A recent descriptive study from Germany has found that use of complementary and alternative medicines (CAMs) is common among renal patients.⁴ This is consistent with other reports that have indicated that the consumption of complementary medicine products, including herbs, herbal teas, or nutritional supplements such as vitamins or minerals, has increased in the last decade.⁵

A high rate of complementary medicine product use has been documented for a number of different patient populations with chronic diseases, such as liver-transplant recipients,⁶ HIV-positive patients,⁷ patients with epilepsy,⁸ and patients with diabetes,⁹ and clinicians are often inadequately informed about CAM consumption by their patients.¹⁰

The prevalence and patterns of CAM utilisation among renal patients with chronic kidney diseases was recently investigated.¹¹ The study revealed the following facts.

• An important finding, which is consistent with current thinking, was that patients reported that only a minority of clinicians had taken an active interest in consumption of CAMs.

• Fifty-seven percent of dialysis patients and 49% of transplant patients reported to be regular CAM consumers.

• CAM consumption was positively associated with female gender and negatively with diabetes as comorbidity.

• Forty-one different CAM products had been named, with mineral supplements and vitamins ranking first.

• Numerous renal patients had regularly consumed herbal teas and citrus juices (50% and 35%, respectively).

• Of concern was that approximately 40% of the documented CAM/health food consumption had potential risks for patients because of constituents that either accumulate in renal failure or interact with pharmaceutical medications.

• Approximately 50% of dialysis patients and 73% of transplant patients used to inform their physicians about CAM consumption.

• Patient awareness of the interaction risks linked to CAM was especially low in dialysis patients when compared to transplant patients (39% versus 78%) and increased when clinicians had routinely questioned patients about their CAM consumption.¹¹

In addition, CAM products (e.g. herbal products, functional foods such as probiotics) and physical therapies (e.g. acupuncture) have been used in other non-chronic associated kidney diseases.¹²

Lifestyle and other risk factors

Age

Kidney function is reduced in older people; that is, greater risk with increasing age.¹³

Obesity is strongly associated with several major health risk factors.¹⁴ These include type 2 diabetes mellitus (T2DM), hypertension and heart disease, which have significant causal correlations to chronic kidney disease.¹⁵ Moreover, studies have reported that Body Mass Index (BMI) was associated with an increased risk of the development of end-stage renal disease.^16,¹⁷

Diabetes

Approximately 40% of new incident dialysis patients have been diagnosed with diabetes which today is considered the most important and increasing risk factor for kidney disease.^18,¹⁹ T2DM (see Chapter 13 on diabetes) is the number 1 cause of kidney failure, responsible for more than 1 of every 3 new cases.¹⁸

High blood pressure (hypertension)

Hypertension is the second most common cause of kidney failure.²⁰ High blood pressure puts more stress on blood vessels throughout the body, including the nephrons. Normal blood pressure is defined as less than 130/85 — and this is the considered target for persons diagnosed with diabetes, heart disease, or chronic kidney disease. Weight control, physical activity (see later in this chapter), and medications can control blood pressure — and can assist in preventing or slowing the progress from kidney disease to kidney failure.

Urinary tract system blockages

Scarring from infections or a malformed lower urinary tract system as a result of a birth defect can force urine backflow, damaging the kidneys.²¹ Blood clots or plaques of cholesterol that block the kidney’s blood vessels can reduce blood flow to the kidneys and also cause damage. Repeated kidney stones can block the flow of urine from the kidneys and is an additional cause of obstruction that can damage the kidneys.

Overuse of medications

A number of pharmaceutical drugs are known to cause renal failure as a side-effect.

Continued use of analgesic medications containing ibuprofen, naproxen, or acetaminophen have been linked to interstitial nephritis, that can lead to kidney failure.²² A US study suggested that ordinary use of analgesics (e.g. 1 pill per day) was not harmful in men who were not at risk for kidney disease.²³ However, concomitant use of NSAIDs and dehydration (e.g. severe diarrhoea) can predispose to renal impairment and failure, especially in the elderly. Allergic reactions to, or side-effects of, antibiotics such as penicillin and vancomycin may also cause nephritis and lead to kidney damage.²⁴ Note that adverse reactions can also occur with complementary medicines (CMs) (e.g. herbs and high-dose vitamins).

