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. 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. Acute kidney injury occurred in 65

Despite organ shortages, the discard rate of deceased donor kidneys is high. Risk factors for this trend warrant further study. 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. 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

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.

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).

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.

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.

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.

Pregnancy in women with a transplanted kidney is always a risk for mother, child, and transplanted organ. We cared for a young woman with hyperoxaluria type 1 and end-stage renal failure by nephrocalcinosis. She underwent a sequential deceased-donor liver transplantation for treatment of the hepato-centric genetic enzyme defect, followed by a living-related kidney transplantation from her mother 2 months later. Both interventions were performed when she was a 10-year-old child. She received cyclosporine, mycophenolate, and prednisolone. The liver was rejected 3 times, which required intravenous steroids. The renal function deteriorated gradually over the years with proteinuria 1 gram protein per 1 gram creatinine and moderate hypertension. However, the woman' s wish for pregnancy was not to be denied, and so it was. We were confronted with the following problems which will be discussed in the article: (1) the problems of transplanting patients with hyperoxaluria type 1 in general; ( 2) the special problem of a pregnancy in a 31-year-old woman with a genetic kidney disease, after transplantation of 2 organs as a child 18 years earlier; (3) an immunologically instable liver transplant and a renal allograft with slowly deteriorating glomerular filtration rate and increasing proteinuria. Our patient generally ignored our advice; her desires were paramount. The general guidelines for pregnancy after renal transplantation are given in comparison to this exceptional case with all parameters beyond the guidelines due to the insisting strong wish of this woman to have a child. Our experience may enable other clinicians faced with similar problems.

ZusammenfassungSchwangerschaft nach Nierentransplantation ist immer ein Risiko sowohl für Mutter und Kind als auch für das Nierentransplantat. Wir beschreiben den Fall einer jungen Frau mit primärer Hyperoxalurie Typ 1 und dadurch bedingtem terminalem Nierenversagen durch Nephrokalzinose. Sie hatte als 10-jähriges Kind eine Lebertransplantation durch Fremdspende erhalten zur Behebung des Enzymdefektes in der Leber sowie 2 Monate später eine Nierentransplantation durch Nierenspende der Mutter. Die Immunsuppression erfolgte durch Cyclosporin, Mycophenolatmofetil und Prednisolon. Das Lebertransplantat hatte 3 Abstoßungen, jeweils behandelt mit Steroidboli. Das Nierentransplantat zeigte eine langsame Funktionsverschlechterung über die Jahre, Entwicklung einer Proteinurie von 1 Gramm Protein pro 1 Gramm Kreatinin sowie eine mittelschwere Hypertonie. Trotzdem hatte die Frau einen persistierenden dringenden Kinderwunsch und setzte sich damit durch. Der Artikel beschreibt die speziellen Probleme dieses Falles: (1) das allgemeine Problem, Patienten mit Hyperoxalurie Typ 1 überhaupt zu transplantieren; (2) das spezielle Problem der Schwangerschaft dieser 31-jährigen Frau mit genetisch bedingter Nierenerkrankung und vorangehender Transplantation von 2 soliden Organen vor 18 Jahren; (3) die mit einem immunologisch instabilen Lebertransplantat und einem Nierentransplantat einhergehende langsam progrediente Funktionsverschlechterung und ansteigende Proteinurie. Die generellen Richtlinien für eine Schwangerschaft nach Nierentransplantation werden aufgezeigt im Vergleich zu dem hier beschriebenen Fall einer Schwangerschaft, bei der fast alle Parameter außerhalb der Richtlinien liegen bei persistierend starkem Kinderwunsch dieser Frau.

