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Chronic Kidney Disease Learning Zone

Treating CKD

Read time: 130 mins
Last updated:25th Apr 2022
Published:21st Oct 2021

Find out about the treatments for chronic kidney disease (CKD) and its comorbidities and explore:

  • Goals for the treatment of CKD in our expert videos with Professor Hiddo Heerspink, Professor Vlado Perkovic and Dr George Bakris
  • Strategies for managing comorbid conditions and end-stage kidney disease (ESKD)
  • CKD treatments just over the horizon and links to CKD guideline resources
  • CKD patient case study quizzes to test your understanding

Treatment goals for chronic kidney disease

What are the priorities for treatment optimisation in chronic kidney disease?

Professor Vlado Perkovic and Dr George Bakris discuss the treatment goals and priorities for optimising treatment of chronic kidney disease (CKD).

The management of CKD relies on a combination of different strategies, including: controlling nephron injury, normalising hyperfiltration, controlling CKD-­related complications, and preparations for kidney replacement therapy.

The core principle of this management is ‘the earlier, the better’, which aims to prevent nephron loss as early as possible and reduce the progression to end-stage renal disease (ESRD)1.

What are the overall goals when managing CKD?

The management of CKD is based on the clinical diagnosis and disease stage, according to glomerular filtration rate (GFR) and albuminuria. Individualised therapies, that are guided by the cause and pathological processes, are determined by the specific clinical diagnosis2. The treatments for CKD aim to2,3:

  • prevent disease development
  • slow disease progression
  • reduce the complications of decreased GFR
  • reduce the risk of cardiovascular disease
  • improve survival and quality of life

The disease stage can also be used to guide non-specific therapies that slow the progression of the disease and reduce the risk of complications2,3. Recommendations based on disease stage are cumulative: early-stage recommendations are included within late-stage recommendations2,3.

How do you control ongoing nephron injury?

As a variety of triggers can drive nephron injury, disrupting these triggers with treatment can slow the progression of CKD to end-stage renal disease (ESRD)1.

For genetic causes of kidney disease, treatments are limited to enzyme replacement therapy or substrate supplementation. In cases of immune mediated nephron injury that have a genetic component, CKD progression associated with C3 glomerulonephritis or atypical haemolytic uraemic syndrome can be treated with complement inhibitors4.

Immunomodulatory drugs can be used to target immune mediated CKD disorders with the aim of limiting nephron injury5

In acute forms of immune mediated nephron injury, presentation is seen as either vasculitis, immune complex glomerulonephritis, or interstitial nephritis (such as allograft rejection).

However, in smouldering immune injuries (such as chronic IgA nephropathy) it is difficult to differentiate immune versus non­immune mechanisms in the progression of CKD and, as a consequence, the efficacy of management through immunosuppression or RAS blockade and blood pressure control is less apparent6.

How do you minimise the stress on remnant nephrons in CKD?

It is essential to minimise the stress on remnant nephrons by preventing further acute kidney injury (AKI). It is therefore important to avoid1:

  • nephrotoxins (such as high volumes of radio contrast media, non-steroidal anti-inflammatory drugs, proton pump inhibitors or occupational toxins)
  • hypovolaemic states
  • urinary outflow obstruction
  • smoking-related cardiovascular disease
  • specific antibiotic treatment (limited to cases of dysuria, bacteriuria, and leukocyturia)

Specific medications do exist to prevent some of these triggers, such as urinary tract obstruction, infections, and some forms of toxic injury; however, the recovery of the lost nephrons is not possible1.

How do you normalise single-nephron hyperfiltration?

Angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) can inhibit the renin-angiotensin system (RAS) and consequently significantly reduce single-nephron GFR and glomerular filtration pressure. This leads to decline in proteinuria and total GFR and moderately increased serum creatinine levels7.

A moderate increase in serum creatinine levels indicating a decline in single nephron GFR, can be a powerful predictor of a nephroprotective effect8

While increased serum creatinine may be disconcerting to patients and some physicians, reducing hyperfiltration in remnant nephrons is essential for reducing the progression of CKD in patients with proteinuria1. Conversely, ACEi or ARBs do not reduce non­proteinuric forms of CKD progression, such as autosomal dominant polycystic kidney disease9.

Various randomised clinical trials have shown that RAS inhibitors can reduce or even prevent CKD progression10. A further reduction in proteinuria and CKD progression can be achieved with a reduction in dietary salt as well as medications that support the control of blood pressure and hyperlipidaemia11,12. These interventions can be particularly necessary where kidney replacement therapy is not available or affordable1.

In diabetic kidney disease (DKD), sodium-glucose cotransporter 2 (SGLT2) inhibition can cause an immediate functional reduction in GFR. The GFR reduction is thought to reduce the tubular transport work and metabolic demand, improving renal cortical oxygenation, which is associated with protection from CKD13,14. The effect of SGLT2 inhibitors to reduce glomerular hyperfiltration is thought to be a shared mechanism between DKD and CKD15. In the DAPA-CKD trial, dapagliflozin was evaluated for proteinuric CKD attributed to hypertension or glomerular diseases that did not require immunosuppression. On a background of RAS inhibition, similar risk reductions for the primary and secondary outcomes were observed irrespective of diabetes status or CKD aetiology, with no evidence of statistical interaction by subgroup across primary and secondary outcomes16.

Why is it important to control the factors associated with CKD progression?

An important part of the management of CKD is addressing the multiple factors that are associated with disease progression. Various general measures have been described in the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines that address cardiovascular health and CKD together, or separately17.

Cardiovascular disease (CVD) risk factors can indirectly and directly impact CKD progression and so general lifestyle measures are recommended to improve17:

  • cardiovascular health
  • blood pressure (BP) control
  • Interruption of the renin-angiotensin-aldosterone system (RAAS)

Metabolic parameters, such as blood sugar, uric acid, acidosis, and dyslipidaemia, are also recommended to monitor and control17.

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