High Protein Diet and Proteinuria: What You Need to Know for Kidney Health

Proteinuria, the presence of excess protein in the urine, is a marker of kidney damage and a predictor of the risk of progression to end-stage renal disease (ESRD). Medical nutrition therapy, particularly protein restriction, plays a crucial role in managing proteinuria and slowing the progression of renal disease. This article explores the relationship between high protein diets and proteinuria, examining nutritional approaches and their influence on kidney health.

Understanding Proteinuria

Proteinuria is a broad term describing the presence of proteins, such as albumin, globulin, Bence-Jones protein, and mucoprotein, in the urine. When persistent, proteinuria indicates kidney damage and is a reliable predictor of the risk of renal failure progression. Kidneys filter wastes created by the foods you eat to help to keep the right balance of nutrients and minerals in your blood and in your body. We all need protein in our diet every day to build muscle, heal, fight infection, and stay healthy. However, excess protein waste can build up in your blood causing nausea, loss of appetite, weakness, and taste changes if you have kidney disease.

The Role of Protein in the Body

Protein is essential for building muscle, healing, fighting infection, and maintaining overall health. Protein needs vary based on age, sex, and general health. Dietary protein comes from animal and plant sources. Animal sources provide all essential amino acids but vary in fat content, with red meat, whole-milk dairy products, and egg yolks being highest in saturated fat. Fish, poultry, and low-fat dairy products are lower in saturated fat. Plant sources may be low in one or more essential amino acids and include beans, lentils, nuts, peanut butter, seeds, and whole grains. A plant-based diet can meet protein needs with careful planning and offers the added benefits of low saturated fat and high fiber content.

Proteinuria as an Independent Risk Factor

Proteinuria is an independent risk factor for progression to end-stage renal disease. Reducing proteinuria is an important strategy in delaying or preventing loss of renal function. Pathophysiological causes correlating proteinuria to kidney damage are various and not entirely known. One important feature is the alteration of the glomerular barrier penetrability, resulting from protease activities and the reduction of the synthesis of proteoglycans. Reactive oxygen species (ROS) and free radicals also play a significant role in the pathogenesis of nephrotic syndromes. Transforming growth factor-beta (TGF-β) cytokine is another factor involved in fibrosis and glomerular sclerosis since it increases the synthesis of the extracellular matrix.

Dietary Protein Intake and Glomerular Filtration

Glomerular filtration is influenced by dietary protein intake, which significantly contributes to kidney workload. Studies have confirmed the renal effects of a protein load and the deleterious role of the renal hyperfiltration response associated with protein intake itself. In chronic kidney disease (CKD), where the number of nephrons is reduced, lowering protein intake can reduce hyperfiltration, potentially enhancing the effects of beneficial drugs like RAAS inhibitors and SGLT2 inhibitors.

Read also: High-Fiber Diet for Better Health

A reduction in protein intake may reduce uremic symptoms and delay the need for dialysis by reducing uremic toxins and improving renal hemodynamics. The effects of a low-protein diet share similarities with those of SGLT2 inhibitors. In CKD patients, a fall of GFR is observed in the first weeks of protein restriction; afterwards, eGFR stabilizes, and the disease tends to progress slower than in patients on an unrestricted diet.

According to the Nutritional Guidelines in CKD (K-DOQI 2020), adults with CKD stages 3-5 (not on dialysis) who are metabolically stable should follow a low-protein diet providing 0.55-0.60 g dietary protein/kg body weight/day or a very low-protein diet providing 0.28-0.43 g dietary protein/kg body weight/day with additional keto acid/amino acid to reduce the risk for end-stage kidney disease. For adults with CKD 3-5 who have diabetes, a dietary protein intake of 0.6-0.8 g/kg body weight per day is reasonable under close clinical supervision to maintain stable nutritional status and optimize glycemic control.

Protein Restriction and Proteinuria Reduction

A low-protein diet may decrease proteinuria, especially in non-diabetic CKD patients. The decrease in proteinuria is associated with beneficial effects on serum albumin levels and lipid metabolism disorders. In hypoalbuminemic patients, it could promote an increase in serum albumin, obviously fostered by the reduction in urinary protein excretion but also by a complex adaptation of protein metabolism linked to postprandial stimulation of protein synthesis, a decline of whole-body proteolysis, and reduction in amino acid oxidation.

Switching animal proteins to vegetable proteins may decrease renal hyperfiltration, proteinuria, and, ideally, in the long term, the risk of developing or worsening renal failure. High dietary protein intake can lead to intraglomerular hypertension, eliciting high levels of TGF-beta and subsequent accumulation of extraglomerular matrix with the development of fibrosis. Studies have shown that a low-protein diet reduces hyperfiltration and glomerular sclerosis in rats.

A meta-analysis of randomized controlled trials demonstrated that the principal target of a low-protein diet was not the improvement of glomerular filtration rate (GFR) but the reduction in proteinuria. In 19 studies, LPD had no significant effect on GFR but had a substantial influence on proteinuria. A reduction of protein intake by 0.1 g/kg/d was associated with a 0.0031 g/24 h reduction in proteinuria. When LPD was continued for over 1 year, proteinuria was significantly reduced.