Illicit drug abuse

The illicit use of drugs involves millions of people worldwide and is associated with a variety of medical complications. Use of certain non-prescription drugs, such as heroin or cocaine, can damage the kidneys, and may lead to kidney failure and the need for dialysis.^25,²⁶

Inflammation and/or diseases

Certain illnesses, like glomerulonephritis, can damage the kidneys and lead to chronic kidney disease.²⁷ Moreover, persons at increased risk of kidney disease include those diagnosed with systemic lupus erythematosus, sickle cell anaemia, cancer, HIV/AIDS, hepatitis C, and congestive heart failure.²⁸^–³²

Family history — surrogate marker for risk of future nephropathy

Persons are at an increased risk if they have 1 or more family members who have chronic kidney disease, are on dialysis, or have had a kidney transplant.³³ Diabetes and high blood pressure can also have familial trends and present with risks for chronic kidney disease (see previous sections in this chapter).

Low birth weight

A recent systematic review has concluded that existing scientific data indicates that low birth weight is associated with subsequent risk of chronic kidney disease.³⁴ Further well-designed population-based studies are required, though, in order to accurately assess birth weight and kidney function and important cofounders, such as maternal and socioeconomic factors.

Trauma and/or accident

Accidents/injuries,³⁵ surgical procedures, and radio-contrast dyes used to monitor blood flow to the heart and other organs are a risk for developing contrast nephropathy due to reduced blood flow to the kidneys, causing acute kidney failure.³⁶

Environmental toxins

The kidneys can be the target of numerous xenobiotic toxicants, including environmental chemicals.³⁷ The kidney’s anatomical, physiological, and biochemical features make it particularly susceptible to many environmental compounds. Factors contributing to the sensitivity of the kidneys include: large blood flow; the presence of a variety of xenobiotic transporters and metabolising enzymes; and concentration of solutes during urine production.³⁶

Glomerulonephritis is the most common cause of end-stage renal failure in most countries, and is exacerbated and may be causal by exposure to chemicals present in the workplace, the home and in the public environment. The most common nephrotoxic chemicals are hydrocarbons, present in organic solvents, glues, fuels, paints and motor exhausts. Exposure is common among painters, printers, cabinet makers, fitters and mechanics, electricians, and in the manufacturing industry.^38,³⁹ Other compounds with nephro-toxicity potential include lead, mercury, cadmium and some pharmaceuticals (e.g. gentamycin).⁴⁰^–⁴³

A recent study has demonstrated that contact with cadmium and lead increases the risk for chronic kidney disease.⁴⁴ Given that these substances are widely distributed in populations at large, this study provides novel evidence of an increased risk with environmental exposure to both metals.

Mind–body medicine

Research shows that regular use of stress management techniques (e.g. cognitive behavioural therapies) can significantly influence those chronic disease conditions that can have adverse health effects on kidney function such as cardiovascular disease (CVD), T2DM and hypertension (see Chapters 10, 13 and 19, respectively).

Furthermore, the psychosocial assessment of the patient with end-stage renal disease is critically important because there is growing evidence that the psychosocial status of the patient significantly impacts medical outcomes and the objective of medical therapy is to maximise a patient’s sense of wellbeing and their quality of life (QOL), in particular for those patients that are receiving chronic peritoneal dialysis.

Muscular relaxation

Progressive muscle relaxation training was investigated in 46 patients who had been treated with dialysis.⁴⁵ The study demonstrated that progressive muscle relaxation training for dialysis patients helped decrease state- and trait-anxiety levels and had a positive impact on the QOL of these patients.

Cognitive behavioural therapy (CBT)

Three small trials have reported benefit with CBT for patients undergoing haemodialysis.^46,^{47, 48} The first study assessed the influence of CBT on chronic haemodialysis patients’ ability for self-care and to achieve fluid intake-related behavioural objectives.⁴⁴

The participants were 10 patients participating in a 4-week base-line phase, a 6-week intervention phase and a 4-week follow-up phase. The results showed that the average achievement of the fluid intake objective in the intervention phase was 65%. Fifty percent of participants achieved their objectives at least 75% of the time without individualised reinforcement. Hence, it was concluded that CBT was effective in helping patients change their fluid intake behaviours.

In a further study with an RCT design, enhancing adherence to haemodialysis fluid restrictions was investigated in a group of 56 participants receiving haemodialysis from 4 renal outpatient settings.⁴⁶ The study showed that applying group-based CBT (4 weeks duration) was feasible and effective in enhancing adherence to haemodialysis fluid restrictions.

