1. Introduction

Proteinuria is a common clinical manifestation of kidney disease. When the qualitative test for protein in urine (such as acetic acid heating method, sulfosalicylic acid method, or protein qualitative test paper method) shows a positive result, it is referred to as proteinuria. Normal adult urine contains trace amounts of protein, and the normal range of urinary protein levels in healthy individuals is <150 mg/24 h urine [1]. Persistent proteinuria can cause damage to the kidneys, leading to glomerular sclerosis due to the kidneys being in a state of high perfusion, high osmotic pressure, and high pressure. Excessive reabsorption of protein by renal tubules leads to protein deposition in the epithelial cells of the renal tubules, causing tubular damage [2, 3]. Therefore, urinary protein can cause the continuous progression of kidney diseases and is an independent risk factor for the deterioration of renal function [4]. Proteinuria, as the most important manifestation of kidney disease, is closely related to its occurrence and development. However, it can also be a transient normal phenomenon in children. Intense physical activity, fever, and dehydration can also cause an increase in urinary protein levels. Recently, there have been reports that the research focus has shifted from “proteinuria” to “urinary albumin.” Epidemiological studies in adults have shown a close relationship between increased urinary albumin and the occurrence of kidney and cardiovascular diseases [5].

Since the 1970s, Japan, South Korea, and China have conducted regular urine screening in schools, and it has been found that a considerable proportion of asymptomatic children have proteinuria. According to reports, screening conducted in Taiwan, China, among 3 million primary and secondary school students since 1990, showed that 5.81 individuals per ten thousand people had severe proteinuria [6]. This indicates that the incidence of proteinuria is increasing year by year. In traditional Chinese medicine theory, the kidneys are considered the main organ responsible for storing Yin essence, and proteinuria is considered a manifestation of Yin essence deficiency. By studying the relationship between the five organs and proteinuria, we can further clarify the etiology and pathogenesis of kidney-related proteinuria in traditional Chinese medicine and develop corresponding treatment systems. By observing the fluid flow between the kidneys and the bladder in the body, we can observe that they are very similar in color and odor, which suggests a close relationship between them. Moreover, the connection between the kidneys and the bladder can also be derived from the theories of traditional Chinese medicine’s zang-fu (viscera) theory. Ancient scholars recognized the mutual influence between the kidneys and the bladder, not only because of their proximity in terms of location but also because they are directly connected. Although the kidneys are located in front of the intestines anatomically, closer to the small and large intestines, they are not matched with the intestines. In addition, traditional Chinese medicine’s theory of zang-xiang (viscera and bowels) states that the kidneys govern water-fluid metabolism, control urine and feces, and are responsible for reproduction, which is closely related to the observed connection between the kidneys, bladder, and external genitalia by ancient scholars. This article aims to provide important theoretical and practical significance by deepening the understanding of the relationship between the five organs and proteinuria and their impact on diseases.

2. Understanding of Proteinuria in Traditional Chinese Medicine

In traditional Chinese medicine, there has never been a specific disease called “urine protein.” It is only mentioned in classical medical literature as “essence,” “fluid,” “liquid,” and “ointment.” Traditional Chinese medicine believes that essence, fluid, liquid, and ointment are general terms for certain “subtle substances” in the human body, apart from Qi and blood. When these “subtle substances” are lost and leaked, they can form proteinuria. The mechanism of proteinuria recognized in the current Chinese medicine field includes deficiencies in kidney essence storage, downward flow of essence, spleen deficiency in essence absorption, downward sinking of clear Qi, upward floating of turbid Qi, and lungs not governing Qi. However, the etiology and pathogenesis of spleen, lung, and kidney deficiencies vary from person to person and should be treated accordingly. Among the weakened organs, the spleen and kidneys are the most important. According to Shi Zhensheng [7], the presence of protein in urine indicates spleen and kidney deficiencies. Spleen deficiency results in improper transportation and failure to distinguish between clear and turbid, while kidney deficiency leads to the loss of Qi transformation authority and failure in essence storage, resulting in the leakage of subtle substances.