Safety of Low-Protein Diets

While protein restriction is effective in reducing proteinuria, the safety of low-protein diets (LPD) and very low-protein diets (VLPD) must be considered. Malnutrition is a serious risk, as LPDs expose the patient to insufficient nutrient intake and protein-energy wasting (PEW). However, a meta-analysis showed that LPD did not cause malnutrition and could maintain an adequate nitrogen balance in nephrotic syndrome. Evidence suggests that this balance is maintained because increasing protein loss could promote essential amino acid saving. Adequate calorie intake (30-35 kcal/kg/d) during LPD is important to prevent malnutrition.

The use of keto analogues could reduce the risk of malnutrition since supplementation improves nitrogen balance and enhances protein status. No definitive conclusions on the safety of LPD and VLPD could be drawn from the above studies as there were several confounding factors, and data on effective protein intake was insufficient.

Type of Protein and Kidney Disease

Clinical trials on diet and kidney disease usually focus on protein intake but rarely on the type of protein. A recent cross-sectional study found that a vegetarian diet was significantly associated with a lower prevalence of CKD. A lower prevalence of proteinuria was associated with the vegan group. Soy protein consumption has been shown to reduce serum creatinine, serum phosphorus, and triglyceride concentrations compared with animal protein. Studies have found that soy diets are not dangerous for the kidney and could probably reduce the decline of glomerular filtrate and progression of proteinuria in the long term.

High Protein Diets: Risks and Considerations

Although high-protein diets continue to be popular for weight loss and type 2 diabetes, evidence suggests that worsening renal function may occur in individuals with-and perhaps without-impaired kidney function. High dietary protein intake can cause intraglomerular hypertension, which may result in kidney hyperfiltration, glomerular injury, and proteinuria. It is possible that long-term high protein intake may lead to de novo CKD.

Compared with protein from plant sources, animal protein has been associated with an increased risk of ESKD in several observational studies. Potential mediators of kidney damage from animal protein include dietary acid load, phosphate content, gut microbiome dysbiosis, and resultant inflammation. Adopting current dietary approaches that include a high proportion of protein for weight reduction or glycemic control should be considered with care in those at high risk for kidney disease.

The estimated average requirement for protein intake is 0.6 g of protein per kilogram of ideal body weight per day. The recommended daily allowance for protein intake is 0.83 g/kg per day. Protein consumption >1.5 g/kg per day is generally considered to be a high-protein diet.

Additional long-term observational studies have also described the association of high protein intake with a decline in kidney function, whereas others have not. Several studies have shown a link between high protein intake and increased albuminuria or proteinuria as an early indicator of kidney damage. Mechanistically, high protein intake may lead to increases in kidney volume and weight in humans, which was demonstrated in a mouse model as mesangial matrix expansion with tubulointerstitial fibrosis.

High dietary intake of protein may lead to higher levels of urea and other nitrogenous waste products. A diet with high protein intake might also lead to metabolic acidosis among patients with advanced CKD who have impaired acid excretion and generation of bicarbonate, particularly in the context of protein sourced from animal-based foods. Plant-based foods can be used to reduce both the dietary acid load and the severity of metabolic acidosis.

Several observational studies have noted the source of dietary protein intake in relation to CKD incidence, finding a strong association between intake of animal protein, especially processed red meat consumption, and incidence and progression of CKD. The pathophysiology of the association of animal protein with CKD remains unclear. One proposed mechanism is the link between animal protein consumption and hypertension.

Special Considerations

Ketogenic Diet

The ketogenic diet, which restricts carbohydrates and emphasizes fat intake, typically includes a moderately high to high level of protein (1.2-2.0 g/kg per day). For patients with existing kidney disease, the diet’s high protein intake may accelerate the progression of their kidney disease. Of equal concern for those without CKD is the high amount of fat in the ketogenic diet. The acid load consumed and generated among those following a ketogenic diet could also lead to metabolic acidosis and related complications.

Solitary Kidney

Persons with a congenital or acquired solitary kidney have decreased renal mass, which may lead to glomerular hypertrophy and hyperfiltration. High-protein diets should be avoided, if possible, and plant-based proteins may be recommended. In general, people with one kidney should avoid excessively high dietary protein intake (>1.2 g/kg per day) and high dietary sodium intake; they should also consume adequate dietary fiber and avoid obesity.

Gaps in Knowledge and Future Research

There are substantial gaps in our knowledge about the effects of high-protein diets on kidney health, which may result from difficulties in implementing methodologically rigorous research in this area. The lack of a uniform definition of a high-protein diet, as well as variation in sources of protein across studies, may have contributed to mixed findings. Further research is needed to fully elucidate the underlying mechanisms by which high protein intake may adversely affect kidney function, particularly in the context of CKD.

Practical Recommendations

Consult a Dietitian: Individuals with kidney disease should consult a kidney dietitian to determine the appropriate amount and type of protein intake.
Limit Protein Intake: People with CKD who are not on dialysis should limit protein intake to slow the loss of kidney function.
Increase Protein Intake on Dialysis: Individuals on dialysis need a higher amount of protein to maintain blood protein levels and improve health.
Choose Plant-Based Proteins: Emphasize plant-based protein sources to reduce renal hyperfiltration and dietary acid load.
Monitor Kidney Function: Regular monitoring of kidney function is essential to adjust diet and medications as needed.
Avoid High Protein Diets: Individuals at high risk for kidney disease should exercise caution with high-protein diets for weight reduction or glycemic control.
Stay Hydrated: Drink two to three quarts of fluid every 24 hours, unless instructed otherwise.

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