Impact of Pre-existing Comorbidities on Long-term Outcomes in Kidney Transplant Recipients.

BACKGROUND: Outcomes of patients with end-stage renal disease are mainly affected by their comorbidities. Detailed data evaluating the impact of pre-transplant comorbidities on long-term outcome after kidney transplantation are largely missing. METHODS: In a long-term retrospective analysis, we investigated 839 deceased donor kidney transplant recipients (KTRs) who received transplants between 1999 and 2014. The prevalence and impact of the most relevant comorbidities were studied in detail. RESULTS: At the time of transplantation, 25% of KTRs had coronary artery disease (CAD), 16% had diabetes mellitus (DM), 11% had peripheral arterial disease (PAD), 8% had chronic heart failure (CHF), and 7% had cerebrovascular disease (CVD). KTRs with pre-existing CAD, DM, PAD, and CHF showed a significantly inferior patient survival. Multivariate analysis adjusting for all relevant factors and comorbidities confirmed CAD as most hazardous independent risk factor for premature death (hazard ratio [HR] 1.70; P = .002). A multivariate analysis revealed CHF and PAD as independent risk factors for death censored graft loss (HR 2.20; P = .003 and HR 1.80; P = .013). Diabetes was independently and significantly associated with T-cell- (HR 1.46; P = .020) and antibody-mediated rejections (HR 2.27; P = .030). CONCLUSIONS: Detailed quantification of the impact of pre-transplant comorbidities may facilitate the evaluation of transplant candidates, guide post-transplant follow-up, and may help to further refine prediction algorithms and allocation systems.

Effect of everolimus on skin lesions in patients treated for subependymal giant cell astrocytoma and renal angiomyolipoma: final 4-year results from the randomized EXIST-1 and EXIST-2 studies.

BACKGROUND: Tuberous sclerosis complex (TSC) is a genetic disorder associated with tumour growth in various organs, including the brain, kidneys, heart and skin. Cutaneous lesions are prevalent manifestations of TSC, occurring in up to 90% of patients. Oral mammalian target of rapamycin inhibitors, such as everolimus, is believed to be effective for treatment of TSC-associated lesions because they act on the underlying disease pathophysiology. OBJECTIVE: We evaluated the long-term effect of oral everolimus on TSC-associated skin lesions as a secondary objective in the phase III studies EXIST-1 (NCT00789828) and EXIST-2 (NCT00790400) after approximately 4 years of treatment. MATERIALS AND METHODS: Everolimus was dosed 4.5 mg/m2 /day (titrated to trough 5-15 ng/mL) in patients with TSC-associated subependymal giant cell astrocytoma in EXIST-1, and 10 mg/day initially in adult patients with TSC- or sporadic lymphangioleiomyomatosis-associated renal angiomyolipoma in EXIST-2. Following positive results from the core phase, remaining patients were offered open-label everolimus in an extension. Skin lesion response rate was the proportion of patients achieving complete or partial clinical response. RESULTS: A total of 105 patients in EXIST-1 and 107 in EXIST-2 received everolimus and had ≥1 skin lesion at baseline. Skin lesion response rate (95% confidence interval) was 58.1% (48.1-67.7%) in EXIST-1 and 68.2% (58.5-76.9%) in EXIST-2; most were partial responses. At week 192 (EXIST-1: n = 55; EXIST-2: n = 56), 69% and 66% had a response. Most common drug-related adverse event was stomatitis (41-45%). CONCLUSION: Oral everolimus improved TSC-related skin lesions, with responses sustained over 4 years of treatment in EXIST-1 and EXIST-2.

Late Steroid Withdrawal Following AB0-Incompatible Renal Transplantation.

