Comparison of eGFR Equations to Guide Dosing of Medications for Kidney Transplant Recipients.

BACKGROUND: Clinicians caring for kidney transplant recipients (KTRs) most commonly use estimated glomerular filtration rate (eGFR) to guide medication dosing as it is the most readily available measure of kidney function. Which eGFR equations provide the most accurate medication dosing guidance for KTRs remains uncertain. METHODS: We studied 415 stable KTRs in Canada and New Zealand. Participants completed same-day measurements of creatinine and cystatin C and measured GFR (diethylenetriaminepentaacetic acid). Chronic Kidney Disease Epidemiology Collaboration, European Kidney Function Consortium, and transplant-specific eGFR equations were compared with both Cockcroft-Gault creatinine clearance (CrCl) and measured GFR. eGFR equations were assessed both indexed to a standardized body surface area (BSA) of 1.73 m2 (milliliter per minute per 1.73 m2, as is conventional reporting from most clinical laboratories) and nonindexed (milliliter per minute) accounting for actual BSA. The primary outcome was the proportion of medication dosing discordance relative to Cockcroft-Gault CrCl or measured GFR for 8 commonly prescribed medications. Stratified analyses were performed on the basis of obesity status. RESULTS: Nonindexed eGFR equations (milliliter per minute) resulted in substantially lower medication dosing discordance compared with indexed eGFR equations (milliliter per minute per 1.73 m2). These findings were most pronounced among KTRs with obesity, in whom underdosing was frequent. When compared with Cockcroft-Gault CrCl, the lowest proportion of discordance was found with the nonindexed 2023 transplant-specific equation. When compared with measured GFR, the lowest proportion of discordance was found with the nonindexed 2021 Chronic Kidney Disease Epidemiology CollaborationCr/CysC equation. CONCLUSIONS: Nonindexed eGFR values accounting for actual BSA should be used by clinicians for medication dosing in KTRs. These findings may inform KT providers about which eGFR equations provide the safest, most accurate medication dosing guidance for KTRs.

Epidemiology of Cancer in Kidney Transplant Recipients.

Kidney transplantation is the ideal treatment modality for patients with end-stage kidney disease, with excellent outcomes post-transplant compared with dialysis. However, kidney transplant recipients are at increased risk of infections and cancer because of the need for immunosuppression. Kidney transplant recipients have approximately two to three times greater risk of developing cancer than the general population, and cancer is a major contributor to morbidity and mortality. Most of the increased risk is driven by viral-mediated cancers such as post-transplant lymphoproliferative disorder, anogenital cancers, and Kaposi sarcoma. Nonmelanoma skin cancer is the most frequent type of cancer in kidney transplant recipients, likely due to an interaction between ultraviolet radiation exposure and decreased immune surveillance. Occurrence of the more common types of solid organ cancers seen in the general population, such as breast, prostate, lung, and colorectal cancers, is not, or is only mildly, increased post-transplant. Clinical care and future research should focus on prevention and on improving outcomes for important immunosuppression-related malignancies, and treatment options for other cancers occurring in the transplant setting. Semin Nephrol 36:x-xx © 20XX Elsevier Inc. All rights reserved.

Infections Following Kidney Transplantation After Exposure to Immunosuppression for Treatment of Glomerulonephritis.

