Immunoglobulin G-4-Related Retroperitoneal Fibrosis.

Retroperitoneal fibrosis is caused by the replacement of normal retroperitoneal tissue with fibrosis. The majority of the cases are idiopathic, but some secondary causes include malignancy, infection, drugs, and radiotherapy. Immunoglobulin G-4 (IgG-4) related disease is a relatively newer disease and one of the rarer causes of retroperitoneal fibrosis. It usually involves the pancreas, lungs, kidneys, aorta lacrimal and salivary glands, or extrapancreatic bile duct. Elevated serum IgG-4 is the biomarker of the disease and its levels correlate with disease activity. High-dose glucocorticoid is the treatment of choice.

Canadian Society of Transplantation and Canadian Society of Nephrology Commentary on the 2017 KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors.

PURPOSE OF REVIEW: To review an international guideline on the evaluation and care of living kidney donors and provide a commentary on the applicability of the recommendations to the Canadian donor population. SOURCES OF INFORMATION: We reviewed the 2017 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors and compared this guideline to the Canadian 2014 Kidney Paired Donation (KPD) Protocol for Participating Donors. METHODS: A working group was formed consisting of members from the Canadian Society of Transplantation and the Canadian Society of Nephrology. Members were selected to have representation from across Canada and in various subspecialties related to living kidney donation, including nephrology, surgery, transplantation, pediatrics, and ethics. KEY FINDINGS: Many of the KDIGO Guideline recommendations align with the KPD Protocol recommendations. Canadian researchers have contributed to much of the evidence on donor evaluation and outcomes used to support the KDIGO Guideline recommendations. LIMITATIONS: Certain outcomes and risk assessment tools have yet to be validated in the Canadian donor population. IMPLICATIONS: Living kidney donors should be counseled on the risks of postdonation outcomes given recent evidence, understanding the limitations of the literature with respect to its generalizability to the Canadian donor population.

JUSTIFICATION: Examiner une directive internationale sur l'évaluation et la prise en charge des donneurs vivants d'un rein et formuler un commentaire sur l'applicabilité de ces recommandations à la population des donneurs canadiens. SOURCES: Nous avons révisé le guide des pratiques cliniques relatives à l'évaluation et à la prise en charge des donneurs vivants d'un rein (Clinical Practice Guideline for Evaluation and Care of Living Kidney Donors) de 2017 du KDIGO (Kidney Disease: Improving Global Outcomes) et nous l'avons comparé aux recommandations canadiennes de 2014 du Protocole de don croisé d'un rein par donneurs participants (Kidney Paired Donation Protocol for Participating Donors). MÉTHODOLOGIE: Un groupe de travail réunissant des membres de la Société canadienne de transplantation et de la Société canadienne de néphrologie a été formé. Les membres ont été sélectionnés pour représenter tout le Canada et plusieurs sous-spécialisations relatives au don vivant d'un rein, notamment la néphrologie, la chirurgie, la transplantation, la pédiatrie et l'éthique. PRINCIPALES CONSTATATIONS: Plusieurs des recommandations du KDIGO s'harmonisent aux recommandations du protocole de don croisé d'un rein. Les chercheurs canadiens ont contribué en grande partie aux données sur l'évaluation des donneurs et des résultats utilisées pour appuyer les recommandations formulées dans les lignes directrices du KDIGO. LIMITES: Certains résultats et outils d'évaluation des risques doivent encore être validés dans la population des donneurs canadiens. CONCLUSION: Compte tenu des plus récentes données, les donneurs vivants d'un rein devraient être mis en garde concernant les risques sur leur santé post-don, tout en comprenant les limites de la littérature en ce qui concerne leur généralisabilité à la population de donneurs canadiens.

Bariatric Surgery Causing Hyperammonemia.

Bariatric surgery is recognized as a highly effective therapy for obesity but it does carry a risk of short term and long term complications since it results in a permanent alteration of the patient's anatomy. We present a case of 45-year-old female presented with a macular rash on extremities and facial rash from a rehabilitation center after having been discharged a month earlier from a revision surgery on her gastric bypass for anastomotic bleeding. She progressively became lethargic with Magnetic Resonance Imaging (MRI) of the brain showed symmetrically restricted diffusion concerning for hypoxic injury. Her ammonia levels were at 142 micromoles per liter (mmol/L) at the initial check which worsened to 432 mmol/L over a few days, despite treatment. Laboratory investigation later revealed her to be deficient in zinc along with many essential and nonessential amino acids. Supplemental nutrition was initiated, specifically fortifying her parenteral feeds with the essential amino acid combinations that were found deficient on testing. This lead to a slow but progressive improvement in encephalopathy. This case highlights the importance of understanding the short and long term complications of bariatric surgery. Although neurological complications are rare with peripheral neuropathy being the most common one, hyperammonemic encephalopathy is a very severe complication, with incompletely understood mechanisms and predispositions, frequently resulting in failure of recognition and subsequent delays in intervention.

Common Questions and Misconceptions in the Management of Renal Transplant Patients: A Guide for Health Care Providers in the Posttransplant Setting.

