10 Renal Function

NH3: filtered and secreted-not reabsorbed

filtered and secreted-not reabsorbed

Glucose

filtered and a portion reabsorbed

Amino acids

filtered and completely reabsorbed

3 basic renal processes

• Glomerular filtration

• Tubular reabsorption

• Tubular secretion

Things that can filter through glomerulus

 water, electrolytes, small dissolved solutes (glucose, amino acids, LMW proteins, urea, creatinine)

Things too big to filter through glomerulus

albumin, plasma proteins, cellular elements, protein-bound substances (lipids, bilirubin) 

Distal Convoluted Tubule

Much shorter than the proximal tubule

Filtrate in this section close to final composition

Function is to affect small adjustments to achieve electrolyte and acid-base balance

Aldosterone

• Produced by the adrenal cortex under the influence of the renin-angiotensin mechanism

• Stimulates sodium reabsorption in the collecting duct and K and H ion secretion

AVP

• Secreted by posterior pituitary in response to increased blood osmolality 

• Makes walls of distal collecting ducts permeable to water and promotes water reabsorption

3 principle NPN

urea, creatinine, and uric acid

Collecting duct

Cl and urea reabsorbed here

Urea

• >75% of NPN waste

• made in liver from ammonia

• Readily filtered by the glomerulus, 40-60% reabsorbed in the collecting ducts

Creatinine

• Muscle contains creatine phosphate metabolized by creatine kinase, first source of muscle fuel

• Daily 20% of total muscle creatine dehydrates and becomes waste produce creatinine

• Readily filtered by glomerulus, not reabsorbed

Uric Acid

• Primary waste product of purine metabolism

• Readily filtered by glomerulus and complex cycle of reabsorption and secretion

• 6-12% finally excreted

Regulator of water balance

AVP

Sodium balance

• Balance controlled only by excretion

• RAAS –major mechanism

Potassium Balance

• Competes with H ions in exchange for Na

• Filtered by glomerulus and reabsorbed

Chloride balance

• Involved in maintenance of extracellular fluid balance

• Passively reabsorbed with Na

Phosphate balance

• Higher concentrations in intracellular fluid than extracellular fluid

• Protein or non-protein bound

• Homeostatic control by PTH (promotes excretion)

Calcium balance

• 2^nd most predominant intracellular cation

• Protein and non-protein bound

• Non-protein can be ionized or unionized

• Ionized filters freely

Magnesium balance

• Enzyme cofactor

• Both protein bound and ionized

  • Ionized filtered and reabsorbed

Hormones produced by kidney

renin, erythropoietin, 1,25-dihydroxyvitamin D, and prostaglandins

Renin

Initial component of RAAS

Produced by renal medulla

Catalyzes synthesis of angiotensin

Erythropoietin

Acts on erythroid progenitor cells in bone marrow

In chronic renal insufficiency—significantly reduced

1,25-Dihydroxyvitamin D

• Site of formation of active Vit D

• Active vit D levels determine phosphate and calcium balance and bone calcification

• Chronic renal insufficiency often associated with osteomalacia

Prostaglandins

• group of potent cyclic fatty acids

• Produced by kidneys increase renal blood flow, sodium and water excretion, renin release

• Act to oppose vasoconstriction due to angiotensin and norepinephrine

eGFR

• calculated based on serum creatinine, age, body size, gender, and race

• No 24h urine collection necessary

• Reported with every creatnine measurement

Cockcroft-Gault Formula

1^st formula for eGFR, not corrected for body surface area, assumes women have lower creatinine clearance by 15% than men

CKD-EPI 2021

eGFR formula used currently only based off of serum Creatinine, age, and sex (sometimes uses cyastin C)

Cystatin C

• Low molecular weight protein, steady state production by most tissues

• Freely filtered by glomerulus, reabsorbed, and catabolized by the proximal tubule

• Rise seen before creatinine or GFR decrease

• between subject biological variation much smaller than within subject biological variation

