Live Kidney Research Articles

Early Complications in Kidney Donors and Course of Health-related Quality of Life 12 mo After Donation: An Analysis of the Swiss Organ Living-Donor Health Registry.

Since 1998, the Swiss Organ Living-Donor Health Registry (SOL-DHR) has recorded peri- and postoperative complications of living kidney (LK) donors, as reported by all Swiss transplant centers and has collected follow-up data prospectively. We analyzed the early complications of 2379 consecutive individuals who donated a kidney between January 1998 and June 2022 and assessed their health-related quality of life (HRQoL) 1 y after donation. In total, 447 early complications in 404/2379 LK donors (17.0%) were reported to the SOL-DHR. The frequency of donors with major complications (ie, Dindo-Clavien classification 3/4) was 2.4%. In total, 31 donors needed reoperation, and in 13/31 (42%), donors reoperation was necessary because of bleeding complications. Independent risk factors for major early complications were older donor age (P = 0.005) and type of surgical approach (ie, the laparoscopic retroperitoneal compared with laparoscopic transabdominal surgery; P = 0.01), but not sex. We observed a U-shaped association of body mass index, where very low/high body mass indexes had higher odds of major early complications, without reaching statistical significance. Although HRQoL was affected by kidney donation, 96.5% of donors indicated that they would donate their kidney again. The only independent risk factor for low HRQoL based on mental health scores was worsening EB after living kidney donation (P < 0.0001). Overall, living kidney donation is a safe procedure, however, donor age and type of surgical approach affect the risk of complications. A decline in emotional bonding with the recipient after donation may worsen the quality of life of the donor.

Immediate Impact of the COVID-19 Pandemic on Heart and Kidney Transplantation andtheRecovery Trends in 30 Developed andLess-Developed Countries.

BACKGROUND The COVID-19 pandemic had multifaceted and disproportionate impacts on various countries. We investigated the decline of heart and kidney transplantation in 2020 and recovery trends in 2020, 2021, and 2022 in 30 developed and developing countries, considering COVID-19 incidence and mortality and pandemic-time economic variables. MATERIAL AND METHODS Data were obtained from reliable open databases. Nations were grouped by hierarchical cluster analysis into high-gross domestic product (GDP), mid-GDP, and low-GDP countries. Expected transplant numbers for 2020 to 2021 were estimated by the artificial neural network method using data from 2015 to 2019. Effect size and its inference were determined through the Hodges-Lemann estimate and Wilcoxon signed-rank test, respectively. The possible disproportionate effect was estimated by the Jonckheere-Tersptra test. Associations between transplantation and economic variables, COVID-19 caseload, and mortality were examined using Kendall rank correlation analysis. RESULTS All nations experienced a decline in 2020 and some real recovery in 2020 to 2022. For high-GDP countries, decline was insignificant and recovery was marginal; for mid-GDP countries, decline was significant for heart and deceased kidneys and recovery was modest; for low-GDP countries, decline was significant for heart, live kidneys, and deceased kidneys and recovery was marginal. The low-GDP countries were disproportionally negatively impacted, although the associations between the impact and economic variables, COVID-19 incidence, and COVID-19 mortality were statistically insignificant. CONCLUSIONS More inclusive studies of socioeconomic and cultural factors that affected the impact of the COVID-19 pandemic in different countries can be useful for better preparedness and reducing disruption in healthcare in future global pandemics.

An early experience on the effect of solid organ transplant status on hospitalized COVID-19 patients.

We compared the outcome of COVID-19 in immunosuppressed solid organ transplant (SOT) patients to a transplant naïve population. In total, 10356 adult hospital admissions for COVID-19 from March 1, 2020 to April 27, 2020 were analyzed. Data were collected on demographics, baseline clinical conditions, medications, immunosuppression, and COVID-19 course. Primary outcome was combined death or mechanical ventilation. We assessed the association between primary outcome and prognostic variables using bivariate and multivariate regression models. We also compared the primary endpoint in SOT patients to an age, gender, and comorbidity-matched control group. Bivariate analysis found transplant status, age, gender, race/ethnicity, body mass index, diabetes, hypertension, cardiovascular disease, COPD, and GFR <60mL/min/1.73m2 to be significant predictors of combined death or mechanical ventilation. After multivariate logistic regression analysis, SOT status had a trend toward significance (odds ratio [OR] 1.29; 95% CI 0.99-1.69, p=.06). Compared to an age, gender, and comorbidity-matched control group, SOT patients had a higher combined risk of death or mechanical ventilation (OR 1.34; 95% CI 1.03-1.74, p=.027).

