Hypertension is a cause of CKD, but it is also a consequence of failing kidneys so the control of blood pressure is important. The use of angiotensin converting enzyme (ACE) inhibitors and/or angiotensin receptor blockers (ARBs) is considered to be the most effective in slowing the progression of CKD. ¹⁶ Proteinuria as a result of increased leakage from the glomeruli or from a decreased tubular reabsorption is a marker of CKD, and may cause progression of CKD. ¹⁷ Albumin:creatinine ratio (ACR) is the test of choice to identify proteinuria in people with diabetes and is already widely used in practice. Albumin is the predominant component of proteinuria in glomerular disease and the ACR test is considered to be a sensitive test for detecting early CKD.

NICE guidelines for recommended blood pressure (BP) targets for CKD are < 140/90 and < 130/80 mmHg in patients with diabetes or those with an ACR > 70 mg/mmol or urinary protein excretion > 1 g/24 h. ⁵

A consistent body of evidence from observational studies and clinical trials indicates that body weight is positively associated with BP and hypertension. A meta-analysis of randomised controlled trials (RCTs) revealed that a weight loss of approximately 5 kg led to a reduction of about 4.4 and 3.6 mmHg in systolic and diastolic BP, respectively. ¹⁸ Expressed per kilogram of weight loss this equates to a reduction of 1.05 mmHg in systolic and 0.92 mmHg in diastolic. Another high-quality systematic review in hypertensive individuals suggested that dietary measures which achieve a 3–9% reduction in body weight are likely to reduce systolic and diastolic pressure by about 3 mmHg. ¹⁹

The relationship between salt and BP is often difficult to establish as accurate intakes of sodium intake or excretion are hard to obtain, and adherence to a salt restriction can often be poor. Some researchers believe individuals should be classified as salt-sensitive or resistant. ²⁰ Although at present there is no way of detecting which individuals are salt sensitive, salt sensitivity appears to be more frequent amongst individuals with hypertension and/or diabetes, in black and/or older individuals. ^21,22 Some believe that salt sensitivity is a transient phenomenon during the pathogenesis and development of hypertension. ²³ Since the phenomenon of salt sensitivity has not been characterised it is not yet possible to identify and develop predictive markers, including genetic polymorphisms, for individuals.

This phenomenon may explain some of the variations found in the literature; however, many findings from epidemiological and intervention studies do conclude a positive relationship between salt and BP. ^{24.25. and 26.} There is also a suggestion by some researchers that salt exposure is linked with kidney tissue injury. ²⁷

Several epidemiologic studies have established that dietary potassium intake is inversely related to BP. ²⁸ An increase in potassium consumption has been shown to lower BP or reduce antihypertensive medication, especially in people who are hypertensive. ^29,30 Dietary recommendations should therefore advise on an increase in fruit and vegetable consumption to help reduce BP, unless blood potassium levels are raised. This can often lead to confusion in CKD patients as they may be advised later on to reduce their intake of fruit and vegetables to help control their blood potassium levels.

For further information on hypertension please refer to the chapter on cardiovascular disease.

In diabetic patients, keeping glycated haemoglobin (HbA1c) levels to normal or near normal (<7.5%) has been shown to either delay the onset of diabetic nephropathy or slow the progression. ^{31.32. and 33.} For further information on glycaemic control please refer to the chapter on diabetes.

The great majority of patients with early CKD will have an increased risk of cardiovascular disease (CVD). ³⁴ It has been stated that patients with a GFR < 60 mL/min/1.73 m ² have a higher risk of cardiovascular death, and 74% of patients on dialysis have heart damage. ^{35.36. and 37.} The risk of CVD in patients with CKD far outweighs the risk of progression of the disease. A retrospective cohort study found that only 4% of 1,076 individuals progressed to ERF over a 5.5-year follow-up period, 69% had died at the end of follow-up and the cause of death was cardiovascular in 46% of cases. ¹¹

In the general population the relationship between dyslipidaemia and CVD is well known; however, in CKD patients it is still controversial. Although dyslipidemia has been associated with CKD, it is still uncertain whether lipid-lowering therapy will reduce CVD. The spectrum of dyslipidaemia in CKD is distinct from the general population and the optimal targets for plasma lipids in people with CKD are not yet known. Lipid levels are found to vary with the stage of CKD and presence of diabetes and/or nephrotic syndrome. ^{38.39.40. and 41.} Lipoprotein(a) is also influenced by CKD and the degree of proteinuria. ^38,42

Lipid-lowering therapy has been found to modestly reduce the rate of kidney function loss in patients with moderately impaired kidney function (stage 3A) with or at risk of CVD. ⁴³ A number of other researchers have also suggested that managing risk factors for CVD may slow the rate of decline of kidney function. ^44,45 Evidence for the beneficial effects of lipid therapy on reducing CVD risk in CKD is, however, scarce. A randomised, placebo-controlled, intervention trial on lipid-lowering therapy in ERF patients with diabetes showed no significant reduction in primary endpoint of cardiovascular death, nonfatal myocardial infarction or stroke by statin therapy. ⁴⁶ One explanation for this could be a higher significance of structural heart disease (e.g. vascular calcification, left ventricular failure) rather than classical myocardial infarction in advanced kidney disease. Results of a larger clinical trial, the Study of Heart and Renal Protection (SHARP), which is currently investigating 9,000 CKD patients will hopefully help to answer the question of whether lipid-lowering therapy is beneficial in CKD. ⁴⁷

The NICE guidelines on CKD currently recommend that people with CKD and coronary disease should be treated according to existing guidelines and those who do not have evidence of coronary disease should be treated according to their estimated risk, using the Joint British Societies Guidelines. ⁵ Statins should be offered for the secondary prevention of CVD irrespective of baseline values.

