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Summary: Increasing use of direct oral anticoagulants (DOACs) has made management of non‐valvular atrial fibrillation and venous thromboembolism easier in most patients. But the presence of co‐existing renal impairment could render the use of DOACs problematic because all of these drugs have varying degrees of renal excretion. In this paper we address misconceptions about the safety and efficacy of DOACs in moderate‐severe renal impairment by presenting a summary of the literature from phase III trials and real‐world studies. It also addresses the important consideration of correct estimate of renal function for DOAC dosing. It is hoped that the review will serve as a valuable resource for clinicians involved in anticoagulation decision‐making in patients with renal impairment to guide the choice of most suitable agent. Accurate dosing is of particular relevance as registry data suggests it is done inconsistently and may be resulting in avoidable thromboembolic and bleeding events. [ABSTRACT FROM AUTHOR]

In this seminal paper, Dr. Kyle pointed out how some, but not all, MGUS patients would develop a plasmacytoid or lymphoproliferative disorder over time, suggesting that the nature of MGUS was undetermined, rather than benign. Prior to this definition, most MGRS patients would have been diagnosed as having MGUS and therefore not deemed eligible for treatment. In a recent retrospective study from the Medical University of Innsbruck, Austria, of over 2900 patients diagnosed with MGUS between 2000 and 2016, only 44 patients (1-5%) were diagnosed with MGRS. [Extracted from the article]

Sickle cell disease (SCD) and apolipoprotein L1 (APOL1) G1/G2 variants increase chronic kidney disease (CKD) risk in African Americans by poorly understood mechanisms. We applied bioinformatics to identify new candidate genes associated with SCD‐related CKD. An interaction network demonstrated APOA1 connecting haemoglobin subunit β (HBB) and APOL1 with 36 other candidate genes. Gene expression revealed upregulation of engulfment and cell motility 1 (ELMO1) and downregulation of APOA1 in the kidney cortex of SCD versus non‐SCD mice. Analysis of candidate genes identified ELMO1 rs10951509 to be associated with albuminuria and APOA1 rs11216132 with haemoglobinuria in patients with SCD. A bioinformatic approach highlights ELMO1 and APOA1 as potentially associated with SCD nephropathy. [ABSTRACT FROM AUTHOR]

The article discusses the drug lenalidomide, which is the most recently approved drug for the treatment of multiple myeloma. The author discusses a previously-written paper describing the problems with renal impairment that have been linked to the drug, and states that more studies are needed to research the efficacy and toxicity of the drug.

Summary: Pregnancy has been linked to various microangiopathies, including primary atypical haemolytic uraemic syndrome (aHUS). Complement dysregulation, often linked to rare variants in complement genes, is key for primary aHUS to manifest and may play a role in pregnancy complications of the mother and fetus. The burden of such complications is unknown, making counselling of women with primary aHUS and asymptomatic relatives difficult. We analyzed the maternal and fetal outcomes of 39 pregnancies from 17 women with primary aHUS and two asymptomatic relatives. Seven out of 39 pregnancies were complicated by pregnancy‐associated aHUS. Five out of 32 pregnancies not linked to pregnancy‐associated aHUS were complicated by pre‐eclampsia or HELLP. Rare genetic variants were identified in 10 women (asymptomatic relatives, n = 2) who had a total of 14 pregnancies, including 10 uncomplicated pregnancies. Thirty‐five out of 39 pregnancies resulted in live birth. Eight out of 19 women had progressed to end‐stage kidney disease, with an incidence of 2·95 (95% confidence interval, 1·37–5·61) per 100 person‐years after the first pregnancy. Thus, we emphasized the frequency of successful pregnancies in women with primary aHUS and asymptomatic relatives. Pregnancies should be monitored closely. Rare genetic variants cannot predict the risk of a given pregnancy. [ABSTRACT FROM AUTHOR]

Keywords: sickle cell disease; orosomucoid; chronic kidney disease; urinary biomarker EN sickle cell disease orosomucoid chronic kidney disease urinary biomarker e45 e48 4 07/01/20 20200701 NES 200701 Chronic kidney disease (CKD) strongly contributes to morbidity and mortality in ageing sickle cell disease (SCD) patients.[1] Biomarkers for early stage CKD, such as proteinuria, microalbuminuria and reduced glomerular filtration rate (GFR), are difficult to detect in SCD patients because of a urine concentration defect. HbSS patients had higher prevalence and more severe kidney disease than HbSC (27-3% of HbSS patients were in stages 3 and 4). This observation supports the previous observation that HbSS patients have higher prevalence of proteinuria and albuminuria than HbSC.[4] 1 TableBasic characteristics and renal function in HbSS and HbSC patients. [Extracted from the article]

