Single Kidney Research Articles

Forecasting of Patient-Specific Kidney Transplant Function With a Sequence-to-Sequence Deep Learning Model

Like other clinical biomarkers, trajectories of estimated glomerular filtration rate (eGFR) after kidney transplant are characterized by intra-individual variability. These fluctuations hamper the distinction between alarming graft functional deterioration or harmless fluctuation within the patient-specific expected reference range of eGFR. To determine whether a deep learning model could accurately predict the patient-specific expected reference range of eGFR after kidney transplant. A multicenter diagnostic study consisted of a derivation cohort of 933 patients who received a kidney transplant between 2004 and 2013 with 100 867 eGFR measurements from University Hospitals Leuven, Belgium, and 2 independent test cohorts: with 39 999 eGFR measurements from 1 170 patients, 1 from University Hospitals Leuven, Belgium, receiving transplants between 2013 and 2018 and 1 from Hannover Medical School, Germany, receiving transplants between 2003 and 2007. Patients receiving a single kidney transplant, with consecutive eGFR measurements were included. Data were analyzed from February 2019 to April 2021. In the derivation cohort 100 867 eGFR measurements were available for analysis and 39 999 eGFR measurements from the independent test cohorts. A sequence-to-sequence model was developed for prediction of a patient-specific expected range of eGFR, based on previous eGFR values. The primary outcome was the performance of the deep learning sequence-to-sequence model in the 2 independent cohorts. In this diagnostic study, a total of 933 patients in the training sets (mean [SD] age, 53.5 [13.3] years; 570 male [61.1%]) and 1170 patients in the independent test sets (cohort 1 [n = 621]: mean [SD] age, 58.5 [12.1] years; 400 male [64.4%]; cohort 2 [n = 549]: mean [SD] age, 50.1 [13.0] years; 316 male [57.6%]) who received a single kidney transplant most frequently from deceased donors, the sequence-to-sequence models accurately predicted future patient-specific eGFR trajectories within the first 3 months after transplant, based on the previous graft eGFR values (root mean square error, 6.4-8.9 mL/min/1.73 m2). The sequence-to-sequence model predictions outperformed the more conventional autoregressive integrated moving average prediction model, at all input/output number of eGFR values. In this diagnostic study, a sequence-to-sequence deep learning model was developed and validated for individual forecasting of kidney transplant function. The patient-specific sequence predictions could be used in clinical practice to guide physicians on deviations from the expected intra-individual variability, rather than relating the individual results to the reference range of the healthy population.

The method of extracorporeal resection of the kidney in conditions of pharmaco-cold ischemia in kidney cancer with orthotopic renal replantation

BACKGROUND: Increasing the effectiveness of the treatment of patients with kidney cancer is one of the main problems of oncourology. In its solution, great importance is attached to the development of new surgical technologies.
 AIM: The aim of the study to evaluate the results of extracorporeal kidney resection in conditions of pharmaco-cold ischemia with orthotopic renal replantation in kidney cancer patients. Our study is aimed at assessing the results of extracorporeal resection of the kidney under pharmaco-cold ischemia with orthotopic replantation of renal vessels in patients with kidney cancer.
 MATERIALS AND METHODS: 44 patients [of them, 70.5% (n = 31) men and 29.5% (n = 13) women] with kidney cancer were recruited in a study. All patients were treated between 2012 and 2021. The mean age of patients was 55.92 12.6 years. The stage was determined using the TNM system: pT1a-3bN0M0-1 G1-3. 75% (n = 33) of patients had stage pT1a1b; 11.4% (n = 5) pT2a2b, one patient was present with multiple lesions; 13.6% (n = 6) pT3a3b, one patient had up to 15 lesions in a single kidney. Two previously operated patients had cancer of a single kidney with intraluminal invasion. The mean R.E.N.A.L nephrometric score was 10.32 1.34.
 RESULTS: The duration of the surgery was 402.07 83.21 minutes. The duration of cold ischemia was 149.9 53.1 minutes. Blood loss 751.1 633.6 ml. Renal vascular replacement was performed in 13 patients. Postoperative complications II degree according to Clavien Dindo were detected in 36.6% (16) of patients. There was only one lethal outcome due to mesenteric thrombosis at day 4. Disease progressed in 6.8% (n = 3) of cases. The GFR level before surgery was on average 72.3 16.8 ml / (min 1.73 m2), in the early postoperative period 58.7 28.3 ml / (min 1.73 m2), 1 year after surgery 69.4 26.2 ml / (min 1.73 m2). One year after surgery it was 69.4 26.2 mol/l. The follow-up period ranged from 8 to 86 months (on average 58.7 19.1 months).
 CONCLUSIONS: This technique is effective in patients with multiple foci, centrally located and large tumors, for hard-to-reach localizations, as well as in patients with the impossibility of intracorporeal pharmaco-cold ischemia, peculiarities of organ blood supply.