3. Definition and Functions of the Five Organs

“The Yellow Emperor’s Inner Canon: Su Wen - Differentiation of the Five Organs” also points out the relationship between the five organs, which are responsible for intake, and the six fu organs, which are responsible for excretion and transformation of substances. The coordination between the “ascending” function of the kidneys and the “descending” function of the six fu organs is necessary to achieve a balance in the metabolism of energy and substances. In the early and middle stages of diabetic nephropathy, proteinuria is one of the main clinical manifestations. Some scholars believe that the leakage of proteinuria is a manifestation of yin essence deficiency, and the storage, consolidation, and transformation of yin essence are mainly controlled by the kidneys. Therefore, insufficient kidney Qi and deficiency of kidney essence are one of the causes [8].

The five organs are important concepts in traditional Chinese medicine theory, referring to the heart, liver, spleen, lungs, and kidneys. They are considered essential components of the human body, playing irreplaceable physiological functions and regulatory roles. Each organ has its unique definition and function.

The heart is the ruler organ, responsible for the circulation of blood in the body and acts as a pump. Additionally, the heart is believed to be the center of emotions and consciousness. In traditional Chinese medicine theory, the heart is closely connected to mental activities, and the state of one’s emotions directly affects heart health.

The liver is the general organ, considered as the main organ for storing and regulating blood. It not only maintains the balance of blood but also produces bile to assist in digestion and absorption. Furthermore, the liver is closely related to emotional regulation, and excessive excitement or depression can have adverse effects on the liver.

The spleen is the official of the granary, mainly responsible for digestion, absorption, and transportation of nutrients. It also plays a role in enhancing the body’s immune system and resisting pathogenic factors.

The lungs are the prime minister organ, responsible for respiration and the transportation of Qi. Additionally, the lungs have the function of moisturizing the skin and regulating sweating, closely related to body temperature regulation.

The kidneys are the strong organ, considered as the storage site of essence and the regulator of water metabolism. They govern the growth, development, and reproductive ability of the body. Moreover, the kidneys are related to bone marrow and brain marrow, and they also have a certain influence on intelligence and memory.

The five organs hold a significant position in the human body, and each organ has its specific definition and function. They work together to maintain a balanced state of health. Understanding the definition and functions of the five organs is of certain significance for us to explore the relationship between the five organs and proteinuria.

4. Diagnosis and Clinical Manifestations of Proteinuria

The normal glomerular filtration membrane allows proteins with a molecular weight of 20,000-40,000 Daltons to pass through, while more than 90% of the proteins filtered by the glomerulus in the primary urine are reabsorbed by the proximal tubules. In a 24-hour urine collection, the total protein excretion in normal individuals should be below 150mg. In adolescents, the total protein excretion may be slightly higher but should not exceed 300mg/day, making it undetectable through conventional methods. Approximately 50-70% of urinary proteins are derived from plasma proteins, while the remaining 30-50% are proteins secreted by the urinary system, such as the loop of Henle and distal tubules, which secrete small amounts of mucoprotein and Tamm-Horsfall protein. These components make up trace amounts of protein. When the total protein in urine exceeds the aforementioned thresholds, it is referred to as proteinuria, which is a common clinical manifestation of kidney diseases [9].

The diagnosis and clinical manifestations of proteinuria are as follows:

(1) Urinary turbidity: Proteinuria refers to an elevated protein content in the urine. Normally, urine should be clear and transparent, but with increased protein levels, the urine becomes turbid.

(2) Increased sediment in urine: Proteinuria can also lead to an increase in sediment in the urine, which is typically observed as white, yellow, or red precipitates. These sediment particles contain a higher amount of protein.

(3) Edema: Proteinuria can cause fluid retention and impair kidney function, resulting in the accumulation of excess fluid in the body. Patients often experience swelling in the face, hands, feet, and may also exhibit pleural or abdominal effusion. In severe cases, it can lead to increased cardiac burden.

(4) Increased foamy urine: The presence of increased protein in the urine can make it more viscous, resulting in an increase in urinary foam that persists over time. The foam becomes denser when the urine is agitated.

(5) Other symptoms: Proteinuria may be accompanied by non-specific symptoms such as fatigue, loss of appetite, and weight loss. These symptoms are generally associated with metabolic disturbances caused by renal dysfunction.

In summary, proteinuria refers to an elevated protein content in the urine compared to normal values. Its clinical manifestations include urinary turbidity, increased sediment in urine, edema, and increased foamy urine. Proteinuria is often an early indicator of related diseases, and early detection and treatment are crucial in preventing disease progression.

