Chronic Kidney Disease -Mineral and Bone Disorder, The CPH-MBD Cohort
Conditions: Chronic Kidney Disease Mineral and Bone Disorder, Chronic Kidney Disease (CKD), Bone Markers
Sponsor: Herlev Hospital

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CPH-MBD cohort v6, 26.09.25 
The CPH-MBD cohort 
Protocol v6, 26-09-2025 
H-25039131 
 
 
Chronic Kidney Disease – Mineral and Bone Disorder 
The CPH-MBD cohort 
 
 
 
 
 
 
 
 
 
 
Ditte Hansen 
Consultant, Professor, PhD, MSc    
Dept of nephrology, Copenhagen University Hospital - Herlev  
Borgmester Ib Juuls Vej 1 
DK-2730 Herlev  
+45 3868 2056 
ditte.hansen.04@regionh.dk 

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CPH-MBD cohort v6, 26.09.25 
1. General information 
1.1 Investigators and collaborators  
Primary Investigator 
Ditte Hansen, professor MD PhD  
Department of Nephrology, Copenhagen University Hospital - Herlev Hospital 
 
CPH-MBD group 
Freja Stæhr Hassager, MD 
Anahita Rashid, MD 
Iain Bressendorff, MD, PhD 
Anders Nordholm, MD, PhD 
Department of Nephrology, Copenhagen University Hospital - Herlev Hospital 
Eva Gravesen, MD, PhD 
Department of Pathology, Copenhagen University Hospital - Herlev Hospital 
Maria Mace, MD, PhD 
Department of Nephrology, Copenhagen University Hospital – Rigshospitalet 
 
Dietary study 
Louise Salomo, MD, PhD  
Department of Nephrology, Copenhagen University Hospital - Herlev Hospital 
Borgmester Ib Juuls Vej 1, 2730 Herlev, Denmark 
phone: +453868 3868 
 
 

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CPH-MBD cohort v6, 26.09.25 
Julian Askøe Bluming, Klinisk diætist, stud scient. Human Nutrition 
Anna Elvina Slott Wittendorff, Cand scient. Klinisk ernæring 
Jens Rikardt Andersen, MD, MPA, lektor emeritus, 
Institut for Idræt og Ernæring, Københavns Universitet 
Rolighedsvej 26, 1958 Frederiksberg  
 
2. Overall aim  
Persons with chronic kidney disease (CKD) have a 3-fold increased risk of bone fracture and a 10-
fold increased risk of cardiovascular disease than the general population. These increased risks are 
related to the disturbances in the mineral metabolism, and this clinical entity is termed Chronic 
Kidney Disease - Mineral and Bone Disorder (CKD-MBD)1.  
The overall aim of the present project is to explore factors that may predict or associate with the 
development of bone and cardiovascular disease in patients with CKD and hopefully provide 
insight into underlying mechanisms and pathophysiological pathways for future treatment and 
prevention. 
In a sub study, we aim to explore the calcium and phosphate balance in patients with CKD and 
describe how these associates with each other as well as the kidney function (eGFR). 
 
3. Background 
Chronic kidney disease (CKD) is a chronic condition where the excretory kidney function 
(estimated glomerular filtration rate (eGFR)) is reduced and/or markers of kidney damage is present 
(often presented as albuminuria). CKD is classified into stages CKD G1-5 according the severity of 
the reduction in eGFR2. 
The prevalence of CKD is increasing world-wide, partly explained by the increase in the ageing 
population and prevalence of diabetes3. In Denmark, the prevalence of CKD in the population is 4-
8% depending on the applied algorithm4. CKD is a devastating disease both due to the risk of 
kidney failure and thereby the need for dialysis or transplantation, but also because the presence of 
CKD increases the risk of bone fracture, cardiovascular disease and mortality2,5.  

