Effect of Intravenous Iron Repletion on Renal Function in Patients With Iron Deficiency and Acute Kidney Injury, Clinical Trial
Phase: PHASE2
Conditions: Anemia, Iron Deficiency, Acute Kidney Injury
Sponsor: Hospital Civil de Guadalajara

  
HOSPITAL No. 278 SHCP 44280 TEL. 3614-5501, 3614-7244 GUADALAJARA, JAL 
 
 
 
Teaching Subdirectorate 
Research Coordination  
 
 
 
 
REGISTRATION OF THE INVESTIGATION PROTOCOL 
 
1. GENERAL DATA  
1.1 TITLE OF THE PROJECT  
 
1.2 START DATE 
FINISH DATE  
 
1.4 PRINCIPAL INVESTIGATOR   
NAME : 
LAST NAME  
 
Chávez  
PATERNAL: 
  
  
 
Iniguez  
MATERNAL:  
  
  
 
 
 
(S):  
SPECIALTY: Nephrology  
NAMES 
Jonathan Samuel  
  
  
 
 
  SERVICE: Nephrology  
 
 
1.5 THESIS DIRECTOR 
 
NAME : 
LAST NAME  
PATERNAL:  
Chávez  
  
  
 
Iniguez  
MATERNAL:  
  
  
 
 
 
(S):  
SPECIALTY: Nephrology  
NAMES 
Jonathan Samuel  
  
  
 
 
  SERVICE: Nephrology  
 
 
Old Civil Hospital of Guadalajara 
"FRAY ANTONIO AlCALDE" 
Start August 2022, end December 2023  
Effect of intravenous iron repletion on renal function in patients with iron deficiency and acute kidney injury, clinical trial. June 2023, HCG/CEI-1232/22 
Version 2.0, 29 June 2023 
RECEPTION DATE  
PROVISIONAL REGISTRATION  
OPD  
DO NOT FILL  
“Effect of intravenous iron repletion on renal function in patients with 
iron deficiency and acute kidney injury, clinical trial” 

  
Old Civil Hospital of Guadalajara 
"FRAY ANTONIO MAYOR" 
  
HOSPITAL No. 278 SHCP 44280 TEL. 3614-5501, 3614-7244 GUADALAJARA, JAL 
 
 
 
 
Teaching Subdirectorate 
Research Coordination  
 
1.6 CO-MANAGER 
NAME :  
 
 
 
LAST NAME 
Ron  
PATERNAL: 
  
  
 
Magaña  
MATERNAL:  
  
  
 
NAMES 
Ana Lucia  
(S):  
  
  
 
 
SPECIALTY:  Hematology  
  
 
SERVICE:  Hematology  
  
 
1.7 ADVISOR 
NAME :  
 
LAST NAME  
PATERNAL:    
  
 
 
MATERNAL:   
  
 
NAMES  
(S):  
  
  
 
 
SPECIALTY:  
  
 
SERVICE:  
  
 
1.8 PARTICIPATING INSTITUTIONS 
 
Civil Hospital of Guadalajara Fray Antonio Alcalde  
INSTITUTION:  
  
 
without agreement  
AGREEMENT:  
  
 
 
 
INSTITUTION:     
   
 
 
AGREEMENT:  
  
   
 
 
INSTITUTION:     
 
 
AGREEMENT:  
  
  
 
Effect of intravenous iron repletion on renal function in patients with iron deficiency and acute 
kidney injury, clinical trial. June 2023, HCG/CEI-1232/22 
Version 2.0, 29 June 2023 

  
Old Civil Hospital of Guadalajara 
"FRAY ANTONIO MAYOR" 
  
HOSPITAL No. 278 SHCP 44280 TEL. 3614-5501, 3614-7244 GUADALAJARA, JAL 
 
 
 