Another study, with a nurse-delivered haemodialysis patient education program incorporating CBT compared to a standard patient education program on patients’ salt intake and weight gain, found that both programs were shown to be effective, but CBT had a longer effect (12 weeks versus 8 weeks).⁴⁷

Patients with end-stage renal disease often are diagnosed with depression⁴⁹ and sleep disorders⁵⁰ which have been linked to increased mortality. A recent randomised controlled pilot trial with 24 peritoneal dialysis patients reported that CBT may be effective for improving the quality of sleep and decreasing fatigue and inflammatory cytokine levels in these patients. CBT was concluded to be an effective non-pharmacological therapy for peritoneal dialysis patients with sleep disturbances.⁵¹

It should be noted though that there are few data to support the role of CBT, social support group interventions, and electroconvulsive therapy for treatment of sleep disturbances and depression in patients with chronic kidney disease. Larger randomised, controlled clinical trials aimed at the treatment of these conditions in patients with end-stage renal disease are very much warranted.

Educational interventions

There is increasing evidence that educational interventions aimed at empowering patients are successful in chronic disease management.

A systematic review of randomised clinical trials was recently conducted from studies that included patients diagnosed with any of the following stages of chronic kidney disease such as early pre-dialysis and dialysis.⁵² Twenty-two studies were identified involving a wide range of multi-component interventions with variable aims and outcomes depending on the area of kidney disease care. Eighteen studies provided significant results for analysis. The majority of studies aimed to improve diet and/or fluid concordance in dialysis patients and involved short- and medium-term follow-up. A single major long-term study was a 20-year follow-up of a pre-dialysis educational intervention that showed increased survival rates. This review concluded that multi-component structured educational interventions were effective in pre-dialysis and dialysis care, but the quality of many studies was suboptimal.⁵² Further, effectively framed and developed educational interventions for implementation and evaluation are required. The study also concluded that this strategy could lead to possible prevention or delay in the progression of kidney disease.

Physical activity/exercise

Exercise can help keep people strong, flexible and better prepared to handle life stressors and illnesses.⁵³ This is important for patients with kidney disease because, for example, independent of the course of kidney disease, physical fitness decreases continuously with the progression of chronic renal disease.⁵⁴ Hence, people with kidney disease, both early and late stage, can benefit from participation in appropriate physical activity programs⁵⁵ given that life expectancy in haemodialysis patients is reduced fourfold on average versus healthy age-matched individuals.⁵⁶

End-stage renal disease patients present many cardiovascular complications and suffer from impaired exercise capacity. A number of studies have investigated exercise programs for patients with renal disease and found beneficial morphological, functional and psychosocial effects in end-stage renal disease patients on haemodialysis.^57,^{58, 59}

One study noted that intense exercise training improved left ventricular systolic function at rest in haemodialysis patients. Moreover, it was reported that both intense and moderate physical training led to enhanced cardiac performance during supine sub-maximal exercise.⁵⁵ An additional study compared the effects of 3 modes of exercise training on aerobic capacity and aimed to identify the most favourable, efficient and preferable to patients on haemodialysis with regard to functional improvements and participation rate in the programs.⁵⁶ Fifty-eight volunteer participants were screened for low-risk status and selected from the dialysis population. The 48 patients who completed the study protocol were randomly assigned either to 1 of the 3 training groups or to a control group. These results showed that intense exercise training on non-dialysis days was the most effective way of training, whereas exercise during haemodialysis was also effective and preferable.⁵⁶ An additional study by the same research group showed that haemodialysis patients can adhere to long-term physical training programs on the non-dialysis days, as well as during haemodialysis, with considerable improvements in physical fitness and health. Also, although training out of haemodialysis seemed to result in better outcomes, the dropout rate was higher.⁵⁷

A more recent study investigated a total of 50 patients with chronic kidney disease (stage 5) on haemodialysis and 35 healthy individuals who served as controls. The 50 chronic kidney disease patients were divided into 2 groups — the haemodialysis group consisted of 31 patients who received usual care without any physical activity during the haemodialysis sessions, while the haemodialysis/physical activity group included 19 patients who followed a program of physical exercise for 6 months.⁶⁰ The study established that exercise training during haemodialysis exerted a beneficial effect on the levels of the vasoactive eicosanoid hormone-like substances in patients on haemodialysis.⁶⁰

A recent single centre prospective study whose objective was to examine the relationship between visceral and somatic protein stores and physical activity in individuals with end-stage renal disease showed that the association between somatic protein and visceral protein stores is weak in patients with chronic kidney disease. Whereas increased levels of physical activity and total daily protein intake were associated with higher lean body mass in patients with chronic kidney disease, higher adiposity was associated with higher C-reactive protein and lower albumin values.⁶¹

Furthermore, an additional study with the objective of determining whether 24 weeks resistance training during haemodialysis could improve exercise capacity, muscle strength, physical functioning and health-related QOL compared to a low-intensity aerobic program was investigated in 27 patients recruited from 2 haemodialysis clinics.⁶² It was concluded that resistance training during haemodialysis significantly improved patient’s physical functioning.