Renal Artery Partial Occlusion After Aortic Dissection Is Associated With Impaired Renal Function in the Affected Kidney

The renal artery is often involved in aortic dissection, leading to kidney ischaemia and renal dysfunction. However, some patients with aortic dissection with combined renal artery involvement do not show clinical renal dysfunction. This study aimed to analyse the relationship between renal artery involvement and renal function. Data and images were collected from 79 patients (Group A), in Beijing Anzhen hospital between January 2015 and December 2017, who had type A aortic dissection, in order to analyse the relationship between renal artery involvement and serum creatinine. In order to further analyse the relationship between renal artery involvement and single kidney function, data from 27 patients (Group B) with aortic dissection from August 2018 to October 2018 were collected. Renal dynamic imaging was conducted, and clinical and image data were recorded. Results showed that patients with one partially occluded renal artery had higher variance of serum creatinine after surgery compared with patients with one false-lumen renal artery (5.8±22.7 μmol/L vs -18.7±22.7 μmol/L; p=0.003). The glomerular filtration rate of a single kidney that had a partially occluded renal artery was lower than that of a single kidney with a normal renal artery (37.77±9.57 vs 42.73±10.54; p=0.04). A partially occluded renal artery in aortic dissection was associated with impaired renal function after surgery, even though patients did not present high serum creatinine. More attention should be paid to those experiencing aortic dissection.

Dosimetric comparison between carbon, proton and photon radiation for renal retroperitoneal soft tissue sarcoma recurrence or metastasis after radical nephrectomy

Objective To compare the dosimetric difference between various modalities in the radiation treatment for renal retroperitoneal soft tissue sarcoma recurrence or metastasis (RRSTSRM) after radical nephrectomy, and assess the dosimetric advantage on protecting the organs at risk (OARs) in the carbon and proton radiotherapy for the patients with a single kidney. Methods A total of 12 patients with RRSTSRM who underwent radical nephrectomy were enrolled in this study. Carbon, proton, and photon radiotherapy were implemented for treatment planning. The prescription dose was fulfilled by simultaneously integrated boosting technique, with giving the planning target volume-1 (PTV-1) 51Gy (RBE) and planning target volume-2 (PTV-2) 60 Gy (RBE). Doses in the patient’s spinal cord, stomach, duodenum, bowel, colon, and contralateral kidney were evaluated. The normal tissue complication probability (NTCP) of the duodenum, bowel, colon, and contralateral kidney was derived under Lyman-Kutcher-Burman (LKB) estimation. Results In the carbon plans, the percentage volume of 95% prescription dose (V95%) covering PTV-1 (PTV-2) was 95.93% ± 3.42% (95.61% ± 4.26%). No significant dosimetric difference on the target was obtained between the four radiation modalities (P > .05). The percentage volume of receiving 40 Gy (RBE) [V40Gy (RBE)] in the duodenum could be reduced from 12.94% ± 15.99% in the IMRT plans to 6.36% ± 8.79% (8.44% ± 12.35%) in the carbon (proton) plans (P < .05). The V40Gy (RBE) in the bowel could be reduced from 13.48% ± 13.12% in the IMRT plans to 7.04% ± 9.32% (7.34% ± 9.89%) in the carbon (proton) plans (P < .05). The mean value of NTCP for the duodenum was 0.43 ± 0.47 (0.45 ± 0.48) by using carbon (proton) radiation. The value was 0.05 (0.03) lower than the IMRT plans on average, with a reduction of 0.20 (0.13) for the patients with lesions <5 mm away from the duodenum. The mean doses of the contralateral kidney were 0.28 ± 0.37 Gy (RBE) [0.28 ± 0.40 Gy (RBE)] in the IMCT (IMPT) plans, which was 92.43% (92.43%) lower than the value in the IMRT plans respectively (P < .05). Conclusion Compared to the conventional radiation techniques, particle radiotherapy of carbon and proton could significantly spare more OARs in the treatment for RRSTSRM after radical nephrectomy. Patients, especially those whose residuals are close to the duodenum would potentially benefit from the particle radiation therapy for RRSTSRM on the decrease in radiation-related side-effect.