BACKGROUND: Current evidence on steroid withdrawal following AB0-incompatible (AB0i) renal transplantation is low. We compared clinical outcomes of patients who agreed to late steroid withdrawal and patients who remained on steroid treatment. METHODS: Steroid withdrawal was carried out in 11 patients at ≥12 months after transplantation (group W). For comparison, we analyzed 19 patients who remained on triple immunosuppression including steroids (group M). Minimum follow-up was 24 months following transplantation and 12 months after steroid withdrawal. RESULTS: Baseline characteristics, including observation times, were not different between groups W and M. Graft survival was 100% in group W compared with 84% (16/19) in group M (P = .15). In group M, 1 patient experienced graft failure because of suspected antibody-mediated rejection (ABMR) following temporary cessation of mycophenolate treatment after a diagnosis of cryptococcal pneumonia. Two patients died with functioning graft because of sepsis. In group W, we observed 1 episode of ABMR following steroid withdrawal. At the end of follow-up, estimated glomerular filtration rates (eGFR) were 54 (19-91) versus 60 (15-85) mL/min/1.73 m2 in group W versus M, respectively (P = .67). CONCLUSIONS: Late steroid withdrawal following AB0i transplantation is feasible at a moderate risk of rejection. We recommend close monitoring of renal function and HLA antibodies during and after steroid withdrawal. On the other hand, the occurrence of severe infections causing death and graft loss in patients on triple maintenance immunosuppression including steroids should remind us to consider the overall immunosuppressive burden.

Identification of urine metabolites associated with 5-year changes in biomarkers of glucose homoeostasis.

AIM: Metabolomics provides information on pathogenetic mechanisms and targets for interventions, and may improve risk stratification. During the last decade, metabolomics studies were used to gain deeper insight into the pathogenesis of diabetes mellitus. However, longitudinal metabolomics studies of possible subclinical states of disturbed glucose metabolism are limited. Therefore, the aim of this study was to analyze the associations between baseline urinary metabolites and 5-year changes in continuous markers of glucose homoeostasis, including fasting glucose, HbA1c and homoeostasis model assessment of insulin resistance (HOMA-IR) index values. METHODS: Urine metabolites in 3986 participants at both baseline and 5-year follow-up of the population-based Inter99 study were analyzed by 1H-NMR spectroscopy. Linear regression and analyses of covariance models were used to detect associations between urine metabolites and 5-year changes in markers of glucose homoeostasis. RESULTS: Higher baseline levels of urinary alanine, betaine, N,N-dimethylglycine (DMG), creatinine and trimethylamine were associated with an increase in HbA1c from baseline to follow-up. In contrast, formic acid and trigonelline levels were associated with a decrease in HbA1c over time. Analyses of 5-year changes in fasting glucose and HOMA-IR index showed similar findings, with high baseline levels of lactic acid, beta-d-glucose, creatinine, alanine and 1-methylnicotinamide associated with increases in both parameters. CONCLUSION: Several urine metabolites were found to be associated with detrimental longitudinal changes in biomarkers of glucose homoeostasis. The identified metabolites point to mechanisms involving betaine and coffee metabolism as well as the possible influence of the gut microbiome.

Long-Term Outcomes of Kidney Transplant Recipients With Primary Idiopathic Focal Segmental Glomerulosclerosis.

BACKGROUND: Few data exist on recurrence rates, treatment response, and long-term outcomes in kidney transplant recipients (KTR) with primary focal segmental glomerulosclerosis (FSGS). METHODS: This retrospective, observational study included 1218 consecutive KTR during 2002 to 2016. All patients with primary idiopathic FSGS were identified through application of strict diagnostic criteria. Outcomes were followed over an average of 70.4 months. RESULTS: We identified 48 KTR (3.9%) with primary FSGS. Seven-year death-censored graft survival rate was 81% (primary FSGS) versus 85% (control) (P = .297). Eighteen KTR had FSGS recurrence (predicted incidence, 50% after 7 years). Seven-year death-censored graft survival rate in KTR with FSGS recurrence was significantly worse than in FSGS KTR without recurrence (63% versus 96%, P = .010). In the case of FSGS recurrence, a multi-modal treatment approach was applied, including plasma exchange (PE) (100% of patients), intravenous cyclosporine (50%), rituximab (61%), and the "Multiple Target Treatment" (39%). The median number of PE sessions was 27. Proteinuria decreased significantly and persistently during the course of treatment. Complete remission of FSGS was observed in 7 patients (39%); another 7 patients (39%) had partial remission (PE dependence was observed in 4 patients [22%]). Four patients (22%) with FSGS recurrence had early graft loss (<6 months after transplant) despite all treatment efforts. CONCLUSIONS: In KTR with primary FSGS, a high proportion of recurrence occurred, and recurrence was associated with significantly worse death-censored graft survival rates. However, a multi-modal treatment approach led to improvement of proteinuria and full or partial remission in most patients. Importantly, overall death-censored graft survival rate in KTR with primary FSGS was comparable with that in the control group.

