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Several scores have been devised for providing a prognosis of outcomes after kidney transplantation. This study is a comprehensive test of these scores in a cohort of deceased donors with kidneys of lower-than-average quality and procurement biopsies. In total, 15 scores were tested on a retrospective cohort consisting of 221 donors, 223 procurement biopsies, and 223 recipient records for performance on delayed graft function, graft function, or death-censored graft loss. The best-performing score for DGF was the purely clinical Chapal score (AUC 0.709), followed by the Irish score (AUC 0.684); for graft function, the Nyberg score; and for transplant loss, the Snoeijs score (AUC 0.630) and the Leuven scores (AUCs 0.637 and 0.620). The only score with an acceptable performance was the Chapal score. Its disadvantage is that knowledge of the cold ischemia time is required, which is not known at allocation. None of the other scores performed acceptably. The scores fared better in discarded kidneys than in transplanted kidneys. Our study shows an unmet need for practical prognostic scores useful at the time of a decision about discarding or accepting deceased donor kidneys of lower-than-average quality in the Eurotransplant consortium. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to identify modifiable risk factors for de novo renal cell carcinoma (RCC) after kidney transplantation in a matched-pair approach matching for unmodifiable factors.Patients and methods: One thousand six hundred fifty-five adults who underwent kidney transplantation in the period 1 January 2000 to 31 December 2012 were analyzed. Patients with RCC after kidney transplantation were matched in a 1:2 ratio with those without RCC using the indication for transplantation, age at transplantation (± 10 years), recipient sex (male/female), number of received transplants, living organ donor transplantation (yes/no), and time of follow-up in days as matching criteria. The paired t test was used to compare continuous variables and the Cochran-Mantel-Haenszel test for categorical variables. Multivariable conditional logistic regression modeling was used to identify independent risk factors for RCC.Results: In matched-pair analysis, a total number of 26 incident cases with RCC after kidney transplantation could be matched. Post-transplant RCC was significantly associated with longer durations of pre-transplant hemodialysis (p = 0.007) and post-transplant immunosuppression with cyclosporine (p = 0.029) and/or mycophenolate mofetil (p = 0.020) and with larger proportions of post-transplant time on mycophenolate mofetil (p = 0.046) and/or prednisolone medication (p = 0.042). Multivariable conditional logistic regression modeling revealed a significant risk increasing multiplicative factor interaction between the duration of pre-transplant dialysis (years) and the time of prednisolone usage (percent/100). Cyclosporine A usage and mycophenolate mofetil usage were also revealed as independent, significant risk factors for RCC development.Conclusions: Longer pre-transplant dialysis, cyclosporine-based protocols and/or intensified immunosuppression with additional mycophenolate mofetil, and larger proportions of time of prednisolone treatment during follow-up increase de novo RCC risk. [ABSTRACT FROM AUTHOR]

Introduction: Predicting outcome after transplantation of marginal kidneys is a challenging task. Donor creatinine or estimated glomerular filtration rate (eGFR) are integral components of the respective risk scores. However, there is uncertainty on which of their values obtained successively during procurement is the most suitable. Material and methods: This is a retrospective study of 221 adult brain death donors with marginal kidneys, transplanted in 223 recipients. We applied logistic regression analysis to investigate the association between initial (at hospital admission), nadir (lowest), zenith (highest) and terminal (at recovery) donor eGFR with primary non‐function (PNF), delayed graft function (DGF), 3‐ and 12‐month graft function and 1‐ and 3‐year patient‐ and death‐censored graft survival. Results: In the multivariate analysis, admission, terminal, and the lowest donor eGFR could most accurately predict DGF. The respective ORs [95% CI] were: 0.875 [0.771–0.993], 0.818 [95% CI: 0.726–0.922] and 0.793 [0.689–0.900]. Although not being significant for DGF (OR 0.931 [95% CI: 0.817–1.106]), the highest eGFR was the best predictor of 3‐month graft function (adjusted b coefficient 1.161 [95% CI: 0.355–1.968]). Analysis of primary nonfunction showed that determination of initial and the highest eGFR proved to be the best predictors. The respective ORs [95% CI] were: 0.804 [0.667–0.968] and 0.750 [0.611–0.919]. There were no differences in the risk associations of each of the four eGFR recordings with patient‐ and graft survival. Conclusion: The various eGFR recordings determined during the procurement process of marginal donors can predict PNF, DGF and 3‐ and 12‐month graft function. Regarding short‐term patient‐ and graft survival, there appears to be impacted by recipient factors rather than donor kidney function. Summary at a glance: Predicting outcomes after transplantation of marginal kidneys is a difficult task. The successive donor creatinine recordings obtained from admission to the hospital until organ recovery associate differently with clinically relevant short‐term endpoints, such as primary non‐function, delayed graft function and graft function up to 1 year. However, one‐ and three‐ year patient‐ and graft survival depend more on recipient‐related factors and less on the donor's kidney function. [ABSTRACT FROM AUTHOR]