Monitoring Hydrogen Peroxide (H2O2) in live kidneys by Multiphoton Microscopy and genetically encoded probes

Hydrogen Peroxide (H2O2) is an important physiological factor in the control of renal function. In the kidney, H2O2 is enhanced in some forms of hypertension and in diabetes, where it may play a role in renal damage. We previously found that H2O2 potently stimulates renin release from mouse juxtaglomerular (JG) cells. While all cells have the capacity to produce H2O2, the relative production levels in the different cell types of the kidney cortex (glomeruli vs proximal tubules vs JG cells), is not clear. Most H2O2 measurements have been performed ex‐vivo or in isolated renal cells, but few measurements of H2O2 have been performed in vivo. To begin addressing this, we used a genetically encoded H2O2 sensor named HyPer and multi‐photon (MP) microscopy imaging of the live mouse kidney. Before using HyPer in vivo, experiments were conducted in cultured cells expressing HyPer to determine the best wavelength for MP excitation and emission, by monitoring the increase in fluorescence after addition of H2O2. Then, HyPer was transduced into the renal cortex by subcapsular infusion of a plasmid, for 7 days. After transduction, mice were anesthetized with isoflurane, the left kidney exteriorized and a carotid cannula for infusion was placed. The renal cortical vasculature and glomeruli were visualized by using Rhodmaine‐R18 simultaneously with HyPer Imaging. We observed strong HyPer fluorescence primarily in proximal tubules, and in a few cases inside glomeruli. We then tested the ability of PEG‐Catalase plus the H2O2 scavenger Ebselen to decrease the HyPer signal in proximal tubules. After finding a region to image, baseline measurements were obtained for 5 minutes at 15 sec intervals, and then Catalase/Ebselen was infused into the carotid artery. Fluorescence was monitored for another 25 minutes. We observed a steady decrease in fluorescence over time that reached 35±5% after 20 minutes (p&lt;0.05, n=3), suggesting a decrease in H2O2. Monitoring H2O2 in specific cell types can be performed by using cell‐selective promoters to drive expression of HyPer. To monitor H2O2 in JG cells we generated adenoviruses encoding HyPer under control of the Ren1 (renin 1) promoter. Renal subcapsular catheters were used to infuse adenoviruses for 7 days. MP imaging was performed to locate glomeruli expressing Hyper in the afferent arteriole or glomerular pole. After finding this, baseline measurements were performed for five minutes and the Catalase/Ebselen was infused. We observed a steady decrease in fluorescence over time that reached 33±7% after 20 minutes (p&lt;0.05, n=3), suggesting a decrease in H2O2 in JG cells expressing HyPer. We conclude that HyPer can be used to monitor and compare H2O2 levels in different cell types in the kidney cortex by using cell‐type specific promoters and MP microscopy. This method should allow the comparison of H2O2 levels in renal cortical cell types between different strains or during pathological conditions in live animals.Support or Funding InformationNIH 5R03DK105300‐03 to MMThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Multivariate Analysis of Health-related Quality of Life in Donors After Live Kidney Donation

BackgroundLive-kidney donation has a low mortality rate. Evidence suggests that live-kidney donors experience a quality of life (QoL) comparable to or even superior to that of the general population. There is limited information on factors associated with a decrease in QoL in particular for baseline factors, which would improve information to the donor, donor selection, and convalescence. MethodsQoL data on 501 live donors included in three prospective studies between 2001 and 2010 were used. The 36-item short form health survey (SF-36) was used to measure QoL up to 1 year after the procedure. Longitudinal effects on both the mental (MCS) and physical component scales (PCS) were analyzed with multilevel linear regression analyses. Baseline variables were age, gender, body mass index (BMI), pain, operation type, and comorbidity. Other covariates were loss of the graft, glomerular filtration rate, and recipient complications. ResultsAfter 1 year we observed a small decrease in PCS (effect size = −0.24), whereas the MCS increased (effect size = 0.32). Both PCS and MCS were still well above the norm of the general Dutch population. Factors associated with a change in PCS were BMI (Cohen's d = −0.17 for 5 BMI points) and age (d = −0.13 for each 10 years older). ConclusionsOverall, QoL after live-donor nephrectomy is excellent. A lowered PCS is related to age and body weight. Expectations towards a decreased postoperative QoL at 1 year are unjustified. However, one should keep in mind that older and obese donors may develop a reduced physical QoL after live-kidney donation.

