Assessing asymmetrical kidney function in living donors: a retrospective cohort study on CT metrics.

BACKGROUND: Live donor kidney transplantation is the preferred kidney replacement therapy for eligible patients but requires thorough donor evaluation to minimise risks. Contemporary guidelines recommend split kidney function measurement in living donors only when there is a significant kidney size discrepancy, yet the evidence for this is poor, and practice varies nationally. This study evaluates the efficacy of CT-derived kidney metrics in detecting significant functional asymmetry. METHODS: We conducted a retrospective cohort analysis of 123 prospective living kidney donors at a regional transplant centre from June 2011 to October 2014, utilising CT to determine kidney and cortical volumes and lengths. Asymmetric kidney function (AKF), defined by > 10% function difference on DMSA scans, was correlated with CT measurements to calculate the diagnostic accuracy of current guidelines. RESULTS: Among the prospective donors, the median age was 42 years, and 59.3% were female. The median split kidney function difference was 4%, with 25 individuals exhibiting > 10% AKF. Kidney length discrepancy proved to be a poor indicator of AKF (sensitivity: 28%, specificity: 84%). While negative predictive values for cortical and kidney volumes were high (96% and 93%, respectively), sensitivity was low, and specificity and positive predictive value did not meet satisfactory thresholds. CONCLUSIONS: CT-derived metrics of kidney length, cortical, and total volume show limited sensitivity and specificity in identifying significant AKF. These findings provide evidence to support revised guideline development in the assessment of living kidney donors.

Safety, pharmacodynamics, and exposure-response modeling results from a first-in-human phase 1 study of nedosiran (PHYOX1) in primary hyperoxaluria.

Primary hyperoxaluria (PH) is a family of ultra-rare autosomal recessive inherited disorders of hepatic glyoxylate metabolism characterized by oxalate overproduction. Nedosiran is an RNA interference agent that inhibits hepatic lactate dehydrogenase, the enzyme responsible for the common, final step of oxalate production in all three genetic subtypes of PH. Here, we assessed in a two-part, randomized, single-ascending-dose, phase 1 study (PHYOX1) the safety, pharmacokinetics, pharmacodynamics, and exposure-response of subcutaneous nedosiran in 25 healthy participants (Group A) and 18 patients with PH1 or PH2 (Group B). Group A received nedosiran (0.3, 1.5, 3.0, 6.0, then 12.0 mg/kg) or placebo, and Group B received open-label nedosiran (1.5, 3.0, or 6.0 mg/kg). No significant safety concerns were identified. Injection site reactions (four or more hours post dose) occurred in 13.3% of participants in Group A and 27.8% of participants in Group B. Mean maximum reduction in 24-hour urinary oxalate excretion from baseline to day 57 (end of study) across Group B dose cohorts was 55% (range: 22%-100%) after single-dose nedosiran, with 33% participants reaching normal 24-hour urinary oxalate excretion. Based on the available modeling and simulation data, a fixed monthly dose of nedosiran 160 mg (free acid; equivalent to 170 mg sodium salt) in adults was associated with the highest proportion of simulated individuals achieving normal or near-normal 24-hour urinary oxalate excretion and fewest fluctuations in urinary oxalate response. Thus, single-dose nedosiran demonstrated acceptable safety and evidence of a pharmacodynamic effect in both PH1 and PH2 subpopulations consistent with its mechanism of action.

Centre variation in mortality following post-hospitalization acute kidney injury: analysis of a large national cohort.

