Mental integrity is undoubtedly a crucial aspect of living a free and independent life. However, any alteration in the composition of our internal environment, even a temporary failure of the kidneys to perform their functions, can lead to the destruction of our mental integrity and personality.

The kidneys, as acknowledged by both Starling and Smith, play a more significant role in regulation rather than excretion. They regulate (1) the osmolality and volumes of body fluids, (2) electrolyte balance, and (3) acid-base balance. Additionally, the kidneys excrete metabolic byproducts and foreign substances, while also producing and secreting hormones.

Maintaining normal cell volume in all body tissues relies on controlling body fluid osmolality. Normal cardiovascular system function necessitates the regulation of body fluid volume. Furthermore, the kidneys are vital in regulating the levels of various important inorganic ions in the body, such as Na+, K+, Cl−, bicarbonate (HCO3 −), hydrogen (H+), Ca++, and inorganic phosphate (Pi). To maintain overall body balance, the excretion of these electrolytes must equal their daily intake. If the intake of an electrolyte surpasses its excretion, the amount of that electrolyte in the body increases, resulting in a positive balance. Conversely, if the excretion of an electrolyte exceeds its intake, the amount in the body decreases, leading to a negative balance. The kidneys serve as the primary or sole route for excretion of many electrolytes from the body.

Regulation of acid-base balance is another vital function of the kidneys. Since many metabolic functions are highly sensitive to pH, maintaining the pH of body fluids within narrow limits is crucial. Normal pH is maintained through buffers within body fluids and the coordinated actions of the lungs, liver, and kidneys.

The kidneys eliminate several end products of metabolism as waste. These waste products include urea (derived from amino acids), uric acid (from nucleic acids), creatinine (from muscle creatine), end products of hemoglobin metabolism, and metabolites of hormones. The kidneys excrete these substances from the body at a rate that matches their production, thus regulating hormone concentrations within body fluids. Additionally, the kidneys play a significant role in eliminating foreign substances such as drugs, toxins (e.g., pesticides), and other chemicals from the body.

Moreover, the kidneys function as important endocrine organs, producing and secreting renin, calcitriol, and erythropoietin. Renin, although not a hormone but an enzyme, activates the renin-angiotensin-aldosterone system, which helps regulate blood pressure and Na+ and K+ balance. Calcitriol, a metabolite of vitamin D3, is essential for the normal absorption of Ca++ by the gastrointestinal tract and its deposition in bone. Patients with renal disease may experience impaired production of calcitriol, leading to reduced hormone levels. This, in turn, decreases Ca++ absorption in the intestine, contributing to bone formation abnormalities observed in individuals with chronic renal disease. Many kidney diseases also result in reduced production and secretion of erythropoietin. Erythropoietin stimulates the production of red blood cells in the bone marrow. The decreased production of erythrocytes contributes to the development of anemia in chronic kidney disease (CKD), which is characterized by a progressive loss of kidney function over an extended period of time.

Numerous diseases can impair kidney function and lead to renal failure. In some cases, the impairment may be temporary, but in many instances, renal function progressively declines. Individuals with a glomerular filtration rate (GFR) less than 10% of normal are classified as having end-stage renal disease (ESRD) and require renal replacement therapy, such as dialysis or kidney transplantation, for survival.
Certainly, mental integrity is a sine qua non of the free and independent life. But let the composition of our internal environment suffer change, let our kidneys fail for even a short time to fulfill their tasks, and our mental integrity, or personality is destroyed.
HOMER W. SMITH—1939
As both Starling and Smith recognized, the kidneys are more appropriately considered regulatory rather than excretory organs. The kidneys regulate (1) body fluid osmolality and volumes, (2) electrolyte balance, and (3) acid-base balance. In addition the kidneys excrete metabolic products and foreign substances and produce and secrete hormones.
Control of body fluid osmolality is important for maintenance of normal cell volume in all tissues of the body. Control of body fluid volume is necessary for normal function of the cardiovascular system. The kidneys are also essential in regulating the amount of several important inorganic ions in the body, including Na+, K+, Cl−, bicarbonate (HCO3 −), hydrogen (H+), Ca++ , and inorganic phosphate (Pi). Excretion of these electrolytes must be equal to daily intake to maintain appropriate total body balance. If intake of an electrolyte exceeds its excretion, the amount of this electrolyte in the body increases and the individual is in positive balance for that electrolyte. Conversely if excretion of an electrolyte exceeds its intake, its amount in the body decreases and the individual is in negative balance for that electrolyte. For many electrolytes the kidneys are the sole or principal route for excretion from the body.
Another important function of the kidneys is regulation of acid-base balance. Many metabolic functions of the body are exquisitely sensitive to pH. Thus the pH of body fluids must be maintained within narrow limits. Normal pH is maintained by buffers within body fluids and by the coordinated action of the lungs, liver, and kidneys.
The kidneys excrete a number of the end products of metabolism. These waste products include urea (from amino acids), uric acid (from nucleic acids), creatinine (from muscle creatine), end products of hemoglobin metabolism, and metabolites of hormones. The kidneys eliminate these substances from the body at a rate that matches their production. Thus the kidneys regulate hormone concentrations within body fluids. The kidneys also represent an important route for elimination of foreign substances such as drugs, toxins (e.g., pesticides), and other chemicals from the body.
Finally, the kidneys are important endocrine organs that produce and secrete renin, calcitriol, and erythropoietin. Renin is not a hormone but an enzyme that activates the renin-angiotensin-aldosterone system, which helps regulate blood pressure and Na+ and K+ balance. Calcitriol, a metabolite of vitamin D3, is necessary for normal absorption of Ca++ by the gastrointestinal tract and for its deposition in bone (see ). In patients with renal disease the kidneys’ ability to produce calcitriol is impaired and levels of this hormone are reduced. As a result, Ca++ absorption by the intestine is decreased, which over time contributes to the bone formation abnormalities seen in patients with chronic renal disease. Another consequence of many kidney diseases is a reduction in erythropoietin production and secretion. Erythropoietin stimulates red blood cell formation by bone marrow. Decreased erythrocyte production contributes to the anemia that occurs in chronic kidney disease (CKD), a progressive loss in kidney function over a period of months or years.
A large variety of diseases impair kidney function and result in renal failure. In some instances the impairment in renal function is transient, but in many cases renal function declines progressively. Patients in whom the glomerular filtration rate (GFR) is less than 10% of normal are said to have end-stage renal disease (ESRD) and must receive renal replacement therapy in the form of either dialysis or kidney transplantation to survive.