The Clinical Utility of Genetic Testing in the Diagnosis and Management of Adults with Chronic Kidney Disease.

SIGNIFICANCE STATEMENT: Accurate diagnosis of a patient's underlying cause of CKD can influence management and ultimately overall health. The single-arm, interventional, prospective Renasight Clinical Application, Review, and Evaluation study assessed the utility of genetic testing with a 385 gene kidney disease panel on the diagnosis and management of 1623 patients with CKD. Among 20.8% of patients who had positive genetic findings, half resulted in a new or reclassified diagnosis. In addition, a change in management because of genetic testing was reported for 90.7% of patients with positive findings, including treatment changes in 32.9%. These findings demonstrate that genetic testing has a significant effect on both CKD diagnosis and management. BACKGROUND: Genetic testing in CKD has recently been shown to have diagnostic utility with many predicted implications for clinical management, but its effect on management has not been prospectively evaluated. METHODS: Renasight Clinical Application, Review, and Evaluation RenaCARE (ClinicalTrials.gov NCT05846113 ) is a single-arm, interventional, prospective, multicenter study that evaluated the utility of genetic testing with a broad, 385 gene panel (the Renasight TM test) on the diagnosis and management of adult patients with CKD recruited from 31 US-based community and academic medical centers. Patient medical history and clinical CKD diagnosis were collected at enrollment. Physician responses to questionnaires regarding patient disease categorization and management were collected before genetic testing and 1 month after the return of test results. Changes in CKD diagnosis and management after genetic testing were assessed. RESULTS: Of 1623 patients with CKD in 13 predefined clinical disease categories (ages, 18-96; median, 55 years), 20.8% ( n =338) had positive genetic findings spanning 54 genes. Positive genetic findings provided a new diagnosis or reclassified a prior diagnosis in 48.8% of those patients. Physicians reported that genetic results altered the management of 90.7% of patients with a positive genetic finding, including changes in treatment plan, which were reported in 32.9% of these patients. CONCLUSIONS: Genetic testing with a CKD-focused 385 gene panel substantially refined clinical diagnoses and had widespread implications for clinical management, including appropriate treatment strategies. These data support the utility of broader integration of panels of genetic tests into the clinical care paradigm for patients with CKD. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: ClinicalTrials.gov, NCT05846113 .

Factors predicting the active treatment of renal angiomyolipoma: 30 years of experience in two tertiary referral centers.

Introduction and objective: This study aimed to identify clinical features representing predictive factors of active treatment (AT) compared to active surveillance (AS) for renal angiomyolipoma (AML). Patients and methods: From 1990 to 2020, patients referred to two institutions for a renal mass and diagnosed with an AML based on typical features on CT were included in the analysis. The study population was divided into two groups based on the treatment received: active surveillance (AS) or active treatment (AT). Age, gender, tuberous sclerosis syndrome, tumor size, contralateral kidney disease, renal function, year of diagnosis, and symptoms at presentation were assessed as potential predictive factors of active treatment using a logistic regression model in univariate and multivariate analyses. Results: In total, 253 patients (mean age 52.3 ± 15.7 years; 70% women; 70.9% incidentally diagnosed) were included in the analysis. One hundred and nine (43%) received AS, whereas 144 (57%) were actively treated. For univariate analysis, age, tuberous sclerosis complex syndrome, tumor size, symptoms at presentation, and contralateral kidney disease were found to be predictors of AT. Only tumor size (p < 0.001) and the year of diagnosis (p < 0.001) remained significant for multivariable analyses. The likelihood of being managed with AS evolved over the study period and was 50% and 75% when diagnosed before and after 2010, respectively. With respect to size, 4-cm and 6-cm tumors had a probability of 50% and 75% of being treated with AS, respectively. Conclusion: The present analysis from a high-volume institution provides evidence that the management of renal masses with typical radiological features of AML has markedly changed over the last three decades with a trend toward AS over AT. Tumor size and the year of diagnosis were significant factors for the treatment strategies.

