DMSA: Mean values are slightly higher in the provoked urines, but the aluminum binding of DMSA and the induced renal excretion seems insignificant.

DMPS i.v.: Mean values are slightly higher for the provoked urine and about equal to DMSA values. The aluminum binding and/or renal excretion following DMPS i.v. seems insignificant.

DMPS i.v. + ZnDTPA i.v. combination therapy
Mean values for the provoked urines are slightly higher than those of the DMSA+DMPS urines. The aluminum binding of the combination treatment, including the renal excretion seem insignificant.

CaEDTA, 1,9g i.v. plus 500mg DMSA oral, and/or NaMgEDTA, 2,5g i.v. plus DMSA oral
The mean concentration of 57µg/g crea for the urines provoked with NaMgEDTA+DMSA and the CaEDTA+DMSA provoked urines (46µg/g crea) are considerably higher than the mean values for DMSA, DMPS and the DMPS/ZnDTPA combination treatment.
The mean concentration for the CaEDTA+DMSA and the NaMgEDTA+DMSA provoked urines are above our reference range of 40µg/g crea.

Assessment:
By comparing mean concentrations of DMSA, DMPS and the combination DMPS+ZnDTPA urines, we could not determine an efficient aluminum binding and renal excretion for any of these chelating agents. These chelating agents may not be the agents of choice in the treatment of aluminum overexposure.

The mean concentration of the urines provoked with CaEDTA+DMSA i.e. MgEDTA+DMSA show an increase in Al-binding and excretion, with 57µg/g crea for MgEDTA/DMSA and 46µg/g crea for CaEDTA/DMSA. The difference may be explained by the application route. CaEDTA is often (wrongly) injected, whereas NaMgEDTA is applied as an infusion. The fluid volume may be responsible for the lower creatinine value of the urines provoked with MgEDTA +DMSA (0.54µg/g crea).

From this data, we cannot safely state that the EDTAs bind aluminum more effectively, especially in lieu of the extreme values detected in baseline urines.
Of 2485 tests, we found 10 exceeding the MCL with a mean concentration of 526µg/g crea! The maximum level was 1256µg/g crea.

We found maximum concentrations exceeding the MCL in all provocation urines, except for the MgEDTA+DMSA urines. See Table 1.

Important information:
Aluminum is widespread in our environment. This indicates that great caution has to be taken during sampling. Our urine containers are metal-free. Make sure you are not re-using sample containers.

Protocol reminders:

		Patients must empty bladder before chelation (oral or i.v.) is started.
		To avoid contamination, we prefer that patients collect all urine in the bladder for the duration of the appropriate collection period.

Urine collection times:

		DMSA oral: 4h
		DMPS oral: 3-4h
		DMPS i.v.: 1-2h
		EDTA: Infusion time plus 45min.
		EDTA+DMSA example: If oral DMSA is provided 1h prior to the start of a 2g EDTA infusion, the collection time is 1h + infusion time + 45min = 3h45min
		ZnDTPA+DMPS: 2h

More information under http://www.microtraceminerals.com/en/chelation-newsarticles

Additional information for chronic or subacute aluminum intoxication/exposure:

Aluminum is, compared with lead or mercury, relatively nontoxic. No known physiologic need exists for aluminum.

Approximately 95% of an aluminum load becomes bound to transferrin and albumin intravascularly and is then eliminated renally. In healthy subjects, only 0.3% of orally administered aluminum is absorbed via a healthy GI. When the GI barrier is bypassed, such as with intravenous infusion or in the presence of advanced renal dysfunction aluminum has the potential to accumulate. As an example, with intravenously infused aluminum, 40% is retained in adults and up to 75% is retained in neonates. Mayor et al suggested that parathyroid hormone may increase intestinal absorption of aluminum.

Up to this time, no biological function has been attributed to this metal, and, more importantly, aluminum accumulation in tissues and organs results in their dysfunction and toxicity. Aluminum is absorbed from the GI tract in the form of oral phosphate-binding agents (aluminum hydroxide), parenterally via immunizations, via dialysate on patients on dialysis or total parenteral nutrition (TPN) contamination, via the urinary mucosa through bladder irrigation, and transdermally in antiperspirants. Lactate, citrate, and ascorbates facilitate GI absorption. If a significant load exceeds the body's excretory capacity, the excess is deposited in various tissues, including bone, brain, liver, heart, spleen, and muscle.

Aluminum can interfere with chromium, iron, magnesium, zinc, calcium and copper. An inadequate supply of essential elements facilitates aluminum uptake. Aluminum absorption in bone is a risk in children with an inadequate intake of dietary calcium or vitamin D. Highly stressed patients with an inadequate magnesium supply are at risk. Leaky gut syndrome or kidney problems support the aluminum uptake.

Aluminum disrupts the Vitamin B6 and Vitamin D Metabolism.

Infants should be protected from Aluminum in nanoparticle form. Vaccines are containing either the mercury-containing thiomersal or aluminum-compounds.

While aluminum cannot be avoided, we can reduce Al-uptake by optimizing the body’s nutritional balance. Providing digestive support in the form of probiotics helps.

We wish you all the best. If you find this newsletter informative, let us know.

E.Blaurock-Busch and team


References:

		Bundesgesundhbl., Bd. 41 (6), (1998), 271
		http://emedicine.medscape.com/article/165315-overview#a0104
		Liu TK, Liu SH, Chang CH, Yang RS: Concentration of metal elements in the blood and urine in the patients  with cementless total knee arthroplasty. Tohoku J Exp Med 1998; 185: 253-262
		O'Shea S, Johnson DW: Review article: Addressing risk factors in chronic kidney disease mineral and bone disorder: Can we influence patient-level outcomes? Nephrology 2009; 14: 416-427
		Meyer-Baron M, Schuper M, Knapp G, van Thriel C: Occupational aluminum exposure: Evidence in support of its neurobehavioral impact. NeuroToxicology 2007; 28: 1068-1078