Isolated arterial mucoid intimal thickening lesion in early post-transplant kidney allograft biopsies.

INTRODUCTION: Thrombotic microangiopathy (TMA) on kidney biopsy shows a variable combination of features: arterial mucoid intimal thickening, acellular closure of glomerular capillary loops, fragmented red blood cells, fibrin thrombi, and arterial fibrinoid necrosis. However, some early post-transplant kidney biopsies show only arterial mucoid intimal thickening. We aimed to elucidate the importance of this finding. METHODS: We identified 19 biopsies showing isolated arterial mucoid intimal thickening and compared them with 22 bona fide TMA biopsies identified based on the pathological findings (excluding rejection) (2011-2020). Additionally, delayed graft function (DGF) (n = 237), and no DGF (control, n = 1314) groups were included for survival analysis. RESULTS: Seven of 19 cases with isolated arterial mucoid intimal thickening showed peripheral blood schistocytes but no other systemic features of TMA. Eight patients underwent adjustments in maintenance immunosuppression (mainly calcineurin inhibitors). None of the cases progressed to full-blown TMA on consecutive biopsies. The overall and death-censored graft survival rates in this group were comparable to the DGF group, but significantly better than the TMA group (P = .005 and .04, respectively). CONCLUSIONS: Isolated arterial mucoid intimal thickening in early post-transplant biopsies may be an early/mild form of TMA, probably requiring adjustment in immunosuppressive regimen. Careful exclusion of known causes of TMA, and donor-derived arterial injury are important.

Complete biopsy-proven resolution of deposits in recurrent proliferative glomerulonephritis with monoclonal IgG deposits (PGNMIGD) following rituximab treatment in renal allograft.

BACKGROUND: Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMIGD) is a disease entity classified under the group of "Monoclonal gammopathy-related kidney diseases", and can recur after transplant. Clinical remission of proteinuria in patients with PGNMIGD has been previously shown following anti-B cell and/or anti-plasma cell therapies. Our case is the first to show complete histologic resolution of the glomerular monoclonal IgG kappa deposits in a case of recurrent PGNMIGD in renal allograft after rituximab and steroid treatment. This is a novel finding and it shows that the deposits are amenable to therapy. This case also highlights the importance of IgG subclass staining in the recognition of the monoclonal nature of the deposits. It is particularly important in PGNMIGD because only 20 to 30% of patients with this disease are reported to have detectable monoclonal gammopathy, and the deposits do not have any organized substructure on electron microscopic examination. Morphologically, they resemble polyclonal immune-type deposits seen in other immune complex glomerulonephritides such as lupus nephritis, infection-associated glomerulonephritis, and membranoproliferative glomerulonephritis (MPGN type I). CASE PRESENTATION: The patient is a 44 year old Caucasian male who received a living unrelated donor kidney transplant for end-stage renal disease diagnosed 7 years before transplant. The reported native kidney biopsy diagnosis was membranoproliferative glomerulonephritis (MPGN) with IgG, C3 and kappa restricted deposits. Fourteen months post-transplant, he presented with abrupt worsening of graft function, proteinuria and serum IgG kappa monoclonal spike. Allograft biopsy was consistent with recurrent PGNMIGD, considering the native kidney diagnosis and interval post-transplant. He underwent plasmapheresis, IV pooled immune globulin, steroid pulse and taper, and anti-CD-20 Rituximab therapy. Patient had gradual decline in proteinuria and complete resolution of the immune deposits on repeat biopsy 3 months later. Unfortunately he subsequently developed chronic antibody-mediated rejection and transplant glomerulopathy and graft failure 34 months post-transplant. CONCLUSIONS: In a transplant setting, repeat allograft biopsies are frequently performed for graft dysfunction. This provides a good opportunity to study the evolution of the immune deposits following treatment. Our case shows complete histologic resolution of the deposits in allograft PGNMIGD.

Differential gene expression pattern in biopsies with renal allograft pyelonephritis and allograft rejection.

