Funsi ginjal ialah

The kidney regulates body homeostasis not only by its excretory functions but also by a number
of synthetic and degradative properties of glomerular cells and tubular epithelial cells. These
properties include synthesis of hormones, degradation of peptides and low-molecular-mass
proteins [less than 50 kilodaltons (kDa)], and metabolic events aimed at conserving energy and
regulating the composition of body fluids. The kidney is the site of synthesis of a number of
hormones [i.e., erythropoietin (EPO), 1,25-dihydroxyvitamin D3 (1,25dihydroxycholecalciferol), and renin] and is an important catabolic site for several polypeptide
hormones [e.g., insulin, glucagon, and parathyroid hormone (PTH)] and glycoproteins (see Table
2-1).
THE CONSEQUENCES OF PROGRESSIVE KIDNEY DISEASE
Accumulation of Substances Excreted by the Kidney
A sustained decrease in glomerular filtration rate (GFR) is the hallmark of progressive kidney
disease. As GFR decreases, solutes that are excreted by the kidney (creatinine and urea)
accumulate in body fluids, and the concentration of solutes in the plasma increases. Other solutes
also can accumulate in body fluids, including phosphates, sulfates, uric acid, and hydrogen ions.
The accumulation of hydrogen ions leads to the development of metabolic acidosis. As renal
insufficiency advances, other compounds that are retained in body fluids include phenols,
guanidines, organic acids, indols, myoinositol and other polyols, polyamines, 2-microglobulin,
certain peptides, urofuremic acids, and trace elements, such as aluminum, zinc, copper, and iron.
2-microglobulin and some trace elements can accumulate in and cause dysfunction of various
organs. Although the most profound changes occur with severe impairment of GFR, many of
these abnormalities with associated adaptive or maladaptive responses begin at GFR of 50
mL/min/1.73 m2 or more. The accumulation of these substances can lead to hormonal
deficiencies (testosterone, fetuin, etc.), inability to appropriately respond to stimuli (insulin
resistance, EPO resistance, etc.), or overproduction (prolactin).
Decreased Flexibility in Responding to Changes in Intake
As kidney function decreases, patients' abilities to adapt to changes in dietary intake, particularly
those involving sodium, potassium, phosphorus, and water, is somewhat restricted. In chronic
kidney disease (CKD), solute and water excretion per nephron increases as kidney function
decreases, but the fewer number of functional nephrons leads to a more restricted range of solute
or water excretion. As kidney disease progresses, the capacity to respond to changes in the intake
of sodium, other solutes, and water becomes less flexible, and this loss of capacity can result in
changes in the volume and composition of the extracellular fluid. Thus, dietary intake in patients
with either acute renal failure or CKD must be adjusted.

Table 2-1. Principal functions of the kidney

Excretion of metabolic waste products (urea, creatinine, uric acid)
Elimination and detoxification of drugs and toxins
Maintenance of volume and ionic composition of body fluids
Acid-base regulation
Regulation of systemic blood pressure (renin, angiotensin, prostaglandins, nitric oxide, sodium
homeostasis)
Production of erythropoietin
Control of mineral metabolism through endocrine synthesis (1,25-dihydroxycholecalciferol and
24,25-dihydroxycholecalciferol)
Degradation and catabolism of peptide hormones (insulin, glucagon, parathyroid hormone) and
low-molecular-weight proteins (2-microglobulin and light chains)
Regulation of metabolic processes (gluconeogenesis, lipid metabolism)
Table 2-2. Circulating levels of hormones in patients with advanced renal insufficiency
Increased
Decreased
Insulin, proinsulin, C-peptide
Erythropoietin
Glucagon
1,25-dihydroxycholecalciferol
Growth hormone
Progesterone
Parathyroid hormone
Testosterone
Calcitonin
Thyroxine
Gastrin
Triiodothyronine
Endothelin
Nitric oxide
Prolactin (particularly in women)
Hepatocyte growth factor
Vasopressin
Bone morphogenic protein-7
Luteinizing hormone
Follicle-stimulating hormone
Luteinizing hormone-releasing hormone
Secretin
Cholecystokinin
Vasoactive intestinal peptide
Gastric inhibitory peptide

The corrected Ca should be maintained in normal range (8.4 to 10.2 mg/dl); however,
to reduce the risk of metastatic calcification, the preferred upper limit of Ca is
9.5 mg/dl.

Decreased Synthetic Functions of the Kidney

The loss of synthetic functions in the kidney contributes to the abnormalities seen in renal
insufficiency. For example, decreased production of EPO, a hormone synthesized in the kidney
that plays a key role in the maturation of erythrocyte precursors in bone m arrow, is a major
cause of the anemia in patients with renal disease. Decreased synthesis of 1,25dihydroxycholecalciferol (calcitriol), the active metabolite of cholecalciferol, by the diseased
kidney leads to decreased serum concentrations of calcitriol and decreased calcium absorption
from the gastrointestinal tract. Decreased concentrations of calcitriol also contribute to the
development of hyperparathyroidism and bone disease in patients with renal insufficiency.
Alterations in Degradation of Hormones and Other Peptides
The kidney is the main site of degradation for several peptides (2-microglobulin and light
chains), proteins, and peptide hormones, including insulin, glucagon, growth hormone, and PTH

(Table 2-1). The kidney is also involved in gluconeogenesis (the synthesis of glucose from
noncarbohydrate precursors) and lipid metabolism. Kidney disease, therefore, leads to multiple
abnormalities that affect intermediary metabolism, the concentrations of circulating hormones,
and the absorption of certain nutrients. As renal failure progresses, anorexia, nausea, and
vomiting can develop and compromise the intake of nutrients and energy.