Abstract: In Santiago de Chile, the combination of recent urbanization patterns, the growing demand for land, and climate change has created challenges, notably in terms of the amplification of hazard generation and hazard exposure. This paper analyses the changes in land use/land cover, their impact on current flood and heat hazards, and the consequences for dwelling exposure. It adopts a hazard and exposure assessment approach to flood and heat hazard that allows for evaluation of the interlinkages and consequences of interweaving processes of urbanization and climate change in the Metropolitan Region of Santiago de Chile. The results clearly show that loss of green spaces and agricultural land to built-up areas goes hand in hand with the loss of important infiltration, cooling and retention areas, all of which leads to greater hazard exposure. The paper furthermore analyses the exposed population in terms of their material housing conditions. Surprisingly, those who are more likely to live in hazard-prone areas cannot be described exclusively as “the poor”, albeit there are striking differences between flood and heat exposure. [Copyright &y& Elsevier]

Background: Advances in next-generation sequencing (NGS) technologies allow comprehensive studies of genetic diversity over the entire genome of human cytomegalovirus (HCMV), a significant pathogen for immunocompromised individuals.Methods: Next-generation sequencing was performed on target enriched sequence libraries prepared directly from a variety of clinical specimens (blood, urine, breast milk, respiratory samples, biopsies, and vitreous humor) obtained longitudinally or from different anatomical compartments from 20 HCMV-infected patients (renal transplant recipients, stem cell transplant recipients, and congenitally infected children).Results: De novo-assembled HCMV genome sequences were obtained for 57 of 68 sequenced samples. Analysis of longitudinal or compartmental HCMV diversity revealed various patterns: no major differences were detected among longitudinal, intraindividual blood samples from 9 of 15 patients and in most of the patients with compartmental samples, whereas a switch of the major HCMV population was observed in 6 individuals with sequential blood samples and upon compartmental analysis of 1 patient with HCMV retinitis. Variant analysis revealed additional aspects of minor virus population dynamics and antiviral-resistance mutations.Conclusions: In immunosuppressed patients, HCMV can remain relatively stable or undergo drastic genomic changes that are suggestive of the emergence of minor resident strains or de novo infection. [ABSTRACT FROM AUTHOR]

Background Altered immune function in patients with renal failure results in both susceptibility to infection and increased inflammatory response. Invariant natural killer T (iNKT) cells are a conserved, immunoregulatory T lymphocyte subset that responds to lipid antigens with near-immediate cytokine production and cytotoxicity. iNKT cells are required for the antibacterial host response. Whether renal failure and renal replacement therapy alter iNKT cell abundance or phenotype has not been investigated. Methods iNKT cells were studied by flow cytometry in the peripheral blood of patients with acute renal failure, chronic haemo- and peritoneal dialysis (PD), chronic kidney disease and after renal transplantation. Results A very marked reduction in iNKT lymphocytes was found in acute renal failure before the first haemodialysis (HD) session. iNKT cells were depleted in end-stage renal disease patients receiving either HD or PD. iNKT cell depletion was accentuated after an HD session. Lesser degrees were observed in patients with non-dialysis-dependent chronic kidney disease. CD56 and CD161 NK cell marker expression was decreased in renal impairment. CD56+ and CD161+ iNKT cells produced more interferon-γ than negative cells of the same donor. Within the first year after kidney transplantation, the decrease in iNKT cells and their NK cell markers was reverted. Conclusions We describe for the first time that iNKT lymphocytes are reduced in end-stage renal disease and further depleted by HD. iNKT cells are important for early host response including activation of other immune cells and their depletion may contribute to immune dysfunction in renal disease. [ABSTRACT FROM AUTHOR]

Background Although major risk factors for post-transplant diabetes ( PTDM) after kidney transplantation have been identified, a systematic study on the impact of rejection and rejection therapy is missing so far. Methods Five hundred and twenty-six kidney transplant recipients transplanted in the years 2000-2007 were included. PTDM was defined according to WHO guidelines, and patients' data were compared with special attention to protocol and for cause biopsies and rejection therapies. Survival analyses were made for graft loss and patient death. Results 16.7% of all patients developed PTDM. Among common risk factors as higher age, body mass index ( BMI), and others, the factor 'acute cellular rejections' was comparably most relevant with a hazard ratio of 3.7. Consequently, antirejective treatment with steroid pulses and conversion to tacrolimus was the factor with the highest relative risk for the onset of PTDM ( RR 3.5). PTDM itself had no impact on graft or patients' survival, but the decreased graft survival in PTDM patients was dominantly influenced by the higher frequency of acute cellular rejections, and patients' survival was reduced due to higher age. Conclusion Based upon a higher rate of acute rejections (AR), the necessity of frequent antirejective treatments was more relevant for the induction of PTDM than age or BMI. [ABSTRACT FROM AUTHOR]

