Successful steroid withdrawal guided by surveillance biopsies-A single-center experience.

Steroid withdrawal following renal transplantation is challenging and widely debated. This retrospective study aimed at investigating the frequency and determinants of successful steroid withdrawal guided by surveillance biopsies. We analyzed 156 pretransplant DSA-negative renal transplants receiving basiliximab induction and maintenance immunosuppression with tacrolimus-mycophenolate-steroids. The absence of rejection in surveillance biopsies at 3 or 6 months post-transplant initiated steroid withdrawal, which was monitored by subsequent indication and/or surveillance biopsies. The primary outcome was the frequency of successful (i.e., rejection-free) steroid withdrawal at 1 year post-transplant. In the whole study population, successful steroid withdrawal was achieved in 73 of 156 patients (47%). Steroid withdrawal was initiated in 98 of 156 patients (63%) and successful in 73 of 98 patients (74%). Subsequent clinical rejection occurred in only one of 98 patients (1%), whereas 24 of 98 patients (24%) experienced subclinical rejection. Steroid withdrawal was not initiated in 58 of 156 patients (37%) mainly due to current or prior severe (Banff TCMR ≥IA) subclinical rejection. Prediction of successful steroid withdrawal by pretransplant or early post-transplant parameters was poor. In conclusion, (sub)clinical rejection-free steroid withdrawal can be expected in about half of pretransplant DSA-negative patients. As successful steroid withdrawal cannot be well predicted by pre- and early post-transplant parameters, guidance by surveillance biopsies is an attractive strategy.

Individualized scheme of immunoadsorption for the recurrence of idiopathic focal segmental glomerulosclerosis in the graft: a single center experience.

OBJECTIVES: To explore the role of immunoadsorption (IA) for the treatment of idiopathic focal segmental glomerulosclerosis (FSGS) recurrence in the renal allograft, if applied in a personalized manner. METHODS: We studied patients with end-stage renal disease (ESRD) due to idiopathic FSGS, transplanted between 2001 and 2010. Patients with FSGS recurrence were treated with daily sessions of IA for the first week, followed by an every other day scheme and then individualized tapering until discontinuation. Complete remission was defined as a reduction of 24-h proteinuria to ≤ 0.5 g/day and partial remission as a reduction of 24-h proteinuria to 50% or more from baseline. RESULTS: Of the 18 renal transplant recipients with ESRD due to idiopathic FSGS, 12 (66.7%) experienced disease recurrence in a mean time of 0.75 months post-transplantation (KTx), with a mean proteinuria of 8.9 g/day at the time of recurrence. The mean recipient age was 30.8 years; the mean donor age was 47.4 years, while living related donors provided the allograft in seven cases. Four of the patients received therapy with rituximab in addition to IA. During a mean time of follow-up of 48.3 months, seven patients (58.3%) achieved complete remission, and five (41.7%) partial remission. At the end of follow-up, eight patients (66.7%) had functioning grafts, being in sustained remission, in contrast to four patients (33.3%), who ended up in ESRD because of FSGS recurrence. CONCLUSIONS: IA was shown efficacious in a small series of patients with recurrent FSGS in the graft. Renal function remained stable in eight of the 12 patients with FSGS recurrence.

Excellent Clinical Long-Term Outcomes of Kidney Transplantation From Small Pediatric Donors (Age ≤ 5 Years) Despite Early Hyperfiltration Injury.