5. The Connection between the Five Organs and Proteinuria

When studying the pathogenesis of proteinuria, we cannot overlook the close relationship between the five organs and proteinuria. The five organs are important organ systems in the human body, including the heart, lungs, liver, kidneys, and spleen. Each organ has its unique functions and roles, collectively maintaining the normal metabolism and function of the human body.

5.1. Relationship with the Kidneys

The kidneys play a crucial role among the five organs. The renal glomerulus is the basic structural unit of the kidneys and the primary site of proteinuria development. The glomerular filtration barrier consists of three layers: endothelial cells of the capillaries, basement membrane, and podocytes, which serve as a filtration mechanism. Under normal circumstances, only small molecular weight solutes and trace amounts of proteins can pass through this barrier, while large molecular weight proteins are prevented. When the glomerular filtration barrier is damaged, such as endothelial cell injury, thickening of the basement membrane, or podocyte detachment, it leads to an increased excretion of protein in the urine, resulting in the occurrence of proteinuria [9].

Furthermore, the renal tubules are important excretory pathways in the kidneys, participating in the reabsorption process of proteins. Under normal conditions, most of the proteins filtered into the renal tubules undergo reabsorption by the renal tubular epithelial cells, reducing the loss of proteins in the urine. Proteinuria is mainly caused by abnormalities in the structure and function of the glomerular filtration barrier and impairment of tubular reabsorption function, leading to increased excretion of protein in the urine [10].

In addition, the kidneys are also involved in the regulation of blood pressure, which is related to the occurrence of proteinuria. The kidneys regulate the constriction and dilation of the renal arteries, adjusting the glomerular filtration rate and perfusion pressure, thereby affecting the excretion of proteins. When kidney function is impaired, such as inadequate constriction of renal arteries or high perfusion pressure, it can lead to damage to the glomerular filtration barrier and an increase in protein loss in the urine, resulting in proteinuria [11].

In patients with chronic kidney disease (CKD) such as diabetic nephropathy, IgA nephropathy, focal segmental glomerulosclerosis, and hypertensive kidney injury, proteinuria is caused by immune and/or non-immune factors that lead to damage to the glomerular filtration barrier or renal tubules, resulting in the production of proteinuria.

Traditional Chinese medicine believes that dysfunction of the kidneys’ solid storage function leads to the leakage of essence substances, and proteinuria is considered one of the essence substances. The relationship between solid storage function and proteinuria is explained from the physiological basis, diagnosis, and treatment of solid storage function dysfunction [12]. Therefore, all five organs have the nature of “master of storage” and should not be singularly attributed to the kidneys. By considering the connection between the kidneys and the essence stored by the five organs, it can be understood that the occurrence of essence leakage in other organs is also related to the kidneys.

5.2. Relationship with the Heart

The heart and the cardiovascular system are also crucial for maintaining normal kidney function. The heart pumps oxygenated blood to various organs in the body, including the kidneys. Nutrients and oxygen in the blood enter the kidney tissues through blood vessels, providing the necessary energy and substances for renal units. Therefore, abnormal heart function or decreased blood flow may lead to inadequate blood supply to the kidneys, thereby affecting renal filtration function and causing proteinuria.

The presence of proteinuria indicates widespread dysfunction of the endothelium or systemic vascular disease. Dysfunction of the endothelium may promote increased leakage of lipoprotein particles into the arterial wall, ultimately leading to a significantly increased risk of atherosclerosis. It is considered an independent risk factor for cardiovascular disease and cardiovascular death in patients with type I and type II diabetes [13]. Whether proteinuria is a risk factor for cerebrovascular disease or simply a marker of cardiovascular-related diseases, it helps identify high-risk patients.

Heart diseases can cause changes in the permeability of the glomerular filtration membrane, leading to the occurrence of proteinuria by increasing the pressure within the kidneys. Heart failure is one of the most common heart diseases that can cause this condition. Chronic heart failure can lead to increased secretion of angiotensin in the body. However, angiotensin can bind to angiotensin receptors in the renal glomerular arteries, causing constriction and resulting in abnormal glomerular filtration, leading to proteinuria [14].