Renal Genetics Clinic: 3-Year Experience in the Cleveland Clinic.

Rationale & Objective: There has been an increasing demand for the expertise provided by a renal genetics clinic. Such programs are limited in the United States and typically operate in a genomics research setting. Here we report a 3-year, real-world, single-center renal genetics clinic experience. Study Design: Retrospective cohort. Setting & Participants: Outpatient cases referred to the renal genetics clinic of the Cleveland Clinic between January 2019 and March 2022 were reviewed. Analytical Approach: Clinical and laboratory characteristics were analyzed. All genetic testing was performed in clinical labs. Results: 309 new patients referred from 15 specialties were evaluated, including 118 males and 191 females aged 35.1 ± 20.3 years. Glomerular diseases were the leading presentation followed by cystic kidney diseases, electrolyte disorders, congenital anomalies of kidneys and urinary tract, nephrolithiasis, and tubulointerstitial kidney diseases. Dysmorphic features were noted in 27 (8.7%) patients. Genetic testing was recommended in 292 (94.5%) patients including chromosomal microarray (8.9%), single-gene tests (19.5%), multigene panels (77.3%), and exome sequencing (17.5%). 80.5% of patients received insurance coverage for genetic testing. 45% (115/256) of patients had positive results, 25% (64/256) had variants of unknown significance, and 22.3% (57/256) had negative results. 43 distinct monogenic disorders were diagnosed. Family history of kidney disease was present in 52.8% of patients and associated with positive genetic findings (OR, 2.28; 95% CI, 1.40-3.74). 69% of patients with positive results received a new diagnosis and/or a change in the diagnosis. Among these, 39.7% (31/78) of patients received a significant change in disease management. Limitations: Retrospective and single-center study. Conclusions: The renal genetics clinic plays important roles in the diagnosis and management of patients with genetic kidney diseases. Multigene panels are the most frequently used testing modality with a high diagnostic yield. Family history of kidney disease is a strong indication for renal genetics clinic referral.

Analysis of Native Kidney Function Recovery With Renal Scintigraphy Following Simultaneous Liver-Kidney Transplantation.

BACKGROUND: Patients undergoing simultaneous liver-kidney transplantation (SLK) have impaired native kidney function. The relative contribution of allograft versus native function after SLK is unknown. We sought to characterize the return of native kidney function following SLK. METHODS: Following SLK, patients underwent technetium-99 m-mercaptoacetyltriglycine renal scintigraphy following serum creatinine nadir. Kidney contributions to estimated glomerular filtration rate (eGFR) were determined. Patients with native kidney function at serum creatinine nadir contributing eGFR ≥30 versus <30 mL/min/1.73 m 2 were compared, and multiple linear regression analysis for native eGFR improvement was performed. RESULTS: Thirty-one patients were included in this analysis. Average native kidney contribution to overall kidney function following SLK was 51.1% corresponding to native kidney eGFR of 44.5 mL/min/1.73 m 2 and native kidney function eGFR improvement of 30.3 mL/min/1.73 m 2 ( P < 0.001). Twenty-six of 31 patients had native kidney contribution of eGFR ≥30 mL/min/1.73 m 2 . Hepatorenal syndrome as the sole primary etiology of kidney dysfunction was 100% specific for native kidney eGFR >30 mL/min/1.73 m 2 and predicted native eGFR improvement ( P = 0.03). CONCLUSIONS: Substantial improvement in native kidney function follows SLK, and hepatorenal syndrome as the sole primary etiology of kidney dysfunction is predictive of improvement. Whether such patients are suitable for liver transplant followed by surveillance with option for subsequent kidney transplants requires investigation.

Self-reported marijuana use and its effects on overall approval in potential living kidney donors.