Differentiating acute pyelonephritis (APN) from acute rejection (AR) in renal allograft biopsies can sometimes be difficult because of overlapping clinical and histologic features, lack of positive urine cultures,and variable response to antibiotics. We wanted to study differential gene expression between AR and APN using biopsy tissue. Thirty-three biopsies were analyzed using NanoString multiplex platform and PCR (6 transplant baseline biopsies, 8 AR, 15 APN [8 culture positive, 7 culture negative], and 4 native pyelonephritis [NP]). Additional 22 biopsies were tested by PCR to validate the results. CXCL9, CXCL10, CXCL11, and IDO1 were the top differentially expressed genes, upregulated in AR. Lactoferrin (LTF) and CXCL1 were higher in APN and NP. No statistically significant difference in transcript levels was seen between culture-positive and culture-negative APN biopsies. Comparing the overall mRNA signature using Ingenuity pathway analysis, interferon-gamma emerged as the dominant upstream regulator in AR and allograft APN, but not in NP (which clustered separately). Our study suggests that chemokine pathways in graft APN may differ from NP and in fact resemble AR, due to a component of alloreactivity, resulting in variable response to antibiotic treatment. Therefore, cautious addition of steroids might help in resistant cases of graft APN.

An unexpected cause of acute kidney injury in a patient with ANCA associated vasculitis.

Diagnostic kidney biopsies sometimes yield clinically unsuspected diagnoses. We present a case of a 69-year-old woman with established ANCA-associated vasculitis (AAV) of 4 years duration who was in clinical remission following cytotoxic therapy and was on maintenance immunosuppression. She presented to the hospital with acute kidney injury (AKI), symptoms suggestive of a systemic vasculitis, and in addition had hypercalcemia, metabolic alkalosis. A relapse in the AAV was suspected but a diagnostic kidney biopsy showed acute tubular necrosis, patchy interstitial inflammation, and calcium phosphate deposits. It was found that the patient recently started consuming large doses of over-the-counter calcium-containing antacids and vitamin Dcontaining multivitamin supplements. Cessation of these drugs led to improvement of renal function to baseline. This case highlights several teaching points: (1) the kidney biopsy can prove to be critically important even in cases where there appears to be a more obvious clinical diagnosis, (2) AK due to calcium-alkali syndrome has characteristic histopathological changes, and (3) that the triad of hypercalcemia, metabolic alkalosis, and AKI is exclusively associated with the ingestion of excessive quantities of calcium-containing antacids. The physician should keep this in mind, and pro-actively seek pertinent medication history from the patient. A brief review of calcium-alkali syndrome is given.

Impact of post-kidney transplant parathyroidectomy on allograft function.

BACKGROUND: The impact of parathyroidectomy on allograft function in kidney transplant patients is unclear. METHODS: We conducted a retrospective, observational study of all kidney transplant recipients from 1988 to 2008 who underwent parathyroidectomy for uncontrolled hyperparathyroidism (n = 32). Post-parathyroidectomy, changes in estimated glomerular filtration rate (eGFR) and graft loss were recorded. Cross-sectional associations at baseline between eGFR and serum calcium, phosphate, and parathyroid hormone (PTH), and associations between their changes within subjects during the first two months post-parathyroidectomy were assessed. RESULTS: Post-parathyroidectomy, the mean eGFR declined from 51.19 mL/min/1.73 m(2) at parathyroidectomy to 44.78 mL/min/1.73 m(2) at two months (p < 0.0001). Subsequently, graft function improved, and by 12 months, mean eGFR recovered to 49.76 mL/min/1.73 m(2) (p = 0.035). Decrease in serum PTH was accompanied by a decrease in eGFR (p = 0.0127) in the first two months post-parathyroidectomy. Patients whose eGFR declined by ≥20% (group 1) in the first two months post-parathyroidectomy were distinguished from the patients whose eGFR declined by <20% (group 2). The two groups were similar except that group 1 had a higher baseline mean serum PTH compared with group 2, although not significant (1046.7 ± 1034.2 vs. 476.6 ± 444.9, p = 0.14). In group 1, eGFR declined at an average rate of 32% (p < 0.0001) during the first month post-parathyroidectomy compared with 7% (p = 0.1399) in group 2, and the difference between these two groups was significant (p = 0.0003). The graft function recovered in both groups by one yr. During median follow-up of 66.00 ± 49.45 months, 6 (18%) patients lost their graft with a mean time to graft loss from parathyroidectomy of 37.2 ± 21.6 months. The causes of graft loss were rejection (n = 2), pyelonephritis (n = 1) and chronic allograft nephropathy (n = 3). No graft loss occurred during the first-year post-surgery. CONCLUSION: Parathyroidectomy may lead to transient kidney allograft dysfunction with eventual recovery of graft function by 12 months post-parathyroidectomy. Higher level of serum PTH pre-parathyoidectomy is associated with a more profound decrease in eGFR post-parathyroidectomy.