Background ABO incompatibility is no longer a barrier in kidney transplantation. C4d is frequently positive in ABO-incompatible (iABO) biopsies without further signs of microcirculation injury. This phenomenon is assumed to represent graft accommodation. However, ultrastructural examination of glomerular and peritubular capillary endothelium might reveal subtle endothelial damage. Methods We studied the ultrastructural appearance of the endothelium in 67 biopsies from 21 patients with iABO allografts and compared it with 20 patients (29 biopsies) with ABO-compatible (cABO) grafts with C4d positivity and 25 ABO-compatible control patients (25 biopsies) without serological or histological evidence of humoral rejection (C4d negative). Ten ultrastructural parameters indicative of chronic and acute glomerular and peritubular capillary damage in transmission electron microscopy (TEM) were semi-quantitatively graded and expressed in a sum score. Clinico-pathological data were compared as well as graft function at the time of biopsy and follow-up. Results Ultrastructural parameters did not significantly differ between iABO and controls. In contrast, C4d-positive cABO had the highest TEM sum score (P = 0.001 versus iABO, P = 0.002 versus controls). The sum score did not differ between C4d-positive and C4d-negative iABO but did differ between patients with and without anti-HLA donor-specific antibodies (DSA). Graft function in iABO at the time of biopsy and at follow-up was similar to controls. Conclusions Our ultrastructural observations support the concept of endothelial accommodation in iABO renal transplants. C4d positivity in the ABO-incompatible situation does not indicate injurious activation of the complement cascade and does not seem to impact on the graft function, in contrast to C4d deposition in cABO with antibody-mediated rejection. [ABSTRACT FROM AUTHOR]

Introduction: Severe neurological symptoms in Shiga toxin-producing Escherichia coli infection associated hemolytic-uremic syndrome (STEC-HUS) are often accompanied by none or only mild alterations of cerebral magnetic resonance imaging (MRI). This study aims to analyze if quantitative MRI is able to reveal cerebral pathological alterations invisible for conventional MRI. Methods: In nine patients with STEC-HUS associated severe neurological symptoms but inconspicuous cerebral MRI findings maps of the parameters T2 relaxation time, relative proton density (PD), apparent diffusion coefficient (ADC), and fractional anisotropy (FA) were generated. Quantitative values of these parameters were measured at the basal ganglia, thalamus, and white matter of the frontal and parietal lobe and compared to those of nine age- and sex-matched controls. Results: Significant T2 prolongation ( p < 0.01) was found in the basal ganglia of all patients compared to controls. PD and ADC were not significantly altered. A significant reduction of FA in patients was seen at caput nuclei caudati ( p < 0.01). Conclusion: Prolonged T2 relaxation time indicates cerebral microstructural damages in these patients despite their inconspicuous MRI findings. T2 relaxometry could be used as a complementary tool for the assessment of metabolic-toxic brain syndromes. [ABSTRACT FROM AUTHOR]

In this study we focused on the quality of life and satisfaction of living kidney donors comparing traditional lumbar (LDN) and mini-incision donor nephrectomy (MIDN). From May 1996 to December 2002, 174 donor nephrectomies including 127 cases of LDN and 47 cases of MIDN were performed. Donors were evaluated using the SF-36 quality-of-life survey as well as a questionnaire dealing with donors‘ attitude towards kidney donation, financial burdens, pain, cosmetic satisfaction and duration of sick leave. Our donors achieved comparable or even higher scores in all the SF-36 categories in comparison to the general US population. Following MIDN, quality of life tended to be superior compared to that of LDN donors; however, statistical significance was reached only in one of the eight categories. Duration of sick leave following surgery was in favor of MIDN compared to LDN donors. Statistically significant differences favoring MIDN were observed regarding postoperative hospital stay and cosmetic satisfaction. The procedure would be again undergone by 94 of LDN and 97% of MIDN donors. Open-donor nephrectomy is a safe and cost-effective procedure. Introduction of the here-described MIDN has led to comparable or even improved results compared to LDN. [ABSTRACT FROM AUTHOR]

After renal transplantation, different immunological and non-immunological factors lead to long-term allograft deterioration. Acute rejection episodes are one risk factor for chronic renal allograft dysfunction (CRAD). Following the current Banff classification the histological grade in acute rejection episodes is of limited prognostic value, therefore, additional morphological surrogate markers would be helpful. We investigated the biopsies of 91 patients with early acute rejection episodes for the immunohistochemical expression of key molecules (perforin, granzyme B, TIA-1, CD40) in the T cell-mediated rejection process. Staining results were correlated to long-term allograft outcome. Patients with greater than 2% of granzyme B or greater than 25% of CD40-positive cells in the interstitial infiltrate showed significantly shorter allograft survival. Patients with a CD40-positive vascular rejection or greater than 2% of granzyme B-positive cells in the interstitial infiltrate were significantly correlated with an earlier onset of CRAD. Our findings provide potential morphological surrogate markers in biopsies with early acute rejection episodes after renal transplantation. These could become part of combined clinical and histological algorithms, allowing patient-specific risk estimation and customized therapy options to be made. [ABSTRACT FROM AUTHOR]