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Disturbances in the mineral metabolism, including hyperphosphatemia and hyperparathyroidism 
develops as kidney function declines. These disturbances are closely related to the increased risk of 
bone and cardiovascular disease, and this relation has been gathered since 2009 in the clinical entity 
named Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD)1,6. 
The bone pathology in patients with CKD, named renal osteodystrophy, can be classified by the 
TMV classification. The TMV classification describes the bone Turnover, the bone Mineralization 
and the bone Volume, which may all be disturbed in renal osteodystrophy7.  
Per see, disturbances in the bone pathology, especially in the bone turnover is considered harmful to 
the bone strength8. However, no studies have addressed if disturbances in the bone turnover 
increases the risk of bone fracture. This is the primary aim of the present study.  
The golden standard for description of bone turnover is a bone biopsy. However, bone turnover 
markers may describe the bone turnover with a reasonable validity9,10, and will be used in the 
present study to describe the turnover, as bone biopsy is not considered feasible in 1000 patients. 
Especially, the low bone turnover has been a frightened condition as former studies have found an 
association between low bone turnover and progression of vascular calcification11. However, these 
were executed when treatment with active vitamin D and calcium were more aggressive than today. 
Treatments that may also affect the vascular calcification. Therefore, it is uncertain if low bone 
turnover predicts cardiovascular disease. This will also be explored in the present study.   
Bone and cardiovascular disease often co-occur in patients with CKD. Preclinical and clinical 
studies has suggested a bone vascular tissue crosstalk in CKD that may be a mediator of the high 
risk of fracture and cardiovascular events in patients with CKD12,13. In the present study, it will be 
possible to explore how these factors, including sclerostin, Dkk-1, and Activin A, associate with 
changes in bone mineral density (BMD) and future fracture and cardiovascular disease. 
Sarcopenia is an age-related disease characterized by a progressive decline in muscle function and 
mass 14. Sarcopenia is associated with numerous adverse health outcomes in the general population, 
including increased risk of falls, fractures, and mortality 15. Low BMD predicts an increased risk of 
fracture in the general population as well as in patients with CKD 6.  A few studies have found an 
association between osteoporosis and sarcopenia in patients with CKD 16. This association between 
bone fragility and sarcopenia may be due to common risk factors such as age, sex, and malnutrition 
17, but increasing evidence points towards an interaction between muscles and bone, giving rise to 

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the uniting term osteosarcopenia 18,19. The present study will explore if sarcopenia predicts decline 
in BMD and future fracture. 
Patients with CKD are often put on a strict diet to reduce their intake of phosphorous, potassium, 
sodium and protein. In theory, these dietary restrictions may in turn cause malnutrition, sarcopenia 
and increased risk of fall and fracture. Especially, the reduced calcium intake due to phosphorous 
restriction have been speculated to impact on the bone quality20. This study will determine the 
habitual dietary intake in patients with CKD4-5 and explore the association with bone quantity and 
sarcopenia. 
A novel urine acid/base-score (calculated on the basis of urine pH and urine ammonium) assesses 
the renal tubular capacity for acid excretion and the degree of subclinical acid retention. This 
disease marker has been found to be largely independent of traditional kidney disease markers and 
robustly associated with CKD progression and incident ESKD in CKD stage 3-4 patients21. This 
study will determine the association between the subclinical acid retention and clinical outcomes. 
 
4. Research questions 
The primary research question is: 
Does low bone turnover increase the future risk of fracture in patients with CKD? 
Bone turnover will be quantified as bone turnover markers (described in section 7.6).  
The 0-hypothesis is that low bone turnover does not increase the risk of future fracture in patients 
with CKD. 
This prospective cohort study will provide broad insight into several aspects of CKD-MBD. Other 
future research questions can be addressed within this cohort study and will therefore provide 
valuable insight into different aspects of CKD-MBD.  
Bone 
1) Do bone turnover associate with decline in BMD? 
2) Do bone turnover associate with increased risk of cardiovascular events? 