The feasibility of Technology, Application, Self-Management for Kidney (TASK) intervention in post-kidney transplant recipients using a pre/posttest design.

BACKGROUND: Weight gain after a kidney transplant remains a major problem that can lead to adverse effects on morbidity and mortality. The posttransplant phase provides a window of opportunity to improve the engagement of self-management of care for lifestyle modifications for diet and physical activity. The purpose of our study was to (1) test the feasibility of recruitment, retention, and adherence for using the Technology, Application, Self-Management for Kidney (TASK) intervention in post-kidney transplant recipients (≥ 18 years of age) at baseline, 4, 8, and 12 weeks; and (2) estimate the preliminary effects of the TASK intervention in producing change over time for blood pressure (BP), weight, fruits/vegetable intake, fiber intake, sodium intake, self-efficacy to exercise, and perceived stress. METHODS: This study used a 12-week pre/posttest design using to test the feasibility of the TASK intervention. We applied paired t-tests and McNemar's test to compare the outcomes at weeks 4, 8, and 12. RESULTS: We met our recruitment goal (N = 20) and found a 15% attrition rate (n = 3) at Week 12. Adherence rate among the study completers for recording daily food intake was 83-94% over the 12 weeks and for recording daily physical activity was 17-33% over the 12 weeks. We observed improvements over time for BP, weight, fruits/vegetable intake, fiber intake, and sodium intake; these differences were non-significant, although clinically important. We did find a significant difference from baseline to 12 weeks in weight reduction (p = 0.02), self-efficacy to exercise (p = 0.003), and perceived stress (p = 0.04). CONCLUSIONS: The data suggest the TASK intervention was feasible for kidney recipients to use and resulted in weight control, increased self-efficacy to exercise, and decreased perceived stress. TRIAL REGISTRATION: ClinicalTrials.gov #:NCT05151445.

Tryptase is not cleared by the kidneys into the urine.

BACKGROUND: Patients with chronic kidney disease have been reported to have increased concentrations of blood tryptase. Detection of tryptase in the urine of healthy subjects has been reported. OBJECTIVE: The objective is to determine whether tryptase is indeed cleared by the kidneys. METHODS: Blood and urine collections were performed in healthy and systemic mastocytosis subjects. Total and mature tryptase concentrations in blood and total tryptase concentrations in urine were determined. RESULTS: Total tryptase levels in urine were below the limit of detection in both healthy subjects and those with systemic mastocytosis, even after concentrating the urine 10-fold. Thus, both mature and protryptase levels in urine are <0.2 ng/ml. CONCLUSION: Tryptase is not cleared by the kidneys into the urine.

Bias and Racism Teaching Rounds at an Academic Medical Center.