BACKGROUND: Past and present substance use is an important part of the psychosocial evaluation of potential living kidney donors (LKDs). Increasing state legalizations and social acceptance of marijuana (MJ) use can create challenges for transplant centers. METHODS: We investigated the frequency of reporting MJ use, and its effect on the LKD evaluation. A retrospective chart review was performed on all living donor candidates from December 2016 to December 2019 for reports of MJ use, both on an electronic intake form and during clinical evaluation with a licensed social worker (SW). Active MJ use was defined as current use or use within 1 year of evaluation. Baseline characteristics between MJ users and non-users were compared at each step of donor evaluation. We explored variables associated with MJ use including additional consults and testing during the donor evaluation. Overall approval and donation rates for living donors with active MJ use were compared to non-users. Additionally, 1-year donor follow-up was compared between the two groups. Results of 1818 living donor candidates who completed the intake form, 132 admitted to active MJ use. Compared to non-users, MJ users were more likely to be younger, male, single, renting a home, and with a lower level of education. Thirty three out of 338 candidates who completed a social work evaluation reported MJ use. Compared to non-users, MJ users were more frequently classified as moderate or high risk on SW evaluation, and often required a toxicology screen or psychiatry visit for clearance to donate. Altogether 24.2% of MJ users versus 9.5% of non-users discontinued their evaluation (p < .01). Altogether 42.4% of MJ users versus 56.1% of non-users donated their kidney (p = .13). For those who donated, MJ users were less likely than non-users to follow up at 1 year (57.1% vs. 83.0, p-value .02). CONCLUSION: MJ users were often asked to complete additional steps in their evaluation before an approval decision was made, which may have led to the higher rate of donor drop out observed in this group. Further research is needed to assess the effects of MJ use on living donor candidacy, as well as any effects of MJ use on long-term donor outcomes.

Extraosseous calcification in kidney disease.

A consequence of chronic and end-stage kidney disease is a higher risk of calcium deposition in sites other than the bones. The authors of this review outline current understanding of the pathogenesis, presentation, diagnosis, and treatment of this group of disorders.

Granulomatous Tubulointerstitial Nephritis in a Kidney Transplant Recipient: Case Report and Review of the Literature.

BACKGROUND: Granulomatous tubulointerstitial nephritis (GTIN) is a rare pathologic finding on kidney biopsy. GTIN can be associated with drugs, infection, systemic granulomatous disease, and tubulointerstitial nephritis with uveitis syndrome. We present a case of GTIN in a kidney transplant recipient (KTR) and a literature review of published cases of GTIN in KTRs. CASE PRESENTATION: A 65-year-old man with a history of pulmonary and ocular tuberculosis (TB), who had undergone deceased donor kidney transplant 8 years prior, was admitted for acute kidney injury, hypercalcemia, and uveitis. His medications included rifabutin, isoniazid, and tacrolimus. Serum laboratory tests revealed creatinine of 2.65 mg/dL (baseline 1.1-1.5 mg/dL) and corrected calcium of 13.2 mg/dL. Hypercalcemia workup showed parathyroid hormone 7 pg/mL, 1,25(OH) vitamin D 54 pg/mL, parathyroid hormone-related peptide <2.0 pmol/L, and angiotensin-converting enzyme 47 U/L. Kidney biopsy showed GTIN with noncaseating granulomas. Universal polymerase chain reaction testing for acid-fast bacilli, fungus, and bacteria was negative. He was treated with prednisone, and his kidney function returned to baseline, and his hypercalcemia resolved. DISCUSSION: GTIN is a rare entity seen in less than 1% of transplanted kidney biopsies. The exactly etiology of this GTIN case remains unknown. TB could not be entirely ruled out, because the patient was receiving active anti-TB therapy. Our literature review showed infection to be the leading cause of GTIN in KTRs and that GTIN with concomitant uveitis remains exceedingly rare. Steroids may be useful in certain cases.

Early post-transplant cutaneous bacillary angiomatosis in a kidney recipient: Case report and review of the literature.