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3) Do disturbances in the mineral metabolism associate with the presence and progression of 
osteoporosis (presence of osteoporosis defined as T-score < -2,5 and progression defined as 
decreasing bone density measured with DEXA-scan)? 
4) Do vascular derived biomarkers associate with decline in BMD and increased risk of 
cardiovascular events? 
5) Does progression of osteoporosis associate with progression of CKD and cardiovascular 
events? 
6) Does the bone phenotype and fracture risk differ between patients with and without 
diabetes? 
7) Do bone turnover associate with novel circulating CKD-MBD biomarkers including Wnt- 
and TGF-β-signaling factors? 
8) Do systemic and urinary markers of acid/base balance (measured as pH in blood and urine) 
associate with decline in BMD, increased risk of fractures or cardiovascular events? 
For detailed description of measure of biomarkers measured in this trial, see section 7.6.  
Sarcopenia 
Does sarcopenia increase the risk of decline in BMD and future fracture and cardiovascular disease? 
1) Does sarcopenia associate with low physical activity? 
2) Does sarcopenia associate with a specific bone phenotype? 
3) Do systemic and urinary markers of acid/base balance associate with sarcopenia? 
Diet 
1) Does low dietary calcium intake associate with low BMD and decline in BMD? 
2) Does low dietary phosphate intake associate with low BMD and decline in BMD? 
3) Does low dietary intake of protein associate with low muscle mass and strength? 
4) Does a high dietary acid load associate with low muscle mass and strength? 
5) Does high dietary potassium intake from fruit and vegetables induce hyperkalemia? 
6) Does low dietary phosphorus intake associate with cardiovascular disease? 
7) Does sodium intake and urinary sodium excretion associate with the progression of CKD 
and cardiovascular disease? 
8) Does the source of protein (vegetarian versus animal) intake affect albuminuria?  
9) Does the diet and acid production (pH in urine) associate with the progression of CKD 

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10) Does the source of phosphate (food or additive) affect the urinary excretion? 
11)  Does the balance between the dietary calcium and phosphate intake and the urinary 
excretion associate with the eGFR?  
12) Does the product of p-calcium and p-phosphate associate with the eGFR? 
13) How do the intake of phosphate associate with the intake of calcium 
5. Outcomes 
Primary outcome 
The primary outcome is the difference in time to first fracture between patients with normal bone 
turnover and low bone turnover based on bone turnover markers at baseline. 
 
Design 
This is a prospective cohort study. Patients will be characterized at baseline and reassessed after 3 
years. Bone fractures, cardiovascular events, progression of kidney disease, end-stage kidney 
disease and death will be collected through linkage with registries during follow-up (see section 
11). The follow-up will continue until death or end of approvals. 
6. Study population 
The study will include 1000 patients with chronic kidney disease. The patients will be recruited 
from the outpatient clinic at the Department of Nephrology at Herlev Hospital. 
6.1 Inclusion criteria 
○ Age ≥18 years 
○ CKD stage 4-5nonD (eGFR ≤ 29 ml/min) according to KDIGO (Kidney Disease Improving 
Global Outcome) definition22. 
6.2 Exclusion criteria 
None 
 

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CPH-MBD cohort v6, 26.09.25 
7. Study procedures 
The procedures are summarized in Table 1. 
7.1 Informed consent 
Patients eligible for the study are identified with the help of the treatment-responsible staff at the 
outpatient clinic at department of Nephrology, Herlev Hospital. The outpatient clinic has ~8000 
patients of which 1500 have an eGFR< 30 ml/min/1.73m2. Information about civil registration 
number, phone number, and CKD-stage is provided by the treatment-responsible staff and passed 
on to the study investigator prior to consent. Data used for screening patients will be from 0 to 10 
years old, according on how long time the patient has been followed in our outpatient clinic. This 
information is used for identifying possible participants and for recruitment. Eligible patients will 
be invited to participate via a letter sent to them or during one of their ordinary visits at the 
outpatient clinic, where the written information is provided. Those who receive a letter will, if they 
don’t contact us within 2 weeks, receive a follow-up phone call from us. If patients so desire, they 
can make a later appointment with the site investigator after having received written information 
about the trial. They are informed that they can bring one other person at this later appointment, and 
at that appointment they are once more verbally informed about the trial. The appointment takes 
place in a calm and undisturbed room in the outpatient clinic, with appropriate time for information 
and questions. After the meeting the patients may deliberate on the study participation for up to 
seven days. If the subjects decide to participate in the study, the written informed consent must be 
collected and signed before any study activity can take place. It is only possible to participate in the 
study if the subject is capable to give written consent. The patients will be informed that they at any 
time during the study may withdraw their informed consent with no consequence to their present or 
future treatment. If significant changes to the study are made, or if new risks associated with the 
study come to our knowledge, the participants will be informed of this, and they will be asked to 
renew their written informed consent. 
7.2 Consent for long-term storage of blood samples in biobank and access to source data 
Each patient will also be asked to give a separate consent to have their surplus materials included in 
a biobank, where samples will be stored until 1/8-2050 and then it will be destroyed. The subjects 
can participate in the study without their samples stored in the biobank for 25 years. 
Permission to gain access to source data/documents (including medical records) regarding the 