 
Teaching Subdirectorate 
Research Coordination  
 
2.1 PROJECT SUMMARY  
  
  
Effect of intravenous iron repletion on renal function in patients with iron deficiency and acute 
kidney injury, clinical trial. June 2023, HCG/CEI-1232/22 
Version 2.0, 29 June 2023 
The purpose of this clinical trial is to carry out research on the effect on 
hemoglobin and renal function of the intravenous administration of iron 
dextran as a repletion strategy in patients with iron deficiency anemia and acute 
kidney injury, in which the patient You may benefit from this medication since it 
is expected to correct anemia, iron deficiency and renal function parameters, 
when compared with a control group (placebo), the safety of the drug will also 
be evaluated by recording adverse effects. I will point out with the patient the 
risks and benefits of including her in this type of study and I will answer all the 
doubts that arise, and I will also immediately report any serious adverse effect 
to the research ethics committee.  

  
Old Civil Hospital of Guadalajara 
"FRAY ANTONIO MAYOR" 
  
HOSPITAL No. 278 SHCP 44280 TEL. 3614-5501, 3614-7244 GUADALAJARA, JAL 
 
 
 
 
Teaching Subdirectorate 
Research Coordination  
 
2.2 INTRODUCTION  
 
 
 
2.3 JUSTIFICATION  
  
  
  
Effect of intravenous iron repletion on renal function in patients with iron deficiency and acute 
kidney injury, clinical trial. June 2023, HCG/CEI-1232/22 
Version 2.0, 29 June 2023 
Acute kidney damage is a complication that occurs in up to 30% of hospitalized 
patients. Iron deficiency has a high  incidence in the  population  of  critically ill 
patients and has been associated with multiple complications such as the 
development of anemia and renal dysfunction. The presence of iron deficiency, 
anemia and acute kidney injury is a common  combination in  critically  ill  patients 
and iron deficiency has been shown to promote mitochondrial dysfunction and this 
can be improved with intravenous iron correction, as has happened in clinical trials  
of patients with failure exacerbated cardiac arrest, improving its clinical evolution.  
 
The kidney is the second organ with the most mitochondria and mitochondrial 
dysfunction is a new therapeutic goal in acute kidney injury. It is possible that this 
combination is associated with an unfavorable clinical course in these patients.  
There is insufficient evidence for the implementation of intravenous iron in order to 
improve the parameters of iron deficiency anemia in patients with acute kidney 
injury.  
To our knowledge, there is no clinical trial that has explored our  
objectives.  

  
Old Civil Hospital of Guadalajara 
"FRAY ANTONIO MAYOR" 
  
HOSPITAL No. 278 SHCP 44280 TEL. 3614-5501, 3614-7244 GUADALAJARA, JAL 
 
 
 
 
Teaching Subdirectorate 
Research Coordination  
 
 
2.4 SCIENTIFIC BACKGROUND  
 
Acute kidney injury (ARD) is a serious complication that is independently 
associated with poor outcomes [1, 2]. Approximately one in five patients with 
non-severe sepsis develops AKI [3], which increases to two-thirds in critically ill 
patients. About 50% of ICU patients with AKI die (4-12), and those who survive 
an episode of AKI have a higher risk of progressing to chronic kidney disease 
(CKD). Currently, there are few pharmacological therapeutic options available to 
prevent or treat AKI, and management is  limited to alleviating hemodynamic  
and toxic renal lesions. support measures, such as dialysis.  
Iron deficiency occurs in up to 30% of hospitalized patients and has been linked 
to worse clinical evolution, even in the absence of anemia. This iron deficiency is 
worse even when anemia figures are reached. It has been documented that 
critically ill patients develop anemia as part of the process of their pathology. It 
has been seen that during processes of exacerbation of pathologies such as 
heart failure, the administration of intravenous iron avoids the probability of 
hospitalization and clinical evolution (13-16). It has been shown that in DRA  
there is mitochondrial dysfunction (17), specifically in the renal tubule where the 
greatest amount of mitochondria is concentrated,  
Effect of intravenous iron repletion on renal function in patients with iron deficiency and acute 
kidney injury, clinical trial. June 2023, HCG/CEI-1232/22 
Version 2.0, 29 June 2023 