BACKGROUND: Routine monitoring of outcomes for patients with acute kidney injury (AKI) is important to drive ongoing quality improvement in patient care. In this study we describe the development of a case mix-adjusted 30-day mortality indicator for patients with post-hospitalization AKI (PH-AKI) across England to facilitate identification of any unwarranted centre variation in outcomes. METHODS: We utilized a routinely collected national dataset of biochemically detected AKI cases linked with national hospitals administrative and mortality data. A total of 250 504 PH-AKI episodes were studied across 103 National Health Service hospital trusts between January 2017 and December 2018. Standardized mortality ratios (SMRs) were calculated for each trust using logistic regression, adjusting for age, sex, primary diagnosis, comorbidity score, AKI severity, month of AKI and admission method. RESULTS: The mean 30-day mortality rate was high, at 28.6%. SMRs for 23/103 trusts were classed as outliers, 12 above and 11 below the 95% confidence limits. Patients with PH-AKI had mortality rates >5 times higher than the overall hospitalized population in 90/136 diagnosis groups and >10 times higher in 60/136 groups. Presentation at trusts with a co-located specialist nephrology service was associated with a lower mortality risk, as was South Asian or Black ethnicity. Deprivation, however, was associated with higher mortality. CONCLUSIONS: This is the largest multicentre analysis of mortality for patients with biochemically ascertained PH-AKI to date, demonstrating once again the considerable risk associated with developing even mild elevations in serum creatinine. Mortality rates varied considerably across centres and those identified as outliers will now need to carefully interrogate local care pathways to understand and address the reasons for this, with national policy required to tackle the identified health disparities.

Pregnancy in cystinosis patients with chronic kidney disease: A European case series.

Cystinosis is a rare autosomal recessive disease leading to end-stage renal disease within the second or third decade of life. Since the era of specific treatment with cysteamine, prognosis has substantially improved and pregnancy becomes an increasing concern. Pregnancy data in patients with cystinosis were collected through an anonymized survey. We collected data for 19 pregnancies in 12 women. Seventeen patients were transplanted, 1 was on hemodialysis and 1 had chronic kidney disease (CKD) stage 4. These 19 pregnancies resulted in 13 live births (68.4%): 3 spontaneous early miscarriages, 1 ectopic pregnancy, 1 early pre-eclampsia (at 21 weeks), and 1 preterm birth with neonatal death at 24 weeks were reported. After exclusion of early miscarriage or termination, pregnancy success rate was 86.7%. In successful pregnancies, median gestational age at delivery was 34 weeks (24-37). Preeclampsia occurred in seven pregnancies (7/15, 46.7%). A cesarean section was performed in all pregnancies. Median baby weight at delivery was 2175 g (620-3374 g). After pregnancy, one patient reached end-stage renal disease, but she already had advanced CKD before pregnancy (creatinine 239 µmol/L, eGFR 23 ml/min/1.73 m2 ). In three other patients, there was a decrease of eGFR of 8, 20, and 53 ml/min/1.73 m2 , respectively. The majority of pregnancies were successful, but severe antenatal and post-natal complications may occur, in particular preeclampsia that was noticed in nearly half of patients and fetal loss in one-third of them. These results may help pre-pregnancy counseling and pregnancy management.

Young adults have worse kidney transplant outcomes than other age groups.

BACKGROUND: The objective of this study was to establish if renal transplant outcomes (graft and patient survival) for young adults in England were worse than for other age groups. METHODS: Outcomes for all renal transplant recipients in England (n = 26 874) were collected from Hospital Episode Statistics and the Office for National Statistics databases over 12 years. Graft and patient outcomes, follow-up and admissions were studied for all patients, stratified by age bands. RESULTS: Young adults (14-23 years) had substantially greater likelihood [hazard ratio (HR) = 1.26, 95% confidence interval (CI) 1.10-1.19; P < 0.001] of kidney transplant failure than any other age band. They had a higher non-attendance rate for clinic appointments (1.6 versus 1.2/year; P < 0.001) and more emergency admissions post-transplantation (25% of young adults on average are admitted each year, compared with 15-20% of 34- to 43-year olds). Taking into account deprivation, ethnicity, transplant type and transplant centre, in the 14- to 23-year group, return to dialysis remained significantly worse than all other age bands (HR = 1.41, 95% CI 1.26-1.57). For the whole cohort, increasing deprivation related to poorer outcomes and black ethnicity was associated with poorer outcomes. However, neither ethnicity nor deprivation was over-represented in the young adult cohort. CONCLUSIONS: Young adults who receive a kidney transplant have a significant increased likelihood of a return to dialysis in the first 10 years post-transplant when compared with those aged 34-43 years in multivariable analysis.