Bacillary angiomatosis (BA) is an uncommon systemic disease caused by Bartonella henselae (BH) or Bartonella quintana (BQ) that occurs primarily in immunocompromised hosts. Few cases of BA recipients have been reported in adult solid transplant recipients over the years, with most cases presenting years after transplant. We describe a case of a kidney transplant recipient who developed cutaneous BA very early in the post-transplant period despite not having any exposures. Retrospective testing of donor and recipient's serum was performed and raised the concern for possible donor-derived infection. A literature review encompassing 1990 to present was also performed in order to better understand the clinical presentation, diagnostics and therapeutic approach of this unusual disease. Combined serology, histopathology and molecular testing (polymerase chain reaction [PCR]) were useful in diagnosing BA in our patient as serology alone might be unreliable. Macrolides or doxycycline for at least 3 months is the recommended therapeutic strategy; however, the optimal duration of treatment is not well established in transplant recipients. In our patient, we decided to use doxycycline for 1 year due to gradual resolution of lesions and ongoing immunosuppression. Patient responded successfully without any documented relapse.

Effects of body mass index on kidney transplant outcomes are significantly modified by patient characteristics.

Body mass index (BMI) is a known risk factor associated with kidney transplant outcomes and is incorporated for determining transplant candidate eligibility. However, BMI is a coarse health measure and risks associated with BMI may vary by patient characteristics. We evaluated 296 807 adult (age > 17) solitary kidney transplant recipients from the Scientific Registry of Transplant Recipients (2000-2019). We examined effects of BMI using survival models and tested interactions with recipient characteristics. Overall, BMI demonstrated a "J-Shaped" risk profile with elevated risks for overall graft loss with low BMI and obesity. However, multivariable models indicated interactions between BMI with recipient age, diagnosis, gender, and race/ethnicity. Low BMI was relatively higher risk for older recipients (>60 years), people with type I diabetes, and males and demonstrated no additional risk among younger (18-39) and Hispanic recipients. High BMI was associated with elevated risk for Caucasians and attenuated risk among African Americans and people with type II diabetes. Effects of BMI had variable risks for mortality vs graft loss by recipient characteristics in competing risks models. The association of BMI with posttransplant outcomes is highly variable among kidney transplant recipients. Results are important considerations for personalized care and risk stratification. Findings suggest that transplant contraindications should not be based on absolute BMI thresholds but modified based on patient characteristics.

Continuous function of 80 primary renal allografts for 30-47 years with maintenance prednisone and azathioprine/mycophenolate mofetil therapy: A clinical mosaic of long-term successes.

Eighty primary renal allograft recipients, 61 living-related and 19 deceased donor, transplanted from 1963 through 1984 had continuous graft function for 30-47 years. They were treated with three different early immunosuppression programs (1963-1970: thymectomy, splenectomy, high oral prednisone; 1971-1979: divided-dose intravenous methylprednisolone; and 1980-1984: antilymphocyte globulin) each with maintenance prednisone and azathioprine, and no calcineurin inhibitor. Long-term treatment often included the anti-platelet medication, dipyridamole. Although both recipient and donor ages were young (27.2 ± 9.5 and 33.1 ± 12.0 years, respectively), six recipients with a parent donor had >40-year success. At 35 years, death-censored graft survival was 85.3% and death with a functioning graft 84.2%; overall graft survival was 69.5% (Kaplan-Meier estimate). Biopsy-documented early acute cellular and highly probable antibody-mediated rejections were reversed with divided-dose intravenous methylprednisolone. Complications are detailed in an integrated timeline. Hypogammaglobulinemia identified after 20 years doubled the infection rate. An association between a monoclonal gammopathy of undetermined significance and non-plasma-cell malignancies was identified. Twenty-seven azathioprine-treated patients tested after 37 years had extremely low levels of T1/T2 B lymphocytes representing a "low immunosuppression state of allograft acceptance (LISAA)". The lifetime achievements of these patients following a single renal allograft and low-dose maintenance immunosuppression are remarkable. Their success evolved as a clinical mosaic.