Immunologic Long-term Outcomes of Living-Related Kidney Transplantations Depending on the Donor-Recipient Relationship.

BACKGROUND: The aim of this study is to analyze the long-term immunologic outcomes of living-related kidney transplantations depending on the donor-recipient relationship. METHODS: This retrospective single-center study included adult kidney transplant recipients (KTR) transplanted between 2000 and 2014. Among 1117 KTRs, 178 patients (15.9%) received living-related donations. Those patients were further categorized according to the donor-recipient relationship: 65 transplantations between siblings, 39 father-to-child (F-t-C) and 74 mother-to-child (M-t-C) donations. Allograft biopsies were performed for clinically suspected rejections. Data analysis included patient and graft survival, biopsy proven rejections (T-cell mediated [TCMR] or antibody mediated) and development of de novo donor-specific antibody. Outcome data were assessed over a period of a maximum 14 years. RESULTS: There was no significant difference between the groups (F-t-C, M-t-C, and siblings) with regard to HLA-mismatches, prior kidney transplantations, time on dialysis, and cold ischemia time. Among KTRs with related donors, the type of relationship had no significant influence on graft survival. F-t-C and M-t-C pairs showed comparable incidences of TCMR at 7 years post-transplantation, both significantly exceeding the rate in sibling-to-sibling pairs (26.2% and 26.8% vs 10%, respectively; P = .043). A multivariate Cox regression analysis adjusted for recipient age, donor age, and HLA (A, B, DR)-mismatches identified both M-t-C- and F-t-C-donations as important independent risk factors for TCMR (hazard ratio: 8.13; P < .001 and hazard ratio: 8.09; P = .001, respectively). There was no significant difference between the groups concerning the incidence of antibody-mediated rejection and de novo donor-specific antibody. CONCLUSION: Our results indicate that parent-to-child kidney donation is an independent risk factor for TCMR.

Incidence of Infectious Disease and Malignancies After Rituximab Therapy in Kidney Transplant Recipients: Results From a Cohort in Germany.

BACKGROUND: Rituximab is frequently used in solid organ transplantation off-label, especially in patients with renal allografts. Few data are available on the safety aspects of solid organ transplant recipients receiving rituximab. There is a knowledge gap on long-term follow-up data, in particular on infectious complications. PATIENTS AND METHODS: A retrospective observational registry study (German Registry on Autoimmune Diseases) comprising a total of 681 patients was conducted. The data of 63 adult kidney transplant recipients who received rituximab between 2006 and 2013 were used in this analysis. RESULTS: Median follow-up was 42 (1-109) months. At least 1 severe infection occurred in 57% of patients. The median time between the first rituximab infusion and the first infection was 4 (1-48) months. Of the overall 88 infections, 74 were severe bacterial infections, 5 were severe viral infections, 3 were severe fungal infections, 2 were combined severe bacterial and fungal infections, and 4 were combined severe viral, fungal and bacterial infections. Seven patients died during the observational period, 2 of them due to infectious complications. In the observational period, 1 case of squamous cell carcinoma but no other malignancies were observed. CONCLUSION: Consistent with previous data, a high incidence of infections was observed after rituximab treatment in kidney transplant recipients. Most infections occurred within 6 months after rituximab initiation. With more than 3 years of follow-up, we were able to document a low incidence of secondary malignancies after rituximab with only 1 case in our cohort.

Prolonged Low-Dose Prophylaxis With Valganciclovir in Cytomegalovirus-Negative Recipients of Kidney Transplants From Cytomegalovirus-Positive Donors Allows Seroconversion and Prevents Cytomegalovirus Disease.