Patient and clinician opinions of patient reported outcome measures (PROMs) in the management of patients with rare diseases: a qualitative study.

BACKGROUND: Rare diseases may be life-threatening or chronically debilitating conditions. Patient care needs are often complex and challenging to coordinate and deliver effectively. Rare diseases and their clinical management may therefore substantially impact on patients' health-related quality of life (HRQOL). The use of patient-reported outcome measures (PROMs) may complement clinical assessments by elucidating patients' perspectives on their health status and care priorities. This study explored the opinions of patients and clinicians on the use of PROMs in the management of patients with rare diseases in routine clinical practice. METHODS: A total of 15 semi-structured one-to-one interviews were conducted with four patients with primary sclerosing cholangitis (PSC); five renal transplant recipients; and six PSC doctors from University Hospitals Birmingham (UHB) NHS Foundation Trust. A focus group session was also conducted with 10 clinical staff members (doctors, nurses and other allied health professionals from UHB). The suitability and acceptability of the Chronic Liver Disease Questionnaire (CLDQ) and the Short Form 12 (SF12) were assessed by patients with PSC and their doctors while the Paediatric quality of life inventory Transplant Module (PedsQL-TM) and the EuroQoL-5 dimensions (EQ. 5D) were evaluated by the renal transplant recipients and their doctors. The discussions were audio recorded and transcribed verbatim. Coding of the transcripts was done using the Nvivo 11 Plus software. Thematic analysis was conducted to identify the main themes and subthemes. RESULTS: Four themes were identified, namely: (i) potential benefits of PROMs in the management of rare diseases; (ii) views on selected questionnaires; (iii) practical considerations for implementation; and (iv) potential facilitators and barriers of implementation. Patients and clinicians suggested that the use of ePROMs may facilitate patient-centred care by promoting patient-clinician communication, highlighting aspects of HRQOL that are important to patients and encouraging patient involvement in their care. They also felt that the disease-specific CLDQ and PedsQL-TM were more relevant than the generic SF12 and EQ-5D. CONCLUSIONS: Patients with rare diseases often experience impaired HRQOL. The use of an ePROM system may enhance the routine management of patients with rare diseases.

Patients with primary hyperoxaluria type 2 have significant morbidity and require careful follow-up.

Primary hyperoxaluria type 2 is a rare inherited disorder of glyoxylate metabolism causing nephrocalcinosis, renal stone formation and ultimately kidney failure. Previously, primary hyperoxaluria type 2 was considered to have a more favorable prognosis than primary hyperoxaluria type 1, but earlier reports are limited by low patient numbers and short follow up periods. Here we report on the clinical, genetic, and biochemical findings from the largest cohort of patients with primary hyperoxaluria type 2, obtained by a retrospective record review of genetically confirmed cases in the OxalEurope registry, a dataset containing 101 patients from eleven countries. Median follow up was 12.4 years. Median ages at first symptom and diagnosis for index cases were 3.2 years and 8.0 years, respectively. Urolithiasis was the most common presenting feature (82.8% of patients). Genetic analysis revealed 18 novel mutations in the GRHPR gene. Of 238 spot-urine analyses, 23 (9.7%) were within the normal range for oxalate as compared to less than 4% of 24-hour urine collections. Median intra-individual variation of 24-hour oxalate excretion was substantial (34.1%). At time of review, 12 patients were lost to follow-up; 45 of the remaining 89 patients experienced chronic kidney disease stage 2 or greater and 22 patients had reached stage 5. Median renal survival was 43.3 years, including 15 kidney transplantations in 11 patients (1 combined with liver transplantation). Renal outcome did not correlate with genotype, biochemical parameters or initially present nephrocalcinosis. Thus, primary hyperoxaluria type 2 is a disease with significant morbidity. Accurate diagnosis by 24-hour urine analysis and genetic testing are required with careful follow-up.

Combined liver-kidney transplantation versus liver transplant alone based on KDIGO stratification of estimated glomerular filtration rate: data from the United Kingdom Transplant registry - a retrospective cohort study.