First experience of superselective embolization of renal arteries supplying the tumor with subsequent laparoscopic kidney resection

Background. Patients with signs of tumor lesions in a single kidney or in the only one functioning kidney, with bilateral renal tumors are at high risk of functional failure or insufficiency of the kidney after surgery. Joint discussions with specialists in X-ray endovascular surgeries resulted in the development of a treatment algorithm for patients with localized kidney cancer who require organ-sparing surgery without ischemic kidney resection.Objective: to evaluation of the immediate results of two-stage surgical treatment of localized kidney cancer in patients with signs of tumor lesions in a single kidney or in the only one functioning kidney, with bilateral renal tumors, including superselective embolization of the artery supplying the tumor at the first stage, and laparoscopic kidney resection without renal ischemia parenchyma at the second stage.Materials and methods. This study included 5 patients with localized kidney cancer, who underwent two-stage treatment at Moscow Regional Oncology Dispensary between 24.03.2021 and 19.04.2021. The first stage included superselective embolization of the artery supplying the tumor; the second stage implied laparoscopic kidney resection 6-7 days following the first stage.Results. The median age of the patients was 62 years (range: 42-73 years). Four patients (80%) had unilateral kidney lesions, while 1 patient (20 %) had bilateral (synchronous) kidney cancer. The mean RENAL score was 8 (range: 6-10); patients were distributed as follows: score 4-6 in 40 %, score 7-9 in 40 %, and score &gt;10 in 20 % of patients. At the first stage, patients underwent endovascular embolization of the branches of the renal artery. Patients had superselective embolization of either middle (n = 3; 60 %), upper (n = 1; 20 %), or lower (n = 1; 20 %) segmental arteries supplying the tumor. In one of them (20 %), we identified 3 large arterial branches; in another one (20 %), we identified 2 large arterial branches.At the second stage, we performed laparoscopic kidney resection. None of the patients required renal artery clamping, because there was an excellent visualization of the demarcation zone and no significant blood loss. The resection area was sutured in 1 case (20 %). In 2 individuals (40 %), a hemostatic sponge was installed in the removed tumor bed. In the remaining 2 cases (40 %), hemostasis was ensured by coagulation. The median blood loss was 100 mL (range: 50-200 mL). The postoperative period was uneventful in all patients. None of the patients developed symptoms of acute renal failure.Conclusion. Thus, superselective embolization of arteries supplying a kidney tumor has undeniable advantages in organ-sparing surgeries for patients with localized kidney cancer and some additional kidney problems, when organ preservation is crucial for patient's life.

