This study investigated whether daily furosemide could preserve urine volume and slow the decline of residual renal function in patients on continuous ambulatory peritoneal dialysis (CAPD) without side effects. Sixty-one new CAPD patients were randomly assigned to receive either daily furosemide 250mg plus additional metolazone if needed or no treatment. After one year, urine volume declined less in the diuretic group compared to the control group. However, urinary urea and creatinine clearance declined at the same rate in both groups. While furosemide maintained higher urine volume, it did not slow the decline of residual renal function. Larger studies are still needed to determine if the urine volume preservation

1. Role of Diuretics in the preservation of residual renal function in patients on continuous ambulatory peritoneal dialysis Lakshmi Turlapati, M.D. Journal Club, March 18,2010

2. Introduction Most patients upon initiation of dialysis have some degree of Residual renal function, and may have normal or even high rates of urine output. This level of Residual renal function may persist for few years, adding continuous solute clearance to the intermittent clearances provided by dialysis treatments. Residual renal function also helps in maintenance of steady state fluid balance which is important in preventing persistent volume overload, hypertension and cardiac hypertrophy.

3. Introduction Hence KDOQI guidelines recommend to preserve residual renal function. Strategies to preserve RRF include use of ACE/ARB, Control of BP, Avoiding nephrotoxins, Avoidance of excessive ultra filtration and hypotension, use of biocompatible dialyzer membranes, use of bicarbonate based dialysate, use of ultrapure dialysate.

4. Introduction This study investigates whether Furosemide given long term to patients on Peritoneal dialysis would preserve urine volume and slow the decline of Residual Renal function without unwanted side effects.

5. Study Design Prospective Randomized Open label

6. Methods 61 new patients greater than 16 years of age starting CAPD were enrolled between June 1996 and November 1997. Followed for one year. Patients who had previously received more than 2 weeks of hemodialysis and those with a failing renal transplant were excluded.

7. Randomization and Treatment Randomized to receive either furosemide 250 mg daily or no treatment. Patients in diuretic treated group were given additionally Metolazone 5 mg orally daily if their urine volume did not exceed 500 ml/24 hrs at any follow up visit. Study assessment done at 6 and 12 months.

8. Randomization and Treatment Dialytic prescription was adjusted independent of the study and was guided by clinical parameters and calculated clearances. Urea clearance (Kt/V) of 1.7 or greater was obtained. Blood pressure was controlled, first by reduction of target weight before introduction of antihypertensives.

10. Study Measurements Urine volume was recorded at randomization, and at 6 and 12 months by 24 r collection Urinary and Dialytic urea and Crcl was calculated. Urinary electrolytes and osmolality were measured on 24 hr urine collections to allow calculation of free water and electrolyte free water clearances. PET test was done. Statistical Analysis was intention to treat using unpaired t test.

11. Results Urine volume at randomization was comparable between 2 groups.( 1020+-104 vs 1040+-130 ml/24 hrs) After 1 year of CAPD, UV declined in control group to 733+-124 ml/24 hrs whereas in the diuretic treated group it was 1070+-193 ml/24 hrs. However, urinary urea and Crcl declined at a constant rate in both groups.

15. Discussion The study shows that Daily Furosemide maintains the urine volume over a year of PD by a clinically significant mean difference of 340 cc/day at one yr. However, it doesn’t slow the decline of urinary urea and Cr clearance. Although proportion of patients with DM was higher in the diuretic-treated group, repeat analysis excluding pts with diabetes showed similar results.

16. Discussion Strengths: randomized, prospective study. Limitations: small sample size, unknown race/drugs/comorbidities, Unknown if Bp control adequate in study.

17. Discussion However, since preservation of urine volume is beneficial to maintain steady state fluid balance, reduce volume overload between intermittent dialysis treatments and thus prevent cardiac hypertrophy, it might be beneficial to use furosemide in dialysis pts. DOPPS is a large scale observational study in HD patients showing that diuretic use is associated with reduction in all cause and cardiac mortality in HD patients. Further large scale randomized studies are needed to investigate this survival benefit.