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.