Patients hospitalized in intensive care units (ICU) are particularly susceptible to vitamin D3 deficiencies. This can be due to the severity of their underlying disease, the type of treatment they are on, malnutrition before and inadequate nutrition during the hospitalisation preceding ICU admission, as well as advanced age. It has also been established that plasma levels of 25(OH)D3 tend to systematically decrease during ICU treatment. Therapeutic interventions administered in ICU settings such as fluid resuscitation or extracorporeal therapies can cause additional vitamin D3 deficiencies. The incidence of deficiency in critically ill patients can reach up to 90%, and even 30% of ICU patients can have undetectable plasma levels. It is impossible to replenish vitamin D3 levels in critically ill patients with traditional enteral and parenteral nutrition treatment regimens, because nutritional products contain too little of the vitamin. Vitamin D3 deficiency in critically ill patients has been associated with acute kidney injury, acute respiratory failure, sepsis, septic shock and increased all-cause ICU mortality. Despite that, assessment of plasma 25(OH)D3 levels is not a routine practice in ICUs. In view of the prevalence of vitamin D3 deficiencies in ICU patients, rapid replenishment of this deficiency with an increased supplementation dose should be considered as a potential means to improve prognosis in this patient population. The current standard therapy is the administration of 500,000 IU of vitamin D3 via the enteral route in ICU patients with severe deficiency (recommended by ESPEN). The NephroD study is meant to help answer the question whether increasing the standard ICU supplementation dose of vitamin D3 by 50% will ensure a more effective replenishment of this vitamin in critically ill patients undergoing CRRT.

Inclusion Criteria:

1. Presence of the following indications for initiation of CRRT with CVVHDF or CVVHF (acc. to KDIGO, Clinical Practice Guideline for Acute Kidney Injury):

   • replacement of kidney function in acute kidney injury
   • hyperkalaemia
   • metabolic acidosis
   • pulmonary oedema
   • uraemic complications (bleeding disorder, pericarditis)
   • hypervolaemia
   • support of renal function (volume control, regulation of acid-base and electrolyte status)

2. Sequential Organ Failure Assessment (SOFA) score of minimum 5 points at enrolment

3. Age of >18 years

4. Plasma 25(OH)D3 levels ≤12.5 ng/ml as measured by the local laboratory of a participating hospital

5. Properly managed enteral nutrition regardless of dosing

Exclusion Criteria:

1. Acute or advanced chronic liver failure (estimated on the basis of the clinical picture and biochemical markers: plasma bilirubin, plasma AST and ALT, high plasma AST/ALT ratio, glycaemia, INR)
2. Hypercalcaemia (total calcium concentration >11 mg/dl)
3. Any parathyroid disorder
4. End stage renal disease according to the KDIGO classification
5. Patients undergoing plasmapheresis, extracorporeal membrane oxygenation (ECMO), extracorporeal carbon dioxide removal (ECCO2R)
6. Patients who, in the opinion of the investigator, are not expected to survive 72 hours since enrolment
7. A history of nephrolithiasis or de novo nephrolithiasis
8. Patient qualified to a protocol for the avoidance of futile therapy
9. Pregnancy
10. Sarcoidosis
11. Risk of impaired intestinal absorption caused by the critical illness, associated with impaired peristalsis and delayed gastric emptying, constipation, diarrhoea, shock-induced intestinal hypoperfusion, hyperhydration with resulting intestinal oedema following fluid resuscitation, intestinal flora disorders.