Abstract-Mutations in SCN5A, the gene encoding the cardiac Na ϩ channel, have been identified in 2 distinct diseases associated with sudden death: one form of the long-QT syndrome (LQT 3 ) and the Brugada syndrome. We have screened SCN5A in a large 8-generation kindred characterized by a high incidence of nocturnal sudden death, and QT-interval prolongation and the "Brugada ECG" occurring in the same subjects. An insertion of 3 nucleotides (TGA) at position 5537, predicted to cause an insertion of aspartic acid (1795insD) in the C-terminal domain of the protein, was linked to the phenotype and was identified in all electrocardiographically affected family members. ECGs were obtained from 79 adults with a defined genetic status (carriers, nϭ43; noncarriers, nϭ36). In affected individuals, PR and QRS durations and QT intervals are prolonged (PϽ0.0001 for all parameters). ST segment elevation in the right precordial leads is present as well (PϽ0.0001). Twenty-five family members died suddenly, 16 of them during the night. Expression of wild-type and mutant Na ϩ channels in Xenopus oocytes revealed that the 1795insD mutation gives rise to a 7.3-mV negative shift of the steady-state inactivation curve and an 8.1-mV positive shift of the steady-state activation curve. The functional consequence of both shifts is likely to be a reduced Na ϩ current during the upstroke of the action potential. LQT 3 and Brugada syndrome are allelic disorders but may also share a common genotype. Key Words: long-QT syndrome Ⅲ Brugada syndrome Ⅲ SCN5A Ⅲ arrhythmia Ⅲ Na ϩ channel S CN5A, the gene that encodes the human cardiac Na ϩ channel ␣ subunit, 1 is mutated in one form of the long-QT syndrome (LQT 3 ) and in Brugada syndrome. 2,3 There are characteristic and readily distinguishable ECG patterns in these 2 syndromes. In LQT 3 patients, a long isoelectric ST segment precedes a peaked T wave. 4 Brugada syndrome is diagnosed on the basis of characteristic ECG features in the absence of structural heart disease; these features include right precordial ST-segment elevation, which may be intermittent, and which is exacerbated by Na ϩ channel block and ameliorated by isoproterenol. 5,6 QT intervals have been reported to be normal in patients with Brugada syndrome. 5 Clinically, there appears to be some overlap between the 2 syndromes, as both exhibit a relatively high incidence of nocturnal sudden cardiac death without prior symptoms. 6 -8 The prolonged QT interval in LQT 3 results from persistent inward Na ϩ current during the plateau phase of the action potential, secondary to incomplete inactivation of mutated channels. 9 Changes in the ␣ and ␤ 1 subunit interaction have also been implicated. 10 Although functional abnormalities have been described for Brugada syndrome-related SCN5A mutant channels, 3,11 the mechanism(s) whereby these explain the Brugada phenotype are less clear.In this study we present clinical and genetic data of a single large SCN5A-linked family, phenotypically characterized by nocturnal death and electrocardiograph...

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Kidney transplantation from living donors is important to reduce organ shortage. Reliable pre-operative estimation of post-donation renal function is essential. We evaluated the predictive potential of pre-donation glomerular filtration rate (GFR) (iothalamate) and renal reserve capacity for post-donation GFR in kidney donors.GFR was measured in 125 consecutive donors (age 49 ± 11 years; 36% male) 119 ± 99 days before baseline GFR (GFR b ) and 57 ± 16 days after donation (GFR post ). Reserve capacity was assessed as GFR during stimulation by low-dose dopamine (GFR dopa ), amino acids (GFR AA ) and both (GFR max ). GFR allows a relatively reliable prediction of postdonation GFR, improving by taking age and stimulated GFR into account. Long-term studies are needed to further assess the prognostic value of pre-donation characteristics and to prospectively identify subjects with higher risk for renal function loss.

Conclusions: A higher level of GFR as such is associated with larger absolute underestimation of true GFR by eGFR. For donor screening purposes, eGFR should be interpreted with great caution; when in doubt, true GFR should be performed to prevent unjustified decline of prospective kidney donors.