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CPH-MBD cohort v6, 26.09.25 
participants will be collected from the subjects in writing. They will also give consent to, that the 
investigator can obtain access to all relevant documents and records if inspections from different 
regulatory authorities or Ethics Committees are performed.  
7.3 Subject ID number 
All subjects enrolled must be identifiable in a pseudoanonymized form. All data will be registered 
in RedCap where a study ID number is given to the patient at the first visit. 
7.4 Demographic data, medical history and medication  
Date of birth and gender will be registered from medical records. Height and weight will be 
measured during visits., We will ask participants about ethnic origin/race, alcohol and smoking 
habits, eating habits, fall within the last 2 years, previous bone fractures, previous treatment with 
medicine containing steroid, current consumption of vitamin D, calcium, vitamin K, and proton 
pump inhibitors as well as their height at the age of 18 if this is known. The reason to ask for 
ethnicity is because of the possible effect on endpoints, we therefore wish to correct for ethnicity in 
the analysis. 
Medical history and present disease are registered. Information of the above will be obtained from 
the participating subject and from their medical records and it will be recorded at baseline and at 3 
years follow-up. Demographic and medical data is collected from medical records to be able to 
describe the cohort characteristics as it is known that a broad palette of characteristics affects our 
endpoints of interest. The informed consent from the participant will give investigators direct access 
to the above mentioned information.  
Medication at baseline and at 3 years follow-up are registered.  
 
 7.5 Vital signs and physical examination 
Height, weight, hip and waist circumference, blood pressure, and heart rate will be measured with 
validated automated devices at baseline and at 3 years follow-up. 
7.6 Blood and urine samples 
Blood samples are collected from all participants using standardised vein puncture techniques. 20 
ml of blood is collected for routine analysis at baseline and after 3 years of follow-up: creatinine, 

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urea, ionized calcium, phosphate, magnesium, PTH, 25OH vitamin D, totalCO2, bicarbonate, 
sodium, potassium, urate, haemoglobin, albumin. These blood samples are analysed immediately by 
Department of Clinical Biochemistry.  
Participants are instructed to collect a 24-hour urine at baseline for calcium, phosphate, magnesium, 
sodium, urea, acid/base parameters (ammonium and pH), creatinine and albumin analyses. 
Extra 8 ml of plasma and 8 ml of serum will be collected at baseline and 3 years follow-up. These 
will be frozen at minimum -70°C and kept in the research biobank so that they can be analysed in 
batches. Bone turnover markers, osteocalcin, RANKL, OPG, Klotho, FGF23, wnt signalling factors 
including sclerostin and Dkk-1, TGFβ signalling factors including Activin A, myokines, adipokines, 
osteopontin, MGP, T50, fetuin A and CPPs, inflammation markers (such as IL-6, TNF-α), 
endothelial markers (i.e. VCAM, ICAM) are planned to be determined. The remaining material will 
be destroyed after all analyses have been performed and no later than 1/8-2035.  
For future research further blood samples consisting of 8 ml serum, 10 ml EDTA-plasma, 6 mL 
heparin-plasma, buffycoat 2 ml, urine 4 ml will be collected and frozen at minimum -70°C for 
future research and kept for up to 25 years (1/8-2050).  
 7.7 DEXA scan 
DEXA scans are performed on all participants at baseline and after 3 years follow-up. The DEXA 
scan estimates body composition, bone mineral density and vertebral fractures with a whole-body 
scan.  
DEXA provides estimates of three compartments in the body composition: fat mass (FM), fat free 
mass (FFM), total bone mass (BMC).  Appendicular lean mass (ALM) is defined as the sum of lean 
soft tissue from the arms and legs. Relative ALM is acquired by normalizing ALM to height to 
account for allometric differences in body size.  
The content of calcium in the bones are assessed by the amount of calcium compared to the 
measured area in g/cm2.The scan of the lumbar spine and the hips are performed while the subject is 
lying down, while the scan of the forearms is performed while sitting. The scan can be performed 
with clothes on, if the clothes does not contain any metal. The T- and Z-scores are calculated. 
Radiation from one DEXA-scan varies from 3 to 30 microsievert. 