Racism and events of racial violence have dominated the US news in 2020 almost as much as the novel coronavirus pandemic. The resultant civil unrest and demands for racial justice have spawned a global call for change. As a subset of a society that struggles with racism and other explicit biases, it is inescapable that some physicians and health-care employees will have the same explicit biases as the general population. Patients who receive care at academic medical centers interact with multiple individuals, some of whom may have explicit and implicit biases that influence patient care. In fact, multiple reports have documented that some physicians, health-care workers, and health professional students have negative biases based on race, ethnicity, obesity, religion, and sexual identity, among others. These biases can influence decision-making and aggravate health-care disparities and patient-physician mistrust. We review four actual cases from academic medical centers that illustrate how well-intended physicians and health-care workers can be influenced by bias and how this can put patients at risk. Strategies to mitigate bias are discussed and recommended. We introduce what we believe can be a powerful teaching tool: periodic "bias and racism rounds" in teaching hospitals, in which real patient interactions are reviewed critically to identify opportunities to reduce bias and racism and to attenuate the impact of bias and racism on patient outcomes.

Kidney transplantation in the elderly.

PURPOSE OF REVIEW: Recent outcome data, ongoing organ shortage and proposed changes in allocation policies are driving the need to review current practices and possible future course of kidney transplantation in the elderly patients. RECENT FINDINGS: A proposed new kidney allocation system based on matching donor and recipient characteristics to enable 'age-matched' kidney allocation is currently being discussed in the USA. While this system benefits younger recipients, implications for elderly recipients receiving older grafts remain a matter of debate. SUMMARY: Despite improved outcomes, there remain significant challenges to kidney transplantation in the elderly, including organ shortage, poor transplant rate, evolving allocation policies, high wait-list mortality and nonstandardized immunosuppression. Prospective studies are needed to evaluate the strategies to meet these challenges and to study the impact of proposed new allocation system.

Comparison of low-dose gentamicin with minocycline as catheter lock solutions in the prevention of catheter-related bacteremia.

BACKGROUND: Catheter-restricted antibiotic lock solutions were found to be effective in the prevention of catheter-related bacteremia (CRB), but insufficient data are available about the ideal agent and dose. We hypothesized that a low concentration of gentamicin would be as effective as the high doses studied in the past. METHODS: In this prospective, open-labeled, randomized, clinical trial of patients on long-term hemodialysis therapy, patients were randomly assigned to administration of an antibiotic lock solution of gentamicin/citrate (4 mg/mL), minocycline/EDTA, or the control solution of heparin. Patients were followed up until the study end point of CRB was reached or a censoring event occurred. Interim data analysis was performed after 6 months to assess data safety; efficacy was noted and the study was terminated early. RESULTS: Sixty-two patients were enrolled into the study, evenly distributed in 3 arms, with data from 1 patient excluded from analysis. Seven of 20 patients in the heparin group (4.0 events/1,000 catheter days), 1 of 21 patients in the minocycline group (0.4 events/1,000 catheter days), and none of 20 patients in the gentamicin group developed bacteremia. Results were statistically significant by using 2-tailed Fisher exact test; heparin versus gentamicin, P = 0.008, and heparin versus minocycline, P = 0.020. CONCLUSION: Antibiotic lock solutions are superior to the standard heparin lock alone in the prevention of CRBs, and low-dose gentamicin solution has efficacy similar to that of greater concentrations used in previous studies.

Acute pyelonephritis in renal allografts: a new role for microRNAs?

BACKGROUND: Acute pyelonephritis (APN) versus acute rejection (AR) is a frequently encountered diagnostic and therapeutic dilemma in kidney transplants. Variable culture results, overlapping histologic features, and persistent graft dysfunction despite antibiotics are frequently encountered. Therefore, we explored the utility of intragraft microRNA profiles to distinguish between allograft APN and AR. MATERIALS AND METHODS: Between 2003 and 2011, we identified 49 patients with biopsy features of APN, within the first 2 years posttransplant. MicroRNA profiling was performed on 20 biopsies (normal kidney, n=4; unequivocal AR, n=5; features of APN, n=11). RESULTS: Only 32% (16/49) of the patients had concomitant positive urine cultures at biopsy, and in 8 of 16 patients, colony count was less than 10 CFU/mL. In 14 of 49 patients, positive urine culture did not coincide with the biopsy, and in 19 of 49 patients, urine cultures were negative. On microRNA profiling, good clustering was seen among the normal kidneys and among AR biopsies. Among the 11 biopsies with features of APN, 4 biopsies showed good clustering with a pattern distinct from AR; (these patients recovered graft function with antibiotics); 7 of 11 biopsies showed heterogeneity in microRNA profiles and variable outcomes with antibiotic treatment. We identified a panel of 25 microRNAs showing statistical difference in expression between AR and APN. MiR-99b, miR-23b let-7b-5p, miR-30a, and miR-145 were validated using qPCR. CONCLUSION: Allograft pyelonephritis can be a diagnostic and therapeutic challenge. A gestalt approach is required. In addition to histology and cultures, differential intragraft microRNA expression may prove helpful to distinguish APN from AR in renal allograft biopsies.