RATIONALE & OBJECTIVE: Kidney transplant patients with glomerulonephritis (GN) as their native disease commonly have received pretransplant immunosuppression (PTI). This may contribute to the immunosuppression burden potentially increasing the risk for infections after transplantation. STUDY DESIGN: Single-center, retrospective cohort study. SETTING & PARTICIPANTS: Recipients of a kidney transplant from January 2005 until May 2020 at a tertiary care university teaching hospital. EXPOSURE: Patients with GN as their native kidney disease who received PTI for treatment of GN (n=184) were compared with nondiabetic recipients of kidney transplants who did not receive PTI (n = 579). OUTCOME: First occurrence after transplantation of an infection outcome, either viral (BK or cytomegalovirus [CMV] infection) or bacterial. ANALYTICAL APPROACH: Cox regression analysis adjusted for age at transplant, sex, race, donor type, year of transplant surgery, dialysis vintage, receipt of T-cell depleting induction, and CMV transplant status. RESULTS: Over a median follow-up period of 5.7 years, patients with GN PTI were not at an increased risk for developing any first viral infection compared with controls (adjusted HR [AHR] 0.69 [95% CI, 0.52-0.91]) nor at increased risk for specific viral infections: BK infection 19.6% vs 26.3% (AHR 0.72 [95% CI, 0.50-1.05]) or CMV infection, 24.5% vs 29.0% (AHR, 0.76 [95% CI, 0.54-1.07]), respectively. There was also no increased risk of developing a first bacterial infection: 54.5% vs 57.5% (AHR, 0.90 [95% CI, 0.71-1.13]). These findings of no increased risk for infection were independent of the type of PTI used (cyclophosphamide, rituximab, mycophenolate mofetil, or calcineurin inhibitor) or the type of T-cell depleting induction therapy (alemtuzumab or antithymocyte globulin) administered. LIMITATIONS: Single-center study, no data on methylprednisone use for PTI, unmeasured confounding. CONCLUSIONS: Use of PTI for the treatment of GN was not associated with an increased risk of viral (BK or CMV) or bacterial infection after transplantation. Additional surveillance for infection after transplantation for patients who received PTI may not be necessary. PLAIN-LANGUAGE SUMMARY: Many kidney transplant patients have glomerular disease as the cause of kidney failure. These patients may be exposed to immunosuppression before transplantation, which could increase the risk for infections after receipt of a transplanted kidney. We identified kidney transplant recipients at a university teaching hospital who received immunosuppression before transplant for the treatment of glomerular kidney disease. We examined their risk for infection after transplantation by comparing it with the risk among transplant patients who were not exposed to immunosuppression before transplant. We observed no increased risk for infection after exposure to prior immunosuppression. Therefore, patients exposed to significant amounts of immunosuppression before transplantation may not require special surveillance or medication adjustment for fear of infection after their receipt of a kidney transplant.

Risk of venous thromboembolism or hemorrhage among individuals with chronic kidney disease on prophylactic anticoagulant after hip or knee arthroplasty.

Chronic kidney disease (CKD) confers a high risk of thrombosis and bleeding. However, little evidence exists regarding the optimal choice of postoperative thromboprophylaxis in these patients. We conducted a population-based, retrospective cohort study among adults ≥66 years old with CKD undergoing hip or knee arthroplasty who had filled an outpatient prophylactic anticoagulant prescription between 2010 and 2020 in Ontario, Canada. The primary outcomes of venous thrombosis (VTE) and hemorrhage were identified by validated algorithms using relevant diagnoses and billing codes. Overlap-weighted cause-specific Cox proportional hazard models were used to examine the association of direct oral anticoagulants (DOAC) on the 90-day risk of VTE and hemorrhage compared with low-molecular-weight heparin (LMWH). A total of 27 645 patients were prescribed DOAC (N = 22 943) or LMWH (N = 4702) after arthroplasty. Rivaroxaban was the predominant DOAC (94.5%), while LMWH mainly included enoxaparin (67%) and dalteparin (31.5%). DOAC users had higher eGFRs, fewer co-morbidities, and surgery in more recent years compared to LMWH users. After weighing, DOAC (compared with LMWH) was associated with a lower risk of VTE (DOAC: 1.5% vs. LMWH: 2.1%, weighted hazard ratio [HR] 0.75, 95% confidence interval [CI] 0.59-0.94) and a higher risk of hemorrhage (DOAC: 1.3% vs. LMWH: 1.0%, weighted HR 1.44, 95% CI 1.04-1.99). Additional analyses including a more stringent VTE defining algorithm, different eGFR cut-offs, and limiting to rivaroxaban and enoxaparin showed consistent findings. Among elderly adults with CKD, DOAC was associated with a lower VTE risk and a higher hemorrhage risk compared to LMWH following hip or knee arthroplasty.

CanVasc consensus recommendations for the use of avacopan in antineutrophil cytoplasm antibody-associated vasculitis: 2022 addendum.

OBJECTIVE: In 2020, the Canadian Vasculitis Research Network (CanVasc) published their updated recommendations for the management of ANCA-associated vasculitides (AAV). The current addendum provides further recommendations regarding the use of avacopan in AAV based on a review of newly available evidence. METHODS: An updated systematic literature review on avacopan (formerly, CCX168) using Medline, Embase, and the Cochrane Library was performed for publications up to September 2022. New recommendations were developed and categorized according to the EULAR grading levels, as done for previous CanVasc recommendations. A modified Delphi procedure and videoconferences were used to reach ≥80% consensus on the inclusion, wording and grading of each recommendation. RESULTS: Three new recommendations were developed. They focus on avacopan therapy indication and duration, as well as timely glucocorticoid tapering. CONCLUSION: These 2022 addended recommendations provide rheumatologists, nephrologists and other specialists caring for patients with AAV with guidance for the use of avacopan, based on current evidence and consensus from Canadian experts.