A recent review presented empirical evidence that intradialytic exercise can mitigate primary independent risk factors for early mortality in end-stage renal disease, hence, reducing the progression of skeletal muscle wasting, improving systemic inflammation, cardiovascular function and dialysis adequacy.⁶³ The review concludes that intradialytic cycling and/or progressive resistance training can alleviate primary independent risk factors for early mortality in end-stage renal disease.

Clinical trials have further supported the benefits gained with resistance training exercise by end-stage renal disease patients on haemodialysis.^64,⁶⁵ The first study which was a single-blinded, randomised, placebo-controlled trial of an exercise intervention in haemodialysis patients administered erythropoietin. The intervention consisted of progressive resisted isotonic quadriceps and hamstrings exercises and training on a cycle ergometer 3 times weekly for 12 weeks. The results showed that the exercise program improved physical impairment measures, but had no effect on symptoms or health-related QOL.⁶² The second randomised study was designed to determine whether anabolic steroid administration and resistance exercise training combined induced anabolic effects among patients who were receiving maintenance haemodialysis.⁶³ This study found that patients who exercised increased their strength in a training-specific fashion, and exercise was associated with a significant improvement in self-reported physical functioning as compared with non-exercising groups. Nandrolone decanoate and resistance exercise combined produced anabolic effects among patients who were on haemodialysis.

Moreover it should be noted that as of 2008 there have been over 50 reports, including several randomised controlled trials (RCTs) that have evaluated the effects of intradialytic exercise in end-stage kidney disease.⁶¹

Nutritional influences

Diets and nutritional practices have significant multiple health-related risk factors with ramifications that, if prolonged, can lead to kidney disease.⁶⁶ An example of such a multiple health-related risk factor is obesity and its related risks (see Chapters 10, cardiovascular disease; 13, diabetes; and 19, hypertension).

Weight loss management of obese patients is crucial.^14,^{15, 16}

Mediterranean diet

Traditional diets among Mediterranean cultures (Mediterranean diet) are characterised by the abundance of natural whole foods, especially fruits and vegetables, along with olive oil, fish, and nuts. The diet includes moderate amounts of wine and is low in saturated fat.⁶⁷

A study reported that adhering to a Mediterranean diet provides for a healthier and nutritional hypolipidemic approach in renal transplant recipients.⁶⁸ This study reported that this diet led to a significant reduction in total cholesterol levels by 10%, triglycerides by 6.5%, low-density lipoprotein-cholesterol (LDL-cholesterol) by 10.4% and the ratio of LDL-cholesterol to high-density lipoprotein-cholesterol (HDL-cholesterol) decreased by 10%, while HDL-cholesterol levels remained unchanged. This provided a reduction instead of an increase in the number of participants with hypercholesterolemia, permitting the selection of individual candidates for further pharmacological treatment by carefully evaluating risk–benefit costs. Recently it was reported that the Mediterranean diet was found to be ideal for post-transplantation patients without serious pathologic dyslipidemia.⁶⁹ Moreover, it was concluded that in the case of patients with substantial dyslipidemia, appropriate pharmacologic treatment lowering proatherosclerotic lipid levels should be used in combination with the Mediterranean diet.

A further benefit that has been attributed to the Mediterranean diet for patients with kidney disease is that the diet, being rich in seafood and vegetables, was associated with less interdialytic weight gain compared with a diet rich in protein and carbohydrates.⁷⁰

Given that T2DM is a risk factor for developing kidney disease, recently it has been reported that adherence to a Mediterranean diet may delay the use of antihyperglycemic drug therapy in patients with newly diagnosed T2DM, thereby extending an additional benefit to the kidneys.⁷¹

Dietary Approaches to Stop Hypertension (DASH) diet

The association between obesity, hypertension and nephrolithiasis has been recently reviewed.⁷² The review concluded that adopting a lower sodium diet with increased fruits and vegetables and low-fat dairy products (e.g. as stipulated in the Dietary Approaches to Stop Hypertension [DASH] diet) may be useful for the prevention of both kidney stones and hypertension. It was also suggested that in those patients in whom dietary modification and weight loss was ineffective, thiazide diuretics are likely to improve blood pressure control and decrease calciuria.

