**7. Summary**

36 Novel Insights on Chronic Kidney Disease, Acute Kidney Injury and Polycystic Kidney Disease

Ho and colleagues conducted an observational case-control study of unselected ESKD patients on haemodialysis (Ho et. al., 2010). Patients served as their own control. They compared 2x/month laboratory haemoglobin measurements and use of a computerised algorithm to analyse 12x/month monitoring of Crit-line haemoglobin measurements. They found that haemoglobin variability, measured by the mean standard deviation of the residuals, significantly improved during the phase of frequent haemoglobin monitoring. However, this was not a randomised controlled trial. Also, the sample size was small and it was an unblinded study in a single-centre. Nonetheless, the study highlights the importance of frequent monitoring of haemoglobin as it may provide an opportunity to titrate the ESA

Gaweda and colleagues conducted a case-controlled observational study in which 49 ESKD patients on haemodialysis were included (Gaweda et. al., 2010). The investigators measured haemoglobin using Crit-line at various intervals: twice weekly or 8x/mo, once weekly or 4x/mo, every 2 weeks or 2x/mo and every 4 weeks or 1x/mo. They also calculated the haemoglobin estimation error as a root mean-squared difference between the observed and estimated haemoglobin and compared it with the measurement error. They found that the most accurate haemoglobin estimation was achieved with twice weekly haemoglobin sampling, although it exceeded the accuracy of the measurement device. Twice and once weekly haemoglobin measurements were found to be optimal in 31% and 45% patients,

These two studies highlight the paucity of evidence in the area of management of haemoglobin variability. Considering the cost and possible amount of blood loss associated with frequent hemoglobin monitoring, currently available evidence is not sufficient to make

There is substantial heterogeneity in the haematological response to ESAs. Although the factors underpinning ESA-hyporesponsiveness are well characterised, those contributing to haemoglobin variability are poorly understood. Future studies should include prospective and systematic data collection to evaluate these factors. Investigations should also be carried out to develop a single and uniformly accepted method to measure haemoglobin variability that is clinically relevant and reproducible, since there is no consensus on a single method

The data on the effect of haemoglobin variability on mortality are conflicting. This could be due to several reasons. Firstly, most of the data originates from retrospective and observational studies. Secondly, the studies are arbitrarily limited to sampling during 6 month periods where monthly haemoglobin values for each month were available. This cross-sectional nature of the study does not reflect long-term fluctuations in haemoglobin values. Thirdly, due to highly selective nature of the study cohorts, sampling bias could be potentially introduced. Most of these studies had a very short follow up period ranging from 6 months to 18 months. Furthermore, different statistical models have demonstrated inconsistent and non-reproducible results due considerable between-study variation in the covariates included in the adjusted models. Therefore, the exact nature and quantification of

the effect of haemoglobin variability on mortality is still poorly understood.

respectively. This was also a single-centre study with a small sample size.

any clinical practice recommendations.

for the measurement of haemoglobin variability.

**6. Future research** 

dose early.

Haemoglobin variability is highly prevalent in both non-dialysis and dialysis CKD patients. The factors contributing to haemoglobin variability are not entirely clear. However, the currently available evidence has identified the following factors: younger age, female gender, low body mass index, the presence of comorbid conditions, and the use of ESA and less frequent monitoring of haemoglobin. There is conflicting evidence on the effect of haemoglobin variability on mortality with some studies demonstrating a strong association and others showing no association with mortality. A few small prospective observational studies have found that frequent monitoring of haemoglobin may reduce short-term haemoglobin variability, although the optimal frequency of haemoglobin monitoring is yet to be defined. Evidence-based treatment strategies cannot be currently recommended due to a lack of high quality data. In conclusion, maintaining haemoglobin within a target range continues to pose a challenge to clinicians. Further research is urgently needed in this insufficiently researched field.