BACKGROUND: Cytomegalovirus-negative recipients of kidneys from cytomegalovirus (CMV)-positive donors (D+/R-) are at high risk to develop severe clinical manifestations of CMV disease. Long-term data about incidence and timing of CMV seroconversion, CMV disease, and the influence of prolonged valganciclovir prophylaxis on the clinical course of CMV infection are missing. METHODS: We conducted a retrospective long-term study of 89 consecutive CMV D+/R- kidney transplant recipients transplanted between 2003 and 2012. All recipients received valganciclovir prophylaxis after transplantation (median 187 [126-261] days) with a median dose of 213 (181-338) mg/d. Long-term outcome was assessed over a maximum of 10 years post-transplant. RESULTS: During follow-up (median 62 months) 60 of 89 (67%) patients had CMV seroconversion, and 29 of 89 (33%) developed symptomatic CMV disease. In addition, in 38 of the 60 (63%), seroconversion occurred during prophylaxis (median 154 days post-transplant), and in 22 patients, after the end of prophylaxis (median 320 days after transplantation). Baseline characteristics of the 2 groups did not differ significantly. Seroconversion during prophylaxis vs seroconversion after the end of prophylaxis was associated with significantly lower incidence of CMV disease (34% vs 73%, P = .007), less severe CMV disease (16% vs 64%, P < .001), and fewer organ manifestations (26% vs 64%, P = .006). The risk of CMV disease was limited to the first 475 days after transplantation. Valganciclovir resistance occurred in just 1 case (1%). CONCLUSIONS: Prolonged prophylaxis with low-dose valganciclovir allowed CMV seroconversion during prophylaxis in a high proportion of D+/R- patients. Seroconversion occurred after a median of 154 days and was associated with significantly lower incidence of CMV disease, less severe CMV disease, and fewer CMV complications.

Late Conversion to Belatacept After Kidney Transplantation: Outcome and Prognostic Factors.

BACKGROUND: Conversion to belatacept at a later point after kidney transplantation (KT) as a rescue therapy has been shown to be beneficiary in an increasing number of patients, but prognostic factors for a favorable outcome have never been investigated. METHODS: The present study analyzed all KT patients after late conversion to belatacept in a single center regarding graft survival and changes in estimated glomerular filtration rate (eGFR), proteinuria, and mean fluorescence intensity (MFI) of donor-specific antibodies (DSA). RESULTS: A total of 69 KT patients were converted to belatacept. eGFR increased from 28.9 ± 18.2 mL/min/1.73 m2 at time of conversion to 34.8 ± 20.1 mL/min/1.73 m2 after 18 months (P = .025). After conversion, 26/69 patients (37.7%) showed a sustained increase in eGFR of >5 mL/min/1.73 m2 after 12 months and were defined as responders. All other patients (43/69, 62.3%) were defined as nonresponders. In multivariate analysis, nonresponders presented with significantly higher proteinuria (552 ± 690 vs 165 ± 158 mg/L; P = .004) at the time of conversion. Changes of eGFR from before conversion and the time of conversion were similar in both subgroups (-5.7 ± 9.2 and 29.2 ± 17.3 mL/min/1.73 m2 in responders and -4.6 ± 10.7 and 28.7 ± 19.0 mL/min/1.73 m2 in nonresponders). HLA antibody panel reactivity did not change after conversion. DSA-MFI was higher in nonresponders (7,155 ± 6,785) than in responders (2,336 ± 2,173; P = .001). One patient (1/69, 1.4%) developed de novo DSA after conversion, and no antibody-mediated rejection was diagnosed within 1,540 treatment months. CONCLUSIONS: Late conversion to belatacept is beneficiary for a subgroup of patients, with lower proteinuria at the time of conversion being an indicator for a favorable outcome.

Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae-Related Urinary Tract Infection in Kidney Transplant Recipients: Risk Factors, Treatment, and Long-Term Outcome.

BACKGROUND: Prevalence of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) has risen in kidney transplant (KT) patients, with no long-term data so far on graft function or survival. METHODS: KT patients with ESBL-E-positive urine culture were retrospectively analyzed regarding initial adequate antimicrobial therapy, recurrent infection, transplant function, and survival compared with an ESBL-E-negative KT control cohort. RESULTS: ESBL-E-positive KT patients (n = 93) were older (55.5 ± 16.1 vs 49.5 ± 16.8 y; P = .001), presented with higher trough levels of cyclosporine and tacrolimus (121 ± 71 vs 102 ± 32 ng/mL [P = .04]; and 7.9 ± 3.3 vs 7.0 ± 2.3 ng/mL [P = .04], respectively), higher dosages of mycophenolate (1,533 ± 670 vs 1,493 ± 436; P = .001), and more acute rejection episodes within 3 months before diagnosis (12.9% vs 0.8%; P < .0001) compared with control subjects (n = 591). Five-year patient survival was superior in control subjects compared with ESBL-E-positive patients (91.2% vs 83.5%; P = .034) but long-term graft function was similar. Hospitalization rates were higher in patients presenting with ESBL-E-related urinary tract infection (UTI) compared with control subjects with ESBL-E-negative UTI (60.3% vs 31.3%; P = .002) but 5-year graft survival was superior in patients presenting with ESBL-E-related UTI (88.6% vs 69.8%; P = .035) compared with control subjects with ESBL-E-negative UTI. Recurrence rates were similar in patients with or without ESBL-E-related UTI. Initial antibiotic treatment was adequate in 41.2% of patients presenting with ESBL-E-related urosepsis, resulting in a reevaluation of antibiotic stewardship in our clinic. CONCLUSIONS: ESBL-E detection in general was associated with higher mortality, but graft survival in patients with ESBL-E-related UTI was significantly better compared with ESBL-E-negative UTI.