Once renal transplant recipients are stabilized and require less frequent follow-up with their transplant team, health care providers outside of the transplant setting play an integral role in patients' ongoing medical care. Given renal transplant recipients' inherent complexity, these health care providers often seek consult regarding decisions that may affect transplant-related medications or outcomes. In this review, we discuss answers to 10 of the questions commonly posed to our renal transplant team by other health care providers.

The CLEAR study: a 5-day, 3-g loading dose of mycophenolate mofetil versus standard 2-g dosing in renal transplantation.

BACKGROUND AND OBJECTIVES: Adequate early mycophenolic acid (MPA) exposure is associated with lower rates of acute rejection in renal transplantation. The aim of this randomized controlled trial was to determine if higher initial mycophenolate mofetil (MMF) doses increased the proportion of patients reaching therapeutic MPA levels (30 to 60 mg.h/L) by day 5. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: De novo renal transplant patients were randomized to receive intensified dosing of MMF (1.5 g twice daily on days 1 to 5, then 1.0 g twice daily) or standard dosing (1.0 g twice daily). All recipients received tacrolimus and prednisone. Full MPA areas under the curve (AUCs) were completed on days 3 and 5, whereas a limited sampling strategy was utilized at four subsequent time points. RESULTS: At day 5, 47.5% of the MMF 3-g arm achieved the MPA therapeutic window versus 54.4% of the MMF 2-g arm. However, MPA AUC levels were significantly higher in the 3-g arm at day 3 and 5. This resulted in a trend for fewer treated acute rejections at 6 months. Significantly more acute rejections (treated, biopsy-proven including and excluding borderline) occurred in patients with MPA AUC levels<30 mg.h/L compared with those >or=30 mg.h/L at day 5. No significant differences were seen in common adverse events. CONCLUSIONS: A limited intensified dose of MMF increased early MPA exposure and was well tolerated. Further studies are required to determine whether limited intensified MMF dosing can reduce acute rejection.

Screening for de novo anti-human leukocyte antigen antibodies in nonsensitized kidney transplant recipients does not predict acute rejection.

BACKGROUND: The purpose of this study was to determine whether screening for anti-human leukocyte antigen (HLA) antibodies (Abs) could predict development of acute rejection (AR) before clinical evidence of kidney allograft dysfunction in nonsensitized recipients. METHODS: Eighty-four non-HLA identical kidney transplant recipients were prospectively tested for anti-HLA Abs (FlowPRA analysis and anti-HLA Ab specificity determination) at 0, 10, 20, 30, 60, 90, 180 and 365 posttransplantation, and at the time of clinical suspicion of AR. Allograft biopsies were performed at the time of engraftment, 3 and 12 months posttransplantation, when patients developed new anti-HLA Abs, or when clinically indicated. RESULTS: Among the 70 patients without preformed anti-HLA Abs, 11 developed de novo anti-HLA Abs (8 donor-specific Abs) at a median of 30 days (q1-q3=10-180 days) after transplantation. Patients with de novo anti-HLA Abs had a shorter time to AR than patients without de novo anti-HLA Abs, P=0.06. However, in all cases, de novo anti-HLA Abs developed concomitantly or after a clinically evident AR. CONCLUSIONS: Although de novo anti-HLA Abs were associated with AR, routine screening for anti-HLA Abs was not useful in identifying patients at risk for AR before clinical evidence of allograft dysfunction.

Factors associated with progression of interstitial fibrosis in renal transplant patients receiving tacrolimus and mycophenolate mofetil.

BACKGROUND: We recently reported a randomized study in renal transplant patients (RTP) receiving tacrolimus, mycophenolate mofetil, and prednisone in which patients who had early protocol biopsies (PBx) derived no benefit compared with controls (no PBx) at 6 months, likely due to the low prevalence of subclinical rejection. We report on the follow-up of these patients to 24 months at which time a repeat PBx and tests of renal function were performed. METHODS: Of the 240 RTP randomized, 22 were excluded for a protocol violation. Approximately 75% of the remaining 218 (111 PBx and 107 controls) completed the study. RESULTS: At 24 months, graft function was excellent with a mean creatinine clearance of approximately 74 mL/min and negligible proteinuria; however, the prevalence of interstitial fibrosis and tubular atrophy (IF/TA)-ci + ct more than or equal to 2-increased from approximately 3% at baseline to up to 40% to 50%. By logistic regression analysis, the only independent positive correlate of IF/TA was transplantation with a deceased donor. However, by post hoc analysis, use of angiotensin-II-converting enzyme inhibitors or angiotensin II receptor blockers was negatively correlated with both the prevalence of IF/TA at 24 months and its progression between 6 and 24 months in RTP that had paired biopsies. CONCLUSIONS: A regimen of tacrolimus, mycophenolate mofetil, and prednisone results in excellent renal function at 24 months posttransplant but with a progressive increase in IF/TA. A potential inhibitory effect of angiotensin-II-converting enzyme inhibitor/angiotensin II receptor blockers on IF/TA is suggested that requires confirmation in a randomized study.