In addition, certain heart surgeries and interventions can also cause proteinuria. For example, coronary artery bypass grafting (CABG) is a common cardiac surgery used to treat coronary artery disease. Studies have found that after CABG surgery, patients have a higher incidence of proteinuria, which lasts for a longer duration. This may be due to factors such as increased aortic pressure during surgery and renal glomerular filtration membrane permeability changes caused by myocardial ischemia-reperfusion injury after surgery [15].

5.3. Relationship with the Liver

As an important metabolic organ in the body, liver disease can have certain effects on renal function, mainly manifested as proteinuria. The occurrence of proteinuria in liver diseases is generally associated with the following factors.

The liver plays a crucial role in the synthesis of plasma proteins, including albumin and globulin. Albumin is the most abundant protein in plasma and is primarily synthesized by the liver. All liver cells have the ability to synthesize albumin, but usually only one-third of them are active in this role, while the remaining two-thirds are in a resting state. In hypoalbuminemia, the synthesis rate of liver albumin increases, which is a key factor in the occurrence of compensatory reactions in the body. Studies have shown that liver albumin synthesis is mildly elevated in nephrotic syndrome, but the degree of elevation is often insufficient to compensate for urinary losses [16-17], suggesting that the compensatory capacity of liver albumin synthesis in kidney disease is strong but inhibited.

Liver disease can also cause kidney damage, leading to proteinuria. The liver is one of the main detoxification organs in the body, and when liver function is impaired, toxins can accumulate in the body. Some of these toxins are excreted through the kidneys. The accumulation of toxins can damage the glomerular filtration membrane, allowing protein molecules to filter into the urine, resulting in proteinuria.

Liver disease may also cause abnormal renal tubular function, leading to proteinuria. Renal tubules are responsible for the reabsorption of proteins in urine. In the case of liver disease, renal tubules may be damaged, reducing their reabsorption function, increasing the excretion of proteins in urine, and ultimately leading to proteinuria.

Liver disease may be related to inflammatory reactions, which can trigger renal damage and proteinuria to a certain extent. Research has found that liver inflammation is one of the important mechanisms by which liver disease causes proteinuria, damaging the glomerular filtration membrane and renal tubules.

5.4. Relationship with Other Organs

The association between proteinuria and diseases of other organs besides the kidneys, heart, and liver is worth further investigation. These organs include the spleen, lungs, stomach, pancreas, and intestines. These organs play important roles in maintaining normal metabolic processes in the human body, and their relationship with proteinuria in diseases is also worth our attention.

Firstly, the connection between spleen disease and proteinuria has been confirmed in clinical practice. The spleen is an important immune organ in the body, responsible for the production of immune cells and the maintenance of immune function. When the spleen is diseased, it may lead to dysfunction of the spleen, which in turn affects the metabolism and clearance of proteins. Therefore, there is a certain connection between spleen disease and proteinuria.

Secondly, lung diseases are also associated with proteinuria. The lungs are vital respiratory organs in the human body, responsible not only for respiration but also for the elimination of waste gases and moisture. When the lungs are damaged, it may lead to abnormal protein metabolism in the body, resulting in proteinuria. The relationship between lung disease and proteinuria has received widespread attention in recent years, and important findings have been made in related research.

In addition, diseases of the digestive system organs such as the stomach, pancreas, and intestines are closely related to proteinuria. The stomach is the starting organ of the digestive process, while the pancreas is responsible for the secretion of digestive enzymes and the synthesis of insulin. When these organs are affected by disease, it may cause metabolic disorders, leading to the occurrence of proteinuria. Although there is still relatively limited research on the relationship between digestive system organs and proteinuria, some research results have indicated their association.

In conclusion, besides kidney, heart, and liver diseases, there is also a certain relationship between diseases of other organs and proteinuria. The connections between spleen diseases, lung diseases, and diseases of the digestive system organs, and proteinuria have been preliminarily confirmed in clinical practice, providing important insights for further exploration of the relationship between these organs and proteinuria. However, current research on these associations is still relatively limited, and further in-depth experimental studies and clinical observations are needed to further clarify the mechanisms and clinical significance of these relationships.