Erdheim–Chester disease (ECD) is a rare non-Langerhans’ form of histiocytosis with a plethora of different clinical manifestations owing to multiple organ involvement. We report two patients who presented initially with different clinical symptoms. The presenting complaint of the first patient was bone pain, predominantly in the legs, whereas in the other patient the initial symptoms were related to obstruction of both ureters, as in idiopathic retroperitoneal fibrosis. Ultimately, ECD was diagnosed in both patients by the occurrence of both pathognomonic manifestations, the histologic presence of non-Langerhans’ histiocytes in bone biopsies, and osteosclerotic lesions of the long bones. Because the extraosseous manifestations progressed and a single application of corticosteroids was ineffective, sequential treatment with vinblastine and mycophenolate mofetil, together with prednisolone, was started. At follow-up respectively 15 and 16 months after the start of treatment a beneficial effect was noted in both patients. These cases illustrate the clinical spectrum of ECD, detail the pathognomonic manifestations of this rare disease, emphasize the need to consider ECD as an uncommon but important differential diagnosis in patients with arthralgias or systemic fibrosis, and give the first evidence for a new treatment option. [ABSTRACT FROM AUTHOR]

Background: Most renal transplants fail because of chronic allograft nephropathy or because the recipient dies, but no reliable factor predicting long-term outcome has been identified. We tested whether a renal arterial resistance index of less than 80 was predictive of long-term allograft survival. Methods: The renal segmental arterial resistance index (the percentage reduction of the end-diastolic flow as compared with the systolic flow) was measured by Doppler ultrasonography in 601 patients at least three months after transplantation between August 1997 and November 1998. All patients were followed for three or more years. The combined end point was a decrease of 50 percent or more in the creatinine clearance rate, allograft failure (indicated by the need for dialysis), or death. Results: A total of 122 patients (20 percent) had a resistance index of 80 or higher. Eighty-four of these patients (69 percent) had a decrease of 50 percent or more in creatinine clearance, as compared with 56 of the 479 patients with a resistance index of less than 80 (12 percent); 57 patients with a higher resistance index (47 percent) required dialysis, as compared with 43 patients with a lower resistance index (9 percent); and 36 patients with a higher resistance index (30 percent) died, as compared with 33 patients with a lower resistance index (7 percent) (P<0.001 for all comparisons). A total of 107 patients with a higher resistance index (88 percent) reached the combined end point, as compared with 83 of those with a lower resistance index (17 percent, P<0.001). The multivariate relative risk of graft loss among patients with a higher resistance index was 9.1 (95 percent confidence interval, 6.6 to 12.7). Proteinuria (protein excretion, 1 g per day or more), symptomatic cytomegalovirus infection, and a creatinine clearance rate of less than 30 ml per minute per 1.73 m2 of body-surface area after transplantation also increased the risk. Conclusions: A renal arterial resistance index of 80 or higher measured at least three months after transplantation is associated with poor subsequent allograft performance and death. N Engl J Med 2003;349:115-24. [ABSTRACT FROM AUTHOR]