Summary: Monoclonal gammopathy of undetermined significance (MGUS) affects 3·2% of adults aged >50 years. MGUS carries a life‐long risk of progression to multiple myeloma and causes complications including infection and renal impairment; common causes of hospital admission. This study aimed to assess MGUS prevalence in emergency medical hospital admissions. Patients were recruited from unselected emergency medical admissions in a hospital in the United Kingdom. Serum protein electrophoresis was performed, with immunofixation of abnormal results. Reason for admission and routine test results were recorded. After education about MGUS and myeloma, patients chose whether they wished to be informed of new diagnoses. A total of 660 patients were tested and 35 had a paraprotein suggestive of MGUS. The overall rate of MGUS was 5·3%. MGUS prevalence in those aged >50 years was 6·94%, higher than the previously published rate of 3·2% (P < 0·0005). There were higher rates in those with chronic kidney disease (13·75% vs. 4·14%, P = 0·002), heart failure (14% vs. 4·59%, P = 0·012), anaemia (8·96% vs. 3·41%, P = 0·003) or leucocytosis (9·33% vs. 3·04%, P = 0·002). In all, 96% of patients wished to be informed of their screening results. The prevalence of MGUS in emergency hospital admissions is higher than expected based on previous population‐based rates. This may suggest a selected population for screening. [ABSTRACT FROM AUTHOR]

Summary: There is an increasing understanding of the risks from atrial fibrillation (AF) in the current era. In patients with end‐stage renal disease (ESRD) on dialysis, the prevalence of AF is significantly higher compared to the general population and those with earlier stages of CKD. Although anticoagulation of these patients may seem appropriate, there is a lack of conclusive evidence that it provides the same protection from thromboembolic complications as it does in patients not on dialysis. In addition, the increased risk of bleeding in patients requiring dialysis makes the use of anticoagulants less favourable. This article aims to discuss the problem of AF in dialysis patients, summarise the current evidence around the use of oral anticoagulants for AF in ESRD and provide some practical suggestions on management of AF in the haemodialysis population. [ABSTRACT FROM AUTHOR]

In African-American patients with sickle cell disease (SCD), APOL1 G1 and G2 variants are associated with increased risk of sickle cell nephropathy (SCN). To determine the role of APOL1 variants in SCD patients living in Europe, we genotyped 152 SCD patients [aged 30·4 (24·3-36·4) years], mainly of Sub-Saharan African ancestry, for APOL1 G1 and G2 and for variants of four genes with kidney tropism ( GSTM1, GSTT1, GSTP1, and HMOX1). Homozygous or double-heterozygous APOL G1 and G2 genotypes were strongly associated with end stage renal disease ( P = 0·003) and worse Kidney Disease: Improving Global Outcomes stages ( P = 0·001). Further, these genotypes were associated in an age-dependent manner with lower estimated glomerular filtration rate (eGFR, P = 0·008), proteinuria ( P = 0·009) and albuminuria ( P < 0·001) but not with other SCD complications. Compared to APOL1 G1/wild type (WT), the APOL1 G2/WT genotype was associated with a lower eGFR ( P = 0·04) in an age-dependent manner, suggesting that the G2/WT patients are likely to have worse kidney prognosis. Other genes variants analysed were not associated with SCN or other SCD complications. Our data indicate that APOL1 screening should be considered for the management of SCD patients, including those of non-African-American origin, as those with homozygous or double heterozygous variants are clearly at higher risk of SCN . [ABSTRACT FROM AUTHOR]