  
Old Civil Hospital of Guadalajara 
"FRAY ANTONIO MAYOR" 
  
HOSPITAL No. 278 SHCP 44280 TEL. 3614-5501, 3614-7244 GUADALAJARA, JAL 
 
 
 
 
Teaching Subdirectorate 
Research Coordination  
 
 
 
 
2.5 OBJECTIVES  
 
 
Primary objective:  
The endpoint of interest was the proportion of patients meeting one or more criteria for Major 
Adverse Kidney Events within 30 days (MAKE30): in-hospital mortality; receipt of new RRT; or 
persistent renal dysfunction.   
In hospital mortality was defined as death from any cause prior to hospital discharge censored at 
30 days after ICU admission. Receipt of new RRT was defined as receipt of any modality of RRT 
between ICU admission and the first of (1) hospital discharge or (2) 30 days in a patient not 
known to have received RRT prior to ICU admission. Persistent renal dysfunction was defined as 
a final serum creatinine value before hospital discharge (censored at 30 days after enrollment) 
that was ≥ 200 % of the baseline creatinine value.  
And will be evaluated at 60 and 90 days.  
 
Secondary objectives:all the following will be at hospital discharge and 28 days 
after hospital discharge between the intervention group (iron replacement) compared 
to the control group (placebo).  
• 
ferritin value, (pg/dL)  
• 
transferrin saturation (%)  
• 
Hemoglobin (g/dL)  
• 
serum creatinine (mg/dL)  
• 
start of renal support therapy (any type of renal support such as: 
intermittent hemodialysis, peritoneal dialysis or continuous therapies)  
• 
recovery of renal function, considered as a decrease in serum 
creatinine and approaching <0.3mg/dL of basal creatinine  
• 
death  
 
Exploratory objectives: 
• 
safety of intravenous iron administration compared to placebo: assessed 
by the occurrence of adverse events such as allergic reaction, 
hypotension, dyspnea, rash, erythema. These will be evaluated during  
Effect of intravenous iron repletion on renal function in patients with iron deficiency and acute 
kidney injury, clinical trial. June 2023, HCG/CEI-1232/22 
Version 2.0, 29 June 2023 

  
Old Civil Hospital of Guadalajara 
"FRAY ANTONIO MAYOR" 
  
HOSPITAL No. 278 SHCP 44280 TEL. 3614-5501, 3614-7244 GUADALAJARA, JAL 
 
 
drug administration and during hospitalization frequently every 24 
hours by the nephrology staff, including the study investigators.  
Effect of intravenous iron repletion on renal function in patients with iron deficiency and acute 
kidney injury, clinical trial. June 2023, HCG/CEI-1232/22 
Version 2.0, 29 June 2023 

  
Old Civil Hospital of Guadalajara 
"FRAY ANTONIO MAYOR" 
  
HOSPITAL No. 278 SHCP 44280 TEL. 3614-5501, 3614-7244 GUADALAJARA, JAL 
 
 
 
 
Teaching Subdirectorate 
Research Coordination  
 
 
2.6 HYPOTHESIS  
 
 
 
2. DESIGN OF THE STUDY 
Randomized placebo-controlled clinical trial, randomization method in blocks of 5 by 
frequency of occurrence. In patients with acute kidney injury, they will be randomized to 
receive the administration of intravenous iron dextran in a single exhibition according to the 
Mg provided by the Virizzi formula compared to placebo.  
 
The sample size determined 55 patients per group, with a standard deviation of 1.5.  
 
 
 
 
n = [(Zα/2+zβ)2× {2(or)2}]/ (μ1 - μ2)2  
n = [(1.96+ 0.84)2×{2(1.5)2}]/ (10.8 - 10)2 
n=55,125 
 
n = sample size required in each group μ1-μ2 = 
clinically significant difference = 0.8 or = standard 
deviation = 1.5  
zα/2: 1.96  
zβ: 0.84  
Effect of intravenous iron repletion on renal function in patients with iron deficiency and acute 
kidney injury, clinical trial. June 2023, HCG/CEI-1232/22 
Version 2.0, 29 June 2023 
Our hypothesis is that intravenous iron dextran repletion during the 
treatment of acute kidney injury will improve renal function parameters, iron 
deficiency, anemia, and also that it will be safe compared to placebo.  