Patient selection for combined liver-kidney transplantation (CLKT) is a current issue on the background of organ shortage. This study aimed to compare outcomes and post-transplant renal function for patients receiving CLKT and liver transplantation alone (LTA) based on native renal function using estimated glomerular filtration rate (eGFR) stratification. Using the UK National transplant database (NHSBT) 6035 patients receiving a LTA (N = 5912; 98%) or CLKT (N = 123; 2%) [2001-2013] were analysed, and stratified by KDIGO stages of eGFR at transplant (eGFR group-strata). There was no difference in patient/graft survival between LTA and CLKT in eGFR group-strata (P > 0.05). Of 377 patients undergoing renal replacement therapy (RRT) at time of transplantation, 305 (81%) and 72 (19%) patients received LTA and CLKT respectively. A significantly greater proportion of CLKT patients had severe end-stage renal disease (eGFR < 30 ml/min/1.73 m2 ) at 1 year post-transplant compared to LTA (9.5% vs. 5.7%, P = 0.001). Patient and graft survival benefit for patients on RRT at transplantation was favouring CLKT versus LTA (P = 0.038 and P = 0.018, respectively) but the renal function of the long-term survivors was not superior following CLKT. The data does not support CLKT approach based on eGFR alone, and the advantage of CLKT appear to benefit only those who are on established RRT at the time of transplant.

Rapidly progressive intravascular primary effusion lymphoma in an HIV-positive renal transplant recipient.

We describe the clinical and post-mortem findings of a case of rapidly progressive, ultimately fatal primary effusion lymphoma (PEL) arising in an HIV-positive man 2 years after renal transplantation. Disseminated multi-organ involvement associated with a peculiar intravascular pattern of growth, as seen in this case, has only been reported once previously. This is also, to our knowledge, the first detailed description of a lymphoma arising post-transplant in an HIV-positive patient.

Glomerular filtration rate: new age- and gender- specific reference ranges and thresholds for living kidney donation.

BACKGROUND: There is a need for a large, contemporary, multi-centre series of measured glomerular filtration rates (mGFR) from healthy individuals to determine age- and gender-specific reference ranges for GFR. We aimed to address this and to use the ranges to provide age- and gender-specific advisory GFR thresholds considered acceptable for living kidney donation. METHODS: Individual-level data including pre-donation mGFR from 2974 prospective living kidney donors from 18 UK renal centres performed between 2003 and 2015 were amalgamated. Age- and gender-specific GFR reference ranges were determined by segmented multiple linear regression and presented as means ± two standard deviations. RESULTS: Males had a higher GFR than females (92.0 vs 88.1 mL/min/1.73m2, P < 0.0001). Mean mGFR was 100 mL/min/1.73m2 until 35 years of age, following which there was a linear decline that was faster in females compared to males (7.7 vs 6.6 mL/min/1.73m2/decade, P = 0.013); 10.5% of individuals aged > 60 years had a GFR < 60 mL/min/1.73m2. The GFR ranges were used along with other published evidence to provide advisory age- and gender-specific GFR thresholds for living kidney donation. CONCLUSIONS: These data suggest that GFR declines after 35 years of age, and the decline is faster in females. A significant proportion of the healthy population over 60 years of age have a GFR < 60 mL/min/1.73m2 which may have implications for the definition of chronic kidney disease. Age and gender differences in normal GFR can be used to determine advisory GFR thresholds for living kidney donation.

Identification of occult active infection using PET-CT in a combined liver-kidney transplant candidate.

This case describes a patient being considered for combined liver-kidney transplantation for Caroli's disease with a failed renal transplant. A chronic septic focus could not be located with standard imaging techniques, such as ultrasonography and computed tomography. This case report highlights the observation that a retained non-functioning transplant can be the cause of fever of unknown origin and PET-CT can be useful in diagnosing these challenging cases.

Controversies and research agenda in nephropathic cystinosis: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference.

