Kidney Anatomy, Physiology, and Measuring GFR: Pathology Final

Anatomy of the genitourinary system

2 kidneys in the retroperitoneal space around the 11th-12th ribs

Connected to ureters which is connected to the bladder

How much cardiac output do the kidneys recieve

Around 25%

Size of the kidneys

120-150g, 10-12cm

Nephron

Functional unit of the kidney

Approximately 1 million nephrons per kidney (more than we need)

Contains the afferent and efferent arterioles, glomerulus in the Bowman's capsule, proximal tubule, loop of Henle, distal tubule, and collecting duct

From the collecting duct urine goes into the urinary bladder

Highly vascularized and folded in on itself

The glomerulus

Has the afferent and efferent arterioles and a ball of capillaries surrounded by podocytes

Capillaries and podocytes make up the glomerular basement membrane

Surrounding the epithelial cells there is an endothelial layer (Bowman's capsule). Inside of the Bowman's capsule there are mesangial cells

Glomerular basement membrane

Made of epithelial cells and podocytes

Mesangial cells

Cells that exist inside of the Bowman's capsule

Glomerular filtration by percents

Only filters about 20% of what comes to it, out of that 20%, 19% is resorbed and 1% goes into the urine

Where does filtration happen

At the glomerulus

Where does majority of resorption occur

Proximal tubule, fine tuned by loop of Henle and distal tubule

Kidney functions

- Metabolic

- Hemodynamic

- Endocrine

Metabolic kidney functions

- Electrolytes

- Acid/base status

- Excretions of toxins, drugs, metabolic biproducts

Hemodynamic function of the kidney

- Maintenance of blood pressure (through RAAS)

- Maintenance of body volume

Endocrine function of the kidney

- Release erythropoietin needed to make RBC

- Maintain bone homeostasis (involved in production of active vitamin D3)

Why is the kidney involved in bone homeostasis

Involved in the production of active vitamin D3

Glomerular filtration rate is determined by

- Filtration pressure

- Filtration coefficient (how much can get through the membrane)

Can we measure GFR directly?

No, need a surrogate measure

Autoregulation

Actions done by the kidney to maintain a constant GFR

Perfect molecule for measuring GFR

- Endogenous

- Only filtered, no secretion or resorption

- Easy to measure in blood/urine

- Inexpensive

The perfect marker does not exist!

Endogenous markers for GFR

- Creatinine

- Cystatin C

- Urea

Creatinine as a marker for GFR

Endogenous marker

- Most commonly used

- Related to muscle mass

- Freely filtered, secreted, no resorption

- Extra-renal secretion

Cystatin C as a marker for GFR

Endogenous marker

-More readily available as a test but more expensive

- Not related to muscle mass (good to use in those who have high or low protein diet or for extremes of body size)

- Non glycosylated protein

- Filtered but not absorbed

When is using cystatin C as a marker for GFR inaccurate

Hypothyroid or steroid use

Urea as a marker for GFR

Endogenous marker

- Not used in clinical practice

- Easy to measure

- Altered by protein intake/catabolism

- 50% reabsorbed

Inulin as a marker for GFR

Exogenous marker

- Gold standard

- 100% excreted

- Inert sugar

- Difficult and expensive

Iothalamate as marker for GFR

Exogenous marker, not used anymore

- Actively secreted leading to overestimation of GFR

- Expensive and difficult

DTPA/EDTA as marker for GFR

Exogenous marker

Attached to radioisotope that can dissociate from the molecule leading to underestimation of GFR

Expensive and difficult

How do we estimate GFR

Using equations! Most accepted one is CKD-EPI 2021

Others exist: Cockroft Gault, MDRD but not applicable to modern patient populations

Measuring blood and urine levels of endogenous marker

Requires 24 hour urine collection, cannot use cystatin C as it is not excreted (can only use creatinine)

3 assumptions made about creatinine when we are using it to calculate GFR

- Meets criteria for ideal marker for GFR

- Production = excretion, when GFR falls creatinine increases proportionally

- Accurate and reproducible

Between what values is GFR the most accurate

Between 30-60mL/minute

This is when there is a linear relationship between GFR and serum creatinine, after that it falls off

Does a change in creatinine equal a change in GFR

No, other things can be changing the creatinine such as:

- Aging

- Female sex

- Race

- Body habitus

- Chronic illness

- Diet

Creatinine in rapidly changing GFR

There is a lag between creatinine and GFR. If you were to remove someones kidneys the GFR would be 0, but the serum creatinine would not increase until later on. Then, it would increase at the rate of creatinine production.

When do we use cystatin c

- Medication that impairs creatinine kinase pathway

- Extremes of body mass

- Extremes of protein intake

CKD-EPI 2021

Currently used formula to estimate GFR, uses serum creatinine, age, and sex

Most accurate when eGFR is below 60mL/min

MDRD

Estimation of GFR, not used because it was created in a population with non-diabetic CKD and underestimates GFR

Cockcroft Gault

Estimation of GFR, measures creatinine clearance

Females adjusted by 0.85 but there is no evidence to prove that this should be done

Historically used in drug dosing

When does the Cockcroft Gault overestimate GFR

Edematous or obese patients

Developed before obesity was common

Race and GFR estimation

Used to be included in the CKD-EPI but has been taken out

Self reported black patients were seen to have higher eGFR (mechanism unknown)

Ultimately removed because race is a social construct and there is great diversity among black patients

24 hour urine collection

Patient collects urine for 24 hours, assumes production = excretion

Difficult for patients and prone to errors

Nuclear scan

Isotope is injected into kidneys to determine if there is a differential split in the kidneys

Often done before kidney donation to make sure there is not a split before donation