Chronic Kidney Disease, Metabolic Acidosis, Sickle Cell Anemia
Conditions
Keywords
Sickle cell disease, Chronic kidney disease, Bicarbonate therapy
Brief summary
The objective of this study is to assess the effect of alkali administration on bicarbonate and potassium levels in patients with Sickle Cell Disease (SCD) and depressed serum bicarbonate levels. The study is a prospective non-blinded evaluation of tolerability and efficacy of alkali repletion with 4 weeks of observation and two sequential 4 week courses of escalating oral sodium bicarbonate treatment.
Detailed description
Primary Objective: To assess the effect of alkali administration on bicarbonate and potassium levels in patients with SCD and depressed serum bicarbonate levels. Secondary Objectives: To assess the effect of alkali administration on improvement in hemolysis and on sequelae of impaired kidney function, ie, LDH, Hgb, reticulocyte count, red cell half-life, and muscle strength, Vitamin D levels, and markers of bone turnover, respectively. To assess the influence of alkali administrations on markers of kidney tubule inflammation. To evaluate intraparenchymal iron in patients with SCD and renal dysfunction. Safety and adverse events of alkali patients with sickle cell disease will be monitored. This research will supplement current knowledge about management of the clinically important subset of people with SCD who have renal insufficiency and acid-base perturbation.
Interventions
DRUGSodium Bicarbonate
Oral sodium bicarbonate tablets administered at a starting dose of 0.6 mEQ/Kg body weight and will be escalated once, at 4 weeks, to 0.9 mEQ/Kg body weight. Weekly schedule: 0-4 weeks: Serial Measurement at baseline, without therapy 4-8 weeks: \*\ 0.6 mEq/kg of ideal body weight of Sodium Bicarbonate tablets divided into TID dosing 8-12 weeks: \*\ 0.9 mEq/kg of ideal body weight of Sodium Bicarbonate tablets divided into TID dosing \* to the closest dose of 650 mg (7.74 mEq) Ideal Body Weight is defined by the following formulas (Devine Calculation): Ideal Body Weight (men) = 50 + 2.3 (Height (in) - 60) Ideal Body Weight (women) = 45.5 + 2.3 ( Height (in) - 60)
Sponsors
University Hospitals Cleveland Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Sickle cell disease patients with HbSS * eGFR \<90 ml/min/1.73m2 (determined by abbreviated 4 variable modification MDRD equation) and/or measured urinary albumin to creatinine ratio \>30mg/g. * Age ≥18 years
Exclusion criteria
* Previous chronic treatment with alkali (including sodium bicarbonate, calcium carbonate or baking soda) * Bicarbonate level \>25 mEq/L * Decompensated heart failure * Uncontrolled systolic blood pressure \>140 mm/Hg (the cutoff for systolic hypertension in SCD is lower than in non-SCD) * Moderate-to-severe lower extremity edema * Projected progression to ESRD within 6 months * Kidney transplantation * Treatment with immunosuppressives within the last 3 months * Vasoocclusive (VOC) within 1 week of study entry * Active (open) leg ulcer * Change in hydroxyurea dose within the last 3 months, unless a self-limited interruption of a stable dose * Blood transfusion within 8 weeks, unless on chronic transfusions * Pregnancy * Inability to give informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum bicarbonate level | 12 weeks | To assess the effect of alkali administration on bicarbonate and potassium levels in patients with SCD and depressed serum bicarbonate levels. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hemolysis markers | 12 weeks | To assess the effect of alkali administration on improvement in hemolysis and on sequelae of impaired kidney function, ie, LDH, Hgb, reticulocyte count, red cell half-life, and muscle strength, Vitamin D levels, and markers of bone turnover, respectively. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Tubular effect | 12 weeks | To assess the influence of alkali administrations on markers of kidney tubule inflammation. |
Countries
United States
Outcome results
None listed