Nephropathic cystinosis is an autosomal recessive metabolic, lifelong disease characterized by lysosomal cystine accumulation throughout the body that commonly presents in infancy with a renal Fanconi syndrome and, if untreated, leads to end-stage kidney disease (ESKD) in the later childhood years. The molecular basis is due to mutations in CTNS, the gene encoding for the lysosomal cystine-proton cotransporter, cystinosin. During adolescence and adulthood, extrarenal manifestations of cystinosis develop and require multidisciplinary care. Despite substantial improvement in prognosis due to cystine-depleting therapy with cysteamine, no cure of the disease is currently available. Kidney Disease: Improving Global Outcomes (KDIGO) convened a Controversies Conference on cystinosis to review the state-of-the-art knowledge and to address areas of controversies in pathophysiology, diagnostics, monitoring, and treatment in different age groups. More importantly, promising areas of investigation that may lead to optimal outcomes for patients afflicted with this lifelong, systemic disease were discussed with a research agenda proposed for the future.

Predicting 5-year risk of kidney transplant failure: a prediction instrument using data available at 1 year posttransplantation.

BACKGROUND: Accurate prediction of kidney transplant failure remains imperfect. The objective of this study was to develop and validate risk scores predicting 5-year transplant failure, based on data available 12 months posttransplantation. STUDY DESIGN: Development and then independent multicenter validation of risk scores predicting death-censored and overall transplant failure. SETTING & PARTICIPANTS: Outcomes of kidney transplant recipients (n=651) alive with transplant function 12 months posttransplantation in Birmingham, United Kingdom, were used to develop models predicting transplant failure risk 5 years posttransplantation. The resulting risk scores were evaluated for prognostic utility (discrimination, calibration, and risk reclassification) in independent cohorts from Tours, France (n=736); Leeds, United Kingdom (n=787); and Halifax, Canada (n=475). PREDICTORS: Weighted regression coefficients for baseline and 12-month demographic and clinical predictor characteristics. OUTCOMES: Death-censored and overall transplant failure 5 years posttransplantation. MEASUREMENTS: Baseline data and time to transplant failure. RESULTS: Following model development, variables included in separate scores for death-censored and overall transplant failure included recipient age, sex, and race; acute rejection; transplant function; serum albumin level; and proteinuria. In the validation cohorts, these scores showed good to excellent discrimination for death-censored transplant failure (C statistics, 0.78-0.90) and moderate to good discrimination for overall transplant failure (C statistics, 0.75-0.81). Both scores demonstrated good calibration (Hosmer-Lemeshow P>0.05 in all cohorts). Compared with estimated glomerular filtration rate in isolation, application of the scores resulted in statistically significant and clinically relevant risk reclassification for death-censored transplant failure (net reclassification improvement [NRI], 36.1%-83.0%; all P<0.001) and overall transplant failure (NRI, 38.7%-53.5%; all P<0.001). Compared with the previously described US Renal Data System-based risk calculator, significant and relevant risk reclassification for overall transplant failure was seen (NRI, 30.0%; P<0.001). LIMITATIONS: Validation is required in further populations. CONCLUSIONS: These validated risk scores may be of prognostic utility in kidney transplantation, accurately identifying at-risk transplants, and informing clinicians and patients.

Nedosiran Safety and Efficacy in PH1: Interim Analysis of PHYOX3.