Anaemia is very common in CKD due to a reduction in erythropoietin production. There is increasing evidence that correcting anaemia may have favourable effects on the progression of CKD. ⁴⁸ Guidelines for haemoglobin targets have been developed, but there is no consistent agreement on the appropriate level . NICE recommend anaemia treatment should aim to maintain stable haemoglobin levels between 10.5 and 12.5 g/dL. One study, the Correction of Hemoglobin and Outcomes in Renal Insufficiency (CHOIR), investigating whether achieving higher haemoglobin targets of 13.5 g/dL is beneficial was terminated as findings suggested an increased risk of CVD outcomes with these higher levels. ⁴⁹

In the 1980s a number of animal studies showed that a low protein diet improved survival and slowed the progression of renal failure. ^{50.51. and 52.} A meta-analysis in 1992 concluded that the use of low protein diets in humans also slowed the progression of renal disease. ⁵³ In this meta-analysis 46 trials were looked at but only 6 reports of RCTs were selected. Many of the earlier human studies reporting benefits of low protein diets were flawed in their methodological approach, compliance with the prescribed protein intake was poor and little or no nutritional assessment was undertaken.

Results of two large multicentred studies were published in the 1990s. The Northern Italian Cooperative Study investigated 456 patients and found no difference in creatinine clearance when patients were randomly allocated protein intakes of either 1 g/kg or 0.6 g/kg body weight for a 2-year period. In this study the authors concluded that the underlying disease was more influential than the dietary changes but noted that compliance was poor with the 0.6 g/kg protein diet. ⁵⁴

The other study published was the MDRD study from the USA. ¹ This trial operated as two concurrent studies, involving a total of 840 patients. In study 1 patients with a GFR of 25–55 mL/min/1.73 m ² were randomly assigned to a usual protein diet (1.3 g/kg/day) or a low-protein diet (0.58 g/kg/day). Patients in study 2, with a GFR of 13–24 mL/min/1.73 m ^2, were randomly assigned to the low protein diet or to a very low protein diet (0.28 g/kg/day) with a keto acid–amino acid supplement. No significant difference was found between the groups in the rate of decline of renal function in study 1. In study 2 the very low protein group had a marginally slower decline in glomerular filtration than the low protein group but there was no difference in the time to reach ERF or death.

As there were problems with compliance with the prescribed protein intake in the MDRD study, a secondary analysis was undertaken to examine the relationship between actual achieved protein intake and the rate of decline of renal function. ⁵⁵ This secondary analysis pointed to a correlation between actual protein intake and a decreased rate of decline in GFR. However, as the analyses were made by correlation rather than ‘intention to treat’, this finding cannot be directly applied to the clinical setting.

A Cochrane review published in 2007 looked at 12 studies, including 9 RCTs, to assess the effects of protein restriction in diabetic renal patients. ⁵⁶ The authors concluded that reducing protein intake appears to slightly slow progression of diabetic kidney disease but this is not statistically significant. The authors commented that individual variation existed so protein restriction may be beneficial in some individuals. No data were found on the effects of low protein diets on health-related quality of life.

Despite much research, the area of protein restriction and its possible effect of slowing the progression of CKD still remain controversial. Suggested reasons for limiting the protein intake of CKD patients include reducing uraemic symptoms, reducing acidosis and proteinuria and slowing the decline of kidney damage. Limitations over restricting protein intake have arisen, firstly, as concerns over a deterioration in nutritional status and associations between hypoalbuminaemia and increased mortality, and secondly because many patients already self-restrict their protein intake through imposed dietary restrictions or due to a loss of appetite and generally feeling unwell. ^57,58 In view of the conflicting evidence, nutritional status and quality of life issues many UK units currently choose a moderate protein restriction of 0.8–1 g protein/kg ideal body weight.

The incidence of protein energy malnutrition (PEM) increases with deteriorating kidney function and is associated with a poor outcome; therefore early dietetic intervention is important. ⁵⁸ Most patients with a GFR < 30 should be referred to a dietitian. In view of the conflicting evidence around protein restriction many UK units choose a moderate protein restriction of 0.8–1 g protein/kg IBW. Renal dietitians will use protein exchanges to assess a patient’s intake. Either 6 or 7 g protein exchanges are used for HBV protein and 2-g exchanges for low biological value (LBV) protein. It may not be appropriate to teach these to the patient. As patients become uraemic and symptomatic they often self-restrict protein anyway. Symptoms of uraemia can include loss of appetite, nausea and vomiting, taste changes, tiredness and itching.