  
Old Civil Hospital of Guadalajara 
"FRAY ANTONIO MAYOR" 
  
HOSPITAL No. 278 SHCP 44280 TEL. 3614-5501, 3614-7244 GUADALAJARA, JAL 
 
 
 
 
Teaching Subdirectorate 
Research Coordination  
 
The randomization process by random assignment was carried out with the  
toolNCI Clinical Trial Randomization Tool:  
https://ctrandomization.cancer.gov/  
 
 
Sequences have been generated for each arm and stratum of 
your trial using maximum asymptotic randomization.  
  
  
  
  
group  
Subject  
Assignment  
Assigned Arm Index  
all  
1  
placebo  
2  
all  
2  
Dextran Iron  
1  
all  
3  
Dextran Iron  
1  
all  
4  
placebo  
2  
all  
5  
Dextran Iron  
1  
all  
6  
placebo  
2  
all  
7  
placebo  
2  
all  
8  
Dextran Iron  
1  
all  
9  
placebo  
2  
all  
10  
Dextran Iron  
1  
all  
  
11  
Dextran Iron  
1  
all  
12  
placebo  
2  
all  
13  
Dextran Iron  
1  
all  
14  
Dextran Iron  
1  
all  
  
15  
placebo  
2  
all  
16  
Dextran Iron  
1  
all  
17  
Dextran Iron  
1  
all  
18  
placebo  
2  
all  
19  
placebo  
2  
all  
  
20  
Dextran Iron  
1  
all  
21  
Dextran Iron  
1  
all  
22  
placebo  
2  
Effect of intravenous iron repletion on renal function in patients with iron deficiency and acute 
kidney injury, clinical trial. June 2023, HCG/CEI-1232/22 
Version 2.0, 29 June 2023 

  
Old Civil Hospital of Guadalajara 
"FRAY ANTONIO MAYOR" 
  
HOSPITAL No. 278 SHCP 44280 TEL. 3614-5501, 3614-7244 GUADALAJARA, JAL 
 
 
all  
23  
Dextran Iron  
1  
 
Effect of intravenous iron repletion on renal function in patients with iron deficiency and acute 
kidney injury, clinical trial. June 2023, HCG/CEI-1232/22 
Version 2.0, 29 June 2023 

  
Old Civil Hospital of Guadalajara 
"FRAY ANTONIO MAYOR" 
  
HOSPITAL No. 278 SHCP 44280 TEL. 3614-5501, 3614-7244 GUADALAJARA, JAL 
 
 
 
 
Teaching Subdirectorate 
Research Coordination  
  
all  
24  
placebo  
2  
all  
25  
placebo  
2  
all  
26  
placebo  
2  
all  
27  
Dextran Iron  
1  
all  
28  
placebo  
2  
all  
29  
placebo  
2  
all  
30  
Dextran Iron  
1  
all  
31  
placebo  
2  
all  
32  
Dextran Iron  
1  
all  
33  
placebo  
2  
all  
34  
placebo  
2  
all  
35  
placebo  
2  
all  
36  
Dextran Iron  
1  
all  
37  
Dextran Iron  
1  
all  
38  
Dextran Iron  
1  
all  
39  
Dextran Iron  
1  
all  
40  
Dextran Iron  
1  
all  
41  
placebo  
2  
all  
42  
placebo  
2  
all  
43  
Dextran Iron  
1  
all  
44  
placebo  
2  
all  
  
             45  
placebo  
2  
all  
46  
Dextran Iron  
1  
all  
47  
Dextran Iron  
1  
all  
48  
placebo  
2  
all  
49  
Dextran Iron  
1  
all  
50  
placebo  
2  
all  
51  
placebo  
2  
all  
52  
Dextran Iron  
1  
all  
53  
placebo  
2  
all  
54  
placebo  
2  
all  
55  
Dextran Iron  
1  
all  
56  
placebo  
2  
all  
57  
Dextran Iron  
1  
all  
58  
Dextran Iron  
1  
Effect of intravenous iron repletion on renal function in patients with iron deficiency and acute 
kidney injury, clinical trial. June 2023, HCG/CEI-1232/22 
Version 2.0, 29 June 2023 