Introduction: Primary hyperoxaluria (PH) is a rare genetic disorder of hepatic glyoxylate metabolism. Nedosiran is an RNA interference (RNAi) therapeutic that the US Food and Drug Administration has approved for treatment of PH1. PHYOX3 is a trial evaluating monthly nedosiran in patients with PH. Methods: In this PHYOX3 interim analysis, participants with PH1 who continued from a single-dose nedosiran trial (PHYOX1), with no previous kidney or liver transplantation, dialysis, or evidence of systemic oxalosis were eligible. The safety and efficacy of once-monthly nedosiran was assessed over 30 months. Results: Thirteen participants completed PHYOX1 and continued into PHYOX3. At baseline, the mean (SD) and median (range) age was 24.2 (6.6) years and 23.0 (14-39) years, respectively; 53.8% were female and 61.5% were White. Mean estimated glomerular filtration rate (eGFR) remained stable (62-84.2 mL/min per 1.73 m2) to month 30. Mean 24-hour urinary oxalate (Uox) excretion showed a sustained reduction from baseline of ≥60% at every visit (months 2-30). From month 2, at least 10 of 13 (76.9%) participants achieved normal (<0.46 mmol/24h; upper limit of assay-normal [ULN]) or near-normal (≥0.46 to <0.60 mmol/24h; ≥ULN to <1.3 × ULN) 24-hour Uox excretion. All participants experienced ≥1 adverse event (AE), mostly mild or moderate in severity (primarily, injection site events). Three serious, not treatment-related AEs were reported; there were no deaths or study discontinuations due to AEs. Conclusion: Nedosiran was well-tolerated in patients with PH1, and treatment resulted in a sustained, substantial reduction in Uox excretion for at least 30 months in this long-term study. No safety signals have been identified to date. The PHYOX3 study is ongoing.

Pre-eclampsia is associated with complement pathway activation in the maternal and fetal circulation, and placental tissue.

OBJECTIVES: Pre-eclampsia (PE) is a leading cause of obstetric morbidity, with no definitive therapy other than delivery. We aimed to compare complement markers in maternal and fetal circulation, and placental tissue, between women with PE and healthy pregnant controls. STUDY DESIGN: Maternal and umbilical cord blood was tested for iC3b, C3, C4, properdin, Ba and C5b-9, and placental tissue for C3d, C4d, C9 and C1q, from women with PE (n = 34) and healthy pregnant controls (n = 33). Maternal properdin and Ba tests were repeated in a separate validation cohort (PE n = 35; healthy pregnant controls n = 35). MAIN OUTCOME MEASURES: Complement concentrations in maternal and umbilical cord blood, and placental immunohistochemical complement deposition. RESULTS: Women with PE had significantly lower concentrations of properdin (mean: 4828 vs 6877 ng/ml, p < 0.001) and C4 (mean: 0.20 vs 0.31 g/l, p < 0.001), and higher Ba (median: 150 vs 113 ng/ml, p = 0.012), compared to controls. After controlling for gestational age at blood draw, average properdin concentration was 1945 ng/ml lower in PE vs controls (95 % CI: 1487-2402, p < 0.001). Of the cord blood markers assessed, only Ba differed significantly between PE and controls (median: 337 vs 233 ng/ml, p = 0.004). C4d staining of the syncytiotrophoblast membrane was increased in PE vs controls (median immunoreactivity score 3 vs 0, p < 0.001). Maternal properdin and C4 were significantly negatively correlated with placental C4d staining. CONCLUSIONS: Our data confirm excessive placental complement deposition associated with significant concurrent changes in maternal and fetal circulating complement biomarkers in PE. Inhibition of complement activation is a potential therapeutic target.

Determinants of Kidney Failure in Primary Hyperoxaluria Type 1: Findings of the European Hyperoxaluria Consortium.

Introduction: Primary hyperoxaluria type 1 (PH1) has a highly heterogeneous disease course. Apart from the c.508G>A (p.Gly170Arg) AGXT variant, which imparts a relatively favorable outcome, little is known about determinants of kidney failure. Identifying these is crucial for disease management, especially in this era of new therapies. Methods: In this retrospective study of 932 patients with PH1 included in the OxalEurope registry, we analyzed genotype-phenotype correlations as well as the impact of nephrocalcinosis, urolithiasis, and urinary oxalate and glycolate excretion on the development of kidney failure, using survival and mixed model analyses. Results: The risk of developing kidney failure was the highest for 175 vitamin-B6 unresponsive ("null") homozygotes and lowest for 155 patients with c.508G>A and c.454T>A (p.Phe152Ile) variants, with a median age of onset of kidney failure of 7.8 and 31.8 years, respectively. Fifty patients with c.731T>C (p.Ile244Thr) homozygote variants had better kidney survival than null homozygotes (P = 0.003). Poor outcomes were found in patients with other potentially vitamin B6-responsive variants. Nephrocalcinosis increased the risk of kidney failure significantly (hazard ratio [HR] 3.17 [2.03-4.94], P < 0.001). Urinary oxalate and glycolate measurements were available in 620 and 579 twenty-four-hour urine collections from 117 and 87 patients, respectively. Urinary oxalate excretion, unlike glycolate, was higher in patients who subsequently developed kidney failure (P = 0.034). However, the 41% intraindividual variation of urinary oxalate resulted in wide confidence intervals. Conclusion: In conclusion, homozygosity for AGXT null variants and nephrocalcinosis were the strongest determinants for kidney failure in PH1.