Incidental nephrolithiasis in live related kidney donors: Epidemiology; long-term outcome of donor and recipient

Incidental nephrolithiasis in live related kidney donors: Epidemiology; long-term outcome of donor and recipient

Preliminary study of interactivity between mercury and cells labeled with carboxymethyl chitosan coated quantum dots.

This paper describes the development of a simplified and rapid method for the aqueous synthesis of quantum dots (QDs) with CdTe cores and gradient CdS external shells (CdTe/CdS QDs) aided by microwave irradiation. In order to improve the biocompatibility of the CdTe/CdS QDs, these QDs were then interacted with carboxymethyl chitosan (CMC) so as they could be used as fluorescent probes in the aqueous phase. As fluorescent probes, these modified QDs were successfully used for imaging live Madin-Darby canine kidney (MDCK) cells. Then mercury was incubated with the micro-system formed by quantum dots labeled MDCK. Fluorescence quenching was occurred in the micro-system after 24 h. The micro-system's fluorescence quenching caused by mercury(II) was consistent with the fluorescence quenching equation and displayed a good linearity between the quenched fluorescence intensity of mercury(II). The preliminary results indicated that this micro-system can be used for detection of trace amounts of mercury in vivo and interaction process investigation between mercury and cells.

HOW TO IMPLEMENT IMMUNOADSORPTION IN A POLYVALENT DIALYSIS UNIT: A REVIEW

Many kidney-transplant candidates have anti-HLA alloantibodies (HLAi): these make transplantation difficult, even from a living kidney (LK) donor, because of the presence of donor-specific anti-HLA alloantibodies. Due to the shortage of deceased kidney donors, the number of LK transplants is increasing, but is potentially limited by ABO incompatibility (ABOi). To make ABOi and/or HLAi patients suitable for kidney transplantation they need to be desensitised: this strategy is mainly based on rituximab therapy combined with either plasmapheresis (PP) or immunoadsorption (IA). IA can be more efficient than PP because greater plasma volumes can be treated within a single session than a PP session (>4 vs. 1.5-2). IA can be specific (ABOi setting) or non-specific (HLAi). We describe how we designed and implemented a desensitisation programme based on IA. This was started in the first trimester of 2010 within the Acute Polyvalent Haemodialysis and Apheresis Unit in Toulouse University Hospital, France. So far, we have performed >200 IA sessions with good results. The IA sessions were associated with a net body-weight gain of ∼1 kg. Normally, IA is performed first and then haemodialysis on the same or next day; however, we have been able to, for the first time, couple IA with haemodialysis. Moreover, we can now carry out this procedure 24 hours a day, seven days a week. This procedure has improved patient care and reduced costs. The IA desensitisation programme has enabled successful transplantation in 24 patients to date.

A method to facilitate and monitor expression of exogenous genes in the rat kidney using plasmid and viral vectors

Gene therapy has been proposed as a novel alternative to treat kidney disease. This goal has been hindered by the inability to reliably deliver transgenes to target cells throughout the kidney, while minimizing injury. Since hydrodynamic forces have previously shown promising results, we optimized this approach and designed a method that utilizes retrograde renal vein injections to facilitate transgene expression in rat kidneys. We show, using intravital fluorescence two-photon microscopy, that fluorescent albumin and dextrans injected into the renal vein under defined conditions of hydrodynamic pressure distribute broadly throughout the kidney in live animals. We found injection parameters that result in no kidney injury as determined by intravital microscopy, histology, and serum creatinine measurements. Plasmids, baculovirus, and adenovirus vectors, designed to express EGFP, EGFP-actin, EGFP-occludin, EGFP-tubulin, tdTomato-H2B, or RFP-actin fusion proteins, were introduced into live kidneys in a similar fashion. Gene expression was then observed in live and ex vivo kidneys using two-photon imaging and confocal laser scanning microscopy. We recorded widespread fluorescent protein expression lasting more than 1 mo after introduction of transgenes. Plasmid and adenovirus vectors provided gene transfer efficiencies ranging from 50 to 90%, compared with 10-50% using baculovirus. Using plasmids and adenovirus, fluorescent protein expression was observed 1) in proximal and distal tubule epithelial cells; 2) within glomeruli; and 3) within the peritubular interstitium. In isolated kidneys, fluorescent protein expression was observed from the cortex to the papilla. These results provide a robust approach for gene delivery and the study of protein function in live mammal kidneys.