6. Treatment and Prevention of Proteinuria

6.1. Medication Treatment

In Western medicine, the control of blood pressure, blood sugar, and blood lipids is mainly achieved through dietary regulation. Additionally, antiplatelet or anticoagulant medications may be used, as well as hormones and immunosuppressants. Clinical trials have shown that reducing proteinuria can protect the kidneys, and it is believed that treating urinary protein can maximize kidney protection [18]. Glucocorticoids and immunosuppressants are used for etiological treatment. The preferred antihypertensive drugs are angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs).

ACEIs or ARBs, as angiotensin II receptor antagonists, have the functions of reducing glomerular pressure and decreasing urinary protein leakage. They can also inhibit abnormal proliferation of mesangial cells in the glomerulus, block the synthesis of extracellular matrix, delay the progression of glomerulosclerosis, downregulate the expression of transforming growth factors, and reduce the expression and deposition of extracellular matrix proteins such as glycogen and collagen [19]. They may also lower the levels of plasma inflammatory factors such as high-sensitivity C-reactive protein (hs-CRP), interleukin-2 (IL-2), and tumor necrosis factor-alpha (TNF-α), improve glomerular filtration rate, and reduce urinary protein excretion [20].

In theory, the combination of ACEIs and ARBs should achieve a synergistic effect. Previous clinical studies have also emphasized the use of combined therapy with ACEIs and ARBs, and it has been found that combined treatment has a stronger protein-lowering effect than high-dose monotherapy. Mongensen et al. [21] randomly divided 199 type 2 diabetic nephropathy (DN) patients into candesartan group, ramipril group, and combination therapy group. The results showed that the urinary albumin/creatinine ratio decreased by 24%, 39%, and 50% in the three groups, respectively. In a prospective randomized treatment of 24 non-DN patients, it was found that the urinary protein decreased by 56% in the combination therapy group, 45.9% in the benazepril group, and 41.5% in the valsartan group; the urinary protein/creatinine ratio showed a similar trend. Currently, it is recommended to add ARBs or ACEIs to patients who do not respond to the maximum dose of ACEI or ARB in terms of protein reduction.

6.2. Traditional Chinese Medicine Treatment for Proteinuria

Although Western medicine has many treatment methods for proteinuria, their effectiveness is limited and they have significant side effects. Therefore, it is necessary to seek other safe and effective treatment methods. Traditional Chinese medicine (TCM) can play a “reducing toxicity and enhancing efficacy” role when used in combination with Western medicine, and it can also achieve better results when used alone. Most kidney disease patients have a long course of disease, during which their physical condition declines due to the long-term loss of “essential substances”. It is crucial not to neglect the presence of pathogenic factors in deficiency patterns. Therefore, the principle of treatment should be to tonify the body’s deficiency while dispelling pathogenic factors, i.e., not forgetting to expel pathogens while tonifying deficiencies and not neglecting deficiencies when expelling pathogens. Failure to follow this principle may lead to poor treatment outcomes or even worsen the condition. The kidney is the organ of water and fire, and the treatment should aim for a balance between water and fire. However, when the disease progresses to the late stage, the organs are vulnerable, and if medication is not taken with caution, it may result in overcompensation. Therefore, when selecting prescriptions and medications, it is essential to choose mild and balanced options and avoid aggressive approaches. In the treatment of proteinuria, it is important to use TCM for syndrome differentiation and treatment as much as possible. However, in necessary situations, it is still necessary to use Western medicine in combination, such as hormones and cytotoxic drugs. Timely use of Western medicine is still required for treatment. In TCM, proteinuria in kidney diseases is caused by multiple factors, involves multiple levels, and manifests in various attributes. Therefore, the key to treating proteinuria lies in distinguishing between deficiency and excess patterns. Since the treatment of this disease requires long-term medication, patients should be encouraged to adhere to the prescribed treatment, as relapses are common if medications are not taken consistently. In addition, as the condition gradually improves, the dosage can be reduced from once daily to once every other day, and the interval between medication can be gradually extended [22].

6.3. Prevention of Proteinuria

Prevention plays an important role in controlling the occurrence and development of proteinuria. Below, we will introduce several effective preventive measures from various aspects.

