Renal Function

A systemic disorder characterized by the overlapping pathophysiology of heart disease, kidney disease, and metabolic disorders (like type 2 diabetes and obesity)

Cardio-kidney metabolic syndrome

CKM; includes heart failure, atrial fibrillation, and coronary heart disease

Cardiovascular disease

CKM; defined as abnormalities of kidney structure or function present for over 3 months

Chronic kidney disease

CKM; a cluster of conditions (high blood sugar, excess body fat around the waist, and abnormal cholesterol levels) that increase the risk of heart disease and stroke

Metabolic syndrome

The heart and kidneys are ___________ linked; a decline in the function in one often leads to a decline in the other

Hemodynamically

There are approximately 1 million per kidney; they filter blood and remove waste products like urea

Nephron

A cluster of capillaries where blood filtration begins

Glomerulus

Surrounds the glomerulus to collect filtrate

Bowman’s capsule

Where water, electrolytes, and nutrients are reabsorbed back into the blood

Tubules

Final site for urine concentration before it moves to the renal pelvis

Collecting duct

Carries unfiltered blood into the kidney

Renal artery

Leads blood into the glomerulus

Afferent arteriole

Carries blood away from the glomerulus

Efferent arteriole

Network surrounding the tubules for reabsorption and secretion

Peritubular capillaries

A waste product used to estimate how well the kidneys filter; sCr

Serum creatinine

A measure of GFR using creatinine levels; eCrCl

Estimated creatinine clearance

The “gold standard” for checking kidney function, though harder to perform than “estimated” versions; mGFR

Measured GFR

The preferred equation used to estimate GFR in clinical practice

CKD-EPI

A protein used as an alternative biomarker to creatinine for GFR estimation (less affected by muscle mass)

Cystatin C

The process where the nephron removes substances (like drugs or ions) from the blood into the urine

Tubular secretion

A high-pressure capillary bed where filtration occurs

Glomerulus

Surrounds the glomerulus; collects the filtrate

Bowman’s capsule

Supplies blood to the glomerulus

Afferent arteriole

Carries blood away from the glomerulus

Efferent arteriole

The ___________ ________ _____ is regulated by adjusting the pressure within the glomerulus via the constriction or dilation of arterioles

Glomerular filtration rate

The primary site for reabsorption of water, ions, and all organic nutrients

Proximal convoluted tubule

Perform regulated reabsorption and secretion; it is located near the renal corpuscle to facilitate feedback

Distal convoluted tubule

Receives fluid from many nephrons; leads to the papilla of the pyramid and eventually the renal pelvis

Collecting duct

Specialized capillary networks surrounding the Loop of Henle in juxtamedullary nephrons; essential for maintaining the medullary osmotic gradient

Vasa recta

Located where the DCT touches the afferent arteriole; this is the critical site where renin is synthesized, acting as a primary regulator of blood pressure

Juxtaglomerular apparatus

Site of renin production

Juxtaglomerular apparatus

Hormone produced in adrenal glands that regulates metabolism (glucose levels) and helps the body respond to long-term stress

Cortisol

Hormone produced in the adrenal glands that acts on the DCT and collecting ducts of the nephron to conserve sodium and water, thereby increasing blood pressure

Aldosterone

Hormone produced by adrenal glands that triggers the “fight or flight” response, affecting heart rate and blood flow during acute stress

Epinephrine

Mnemonic for kidney functions

A WET BED

What are the seven key kidney functions?

Acid-base balance, water balance, electrolyte balance, toxin removal, blood pressure control, erythropoietin production, and vitamin d activation

Kidneys maintain _____ volume to regulate blood pressure

Fluid

Kidneys regulate levels of __________ - sodium, potassium, and calcium

Electrolytes

Kidneys excrete ______ ______ (urea, uric acid) and water

Metabolic waste

Kidneys control blood pressure via the ______ system

RAAS

Kidneys stimulate the bone marrow via erythropoietin to produce _____ ______ ______

Red blood cells

Kidneys convert vitamin D to its active form for ____ mineral metabolism

Bone

The kidney can synthesize _____ during prolonged fasting

Glucose

What does excretion equal?