Long-term survival benefit from dual kidney transplantation using kidneys from donors with very extended criteria-a French cohort between 2002 and 2014.

This national multicentre retrospective cohort study aimed to assess the long-term outcomes of dual kidney transplantation (DKT) and compare them with those obtained from single kidney transplantation (SKT). Our first analysis concerned all first transplants performed between May 2002 and December 2014, from marginal donors, defined as brain death donors older than 65 years, with an estimated glomerular filtration rate (eGFR) lower than 90mL/min/1.73 m2. The second analysis was restricted to transplants adequately allocated according to the French DKT program based on donor eGFR: DKT for eGFR between 30 and 60, SKT for eGFR between 60 and 90mL/min/1.73 m2. Recipients younger than 65 years or with a panel-reactive antibody percentage≥25% were excluded. The first analysis included 461 DKT and 1131 SKT. DKT donors were significantly older (77.6 versus 74 years), had a more frequent history of hypertension and a lower eGFR (55.1 versus 63.6mL/min/1.73 m2). While primary nonfunction and delayed graft function did not differ between SKT and DKT, 1-year eGFR was lower in SKT recipients (39versus 49mL/min/1.73 m2, P<0.001). Graft survival was significantly better in DKT, even after adjustment for recipient and donor risk factors. Nevertheless, patient survival did not differ between these groups. The second analysis included 293 DKT and 687 SKT adequately allocated with donor eGFR and displayed similar results but with a smaller benefit in terms of graft survival. In a context of organ shortage, DKT is a good option for optimizing the use of kidneys from very expanded criteria donors.

Nephrolithiasis (part 2): Diagnosis, management and prevention of recurrent nephrolithiasis

Work-up of patients with calcium oxalate stones should be restricted to those who have multiple episodes (50% of stone formers). There are exceptions, such as pilots, fire-workers, people in the armed forces, those with a single kidney and children (&lt;19 years old). The most important aspect of therapy is to correct dietary aberrations, i.e. the ‘clinic effect’. The four golden rules to correct dietary influences are to maintain an adequate 24-hour urine volume, to restrict salt intake, to avoid red meat and to avoid a diet high in oxalate. In particular, Ceylon tea is contraindicated, as it contains excess oxalate. Drink coffee instead. In patients with hypocitraturia, the drug of choice is potassium citrate, which is the only acceptable urinary alkaliser. Other preparations, such as Urolyte-U, Citrosoda, etc., all have a high sodium content, which will influence urinary calcium excretion. In patients with ongoing hypercalciuria, thiazides are contraindicated in the management of recurrent calcium oxalate stones, and indapamide is the drug of choice. The treatment and follow-up are lifelong. In addition, poor adherence to treatment, coupled with repeated urological procedures, may result in renal functional deterioration and even occasionally renal failure.

Small donors for small recipients - excellent growth and long-term function of single kidney grafts.

Small-donor kidneys (≤20kg donor weight, SDK) are preferably transplanted en bloc in adults. Concerns about thrombotic complications or hyperfiltration hinder their use in children, particularly as single grafts. Low centre experience and donor-to-recipient size are rated critical regarding outcomes. We evaluated SDK transplantation (SDTx) in paediatric recipients at a specialized transplant centre. Between 2008 and 2018, SDTx was performed in 40 children (mean age 5.4±1.4years, single grafts n=38, donor weight ≤10kg: n=10). Perioperative complications were rare (n=3), mainly thromboses despite immediate heparinization and resulted in graft loss in one patient. Overall, early and long-term GFR were excellent (76±21 and 100±11ml/min/1.73m2 , first month and year 5, respectively). Three patients presented with delayed graft function. Graft volume increased significantly (69±38 vs. 111±33ml within 5years; P<0.0001). Patients showed catch-up growth to normal range (SDS for height -2.06±1.6 to -1.60±1.5). Stratification by recipient age and donor weight revealed superior results in young recipients (≤3years) and ≤10kg donors, respectively. Outcome of single SDK grafts was excellent. Gain of GFR and graft volume was even higher in patients with very small donor or recipient size, regardless of a reduced donor-to-recipient weight ratio. Therefore, SDTx should be considered favouring small paediatric recipients.