Diet plays an important role in the pathogenesis of kidney stones. A recent report has prospectively examined the relationship between a DASH-style diet and incident kidney stones in the Health Professionals Follow-up Study (n = 45 821 men; 18-year follow-up), Nurses Health Study I (n = 94 108 older women; 18-year follow-up), and Nurses Health Study II (n = 101 837 younger women; 14-year follow-up). Consumption of a DASH-style diet was found to be associated with a marked decrease in kidney stone risk.⁷³

It is interesting to note that the DASH diet has been reported to not increase albumin excretion rates despite a 3% increase in energy from the consumed protein.⁷⁴

Protein diet

Low protein diets are commonly prescribed for patients with idiopathic calcium nephrolithiasis.

A recent Cochrane review of 10 studies from over 40 studies with a total of 2000 patients were analysed, of which 1002 had received reduced protein intake and 998 a higher protein intake.⁷⁵ The review concluded that studies investigating protein intake reductions in patients with chronic kidney disease reduced the occurrence of renal death by 32% as compared with those studies with patients on higher or on unrestricted protein intake. Also, the study concluded that the optimal level of protein intake could not be confirmed from these data. An earlier Cochrane review investigating protein intake in children with chronic renal failure found that reducing protein intake did not appear to have a significant impact in delaying the progression to end-stage kidney disease in children.⁷⁶

A recent study compared the effect of very low protein diet supplemented with keto-analogs of essential amino acids (dose of 0.35g/kg/day), low protein diet (dose of 0.60g/kg/day), and free diet on blood pressure in patients with chronic kidney disease stages 4 and 5.⁷⁷ It was shown that in moderate to advanced chronic kidney disease, a very low protein diet had antihypertensive effects that were likely due to a reduction of salt intake, type of proteins, and keto-analog supplementation, independent of actual protein intake.

Results of several case-control studies suggest that high consumption of meat (all meat, red meat, or processed meat) is associated with an increased risk of renal cell cancer. Recently a pooled analysis of 13 prospective studies was conducted that included 530 469 women and 244 483 men and had follow-up times of up to 7–20 years to examine associations between meat, fat, and protein intakes and the risk of renal cell cancer.⁷⁸ The study concluded that consumption of fat and protein or their subtypes, such as red meat, processed meat, poultry and seafood, were not associated with risk of renal cell cancer.

In a prospective, stratified, multi-centre randomised trial, 191 children aged 2–18 years, who were diagnosed with chronic renal failure from 25 paediatric nephrology centres across Europe, were included in the study. This study was designed to determine whether a low-protein diet could slow disease progression.⁷⁹ Patients were divided into 3 groups according to their primary renal disease, and then stratified based on whether their disease was progressive or non-progressive. There was random assignment to the control and diet groups. Protein intake in the diet group was 0.8 to 1.1g/kg/day, with adjustments made for age. There were no protein intake restrictions in the control group. The study continued in all patients for 2 years, and 112 of the participants agreed to continue for an additional year. There were realistic rates of compliance (66%), and no statistically significant differences in the decline of creatinine clearance were found. Furthermore no adverse effects were reported, including no adverse effects on growth from a protein-restricted diet. This study suggests that there is little value in protein restriction in paediatric chronic renal failure.

Vegetarian diet and fluid intake

A diet that is reduced in saturated fat and cholesterol, and that emphasises fruits, vegetables and low-fat dairy products, dietary and soluble fibre, whole grains and protein from plant sources is advantageous for health.⁸⁰

A recent epidemiological case-control study has highlighted the importance of the role of specific foods or nutrients on cancer development, in particular renal cell cancer.⁸¹ This study has reported a significant direct trend in risk for bread (highest versus the lowest intake quintile), and a modest excess of risk was observed for pasta and rice, and milk and yoghurt. Poultry, processed meat and vegetables were inversely associated with renal cell cancer risk. No relation was found for coffee and tea, soups, eggs, red meat, fish, cheese, pulses, potatoes, fruits, desserts and sugars. The results of this study provide additional clues on dietary correlates for renal cell cancer and in particular indicate that a diet rich in refined cereals and poor in vegetables may have an adverse role on renal cell cancer. It is interesting to note that subsequent to this, a study tested whether an underlying intolerance of bread ingredients was responsible for the adverse influence of bread on renal cell cancer.⁸² This study reported that serum levels of IgG against Saccharomyces cerevisiae may well predict survival in patients with metastatic renal cell cancer. The data reported in this study suggested that it was not cereals but baker’s yeast, the critical component of bread, that may cause immune deviation and impaired immune surveillance in predisposed patients with renal cell cancer.

