Case Report: Silicosis and IgA nephropathy, an exceptional association

A 57-year-old male who had been working in masonry for 33 years was hospitalized for renal function decline associated with exertional dyspnea. He presented with hypertension and limb edema. Urinalysis revealed an active urine sediment with glomerular proteinuria at 1.5 g/24h and the renal biopsy identified mesangial IgA Nephropathy. Chest tomography scans showed signs of silicosis. The patient received Angiotensin-Converting Enzyme Inhibitors with stable renal function. To our knowledge, the association of silicosis-IgA nephropathy has rarely been reported in the literature. This case highlights the effect of chronic exposure to silica dust and its association with both silica and renal disease.

Kidney trajectory charts to assist general practitioners in the assessment of patients with reduced kidney function: a randomised vignette study

ObjectiveTo investigate the decisional impact of an age-based chart of kidney function decline to support general practitioners (GPs) to appropriately interpret estimated glomerular filtration rate (eGFR) and identify patients with a clinically relevant kidney problem.Design and settingRandomised vignette studyParticipants372 Australian GPs from August 2018 to November 2018.InterventionGPs were given two patient case scenarios: (1) an older woman with reduced but stable renal function and (2) a younger Aboriginal man with declining kidney function still in the normal range. One group was given an age-based chart of kidney function to assist their assessment of the patient (initial chart group); the second group was asked to assess the patients without the chart, and then again using the chart (delayed chart group).Main outcome measuresGPs’ assessment of the likelihood—on a Likert scale—that the patients had chronic kidney disease (CKD) according to the usual definition or a clinical problem with their kidneys.ResultsPrior to viewing the age-based chart GPs were evenly distributed as to whether they thought case 1—the older woman—had CKD or a clinically relevant kidney problem. GPs who had initial access to the chart were less likely to think that the older woman had CKD, and less likely to think she had a clinically relevant problem with her kidneys than GPs who had not viewed the chart. After subsequently viewing the chart, 14% of GPs in the delayed chart group changed their opinion, to indicate she was unlikely to have a clinically relevant problem with her kidneys.Prior to viewing the chart, the majority of GPs (66%) thought case 2—the younger man—did not have CKD, and were evenly distributed as to whether they thought he had a clinically relevant kidney problem. In contrast, GPs who had initial access to the chart were more likely to think he had CKD and the majority (72%) thought he had a clinically relevant kidney problem. After subsequently viewing the chart, 37% of GPs in the delayed chart group changed their opinion to indicate he likely had a clinically relevant problem with his kidneys.ConclusionsUse of the chart changed GPs interpretation of eGFR, with increased recognition of the younger male patient’s clinically relevant kidney problem, and increased numbers classifying the older female patient’s kidney function as normal for her age. This study has shown the potential of an age-based kidney function chart to reduce both overdiagnosis and underdiagnosis.

Case Report: Silicosis and IgA nephropathy, an exceptional association

A 57-year-old male who had been working in masonry for 33 years was hospitalized for renal function decline associated with exertional dyspnea. He presented with hypertension and limb edema. Urinalysis revealed an active urine sediment with glomerular proteinuria at 1.5 g/24h and the renal biopsy identified mesangial IgA Nephropathy. Chest tomography scans showed signs of silicosis. The patient received Angiotensin-Converting Enzyme Inhibitors with stable renal function. To our knowledge, the association of silicosis-IgA nephropathy has rarely been reported in the literature. This case highlights the effect of chronic exposure to silica dust and its association with both silica and renal disease.

Establishment of Durable Chimerism with Minimal GvHD in Highly Mismatched Recipients Receiving an Investigational Facilitated Allo-HSCT