Recommending exercise for children with a single kidney.

Recommending exercise for children with a single kidney.

Encouraging outcomes of using a small-donor single graft in pediatric kidney transplantation.

The use of small pediatric kidneys as single graftsfor transplantation is controversial, due to the potential risk for graft thrombosis and insufficient nephron mass. Aiming to test the benefits of transplanting these kidneys, 375 children who underwent kidney transplantation in a single center were evaluated: 49 (13.1%) received a single graft from a small pediatric donor (≤ 15kg, SPD group), 244 (65.1%) from a bigger pediatric donor (> 15kg, BPD group), and 82 (21.9%) from adult living donors (group ALD). Groups had similar baseline main characteristics. After 5years of follow-up, children from the SPD group were comparable to children from BPD and ALD in patient survival (94%, 96%, and 98%, respectively, p = 0.423); graft survival (89%, 88%, and 93%, respectively, p = 0.426); the frequency of acute rejection (p = 0.998); the incidence of post-transplant lymphoproliferative disease (p = 0.671); the odds ratio for severely increased proteinuria (p = 0.357); the rates of vascular thrombosis (p = 0.846); and the necessity for post-transplant surgical intervention prior to discharge (p = 0.905). The longitudinal evolution of eGFR was not uniform among groups. The three groups presented a decrease in eGFR, but the slope of the curve was steeper in ALD children. At 5years, the eGFR of the ALD group was 10ml/min/1.73m2 inferior to the others. At that time, the eGFR from the SPD group was statistically similar to the BPD group (p = 0.952). In a specialized transplant center, the use of a single small pediatric donor kidney for transplantation is as successful as bigger pediatric or adult living donors, after 5years of follow-up. A higher resolution version of the Graphical abstract is available as Supplementary information.

Hemodynamics and functional state of the contralateral kidney in the early postoperative period after surgical treatment of kidney cancer

AIM: To study the hemodynamics and functional state of the renal tissue of the contralateral kidney in the early postoperative period after surgical treatment of kidney cancer.&#x0D; MATERIALS AND METHODS: The prospective study included 58 patients with renal cell carcinoma, 36 (62.1%) of whom underwent radical nephrectomy, and 22 (37.9%) underwent partial nephrectomy. Tumor sizes ranged from 1.0 to 12.0 cm. All patients before surgery and in the early postoperative period underwent ultrasound examination of the structure and size of the kidneys, Doppler ultrasonography of the renal vessels, biomicroscopy of the bulbar conjunctiva, measured peripheral blood pressure, determined the glomerular filtration rate (GFR) and performed a coagulogram. The control group included 16 healthy adults.&#x0D; RESULTS: In 83.3% of patients after radical nephrectomy and in 13.6% of patients after partial nephrectomy a tendency towards an increase in blood pressure compared with the initial values was noted by the 2-4th day after the operation. By the 5th day after surgery, the volume of the only kidney remaining after radical nephrectomy increased by an average of 4% (from 126.1 1.4 to 131.2 2.1 cm3, p 0.05), while after partial nephrectomy has not changed reliably. After surgery, a decrease in GFR was detected in 34 (58.6%; p 0.05) patients, including after radical nephrectomy (n = 28) up to 73.4 8.2 ml / min / 1.73 m2, after partial nephrectomy (n = 6) up to 98.2 3.4 ml / min / 1.73 m2. Doppler ultrasonography of the vessels of a single kidney in patients after radical nephrectomy showed a moderate increase in linear blood flow, an increase in the resistance index in the main trunk of the renal artery, and a decrease in the pulsation index in the segmental and arc arteries. In patients after partial nephrectomy in the contralateral kidney these changes were not observed. When performing biomicroscopy of the bulbar conjunctiva in 83.3% of patients after radical nephrectomy and in 13.6% of patients after partial nephrectomy, changes in the microvasculature were revealed: narrowing of arterioles, expansion of venules, slowing of venular and capillary blood flow. Before the operation and in the early postoperative period, the content of fibrinogen and soluble fibrin-monomer complex in the blood of patients with renal cell carcinoma was significantly higher than in the control group.&#x0D; CONCLUSIONS: In patients with renal cell carcinoma, changes in the contralateral kidney in the early postoperative period after radical nephrectomy are significantly more pronounced than after partial nephrectomy, and are accompanied by changes in systemic and local hemodynamics and kidney function. The results of the study confirm the feasibility of performing organ-preserving surgeries in patients with renal cell carcinoma.