Approximately 80% of kidney stones contain calcium, and the majority of calcium stones consist primarily of calcium oxalate.⁸³ Small increases in urinary oxalate can have a major effect on calcium oxalate crystal formation and higher levels of urinary oxalate are a major risk factor for the formation of calcium oxalate kidney stones.⁷⁹

An RCT investigated nephrolithiasis by randomly assigning 99 participants who had calcium oxalate stones for the first time to a low animal protein, high fibre diet that contained approximately 56–64g/day of protein, 75mg/day of purine (primarily from animal protein and legumes), one-quarter cup of wheat bran supplement, and fruits and vegetables.⁸⁴ After adjustment for possible confounders of age, gender, education and baseline protein and fluid consumption the study showed that the relative risk of a recurrent stone in the intervention group was 5.6 compared with the control group. It was concluded that following a low animal protein, high fibre, high fluid diet had no advantage over advice to increase fluid intake alone.

Dietary oxalate and kidney stone risk is centred on the contribution of oxalate intake to urinary oxalate excretion. A recent study that investigated the intake of oxalate and the risk for nephrolithiasis found that the relative risks for participants who consumed 8 or more servings of spinach per month compared with fewer than 1 serving per month were 1.30 for men and 1.34 for older women.⁸⁵

Foods high in oxalic acids include rhubarb, spinach, beans, eggplant, garlic, cauliflower, broccoli and carrots. Fluids high in oxalic acids include cranberry juice, orange juice, black tea and cocoa. Reducing the intake of these foods and/or fluids in patients with renal impairment and/or those with a tendency to oxalate calcium may help.⁸⁶

For secondary prevention of nephrolithiasis a recent Cochrane review that determined efficacy and safety of diet, fluid, or supplement interventions found that high fluid intake decreased risk of recurrent nephrolithiasis. The review also found that reduced soft drink intake lowered risk in patients with high baseline soft drink consumption.⁸⁷ (See also ‘Water intake’ later this chapter.)

A small study with 10 patients investigated dietary sodium supplementation in stone-forming patients with hypocitraturia.⁸⁹ The results demonstrated that dietary sodium supplementation increased voided urine volume and decreased the relative risk super-saturation ratio for calcium oxalate stones in patients with a history of hypocitraturic calcium oxalate nephrolithiasis.

An early study investigated a vegetarian soy diet and its effects on hyperlipidemia in a prospective cross-over trial of 20 participants, aged 17–71 years (mean age 41 years) with nephrotic syndrome.⁹⁰ Following a 2-month baseline period in which the patients consumed their usual diets, the participants were changed to the vegetarian soy diet for 2 months, after which they resumed their usual diet for a further 2-month washout period. The vegetarian soy diet was rich in monounsaturated and polyunsaturated fatty acids and fibre, low in fat and protein, and free of cholesterol.

During the 2-month vegetarian/soy diet period, serum concentrations of total cholesterol, LDL-cholesterol, HDL-cholesterol, and apolipoproteins a and b were significantly lower than they were during the baseline period — although still not within normal limits. There was also a significant decrease in urinary protein excretion during the soy diet period. All values returned toward baseline levels during the washout period, but remained lower than the pre-diet values. The study concluded that the decreases were similar to the result of a 6-week treatment regimen with 40mg/day of a statin drug (lovastatin). It was also concluded that further studies were needed to confirm these effects and to evaluate patient compliance to more long-term dietary restriction.

Additional studies have investigated the beneficial effects of soy diets on patients with T2DM and nephropathy.^91, ⁹² These studies have found that isolated soy protein consumption improved several markers (i.e. decreased albumin excretion, improvement of LDL:HDL ratios) that may be beneficial for T2DM patients with nephropathy.