Background: Kidney biopsies are routinely used for diagnostic and prognostic purposes but their utility in the intensive care unit (ICU) setting is limited. We investigated the associations of clinical and histopathological risk factors with ICU-acute kidney injury (AKI) in donors with brain death (DBD) with kidneys of lower quality and procurement biopsies., Methods: Overall, 221 donors with brain death, 239 biopsies and 197 recipients were included. The biopsies were reread and scored according to the Banff recommendations. Clinical and histopathological data were compared between donors with and without AKI defined by serum creatinine and by urine output. Logistic regression analysis was applied to identify independent clinical and histopathological risk factors for both phenotypes. Lastly, the impact of each AKI phenotype on outcome was explored. AKI was diagnosed based on the RIFLE (Risk, Injury, Failure, Loss of function, End-stage kidney disease) AKIN (Acute Kidney Injury Network) or KDIGO (Kidney Disease Improving Global Outcomes) criteria., Results: Acute kidney injury occurred in 65% of donors based both upon serum creatinine and by urine output. Serum creatinine was able to better discriminate AKI. Multiorgan failure and severe AKI were captured by serum creatinine, and hemodynamic instability by urine output. Donors with serum creatinine-AKI showed lower chronic macrovascular scores, while donors with urine output-AKI had higher chronic microvascular and tubulointerstitial scores. Tubular injury was similar between the subgroups. Except for delayed graft function and one-year death-censored graft survival, the other short-term recipient outcomes were similar for both AKI phenotypes., Conclusion: Serum creatinine is more suitable than urine output for defining AKI in donors with brain death. There are distinct clinical risk factors for each AKI-ICU phenotype. Donor AKI phenotype does not predict the recipient´s prognosis. Kidney biopsies do not seem to confer any tangible benefit in defining AKI in donors with brain death., (© 2024. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Background: Despite organ shortages, the discard rate of deceased donor kidneys is high. Risk factors for this trend warrant further study., Methods: We investigated reasons for discard in a cohort of brain death donors with marginal kidneys and procurement biopsies. Paraffin embedded procurement biopsies were systematically reevaluated and graded for the purpose of the study. Assessment included percentage of global glomerulosclerosis, Banff Lesion scores and tubular epithelial damage. Donor-, transplant process-, perfusion quality-, histopathology-, and recipient-related parameters were compared between discarded and transplanted organs., Results: Although most clinical characteristics were similar between donors whose kidneys were transplanted and those whose kidneys were procured but discarded, discarded kidneys were more likely to be from donors with hepatitis C, to have undergone wedge biopsies, to show changes of acute and chronic injury and to be deemed poor quality. Except for obvious anatomic abnormalities, kidneys were often discarded due to the findings of procurement biopsies. Donors of kidneys discarded for histologic reasons more often had hypertension, coronary artery disease, stroke, and increased serum creatinine. The reason for discard was unknown in 20% of cases. Discarded kidneys came from donors who appeared to be clinically similar to donors whose kidneys were utilized for transplant., Conclusion: A considerable proportion of discarded kidneys were of acceptable quality. The analysis of the outcome of every recovered organ could help to overcome this problem. Procurement biopsies more often lead to discard than to transplantation of recovered organs. Proper handling during allocation has to be determined., (© 2023. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Background: Deceased donor kidneys with acute kidney injury (AKI) are often discarded because of concerns about inferior transplant outcomes. A means of grading the quality of such kidneys is the performance of procurement biopsies., Methods: This is a retrospective study of 221 brain death donors with marginal kidneys transplanted in 223 recipients in Germany. Marginal kidneys were defined as kidneys with procurement biopsies done exceptionally to assess suitability for transplantation in otherwise potentially discarded organs. The impact of deceased donor AKI on patient survival and death-censored graft survival at 1, 3 and 5 years and graft function at 1 and 3 years after transplantation was investigated., Results: Recipients of kidneys with stage 3 AKI had a greater incidence of delayed graft function [DGF; OR Stage 1 : 1.435 (95% CI 0.438-0.702), OR Stage 2 : 2.463 (95% CI 0.656-9.245), OR Stage 3 : 4.784 (95% CI 1.421-16.101)] but a similar graft and patient survival compared to recipients of donors without AKI and with AKI stage 1 and 2 as well. The coexistence of recipient DGF and donor AKI was associated with the lowest graft survival and function rates., Conclusion: The transplantation of deceased donor marginal kidneys with AKI confers a higher risk for DGF but is associated with acceptable graft and patient outcomes, which do not differ in comparison with marginal donor kidneys without AKI. Graft prognosis is especially poor if donor AKI and recipient DGF concur. Donor AKI was a risk factor independent of the histological lesions of procurement biopsies., (© 2022. The Author(s).)

Background: After kidney transplantation, pregnancy and graft function may have a reciprocal interaction. We evaluated the influence of graft function on the course of pregnancy and vice versa., Methods: We performed a retrospective observational study of 92 pregnancies beyond the first trimester in 67 women after renal transplantation from 1972 to 2019. Pre-pregnancy eGFR was correlated with outcome parameters; graft function was evaluated by Kaplan Meier analysis. The course of graft function in 28 women who became pregnant after kidney transplantation with an eGFR of < 50 mL/min/1.73m 2 was compared to a control group of 79 non-pregnant women after kidney transplantation during a comparable time period and with a matched basal graft function., Results: Live births were 90.5% (fetal death n = 9). Maternal complications of pregnancy were preeclampsia 24% (graft loss 1, fetal death 3), graft rejection 5.4% (graft loss 1), hemolytic uremic syndrome 2% (graft loss 1, fetal death 1), maternal hemorrhage 2% (fetal death 1), urinary obstruction 10%, and cesarian section. (76%). Fetal complications were low gestational age (34.44 ± 5.02 weeks) and low birth weight (2322.26 ± 781.98 g). Mean pre-pregnancy eGFR was 59.39 ± 17.62 mL/min/1.73m 2 (15% of cases < 40 mL/min/1.73m 2 ). Pre-pregnancy eGFR correlated with gestation week at delivery (R = 0.393, p = 0.01) and with percent eGFR decline during pregnancy (R = 0.243, p = 0.04). Pregnancy-related eGFR decline was inversely correlated with the time from end of pregnancy to chronic graft failure or maternal death (R = -0.47, p = 0.001). Kaplan Meier curves comparing women with pre-pregnancy eGFR of ≥ 50 to < 50 mL/min showed a significantly longer post-pregnancy graft survival in the higher eGFR group (p = 0.04). Women after kidney transplantation who became pregnant with a low eGFR of > 25 to < 50 mL/min/1.73m 2 had a marked decline of renal function compared to a matched non-pregnant control group (eGFR decline in percent of basal eGFR 19.34 ± 22.10%, n = 28, versus 2.61 ± 10.95%, n = 79, p < 0.0001)., Conclusions: After renal transplantation, pre-pregnancy graft function has a key role for pregnancy outcomes and graft function. In women with a low pre-pregnancy eGFR, pregnancy per se has a deleterious influence on graft function., Trial Registration: Since this was a retrospective observational case series and written consent of the patients was obtained for publication, according to our ethics' board the analysis was exempt from IRB approval. Clinical Trial Registration was not done. The study protocol was approved by the Ethics Committee of Hannover Medical School, Chairman Prof. Dr. H. D. Troeger, Hannover, December 12, 2015 (IRB No. 2995-2015)., (© 2022. The Author(s).)