Critical timing of ACEi initiation prevents compensatory glomerular hypertrophy in the remaining single kidney

Increasing evidence suggests that single in kidney states (e.g., kidney transplantation and living donation) progressive glomerulosclerosis limits kidney lifespan. Modeling shows that post-nephrectomy compensatory glomerular volume (GV) increase drives podocyte depletion and hypertrophic stress resulting in proteinuria and glomerulosclerosis, implying that GV increase could serve as a therapeutic target to prevent progression. In this report we examine how Angiotensin Converting Enzyme inhibition (ACEi), started before uninephrectomy can reduce compensatory GV increase in wild-type Fischer344 rats. An unbiased computer-assisted method was used for morphometric analysis. Urine Insulin-like growth factor-1 (IGF-1), the major diver of body and kidney growth, was used as a readout. In long-term (40-week) studies of uni-nephrectomized versus sham-nephrectomized rats a 2.2-fold increase in GV was associated with reduced podocyte density, increased proteinuria and glomerulosclerosis. Compensatory GV increase was largely prevented by ACEi started a week before but not after uni-nephrectomy with no measurable impact on long-term eGFR. Similarly, in short-term (14-day) studies, ACEi started a week before uni-nephrectomy reduced both GV increase and urine IGF-1 excretion. Thus, timing of ACEi in relation to uni-nephrectomy had significant impact on post-nephrectomy “compensatory” glomerular growth and outcomes that could potentially be used to improve kidney transplantation and live kidney donation outcomes.

Outcomes of small pediatric donor kidney transplants according to donor weight.

A small pediatric deceased donor (SPD) weight cutoff whether to transplant as en bloc (EB) or single pediatric (SP) kidney is uncertain. Using UNOS/OPTN data (2000-2019), 27 875 SPDs were divided by (i) EB (11.4%) or SP (88.6%) and (ii) donor weight [≤10 (5.4%), >10-15 (8.3%), >15-18 (3.7%), >18-20 (2.9%), and >20 kg (79.7%)]. SP >20 kg and adult deceased donors (grouped by Kidney Donor Profile Index, KDPI, <30, 30-85, and >85) were used as references. The primary outcome was 10-year graft failure. In SP <10 kg, the hazard ratio (HR) for overall graft failure was 1.64 (1.38-2.20) compared with EB <10 kg, and 1.45 (1.18-1.80) compared with SP >20 kg. In SP >10-15 kg, HR was 1.31 (1.12-1.54) compared with EB >10-15 kg, and 1.04 (0.91-1.18) compared with SP >20 kg. In SP >15 kg, the risk was the same as SP >20 kg. Ten-year overall graft survival of SP 12 kg was comparable to SP >20 kg (62% vs. 57%). Ten-year death censored graft failure of SP >10-15 kg (70%) and SP >15-18 kg (70%) was like the adult donors with KDPI 30-85 (67%). In conclusion, we recommend single kidney transplants from SPDs with weight >12 kg to adult recipients in centers with experience in SPD transplants to optimize organ utilization.

