Cortese, Cherise

AbstractBackgroundHistologic acute graft pyelonephritis (HAGPN) after kidney transplantation (KT) has been assessed less frequently than urinary tract infections (UTIs) or clinical acute graft pyelonephritis. Risk factors for HAGPN, its association with graft loss, and measures that might prevent it are not known.MethodsWe performed a retrospective review of HAGPN cases identified from KT occurring between January 2008 and December 2017 at our institution. We compared the HAGPN cases to a randomly selected control group of KTs to identify risk factors using univariate and multivariate Cox regression models. The association between HAGPN and graft loss was also assessed, similarly.ResultsHAGPN was identified in 46 of 1391 patients (cumulative incidence, 5% [95% CI, 3%–7%]) undergoing KT at a single center from January 2008 through December 2017 (median time to diagnosis, 241 days after KT; interquartile range, 122–755 days). Indications for biopsy were follow‐up of treated rejection (n = 20 [43%]), KT protocol biopsy (n = 19 [41%]), and acute kidney injury (n = 7 [15%]). Histologic rejection, UTI, and asymptomatic bacteriuria (ASB) were present in 23 (50%), 9 (20%), and 16 (35%). Multivariate Cox proportional hazards models comparing KT recipients with or without HAGPN (n = 46 and n = 138, respectively) showed that HAGPN was associated with urologic complication by day 30, delayed graft function, previous UTI or ASB, and a history of rejection. In the univariate and multivariate analyses, HAGPN was associated with an increased risk of graft loss.ConclusionHAGPN is an infrequent, unanticipated, and clinically significant complication of KT.

Fibrillary glomerulonephritis (FGN) and complement 3 glomerulopathy (C3G) are rare forms of glomerulonephritis with distinct aetiologies. Both FGN and C3G can present with nephritic syndrome. FGN is associated with autoimmune disease, dysproteinaemia, malignancy and hepatitis C infection. C3G is caused by the unregulated activation of the alternative complement pathway. We present a rare case of diffuse necrotising crescentic glomerulonephritis with dominant C3 glomerular staining on immunofluorescence—consistent with C3G—but electron microscopy (EM) findings of randomly oriented fibrils with a mean diameter of 14 nm and positive immunohistochemistry for DNAJB9—suggestive of FGN. To the best of our knowledge, this is the first reported case of FGN to show dominant C3 glomerular deposits. This case report reaffirms the utility of EM in the evaluation of nephritic syndrome and highlights the value of DNAJB9—a novel biomarker with a sensitivity and specificity near 100% for FGN.

Abstract Background Histologic acute graft pyelonephritis (HAGPN) is a complication of kidney transplantation (KT) diagnosed serendipitously by renal biopsy. A retrospective review of 1391 patients who underwent KT at our institution between 2008 and 2017 identified 46 cases (cumulative incidence 5%). Rejection was present in 50% of biopsies demonstrating HAGPN, complicating management. The aims of this study were to identify risk factors and outcomes of HAGPN. Methods Recipient, donor, operative and post-transplant characteristics of 46 cases of HAGPN and 138 controls randomly selected from the 1345 patients who underwent KT between 2008 and 2017 were assessed in univariable and multivariable Cox regression models. Associations of HAGPN with death or graft failure were assessed in univariable models. Results In univariable analysis, characteristics associated with increased risk of HAGPN in order of decreasing hazard ratio (HR) were rejection (HR 10.82, 5.66-20.72), urinary tract infections (UTI) or asymptomatic bacteriuria (ASB) (HR 6.28, 3.43-11.50), urologic malfunction (UM) within 30 days of KT, (HR 5.34, 2.85-10.02), less than 4 matches at HLA A/B/DR loci (HR 3.74, 1.19-11.76), delayed graft function (DGF) (HR 2.1, 1.47-3.00), basiliximab induction (HR 1.59, 1.05-2.42), diabetes mellitus (DM) at KT (HR 1.52, 1.07-2.16), operative time (HR 1.11, 1.03-1.19) and cold ischemic time (CIT) (HR 1.05, 1.02-1.06). UM, rejection and UTI or ASB were the most significant risk factors based on clinical and statistical importance, and after adjusting for them, DM, transplant type, CIT, ureteral stent placement and DGF remained significant risk factors. In univariable analysis, ureteral stent placement at transplant (HR 0.60, 0.43-0.88) and living-related donor (HR 0.18, 0.04-0.78) were each associated with reduced risk of HAGPN which persisted after multivariable analysis. In univariable analysis, HAGPN was associated with death (HR 17.04, 7.93-39.31) and graft failure (HR 3.77, 1.73, 8.20). Conclusion HAGPN is an infrequent, unanticipated, clinically significant complication of renal transplantation. Post-transplant dysfunction of the allograft collection system may be a modifiable risk factor. Disclosures All Authors: No reported disclosures