Malignancy risk in kidney transplant recipients exposed to immunosuppression pre-transplant for the treatment of glomerulonephritis.

BACKGROUND: Kidney transplant patients with glomerulonephritis (GN) as their native disease may receive significant amounts of pre-transplant immunosuppression (PTI), which could increase the risk for development of malignancy post-transplant. METHODS: We conducted a single-center, retrospective study of kidney transplant recipients from January 2005 until May 2020. Patients with GN as their native kidney disease who received PTI for treatment of GN (n = 184) were compared with a control cohort (n = 579) of non-diabetic, non-PTI-receiving kidney transplant patients. We calculated hazard ratios (HR) with 95% confidence intervals (95% CI) for outcomes of first occurrence of solid or hematologic malignancy, non-melanoma skin cancer (NMSC) and post-transplant lymphoproliferative disorder (PTLD). RESULTS: Over a median follow-up of 5.7 years, PTI for GN was associated with significantly increased risk for malignancy compared with controls [13.0%  vs 9.7%, respectively; adjusted HR 1.82 (95% CI 1.10-3.00)], but not for NMSC [10.3% vs 11.4%, respectively; adjusted HR 1.09 (95% CI 0.64-1.83)] or PTLD [3.3% vs 3.1%, respectively; adjusted HR 1.02 (95% CI 0.40-2.61)]. The risk for malignancy was significantly increased in those who received cyclophosphamide [HR 2.59 (95% CI 1.48-4.55)] or rituximab [HR 3.82 (95% CI 1.69-8.65)] pre-transplant, and particularly in those who received both cyclophosphamide and rituximab, but not for calcineurin inhibitors or mycophenolate. CONCLUSION: The use of PTI for treatment of GN, especially cyclophosphamide or even with rituximab, is associated with increased risk for development of solid or hematologic malignancy post-transplant. These data highlight potential risks with treatment of GN and underscore the importance of post-transplant malignancy surveillance in this patient population.

The value of repeat kidney biopsy during an atypical course of membranous nephropathy.

BACKGROUND: The clinical trajectory for patients with primary membranous nephropathy ranges widely from spontaneous remission to a rapid decline in kidney function. Etiologies for rapid progression with membranous nephropathy include concurrent bilateral renal vein thrombosis, malignant hypertension, and crescentic membranous nephropathy. Given the wide heterogeneity in prognosis, timing of immunosuppressive therapy is often challenging and centers around an individual patient's perceived risk for rapidly progressive disease. CASE PRESENTATION: Herein, we describe the clinical course of a young patient who initially developed a typical presentation of membranous nephropathy with consistent kidney biopsy findings. Given clinical stability, a six month observation period was undertaken prior to initiating immunosuppression. Within this observation window, the patient developed community acquired pneumonia followed several weeks later by a sudden, rapid decline in kidney function requiring dialysis. Repeat kidney biopsy revealed post-infectious glomerulonephritis superimposed upon a background of membranous nephropathy. Immunosuppressive therapy resulted in a favorable long-term outcome with normalization of kidney function and remission of nephrotic syndrome. To our knowledge, this is the first report of the simultaneous occurrence of these two glomerular disease processes. CONCLUSION: This case illustrates the value of repeat kidney biopsy during an atypical course of membranous nephropathy. Superimposed glomerular disease processes should be considered during a course of rapidly progressive membranous nephropathy.

Glomerular Hematuria and the Utility of Urine Microscopy: A Review.

Evaluation of hematuria and microscopic examination of urine sediment are commonly used tools by nephrologists in their assessment of glomerular diseases. Certain morphological aspects of urine red blood cells (RBCs) seen by microscopy may help in identifying the source of hematuria as glomerular or not. Recognized signs of glomerular injury are RBC casts or dysmorphic RBCs, in particular acanthocytes (ring-shaped RBCs with protruding blebs). Despite being a highly operator-dependent test, urine sediment examination revealing these signs of glomerular hematuria has demonstrated specificities and positive predictive values ranging between 90%-100% for diagnosing glomerular disease, although sensitivity can be quite variable. Hematuria is a commonly used tool for diagnosing patients with proliferative glomerulonephritis such as IgA nephropathy, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, and lupus nephritis, sometimes even as a surrogate for kidney involvement. Studies examining the role for hematuria in monitoring and predicting adverse outcomes in these diseases have shown inconsistent results, possibly due to inconsistent definitions that often fail to consider specific markers of glomerular hematuria such as dysmorphic RBCs, acanthocytes, or RBC casts. A consensus definition of what constitutes glomerular hematuria would help standardize use in future studies and likely improve the diagnostic and prognostic value of hematuria as a marker of glomerulonephritis.