Hypercalcemia is a frequent side effect of 13-cis-retinoic acid treatment in patients with high-risk neuroblastoma.

13-cis-Retinoic acid (13-cisRA) is used as a postconsolidation treatment in patients with high-risk neuroblastoma. Hypercalcemia is a known side effect of retinoids. Frequency, symptoms, treatment, and risk factors for hypercalcemia were analyzed. Data were retrospectively analyzed for 350 patients registered in the German Neuroblastoma trials NB97 and NB04 who were treated with high-risk protocols-including myeloablative chemotherapy with autologous stem cell transplantation (SCT) or maintenance therapy-and had received 13-cisRA between January 1, 2000 and December 31, 2010. Hypercalcemia was reported in 78 patients (22.3%), and 37 patients (10.6%) developed Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or 4 hypercalcemia. The calcium levels were 2.5-4.6mmol/L (median 3.1mmol/L). Patients with a single kidney were at a higher risk of developing hypercalcemia (p=.001). Regarding postinduction treatment, 69 of 280 patients with SCT (24.6%) and nine of 70 patients without SCT (12.9%) developed hypercalcemia during 13-cisRA treatment (p=.037). Most patients developed hypercalcemia in the first cycle of 13-cisRA, and only in a single cycle. Hypercalcemia symptoms were frequent but moderate. In most patients, treatment with 13-cisRA was continued without dose reduction in subsequent cycles. In this cohort, grades 3 and 4 hypercalcemia were observed more often than previously reported. A single kidney and pretreatment with myeloablative chemotherapy with stem cell transplantation were identified as potential risk factors for the development of hypercalcemia.

Buccal ureteroplasty in a patient with an extended stricture of the proximal ureter of a solitary kidney

Buccal ureteroplasty is considered a rare operation in urology and the indications for its implementation are still not clearly defined. We have described a clinical case of successful replacement of a part of the proximal ureter with a buccal graft in a patient with a single kidney, which was drained for a long time with a nitinol stent, which was subsequently incrustated, which led to the installation of a permanent nephrostomy drainage. The patient had no postoperative complications, the patency of the urinary tract was fully restored.

BSHI/BTS guidance on crossmatching before deceased donor kidney transplantation.

All UK H&I laboratories and transplant units operate under a single national kidney offering policy, but there have been variations in approach regarding when to undertake the pre‐transplant crossmatch test. In order to minimize cold ischaemia times for deceased donor kidney transplantation we sought to find ways to be able to report a crossmatch result as early as possible in the donation process. A panel of experts in transplant surgery, nephrology, specialist nursing in organ donation and H&I (all relevant UK laboratories represented) assessed evidence and opinion concerning five factors that relate to the effectiveness of the crossmatch process, as follows: when the result should be ready for reporting; what level of donor HLA typing is needed; crossmatch sample type and availability; fairness and equity; risks and patient safety. Guidelines aimed at improving practice based on these issues are presented, and we expect that following these will allow H&I laboratories to contribute to reducing CIT in deceased donor kidney transplantation.

A Simplified Model for Heterotopic Heart Valve Transplantation in Rodents.

There is an urgent clinical need for heart valve replacements that can grow in children. Heart valve transplantation is proposed as a new type of transplant with the potential to deliver durable heart valves capable of somatic growth with no requirement for anticoagulation. However, the immunobiology of heart valve transplants remains unexplored, highlighting the need for animal models to study this new type of transplant. Previous rat models for heterotopic aortic valve transplantation into the abdominal aorta have been described, though they are technically challenging and costly. For addressing this challenge, a renal subcapsular transplant model was developed in rodents as a practical and more straightforward method for studying heart valve transplant immunobiology. In this model, a single aortic valve leaflet is harvested and inserted into the renal subcapsular space. The kidney is easily accessible, and the transplanted tissue is securely contained in a subcapsular space that is well vascularized and can accommodate a variety of tissue sizes. Furthermore, because a single rat can provide three donor aortic leaflets and a single kidney can provide multiple sites for transplanted tissue, fewer rats are required for a given study. Here, the transplantation technique is described, providing a significant step forward in studying the transplant immunology of heart valve transplantation.

