Does she drink tea?

I was quickly moving along through my busy university clinic, seeing another CKD patient when the nurse came to inform me that the patient’s hemoglobin was critically low at 5 g/dl, while the patient appeared to be just fine. I reviewed the rest of labs just to find out that the iron studies were even more impressive: iron saturation 3% and ferritin 2 ng/ml.

I inquired about the usual suspects - bleeding from various sources - but no luck there (the patient was post-menopausal and denied GI bleeding, later ruled out by EGD and colonoscopy)... Failing to identify a cause of her iron deficiency, I presented the case to my staff who, after reviewing the data, asked me an unusual question: does she drink tea? To my surprise, indeed, the patient admitted to drinking large quantities of black tea. Still puzzled about the link between the two, I jumped onto Google Scholar.

In the renal world, the only time when we talk about tea is when discussing hyponatremia in patients that are on a “tea and toast” diet. So what did I find out? An interesting South African study demonstrated that black tea inhibits non-heme iron absorption by forming iron tannate complexes. This was confirmed by a UK study which showed that black tea was the most potent out of all polyphenol-rich beverages (coffee, cocoa, etc.) in inhibiting absorption of non-heme iron.

Iron deficiency anemia is common in CKD patients, one of the latest mechanisms to be described involves the hepcidin-ferroportin axis (as recently reviewed in JASN). But today I discovered another one!

Posted by Tomoki Tsukahara

Hemoglobin Targets in CKD

For anyone who would like to read a thorough review of the current evidence with regard to Hb targets and the use of ESAs in  patients with CKD and those on dialysis, I strongly recommend the review published in Nature Reviews Nephrology this month. The field of anemia treatment if CKD has changed completely in the last 10 years. Hb targets have gotten considerably lower and the "one size fits all" model is changing into a model based on individualized Hb targets.

Two questions remain to be answered fully:
- In patients with CKD, is it the high Hb that is dangerous or is it the high doses of ESAs?
- What do we do with patients on dialysis who are not even achieving the new lower targets despite escalating doses of an ESA

My personal bias is that it is the ESA that is the problem rather than the Hb dose. Observational studies have shown that patients who achieve high Hb targets without the use of an ESA have no increased risk of CVD. ESAs are known to activate the vasculature and potentially increase the production of profibrotic and prothrombotic circulating factors. Patients who require very high doses of an ESA to achieve a particular Hb target are a high risk group and it may be that the requirement for such high doses is a marker of disease burden.

The Normal Hematocrit Study (NHCT) was published in the NEJM in 1998 and reported that there was a non-significant increase in mortality in patients in the high Hb group. However, there was a benefit in terms of QOL in patients with a higher Hb. This study has been criticized before and further analysis of the outcomes has shown that when the patients were followed for a longer period, there was a statistically significant increase in mortality in the high Hb group. Last year, a paper in KI reanalyzed the results of this study and found that this increase in mortality was evident even earlier that had been reported.

There was another fascinating finding in this report. The original study reported quality of life in patients based on achieved Hb levels. Thus, higher Hb was associated with better QOL irregardless of whether or not the patient was in the high Hb group. There was no difference in QOL between the randomized groups. In other words, it wasn't the ESA that was making the difference - there was a difference between those patients who had high Hb levels compared to those who did not reach those levels that was not related to the use of an ESA: patients who are healthier and respond better to an ESA have higher QOL scores! There was a misinterpretation of these results to mean that high ESA doses were associated with better QOL which has subsequently been proved wrong.

There was an accompanying editorial with that KI article that is definitely worth a read and advocates for new standards in the reporting of clinical trials.