The kidney,chronic kidney disease and WAGR kidney disease
Jeffrey Kopp, MD CAPT, US Public Health Service Kidney Disease Section
[email protected]
Kidneys on computerized tomography (CT) scan
Kidneys and what they do (1)
Product Waste
Cars Smoke
Homeostasis Urine
Kidneys came early in animal evolution
1 million nephrons in each kidney: each is glomerulus + tubule
Glomerular filtration: filtering small molecules from the circulation
Renal blood flow ~1000 mL/min Renal plasma flow ~600 mL/min Glomerular filtration rate (GFR) ~100 mL/min = ~150 L/day
One kidney, one million nephrons
Tubular reabsorption: reclaiming what we need before it heads down the tubule to the ureter, bladder, and out
THE GOOD (unless excess) Sodium Potassium Chloride Bicarbonate Calcium Magnesium Glucose Amino acids Vitamins B, C etc
THE BAD Urea Uric acid
Creatinine Toxins etc
Why does the kidney filter everything, and then reclaim what is needed and discard the rest? Keeping the baby, throwing out the bathwater
Creatinine physiology Small molecule, released from muscle turnover Production depends on muscle mass
Freely filtered through the the glomerulus Serum levels depend upon muscle mass (higher when muscle mass is higher) and kidney function (higher when kidney function is poor)
When kidney function is impaired GFR declines linearly serum creatinine rises geometrically
Estimating kidney function from serum tests Gold standard test • Infuse iothalamate, measure serum and urine levels, calculate kidney clearance of iothalamate • Requires IV and takes ~3 hr
Population Name
Variables
Children
Schwartz 1976
Creatnine, height
Schwartz 2012
+ BUN, Cystatin C
MDRD
Age, sex, race, creatinine
75%
CKD-EPI (2012)
Same
87%
CKD-EPI-Cr/CystC (2012)
+ Cystatin C
92%
Adults
P30% 40: 28, 52
Chronic kidney disease stages Stage
GFR ml/min/1.73m2
Possible complications
Dose adjustment for meds excreted by kidney
1
Normal GFR; proteinuria or hematuria
>90
BP
-
2
Mild CKD
60-90
BP
-
3
Moderate CKD
30-60
BP, bone, CVD
+
4
Severe CKD
15-30
BP, bone, CVD, anemia
++
5
Kidney failure = ESKD
300 mg/g: macroalbuminuria - kidney disease >1 g/g: nephrotic Protein/creatinine ratio (PCR) 2 g/g: nephrotic
24 hour urine collection (adult values)
NA
Albumin 30-300 mg/d: microalbuminuria >300 mg/d: macroalbuminuria – kidney disease Protein >150 mg/d: proteinuria > 3.5 g/d: nephrotic
WAGR kidney disease
Wilms tumor: CKD is common when there is a genetic basis National registry of Wilms tumor, 1969-1995 N = 5965 enrolled at 2.5 or dialysis WAGR Denys-Drash
Breslow Cancer Res 2000
NIH WAGR study Genotype/phenotype: relate phenotype to genes deleted Random urine A/C in 24 subjects
ACR mg/g