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CPH-MBD cohort v6, 26.09.25 
VFA is a way to assess fractures in columna thoracolumbalis using a DEXA scan. The VFA 
visualises the different vertebras, including a possible deformation of the vertebras. The radiation 
from one VFA is approximately 3 microsievert.  
 7.8 Dietary assessment 
To assess the patients’ weekly intake of vegetables, animal products, and sodium the participants 
must fill in two questionnaires (named “salt screener”, “proteinscreener”). 
Additionally, in a subgroup of 50 patients, dietary intake with special emphasize on intake of 
calcium and phosphate will be assessed using a 24-hour recall based on patient-provided meal 
photographs. The patients will be instructed at visit 2 by an authorized clinical dietitian to 
photograph all meals and beverages consumed during a 24-hour period. At the following visit 2a a 
24-hour recall will be conducted, during which the dietitian will review the photographs together 
with the patient. The patient will be instructed to fill in a 72-hour dietary diary. 
 
7.9 Muscle strength and function 
The hand grip strength will be assessed by a JAMAR meter. The muscle function will be evaluated 
by sit to stand test and 10 m-walk test. The body composition will be measured by bioimpedances. 
These will be performed at baseline and 3 years follow-up. 
7.10 Questionnaires 
Participants will be invited to fill in questionnaires at baseline: 
SARC-F: screening tool for sarcopenia 
KDQOLSF1.3: Quality of life assessment 
Physical Activity Scale 2 (PAS-2): self-estimated physical activity 
Proteinscreener: Assessment of intake of protein 
Saltscreener: Assessment of intake of salt 
The questionnaires will be sent through RedCap to e-boks. 
 

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CPH-MBD cohort v6, 26.09.25 
7.11 Biobanks 
2 biobanks are being established: one research biobank in order to analyse samples at the same 
time, and one future biobank for future research.  
For the research biobank 8 ml of plasma,8 ml of serum and 10 ml urine will be collected at baseline. 
Samples from the research biobank will be destroyed no later than 1/8-2035,  because it is expected 
to take years to include all participants. Residuals will afterwards be transferred to the biobank for 
future research if the participant has signed the informed consent regarding this.   
 
For future research 26 ml blood (8 ml serum, 10 ml EDTA-plasma, 6 mL heparin-plasma, buffycoat 
2 ml) and 4 ml urine 4 ml will be collected. Biobank with samples for future research will be kept 
up to 25 years, afterwards all leftovers will be destroyed. If they have not signed this consent, the 
leftovers from research biobank will be destroyed according to the participating laboratories 
standard procedure. 
Table 1 | Visit Schedule 
Visit  
V0 
V1 
V2 
V2a 
V3 
Time 
< -6 mo 
-6 mo to -3 days 
0 
+2 to  
+ 30 days + 30-42 mo 
Information meeting 
x 
  
  
 
  
Sign informed consent 
  
x 
  
 
  
Preparation for 24 h urine 
  
x 
  
 
  
Demographics 
  
  
x 
 
Vitals 
  
  
x 
 
x 
Dietary substudy 
 
 
x 
x 
 
Blood samples: 
  
  
  
 
  
routine 
  
  
x 
 
x 

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CPH-MBD cohort v6, 26.09.25 
8. Data management 
A RedCap database will be established, in which all data will be registered. Data will be stored for 
25 years, after which they will be anonymized.  
All data are stored securely and only accessible for authorized personnel and trial staff. The trial 
staff will ensure that the subject’s confidentiality is maintained. 
8.1 Information from medical records 
Information of parameters describing inclusion and exclusion criteria will be given from the 
treatment responsible doctor to the researcher in order to identify possible participants. These are 
from the medical records in the outpatient. When a subject has signed informed consent and has 
entered the trial, information about comorbidities and medication will be recorded from the medical 
record. The informed consent will give the investigator, and supervisory bodies access to look into 
the patient file in order to collect data and control the quality of data and monitor data. The study 
will be in compliance with “Databeskyttelsesloven” and will only be initiated after approval from 
“Videnscenter for Dataanmeldelser, RegionH, Denmark”.  
8.2 Case Report Form 
An electronic CRF in RedCap is provided, and all data related to this study will be registered in it. 
This will provide the basis for a central database stored in coded form according to the rules of the 
research biobank 
  