Donor-Recipient Matching Based on Predicted Indirectly Recognizable HLA Epitopes Independently Predicts the Incidence of De Novo Donor-Specific HLA Antibodies Following Renal Transplantation.

De novo donor-specific HLA antibodies (dnDSA) are recognized as a risk factor for premature allograft failure. Determinants of DSA specificity are generated via the indirect allorecognition pathway. Here, we present supportive data for the relevance of predicted indirectly recognizable HLA epitopes (PIRCHE) to predict dnDSA following kidney transplantation. A total of 2787 consecutive kidney transplants performed between 1995 and 2015 without preformed DSA have been analyzed. De novo DSA were detected by single antigen bead assay. HLA epitope mismatches were determined by the HLAMatchmaker and PIRCHE approach and correlated in uni- and multivariate analyses with 10-year allograft survival and incidence of dnDSA. The PIRCHE-II score moderately predicted allograft survival. However, the predictive value of elevated PIRCHE-II scores >9 for the incidence of dnDSA was statistically significant (p < 0.001). In a multivariate Cox regression analysis adjusted for antigen mismatch and HLAMatchmaker epitopes, the PIRCHE-II score could be identified as an independent risk factor for dnDSA. The PIRCHE-II score independently from the antigen mismatch and HLAMatchmaker epitopes could be revealed as being a strong predictor for dnDSA. PIRCHE may help to identify acceptable mismatches with decreased risk of dnDSA and thus improve long-term renal allograft survival.

Biomarkers in acute kidney injury - pathophysiological basis and clinical performance.

Various biomarkers of acute kidney injury (AKI) have been discovered and characterized in the recent past. These molecules can be detected in urine or blood and signify structural damage to the kidney. Clinically, they are proposed as adjunct diagnostics to serum creatinine and urinary output to improve the early detection, differential diagnosis and prognostic assessment of AKI. The most obvious requirements for a biomarker include its reflection of the underlying pathophysiology of the disease. Hence, a biomarker of AKI should derive from the injured kidney and reflect a molecular process intimately connected with tissue injury. Here, we provide an overview of the basic pathophysiology, the cellular sources and the clinical performance of the most important currently proposed biomarkers of AKI: neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), interleukin-18 (IL-18), insulin-like growth factor-binding protein 7 (IGFBP7), tissue inhibitor of metalloproteinase 2 (TIMP-2) and calprotectin (S100A8/9). We also acknowledge each biomarker's advantages and disadvantages as well as important knowledge gaps and perspectives for future studies.

[Sporadic Lymphangioleiomyomatosis (sLAM) and Tuberous Sclerosis Complex (TSC) - Pulmonary Manifestations]. / Sporadische Lymphangioleiomyomatose (sLAM) und Tuberöse-Sklerose-Komplex (TSC) ­ Pulmonale Manifestationen.

Lymphangioleiomyomatosis (LAM) is a rare multi-system disorder affecting predominantly women of childbearing age. The disease entity is divided in sporadic LAM (sLAM) and LAM associated with tuberous sclerosis complex (TSC). In up to 50 % of female TSC-patients pulmonary involvement (TSC-LAM) can be found, with first clinical symptoms usually starting between 25 and 30 years of age. Progressive deterioration of lung function of 3 - 11 % of diffusion capacity per year has been described, that's why all female TSC patients should be screened for LAM (pulmonary function testing, 6-minute walk test, high-resolution chest CT scan). MTOR inhibitors such as Everolimus or Sirolimus are implemented in the treatment of TSC/LAM and found to control disease burden. Screening for all organ manifestations in TSC is recommended and allows to improve prognosis and to prevent complications in TSC.

