3 Research recommendations

The Guideline Development Group has made the following recommendations for research, based on its review of evidence, to improve NICE guidance and patient care in the future.

3.1 Self-management

Does the provision of educational and supportive interventions to people with chronic kidney disease (CKD) by healthcare professionals increase patients' skills and confidence in managing their conditions and improve clinical outcomes?

Why this is important

CKD is a common long-term condition that frequently coexists with other long-term conditions, including diabetes, cardiovascular disease and depression, and is associated with reduced quality of life. Through greater understanding of their conditions and provision of the information needed to support lifestyle change, people with CKD may be better able to live well with their long-term condition(s). Self-management may also improve their biomedical markers, for example, blood pressure.

People with advanced CKD may benefit from education and support on particular issues, such as preparation for renal replacement, symptom management and specific dietary modifications. However, the current evidence base for self-management support in the CKD population is very limited.

3.2 Antiplatelet therapy

For people with CKD at the highest risk of cardiovascular disease, what is the clinical effectiveness of low-dose aspirin compared with placebo for primary prevention of cardiovascular disease?

Why this is important

CKD is a common long-term condition and a powerful independent predictor of cardiovascular disease. The risks are increased as the estimated glomerular filtration rate (eGFR) decreases and level of albuminuria increases. Kidney Disease: Improving Global Outcomes (KDIGO) classifies people with CKD as being at moderate risk, high risk or very high risk of cardiovascular disease according to their eGFR and albumin:creatinine ratio (ACR). However, the current evidence base for reducing cardiovascular risk in the CKD population is very limited.

3.3 Renin–angiotensin–aldosterone system

For people aged over 75 years with CKD, what is the clinical effectiveness of renin–angiotensin–aldosterone system (RAAS) antagonists?

Why this is important

RAAS antagonists are among the most commonly used drugs. They are recommended for people with CKD to reduce the rate of disease progression and mortality. The evidence for the use of RAAS antagonists is not specific to older people, so these recommendations are the same for all adults, regardless of age. However, there is a clinical suspicion that older people have a higher incidence of adverse effects from using RAAS antagonists, and uncertainty as to the balance of benefits and harm of using these agents in older people.

3.4 Uric acid-lowering agents

In people with CKD who are at high risk of progression, what is the clinical and cost effectiveness of uric acid-lowering agents on the progression of CKD and on mortality?

Why this is important

Observational data have suggested that uric acid is an independent predictor of both progression and new incidence of CKD. It has also been proposed that elevated uric acid may have a role in initiating hypertension, arteriolosclerosis, insulin resistance and hypertriglyceridaemia. Hyperuricaemia is also associated with type 2 diabetes. It is difficult to infer causation from the observational data; is hyperuricaemia nephrotoxic or a marker of reduced eGFR? Is the relationship due to residual confounding?

The current randomised evidence for reducing uric acid in CKD patients is very limited and of poor quality, especially relating to the major outcomes of end-stage kidney disease needing renal replacement therapy and mortality.

3.5 Vitamin D supplements in the management of CKD–mineral and bone disorders

In people with hyperparathyroidism secondary to CKD, does treatment with vitamin D or vitamin D analogues improve patient-related outcomes?

Why this is important

Changes in bone and mineral metabolism and alterations in calcium and phosphate homeostasis occur early in the course of CKD and progress as kidney function declines. The prevalence of hyperparathyroidism increases from 5.5% in people with a GFR over 90 ml/min/1.73 m2 to 23%, 44% and 73% in people with a GFR of 45–59, 30–44 and under 30 ml/min/1.73 m2 respectively. 25‑Hydroxyvitamin D deficiency is twice as prevalent in people with a GFR under 30 ml/min/1.73 m2 compared with those with a normal GFR. Decreased bone mass and changes in bone microarchitecture occur and progress early in CKD increasing the risk of bone fracture. Replacing vitamin D in people with CKD is known to reduce hyperparathyroidism but there is little data to suggest any benefit on clinical outcomes (including CKD progression measured by change in eGFR, all-cause mortality, cardiovascular mortality, cardiovascular events, fractures and hypercalcaemia). Potential benefits of vitamin D therapy in people with CKD include increased bone mineral density and muscle strength, reduced risk of falls and fractures, and reduction in hyperparathyroidism. Potential adverse effects are hypercalcaemia and extraskeletal (vascular) calcification, and increased cardiovascular risk.

  • National Institute for Health and Care Excellence (NICE)