  
x 
 
x 
future research biobank 
  
  
x 
 
x 
24 hour urine sample:  
  
  
  
 
  
routine 
  
  
x 
 
research biobank 
  
  
x 
 
future research biobank 
  
  
x 
 
DEXA 
  
  
x 
 
x 
Hand grip, STS and 6 m-walk 
  
  
x 
 
x 
Questionnaires 
  
  
x 
 

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Danish Data Protection Agency. The CRF is to be completed by the study nurse or by the 
investigator at the time of the subjects visit to the clinic.  
9. Statistical evaluation 
Analysis of the primary endpoint will be performed after 200 fractures have occurred. The 
difference in time to first fracture will be analyzed by Cox proportional hazards model. Hazard 
ratios will be given with 95 % confidence intervals and p-values 
Baseline characteristics will be presented with appropriate averages and measures of dispersion 
according to their distribution.  
Continuous outcomes will be presented as graphs of mean and standard error of the mean at each 
time point.  Continuous outcomes with non-normal distribution will be transformed to obtain 
normality before analysis. For outcomes with a baseline and a single follow-up measurement, 
comparison between treatment groups will be performed by ANCOVA, with adjustment for the 
baseline value. Outcomes with baseline and multiple post randomization measurements will be 
compared as baseline adjusted mean follow-up values using a mixed model repeated measures 
approach. Categorical outcomes will be compared by Chi2-test. Hypothesis testing will use a 2-
sided p-value to confirm or reject the null hypothesis. A p-value less than 0.05 is considered 
statistically significant.  
10. Sample size/power calculation 
The incidence of any first fracture is compared between patients with low and non-low turnover as a 
time to event analyses. The prevalence of low-turnover is expected to be 30%9. 
An annual incidence of fracture (proximal humerus, forearm, pelvis and hip) of 2 % is expected in 
the whole cohort23. To be able to detect a 40 % difference in the incidence of fracture (HR 0.6) in 
the patients without low turnover bone disease compared to patients with non-low turnover bone 
disease during 10 years of follow-up, and with a drop out of 20 % a total of 1000 participants will 
be included (β=0.20; α=0.05). The number of events will be monitored, and the sample size may be 
adjusted according to the incidence of fractures. 
The dietary sub study is an exploratory and descriptive study with 50 participants. 
 

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11. End of study 
When 1000 participants have been included the inclusion will stop. All included participants will be 
followed in the Danish registries (Landspatientregisteret, lægemiddelstatistikregisteret, 
dødsårsagsregisteret) until death or end of study which is expected to be after 25 years of follow-up. 
12. Research biobank 
A research biobank will be established. This biobank will store certain blood samples at 
minimum -70°C that needs to be analysed at the same time in order to avoid inter-assay variation. 
In the standard informed consent form, they will also sign that they give their consent to have some 
of their blood stored in this research biobank. It is not possible to decline and still participate in the 
study. From this biobank we will analyse biochemical markers related to this study and described in 
this protocol. Samples from the research biobank will be destroyed no later than 1/8-2035 or 
transferred to the biobank for future research if the participant has signed the informed consent 
regarding this.   
13. Future biobank 
A biobank for future research in bone disease in patients with CKD will be established at Herlev 
Hospital. This biobank will store blood samples and urine samples in coded form at minimum -
70°C for future analysis. Each subject will be asked to give a separate consent to have their surplus 
material stored in this biobank, and subjects who decline this is still able to be part of the study. 
Samples will be stored until 1/8-2050 and after that it will be destroyed, unless dispensation from 
this has been provided. Additional analyses on these blood and urine samples will only be 
performed after approval by the Ethics Committee System on Biomedical Research. Blood and 
urine samples for future research will stored according to local legislation 
(Databeskyttelsesforordningen).  
14. Ethical considerations 
The trial is investigator-initiated by Ditte Hansen and will not be initiated before approval from the 
local scientific ethics committee. The trial will be conducted according to local legislation 
(Databeskyttelsesloven, Databeskyttelsesforordningen and Sundhedsloven) and Declaration of 
Helsinki 2013. 

