Sokratis Stoumpos

Cardiovascular morbidity and mortality after kidney transplantation

Kidney transplantation is the optimal treatment for patients with end stage renal disease (ESRD) who would otherwise require dialysis. Patients with ESRD are at dramatically increased cardiovascular (CV) risk compared with the general population. As well as improving quality of life, successful transplantation accords major benefits by reducing CV risk in these patients. Worldwide, cardiovascular disease remains the leading cause of death with a functioning graft and therefore is a leading cause of graft failure. This review focuses on the mechanisms underpinning excess CV morbidity and mortality and current evidence for improving CV risk in kidney transplant recipients. Conventional CV risk factors such as hypertension, diabetes mellitus, dyslipidaemia and pre‐existing ischaemic heart disease are all highly prevalent in this group. In addition, kidney transplant recipients exhibit a number of risk factors associated with pre‐existing renal disease. Furthermore, complications specific to transplantation may ensue including reduced graft function, side effects of immunosuppression and post‐transplantation diabetes mellitus. Strategies to improve CV outcomes post‐transplantation may include pharmacological intervention including lipid‐lowering or antihypertensive therapy, optimization of graft function, lifestyle intervention and personalizing immunosuppression to the individual patients risk profile.

The association between apolipoprotein E gene polymorphisms and essential hypertension: a meta-analysis of 45 studies including 13,940 cases and 16,364 controls.

The apolipoprotein E single-nucleotide polymorphisms are among the potential candidate genes that may serve as modulators in susceptibility to essential hypertension. In an effort to clarify earlier inconclusive results, we performed a meta-analysis of population-based case–control genetic association studies. Random-effects methods were applied on summary data in order to combine the results of the individual studies. We identified in total 45 studies, including 13 940 hypertensive cases and 16 364 controls. The contrast of E4 carriers versus non-carriers yielded an overall odds ratio (OR) of 1.16 (95% confidence interval (CI): 1.02, 1.31), whereas the contrast of E4 allele versus the others in a subtotal of 6617 cases and 7330 controls, yielded an OR of 1.39 (95% CI: 1.12, 1.72). There was moderate evidence of publication bias in both contrasts, which was eliminated after excluding studies not in Hardy–Weinberg equilibrium. Subgroup analyses revealed that significant estimates arose from studies on Asian populations, as opposed to the Caucasian ones. Furthermore, no evidence of publication bias was demonstrated in the comparisons within this subgroup. Our results are consistent with recent meta-analyses but show that the association is weaker than that has been previously demonstrated. Further studies are needed in order to fully address questions about the etiological mechanism of the particular association, as well as to study the effect in populations of African descent.

Predictors of sustained arteriovenous access use for haemodialysis.

Background: Guidelines encourage early arteriovenous (AV) fistula (AVF) planning for haemodialysis (HD). The aim of this study was to estimate the likelihood of sustained AV access use taking into account age, sex, comorbidity, anatomical site of first AVF and, for pre-dialysis patients, eGFR and proteinuria. Methods: 1,092 patients attending our centre who had AVF as their first AV access procedure between January 1, 2000 and August 23, 2012 were identified from the electronic patient record. The primary end-point was time to first sustained AV access use, defined as use of any AV access for a minimum of 30 consecutive HD sessions. Results: 52.9% (n = 578) of the patients ultimately achieved sustained AV access use. The main reasons for AV access non-use were AVF failure to mature and death. The 3-year Kaplan-Meier probability of sustained AV access use was 68.8% for those not on renal replacement therapy (RRT) (n = 688) and 74.2% for those already on RRT (n = 404) at the time of first AVF. By multivariate analysis in patients not on RRT, male sex (HR 2.22; p < 0.001), uPCR (HR 1.03; p = 0.03) and eGFR (hazard ratio, HR 0.85; p < 0.001) were independent predictors of AV access use. In patients already on RRT, age (HR 0.98; p < 0.001) and peripheral vascular disease (HR 0.48; p = 0.02) were independent predictors of AV access use. Conclusion: Our data suggest that refinement of the current guideline for timing of AV access creation in planning RRT is justified to take into account individual factors that contribute to the likelihood of technical success and clinical need.