Cardiac stress test as a risk-stratification tool for posttransplant cardiac outcomes in diabetic kidney transplant recipients.

BACKGROUND: The utility of cardiac stress testing as a risk-stratification tool before kidney transplantation remains debatable owing to discordance with coronary angiography and outcome yields at different centers. METHODS: We conducted a retrospective study of 273 diabetic kidney transplant recipients from 2006 to 2010. By protocol, all diabetic patients underwent pharmacological radionucleotide stress test or dobutamine stress echocardiography before transplant. We compared the 1-year cardiac outcomes between those with negative stress test results and those with positive stress test results. RESULTS: Patients with a positive stress test result (n=67) underwent coronary angiogram, and significant coronary artery disease (≥70% coronary stenosis) was found in 35 (52.2%) patients. Of the latter, 32 (91.4%) underwent cardiac revascularization (24 underwent cardiac stenting and 8 underwent coronary artery bypass grafting). The rest (n=35) were treated medically. Within 1 year after transplant, the group with positive stress test results experienced more cardiac events (34.3% vs. 3.9%, P<0.001) including acute myocardial infarction (22.4% vs. 3.4%, P<0.001) and ventricular arrhythmias (8.9% vs. 0.05%, P=0.001), higher all-cause mortality (19.4% vs. 4.8%, P<0.001), and cardiac mortality (17.9% vs. 0.9%, P<0.001) compared with the group with negative stress test results. CONCLUSIONS: In this diabetic population, stress testing showed positive and negative predictive values of 34.3% and 96.1%, respectively. Pharmacological cardiac stress testing provided excellent risk stratification in diabetic kidney transplant recipients.

Mortality risk factors in chronic haemodialysis patients with infective endocarditis.

BACKGROUND: It is well documented that infective endocarditis (IE) is strongly associated with morbidity and mortality in haemodialysis (HD) patients. Less clear are the mortality risk factors for IE, particularly in an urban African-American dialysis population. METHODS: IE patients were identified from the medical records for the period from January 1999 to February 2004 and confirmed by Duke criteria. The patients were classified as 'survivors' and 'non-survivors' depending on in-hospital mortality, and risk factors for IE mortality were determined by comparing the two cohorts. Survivors were followed as out-patients with death as the endpoint. RESULTS: A total of 52 patients with 54 episodes of IE were identified. A catheter was the HD access in 40 patients (74%). Mitral valve (50%) was the commonest valve involved, and Gram-positive infections accounted for 87% of IE. In-hospital mortality was high (37%) and valve replacement was required for 13 IE episodes (24%). On logistic regression analyses, mitral valve disease [P = 0.002; odds ratio (OR) = 15.04; 95% confidence interval (CI) = 2.70-83.61] and septic embolism (P = 0.0099; OR = 9.56; 95% CI = 1.72-53.21) were significantly associated with in-hospital mortality. Using the Cox proportional hazards model, mitral valve involvement (P = 0.0008; hazard ratio 4.05; 95% CI = 1.78-9.21) and IE related to drug-resistant organisms such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus sp. (P = 0.016; hazard ratio 2.43; 95% CI = 1.18-5.00) were associated with poor outcome after hospital discharge. CONCLUSIONS: IE was associated with high mortality in our predominantly African-American dialysis population, when the mitral valve was involved, or septic emboli occurred and if MRSA or VRE were the causal organisms.