Adequate pre-dialysis care reduces mortality among end-stage renal disease ( ESRD) patients. We tested the hypothesis that individuals with ESRD due to sickle cell disease ( SCD- ESRD) receiving pre- ESRD care have lower mortality compared to individuals without pre- ESRD care. We examined the association between mortality and pre- ESRD care in incident SCD- ESRD patients who started haemodialysis between 1 June, 2005 and 31 May, 2009 using data provided by the Centers for Medicare and Medicaid Services ( CMS). SCD- ESRD was reported for 410 (0·1%) of 442 017 patients. One year after starting dialysis, 108 (26·3%) patients with incident ESRD attributed to SCD died; the hazard ratio ( HR) for mortality among patients with SCD- ESRD compared to those without SCD as the primary cause of renal failure was 2·80 (95% confidence interval [ CI] 2·31-3·38). Patients with SCD- ESRD receiving pre-dialysis nephrology care had a lower death rate than those with SCD- ESRD who did not receive pre-dialysis nephrology care ( HR = 0·67, 95% CI 0·45-0·99). The one-year mortality rate following an ESRD diagnosis was almost three times higher in individuals with SCD when compared to those without SCD but with ESRD and could be attenuated by pre-dialysis nephrology care. [ABSTRACT FROM AUTHOR]

Large population-based studies are needed to establish the magnitude and duration of the recently suggested association between arterial and venous thromboembolism. In 1997-98, all inhabitants of Groningen, the Netherlands, aged 28-75 years ( n = 85 421), were invited to participate in a study that followed and monitored responding subjects ( n = 40 856) for venous and arterial thromboembolism until 2009. Thromboembolism was verified with national registries of hospital discharge diagnoses and death certificates, anticoagulation clinic and medical records. During a median follow-up of 10·7 years, 549 participants developed venous thromboembolism and 3283 developed arterial thromboembolism. Annual incidence of arterial thromboembolism after venous thromboembolism was 2·03% [95% confidence interval ( CI), 1·48-2·71], compared to 0·87% (95% CI, 0·84-0·90) in subjects without venous thromboembolism. The hazard ratio ( HR) of arterial thromboembolism after venous thromboembolism was 1·40 (95% CI, 1·04-1·88) after adjustment for age, sex and cardiovascular risk factors. This risk was highest during the first year after venous thromboembolism [annual incidence, 3·00% (95% CI, 1·64-5·04); adjusted HR, 2·01 (95% CI, 1·19-3·40)] and after an unprovoked event [annual incidence, 2·53% (95% CI, 1·68-3·66); adjusted HR, 1·62 (95% CI, 1·11-2·34)]. This study showed that subjects with venous thromboembolism are at increased risk for arterial thromboembolism, particularly in the first year after venous thromboembolism and after an unprovoked event. [ABSTRACT FROM AUTHOR]

Patients with chronic renal failure usually require exogenous erythropoietin (epo) to alleviate anaemia resulting from inadequate epo production by the kidneys. We have recently shown that severe anaemia in genetically manipulated epo-deficient mice (EpoTAg) can be corrected by adoptively transferred epo-producing lymphocytes. The aim of this study was to investigate the precise effects of human epo administration by this route on erythropoietic development in epo-deficient mice. The erythroblast compartments of untreated and treated EpoTAg mice were analysed in comparison with wild-type mice. The early erythroblast population was reduced in the bone marrow of epo-deficient mice, whilst the number of erythroid colony-forming units (CFU-E) was not significantly compromised. This paucity in marrow early erythroblasts was restored to normal values in treated mutant mice. In addition, the early erythroblast population was expanded in the spleens of treated animals. These findings show that the early erythroblasts are important targets of epo and that epo corrects anaemia of epo-deficient mice by restoring marrow function and splenic erythropoiesis. [ABSTRACT FROM AUTHOR]

Haematological and infectious toxicity was correlated to renal function in 272 newly diagnosed myeloma patients given standard dose melphalan–prednisone (MP) as initial treatment without dose adjustment for renal impairment. The glomerular filtration rate (GFR) was estimated by calculated creatinine clearance. Haematological toxicity was found to be significantly related to renal dysfunction. Haematological toxicity World Health Organization (WHO) grades 3–4 after the first MP course was seen in 18%, 28% and 36% of patients with a creatinine clearance of>50, 30–50 and<30 ml/min respectively. WHO grades 3–4 infections occurred in 6% and were not significantly related to renal function. We conclude that MP therapy can be used for initial therapy in myeloma patients with renal impairment but suggest that reduction of the melphalan dose should be considered in patients with a GFR of<30 ml/min. As only 2% of our patients had a clearance of≤10 ml/min no conclusions can be drawn for this subgroup. [ABSTRACT FROM AUTHOR]

Part I. Discusses non-endocrine late complications of bone marrow transplantation (BMT) in childhood. Cardiotoxicity in children after BMT; Effect of BMT on the functions of pulmonary organs; Details of acute renal insufficiency after BMT.