Treatment of renal angiomyolipoma in tuberous sclerosis complex (TSC) patients.

In adult tuberous sclerosis complex (TSC) patients, renal complications are the leading cause of death. Beginning in childhood, up to 80 % of patients develop renal angiomyolipoma characterized by a size-dependent risk of life-threatening bleeding. After discovery of the two causative genes, TSC1 and TSC2, and the role of mammalian target of rapamycin (mTOR) regulation in the pathogenesis of TSC, an increasing number of clinical studies evaluating mTOR inhibition in TSC patients have shown impressive results in many organ manifestations, such as brain, lung, and kidney. For renal angiomyolipoma, mTOR inhibitor treatment fundamentally changed the approach from preventive embolization or even partial nephrectomy to everolimus treatment in order to preserve kidney function.

Successful Recovery of Acute Renal Transplant Failure in Recurrent Hepatitis C Virus-Associated Membranoproliferative Glomerulonephritis.

Recurrence of hepatitis C virus (HCV)-associated membranoproliferative glomerulonephritis (MPGN) in the kidney transplant may lead to continuous graft deterioration and the need for further renal replacement therapy. The novel direct-acting antiviral agents (DAAs) allow a highly effective and interferon-free treatment option for chronic HCV-infected patients. Data on the therapeutic safety and efficacy in HCV-infected renal transplant patients are sparse, especially for patients with severe renal impairment. We report the case of a 63-year-old female HCV-positive renal transplant patient with biopsy-proven recurrence of MPGN in the renal graft 3 years after transplant. Because of rapid loss of transplant function and consecutive need for hemodialysis, we initiated a combined anti-HCV-directed therapy regimen consisting of daclatasvir and simeprevir over 12 weeks. Viral clearance of HCV was obtained as early as 2 weeks after start of treatment. No adverse therapy-associated side effects were observed, and immunosuppressive dosing remained unchanged. Importantly, graft function fully recovered and hemodialysis was stopped 2 mo after the end of daclatasvir/simeprevir treatment. We report the first case of successful recovery of dialysis-dependent renal transplant failure after treatment of recurrent HCV-associated MPGN in a kidney transplant recipient by curing the underlying HCV infection with a combination of novel DAAs.

Risk Evaluation and Outcome of Pneumocystis jirovecii Pneumonia in Kidney Transplant Patients.

Pneumocystis jirovecii pneumonia (PJP) affects immunocompromised patients. As a result of effective prophylaxis in the 1st months after kidney transplantation, PJP is increasingly diagnosed in the long term after transplantation. The present study evaluates course and outcome of PJP in a single transplant center from 2010 to 2015. Twenty-three patients presented with PJP at a mean of 53.7 ± 50.2 months after transplantation. Of these, 3 patients underwent ABO-incompatible (ABO-i) living-donor transplantation and 3 patients were treated with the use of belatacept. For risk estimation, 3 control cohorts were defined: a control group of all kidney transplant patients presenting for routine follow up (n = 575), all patients transplanted in an ABO-i setting (n = 45), and all patients treated with belatacept in our clinic (n = 69). Mortality in patients with PJP was 3/23 (13%) and graft loss after PJP was 3/23 (13%) resulting in patient and graft survivals of 87% and 73.9%, respectively. All patients were without PJP prophylaxis at time of diagnosis. Five of the 23 PJP patients received rejection therapy or dose escalation of immunosuppression 6 months before PJP infection, and 1 patient experienced acute rejection within 6 months after PJP treatment. In the course of PJP, 8 patients developed acute respiratory insufficiency. At time of PJP diagnosis, patients presented with severe lymphopenia (mean ± SD lymphocyte count, 0.64 ± 0.27/nL; normal range: 1.5-3/nL). Patients after ABO-i transplantation, as well as patients treated with belatacept, showed an increased risk for PJP (7.3% and 4.3%, respectively); however, in belatacept patients, other risk factors, such as age, low estimated glomerular filtration rate (eGFR), and lymphopenia seemed to contribute to this increased risk.

Structures and processes necessary for providing effective home treatment to severely mentally ill persons: a naturalistic study.