  
Old Civil Hospital of Guadalajara 
"FRAY ANTONIO MAYOR" 
  
HOSPITAL No. 278 SHCP 44280 TEL. 3614-5501, 3614-7244 GUADALAJARA, JAL 
 
 
 
 
Teaching Subdirectorate 
Research Coordination  
  
all  
59  
Dextran Iron  
1  
all  
60  
Dextran Iron  
1  
all  
61  
placebo  
2  
all  
62  
placebo  
2  
all  
63  
Dextran Iron  
1  
all  
64  
placebo  
2  
all  
65  
Dextran Iron  
1  
all  
66  
Dextran Iron  
1  
all  
67  
placebo  
2  
all  
68  
placebo  
2  
all  
69  
placebo  
2  
all  
70  
placebo  
2  
all  
71  
placebo  
2  
all  
72  
Dextran Iron  
1  
all  
73  
Dextran Iron  
1  
all  
74  
Dextran Iron  
1  
all  
75  
Dextran Iron  
1  
all  
76  
placebo  
2  
all  
77  
placebo  
2  
all  
78  
placebo  
2  
all  
79  
Dextran Iron  
1  
all  
80  
Dextran Iron  
1  
all  
81  
placebo  
2  
all  
82  
Dextran Iron  
1  
all  
83  
Dextran Iron  
1  
all  
84  
placebo  
2  
all  
85  
Dextran Iron  
1  
all  
86  
placebo  
2  
all  
87  
Dextran Iron  
1  
all  
88  
placebo  
2  
all  
89  
Dextran Iron  
1  
all  
90  
Dextran Iron  
1  
all  
91  
placebo  
2  
all  
92  
Dextran Iron  
1  
all  
93  
placebo  
2  
Effect of intravenous iron repletion on renal function in patients with iron deficiency and acute 
kidney injury, clinical trial. June 2023, HCG/CEI-1232/22 
Version 2.0, 29 June 2023 

  
Old Civil Hospital of Guadalajara 
"FRAY ANTONIO MAYOR" 
  
HOSPITAL No. 278 SHCP 44280 TEL. 3614-5501, 3614-7244 GUADALAJARA, JAL 
 
 
 
 
Teaching Subdirectorate 
Research Coordination  
 
all  
94  
placebo  
2  
all  
95  
placebo  
2  
all  
96  
placebo  
2  
all  
97  
placebo  
2  
all  
98  
Dextran Iron  
1  
all  
99  
Dextran Iron  
1  
all  
100  
placebo  
2  
all  
101  
Dextran Iron  
1  
all  
102  
placebo  
2  
all  
103  
Dextran Iron  
1  
all  
104  
Dextran Iron  
1  
all  
105  
placebo  
2  
all  
106  
placebo  
2  
all  
107  
placebo  
2  
all  
108  
Dextran Iron  
1  
all  
109  
placebo  
2  
all  
110  
Dextran Iron  
1  
all  
111  
Dextran Iron  
1  
all  
112  
placebo  
2  
all  
113  
Dextran Iron  
1  
all  
114  
Dextran Iron  
1  
all  
115  
placebo  
2  
all  
116  
placebo  
2  
all  
117  
Dextran Iron  
1  
all  
118  
Dextran Iron  
1  
all  
119  
placebo  
2  
all  
120  
placebo  
2  
 
, and members of the nephrology staff, blinded to the allocation groups, 
administered the drugs to each patient every day.  
All patients will have a detailed medical history and physical examination. 
Complete blood count, serum creatinine, serum urea, serum urea nitrogen, 
serum electrolytes, and blood test parameters were measured daily.  
Effect of intravenous iron repletion on renal function in patients with iron deficiency and acute 
kidney injury, clinical trial. June 2023, HCG/CEI-1232/22 
Version 2.0, 29 June 2023 