BACKGROUND Our kidney transplant waitlist includes 20% re-transplantations (TX2). Knowing what to expect is a clinical obligation. MATERIAL AND METHODS We compared graft and patient survival of all 162 TX2 patients, transplanted 2000 to 2009, with 162 patients after first transplantation (TX1) matched for age, sex, living/non-living donation, and transplantation date. Patient follow-up was 10 years. RESULTS TX2 graft and patient survivals were inferior to TX1 (p<0.001 and p=0.047). TX2 patients had a longer cumulative dialysis vintage, more human leucocyte antigen (HLA) mismatches, more panel-reactive HLA antibodies, more often received induction therapy with rabbit-antithymocyte globulin (rATG), and had a lower body mass index (all p<0.05). Death from infection and graft failure by rejection was more frequent after TX2 (both p<0.05) but not after TX1. Multivariable Cox regression analysis revealed that both cohorts had graft failure and death risk associated with infection and cardiovascular disease, and graft failure by humoral rejection. However, only TX2 patients had an additional risk of graft failure with early inferior graft function and of patient death with ≥2 comorbidities. Moreover, Kaplan-Meier analysis showed that TX2 and not TX1 patients had a lower graft and patient survival associated with infection and with ≥2 comorbidities (all p<0.05). CONCLUSIONS Re-transplantation is associated with worse graft outcomes mainly because of immunologic and graft-quality reasons, although the high number of comorbidities and infection severities aside from cardiovascular disease drive mortality. The more frequent rATG induction of TX2 patients could promote infection by enhancing immunosuppression. By addressing comorbidities, outcomes could possibly be improved.

Bevacizumab is a humanized monoclonal IgG1 antibody, which neutralizes vascular endothelial growth factor and is used for treating multiple cancer types. As a known and frequent adverse event, this therapy can lead to renal damage including proteinuria and nephrotic syndrome. In a retrospective approach, we analyzed 17 renal biopsies from patients receiving bevacizumab treatment. We observed a distinctive histopathological pseudothrombotic pattern different from the previously reported thrombotic microangiopathy. Since this pattern includes some features similar to acute and chronic thrombotic microangiopathy, focal segmental glomerulosclerosis and cryoglobulinemic membranoproliferative glomerulonephritis, biopsies with these diagnoses were included for comparison. Clinical, laboratory, light microscopic, immunohistochemical (including a proximity ligation assay), proteomic and electron microscopic features were assessed. Nephrotic syndrome was present in 15 of the 17 bevacizumab-treated patients. All 17 displayed a patchy pattern of variably PAS-positive hyaline pseudothrombi occluding markedly dilated glomerular capillaries in their biopsies. Mass spectrometry-based proteome analysis revealed a special protein pattern demonstrating some features of thrombotic microangiopathy and some of cryoglobulinemic glomerulonephritis, including a strong accumulation of IgG in the pseudothrombi. Proximity ligation assay did not show interaction of IgG with C1q, arguing for accumulation without classic pathway complement activation. In contrast to thrombi in thrombotic microangiopathy cases, the hyaline pseudothrombi did not contain clusters of CD61-positive platelets. Electron microscopy of bevacizumab cases did not show fibrin polymers or extensive loss of podocyte foot processes. Even though cases of bevacizumab-associated microangiopathy share some features with thrombotic microangiopathy, its overall histopathological pattern is quite different from acute or chronic thrombotic microangiopathy cases. We conclude that bevacizumab therapy can lead to a unique hyaline occlusive glomerular microangiopathy, likely arising from endothelial leakage followed by subendothelial accumulation of serum proteins. It can be diagnosed by light microscopy and is an important differential diagnosis in cancer patients with nephrotic syndrome.