Filtration - Reabsorption + Secretion

Filters small weight molecules; albumin should not be present, its presence indicates renal dysfunction

Filtration

Movement from tubule back into the blood; highly ionized compounds generally stay in filtrate

Reabsorption

Active transport from blood into the tubule; mediated by transporters which are sites for drug-drug interactions

Secretion

Primary clinical marker used to assess kidney function

GFR

The flow rate of filtered fluid through the glomeruli into Bowman’s capsule per minute

Glomerular filtration rate

Since direct measurement of GFR is impractical, clinicians use markers like ________ to calculate estimated GFR

Creatinine

________ is both filtered and secreted, which is why it is an effective, if slightly overestimating, marker for GFR

Creatinine

Normal maximum GFR

120 mL/min

Drug elimination occurs not just through GFR, but also through active tubular _______

Secretion

______ can be inhibited or induced by other medications, leading to changes in drug clearance and potential toxicity

Transporters

The _____ is responsible for the excretion of medications and their metabolites

Kidney

There is no ________ substance that is 100% freely filtered without also being secreted or reabsorbed by the tubules

Endogenous

To get an exact “measured GFR” clinicians must use exogeneous markers like _____, _______, or _______

Inulin, Iothalamate, or Iohexal

Criteria for an ideal marker for GFR is _____ metabolism and 100% renal elimination

Zero

An ideal marker for GFR has _____ reabsorption or secretion in the tubules

Zero

mGFR requires ____ _______ and intensive technical expertise; it is rarely used in routine practice but is the benchmark for research

IV administration

Because mGFR is impractical, we use ________ to estimate function based on serum biomarkers

Equations

Uses weight, age, and sex; heavily influenced by BMI; often used for drug dosing

Cockcroft-Gault

Current standard; removed the race variable to promote equity; may use Cystatin C + Creatinine for higher accuracy

CKD-EPI

Historically, a 24-hour ______ _______ for creatinine clearance was the clinical standard, but its use has declined significantly

Urine collection

This method had a high error rate in determining creatinine clearance

Urine collection

Even with a perfect urine collection, the kidney secrestes some creatinine in the tubules, which can cause the result to _________ actual GFR

Overestimate

Cockcroft-gault equation tends to _________ GFR in elderly patients

Underestimate

Cockcroft-gault tends to __________ GFR in obese patients

Overestimate

Waste product from muscle; influenced by diet (cooked meat) and muscle mass

Serum creatinine

A protein produced at a constant rate by all nucleated cells; it is less affected by muscle mass or diet than creatinine, making it a powerful “tie-breaker” for eGFR

Cystatin C

A byproduct of creatinine phosphate metabolism in skeletal muscle

Serum creatinine

Serum creatinine production occurs at a relatively constant rate; directly proportional to _____ _____

Muscle mass

Creatinine is freely filtered by the glomerulus, but approximately 10% is eliminated via tubular _______

Secretion

The relationship between sCr and GFR is ________

Curvilinear

At high GFR (good kidney function), a large drop in GFR results in a _____ rise in sCr

Small

At low GFR, a small drop in GFR respresents a ______ rise in sCr

Large

sCr can remain in the _______ range even if a patient has lost 50% of their kidney function if they start out with good function

Normal

At _____ GFR, a large drop in GFR results in only a small rise in sCr

High

At _____ GFR, a small drop in GFR results in a large rise in sCr

Low

Male, younger age, and black ancestry _______ sCr

Increases

Female, older age (muscle wasting), and asian/hispanic ancestry ______ sCr

Decreases

Dehydration can _______ sCr

Increase

Fluid overload can _______ sCr

Decrease

High muscle mass and ingestion of cooked meat can _______ sCr

Increase

Vegetarian diet, amputation, malnutrition, and obesity can _______ sCr

Decrease

Drugs like trimethoprim, cimetidine, and ACE inhibitors can _______ sCr

Increase

Because 10% of creatinine is secreted, sCr-based equations can _________ actual GFR

Overestimate

sCr is a ______ marker; in acute renal failure, it can take hours to days for sCr to rise after the initial GFR drop

Delayed

Impacted by muscle mass and diet rather than just kidney filtration

Creatinine

A protease inhibitor produced by all nucleated cells at a constant rate

Cystatin C

100% filtered at the glomerulus; it is reabsorbed and metabolized in the proximal tubule, but it does not undergo tubular secretion

Cystatin C

It is not related to muscle mass or diet, making it a more “pure” marker of filtration in specific populations

Cystatin C

While muscle mass doesn’t matter, ______ ____ is still impacted by obesity, smoking, thyroid dysfunction, and high-dose glucocorticoid therapy

Cystatin C

Eliminated by GFR and tubular secretion; impacted by muscle mass, age, race and diet; test is widely available and low cost

Creatinine

Eliminated by GFR only; impacted by obesity, steroids, and thyroid status; less available and more costly

Cystatin C

Often only ordered as a confirmatory test when sCr is unreliable

Cystatin C

A standard blood test used to monitor a patient’s electrolytes, acid-base balance, and renal function

BMP

Labs automatically report an _____ based on the sCr found in the BMP

eGFR

Represents the volume of fluid filtered by the kidney per unit time

eGFR

The 2021 CKD-EPI equation is _____-free meaning it does not use a correctin factor, aiming to reduce health disparities

Race