  
Old Civil Hospital of Guadalajara 
"FRAY ANTONIO MAYOR" 
  
HOSPITAL No. 278 SHCP 44280 TEL. 3614-5501, 3614-7244 GUADALAJARA, JAL 
 
 
 
 
Teaching Subdirectorate 
Research Coordination  
 
urine. The test will be presented in accordance with the CONSORT 2010 explanation 
and elaboration guide. Continuous variables will be presented as mean (SD) when 
they are normally distributed or as medians (interquartile range [IQR]) in the case of 
abnormal distribution, following the test Shapiro-Wilk. One way ANOVA was used to 
compare differences between groups. Categorical variables expressed as proportions 
will be compared with Fisher's x2 test or the exact test, as appropriate. For the rest of 
the tests, p values were two-tailed; p <0.05 will be considered statistically significant. 
Statistical analysis and graphics will be performed with the statistical software 
MedCalc (Ostend, Belgium, see 19.1.3).  
 
 
 
 
 
4.1 INCLUSION AND EXCLUSION CRITERIA  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
Effect of intravenous iron repletion on renal function in patients with iron deficiency and acute 
kidney injury, clinical trial. June 2023, HCG/CEI-1232/22 
Version 2.0, 29 June 2023 
 
criteria of inclusion:  
Hospitalized patients with ARD, will be defined as the diagnosis using the KDIGO 
criteria of serum creatinine (Cr); Patients with AKI > 18 and <85 years, baseline 
creatinine <2 mg/dL and with written informed consent will be included.  
 
Iron deficiency according to the criteria of the 2: serum iron <13 ng/dL, transferrin 
saturation <20%.  

  
Old Civil Hospital of Guadalajara 
"FRAY ANTONIO MAYOR" 
  
HOSPITAL No. 278 SHCP 44280 TEL. 3614-5501, 3614-7244 GUADALAJARA, JAL 
 
 
 
 
 
Teaching Subdirectorate 
Research Coordination  
 
4.2 VARIABLES UNDER STUDY  
 
 
 
 
 
 
4.4 ETHICAL ASPECTS  
 
 
 
YO. 
II.  
RESEARCH WITHOUT RISK RESEARCH WITH    
MINIMAL RISK RESEARCH WITH RISK  
 
 
xxxx  
III.  
  
  
 
  
 
GREATER THAN MINIMAL  
 
 
 
 
 
 
 
 
ANNEX LETTER OF CONSENT  
Effect of intravenous iron repletion on renal function in patients with iron deficiency and acute 
kidney injury, clinical trial. June 2023, HCG/CEI-1232/22 
Version 2.0, 29 June 2023 
Exposure variable is the administration of iron dextran in an infusion bolus as a 
loading strategy.  
Dependent variables will be the value of renal function by eGFR, hemoglobin, 
iron deficiency, renal function and safety parameters.  

  
Old Civil Hospital of Guadalajara 
"FRAY ANTONIO MAYOR" 
  
HOSPITAL No. 278 SHCP 44280 TEL. 3614-5501, 3614-7244 GUADALAJARA, JAL 
 
 
 
 
Teaching Subdirectorate 
Research Coordination  
 
 
Letter of consent attached to the protocol 
 
 
 
Visual summary of the study 
 
Iron dextran IV 
 
 
 
 
 
 
HERE  
 
Guide 
durin 
AKI treatment 
spitalization  
1:1  
 
 
 
iron deficiency  
Placebo 
 
Effect of intravenous iron repletion on renal function in patients with iron deficiency and acute 
kidney injury, clinical trial. June 2023, HCG/CEI-1232/22 
Version 2.0, 29 June 2023 
Secondary goals 
 
 
 
Secondary goals 
 
Start of KRT 
 
 
 
line 
g ho

  
Old Civil Hospital of Guadalajara 
"FRAY ANTONIO MAYOR" 
  