Abstract Background There are few studies of histologic acute graft pyelonephritis (HAGPN) following kidney transplant (KT). The goals of this study are to determine incidence, identify potential risk factors and describe outcomes of HAGPN in a large cohort of KT recipients. Methods Renal allograft biopsies of all patients undergoing first KT at our medical center between 2008 and 2017 were reviewed. HAGPN was defined as the presence of neutrophils within the interstitium and tubules (casts). Medical charts of patients with HAGPN were reviewed. Episodes of bacteriuria (≥10:5 cfu/mL growth in culture) were classified as urinary tract infection (UTI) or asymptomatic bacteruria (ASB) based upon documented symptoms. An episode of acute rejection was defined as pulse parenteral immunosuppressive therapy for histologic evidence of rejection. Results HAGPN was identified in 43 of 1,391 (3.1%) KT recipients at a median of 298 days post-transplant. There were no significant differences between recipient age or gender, donor age or transplant type (deceased, living related, living unrelated) between recipients with and without HAGPN. Urologic malformation was diagnosed in 14 (33%) by day 30 post-transplant. Twenty-five (58%), 17 (40%), and 13 (30%) sustained one or more episodes of acute rejection, UTI and ASB, respectively, prior to HAGPN. At diagnosis of HAGPN, 28 (65%), 7 (16%), and 16 (37%) had histologic evidence of rejection, UTI and ASB, respectively. Twenty-two (51%) and 37 (86%) were treated with pulse immunosuppression and antibiotics, respectively. Median nadir serum creatinine before HAGPN was 1.1 mg/day while median serum creatinine at 6 and 12 months after HAGPN were 1.5 and 1.6. Three patients (7%) developed graft failure within 1 year after HAGPN. Conclusion HAGPN is an infrequent complication of KT. A majority of patients with HAGPN have histologic evidence of rejection and either UTI or ASB at diagnosis, though over 40% have neither UTI nor ASB. When rejection accompanying HAGPN is routinely treated with pulse immunosuppression and antibiotic therapy is administered, graft function is preserved for most patients but a minority (7%) loses graft function within 1 year. Potential risk factors to be assessed in further study include post-transplant urologic dysfunction, acute rejection and UTI. Disclosures All authors: No reported disclosures.

Renal dysfunction is common in liver transplantation (LT) candidates, but differentiating between reversible and irreversible renal injury can be difficult. Kidney biopsy might be helpful in differentiating reversible from irreversible renal injury, but it is associated with significant complications. We aimed to identify pre‐LT predictors of potentially reversible renal injury using histological information obtained on pre‐LT renal biopsy. Data on 128 LT candidates who underwent pre‐LT kidney biopsy were retrospectively collected and correlated with renal histological findings. Indications for kidney biopsy were iothalamate glomerular filtration rate (iGFR) ≤40 mL/minute, proteinuria >500 mg/day, and/or hematuria. According to the biopsy diagnosis, patients were grouped into the following categories: normal (n = 13); acute tubular necrosis (ATN; n = 25); membranoproliferative glomerulonephritis (n = 19); minimal histological changes (n = 24); and advanced interstitial fibrosis (IF) and glomerulosclerosis (GS) (n = 47). Compared with patients having advanced IF/GS, patients with normal biopsies and those with ATN had lower systolic blood pressure (SBP) and diastolic blood pressure (DBP) and higher international normalized ratio and total bilirubin levels (<0.05 for all). Both SBP and DBP directly correlated with the degree of IF and GS (R = 0.3, P ≤ 0.02 for all). SBP ≤90 mm Hg was 100% sensitive and 98% specific in correlating with normal biopsies or ATN, whereas SBP ≥140 mm Hg was 22% sensitive and 90% specific in correlating with advanced IF/GS. Model for End‐Stage Liver Disease score, serum creatinine, iGFR, urinary sodium excretion, and renal size did not correlate with biopsy diagnosis or degree of IF or GS. In conclusion, SBP at the time of LT evaluation correlates with renal histology, and it should be included along with other clinical and laboratory markers in the decision‐making process to list patients with renal dysfunction for LT alone versus simultaneous liver‐kidney transplantation.

Abstract Declining a donor when there is a reasonable possibility that the abnormality on chest imaging could be benign carries the risk of losing out on potentially usable lungs in an already parched landscape of donor organ availability. Cautiously aggressive attitudes to acceptance of borderline donors can help bridge the significant discrepancy that exists between the demand and availability of donor organs. Herein, we present a case highlighting successful bilateral lung transplantation from a relatively imperfect donor.

Cystic fibrosis (CF) is an autosomal recessive disease characterized by mutations in the gene that encodes for the cystic fibrosis transmembrane conductance regulator protein (CFTR). CFTR gene mutations manifest as epithelial cell dysfunction in the airways, biliary tract, pancreas, gut, sweat glands, paranasal sinuses, and genitourinary tract. The clinical manifestations of this dysfunction include respiratory tract infections, bronchiectasis, pancreatic insufficiency, malabsorption, intestinal obstruction, liver disease, and male infertility. The liver disease manifestations of CF can include biliary disease, multilobular cirrhosis, and portal hypertension with and without cirrhosis. Pulmonary disease is the main cause for morbidity and mortality in individuals with CF, and according to the International Society for Heart and Lung Transplantation, CF is the third most common indication for lung transplantation in adults, accounting for 16% of procedures performed. The survival after lung transplantation in individuals with CF continues to improve and is now the highest among end‐stage lung diseases requiring transplant. The survival rate at 10 years is close to 50%. Given the potential presence of liver disease in CF patients undergoing an evaluation for lung transplantation and in lung transplant recipients, it is important to understand the manifestations of liver disease in CF patients and the recommended workup and follow‐up. This review aims to discuss the current literature and provide guidance in the management of these patients.