Background: Both general and spinal anaesthesia with short-acting local anaesthetics are suitable and reliable for knee arthroscopy as an ambulatory procedure. Chloroprocaine (CP) 1% seems to be the ideal spinal local anaesthetic for this indication., Objective: The aim of this study was to compare spinal anaesthesia using CP 1% with general for outpatient knee arthroscopy with regard to procedure times, occurrence of pain, patient satisfaction and recovery, and also costs., Design: A randomised controlled single-centre trial., Setting: University Medical Centre Mannheim, Department of Anaesthesiology and Surgical Intensive Care Medicine, Mannheim, Germany. April 2014 to August 2015., Patients: A total of 50 patients (women/men, 18 to 80 years old, ASA I to III) undergoing outpatient knee arthroscopy were included. A contra-indication to an allocated anaesthetic technique or an allergy to medication required in the protocol led to exclusion., Interventions: Either general anaesthesia with sufentanil, propofol and a laryngeal mask for airway-management or spinal with 40-mg CP 1% were used. We noted procedure times, patient satisfaction/recovery and conducted a 7-day follow-up., Main Outomes: Primary outcome was duration of stay in the day-surgery centre. Secondary outcomes were first occurrence of pain, patient satisfaction, quality of recovery and adverse effects. In addition, we analysed treatment costs., Results: Spinal had faster recovery than general anaesthesia with patients reaching discharge criteria significantly earlier [117 min (66 to 167) versus 142 min (82 to 228), P = 0.0047]. Pain occurred significantly earlier in the general anaesthesia group (P = 0.0072). Costs were less with spinal anaesthesia (cost ratio spinal: general 0.57). Patients felt significantly more uncomfortable after general anaesthesia (P = 0.0096)., Conclusion: Spinal anaesthesia with 40-mg CP 1% leads to a significantly earlier discharge and is cheaper compared with general., Trial Registration: German Clinical Trials Register, www.drks.de, identifier: DRKS00005989.

According to the Banff guidelines for renal transplants, pure endothelialitis without any tubulointerstitial infiltrates (with the Banff components v ≥ 1, i0, t0) has to be called acute cellular rejection (ACR). The pathophysiology of this rare lesion abbreviated as v&#95;only is currently unclear, as well as its clinical, serological, and prognostic implications. Therefore, we conducted this retrospective comparative study. We compared all 23 biopsies with v&#95;only from Hannover Medical School between 2003 and 2010 with 23 matched biopsies with the Banff components v ≥ 1, i ≥ 1, and t ≥ 1 (v&#95;plus) and 23 biopsies with v0, i0, and t0 (v0i0t0). Serological (available in 10, 11, and 14 patients, respectively), histological, and clinical data were compared. Of all biopsies, 0.4 % had findings of v&#95;only. v&#95;only, v&#95;plus, and v0i0t0 only showed minimal differences in the Banff components apart from the cohort-defining components. Endothelialitis in v&#95;only more frequently involved the arcuate arteries than the smaller preglomerular vessels compared to v&#95;plus and vice versa. Combining histopathological data and serological data, v&#95;only more frequently showed criteria for acute humoral rejection than v0i0t0 (albeit not persistent after the Bonferroni-Holm correction in pairwise comparisons), while there was no difference between v&#95;only and v&#95;plus. No difference could be demonstrated regarding clinical presentation at biopsy or outcome. Our results show minimal differences regarding clinical presentation, outcome, and histological features between v&#95;only and v&#95;plus. Patients with v&#95;only should be thoroughly investigated for evidence of acute humoral rejection.

Atypical haemolytic-uremic syndrome (aHUS) is, in most cases, due to hereditary or acquired defects in complement regulation and a life-threatening disease. Despite the rapidly grown knowledge about the primary defects in aHUS, the pathogenesis that links complement dysregulation with microthrombus formation in aHUS is still unknown. Thus, we examined the glomerular microvascular expression of pro- and antithrombotic genes. Glomeruli were microdissected from 12 archival paraffin-embedded biopsies with aHUS and from seven control biopsies. Glomerular mRNA expression was quantified by single real-time PCR reactions after preamplification. In addition immunostains were performed for plasminogen activator inhibitor 1 (PAI-1) and for tissue plasminogen activator (tPA). Results were compared between cases and controls and with clinical data. Glomeruli in aHUS had increased mRNA expression of antifibrinolytic, prothrombotic PAI-1, antithrombotic thrombomodulin (THBD) and CD73 and decreased expression of profibrinolytic, antithrombotic tPA compared to controls. Impaired fibrinolysis due to increased microvascular expression of the antifibrinolytic PAI-1 in combination with the decreased expression of the profibrinolytic tPA seems to be a final common pathway in renal thrombotic microangiopathy that is also effective in aHUS. The concomitant induction of antithrombotic transcripts likely indicates counterregulatory efforts, demonstrating that the capillary bed is not a passive victim of complement attack. Future research should investigate if and how complement activation could induce the reported shift in the expression of PAI-1 and tPA.