Background: The use of small pediatric donors (age ≤ 5 years and body weight < 20kg) for adult transplant recipients is still regarded controversially in terms of early complications, long-term outcomes, and development of hyperfiltration injury due to body size mismatch. Objective: To investigate long-term outcomes of adult renal allograft recipients receiving a kidney from small pediatric donor (SPD) in terms of kidney function and early features of hyperfiltration injury such as histological changes and proteinuria. Design: Retrospective, single center study. Settings: Transplant center of the University Hospital of Basel, Switzerland. Patients: Adult renal allograft recipients receiving a kidney from a small pediatric donor at our center between 2005 and 2017. Methods: The outcome of 47 transplants from SPD were compared with 153 kidney transplants from deceased-standard criteria donors (SCD) occurring during the same time period. Incidence of clinical signs of hyperfiltration injury (eg, proteinuria) was investigated. According to our policy, surveillance biopsies were taken at 3 and 6 months post-transplant and were evaluated in terms of signs of hyperfiltration injury. Results: At a median follow-up of 2.3 years post-transplant, death-censored graft survival of SPD was comparable to transplants from SCD (94% vs 93%; P = .54). Furthermore, allograft function at last follow-up (estimated glomerular filtration rate-Modification of Diet in Renal Disease) was significantly higher in pediatric transplant (80 vs 55 ml/min/1.73 m2, P = .002). We found histological signs of early hyperfiltration injury in 55% of SPD. There was an equally low proteinuria in both groups during follow-up. Limitations: It is a single center and retrospective observational study with small sample size. The outcomes were investigated in a well-selected population of recipients with low body mass index, low immunological risk, and well-controlled hypertension and was not compared with equal selected group of recipients. Conclusions: Early histological and clinical signs of hyperfiltration injury in SPD is frequent. Despite the hyperfiltration injury, there is an equal allograft survival and even superior allograft function in SPD compared with SCD during follow-up. This observation supports the concept of high adaptive capacity of pediatric donor kidneys.

Contexte: Le recours à de très jeunes donneurs pédiatriques (âge: ≤ 5 ans; poids < 20 kg), pour des greffes chez des receveurs adultes, suscite encore des préoccupations quant aux complications précoces, aux résultats à long terme et au développement de lésions d'hyperfiltration liées à la disproportion de taille corporelle. Objectif: Examiner les résultats à long terme de patients adultes greffés rénaux ayant reçu l'organe d'un très jeune donneur pédiatrique (TJDP), soit la fonction rénale et les signes précoces de lésions d'hyperfiltration (p. ex. changements histologiques et protéinurie). Type d'étude: Étude rétrospective dans un seul établissement. Cadre: Le centre de transplantation de l'hôpital universitaire de Bâle (Suisse). Sujets: Les adultes ayant reçu une greffe rénale provenant d'un très jeune donneur pédiatrique dans notre centre entre 2005 et 2017. Méthodologie: Les résultats de 47 transplantations impliquant des TJDP ont été comparés à ceux de 153 transplantations rénales survenues au cours de la même période, mais impliquant des donneurs décédés répondant aux critères standard (DDCS). L'incidence des signes cliniques de lésions d'hyperfiltration (p. ex. protéinurie) a été étudiée. Selon notre politique, des biopsies de surveillance ont été réalisées à 3 et 6 mois post-transplantation et évaluées pour les signes d'hyperfiltration. Résultats: Lors d'un suivi médian de 2,3 ans post-transplantation, le pourcentage de survie du greffon (censurée pour les décès) provenant de TJDP était comparable à celui de DDCS (94 % c. 93 %; p = 0,54). De plus, la fonction du greffon lors du dernier suivi (DFGe basé sur l'équation MDRD) était significativement plus élevée dans les cas de transplantation pédiatrique (80 ml/min/1,73 m2 contre 55 ml/min/1,73 m2; p=0,002). Des signes histologiques de lésions précoces dues à une hyperfiltration ont été observés dans 55 % des cas impliquant un TJDP. La protéinurie était peu importante et équivalente dans les deux groupes au cours du suivi. Limites: Il s'agit d'une étude observationnelle et rétrospective menée dans un seul centre et sur un faible échantillon. Les résultats ont été obtenus dans une population bien précise de receveurs avec un IMC peu élevé, un risque immunologique faible et une hypertension bien contrôlée; ces résultats n'ont pas été comparés à un autre groupe de receveurs équivalents. Conclusion: Des signes histologiques et cliniques précoces de lésion d'hyperfiltration sont fréquents chez les TJDP. Malgré cela, pendant la période de suivi, la survie de greffon provenant d'un TJDP s'est avérée comparable à celles d'organes provenant de DDCS et la fonction supérieure. Cette observation appuie l'hypothèse d'une grande capacité d'adaptation des reins provenant de donneurs pédiatriques.