Kidney thrombotic microangiopathy in lupus nephritis: Impact on treatment and prognosis.

INTRODUCTION: Lupus nephritis (LN) may present with thrombotic microangiopathy (TMA) on kidney biopsy, the impact of which on outcomes is unclear. This study examined the prognostic importance of LN with TMA on kidney biopsy, including response to therapy and long-term outcomes. METHODS: We conducted a single-center, retrospective study of all cases of LN with concomitant TMA on kidney biopsy in the Glomerular Disease Collaborative Network database. Controls were individuals with LN without TMA matched to cases based on demographic and clinical variables. Outcomes were remission at 6- and 12-months, end-stage kidney disease (ESKD) and death. Logistic regression and Cox proportional hazards models were used to ascertain the risks for outcomes, with adjustment for serum creatinine and proteinuria. RESULTS: There were 17 cases and 28 controls. Cases had higher creatinine, higher proteinuria and greater chronicity on biopsy at baseline compared to controls. The rates of remission at 6-months and 12-months were similar between cases and controls (6-months 53.9% vs 46.4%, adjusted OR 2.54, 95% CI 0.48, 13.37; 12-months 53.9% vs 50.0%, adjusted OR 2.95, 95% CI 0.44, 19.78). Cases were at greater risk for ESKD in univariate analysis (HR 3.77; 95% CI 1.24, 11.41) but not when adjusting for serum creatinine and proteinuria (HR 2.20; 95% CI 0.63, 7.71). There was no significant difference in the risk of death between cases and controls. CONCLUSION: Lupus nephritis with renal TMA likely responds to therapy similarly to those without TMA; risk for ESKD is not significantly increased, although the influence of renal function and proteinuria in larger samples is needed.

Validation of the International Classification of Disease 10th Revision Codes for Kidney Transplant Rejection and Failure.

BACKGROUND: Clinical research requires that diagnostic codes captured from routinely collected health administrative data accurately identify individuals with a disease. OBJECTIVE: In this study, we validated the International Classification of Disease 10th Revision (ICD-10) definition for kidney transplant rejection (T86.100) and for kidney transplant failure (T86.101). DESIGN: Retrospective cohort study. SETTING: A large, regional transplantation center in Ontario, Canada. PATIENTS: All adult kidney transplant recipients from 2002 to 2018. MEASUREMENTS: Chart review was undertaken to identify the first occurrence of biopsy-confirmed rejection and graft loss for all participants. For each observation, we determined the first date a single ICD-10 code T86.100 or T86.101 was recorded as a hospital encounter discharge diagnosis. METHODS: Using chart review as the gold standard, we determined the sensitivity, specificity, and positive predictive value (PPV) for the ICD-10 codes T86.100 and T86.101. RESULTS: Our study population comprised of 1,258 kidney transplant recipients. The prevalence of rejection and death-censored graft loss were 15.6 and 9.1%, respectively. For the ICD-10 rejection code (T86.100), sensitivity was 72.9% (95% confidence interval [CI], 66.6-79.2), specificity 97.5% (96.5-98.4), and PPV 83.8% (78.3-89.4). For the ICD-10 graft loss code (T86.101), sensitivity was 21.2% (95% CI, 13.2-29.3), specificity 86.3% (84.3-88.3), and PPV 11.7% (7.0-16.4). LIMITATIONS: Single-center study which may limit generalizability of our findings. CONCLUSIONS: A single ICD-10 code for kidney transplant rejection (T86.100) was present in 84% of true kidney transplant rejections and is an accurate way of identifying kidney transplant recipients with rejection using administrative health data. The ICD-10 code for graft failure (T86.101) performed poorly and should not be used for administrative health research.