Introduction We previously reported the induction of kidney transplant tolerance by the establishment of durable whole blood and T-cell chimerism and withdrawal of immunosuppression (IS) in 26 of 37 highly mismatched recipients of combined stem cell and living donor kidney transplant recipients (KTx) with low risk of graft versus host disease (GvHD), using FCR001, an investigational cell therapy. The focus of the current analysis is to evaluate the impact of degree of bidirectional donor/recipient mismatching using high resolution allele typing at HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1, on the ability to establish durable chimerism, allowing full immunosuppression (IS) withdrawal and the induction of transplant tolerance. Methods In this phase 2 trial, recipients received nonmyeloablative conditioning with fludarabine 30mg/m2 (Days -5, -4, -3), cyclophosphamide 50mg/kg (Days-3 and +3), 200 cGy TBI (Day-1) followed by KTx (Day 0). G-CSF mobilized peripheral blood mononuclear cells were apheresed from the donor >2 weeks prior to KTx, processed to remove GvHD-producing cells yet retain CD34 +cells and tolerogenic CD8+/TCR facilitating cells (FC) and cryopreserved until infusion day+1 after KTx. IS consisted of mycophenolate and tacrolimus. IS was weaned and discontinued in the presence of sustained donor T-cell chimerism (>50%), stable renal function and no evidence of biopsy-proven rejection. Results Samples from 32 of the 37 subject pairs were available for analysis; of these, three subjects did not have sufficient DNA to test for locus DPB1.All 32 recipients, ranging from age 18 - 65 years, have reached at least 4.5 years of follow-up up to 12 years. Two recipients were re-transplants. Of the 29 D/R pairs with data from all 12 alleles, 21 were mismatched between 6 to 12 alleles (6 related, 15 unrelated), 8 were mismatched between 2 and 5 alleles (all related). Of the three D/R pairs missing DP data, one was mismatched 6 of 10, another 10 of 10, and a third 2 of 10 alleles. Despite the high degree of mismatch, durable chimerism allowed for full IS withdrawal in 25 of these 32 subjects (time off IS from 3.5 - 11 years). 12/25 off IS were from unrelated D/R pairs and ≥ 8 HLA mismatches; the majority showed >95% donor whole blood/T cell chimerism. Three have exhibited stable mixed chimerism ranging between 40% - 60%. Of the subjects not off IS, two failed to engraft their cells; four lost chimerism by 4 months, and one developed GVHD. Durably chimeric patients retained chimerism after removal of IS, remain rejection-free without donor-specific antibody (DSA) with up to 12 years following KTx and have not resumed IS. Transiently chimeric subjects resumed endogenous hematopoiesis and are maintained on low dose IS with stable renal function. There have been two cases of GvHD: one grade 2 lower GI acute GvHD that developed during conversion from tacrolimus to sirolimus and responded to steroids; this patient has developed moderate chronic GvHD of the skin. He is off IS with normal renal function. The second presented late following development of severe gastrointestinal symptoms and manifested treatment-resistant lower GI GvHD with associated tissue-invasive CMV colitis that proved fatal at 11 months post-transplant. Conclusions In summary, high levels of durable chimerism and tolerance with a low (5.5%) incidence of GvHD has been achieved in highly mismatched related and unrelated recipients of FCR001 + kidney transplant. Figure 1 Figure 1. Disclosures Krieger: Talaris Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company. Tambur: Viela Bio and Sanofi: Consultancy; ThermoFisher: Speakers Bureau. Schneider: Talaris Therapeutics, Inc.: Current Employment. Olsen: Talaris Therapeutics, Inc.: Current Employment. Ildstad: Talaris Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees.

The stiffness of transplanted kidneys changes with time after renal transplantation

Background Kidney transplantation is one of the most effective ways to treat end-stage kidney disease. However, 5000 renal transplant recipients start or restart dialysis because of chronic allograft nephropathy (CAN) every year in the United States. Detecting changes in the stiffness of transplanted kidneys can help diagnose transplanted kidney disease. Purpose To explore changes in the stiffness of transplanted kidneys after renal transplantation using shear wave elastography (SWE). Material and Methods This study conducted consecutive follow-up observations on 10 patients after kidney transplantation. SWE examination was performed in the first week, second week, first month, second month, third month, fourth month, fifth month, and sixth month after surgery. This study also analyzed the graft stiffness of 86 patients with stable renal function recovery one month after surgery. Results The results show that there is a change in the stiffness of the transplanted kidney over time after renal transplantation. It decreases rapidly within one month after renal transplantation and tends to be stable after one month. The mean renal cortical and pyramidal stiffness of patients with stable renal function were 28.48 ± 4.27 kPa and 21.97 ± 3.90 kPa, respectively. Conclusion Consecutive stiffness measurement of transplanted kidneys is an effective method for monitoring the function of transplanted kidneys. According to the change in transplanted kidney stiffness, we can designate a more scientific review plan to determine the functional status of the transplanted kidney.

Improvement of renal function after transcatheter aortic valve replacement in patients with chronic kidney disease

Background Chronic kidney disease is commonly found in patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) and has marked impact in their prognosis. It has been shown however that TAVR may improve renal function by alleviating the hemodynamic barrier imposed by AS. Nevertheless, the predictors of and clinical consequences of renal function improvement are not well established. Our aim was to assess the predictors of improvement of renal function after TAVR. Methods The present work is an analysis of the Brazilian Registry of TAVR, a national non-randomized prospective study with 22 Brazilian centers. Patients with baseline renal dysfunction (estimated glomerular filtration rate [eGFR] < 60mL/min/1.73m2) were stratified according to renal function after TAVR: increase >10% in eGFR were classified as TAVR induced renal function improvement (TIRFI); decrease > 10% in eGFR were classified as acute kidney injury (AKI) and stable renal function (neither criteria). Results A total of 819 consecutive patients with symptomatic severe AS were included. Of these, baseline renal dysfunction (estimated glomerular filtration rate [eGFR] < 60mL/min/1.73m2) was present in 577 (70%) patients. Considering variance in renal function between baseline and at discharge after TAVR procedure, TIRFI was seen in 197 (34.1%) patients, AKI in 203 (35.2%), and stable renal function in 177 (30.7%). The independent predictors of TIRFI were: absence of coronary artery disease (OR: 0.69; 95% CI 0.48–0.98; P = 0.039) and lower baseline eGFR (OR: 0.98; 95% CI 0.97–1.00; P = 0.039). There was no significant difference in 30-day and 1-year all-cause mortality between patients with stable renal function or TIRFI. Nonetheless, individuals that had AKI after TAVR presented higher mortality compared with TIRFI and stable renal function groups (29.3% vs. 15.4% vs. 9.5%, respectively; p < 0.001). Conclusions TIRFI was frequently found among baseline impaired renal function individuals but was not associated with improved 1-year outcomes.