BACKGROUND: Home treatment for severely mentally ill persons is becoming increasingly popular. This research aims to identify structures and processes in home treatment that impact on patient-related outcomes. METHODS: We analysed 17 networks that provide home treatment to severely mentally ill persons using a naturalistic approach. The networks were similar with regard to central components of home treatment such as case management, 24 h crisis hotline and home visits, but differed in all other aspects such as the multidisciplinary teams, time spent with patients, etc. To determine treatment outcome, patients' psychosocial functioning was measured using the Health of the Nation Outcome Scales (HoNOS). Structures and processes were assessed using claims data and questionnaires answered by the different networks. Primary outcome was highlighted by the change in HoNOS scores from the start of home treatment compared with 6 months later. We sought to explain this outcome through patient and network characteristics using regression analysis. Data on 3,567 patients was available. RESULTS: On average, psychosocial functioning improved by 0.84 across networks between t0 and t1. There were more similarities than differences between the networks with regard to the structures and processes that we tested. A univariate regression analysis found staff's prior experience in mental health care and the effort that they invested in their work correlated positively with patient outcome. This needs to be interpreted under considering that univariate analysis does not show causal relationship. A high case load per case manager, increased and longer patient contact and more family intervention were correlated with worse patient outcome, probably indicating that sicker patients receive more care and intervention. CONCLUSION: Home treatment networks succeed in delivering care tailored to the needs of patients. In order to improve the quality of care in home treatment, this study suggests employing experienced staff who is ready to invest more effort in their patients. Further research needs to consider a longer follow-up time.

Living Donor Transplantation: Long-Term Evolution Related to Age Matching.

The lack of donors is favoring living kidney donor (LKD) transplantation worldwide, quite often beyond the classic age-matching rules. We analysed renal function (RF) at 1 and 5 years in all donor and recipients as well as death-censored graft and patient survival. LKD recipients were divided into 4 subgroups: young recipients-young donors (YR-YD; N = 355), elderly recipients-young donors (ER-YD; N = 13), young recipients-elderly donors (YR-ED; N = 67), and elderly recipients-elderly donors (ER-ED; N = 38). "Elderly" was defined as ≥60 years. RF was better in those who received a young allograft (YR-YD/ER-YD) at any time (P < .001). There was a trend toward higher proteinuria among the recipients of an old allograft (YR-ED/ER-ED) at any time (P = not significant [NS]). However, our population showed low levels of proteinuria and this was not a risk factor for graft failure. Logistic regression model showed that creatinine level at 1 year is a good predictor of graft losses. Graft survival was worse in the allografts from elderly donors (P < .001). Analysing the young recipients, renal survival was inferior in those who received an old kidney (YR-ED; P < .00005) as well as mortality rates at 14 years (P = .03). The RF of young (N = 295) and elderly donors (N = 98) was optimal with no progression to ESRD or deaths registered during follow-up. In conclusion, young recipients of elderly kidneys pay the price of a worse RF, allograft prognosis, and patient prognosis. The pair YR-ED is a doable option, but we recommend age matching when it is possible.

[Immunosuppression and its use in kidney transplantation]. / Immunsuppression und Ergebnisse in der Nierentransplantation.

BACKGROUND: Current immunosuppressive protocols effectively prevent acute rejection of renal allografts. Extensive drug toxicity and the deleterious effects of long-term immunosuppression are associated with significant morbidity and mortality. OBJECTIVES: The purpose of this article is to provide an overview over modern immunosuppressants and their unwanted side effects and to discuss strategies for improved long-term transplant survival. METHODS: Review of the current topic-related literature and discussion of our own experience. RESULTS: The use of antibody induction together with an initial combination therapy of calcineurin inhibitors, mycophenolate and steroids is recommended and results in excellent early outcomes. Detrimental effects include an increased incidence of infections, malignomas, and cardiovascular diseases. Long-term transplant survival is impaired by extensive drug toxicity and the frequent development of donor specific antibodies. Reduction of overall cumulative exposure to immunosuppressants or the reduction of specific toxic drugs such as calcineurin inhibitors and steroids may improve long-term results. Alternative immunosuppressants like mTOR inhibitors and belatacept appear to be effective and safe but their long-term effects on patient and allograft survival needs to be established in clinical trials. CONCLUSIONS: Current immunosuppressants provide effective protection from renal allograft rejection. However, their use is complicated by serious side effects. In the future, development of novel immunosuppressants and optimization of minimization strategies may help to improve long-term success after kidney transplantation.