De novo HNF1 homeobox B mutation as a cause for chronic, treatment-resistant hypomagnesaemia.

29-year-old female presenting with an 8-year history of unexplained hypomagnesaemia, which was severe enough to warrant intermittent inpatient admission for intravenous magnesium. Urinary magnesium was inappropriately normal in the context of hypomagnesaemia indicating magnesium wasting. Ultrasound imaging demonstrated unilateral renal cysts and computed tomography of kidneys, ureters and bladder showed a bicornuate uterus. Referral to genetic services and subsequent testing revealed a de novo HNF1B deletion. Learning points: HNF1B loss-of-function mutations are one of the most common monogenic causes of congenital anomalies of the kidney and urinary tract.Those with HNF1B mutations may have some of a constellation of features (renal and hepatic cysts, deranged liver function tests, maturity onset diabetes of the young type 5 (MODY5), bicornuate uterus, hyperparathyroidism, hyperuricaemic gout, but presenting features are highly heterogeneous amongst patients and no genotype/phenotype correlation exists. HNF1B mutations are inherited in an autosomal dominant pattern but up to 50% of cases are de novo.HNF1B mutations can be part of the Chr17q12 deletion syndrome, a contiguous gene deletion syndrome.Inorganic oral magnesium replacements are generally poorly tolerated with side effects of diarrhoea. Organic magnesium compounds, such as magnesium aspartate, are better absorbed oral replacement therapies.This work was supported by a Wellcome Trust Clinical Training fellowship to CES (grant number 097970/Z/11/Z)

Multidisciplinary management of complicated bilateral renal artery aneurysm in a woman of childbearing age

Ruptured renal artery aneurysm (RAA) during pregnancy is a rare condition associated with high mortality rates to both the mother and the foetus. We report on a 41-year-old woman at her second trimester who presented with shock to the emergency department as a result of a ruptured left RAA. While the bleeding was successfully treated with angiographic embolization, a contralateral RAA, also at risk of rupture, was discovered. Due to its position on the artery bifurcation, this lesion was considered not suitable for interventional radiology and was therefore managed by hand-assisted retroperitoneoscopic nephrectomy, ex-vivo repair and autotransplantation. This was done in order to preserve renal mass and give our patient a chance of having future pregnancies without risk of rupture. Three years later, her renal function is normal, there is no evidence of recurrence, and more importantly she had two successful and uncomplicated pregnancies

Renal transplant and hemostasis: early postoperative changes in recipients and donors

Background The benefit of administering pharmacologic thromboprophylaxis following renal transplantation remains uncertain. Objectives To compare hemostatic parameters before and after renal transplant surgery in both recipients and their donors at predetermined time points. Methods Blood samples were collected at baseline (T1), immediately after surgery (T2), and at 24 hours after surgery (T3) in both recipients and donors and at 72 (T4) and 120 hours (T5) from recipients only. Assays included in vitro thrombin generation, factor VIII (FVIIIc) activity, von Willebrand factor (VWF) antigen, D-dimer, antithrombin activity, prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin complexes, and plasminogen activator inhibitor-1 (PAI-1) antigen. Results Fifty-two patients (28 recipients and 24 donors) were enrolled. Both donors and recipients had increased FVIIIc, VWF, F1 + 2, D-dimer, and PAI immediately after surgery but reduced antithrombin. Mixed-model analysis showed that the magnitude of change over time (between T1 and T3) for FVIIIc (mean estimated difference [MED], 72; 95% CI, 41-102; P < .0001), VWF (MED, 89; 95% CI, 35-142; P = .001), F1 + 2 (MED, 283; 95% CI, 144-422; P < .0001), thrombin-antithrombin complexes (MED, 3.5; 95% CI, 1.9-5.1; P < .0001), D-dimer (MED, 2.2; 95% CI, 1.0-3.3; P < .0001), PAI-1 (MED, 9.2; 95% CI, 3.4-14.9; P = .002), and time to peak thrombin generation (MED, 1.5; 95% CI, 0.35-2.7; P = .01) was more significant in recipients than in donors. Conclusion Persistence of a hypercoagulable state was more prominent in recipients after 24 hours despite recovery in renal function and initiation of thromboprophylaxis

Efficacy and safety of chemical thromboprophylaxis in renal transplantation – A systematic review

Introduction The benefit of administering chemical thromboprophylaxis to chronic kidney disease patients undergoing renal transplantation is unclear and no previous systematic review has addressed this as reflected by variations in national guidelines. Methods A literature search was performed using MEDLINE, Embase, Cochrane, CINAHL, World Health Organisation (WHO) International Clinical Trials Registry Platform and ClinicalTrials.gov databases to December 2019. Studies included participants undergoing renal transplantation only with no contra-indication to thromboprophylaxis, no history/clinical suspicion of acute organ rejection and those describing a form of chemical thromboprophylaxis intervention compared with another form, no intervention or placebo. Results Thirteen studies with 1600 patients were included. There was wide variation concerning type of thromboprophylaxis, time of onset, dosing and duration. Reports of symptomatic/asymptomatic venous thromboembolism and mortality were limited. Seven studies reported on renal allograft thrombosis. When comparing thromboprophylaxis to no intervention, there was no evidence of difference for thrombosis risk (risk ratio 0.2; [95% CI 0.01–4.63]), however all studies were underpowered to answer this question. Six studies reported on major bleeding but type of intervention, timing of onset and duration of thromboprophylaxis varied significantly, making it difficult to pool data for further analysis. Conclusion There is insufficient evidence to advise on efficacy and safety of chemical thromboprophylaxis in patients undergoing renal transplantation or to determine whether one chemical thromboprophylaxis is better than another thromboprophylaxis

Outcomes following kidney transplantation in patients with sickle cell disease: The impact of automated exchange blood transfusion

There are over 12,000 people with sickle cell disease (SCD) in the UK, and 4–12% of patients who develop Sickle Cell Nephropathy (SCN) progress to End Stage Renal Disease (ESRD). Renal transplantation offers the best outcomes for these patients with but their access to transplantation is often limited. Regular automated exchange blood transfusions (EBT) reduce the complications of SCD and may improve outcomes. However, concerns over alloimmunisation limit its widespread implementation. In this retrospective multicenter study, data were collected on 34 SCD patients who received a kidney transplant across 6 London Hospitals between 1997 and 2017. 20/34 patients were on an EBT program, pre or post renal transplantation. Overall patient and graft survival were inferior to contemporaneous UK data in the ESRD population as a whole, a finding which is well-recognised. However, patient survival (CI 95%, p = 0.0032), graft survival and graft function were superior at all time-points in those who received EBT versus those who did not. 4/20 patients (20%) on EBT developed de novo donor specific antibodies (DSAs). 3/14 patients (21%) not on EBT developed de novo DSAs. The incidence of rejection in those on EBT was 5/18 (28%), as compared with 7/13 (54%) not on EBT. In conclusion, our data, while limited by an inevitably small sample size and differences in the date of transplantation, do suggest that long-term automated EBT post renal transplant is effective and safe, with improvement in graft and patient outcomes and no increase in antibody formation or graft rejection