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The kidney,chronic kidney disease and WAGR kidney disease Jeffrey Kopp, MD CAPT, US Public Health Service Kidney Disease Section

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Presentation on theme: "The kidney,chronic kidney disease and WAGR kidney disease Jeffrey Kopp, MD CAPT, US Public Health Service Kidney Disease Section"— Presentation transcript:

1 The kidney,chronic kidney disease and WAGR kidney disease Jeffrey Kopp, MD CAPT, US Public Health Service Kidney Disease Section

2 Kidneys on computerized tomography (CT) scan

3 Kidneys and what they do (1)

4 Product Waste Cars Smoke Homeostasis Urine

5 Kidneys came early in animal evolution

6 1 million nephrons in each kidney: each is glomerulus + tubule

7 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

8 One kidney, one million nephrons

9 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

10 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)

11 When kidney function is impaired GFR declines linearly serum creatinine rises geometrically

12 Estimating kidney function from serum tests PopulationNameVariablesP30% 40: 28, 52 ChildrenSchwartz 1976Creatnine, height Schwartz 2012 + BUN, Cystatin C AdultsMDRDAge, sex, race, creatinine 75% CKD-EPI (2012)Same87% CKD-EPI-Cr/CystC (2012) + Cystatin C92% Gold standard test Infuse iothalamate, measure serum and urine levels, calculate kidney clearance of iothalamate Requires IV and takes ~3 hr

13 Chronic kidney disease stages StageGFR ml/min/1.73m 2 Possible complications Dose adjustment for meds excreted by kidney 1Normal GFR; proteinuria or hematuria >90BP- 2Mild CKD60-90BP- 3Moderate CKD30-60BP, bone, CVD+ 4Severe CKD15-30BP, bone, CVD, anemia ++ 5Kidney failure = ESKD <15BP, bone, CVD, anemia, infection +++

14 Assessing urine protein levels Example of urines taken from the same patient at two different times of the day  Concentrated urine: albumin 10 mg/dL, creatinine 100 mg/dL = ACR 100 mg/g  Dilute urine: albumin 2 mg/dL, creatinine 20 mg/dl = ACR 100 mg/g  Problem: in a particular patient at a particular phase of disease, protein concentration in urine fluctuates with urine concentration from sample to sample  Since the amount of urine creatinine/day is relatively constant, the concentration in urine provides an index of urine concentration or dilution  Solution: the protein/creatinine ratio or albumin/creatinine ratio will adjust for changes in urine concentration

15 Assessing kidney function: urine tests BloodProtein Urinalysis dipstickNegative, Trace, 1, 2, 3 Urinalysis microscopic Did the red blood cells come from the kidney? NA Random urine (children, adults) NAAlbumin/creatinine ratio (ACR) 30-300 mg/g: microalbuminuria (metabolic syndrome, early glomerulosclerosis) >300 mg/g: macroalbuminuria - kidney disease >1 g/g: nephrotic Protein/creatinine ratio (PCR) <0.2 g/g: normal 0.2-2 g/g: proteinuria >2 g/g: nephrotic 24 hour urine collection (adult values) NAAlbumin 30-300 mg/d: microalbuminuria >300 mg/d: macroalbuminuria – kidney disease Protein >150 mg/d: proteinuria > 3.5 g/d: nephrotic

16 WAGR kidney disease

17 Wilms tumor: CKD is common when there is a genetic basis Breslow Cancer Res 2000  National registry of Wilms tumor, 1969-1995  N = 5965 enrolled at <16 yr  Renal failure: cr>2.5 or dialysis WAGR Denys-Drash

18  Genotype/phenotype: relate phenotype to genes deleted  Random urine A/C in 24 subjects NIH WAGR study ACR mg/g<1010-1718+ <30523 30-300043 >300023

19 Patterns of WAGR kidney diseases Immature podocytes Diffuse mesangial sclerosis Focal segmental glomerulosclerosis

20 Screening for WAGR kidney disease  Screening: yearly BP check, serum creatinine and cystatin C, urine ACR (and possibly PCR)  Strive to maintain normal body weight: “bigness” stresses 2 kidneys, more so 1 kidney, and most 1 kidney with glomerulosclerosis  Maintain normal BP: if borderline, restrict dietary salt (2 g/d target) and check BP at home. BP target is 50 th percentile BP for age and height.  If albuminuria appears, consider kidney biopsy to confirm that glomerulosclerosis is present (but probably no biopsy if single kidney)  No role for kidney ultrasound in diagnosing glomerular disease – will be normal until extensive fibrosis develops and substantial loss of function has occurred.

21 Treatment for WAGR kidney disease  Probably start therapy with renin-angiotensin pathway blockers – one drug and possibly two drugs  This approach slows glomerulosclerosis in other diseases but has not been tested in WAGR  These drugs lower BP and rise potassium, so these must be monitored.  Low sodium diet potentiates the anti-proteinuric effect of RAS blockers

22 Renin Angiotensin 1 Angiotensin receptor Angiotensinogen Angiotensin 2 Angiotensin converting enzyme Blood vessel constriction Aldosterone Renin-angiotensin-aldosterone system (RAAS) Spironolactone Eplerenone ACE inhibitors Angiotensin receptor blockers (ARB) Aliskiren Aldosterone receptor Sodium retention Fibrosis Trauma: maintains blood pressure, promotes wound healing Chronic kidney disease: elevates blood pressure, promotes fibrosis – blocking RAAS is a key to slowing or halting kidney disease progression

23 Renal replacement therapy

24 Hemodialysis  Dialysis center or home  3x week or 6x week  Advantages: effective in large people, less for patient/family to do  Disadvantages: needles, vascular access problems, time spent in center, arranging treatments when traveling, disequilibrium after dialysis sessions

25 Peritoneal dialysis  Continuous ambulatory: 4 1-2 liter exchanges/d  Intermittent: 10-15 liters overnight, 1 exchange at night  PD Advantages: mobility, control, no needles  Disadvantages: more patient/family effort, less effective in large person, peritonitis

26 Kidney transplant: the preferred approach to renal replacement therapy

27 Kidney transplant: requirements to be donor  Age 18 – 55  Normal kidney function  No diabetes  No cancer, HIV, hepatitis B or C  Normal BP or possibly on 1 BP medication  Blood group match (can do plasmapheresis if not) USRDS 2011

28 Induction antibody use Figure 7.28 (Volume 2) Patients age 18 & older receiving a first-time, kidney-only transplant. USRDS 2011

29 Immunosuppression use Figure 7.27 (Volume 2) Patients age 18 & older receiving a first-time, kidney-only tx. CsA: cyclosporine A; CsM: cyclosporine microemulsion. USRDS 2011

30 Acute rejection within the first year post-transplant Figure 7.19 (Volume 2) Patients age 18 & older. USRDS 2011

31 Outcomes: living donor transplants Figure 7.18 (Volume 2) Patients age 18 & older receiving a first-time, kidney-only transplant. Adj (survival): age/gender/race/primary diagnosis. USRDS 2011

32 Renal transplant vs chronic dialysis  Longer survival  Better quality of life  There are concerns: immunosuppressive medications, infections (virus), cancer

33 The future  Therapies for chronic kidney disease improve every year  Perhaps we can develop specific therapies for WAGR kidney disease


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