Quantification of NADH:ubiquinone oxidoreductase (complex I) content in biological samples

Impairments in mitochondrial energy metabolism have been implicated in human genetic diseases associated with mitochondrial and nuclear DNA mutations, neurodegenerative and cardiovascular disorders, diabetes, and aging. Alteration in mitochondrial complex I structure and activity has been shown to play a key role in Parkinson's disease and ischemia/reperfusion tissue injury, but significant difficulty remains in assessing the content of this enzyme complex in a given sample. The present study introduces a new method utilizing native polyacrylamide gel electrophoresis in combination with flavin fluorescence scanning to measure the absolute content of complex I, as well as α-ketoglutarate dehydrogenase complex, in any preparation. We show that complex I content is 19 ± 1 pmol/mg of protein in the brain mitochondria, whereas varies up to 10-fold in different mouse tissues. Together with the measurements of NADH-dependent specific activity, our method also allows accurate determination of complex I catalytic turnover, which was calculated as 104 min−1 for NADH:ubiquinone reductase in mouse brain mitochondrial preparations. α-ketoglutarate dehydrogenase complex content was determined to be 65 ± 5 and 123 ± 9 pmol/mg protein for mouse brain and bovine heart mitochondria, respectively. Our approach can also be extended to cultured cells, and we demonstrated that about 90 × 103 complex I molecules are present in a single human embryonic kidney 293 cell. The ability to determine complex I content should provide a valuable tool to investigate the enzyme status in samples after in vivo treatment in mutant organisms, cells in culture, or human biopsies.

Efficacy and safety of Sodium-Glucose-Transporter-2 inhibitors in kidney transplant patients.

This review discusses current evidence and future perspectives for use of SLT2 inhibitors in kidney transplant recipients (KTRs). Sodium-Glucose-Transporter-2 inhibitors (SGLT2is) lower plasma glucose in patients with type 2 diabetes, and protect against heart failure and progression of chronic kidney disease by a glucose-independent mechanism. Most of the current studies with SGLT2is in kidney transplant patients are however short-term retrospective case studies. These, together with one small randomized clinical trial, show that SGLT2is lower glucose also in KTRs with type 2 diabetes or posttransplant diabetes mellitus. Larger reductions in HbA1c (-0.5 to 1.5% points) are seen only in patients with estimated GFR > 60 ml/min/1.73m2 and HbA1c > 8%. With lower gomerular filtration rate (GFR) or glycated hemoglobin (HbA1c) the glucose-lowering effect is trivial. However, a reduction in body weight, blood pressure and uric acid is also seen, whereas the frequency of side effects (mycotic or urinary tract infections) does not seem to exceed what is seen in nontransplanted patients. Long-term effects on GFR have not been studied in kidney transplanted patients, but SGLT2is induce an early dip in GFR also in these patients. This could signal a beneficial long-term effect on renal hemodynamics. SGLT2is lower glucose safely also in patients with single kidney grafts, but long-term kidney function and patient survival are yet to be explored.

MP48-18 FEMALE PATIENTS WITH LOW-GRADE UPPER TRACT UROTHELIAL CARCINOMA: PRIMARY CHEMOABLATION AND DURABILITY OF RESPONSE IN A SUBGROUP ANALYSIS FROM THE OLYMPUS TRIAL

MP48-18 FEMALE PATIENTS WITH LOW-GRADE UPPER TRACT UROTHELIAL CARCINOMA: PRIMARY CHEMOABLATION AND DURABILITY OF RESPONSE IN A SUBGROUP ANALYSIS FROM THE OLYMPUS TRIAL