Background: After renal transplantation, patients have a higher incidence of developing cancer necessitating pelvic radiotherapy, but there is a lack of data for such therapy in this patient group., Patients and Methods: Nine patients with pelvic renal transplants were treated with pelvic radiotherapy between 04/2002 and 06/2011. Treatment was carried out for prostate (n=4), rectal (n=2), and anal cancer (n=1), osseous metastasis (n=1), and Hodgkin's disease (n=1). The mean age of the transplants was 12.6 years., Results: The mean total dose to the target volume was 60.2 Gy, the mean maximum dose to the transplant was 10.0 Gy, with a mean dose of 2.1 Gy. The mean creatinine clearance before start of radiotherapy was 48.9 ml/min. After a mean follow-up of 23 months, no patient showed failure of the transplant and the mean creatinine clearance was 64.2 ml/min., Conclusion: Using modern radiotherapy techniques, low doses to the transplant can be achieved without compromising target treatment and without transplant failure. A mean dose of <4 Gy seems to be well-tolerated by the graft.

Arteriolar hyalinosis in kidney transplants is considered the histopathologic hallmark of chronic calcineurin inhibitor (CNI) toxicity. However, the lesion is not specific. We assessed prevalence, progression, and clinical significance of arteriolar lesions in 1239 renal transplant sequential protocol biopsy samples and 408 biopsy for cause samples in 526 patients. Associations between arteriolar lesions and presumed risk factors, concomitant histopathologic lesions, demographic factors, and graft function were evaluated. The frequency of arteriolar lesions was stable during the first 2 years after transplantation, and increased thereafter (14.8% at 6 months versus 48.6% at >2 years; P < 0.0001). We were unable to find associations with diabetes, hypertension, or CNI therapy. However, patients with early arteriolar lesions received grafts from older donors (mean ± SD age, 54.4 ± 13.4 years versus 43.1 ± 16.6 years; P < 0.0001), and had inferior graft function (estimated glomerular filtration rate 55 ± 21 mL/min versus 63 ± 24 mL/min at 6 weeks, 53 ± 19 mL/min versus 60 ± 23 mL/min at 1 year, and 49 ± 19 mL/min versus 59 ± 22 mL/min at 2 years; P < 0.05). Evaluation of late biopsy samples from patients not receiving CNI therapy revealed a high prevalence of AH without clear-cut identifiable underlying cause. Reproducibility of arteriolar lesions was at best moderate (κ ≤ 0.62). Sampling error in sequential biopsy samples was frequent. In conclusion, in samples from sequential protocol biopsies and biopsies for cause in individual patients, arteriolar lesions in renal transplants not only increase over time without being specific for CNI toxicity but are affected by sampling error and limited reproducibility., (Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Experience with combined liver-kidney transplantation (L-KTx) has increased, but controversy regarding this procedure continues because the indications are not clearly defined yet. Between 1984 and 2000, 38 patients underwent simultaneous L-KTx and 9 patients underwent sequential transplantation, receiving either a liver before a kidney or a kidney before a liver. Main indications for a simultaneous procedure were polycystic liver-kidney disease with cirrhosis and coincidental renal failure. The main indications for sequential procedure were cirrhosis caused by viral infection for the liver and glomerulonephritis for the kidneys. Outcomes in these patients were evaluated retrospectively. Regarding simultaneous transplantation, 28 (73.7%) long-term survivors were followed up for 0.7 to 12.5 years. Currently, 24 (63.2%) patients are alive with good liver function. Fourteen patients died; 10 patients died in the early postoperative phase because of septic complications, and most of them were cirrhotic with a poor preoperative clinical status. Currently, 2 of the surviving patients (8%) have returned to dialysis, 4 (17%) have reduced renal function, and 18 (75%) have good renal function. Five liver and 2 kidney retransplantations were performed during the follow-up. In cases of sequential grafting, patients undergoing kidney transplantation in the presence of a previously transplanted stable liver did better than those who underwent liver transplantation after kidney transplantation. When liver transplantation was performed early and electively before substantial worsening, combined L-KTx is a safe procedure offering excellent long-term palliation.

Ectopic calcification is a frequent complication of many degenerative diseases. Here we identify the serum protein alpha2-Heremans-Schmid glycoprotein (Ahsg, also known as fetuin-A) as an important inhibitor of ectopic calcification acting on the systemic level. Ahsg-deficient mice are phenotypically normal, but develop severe calcification of various organs on a mineral and vitamin D-rich diet and on a normal diet when the deficiency is combined with a DBA/2 genetic background. This phenotype is not associated with apparent changes in calcium and phosphate homeostasis, but with a decreased inhibitory activity of the Ahsg-deficient extracellular fluid on mineral formation. The same underlying principle may contribute to many calcifying disorders including calciphylaxis, a syndrome of severe systemic calcification in patients with chronic renal failure. Taken together, our data demonstrate a critical role of Ahsg as an inhibitor of unwanted mineralization and provide a novel therapeutic concept to prevent ectopic calcification accompanying various diseases.