185 Vascular Hitch Procedure for Accessory Lower Pole Vessels

Introduction The gold standard procedure for pelvi-ureteric junction obstruction has been the Anderson-Hynes dismembered pyeloplasty; involving the repositioning of the ureter and ureteropelvic anastomosis. However, the Hellstroem 'Vascular Hitch Procedure’ dictates the superior translocation of the accessory vessel and its fixation to the anterior pelvic wall. The latter has an estimated success rate &gt;90%. Method During 2016-2020, at Leicester Royal Infirmary, 16 operations occurred on paediatric patients with pelvi-ureteric junction obstruction. The dismembered pyeloplasty was performed on 5 patients, 9 patients underwent the vascular hitch procedure, and 2 patients are currently awaiting the latter operation. All patients had a pre-operative functional magnetic resonance urography (fMRU) to identify and localise the accessory lower pole vessel. Results The mean hospital stay for the vascular hitch procedure was 1.5 days (range=1-2) in comparison to 4 days (range=3-5) for the dismembered pyeloplasty. The follow-up period ranged from 6 months to 3 years. Overall, it was noted that the patients were asymptomatic, had markedly reduced hydronephrosis on imaging as well as stable renal function noted on the MAG 3 renogram scan. Conclusions The laparoscopic vascular hitch procedure appears to be the superior operation for the management of pelvi-uteric junction obstruction as the patients had notably reduced hospital stay lengths.

Living-Related Donor Kidney Transplant in a Patient With Single Ventricle and Fontan Circulation

The hemodynamic profile of the Fontan circulation presents challenges that raise questions about candidacy for organ transplantation. We report a case of a 24-year-old male with double-inlet right ventricle and aortic atresia, who suffered bilateral renal cortical necrosis due to neonatal cardiovascular shock, received a live-donor kidney transplant from his mother at age 17, and has diminished yet stable renal function seven years posttransplant.

BK virus nephropathy in a heart transplant recipient

BK virus nephropathy in kidney transplantation is widely recognized as an important cause of graft dysfunction and loss. In the case of transplants of organs other than kidney, BK virus nephropathy in native kidneys has been recognized as a cause of chronic kidney disease, which is related with immunosuppression; however, the diagnosis is usually late because the renal dysfunction is attributed to other causes, such as toxicity by anticalcineurinic drugs, interstitial nephritis due to medications, hemodynamic changes, diabetes, hypertension, etc. We report a case of BK virus nephropathy in a patient who underwent heart transplantation due to peripartum cardiomyopathy. The kidney biopsy reported active chronic tubulointerstitial nephritis associated with late stage polyomavirus nephritis and the blood viral load for BK virus was positive (logarithm 4.5). The immunosuppressive treatment was reduced, and after two years of follow-up, the patient had stable renal function with a serum creatinine of 2.5 mg/dL (GFR of 23.4 mL/min/1.73m2). We recommend that the BK virus be considered as a cause of renal dysfunction in heart transplant recipients, with the aim of detecting its replication in time to reduce immunosuppressive therapy before irreversible compromise of renal function may manifest.

Prediction of Vancomycin Levels Using Cystatin C in Overweight and Obese Patients: a Retrospective Cohort Study of Hospitalized Patients

ABSTRACTThe use of the kidney function biomarker cystatin C (cysC) can improve the accuracy of vancomycin dosing for target trough attainment in nonobese patients. It is unknown whether cysC can also improve vancomycin target trough attainment in overweight and obese patients. We conducted a retrospective observational study of overweight or obese hospitalized adults with stable renal function administered intravenous vancomycin between January 2011 and July 2019. Linear regression models were used to predict initial steady-state vancomycin troughs using several factors, including various cysC- and serum creatinine (SCr)-based estimates of kidney function. We compared the predicted proportion of patients within the target trough range (10 to 20 mg/liter) using the derived models to that observed from usual care. Of the 200 included patients, the mean trough level was 15 ± 6.3 mg/liter. The optimal model to predict the initial trough included both cysC and SCr (R2 = 0.48) rather than either biomarker alone. This model predicted that 79% (95% confidence interval [CI], 73% to 85%) of troughs could be between 10 and 20 mg/liter compared to the 62% observed in clinical practice (P < 0.001), a 1.3-fold increase. This study is the first to examine the role of cysC in predicting vancomycin levels in an exclusively overweight or obese population. While dosing models based on cysC appear promising in this setting, prospective validation is needed.