Clinical pathways in transplantation: a review and examples from Beth Israel Deaconess Medical Center

Clinical pathways (CP) have been developed to aid in the management of many surgical and medical conditions. Studies show the benefits of CP on outcomes including reduction in length of stay (LOS), morbidity, costs, and improvement in patient satisfaction (Arch Surg 2008: 394: 31; J Eval Clin Pract 2007: 13: 920; Arch Otolaryngol Head Neck Surg 2000: 126: 322; Circulation 2000: 101: 461; BMC Pulm Med 2006: 6: 22; Int J Health Care Qual Assur 2006: 19: 237; Am J Med Qual 2005: 20: 83; Am J Surg 2006: 192: 399; Am Surg 2005: 71: 152). Reports of CP in solid organ transplantation are lacking, possibly given the complexity of the transplant procedures that entail a complex, multidisciplinary pre-operative evaluation, inpatient, and post-operative time frames. We have developed CP from presentation for transplant evaluation to post-transplant follow-up for liver, kidney, and pancreas transplantation and live kidney and live liver donation and are making them available online for viewing. Our CPs encompass the pre-operative, peri-operative, and post-operative period, including both outpatient and inpatient care. We propose that transplantation is an ideal forum for successful implementation of CP, given the rigorous process that centers are subject to for CMS approval and the ample opportunity for improving our patients' lives by improvement in and streamlining of the entire process of clinical care from end-stage organ failure to post-transplant long-term management. Our CPs can be found at http://bidmc.org/CentersandDepartments/Departments/TransplantInstitute/TransplantClinicalPathways.aspx.

Post-Renal Biopsy Nephro-Cutaneous Fistula: A Very Rare Complication After Transplant and Management Options

Abstract Case History: A 30-year-old man underwent live related kidney transplant. Postoperative urine output was about 150 mL/hour with persistently high creatinine of 4.5 mg%. Renal biopsy was do...

FGF-23 IS ASSOCIATED WITH PTH IN LIVING KIDNEY DONORS AFTER NEPHRECTOMY.

FGF-23 IS ASSOCIATED WITH PTH IN LIVING KIDNEY DONORS AFTER NEPHRECTOMY.

A prospective study of quality of life of live related kidney donors

A prospective study of quality of life of live related kidney donors

Living Donor Kidney Transplantation: Analysis of the First 40 Cases Performed in UZ Leuven

Living donation kidney transplantation has been popular worldwide to try to increase the donor pool. In Belgium, the rate of living donation kidney transplantation has been traditionally relatively low compared to other countries. This is - in part - due to the relatively higher cadaveric organ offer that is available in Belgium (around 25 donors per million inhabitants), compared to other countries. However, the increasing waiting times on cadaveric waiting list and the superiority of the results of live donation versus cadaveric kidney transplantation have led to a reappraisal of this strategy. In our center a living donation kidney transplant programme was started in 1997. Since then 40 cases of live donation kidney transplantation have been performed and are reported herein.

Evaluation of ultrasound tissue damage based on changes in image echogenicity in canine kidney

Sufficiently high intensity ultrasound can create hyperechoic regions in an ultrasound image due to local bubble generation. We explore the link between the temporal extent of these hyperechoic regions and tissue damage caused by ultrasound therapy. The decay rate of increased echogenicity from the focal zone in insonated live exteriorized canine kidney was quantified and correlated to the spatial extent of tissue damage. The decay half-time, t(half), defined as the time for echogenicity enhancement to decay by a factor of 2, was observed in all cases to be greater than 41 s in spatial zones in which extensive histological damage was observed. In cases in which the measured thalf was less than 11 s, the damage was limited to minor hemorrhage, or it was not detected. These t(half) discrimination boundaries of 41 and 11 s were not statistically different for cases in which contrast agent was used to enhance therapeutic efficiency. This was true even though contrast agent infusion significantly reduced the therapy pulse duration threshold for damage production.

Bone mineral density in live related kidney transplant children and adolescents.

Successful kidney transplantation corrects many of the metabolic abnormalities associated with development of renal osteodystrophy, but despite a well-functioning graft, osteopenia, remains prevalent in adult and pediatric kidney recipients. The factors that affect the bone mineral density (BMD) and the long term course of BMD after transplantation in children is still unknown. We performed a cross sectional study to determine BMD in 83 recipients who received living renal allotransplants in Mansoura Urology & Nephrology Center between 1981 and 2002 (mean age at transplantation 13.2 +/- 3.1 years) by dual energy x-ray absorptiometry at various time intervals up to 16 years after transplantation (mean duration after transplantation was 48 +/- 34 months, range 12-192 months). The mean +/- SD for BMD was -2.28 +/- 2.06 for lumbar 2-4 spine and -1.44 +/- 1.44 for the total body BMD as corrected for body surface area. Osteopenia/osteoporosis were present in about two thirds of our kidney transplant recipients. The significant risk factors for osteopenia/osteoprosis using univariate analysis were the cyclosporine based immunosuppressive regimen, cumulative dose of steroids/m2 surface area, graft dysfunction and the urinary deoxypyridinoline. Using logistic regression analysis the cumulative steroid dose/m2 surface area and the urinary deoxypyridinoline were the major significant predictors for bone loss. In conclusion, osteopenia and osteoprosis are common in pediatric and adolescent renal transplant patients. The cumulative steroid dose and the urinary deoxypyridinoline were the major predictors for bone loss.