Given that changes in dietary protein consumption have important roles in the prevention and management of several forms of kidney disease, a recent review has hypothesised that perhaps by substituting soy protein for animal protein, this could decrease hyperfiltration in diabetic patients and, hence, may significantly reduce urine albumin excretion and improve renal function.⁹³

Recently it was shown in a large prospective cohort study (375 851 participants recruited in EPIC centres of 8 countries) that total consumption of fruits and vegetables was not related to risk of renal cell cancer.⁹⁴

Alcohol

An early review has reported that alcohol over-consumption has multiple effects on kidney function as well as on water, electrolyte and acid-base homeostasis.⁹⁵ Increased blood pressure was demonstrated in men above 80g and in women above 40g ethanol consumption daily. In contrast, young adults consuming only 10–20g/day had lower blood pressure than the abstinent group, indicating a J-curve relationship. This is consistent with a decreased risk for coronary heart disease associated with regular consumption of small alcohol amounts. In fact, a large prospective cohort study (US Physicians Health Study) has reported that in apparently healthy men, alcohol consumption was not associated with an increased risk of renal dysfunction. Instead, the data suggested an inverse relationship between moderate alcohol consumption and the risk of renal dysfunction.⁹⁶ The study reported that men who had 7 or more drinks of wine per week had a 30% lower risk of raised creatinine levels.⁹⁶

Further investigations into the relationships between wine consumption and kidney disease have been limited. A recent review has reported that there is convincing evidence of a beneficial effect of controlled wine consumption in patients with renal disease.⁹⁷ The evidence is built around the fact that long-term alcohol abuse has been associated with many renal alterations in humans. In experimental studies wine polyphenols enhance kidney antioxidant defences, exert protective effects against renal ischemia/reperfusion injury, and inhibit apoptosis of mesangial cells. Controlled clinical trials are, however, needed to confirm the hypothesis.

The mechanisms responsible for the association between alcohol over-consumption and post-infectious glomerulonephritis remain unclear. Moreover, the severe alcohol abuse that was reported to predispose to acute renal failure appeared to be associated with general catabolic effects.⁸⁹

Water intake

A report from the University of Sydney presented at the Australian and New Zealand Nephrology meeting in 2005, detailed a study that people who drank approximately 3 litres of water per day halved their risk for chronic kidney disease.⁹⁸ This report needs to be verified with further studies. The study also reported that those individuals who had a higher intake of fibre (42.3g/day) also appeared to have a reduced risk for chronic kidney disease with a reduction in risk by 34%.

Coffee

It is an established fact that caffeine has a diuretic effect. Various studies have demonstrated that in healthy volunteers the acute administration of caffeine, or drinks containing it, causes a short-term increase in diuresis with a concomitant excretion of substances such as sodium, potassium, chlorides, magnesium, and calcium.^99,^{100, 101}

Whether caffeine reduces or increases the risk for kidney stones is contentious. In the most recent study from 2004, Massey and Sutton ¹⁰² demonstrated that caffeine consumption at a dose of 6mg/kg of lean mass after 14 hours of fasting in 39 volunteers caused an increase in the excretion of calcium, magnesium and citrate, with an increase in the Tiselius index for calcium oxalate stones formation from 2.4 to 3.1 in those participants with a history of calcium lithiasis and from 1.7 to 2.5 in those participants without this history. In general, the consumption of coffee seemed to increase, albeit modestly, the risk of forming calcium oxalate stones. A report in a less recent study demonstrated that the administration of caffeine in healthy young women caused an increased urinary loss of calcium and magnesium, with a significant reduction in the reabsorption percentage after its consumption whereas other parameters, such as creatinine clearance, were not modified.¹⁰³

Studies on the effects of caffeine in participating patients with nephropathy or chronic renal failure, and in those on dialysis, are scarce and therefore no conclusive information can be provided. It should be noted though that studies on patient populations have shown that the consumption of caffeine during dialysis might become a useful semi-pharmacologic option for the prevention and treatment of symptomatic intradialytic hypotension.^102,¹⁰³ Also it is now a strong consensus that chronic caffeine consumption does not contribute to restless leg syndrome, one of the most frequently observed disturbances of patients on haemodialysis.^106,¹⁰⁷

Hence, from a detailed review of the current literature there are significant conflicting opinions and research data regarding the extremes of the diuretic, prolithiasic and toxic effects of caffeine.¹⁰¹

Food allergy

Early studies have reported on sensitisation to usual foods and idiopathic nephritic syndrome.^106,¹⁰⁷ These reports point to a significant contribution for the role of food hypersensitivity to idiopathic nephritic syndrome. An oligoantigenic diet has been proposed to be useful.

