Level of renal function and serum erythropoietin levels independently predict anaemia post-renal transplantation.

BACKGROUND: Post-renal transplant anaemia is a potentially reversible cardiovascular risk factor. Graft function, immunosuppressive agents and inhibition of the renin-angiotensin system have been implicated in its aetiology. The evaluation of erythropoietin (EPO) levels may contribute to understanding the relative contributions of these factors. METHODS: Two-hundred and seven renal transplant recipients attending the Belfast City Hospital were studied. Clinical and laboratory data were extracted from the medical records and laboratory systems. RESULTS: Of the 207 patients (126 male), 47 (22.7%) were found to be anaemic (males, haemoglobin (Hb)<12 g/dl, females Hb<11 g/dl). The anaemic group had a significantly higher mean serum creatinine level (162.8 micromol/l vs 131.0 micromol/l, P<0.001) and lower mean estimated glomerular filtration rate (eGFR) (41.5 ml/min vs 54.9 ml/min, P<0.001) than the non-anaemic group. Individual immunosuppressive regimens were comparable between those with and those without anaemia. Angiotensin converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) administration was not more prevalent in those with anaemia compared with those without (36.2 vs 38.8%, P=0.88). There was a significant inverse correlation between Hb levels and serum EPO levels (R=-0.29, P<0.001), but not between EPO levels and eGFR (R=0.02, P=0.74). Higher EPO levels were predictive of anaemia, independent of eGFR in multivariate analysis. CONCLUSION: Anaemia is common in post-renal transplant patients. The levels of renal function and serum EPO and not immunosuppressive regimens or ACE-I/ARB use, are strong and independent predictors of anaemia.

Congenital methaemoglobinaemia Type I in a Turkish infant due to a novel mutation, Pro144Ser, in NADH-cytochrome b5 reductase.

A baby centrally cyanosed from birth was investigated for a congenital cardiac defect. Echocardiography and angiography revealed patent foramen ovale without any other cardiac abnormality. Congenital methaemoglobinaemia was considered as the methaemoglobin level was 27%, suggesting either Hb M or a deficiency of the NADH-cytochrome b5 reductase (cytb5r) enzyme. Measurement of the cytb5r enzyme activity of this patient indicated a reduced level of 7.3 IU/g Hb (normal range 11.5-26.9 IU/g Hb). Sequencing the DIA 1 gene that encodes cytb5r revealed a novel C403T base change, predicting a proline to serine change at codon 144. This amino-acid change is not located in the enzyme's active site and does not cause loss of function. Instead it results in reduced stability of the enzyme and development of the less severe or Type I form of recessive congenital methaemoglobinaemia. The infant was started on daily ascorbic acid treatment. She has very mild cyanosis and normal growth and developmental parameters on follow-up at 10 months of age.

Familial idiopathic methemoglobinemia revisited: original cases reveal 2 novel mutations in NADH-cytochrome b5 reductase.

In 1943, the first description of familial idiopathic methemoglobinemia in the United Kingdom was reported in 2 members of one family. Five years later, Quentin Gibson (then of Queen's University, Belfast, Ireland) correctly identified the pathway involved in the reduction of methemoglobin in the family, thereby describing the first hereditary trait involving a specific enzyme deficiency. Recessive congenital methemoglobinemia (RCM) is caused by a deficiency of reduced nicotinamide adenine dinucleotide (NADH)-cytochrome b5 reductase. One of the original propositi with the type 1 disorder has now been traced. He was found to be a compound heterozygote harboring 2 previously undescribed mutations in exon 9, a point mutation Gly873Ala predicting a Gly291Asp substitution, and a 3-bp in-frame deletion of codon 255 (GAG), predicting loss of glutamic acid. A brother and a surviving sister are heterozygous; each bears one of the mutations. Thirty-three different mutations have now been recorded for RCM. The original authors' optimism that RCM would provide material for future genetic studies has been amply justified.