A matched cohort pharmacoepidemiological analysis of steroid free immunosuppression in renal transplantation.

BACKGROUND: This longitudinal, sequential, matched closed-cohort design pharmacoepidemiological analysis examined the influence of maintenance steroid therapy in 380 first graft recipients after renal transplantation under conditions of normal clinical practice. METHODS: Nonexposed (steroid avoidance, n=190) and exposed (steroid treated, n=190) cohorts were matched 1:1 for key demographic factors, including donor source (living or deceased), diabetic status, panel reactive antibody level, recipient age (by decade), and sex. RESULTS: Cohorts were comparable for all variables except median human leukocyte antigen mismatch (4 vs. 3, P=0.03), use of tacrolimus (90.0% vs. 59.5%, P

Probability, predictors, and prognosis of posttransplantation glomerulonephritis.

Glomerulonephritis (GN) is the leading cause of chronic kidney disease among recipients of renal transplants. Because modern immunosuppressive regimens have reduced the incidence of rejection-related graft loss, the probability and clinical significance of posttransplantation GN (PTGN) requires reevaluation. In this Canadian epidemiologic study, we monitored 2026 sequential renal transplant recipients whose original renal disease resulted from biopsy-proven GN (36%), from presumed GN (7.8%), or from disorders other than GN (56%) for 15 yr without loss to follow-up. Kaplan-Meier estimates of PTGN in the whole population were 5.5% at 5 yr, 10.1% at 10 yr, and 15.7% at 15 yr. PTGN was diagnosed in 24.3% of patients whose original renal disease resulted from biopsy-proven GN, compared with 11.8% of those with presumed GN and 10.5% of those with disorders other than GN. Biopsy-proven GN in the native kidney, male gender, younger age, and nonwhite ethnicity predicted PTGN. Current immunosuppressive regimens did not associate with a reduced frequency of PTGN. Patients who developed PTGN had significantly reduced graft survival (10.2 versus 69.7%; P < 0.0001). In summary, in the Canadian population, PTGN is a common and serious complication that causes accelerated graft failure, despite the use of modern immunosuppressive regimens.

A prospective 3-yr evaluation of tacrolimus-based immunosuppressive therapy in immunological high risk renal allograft recipients.

BACKGROUND: There have been no published data on use of the the newer immunosuppressants tacrolimus and mycophenolate mofetil (MMF) in high immunological risk renal transplantation. We therefore undertook a prospective study to systematically assess outcomes using these agents as part of an aggressive immunosuppressive regimen. METHODS: Fifty-nine high-risk renal allograft recipients were enrolled at 10 Canadian sites and given a regimen of: a biological induction agent, tacrolimus, MMF, and corticosteroids. Patients included 10 (17%) who had lost a previous graft to rejection <1 yr, 31 (53%) with a current panel reactive antibody (PRA) >30%, 47 (80%) with a historic PRA >50%, four (7%) who had a positive historical T-cell crossmatch with the current donor, and six (10%) with a current positive B-cell crossmatch. The mean peak PRA was 76 +/- 33%. RESULTS: The estimated 3-yr Kaplan-Meier patient and graft survival estimates were 89% and 75%, respectively. There were nine graft losses other than deaths with a functioning graft, of which six were preceded by delayed graft function (p = 0.01, chi2). Sixteen (27%) recipients experienced at least one episode of biopsy-confirmed acute rejection. Infections included cytomegalovirus in 16 patients, eight of whom had tissue-invasive disease. Only one malignancy occurred. CONCLUSIONS: The immunosuppressive strategy investigated is effective and displays a satisfactory safety profile in high immunological risk renal allograft recipients.

Probability of mortality of critically ill cancer patients at 72 h of intensive care unit (ICU) management.

GOALS: To develop and validate a model for probability of hospital mortality for cancer patients at 72 h of intensive care unit (ICU) management. PATIENTS AND METHODS: This is an inception cohort study performed at four ICUs of academic medical centers in the United States. Defined continuous and categorical variables were collected on consecutive patients with cancer admitted to the ICU. A preliminary model was developed from 827 patients and then validated on an additional 415 patients. Multiple logistic regression modeling was used to develop the models, which were subsequently evaluated for discrimination and calibration. The main outcome measure is in-hospital death. RESULTS: A probability of mortality model, which incorporates ten discrete categorical variables, was developed and validated. All variables were collected at 72 h of ICU care. Variables included evidence of disease progression, performance status before hospitalization, heart rate >100 beats/min, Glasgow coma score 40 mg/dl, and a urine output of <150 ml for any 8 h in the previous 24 h. The p values for the fit of the preliminary and validation models were 0.535 and 0.354 respectively, and the areas under the receiver operating characteristic (ROC) curves were 0.809 and 0.820. CONCLUSIONS: We report a multivariable logistic regression model to estimate the probability of hospital mortality in critically ill cancer patients at 72 h of ICU care. The model is comprised of ten unambiguous and readily available variables. When used in conjunction with clinical judgment, this model should improve discussions about goals of care of these patients. Additional validation in a community hospital setting is warranted.