Firstly, a balanced diet is an important means of preventing proteinuria. Firstly, the intake of protein should be limited, as restricting the intake of protein in the diet can improve renal hemodynamics, reduce toxin accumulation, regulate ammonia metabolism by controlling the expression of multiple genes, reduce renal ammonia excretion, and prevent negative nitrogen balance [23]. Increasing the proportion of amino acids in the body can promote protein synthesis, improve metabolic abnormalities, protect residual renal function [24, 25], and help maintain renal autoregulation to counteract renal glomerular vasoconstriction and injury caused by hypertension [26]. Therefore, in daily diet, it is advisable to control the intake of high-protein foods such as meat and fish, and increase the intake of foods rich in fiber and antioxidants such as vegetables, fruits, and whole grains.

Secondly, salt intake should be moderately controlled in the diet. A high-salt diet can cause excessive sodium ion concentration in the body, leading to sodium and water retention, known as “sodium-water retention” in medicine [27]. High salt intake can increase renal blood flow and glomerular filtration rate, increase renal workload, and cause pathological changes in renal blood vessels [28], thus affecting renal function. Therefore, in daily diet, it is recommended to minimize salt intake, choose fresh foods, and avoid high-salt foods such as processed and canned foods.

Medication also plays a role in preventing proteinuria. Under the guidance of a doctor, appropriate medications can be used to control the occurrence and progression of proteinuria. Commonly used drug treatments include angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), which can inhibit the permeability of the glomerular filtration membrane, reduce protein leakage, and thereby prevent and control proteinuria. Esnault et al. [28] found that diuretics combined with half-dose ACEI/ARB had better therapeutic effects in reducing urinary protein compared to the maximum antihypertensive dose of ACEI/ARB alone. In addition, drug treatments such as blood pressure regulation and glycemic control can also help prevent proteinuria.

Thirdly, developing good lifestyle habits is also very important in preventing proteinuria. Firstly, it is important to maintain good hydration habits and ensure an adequate intake of water every day, which helps dilute and eliminate metabolic waste products in the body and reduce the burden on the kidneys. Secondly, engaging in regular physical exercise to improve physical fitness and enhance immune function can help prevent proteinuria. At the same time, avoiding bad habits such as staying up late and excessive fatigue, maintaining sufficient sleep, is beneficial for body recovery and health maintenance.

In daily life, we should pay attention to the implementation of the above preventive measures. By adopting a balanced diet, medication treatment, and good lifestyle habits, we can help prevent the occurrence and development of proteinuria and maintain kidney health. Of course, specific treatment and prevention for proteinuria should be personalized according to the advice of a doctor. Only by considering multiple factors comprehensively and taking corresponding measures can we better prevent proteinuria and protect kidney function.

7. Conclusion and Prospects

In previous studies, we have conducted in-depth discussions on the relationship between the five organs (heart, liver, spleen, lungs, and kidneys) and proteinuria. However, there are still many issues that require further research. In future studies, we will focus on the following aspects: (1) Explore the specific mechanisms underlying the relationship between proteinuria and the five organs. Although we have clarified the connection between proteinuria and the five organs, we still lack a profound understanding of the specific molecular mechanisms involved. We will start from the cellular and molecular levels and use advanced biotechnology methods to further elucidate the interaction mechanisms. (2) Investigate the impact of different types of proteinuria on the five organs. Current research has mainly focused on common types of proteinuria, such as structural proteinuria and non-structural proteinuria. However, there are other types of proteinuria that deserve further investigation, such as microalbuminuria and glomerular proteinuria. This article will comprehensively examine the relationship between these different types of proteinuria and the five organs. (3) Explore the prospects of applying the research findings to clinical practice. The connection between the five organs and proteinuria is common to various diseases, such as diabetic nephropathy and proteinuric glomerulonephritis. Future research should focus on applying our research findings to clinical practice, providing efficient diagnostic and therapeutic methods for patient health. (4) Expand the research perspective and consider the effects of other influencing factors. The relationship between the five organs and proteinuria is complex, involving not only intrinsic organ factors but also lifestyle, environmental factors, genetic factors, and many other external factors. In future research, we will take these influencing factors into consideration to achieve a comprehensive understanding of the relationship between proteinuria and the five organs.

In summary, through in-depth research on the mechanisms of association, the relationship between different types of proteinuria, the application in clinical practice, and the consideration of other influencing factors, we will gain a deeper understanding of the association between the five organs and proteinuria. This will provide more effective methods and strategies for disease prevention and treatment. Future research will further reveal the profound connection between the five organs and proteinuria and have a greater impact on human health.