Revascularization versus medical therapy for renal-artery stenosis.

BACKGROUND: Percutaneous revascularization of the renal arteries improves patency in atherosclerotic renovascular disease, yet evidence of a clinical benefit is limited. METHODS: In a randomized, unblinded trial, we assigned 806 patients with atherosclerotic renovascular disease either to undergo revascularization in addition to receiving medical therapy or to receive medical therapy alone. The primary outcome was renal function, as measured by the reciprocal of the serum creatinine level (a measure that has a linear relationship with creatinine clearance). Secondary outcomes were blood pressure, the time to renal and major cardiovascular events, and mortality. The median follow-up was 34 months. RESULTS: During a 5-year period, the rate of progression of renal impairment (as shown by the slope of the reciprocal of the serum creatinine level) was -0.07x10(-3) liters per micromole per year in the revascularization group, as compared with -0.13x10(-3) liters per micromole per year in the medical-therapy group, a difference favoring revascularization of 0.06x10(-3) liters per micromole per year (95% confidence interval [CI], -0.002 to 0.13; P=0.06). Over the same time, the mean serum creatinine level was 1.6 micromol per liter (95% CI, -8.4 to 5.2 [0.02 mg per deciliter; 95% CI, -0.10 to 0.06]) lower in the revascularization group than in the medical-therapy group. There was no significant between-group difference in systolic blood pressure; the decrease in diastolic blood pressure was smaller in the revascularization group than in the medical-therapy group. The two study groups had similar rates of renal events (hazard ratio in the revascularization group, 0.97; 95% CI, 0.67 to 1.40; P=0.88), major cardiovascular events (hazard ratio, 0.94; 95% CI, 0.75 to 1.19; P=0.61), and death (hazard ratio, 0.90; 95% CI, 0.69 to 1.18; P=0.46). Serious complications associated with revascularization occurred in 23 patients, including 2 deaths and 3 amputations of toes or limbs. CONCLUSIONS: We found substantial risks but no evidence of a worthwhile clinical benefit from revascularization in patients with atherosclerotic renovascular disease. (Current Controlled Trials number, ISRCTN59586944.)

Comparison of catheters or new arteriovenous fistulas for commencement of haemodialysis in pregnant women with chronic kidney disease: an international observational study.

BACKGROUND: Evidence surrounding vascular access options for commencing dialysis in pregnancy complicated by chronic kidney disease (CKD) is limited. Creation of new arteriovenous fistulas (AVFs) in pregnant women is rare. METHODS: Retrospective cohort study of approaches to vascular access in pregnancy in centres in Australia, the United Kingdom (UK) and Canada (2002-2018). RESULTS: Twenty-three women with advanced CKD commenced dialysis in pregnancy (n = 20) or planned to commence (n = 3). Access at dialysis start was a tunnelled catheter (n = 13), temporary catheter (n = 1), AVF created pre-conception but used in pregnancy (n = 3) and AVF created during pregnancy (n = 3). No women commencing dialysis with an AVF required a catheter. No differences in perinatal outcomes were observed comparing AVFs and catheters at dialysis commencement. No AVFs were created in pregnancy in Canadian women. From Australia and the UK, 10 women had a new AVF created in pregnancy, at median gestation 14.5 weeks (IQR 12.5, 20.75). Four women still needed a catheter for dialysis initiation and 3 eventually used the new AVF. Six AVFs were successfully used in pregnancy at median gestation 24 weeks (IQR 22.5, 28.5), 2 were successfully created but not used and 2 had primary failure. No catheter-associated complications were identified except one episode of catheter-related sepsis. CONCLUSIONS: Catheter-related complications were minimal. In selected women, with sufficient pre-planning, an AVF can be created and successfully used during pregnancy to minimise catheter use if preferred. Pre-conception counselling in advanced CKD should include discussing vascular access options reflecting local expertise and patient preferences.

