGLT-2i treatment plan for CKD patients with diabetes

Remarks: The 2023 KDIGO CKD guideline is similar to the above plan, please wait for the official release of the specific plan.

It is worth noting that a study pointed out that in patients receiving RAASi+SGLT-2i treatment, the annual decline rate of eGFR was only -1.85ml/min/1.73㎡, and it was estimated that it would take about 25 years to develop renal failure; while only Patients receiving RAASi treatment, whose annual eGFR decline rate is -4.6ml/min/1.73㎡, may develop renal failure in about 10 years; while CKD patients who have not received any treatment, their annual eGFR decline rate is 12ml/min /1.73㎡, may develop renal failure in about 5 years (Figure 3). These data suggest that RAASi+SGLT-2i treatment has a significant protective effect on delaying the progression of CKD to renal failure.

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Figure 3 Risk map of renal failure

Note: The gray line is the CKD patients who did not receive any treatment, the orange line is the patients who received only RAASi treatment, and the blue line is the patients who received RAASi+SGLT-2i.

It is well known that patients are highly prone to hyperkalemia with decreased eGFR and increased proteinuria (Fig. 4).

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Figure 4 Risk table of hyperkalemia in CKD patients with or without diabetes

To prevent hyperkalemia in CKD patients, there are 3 lines of treatment.

First-line treatment: ① optimize serum bicarbonate; ② optimize blood sugar control; ③ consider diuretics and SGLT-2i as adjuvant drugs.

Second-line treatment: Assess the content of potassium ions in the diet, and consider adjusting the diet to reduce intake.

The third-line treatment method: ①Adjust the prescription and avoid the use of drugs that may increase blood potassium; ②Use exchangeable resin to reduce potassium.

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In terms of uric acid management, there is currently no evidence that reducing uric acid in patients with CKD complicated with asymptomatic hyperuricemia is beneficial to delay the progression of CKD. The specific clinical recommendations are as follows:

Clinical recommendation 1: CKD patients with symptomatic hyperuricemia should receive urate-lowering therapy (1C).

Clinical recommendation 2: For patients with CKD and asymptomatic hyperuricemia, it is not recommended to use urate-lowering drugs to delay the progression of CKD (2D).

Although metabolic acidosis is a common comorbidity in CKD patients, and its risk is shown in the figure below (Figure 5), not all CKD patients should receive acid-base management. Its practical points are as follows:

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Practice point 1: Consider dietary and/or drug therapy to prevent severe acidosis (bicarbonate target <16mmol/L).

Practical point 2: Blood potassium concentration should be monitored regularly to ensure that blood potassium does not exceed the upper limit of normal and avoid adverse effects on blood pressure and volume.

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Figure 5 Risk of metabolic acidosis

Note: Green is low risk, yellow is medium risk, orange is high risk, and red is very high risk.

Although existing guidelines (Figure 6) state that daily protein intake can be >0.4 g/kg in patients with CKD, the evidence for these guidelines is older and of lower quality. Given this, Professor Magdalena Madero believes that it is necessary to strictly limit the protein intake of patients. Therefore, she chose option A.

Figure 6 Related guidelines for dietary recommendations for CKD

In addition, vegetarian or vegetarian-based diets are beneficial for CKD patients, but such studies still find that protein intake affects the progression of renal disease and comorbidities in patients.

Professor Magdalena Madero summarized the main updates of the 2023 KDIGO CKD guidelines, including the following four points:

Four key updates

①SGLT-2i should be the initial drug for CKD, proteinuria, diabetes, or heart failure;

②Potassium management is the cornerstone of RAASi and non-steroidal mineralocorticoid agonist treatment;

③ There is no data to support the management of non-severe metabolic acidosis or asymptomatic hyperuricemia;

④ There are more data on the lifestyle and diet of CKD patients, although most are observational studies.

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Professor Magdalena Madero reminded us again that the above content is the tip of the iceberg of this guide, and for more content please wait for the official release of the 2023 KDIGO CKD guide. It is reported that this guideline will be released in the next few weeks. Please continue to pay attention to the Yimaitong kidney channel to learn about the latest trends in this guideline!