There is now experience of many thousands of pregnancies over more than 50 years of renal transplantation. Most such patients have some degree of hypertension and chronic kidney disease, and as expected their rates of complications are substantially higher than those of age-matched controls. However, rates of successful pregnancy are now high and pregnancy is no longer an unusual event in transplanted patients. As for other patients with chronic kidney disease, additional risks depend on pre-pregnancy glomerular filtration rate, proteinuria, and hypertension. Fertility returns rapidly after transplantation but delay of at least a year is usually recommended to be sure of stable graft function and drug dosage. Early discussion of these issues with women of childbearing age is essential as drug regimens may need to be altered to agents of known safety, and to stress the importance of planning the pregnancy. The combination of tacrolimus and azathioprine with or without low-dose prednisolone is probably the most common, but in many centres agents such as mycophenolate mofetil, which is teratogenic, are commonly used. Blood pressure should be well controlled as outside pregnancy but some drugs are contraindicated and others are best avoided.

BACKGROUND:Identification and quantification of the relevant factors for death can improve patients' individual risk assessment and decision-making. We used a well-documented patient cohort (n = 892) in a renal transplant programme with protocol biopsies to establish multivariable Cox models for risk assessment at 3 and 12 months post-transplantation.METHODS:Patients transplanted between 2000 and 2007 were observed up to 11 years (total observation 5227 patient-years; median 5.9 years). Loss to follow-up was negligible (n = 15). A total of 2251 protocol biopsies and 1214 biopsies for cause were performed. All rejections and clinical borderline rejections in protocol biopsies were treated.RESULTS:Overall 10-year patient survival was 78%, with inferior survival of patients with graft loss and superior survival of patients with living-donor transplantation. Eight factors were common in the models at 3 and 12 months, including age, pre-transplant heart failure and a score of cardiovascular disease and type 2 diabetes, post-transplant urinary tract infection, treatment of rejection, new-onset heart failure, coronary events and malignancies. Additional variables of the model at 3 months included deceased donor transplantation, transplant lymphocele, BK virus nephropathy and severe infections. Graft function and graft loss were significant factors of the model at 12 months. Internal validation and validation with a separate cohort of patients (n = 349) demonstrated good discrimination of the models.CONCLUSIONS:The identified factors indicate the important areas that need special attention in the pre- and post-transplant care of renal transplant patients. On the basis of these models, we provide nomograms as a tool to weigh individual risks that may contribute to decreased survival.

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.

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.

Antibody-mediated rejection (ABMR) is a major cause of late renal allograft dysfunction and graft loss. Risks and benefits of treatment of late ABMR have not been evaluated in randomized clinical trials. We report on a 35-year-old patient with deterioration in renal function and progressive proteinuria 15 years after transplantation. Recurrent infections after a splenectomy following traumatic splenic rupture 3 years earlier had led to reduction of immunosuppression. Renal transplant biopsy showed glomerular double contours, 40% fibrosis/tubular atrophy, peritubular capillaritis, and positive C4d staining indicating chronic-active ABMR. ABMR treatment was initiated with steroids, plasmapheresis, and rituximab. Fourteen days later, she presented to the emergency department with fever, diarrhea, vomiting, and hypotension. Despite antibiotic treatment she deteriorated with progressive hypotension, capillary leak with pleural effusion, peripheral edema, and progressive respiratory insufficiency. She died due to septic shock five days after admission. Blood cultures showed Streptococcus pneumoniae, consistent with a diagnosis of overwhelming postsplenectomy infection syndrome, despite protective pneumococcus vaccination titers. We assume that the infection was caused by one of the strains not covered by the Pneumovax 23 vaccination. The increased immunosuppression with B cell depletion may have contributed to the overwhelming course of this infection.

offspring's gender percentage was comparable. 2 miscarriage episodes were recorded in two different recipients after which conception was effortlessly accomplished.No malformation was detected among all offspring at birth or after 5 years of age.CONCLUSIONS: In our study, no evidence of MA-associated malformation was observed in the offspring of males under treatment with MA.Further research is needed to confirm our findings and generate much more robust evidence to properly advice KT male recipients that eager to procreate.