Nutritional supplements

Vitamins and minerals

There is limited evidence for the use of multivitamin/mineral preparations for kidney disease. Given that a decline in renal function is related directly to cardiovascular mortality, the administration of vitamins and or minerals that could benefit cardiovascular health may also be useful for maintaining kidney function.¹¹⁰

Folate

A cross-over RCT of 23 children/teenagers with chronic renal failure, aged 7–17 years, was conducted, whereby each participant received 8 weeks of 5mg/m² folic acid per day and 8 weeks of placebo, separated by a washout period of 8 weeks.¹¹¹ There was a significant decrease in homocysteine levels during the folic acid phase from 10.3 mol/L to 8.6 mol/L with an insignificant rise in LDL lag times during the folic acid period. Based on a significantly improved flow mediated vessel diameter in the folic acid group, the study concluded that an 8-week regimen of folic acid could improve endothelial function. Because of the inconclusive folic acid supplementation studies in adults, the authors have speculated that this positive finding might be related to timing of treatment, in that atherosclerosis in children is at an earlier stage of its natural history.¹¹¹ Although folic acid is extremely safe, studies with clinically relevant outcomes are required before folate supplementation can be recommended for routine use in children with chronic renal failure.

Vitamin D

Single vitamin studies have concentrated on reducing the risk for adverse events such as in those patients with chronic kidney disease who have significant abnormalities of bone remodelling and mineral homeostasis and are at increased risk of fracture. A recent systematic study reviewed the scientific evidence of RCTs that reported the use of bisphosphonates, vitamin D sterols, calcitonin, and hormone replacement therapy to treat bone disease following kidney transplantation.¹¹² The review found that treatment with a bisphosphonate or vitamin D sterol or calcitonin after kidney transplantation may protect against immunosuppression-induced reductions in bone mineral density and prevent fracture.

Vitamin C

The role of vitamin C in kidney oxalate urolithiasis remains a risk according to recent studies,¹¹³ particularly in those predisposed to forming kidney stones.¹¹⁴ A recent double-blind cross-over RCT investigated the effects of 2 different vitamin C formulations and found that vitamin C with metabolites (ester-C) significantly reduced urine oxalate levels compared to ascorbic acid.¹¹⁵ This study requires further evaluation with respect to inhibiting oxalate kidney stone formation.

Vitamin E/B6/B12

The Antioxidant Therapy In Chronic Renal Insufficiency (ATIC) Study showed that a multi-step treatment strategy improved carotid intima-media thickness, endothelial function, and microalbuminuria in patients with stages 2–4 chronic kidney disease. Recently an RCT ¹¹⁶ investigated a sequential treatment consisting of pravastatin 40mg/day; after 6 months, vitamin E 300mg/day; and after another 6 months, homocysteine-lowering therapy (folic acid, 5mg/day; pyridoxine, 100mg/day; and vitamin B12, 1mg/day, all in 1 tablet) were added and continued for another year. This regimen was compared to placebo. It was concluded that analysis of separate treatment effects suggested that vitamin E significantly decreased plasma concentrations of asymmetric dimethylarginine (ADMA) — an endogenous inhibitor of nitric oxide synthase (linked to greater CVD risk in patients with chronic kidney failure). Levels were reduced by 4% in the treatment group compared with the placebo group.

A study that investigated dietary supplementation of red grape juice, a source of polyphenols, and vitamin E on neutrophil NADPH-oxidase activity and other cardiovascular risk factors in haemodialysis patients found that the regular ingestion of concentrated red grape juice by haemodialysis patients reduced neutrophil NADPH-oxidase activity and plasma concentrations of oxidised LDL and inflammatory biomarkers to a greater extent than does that of vitamin E.¹¹⁷ This effect of red grape juice consumption may favour a reduction in cardiovascular risk and assist kidney function. The re-regulation of cellular metabolism by polyphenolic compounds may constitute a biologically plausible rescue mechanism of metabolism in patients with chronic kidney disease. Moreover, it has also been recently shown that gamma tocopherol and DHA were well-tolerated and reduced selected biomarkers of inflammation in haemodialysis patients thereby reducing the risk of cardiovascular complications in this patient population.¹¹⁸ Larger trials are required though for further evaluation. Also, on assessing clinical trials utilising vitamin E it is important to distinguish if the supplement and/or compound being investigated is alpha tocopherol or mixed alpha and gamma tocopherols or gamma tocopherol alone.

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