  • better for initial detection of minor renal impairment

Creatinine

• within subject biological variation less than between subject biological variation

  • best for monitoring renal function of an individual over time

β2-Microglobulin

• small, non-glycosylated peptide on surface of most cells, shed at constant rate

• filtered by the glomerulus and 99.9% reabsorbed by proximal tubules

  • Elevated serum levels → increased cell turnover

  • elevated urine levels → reabsorption issue 

Myoglobin

• bind and transport o2 from the plasma membrane to the mitochondria of muscle cells

• increase in acute muscle injury

• overload the proximal tubules and cause acute renal failure

Neutrophil Gelatinase-Associated Lipocalin

• 25-kDa protein expressed by neutrophils and epithelial cells  including those in proximal tubule

• Can be measured in plasma and urine—elevated within 2-6 hours of AKI

• NGAL may also rise in systemic stress without AKI

• Research only!!

Nephrocheck

First FDA cleared test used to determine if critically ill patients are at risk of developing moderate to severe AKI in the next 12 hours

Yellow/amber urine urine

urochromes

Yellowbrown to green urine

bile pigment oxidation

Red/brown after standing urine

porphyrins

Red/brown fresh urine

Hgb/RBC

Brownish black after standing urine

alkaptonuria

RBC cast

diagnostic for glomerular inflammation

WBC cast

diagnostic for inflammation of the nephrons

Epithelial cast

occasional presence normal (not common)

Waxy cast

always pathologic—tubular inflammation or deterioration

Fatty cast

abnormal-lipid inclusions

Broad cast

severe renal stasis

Acute Glomerulonephritis

• inflamed glomerulus with decreased capillary lumen

• Rapid onset of hematuria and proteinuria

• Decreased GFR, anemia, elevated BUN and serum creatinine, oliguria, Na and water retention, CHF (bc of too much fluid)

• Hyaline and granular casts are numerous

• RBCs casts highly suggestive

Chronic Glomerulonephritis

• leads to scarring and loss of functioning nephrons

• Goes undetected at first 

• Only minor decreases in renal function, slight proteinuria and hematuria are observed

Nephrotic Syndrome

• Caused by different diseases that result in injury and increased permeability of the glomerular basement membrane

• Massive proteinuria and resultant hypoalbuminemia

• Generalized edema

• Hyperlipidemia and lipiduria

Distal renal tubular acidosis (RTA)

renal tubules unable to keep up the vital pH gradient between the blood and tubular fluid

• Abnormally low serum values for phosphorus and uric acid

• Find glucose and amino acids in the urine, some proteinuria

Proximal renal tubular acidosis (RTA)

decreased bicarbonate reabsorption, results in hyperchloremic acidosis

• Abnormally low serum values for phosphorus and uric acid

• Find glucose and amino acids in the urine, some proteinuria

Pyelonephritis

Infection in kidney

Cystitis

Infection in bladder

Kidney obstruction disease pathway (2)

• Gradually raise the intratubular pressure until nephrons necrose and chronic renal failure starts

• Predispose the urinary tract to repeated infections

Acute Kidney Injury (AKI)

Sudden, sharp decline in renal function—due to acute toxic or hypoxic insult to kidneys

Prerenal AKI

• Defect in blood supply before it reaches the kidney

• Cardiovascular system failure and consequence hypovolemia

Intrinsic AKI

• Most common cause: acute tubular necrosis

• other causes: Vascular obstruction/inflammations and glomerulonephritis

Post renal AKI

• Defect in post kidney urinary tract

• Lower urinary tract obstruction or rupture of the urinary bladder

Chronic Kidney Disease (CKD)

• gradual decline in kidney function

• 1/10 adults have this

  • diabetes is the leading cause

>60 gfr (CKD)

over >90 is still good gfr function, 60-90 is decreased function but still ok

<15 gfr (CKD)

Kidney failure