Electron paramagnetic resonance imaging of nitric oxide organ distribution in lipopolysuccaride treated mice.

The recent development of electron paramagnetic resonance (EPR) permits its application for in vivo studies of nitric oxide (NO). In this study, we tried to obtain 3D EPR images of endogenous NO in the abdominal organs of lipopolysuccaride (LPS) treated mice. Male ICR mice, each weighing about 30 g, received 10 mg/kg of LPS intraperitoneally. Six hours later, a spin trapping reagent comprised of iron and an N-dithiocarboxy sarcosine complex (Fe(DTCS)2, Fe 200 mM, DTCS/Fe = 3) were injected subcutaneously. Two hours after this treatment, the mice were fixed in a plastic holder and set in the EPR system, equipped with a loop-gap resonator and a 1 GHz microwave. NO was detected as an NO-Fe(DTCS)2 complex, which had a characteristic 3-line EPR spectrum. NO-Fe(DTCS)2 complexes in organ homogenates were also measured using a conventional X-band EPR system. NO-Fe(DTCS)2 spectra were obtained in the upper abdominal area of LPS treated mice at 8 h after the LPS injection. 3D EPR tiled and stereoscopic images of the NO distribution in the hepatic and renal areas were obtained at the same time. The NO-Fe(DTCS)2 distribution in abdominal organs was confirmed in each organ homogenate using conventional X-band EPR. This is the first known EPR image of NO in live mice kidneys.

A Comparative Study of Methods of Estimating Renal Size in Normal Adults

One hundred live related voluntary kidney donors were studied prospectively. During donor nephrectomy the actual kidney bipolar length was measured and compared to the renal bipolar length estimated from abdominal sonogram, abdominal plain X-ray, intravenous pyelogram, and renal angiogram. Ultrasound was found to measure the kidney more accurately (mean difference between estimated size and actual = -3.4 mm +/- SD 6.96), than plain X-ray (mean difference from actual 13mm +/- SD 5.24), IVP (mean difference from actual 16.9 mm +/- SD 5.74), and renal angiogram (mean difference from actual 15.2 mm +/- SD 5.77).

Effects of polychlorinated biphenyls on poultry

Abstract ‘Aroclor 1254’ was fed to laying pullets at 0, 0.1, 1, 10, and 100 mg per kg of diet. After 24 weeks the concentration of total polychlorinated biphenyls in body fat was 11–17 times the dietary level and the relative concentrations in body fat, liver, muscle, and whole eggs were 40, 4, 1, and 1, respectively. The concentration in body fat and in eggs was reduced to one half 14 weeks and 6 weeks respectively after withdrawal of the treated diet. Live body weights, brain, kidney, and egg weights, and eggshell thickness were unaffected. High doses generally increased liver and heart weights. Egg production and hatchability were reduced at higher doses. No signs of toxicity were observed. The use of local meat meal and fish meal in a mash is not likely to result in any significant accumulation of polychlorinated biphenyls in poultry products.

Effect of change in flow rate upon renal vascular resistance.

The effect of changing renal flow rate upon renal vascular resistance has been studied in 82 anesthetized dogs. Resistance decreased and then increased as a function of blood flow rate. The onset of the increase in resistance was more dependent upon flow rate than arterial pressure. These relationships were unaltered by section of renal nerves, infusion of phentolamine, infusion of phentolamine and eserine and ventilation with 20% CO2. The increase in resistance remained following decapsulation but began at lower levels of flow rate and pressure. The increase in resistance was absent during perfusion with blood when dextran was intermittently used as the perfusate, during perfusion with dextran in live or dead kidneys and during perfusion with blood in dead kidneys. Elevation of arterial pressure failed to greatly elevate the flow rate of renal lymph. These observations indicate that the increase in resistance results from active vasoconstriction initiated by some local mechanism which is independent of nerves, circulating adrenalines, CO2 tension and [H+]. The mechanism likely is activated by change in flow rate.