1. E XTRA CASE 2

2. PRESENTATION Ellen, 85 years, regular patient PC: nocturia disturbing her sleep HPC: happening for several weeks

3. W HAT BASIC MECHANISMS OR PROCESSES CAN CAUSE NOCTURIA ? R ATHER THAN TRYING TO GENERATE A LARGE, RANDOM LIST OF HYPOTHESES, TRY TO THINK OF THE MOST BASIC MECHANISMS FIRST, AND THEN BUILD FROM THERE.

4. W HAT BASIC MECHANISMS OR PROCESSES CAN CAUSE NOCTURIA ? Polyuria DM Psychogenic polydipsia Diuretics b-blockers Caffeine RHF Dec bladder capacity External/internal pressure (bladder/prostate cancer; cyst) Incomplete bladder voiding Subvesical obstruction Calculi Detrusor instability Neurogenic bladder disorders Overactive bladder Bladder inflammation Distal ureteral stone

5. PMH HT for decades  taking ACEI and thiazide BP always well-controlled Weight 42kg; height 152cm; looks frail Lives alone, but manages well

6. I T IS IMPORTANT TO REMEMBER THAT PROBLEMS OUTSIDE OF THE URINARY SYSTEM CAN CAUSE URINARY SYMPTOMS, AND YOU SHOULD HAVE COVERED MANY OF THESE IN CONSIDERING YOUR ANSWER TO Q1. R EALISTICALLY – WHAT ARE THE LIKELY PROBLEMS ( OCCURRING OUTSIDE OF THE URINARY SYSTEM ITSELF ) IN A WOMAN OF THIS AGE AND GENERAL CIRCUMSTANCES, THAT MIGHT BE IMPLICATED IN HER PROBLEM OF NOCTURIA ? R EMEMBER THAT COMMON THINGS OCCUR COMMONLY !

7. W HAT PROBLEMS OUTSIDE OF THE URINARY SYSTEM COULD CAUSE THESE SX IN ELLEN ? T2DM Metabolic syndrome RHF Cervical/uterine cancer

8. INVESTIGATIONS Serum creatinine: 150umol/L

9. W HY IS CREATININE AN APPROPRIATE SUBSTANCE TO USE WHEN ESTIMATING GFR? Produced at an ~constant rate Freely filtered at glomerulus Neither absorbed nor secreted along tubules Plasma levels increase as filtration decreases (but large reserve) Creatinine clearance will decrease as filtration decreases Inulin clearance is gold standard, but this is invasive (requires injection) whereas creatinine is produced naturally

10. W HAT ARE THE PITFALLS IN USING SERUM CREATININE TO ESTIMATE KIDNEY FUNCTION ? Large reserve  renal function needs to drop by ~50% to affect serum creatinine Does not differentiate between dec GFR, damaged tubules, blockage of outflow, etc

11. W HAT ABOUT ARRANGING CREATININE CLEARANCE MEASUREMENT ? W HY WOULD YOU NOT DO THIS ? She is frail, lives alone. Collection of 24 hour urine MUST include all urine passed within 24 hour period, therefore it can be difficult to collect all. eGFR can provide a good estimate. INSTRUCTIONS FROM UPTODATE ON 24 HR URINE COLLECTION You should collect every drop of urine during each 24-hour period. It does not matter how much or little urine is passed each time, as long as every drop is collected. Begin the urine collection in the morning after you wake up, after you have emptied your bladder for the first time. Urinate (empty the bladder) for the first time and flush it down the toilet. Note the exact time (eg, 6:15 AM). You will begin the urine collection at this time. Collect every drop of urine during the day and night in an empty collection bottle. Store the bottle at room temperature or in the refrigerator. If you need to have a bowel movement, any urine passed with the bowel movement should be collected. Try not to include feces with the urine collection. If feces does get mixed in, do not try to remove the feces from the urine collection bottle. Finish by collecting the first urine passed the next morning, adding it to the collection bottle. This should be within ten minutes before or after the time of the first morning void on the first day (which was flushed). In this example, you would try to void between 6:05 and 6:25 on the second day. If you need to urinate one hour before the final collection time, drink a full glass of water so that you can void again at the appropriate time. If you have to urinate 20 minutes before, try to hold the urine until the proper time. Please note the exact time of the final collection, even if it is not the same time as when collection began on day one.

12. E STIMATE ELLEN ’ S GFR http://www.kidney.org.au/HealthProfession als/eGFRClinicalTools/tabid/632/Default.asp x Ellen: wt 42 kg, age 85 Serum creatinine: 150μmol/L MDRD calculator formula: Answer: 29mL/min/1.73m 3

13. W HAT STAGE OF CHRONIC KIDNEY DISEASE DOES THIS REPRESENT

14. C ALCULATE THE E GFR, USING THE MDRD GFR CALCULATOR AND THE C OCKCROFT AND G AULT EQUATION CALCULATOR http://www.sydpath.stvincents.com.au/other/Calc sCrClCGumol.htm Constant is 1.23 for men and 1.04 for women

15. S ERUM CREATININE LEVELS IN M L/ MIN ??? I’ M GOING TO ASSUME A MISTAKE AND TRY FOR THESE AS ΜMOL /L Male aged 46, wt. 70 kg, Serum creatinine 110 mL/min – MDRD: 63, C-G: 74 Male aged 46, wt. 110 kg, Serum creatinine 110 mL/min – MDRD: 63, C-G: 116 Female aged 46, wt. 70 kg, Serum creatinine 90 mL/min - MDRD: 58, C-G: 76 Female aged 46 wt. 110 k, Serum creatinine 90 mL/min - MDRD: 58, C-G: 120 Female aged 85, wt. 45 kg, Serum creatinine 90 mL/min - MDRD: 52, C-G: 29 Female aged 85, wt. 65kg, Serum creatinine 90 mL/min – MDRD: 52, C-G: 41 Female aged 25, wt. 45 kg, Serum creatinine 90 mL/min - MDRD: 66, C-G: 60 Female aged 25, wt. 65kg, Serum creatinine 90 mL/min - MDRD: 66, C-G: 87 All units of eGFR in mL/min/1.73m 3 These examples show how MDRD equation for eGFR do not take into account the patient’s weight, and how this can have a dramatic effect on the eGFR.