Immunohistochemical Expression of FOXP3+ Regulatory T Cells in Proteinuric Primary Glomerulopathies.

FOXP3+ regulatory T-cell (Tregs) detection in renal allograft biopsies has been associated with a less intense immune response. Data about FOXP3+ Tregs' presence and role in primary glomerulopathies of native kidneys are minimal. We comparatively studied the immunohistochemical expression of FOXP3+ Tregs, CD4+ and CD3+ T cells in IgA nephropathy (IgAN), focal segmental glomerulosclerosis (FSGS), and membranous glomerulopathy (MGN). We retrospectively reviewed 71 renal biopsies (28 from patients with IgAN, 22 from patients with FSGS and 21 from patients with MGN) performed with proteinuria as the main indication. FOXP3+ Tregs and CD4+ and CD3+ T cells in inflammatory cell infiltrates of the interstitial tissue and periglomerular space were automatically counted using image analysis software. Univariable and multivariable logistic regressions were applied for statistical analysis. Nuclear FOXP3+ immunohistochemical expression was observed in T cells in 64% of IgAN cases, 77% of FSGS cases, and 76% of MGN cases (p > 0.05). Absolute FOXP3+ Tregs count in the interstitial tissue was higher in patients without arteriolar hyalinosis than in those with arteriolar hyalinosis (1.814 ± 2.160 vs. 831 ± 696; p = 0.029). In patients with a high FOXP3+/CD4+ ratio in the interstitial tissue, the odds ratio for CKD-EPI eGFR ≥60 ml/min/1.73 m2 at biopsy was 4.80 (95% CI: 1.29-17.91; p = 0.019). FOXP3+ Tregs intrarenal infiltration in primary glomerulopathies is common. FOXP3+ Tregs' increased expression may be associated with milder histological lesions. High FOXP3+/CD4+ ratio in the interstitial tissue may have prognostic significance for renal function preservation.

Pathophysiology of Contrast-Induced Acute Kidney Injury (CIAKI).

Contrast-induced acute kidney injury (CIAKI) is a severe complication associated with the use of iodinated contrast media (CM); a sudden but potentially reversible fall in glomerular filtration rate (GFR) typically occurring 48-72 hours after CM administration. Principal risk factors related with the presentation of CIAKI are preexisting chronic kidney disease and diabetes mellitus. Studies on CIAKI present considerable complexity because of differences in CM type and dose, controversies in definition and baseline comorbidities. Despite that, it should be noted that CIAKI poses a serious health problem because it is a very common cause of hospitalacquired AKI, linked to increased morbidity and mortality and utilizing growing healthcare resources. The pathogenesis of CIAKI is heterogeneous and, thus, is incompletely understood. Three basic mechanisms appear to simultaneously occur for CIAKI development: Renal vasoconstriction and medullary hypoxia, tubular cell toxicity and reactive oxygen species formation. The relative contribution of each one of these mechanisms is unknown but they ultimately lead to epithelial and endothelial cell apoptosis and GFR reduction. Further research is needed in order to better clarify CIAKI pathophysiology and accordingly introduce effective preventive and therapeutic strategies.

Acute Rejection Phenotypes in the Current Era of Immunosuppression: A Single-Center Analysis.

BACKGROUND: Besides 'definitive rejection', the Banff classification includes categories for 'suspicious for rejection' phenotypes. The aim of this study was to determine the frequency and phenotypes of rejection episodes in 316 consecutive renal transplants from 2009 to 2014 grouped into patients without/with pretransplant HLA-DSA (ptDSAneg, n = 251; ptDSApos, n = 65). METHODS: All adequate indication (n = 125) and surveillance biopsies (n = 538) performed within the first year posttransplant were classified according to the current Banff criteria. RESULTS: 'Suspicious for rejection' phenotypes were 3 times more common than 'definitive rejection' phenotypes in biopsies from ptDSAneg patients (35% vs 11%) and equally common in biopsies from ptDSApos patients (25% vs 27%). In both groups, 'suspicious for rejection' phenotypes were more frequent in surveillance than in indication biopsies (28% vs 16% in ptDSAneg patients, and 37% vs 29% in ptDSApos patients). 'Borderline changes: 'Suspicious' for acute T-cell mediated rejection' (91%) were the dominant 'suspicious for rejection' phenotype in ptDSAneg patients, whereas 'borderline changes' (58%) and 'suspicious for acute/active antibody-mediated rejection' (42%) were equally frequent in biopsies from ptDSApos patients. Inclusion of 'suspicious for rejection' phenotypes increased the 1-year incidence of clinical (ptDSAneg patients: 18% vs 8%, P = 0.0005; ptDSApos patients: 24% vs 18%, P = 0.31) and (sub)clinical rejection (ptDSAneg patients: 59% vs 22%, P < 0.0001; ptDSApos patients: 68% vs 40%, P = 0.004). CONCLUSIONS: 'Suspicious for rejection' phenotypes are very common in the current era and outnumber the frequency of 'definitive rejection' within the first year posttransplant.