Long-Term Transplantation Outcomes in Patients With Primary Hyperoxaluria Type 1 Included in the European Hyperoxaluria Consortium (OxalEurope) Registry.

INTRODUCTION: In primary hyperoxaluria type 1 (PH1), oxalate overproduction frequently causes kidney stones, nephrocalcinosis, and kidney failure. As PH1 is caused by a congenital liver enzyme defect, combined liver-kidney transplantation (CLKT) has been recommended in patients with kidney failure. Nevertheless, systematic analyses on long-term transplantation outcomes are scarce. The merits of a sequential over combined procedure regarding kidney graft survival remain unclear as is the place of isolated kidney transplantation (KT) for patients with vitamin B6-responsive genotypes. METHODS: We used the OxalEurope registry for retrospective analyses of patients with PH1 who underwent transplantation. Analyses of crude Kaplan-Meier survival curves and adjusted relative hazards from the Cox proportional hazards model were performed. RESULTS: A total of 267 patients with PH1 underwent transplantation between 1978 and 2019. Data of 244 patients (159 CLKTs, 48 isolated KTs, 37 sequential liver-KTs [SLKTs]) were eligible for comparative analyses. Comparing CLKTs with isolated KTs, adjusted mortality was similar in patients with B6-unresponsive genotypes but lower after isolated KT in patients with B6-responsive genotypes (adjusted hazard ratio 0.07, 95% CI: 0.01-0.75, P = 0.028). CLKT yielded higher adjusted event-free survival and death-censored kidney graft survival in patients with B6-unresponsive genotypes (P = 0.025, P < 0.001) but not in patients with B6-responsive genotypes (P = 0.145, P = 0.421). Outcomes for 159 combined procedures versus 37 sequential procedures were comparable. There were 12 patients who underwent pre-emptive liver transplantation (PLT) with poor outcomes. CONCLUSION: The CLKT or SLKT remains the preferred transplantation modality in patients with PH1 with B6-unresponsive genotypes, but isolated KT could be an alternative approach in patients with B6-responsive genotypes.

Comparison of Medium-term Outcomes of Living Kidney Donors With Longitudinal Healthy Control in the United Kingdom.

BACKGROUND: Understanding the outcomes and risks for live kidney donors (LD) is increasingly important; this study investigated all-cause mortality and morbidity outcomes of LD compared with a healthy cohort. METHODS: Live donor dataset was obtained from the UK Transplant Registry and a comparator nondonor cohort selected from The Health Improvement Network (THIN) database, a UK primary healthcare database. All LD from January 1, 2001, to December 31, 2013, were included, with follow-up until December 31, 2016. RESULTS: There were 9750 LD and 19 071 THIN participants. Median follow-up (interquartile range) for LD was 8.4 (6.0-11.3) years and for THIN was 5.4 (2.6-8.5) years. In up to 15 years, follow-up end-stage renal disease was observed in 1 LD versus 7 THIN (P = 0.280). Nine LD had estimated glomerular filtration rate of <30 mL/min/1.73 m versus 43 in THIN (P = 0.012), but no statistically significant difference in adjusted logistic regression analyses. Risk of diabetes mellitus, depression, and cardiovascular disease was significantly higher for THIN cohort in adjusted analyses. The risk of hypertension was higher for LD at 5 years but was not significantly different in fully adjusted analyses at 10 years. There were 68 deaths in LD and 485 in THIN over the follow-up period, with significant difference in mortality favoring LD (P < 0.001). CONCLUSIONS: The medium-term morbidity and mortality outcomes of live donors in comparison with a healthy cohort suggest that live donation is not associated with excess mortality, end-stage renal disease, or morbidity, in at least 10 years follow-up.