An energy intake of 35 kcal/kg IBW is recommended to prevent nitrogen catabolism; however, obesity should be avoided as a BMI > 30 is associated with a variety of health problems. There are no randomised trials examining the safety and efficacy of low-fat diets in patients with CKD although dyslipidaemia is evident in a number of patients. Where possible lipid-lowering dietary measures should be advised when this is not at the detriment of the patient’s nutritional status. Tight glycaemic control is essential in patients with diabetes to help slow the progression of CKD.

The risk of developing hyperkalaemia is inversely related to renal function and it is only when at least 50% of the kidney function has been lost that the blood biochemistry is affected. Hyperkalaemia may occur as a result of impaired tubular secretion of potassium in patients with mild CKD. It is important for the dietitian to be aware that a number of other factors can contribute to hyperkalaemia: catabolism, certain medications (i.e. ACE inhibitors, potassium sparing diuretics, angiotensin receptor blockers), metabolic acidosis, blood transfusions, dehydration and constipation. Metabolic acidosis can develop with the progression of renal disease, and results in both hyperkalaemia and increased protein catabolism. Oral bicarbonate supplementation (or increasing the dialysate bicarbonate concentration if on dialysis) may be given to correct this, although this may contribute to greater sodium retention and hypertension.

Patients with serum potassium levels over 5.5 mmol/L are usually targeted for dietary advice if hyperkalaemia cannot be corrected by other means. It is important to check local guidelines for normal potassium ranges. Generally, a slow rise in serum potassium level, as seen with CKD, is tolerated better than an abrupt rise in potassium levels. Many patients with hyperkalaemia are asymptomatic, but the consequences of hyperkalaemia can be fatal as listed below:

Dietary advice for potassium restriction should be individually tailored to the patient. Advice should focus on altered cooking methods, suitable portion sizes and lower potassium food sources. As potassium is water-soluble one example of an altered cooking method is to recommend boiling potatoes and vegetables in large amounts of water instead of cooking in the microwave or steaming. The vegetable water must not be used to make gravy, soups or sauces.

If the serum potassium is slightly raised, only a few dietary changes may be advised although the patient should still be educated on which foods are high in potassium to avoid further problems. Table 16.5 gives a list of foods high in potassium which are normally limited and examples of lower potassium alternatives. The use of 4-mmol potassium exchanges can be useful for the renal dietitian and some patients may also benefit from this knowledge to allow more variety in their diet. Other patients may find this method too complex.

Potassium restrictions should only be advised if absolutely necessary as once patients have been advised to avoid certain foods they will often find it difficult to reintroduce these foods again. Remember to check the biochemistry first to see whether potassium restrictions are really required.

The kidneys play a crucial role in regulating serum phosphate and calcium homeostasis, both directly and through the activation of vitamin D. Problems start to occur with the control mechanisms essential for calcium and phosphate homeostasis early in the course of CKD, before any abnormalities are seen in the biochemistry, and continue to progress as kidney function decreases. ⁶⁶ As CKD advances, phosphate retention occurs and hypocalcaemia develops as the kidneys fail to activate vitamin D. Both hypocalcaemia and hyperphosphataemia stimulate an increase in the parathyroid hormone (PTH). ^67,68 This condition shown in Figure 16.1 is known as secondary hyperparathyroidism. The excess parathyroid hormone then acts on bone to increase the release of calcium and phosphate. The blood levels of calcium and phosphate then increase, while the bones become weaker, a condition known as renal bone disease. Excess phosphate binds with calcium to form calcium phosphate which can be deposited in the heart, lungs, kidneys and other soft tissues. This is referred to as soft tissue calcification. There is evidence that poor calcium and phosphate control affect morbidity and mortality due to cardiovascular calcification. ⁶⁹ Although many patients complain of itching, most are not aware of these serious developments until they experience bone pain and fractures.

Treatment for suppressing PTH levels includes a dietary phosphorus restriction, phosphate binders to limit the absorption of phosphorus and supplementation with active vitamin D and calcium-containing phosphate binders to help correct hypocalcaemia. In practice dietary phosphorus is normally referred to as phosphate to avoid confusion for patients.

Dietary phosphorus is mainly found in protein-rich foods as shown in Box 16.1. When advising on restrictions care should be taken that patients are not put at risk of PEM. Providing that the patient is not malnourished it is believed to be beneficial to consider a dietary phosphorus restriction early. PTH levels begin to rise when GFR falls below 60 mL/min/1.73 m ² (CKD stage 3), even though serum phosphorus levels are normal, so levels of PTH are believed to be a better indicator of when to begin a dietary phosphorus restriction. K/DOQI clinical practice guidelines on bone metabolism and disease in CKD recommend that dietary phosphorus restrictions should be initiated when blood PTH levels begin to rise and/or when serum phosphate levels are elevated at any stage of CKD (normally > 1.4 mmol/L). ⁷⁰