Association Between Urine Concentration Ability and the Progression of Chronic Kidney Disease

Design: Prospective observational study Setting: Predialysis clinic. Participants: We will include adults \>18 years providing signed informed consent. Inclusion: Patients with CKD and estimated GFR of less then 50 mL per minute estimated by the short MDRD equation base on two creatinine values taken at least two weeks apart and are not getting steroids or immunosuppressive medication as treatment for their primary kidney disease. Exclusion: 1. Life expectancy of less then 6 month. 2. Expected to start renal replacement therapy within 3 month. 3. Acute or acute on chronic renal failure with reversible component. 4. Treatment with AVP inhibitors. 5. Chronic hyponatremia (Na+\<135 in two measurement two weeks apart). 6. Primary polydipsia. 7. Inability to give informed consent. 8. Clinical hypovolemia. Outcomes: Primary outcomes: Rate of GFR decline as assessed by short MDRD equation with at least three measurements at least three month apart. . Secondary efficacy 1. Rate of ESKD define as need RRT. 2. Overall mortality. 3. ESKD and overall mortality. 4. Blood pressure as assessed by clinic measurement. 5. Protein creatinine ratio in random urine sample. 6. Hemoglobin level. 7. Need for erythropoietin treatment. 8. Blood level of 25OH vitamin D and 1,25OH vitamin D. 9. PTH, calcium and phosphate level. 10. The occurrence of edema by physical evaluation. Predefined subgroup analysis: 1. Diabetic patients. 2. Patients treated with diuretics. Sample size: We will need to recruit about 200 patients. Statistical methods: We will use linear regression analysis with 95% CI for the continuous variable. And chi square for dichotomous variable. Data collection and trial flow: All patients in predialysis clinic of Dan district of "Kupat holim clalit" will be screen. Patients fulfilling inclusion criteria will be approached by trial investigator for informed consent and trial recruitment. For patients fulfilling inclusion criteria that will not consent to participate we will be record name and ID without further details. Consenting patients will bring the three samples of first voided urine of the morning for osmolarity, PH, sodium, potassium and chloride. Patient recruitment: Baseline data collection: Collection of data will include baseline conditions, primary kidney disease, current medications, clinical evaluation for edema and blood pressure. Laboratory results will include creatinine, urea, sodium, potassium, GFR assessed by short MDRD equation, protein creatinine ratio in random urine sample Hb level, vitamin D level calcium, phosphorus and PTH. Follow-up and outcome data collection: 1. Creatinine, estimated GFR, urea, sodium, potassium chloride, hemoglobin and protein creatinine ratio in random urine sample at least every three month 2. Clinical assessment for edema and blood pressure ant least every three month. 3. Time to initiation of dialysis or transplantation. 4. Mortality of any cause and cardiovascular mortality. 5. Hospitalization for any cause and the length of hospital stay. 6. The need for ESA treatment and ESA dose will be recorded.