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CKD puts patients at high risk of cardiovascular and bone disease. This cohort will provide 
important information regarding diagnosis and prognosis for this condition. The participants will 
have their bone and dietary intake described in depth, which may be an advantage for each 
individual. The participants may not have any direct advantage of the results of the overall study, 
but provide information for improvement of diagnosis, prognostication and treatment of future 
patients with CKD. 
Patients in the dietary-assessment subgroup will be offered a 1-hour consultation with an authorized 
dietitian. During the session the patients will get a detailed registration of their calcium and 
phosphate intake and will gain insight into common dietary phosphate sources. Participants will 
have the opportunity to ask questions related to diet and kidney disease. 
14.1 Screening 
The study will be streamlined and integrated as much as possible into the usual care to reduce the 
burden on the participants and study staff.  
We expect to screen 1500 patients to be able to include 1000 participants in our study. See section 
7.1 for information given to the researchers before consent.   
14.2 Risk and discomfort for the patient 
Blood samples will be drawn using standard sterile technique in a peripheral vein. The potential 
risks and discomforts in association to this is pain, hematoma, rarely an infection. A total of 
approximately 124 ml will be drawn over a 3-year period, maximally 62 ml at once. In section 7.6 
is described specific analyses made on blood samples. There will be taken the same amount of 
blood as in the clinic (20 ml per visit) added with 42 ml to biobanks. As comparison, a blood donor 
donates 500 ml of blood at a time. The subjects undergo DEXA scans and VFA of columna 2 times. 
The known risk for the patient in relation to these scanning techniques is radiation. The radiation 
dose from one DEXA scan varies from 3-30 µSv, corresponding to <2 weeks of background 
radiation.  
 
 

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15. Financing and insurance 
15.1 Financing 
Neither the investigators nor the research group related to this study have any financial interests in 
the execution or the results of this study. Funding will be sought from national and international 
funds. Participants and the local scientific ethics committee will be informed as funding is secured.  
Those who support the study with funding will have no influence on the setup of the study, the 
interpretation of or the publication of data. Patients will not receive any financial compensation for 
their participation. 
15.2 Insurance 
If, against expectations, any harm should happen, patients will be covered according to current law 
on patient-insurance.  
16. Publication 
The results or partial results of the study will be written in one or more manuscripts with the 
purpose to be published in one or more international peer-reviewed journals. Both negative, neutral, 
inconclusive, and positive results will be published as quick as possible, academically sound and in 
accordance with law on the processing of personal data. Ditte Hansen, professor MD PhD, will be 
last author on publications of the main results. Authorships will be granted any persons who have 
contributed to the publications according to the Vancouver Guidelines.  
 
 
 
 
 
 
 
 

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17. References 
1. 
KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and 
treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl 
S1-130 (2009) doi:10.1038/ki.2009.188. 
2. 
Stevens, P. E. & Levin, A. Evaluation and management of chronic kidney disease: 
synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann. 
Intern. Med. 158, 825–830 (2013). 
3. 
Xie, Y. et al. Analysis of the Global Burden of Disease study highlights the global, 
regional, and national trends of chronic kidney disease epidemiology from 1990 to 2016. Kidney 
Int. 94, 567–581 (2018). 
4. 
Vestergaard, S. V., Christiansen, C. F., Thomsen, R. W., Birn, H. & Heide-Jørgensen, 
U. Identification of Patients with CKD in Medical Databases: A Comparison of Different 
Algorithms. Clin. J. Am. Soc. Nephrol. 16, 543–551 (2021). 
5. 
KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, 
Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). 
Kidney Int. Suppl. 7, 1–59 (2017). 
6. 
KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, 
Prevention, and Treatment of Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD). 
Kidney Int. Suppl. 7, 1–59 (2017). 
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