Donor-transmitted HTLV-1-associated myelopathy in a kidney transplant recipient--case report and literature review.

Clinical disease due to human T cell lymphotropic virus type 1 (HTLV-1), a retrovirus endemic in certain regions of the world, is rarely reported after solid organ transplantation. In 2009, universal deceased donor organ screening for HTLV-1 was discontinued in the United States. We report the first case of donor-derived HTLV-1-associated myelopathy in a kidney transplant recipient from the United States. The patient, who was HTLV-1-seronegative prior to transplantation, likely acquired HTLV-1 infection from a seropositive organ donor. In this era when screening of donors and recipients for HTLV infection is not mandatory, clinicians should be vigilant in recognizing the risk and potential occurrence of this donor-derived infection in recipients with epidemiologic exposures.

Recurrent idiopathic membranous nephropathy: early diagnosis by protocol biopsies and treatment with anti-CD20 monoclonal antibodies.

Membranous nephropathy (MN) recurs posttransplant in 42% of patients. We compared MN recurrence rates in a historical cohort transplanted between 1990 and 1999 and in a current cohort diagnosed by protocol biopsies, we analyzed the progression of the disease and we assessed the effects of anti-CD20 antibodies (Rituximab) on recurrent MN. The incidence of recurrent MN was similar in the historical (53%) and the current cohorts (41%), although in the later the diagnosis was made earlier (median, 4[2-21] months vs. 83[6-149], p = 0.002) and the disease was clinically milder. Twelve out of 14 patients (86%) with recurrent MN in the current cohort had progressive increases in proteinuria. Eight recipients were treated with Rituximab after their proteinuria increased from median, 211 mg/day (64-4898) at diagnosis to 4489 (898-13 855) (p = 0.038). Twelve months post-Rituximab, 75% of patients had either partial (PR) or complete remission (CR). After 24 months 6/7 (86%) had PR/CR and one patient relapsed. Posttreatment biopsies showed resorption of electron dense immune deposits in 6/7 cases and were negative for C3 (4/7) and IgG (3/7). Protocol biopsies allow early diagnosis of subclinical recurrent MN, which is often progressive. Treatment of recurrent MN with Rituximab is promising and should be evaluated in a prospective randomized controlled trial.

Maternal and foetal outcomes in pregnant patients with active lupus nephritis.

The objective of this study was to determine the impact of lupus nephritis disease activity on maternal and foetal outcomes in pregnant patients with systemic lupus erythematosus (SLE). Medical records of all pregnant patients with SLE treated at our institution between 1976 and 2007 were reviewed. All patients met American College of Rheumatology classification criteria for SLE. Demographic data, history of lupus nephritis, nephritis disease activity and maternal and foetal outcomes of pregnancy were abstracted. Active lupus nephritis was defined as the presence of proteinuria >0.5 g/day and/or active urinary sediment with or without an elevation in serum creatinine (Cr). Quiescent lupus nephritis was confirmed in the presence of proteinuria <0.5 mg/day and inactive urinary sediment. We identified 58 patients with 90 pregnancies. Compared with pregnancies in SLE patients without renal involvement (n = 47), pregnancies in patients with active lupus nephritis (n = 23) were associated with a higher incidence of maternal complications (57% vs 11%, P < 0.001), whereas those with quiescent lupus nephritis (n = 20) were not (35% vs 11%, P = 0.10). Women with active lupus nephritis were more likely to deliver preterm than women without lupus nephritis, median of 34 weeks vs 40 gestational weeks, respectively (P = 0.002) and were more likely to suffer foetal loss (35% vs 9%, P = 0.031). Active, but not quiescent, lupus nephritis during pregnancy is associated with a higher incidence of maternal and foetal complications compared with pregnancies in SLE patients without renal involvement.

Recurrent idiopathic membranous nephropathy after kidney transplantation: a surveillance biopsy study.

Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults. MN can recur after kidney transplantation causing proteinuria, allograft dysfunction and graft failure. In this study we assessed the incidence of MN recurrence utilizing surveillance graft biopsies. The study included 1310 renal allograft recipients from 2000 to 2006. Glomerular diseases were the cause of kidney failure in 28% of patients and 23 (2%) had idiopathic MN. Recurrent MN was diagnosed in eight of 19 patients included in this analysis (42%) 13 +/- 20 months (median = 4; range 2-61 months) after transplant. The initial clinical manifestations of recurrent MN were mild or absent. Urine protein excretion was 825 +/- 959 (64-2286) mg/day and three patients had no proteinuria. Five of seven patients who did not receive additional immunosuppression for MN had significant increases in proteinuria during follow up and three became nephrotic. At diagnosis, light microscopic changes were subtle or absent. All patients had granular glomerular basement membrane deposits of IgG but little or absent C3 by immunofluorescence. Subepithelial deposits were observed in all cases by electron microscopy. In conclusion, idiopathic MN recurred in 42% of patients after transplantation. The initial clinical and histologic manifestations are subtle but the disease is progressive.

Reactive oxygen species and acute renal failure.