Continued monitoring of acute kidney injury survivors mightnot be necessary in those regaining an estimated glomerularfiltration rate>60 mL/min at 1 year

Background. Severe acute kidney injury (AKI) among hospitalized patients often necessitates initiation of short-term dialysis. Little is known about the long-term outcome of those who recover to normal renal function. The aim of this study was to determine the long-term renal outcome of patients experiencing AKI requiring dialysis secondary to hypoperfusion injury and/or sepsis who recovered to apparently normal renal function. Methods. All adult patients with AKI requiring dialysis in our centre between 1 January 1980 and 31 December 2010 were identified. We included patients who had estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2 12 months or later after the episode of AKI. Patients were followed up until 3 March 2015. The primary outcome was time to chronic kidney disease (CKD) (defined as eGFR persistently <60 mL/min/1.73 m2) from first dialysis for AKI. Results. Among 2922 patients with a single episode of dialysis-requiring AKI, 396 patients met the study inclusion criteria. The mean age was 49.8 (standard deviation 16.5) years and median follow-up was 7.9 [interquartile range (IQR) 4.8–12.7] years. Thirty-five (8.8%) of the patients ultimately developed CKD after a median of 5.3 (IQR 2.8–8.0) years from first dialysis for AKI giving an incidence rate of 1 per 100 person-years. Increasing age, diabetes and vascular disease were associated with higher risk of progression to CKD [adjusted hazard ratios (95% confidence interval): 1.06 (1.03, 1.09), 3.05 (1.41, 6.57) and 3.56 (1.80, 7.03), respectively]. Conclusions. Recovery from AKI necessitating in-hospital dialysis was associated with a very low risk of progression to CKD. Most of the patients who progressed to CKD had concurrent medical conditions meriting monitoring of renal function. Therefore, it seems unlikely that regular follow-up of renal function is beneficial in patients who recover to eGFR >60 mL/min/1.73 m2 by 12 months after an episode of AKI.

Obstetric and long-term kidney outcomes in renal transplant recipients: a 40-yr single-center study.

Female renal transplant recipients of childbearing age may ask what the outcomes are for pregnancy and whether pregnancy will affect graft function. We analyzed obstetric and transplant outcomes among renal transplant recipients in our center who have been pregnant between 1973 and 2013. A case−cohort study was performed identifying 83 pairs of pregnant and non‐pregnant controls matched for sex, age, transplant vintage, and creatinine. There were 138 pregnancies reported from 89 renal transplant recipients. There were live births in 74% of pregnancies with high prevalence of prematurity (61%), low birth weight (52%), and pre‐eclampsia (14%). Lower eGFR (OR 0.98; p = 0.05) and higher uPCR (OR 1.86; p = 0.02) at conception were independent predictors for poor composite obstetric outcome. Lower eGFR (OR 0.98; p = 0.04), higher uPCR (OR 1.50; p = 0.04), and live organ donation (OR 0.35; p = 0.02) were predictors of ≥20% loss of eGFR between immediately pre‐pregnancy and one yr after delivery. There was no difference in eGFR at one, five, and 10 yr in pregnant women compared with non‐pregnant controls and a pregnancy was not associated with poorer 10‐yr transplant or 20‐yr patient survival. Despite high rates of obstetric complications, most women had successful pregnancies with good long‐term transplant function.

The utility of anti-Müllerian hormone in women with chronic kidney disease, on haemodialysis and after kidney transplantation

Women with renal disease have menstrual and gonadal dysfunction manifesting as hormonal imbalance. Anti-Müllerian hormone (AMH) is a potential measure of ovarian reserve. We examined circulating AMH concentrations in young women with renal failure, determined associations with clinical characteristics, and compared AMH with age-matched healthy individuals. AMH was measured in 77 women: 26 had chronic kidney disease (CKD), 26 were on haemodialysis (HD), and 25 had a kidney transplant. Random AMH levels were highest in women on HD [HD 2.9 (1.1-5.2), CKD 1.6 (0.7-2.2), transplant 1.5 (1.0-4.2) ng/ml]. On multiple linear regression, AMH was 53% higher [95% CI 0.20-0.98, P = 0.002] in women on HD and decreased by 20% per 5-year increase in age (P < 0.001). AMH was 43% lower in women with renal failure compared with 600 age-matched controls [1.7 (0.9-3.8) versus 3.0 (1.9-5.0) ng/ml, P < 0.001]; however, we found no difference in AMH between those on HD and healthy individuals [2.9 (1.1-5.2) versus 3.0 (1.9-5.0) ng/ml]. AMH may be a useful biomarker in female renal patients with non-dialysis dependent renal disease pursuing pregnancy. In contrast, AMH levels are higher in HD but unlikely to reflect ovarian reserve.

