Clinical trial NCT02875886: DD-study: Diet or Diuretics for Salt-sensitivity in Chronic Kidney Disease
Official title: DD-study: Diet or Diuretics for Salt-sensitivity in Chronic Kidney Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Kidney Disease
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
First posted: 2016-08-23
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: In this clinical study the anti-hypertensive response to dietary salt restriction is compared with the anti-hypertensive response to the diuretics hydrochlorothiazide/amiloride in adult patients with chronic kidney disease.

Detailed description: Patients with chronic kidney disease (CKD) are exquisitely salt-sensitive. Salt-sensitivity in CKD is linked to hypertension and cardiovascular outcomes. Dietary salt restriction is an accepted intervention for salt-sensitivity in CKD. Another strategy, however, could be to block sodium uptake by the kidney pharmacologically by diuretics. Especially diuretics acting on the distal tubule may be effective, because this appears to be the site of increased sodium reabsorption in CKD. It is currently unknown how these two strategies, diet or diuretics, relate. The investigators hypothesize that diuretics are non-inferior to diet.

Eligibility criteria: Inclusion Criteria:

* Age \> 18 years.
* CKD stage 3 or 4 (MDRD-GFR 15-60 ml/min)
* Use of any anti-hypertensive drugs
* No anti-hypertensive drugs but an average office systolic blood pressure \> 140 mmHg (as measured by datascope)

Exclusion Criteria:

* Salt-wasting CKD
* Nephrotic syndrome
* Pregnant or breastfeeding women
* Life expectancy \< 6 months
* Severe heart failure (NYHA III or IV) or liver cirrhosis with ascites and the inability to withdraw diuretics
* Rapidly declining kidney function with high likelihood of dialysis or kidney transplantation in the coming 4 months
* Kidney transplant recipients
* Use of immunosuppressive drugs
* Use of non-steroidal anti-inflammatory drugs
* Previous intolerance or allergy to hydrochlorothiazide or amiloride
* Serum sodium \< 135 mmol/l
* Serum potassium \< 3.5 mmol/l or \> 5.0 mmol/l
* Inability to adhere to the study protocol (due to language, incapacitated subjects, subjects with intellectual disability)

Primary outcomes:
measure: 24 hour blood pressure
timeFrame: Two weeks after start of each intervention
Secondary outcomes:
Other outcomes:
Locations:
city: Rotterdam
country: Netherlands
facility: ErasmusMC
Study officials:
affiliation: Erasmus Medical Center
name: Ewout J Hoorn, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Meng L, Fu B, Zhang T, Han Z, Yang M. Salt sensitivity of blood pressure in non-dialysis patients with chronic kidney disease. Ren Fail. 2014 Apr;36(3):345-50. doi: 10.3109/0886022X.2013.866008. Epub 2013 Dec 17.
citation: McMahon EJ, Campbell KL, Bauer JD, Mudge DW. Altered dietary salt intake for people with chronic kidney disease. Cochrane Database Syst Rev. 2015 Feb 18;(2):CD010070. doi: 10.1002/14651858.CD010070.pub2.
citation: Agarwal R, Sinha AD, Pappas MK, Ammous F. Chlorthalidone for poorly controlled hypertension in chronic kidney disease: an interventional pilot study. Am J Nephrol. 2014;39(2):171-82. doi: 10.1159/000358603. Epub 2014 Feb 11.
citation: Slagman MC, Nguyen TQ, Waanders F, Vogt L, Hemmelder MH, Laverman GD, Goldschmeding R, Navis G. Effects of antiproteinuric intervention on elevated connective tissue growth factor (CTGF/CCN-2) plasma and urine levels in nondiabetic nephropathy. Clin J Am Soc Nephrol. 2011 Aug;6(8):1845-50. doi: 10.2215/CJN.08190910. Epub 2011 Jul 22.
citation: Levy Yeyati N, Fellet A, Arranz C, Balaszczuk AM, Adrogue HJ. Amiloride-sensitive and amiloride-insensitive kaliuresis in advanced chronic kidney disease. J Nephrol. 2008 Jan-Feb;21(1):93-8.
citation: McMahon EJ, Campbell KL, Bauer JD, Mudge DW, Kelly JT. Altered dietary salt intake for people with chronic kidney disease. Cochrane Database Syst Rev. 2021 Jun 24;6(6):CD010070. doi: 10.1002/14651858.CD010070.pub3.
citation: Bovee DM, Visser WJ, Middel I, De Mik-van Egmond A, Greupink R, Masereeuw R, Russel FGM, Danser AHJ, Zietse R, Hoorn EJ. A Randomized Trial of Distal Diuretics versus Dietary Sodium Restriction for Hypertension in Chronic Kidney Disease. J Am Soc Nephrol. 2020 Mar;31(3):650-662. doi: 10.1681/ASN.2019090905. Epub 2020 Jan 29.