2222 kidney transplantations at the University Hospital Basel: a story of success and new challenges.

QUESTIONS UNDER STUDY: The aim was to investigate changes in kidney allograft donor/recipient characteristics and outcomes at our centre. METHODS: We retrospectively reviewed all 2222 kidney transplantations performed between 1967 and 2015. The population was divided into four eras on the basis of time intervals corresponding to major changes in immunosuppression and pretransplant risk stratification: (i.) 1967-1980 (n = 231), (ii.) 1981-1997 (n = 883), (iii.) 1998-2004 (n = 437), (iv.) 2005-2015 (n = 671). RESULTS: In deceased donor transplants, we observed a continuous increase of the median recipient (45, 51, 56 and 58 years; p <0.0001) and donor (26, 36, 49 and 54 years; p <0.0001) age. Notably, the frequency of expanded criteria donors increased dramatically (1%, 10%, 28%, 40%, p <0.0001). Graft survival at 1 year (63%, 82%, 89%, 95%), 5 years (46%, 66%, 72%, 78%) and 10 years (27%, 46%, 48%, 61%) significantly improved (p <0.0001). Patient survival also significantly improved and remained stable at a high level within the last three eras (1 year: 97%; 5 years: 87%; 10 years: 71%). Similar trends along with slightly better outcomes were noticed in living donor transplantations. In the most recent era, graft losses in elderly patients were in 81% of cases related to the patient's death, whereas in young patients 83% of graft losses were caused by transplant failure (mainly rejection). Allograft function at the time of patients' deaths would have allowed for calculated 10 additional years with an estimated glomerular filtration rate >15 ml/min. CONCLUSION: Despite increasing donor and recipient age, outcomes improved, illustrating ongoing progress in kidney transplantation. A major new challenge is to match the functional capacity of the donor organ with the anticipated lifespan of the recipient.

Plasma Exchange for the Recurrence of Primary Focal Segmental Glomerulosclerosis in Adult Renal Transplant Recipients: A Meta-Analysis.

Background. Posttransplant recurrence of primary focal segmental glomerulosclerosis (rFSGS) in the form of massive proteinuria is not uncommon and has detrimental consequences on renal allograft survival. A putative circulating permeability factor has been implicated in the pathogenesis leading to widespread use of plasma exchange (PLEX). We reviewed published studies to assess the role of PLEX on treatment of rFSGS in adults. Methods. Eligible manuscripts compared PLEX or variants with conventional care for inducing proteinuria remission (PR) in rFSGS and were identified through MEDLINE and reference lists. Data were abstracted in parallel by two reviewers. Results. We detected 6 nonrandomized studies with 117 cases enrolled. In a random effects model, the pooled risk ratio for the composite endpoint of partial or complete PR was 0,38 in favour of PLEX (95% CI: 0,23-0,61). No statistical heterogeneity was observed among included studies (I (2) = 0%, p = 0,42). On average, 9-26 PLEX sessions were performed to achieve PR. Renal allograft loss due to recurrence was lower (range: 0%-67%) in patients treated with PLEX. Conclusion. Notwithstanding the inherent limitations of small, observational trials, PLEX appears to be effective for PR in rFSGS. Additional research is needed to further elucidate its optimal use and impact on long-term allograft survival.