HOSPITAL No. 278 SHCP 44280 TEL. 3614-5501, 3614-7244 GUADALAJARA, JAL 
 
 
 
 
Teaching Subdirectorate 
Research Coordination  
 
 
 
 
 
 
 
 
 
5.1 SCHEDULE OF ACTIVITIES ATTACH 
FORMAT  
Effect of intravenous iron repletion on renal function in patients with iron deficiency and acute 
kidney injury, clinical trial. June 2023, HCG/CEI-1232/22 
Version 2.0, 29 June 2023 

  
Old Civil Hospital of Guadalajara 
"FRAY ANTONIO MAYOR" 
  
HOSPITAL No. 278 SHCP 44280 TEL. 3614-5501, 3614-7244 GUADALAJARA, JAL 
 
 
 
Year 
subd  
color  
 
 
 
 
  AND  
B. 
  AND  
Effect of intravenous iron repletion on renal function in patients with iron deficiency and acute 
kidney injury, clinical trial. June 2023, HCG/CEI-1232/22 
Version 2.0, 29 June 2023 
N .D 
R  
 
 
 
  
 
 
 
O    
   
        
  
 
EITH 
uV 
S 
 
 RG.   A 
  EITHER     P  
  
  
  
  

  
Old Civil Hospital of Guadalajara 
"FRAY ANTONIO MAYOR" 
  
HOSPITAL No. 278 SHCP 44280 TEL. 3614-5501, 3614-7244 GUADALAJARA, JAL 
 
 
 
 
Teaching Subdirectorate 
Research Coordination  
  
  
Analysis of data  
 
  
Comparison with  
theoretical  referents  
 
  
Final report of the 
investigation  
 
 
Effect of intravenous iron repletion on renal function in patients with iron deficiency and acute 
kidney injury, clinical trial. June 2023, HCG/CEI-1232/22 
Version 2.0, 29 June 2023 

  
Old Civil Hospital of Guadalajara 
"FRAY ANTONIO MAYOR" 
  
HOSPITAL No. 278 SHCP 44280 TEL. 3614-5501, 3614-7244 GUADALAJARA, JAL 
 
 
 
 
Teaching Subdirectorate 
Research Coordination  
 
DOCUMENTARY REFERENCES  
 
 
 
1. Lameire NH, Bagga A, Cruz D, De Maeseneer J, Endre Z, Kellum JA, Liu KD, Mehta RL, Pannu 
N, Van Biesen W, et al. Acute kidney injury: an increasing global concern. Lancet. 
2013;382(9887):170–9.  
2. Siew ED, Davenport A. The growth of acute kidney injury: a rising tide or just closer 
attention to detail? Kidney Int. 2015;87(1):46–61.  
3. Murugan R, Karajala-Subramanyam V, Lee M, Yende S, Kong L, Carter M, Angus DC, 
Kellum JA. Acute kidney injury in non-severe pneumonia is associated with an increased 
immune response and lower survival. Kidney Int. 2010;77(6):527–35.  
4. Nisula S, Kaukonen KM, Vaara ST, Korhonen AM, Poukkanen M, Karlsson S, Haapio M, 
Inkinen O, Parviainen I, Suojaranta-Ylinen R, et al. Incidence, risk factors and 90-day mortality 
of patients with acute kidney injury in Finnish intensive care units: the FINNAKI study.  
Intensive Care Med. 2013;39(3):420–8.  
5. Bagshaw SM, George C, Dinu I, Bellomo R. A multi-centre evaluation of the RIFLE criteria for 
early acute kidney injury in critically ill patients. Nephrol Dial Transplant. 2008;23(4):1203–10.  
 