CONTEXTE: La recherche clinique exige que les codes de diagnostic, qui sont couramment saisis à partir des données administratives de santé, permettent d'identifier précisément les personnes atteintes d'une maladie. OBJECTIF: Dans cette étude, nous avons validé les définitions de rejet (T86.100) et d'échec (T86.101) d'une greffe rénale de la Classification internationale des maladies et des causes de décès (CIM-10). TYPE D'ÉTUDE: Étude de cohorte rétrospective. CADRE: Un grand center régional de transplantation en Ontario (Canada). SUJETS: Tous les adultes receveurs d'une greffe rénale entre 2002 et 2018. MESURES: Les dossiers médicaux de tous les patients ont été examinés pour repérer la première occurrence confirmée par biopsie d'un rejet ou de la perte du greffon. Pour chaque observation, nous avons déterminé la première date à laquelle un code CIM-10 unique T86.100 ou T86.101 avait été enregistré comme diagnostic de sortie de l'hôpital. MÉTHODOLOGIE: Avec l'examen des dossiers médicaux comme étalon-or, nous avons déterminé la sensibilité, la spécificité et la valeur prédictive positive (VPP) des codes T86.100 et T86.101 de la CIM-10. RÉSULTATS: Notre cohorte était constituée de 1 258 receveurs d'une greffe rénale. La prévalence d'un rejet et de la perte du greffon censurée par le décès s'établissait à 15,6 % et à 9,1 % respectivement. La sensibilité du code CIM-10 pour un rejet (T86.100) s'élevait à 72,9 % (IC 95 %: 66,6 à 79,2), sa spécificité à 97,5 % (96,5 à 98,4) et sa VPP à 83,8 % (78,3 à 89,4). Quant au code CIM-10 pour la perte du greffon (T86.101), sa sensibilité s'établissait à 21,2 % (IC 95 %: 13,2 à 29,3), sa spécificité à 86,3 % (84,3 à 88,3) et sa VPP à 11,7 % (7,0 à 16,4). LIMITES: L'étude est monocentrique, ce qui pourrait limiter la généralisabilité de nos résultats. CONCLUSION: Un code CIM-10 unique de rejet de la greffe (T86.100) était présent dans 84 % des cas réels de rejet, ce qui en fait un outil fiable pour identifier les patients ayant expérimenté un rejet de la greffe à partir des données administratives de santé. Quant au code CIM-10 de perte du greffon (T86.101), nettement moins performant, il ne devrait pas être utilisé pour la recherche à partir des données administratives de santé.

Uremic leontiasis ossea due to secondary hyperparathyroidism complicated by vitamin C deficiency in a non-adherent chronic hemodialysis patient: A case report.

Non-adherence to medical therapy in patients with end-stage kidney disease (ESKD) can lead to severe metabolic derangements rarely seen in the current medical era. Such complications may take the form of secondary hyperparathyroidism (HPT) leading to rare manifestations of bone mineral disease, and profound vitamin C deficiency from poor nutrition combined with removal of water-soluble vitamins during dialysis. Secondary HPT causes renal osteodystrophy which can lead to diffuse enlargement of the facial skeleton and morphological changes suggestive of leontiasis ossea. We report a 36-year-old, non-adherent woman on chronic dialysis for over 10 years who developed progressive, diffuse facial bone enlargement in the context of years of extreme HPT and newly diagnosed severe vitamin C deficiency. Imaging revealed diffuse hypertrophy of the maxillary and mandibular bones. Histopathology showed extensive fibro-osseous proliferation without evidence of Brown tumor, suggestive of uremic leontiasis ossea. In this report, we discuss the orofacial manifestations of secondary HPT and the possible potentiating role of vitamin C deficiency on the development of renal osteodystrophy through altered vitamin D metabolism. Non-adherent patients on chronic dialysis should be evaluated for vitamin C deficiency, and the development of uremic leontiasis ossea should be considered when such patients present with distortion of facial features in the context of severe secondary HPT.

Transient mediastinal mass from fluid overload.

Mediastinal masses incidentally discovered on chest imaging often suggest underlying malignancy such as lymphoma or metastatic cancer. However, the radiographic appearance of mediastinal edema can mimic a mediastinal mass in the context of acute fluid overload. We describe the case of a 75 year old woman known for end-stage renal disease on hemodialysis who presented with acute pulmonary edema in the context of a Non ST-Elevation Myocardial Infarction. Chest CT imaging showed pulmonary edema, pleural effusions, and a middle mediastinum soft-tissue mass of 4.2 × 2.5cm. Malignancy was initially suspected, however given the clinical context of fluid overload and absence of other signs of malignancy, the possibility of the mass representing soft-tissue edema was raised. Therefore, the patient's fluid overload was treated with a progressive reduction in the dry weight used for dialysis and a repeat chest CT was obtained 8 weeks later once the patient was euvolemic. The repeat CT showed complete resolution of the mediastinal mass. Fluid overload can manifest in many different ways on chest imaging. Mediastinal masses lead to concerns about a potentially malignant process and often prompt further evaluation with invasive procedures that carry significant risks. In the appropriate clinical context, it is important to consider the possibility of mediastinal edema presenting as a mass on chest imaging. Under such circumstances, it is more prudent to correct the fluid overload and repeat chest imaging before undertaking invasive diagnostic procedures with the potential to cause harm.