MO036A FRAMEWORK FOR TARGETING QUALITY IMPROVEMENT IN HAEMODIALYSIS VASCULAR ACCESS

Sokratis Stoumpos1, Eleanor C Murray2, David B Kingsmore3, Ram Kasthuri4 and Peter C Thomson1 Queen Elizabeth University Hospital, Renal & Transplant Unit, Glasgow, UNITED KINGDOM, Queen Elizabeth University Hospital, Queen Elizabeth University Hospital, Glasgow, UNITED KINGDOM, Queen Elizabeth University Hospital, Glasgow Renal & Transplant Unit, Glasgow, UNITED KINGDOM, Queen Elizabeth University Hospital, Department of Radiology, Glasgow, UNITED KINGDOM

A CANDIDATE KIDNEY DONOR WITH ANATOMIC VARIATIONS IN RENAL ARTERIES

A 53 year old man was admitted to the hospital for a preoperative assessment as a candidate donor of a renal graft. His medical history included coronary artery disease, which was treated with balloon angioplasty and the placement of an intraluminal coronary artery stent in the left anterior descending artery 1 year before his admission. Digital subtraction angiography (DSA) of the renal arteries manifested the presence of four renal arteries in the left kidney (Fig. 1) and the coexistence of a main and a polar artery in the right kidney. The right polar artery supplied a segment of the lower pole of the right kidney and stemmed from a common branch with the ipsilateral inferior phrenic artery. The high frequency of polar arteries, multiple arteries and the origin of renal arteries from the aorta at different heights or from other arteries can be explained by the embryological development of the kidney. The occurrence of four renal arteries is of a rare incidence (<1%) while a lower polar artery correlates with an increased rate of recipient ureteral complications. Polar arteries and multiple renal arteries are important in kidney transplantation. Multiple renal arteries (MRA) are the most frequently encountered anatomical variation in kidneys. In one report the incidence of unilateral MRA was 23%, and that of bilateral MRA was 10%. Keller JE et al. reviewed a total of 230 laparoscopic donor nephrectomies performed at a single institution. Multiple arteries were present in 37 donors. No significant difference in estimated blood loss, transfusions, operative time or length of hospital stay was noted between multiple and single laparoscopic donor nephrectomies. Benedetti et al. reported the same results among 163 patients with MRA versus 835 with single renal arteries. Available studies support that donor morbidity and recipient intraoperative, early and late postoperative outcomes do not differ between donors with multiple renal arteries and those with a single renal artery. The gold standard technique for preoperative donor evaluation is a DSA as it provides a precise evaluation of supernumerary and accessory renal vessels. However, the procedure is invasive, uses ionizing radiation and large amounts of nephrotoxic opaque material. Additionally, selective catheter placement in the renal arteries comprises an increased risk for intimal injury, dissection and subsequent stenosis of the vessel. Magnetic resonance angiography (MRA) is an acceptable alternative non-invasive imaging modality in donors because it has the added benefits of no iodinated contrast material and no exposure to ionizing radiation. MRA is inadequate in detecting supernumerary vessels, accessory renal arteries and the presence of smalldiameter vessels and it cannot be recommended as the sole diagnostic tool in unclear cases. Multidetector row computerized tomography angiography is non-invasive and it can provide sufficient information about renal and extrarenal anatomy. Multidetector row computerized tomography angiography visualizes renal veins with high accuracy and its spatial resolution is superior to that of MRA. Radiation exposure of healthy kidney donors must be considered when using CT angiography, although, the total radiation dose for a triple-phase CT was shown to be less than that with the DSA. There has been some controversial discussion regarding the best approach to follow. Selection of a procedure should be guided by the experience of the radiologist, the Fig. 1 Digital subtraction angiography depicting the vasculature of the left kidney with the four renal arteries stemmed from different branches of the descending aorta. Correspondence