6. Ostermann M, Chang RW. Acute kidney injury in the intensive care unit according to 
RIFLE. Crit Care Med. 2007;35(8):1837–43. quiz 1852  
7. Hoste EA, Clermont G, Kersten A, Venkataraman R, Angus DC, De Bacquer D, Kellum JA: RIFLE 
criteria for acute kidney injury are associated with hospital mortality in critically ill patients: a 
cohort analysis. CritCare 2006, 10(3):R73.  
8. Hoste EA, Bagshaw SM, Bellomo R, Cely CM, Colman R, Cruz DN, Edipidis K, Forni LG, 
Gomersall CD, Govil D, et al. Epidemiology of acute kidney injury in critically ill patients: the 
multinational AKI-EPI study. Intensive Care Med. 2015;41(8):1411–23.  
Effect of intravenous iron repletion on renal function in patients with iron deficiency and acute 
kidney injury, clinical trial. June 2023, HCG/CEI-1232/22 
Version 2.0, 29 June 2023 

  
Old Civil Hospital of Guadalajara 
"FRAY ANTONIO MAYOR" 
  
HOSPITAL No. 278 SHCP 44280 TEL. 3614-5501, 3614-7244 GUADALAJARA, JAL 
 
 
 
 
Teaching Subdirectorate 
Research Coordination  
 
9. Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, Moreno R, Carlet J, Le 
Gall JR, Payen D, et al. Sepsis in European intensive care units: results of the SOAP study. Crit 
Care Med. 2006;34(2):344–53.  
 
10. Case J, Khan S, Khalid R, Khan A. Epidemiology of acute kidney injury in the intensive care 
unit. Crit Care Res Pract. 2013;2013:479730.  
11. Chawla LS, Amdur RL, Amodeo S, Kimmel PL, Palant CE. The severity of acute kidney injury 
predicts progression to chronic kidney disease. Kidney Int. 2011;79(12):1361–9.  
12. Wang HE, Muntner P, Chertow GM, Warnock DG. Acute kidney injury and mortality in 
hospitalized patients. Am J Nephrol. 2012;35(4):349-55.  
13. Zarjou A, Agarwal A. Sepsis and acute kidney injury. J Am Soc Nephrol. 2011;22(6):999–1006.  
 
 
14.- Andreini C, Putignano V, Rosato A, Banci L. The human iron-proteome. Metallomics. 
2018 Sep 19;10(9):1223-1231. doi: 10.1039/c8mt00146d. PMID: 30095136.  
 
15.-Alnuwaysir RIS, Hoes MF, van Veldhuisen DJ, van der Meer P, Beverborg NG. Iron 
deficiency in heart failure: mechanisms and pathophysiology. J Clin Med. 2021 Dec 
27;11(1):125. doi: 10.3390/jcm11010125. PMID: 35011874; PMCID: PMC8745653.  
 
16.- Melenovsky V, Petrak J, Mracek T, Benes J, Borlaug BA, Nuskova H, Pluhacek T, Spatenka J, 
Kovalcikova J, Drahota Z, Kautzner J, Pirk J,  Houstek J.  Myocardial iron content and 
mitochondrial function in human Heart failure: a direct tissue analysis. Eur J Heart Fail. 2017 
Apr;19(4):522-530. doi: 10.1002/ejhf.640. Epub 2016 Sep 19. PMID: 27647766.  
Effect of intravenous iron repletion on renal function in patients with iron deficiency and acute 
kidney injury, clinical trial. June 2023, HCG/CEI-1232/22 
Version 2.0, 29 June 2023 

  
Old Civil Hospital of Guadalajara 
"FRAY ANTONIO MAYOR" 
  
HOSPITAL No. 278 SHCP 44280 TEL. 3614-5501, 3614-7244 GUADALAJARA, JAL 
 
 
 
 
Teaching Subdirectorate 
Research Coordination  
 
17. Hepokoski M, Singh P. Mitochondria as mediators of systemic inflammation and organ cross 
talk in acute kidney injury. Am J Physiol Renal Physiol. 2022 Jun 1;322(6):F589-F596. doi: 
10.1152/ajprenal.00372.2021. Epub 2022 Apr 4. PMID: 35379000; PMCID: PMC9054254.  
Effect of intravenous iron repletion on renal function in patients with iron deficiency and acute 
kidney injury, clinical trial. June 2023, HCG/CEI-1232/22 
Version 2.0, 29 June 2023