Acute renal failure is commonly due to acute tubular necrosis (ATN), the latter representing an acute, usually reversible loss of renal function incurred from ischemic or nephrotoxic insults occurring singly or in combination. Such insults instigate a number of processes-hemodynamic alterations, aberrant vascular responses, sublethal and lethal cell damage, inflammatory responses, and nephron obstruction-that initiate and maintain ATN. Eventually, reparative and regenerative processes facilitate the resolution of renal injury and the recovery of renal function. Focusing mainly on ischemic ATN, this article reviews evidence indicating that the inordinate or aberrant generation of reactive oxygen species (ROS) may contribute to the initiation and maintenance of ATN. This review also discusses the possibility that ROS may instigate adaptive as well as maladaptive responses in the kidney with ATN, and raises the possibility that ROS may participate in the recovery phase of ATN.

Y-chromosomal diversity in Europe is clinal and influenced primarily by geography, rather than by language.

Clinal patterns of autosomal genetic diversity within Europe have been interpreted in previous studies in terms of a Neolithic demic diffusion model for the spread of agriculture; in contrast, studies using mtDNA have traced many founding lineages to the Paleolithic and have not shown strongly clinal variation. We have used 11 human Y-chromosomal biallelic polymorphisms, defining 10 haplogroups, to analyze a sample of 3,616 Y chromosomes belonging to 47 European and circum-European populations. Patterns of geographic differentiation are highly nonrandom, and, when they are assessed using spatial autocorrelation analysis, they show significant clines for five of six haplogroups analyzed. Clines for two haplogroups, representing 45% of the chromosomes, are continentwide and consistent with the demic diffusion hypothesis. Clines for three other haplogroups each have different foci and are more regionally restricted and are likely to reflect distinct population movements, including one from north of the Black Sea. Principal-components analysis suggests that populations are related primarily on the basis of geography, rather than on the basis of linguistic affinity. This is confirmed in Mantel tests, which show a strong and highly significant partial correlation between genetics and geography but a low, nonsignificant partial correlation between genetics and language. Genetic-barrier analysis also indicates the primacy of geography in the shaping of patterns of variation. These patterns retain a strong signal of expansion from the Near East but also suggest that the demographic history of Europe has been complex and influenced by other major population movements, as well as by linguistic and geographic heterogeneities and the effects of drift.

Tracing European founder lineages in the Near Eastern mtDNA pool.

Founder analysis is a method for analysis of nonrecombining DNA sequence data, with the aim of identification and dating of migrations into new territory. The method picks out founder sequence types in potential source populations and dates lineage clusters deriving from them in the settlement zone of interest. Here, using mtDNA, we apply the approach to the colonization of Europe, to estimate the proportion of modern lineages whose ancestors arrived during each major phase of settlement. To estimate the Palaeolithic and Neolithic contributions to European mtDNA diversity more accurately than was previously achievable, we have now extended the Near Eastern, European, and northern-Caucasus databases to 1,234, 2, 804, and 208 samples, respectively. Both back-migration into the source population and recurrent mutation in the source and derived populations represent major obstacles to this approach. We have developed phylogenetic criteria to take account of both these factors, and we suggest a way to account for multiple dispersals of common sequence types. We conclude that (i) there has been substantial back-migration into the Near East, (ii) the majority of extant mtDNA lineages entered Europe in several waves during the Upper Palaeolithic, (iii) there was a founder effect or bottleneck associated with the Last Glacial Maximum, 20,000 years ago, from which derives the largest fraction of surviving lineages, and (iv) the immigrant Neolithic component is likely to comprise less than one-quarter of the mtDNA pool of modern Europeans.

mtDNA variation among Greenland Eskimos: the edge of the Beringian expansion.

The Eskimo-Aleut language phylum is distributed from coastal Siberia across Alaska and Canada to Greenland and is well distinguished from the neighboring Na Dene languages. Genetically, however, the distinction between Na Dene and Eskimo-Aleut speakers is less clear. In order to improve the genetic characterization of Eskimos in general and Greenlanders in particular, we have sequenced hypervariable segment I (HVS-I) of the mitochondrial DNA (mtDNA) control region and typed relevant RFLP sites in the mtDNA of 82 Eskimos from Greenland. A comparison of our data with published sequences demonstrates major mtDNA types shared between Na Dene and Eskimo, indicating a common Beringian history within the Holocene. We further confirm the presence of an Eskimo-specific mtDNA subgroup characterized by nucleotide position 16265G within mtDNA group A2. This subgroup is found in all Eskimo groups analyzed so far and is estimated to have originated <3,000 years ago. A founder analysis of all Eskimo and Chukchi A2 types indicates that the Siberian and Greenland ancestral mtDNA pools separated around the time when the Neo-Eskimo culture emerged. The Greenland mtDNA types are a subset of the Alaskan mtDNA variation: they lack the groups D2 and D3 found in Siberia and Alaska and are exclusively A2 but at the same time lack the A2 root type. The data are in agreement with the view that the present Greenland Eskimos essentially descend from Alaskan Neo-Eskimos. European mtDNA types are absent in our Eskimo sample.

Mitochondrial DNA variant 11719G is a marker for the mtDNA haplogroup cluster HV.

Based on sequencing data and results obtained from applying a tailored mismatch polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, we report that the G allele of the mitochondrial DNA (mtDNA) polymorphism at nucleotide position 11719 is associated with the European mtDNA haplogroup cluster HV, and that 11719A is therefore the ancestral allele.