Detection and characterization of mosaicism in autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited, progressive nephropathy accounting for 4-10% of end stage renal disease worldwide. PKD1 and PKD2 are the most common disease loci, but even accounting for other genetic causes, about 7% of families remain unresolved. Typically, these unsolved cases have relatively mild kidney disease and often have a negative family history. Mosaicism, due to de novo mutation in the early embryo, has rarely been identified by conventional genetic analysis of ADPKD families. Here we screened for mosaicism by employing two next generation sequencing screens, specific analysis of PKD1 and PKD2 employing long-range polymerase chain reaction, or targeted capture of cystogenes. We characterized mosaicism in 20 ADPKD families; the pathogenic variant was transmitted to the next generation in five families and sporadic in 15. The mosaic pathogenic variant was newly discovered by next generation sequencing in 13 families, and these methods precisely quantified the level of mosaicism in all. All of the mosaic cases had PKD1 mutations, 14 were deletions or insertions, and 16 occurred in females. Analysis of kidney size and function showed the mosaic cases had milder disease than a control PKD1 population, but only a few had clearly asymmetric disease. Thus, in a typical ADPKD population, readily detectable mosaicism by next generation sequencing accounts for about 1% of cases, and about 10% of genetically unresolved cases with an uncertain family history. Hence, identification of mosaicism is important to fully characterize ADPKD populations and provides informed prognostic information.

Reverse Remodeling and Prognosis Following Kidney Transplantation in Contemporary Patients With Cardiac Dysfunction.

BACKGROUND: Cardiac dysfunction influences candidate selection for kidney transplantation. There is a paucity of data regarding predictors of myocardial recovery following kidney transplantation and long-term outcomes. OBJECTIVES: The purpose of this study was to identify the extent of reverse remodeling in our kidney transplant population and the predictors of such changes, and to assess outcomes in these patients. METHODS: We reviewed 232 patients who underwent kidney transplantation at the Cleveland Clinic from 2003 to 2013 and who had baseline and post-transplant echocardiograms; patients with simultaneous heart transplantation were excluded. RESULTS: Post-transplantation mean left ventricular ejection fraction (LVEF) improved in those with LV dysfunction (increased from 41% to 50%; p < 0.0001; n = 66). There was significant improvement in other parameters, including diastolic function, LV end-diastolic dimension, LV mass, and right ventricular systolic pressure. After adjusting for multiple clinical variables, increased hemoglobin following transplantation was associated with an improved LVEF (odds ratio: 1.50; 95% confidence interval [CI]: 1.07 to 2.14; p = 0.016) and reduced mortality (hazard ratio [HR]: 0.65; 95% CI: 0.49 to 0.87; p = 0.004). An improved LVEF ≥10% predicted survival independently of a pre-transplantation LVEF (HR: 0.46; 95% CI: 0.21 to 0.93; p = 0.031). CONCLUSIONS: Kidney transplantation is associated with improved cardiac structure and function. A rise in post-transplantation hemoglobin was a significant factor associated with such changes, in addition to conferring a survival advantage.

Telemedicine as an ethics teaching tool for medical students within the nephrology curriculum.

A novel patient-centered approach was used to deliver ethics curriculum to medical students. Two medical school clinicians designed a telemedicine session linking their facilities (across 2 continents). The session, Exploring the Patient Experience Through Telemedicine: Dialysis and End-Stage Renal Disease, allowed second-year medical students to explore various parameters of quality of life experienced by dialysis patients. A panel of 4 medical students interviewed a dialysis patient via Skype video connection between the medical school and the hospital's dialysis unit. Interview questions were adapted from the Kidney Disease Quality of Life instrument. During the live video-streamed interview, the remaining 23 second-year medical students observed the session. Afterward, the 23 were offered a voluntary anonymous online feedback survey (15 responded). The 4 panelists submitted narrative responses to 2 open-ended questions about their experience. All 15 responding students "Strongly agreed" or "Agreed" that the session was an aid to their professionalism skills and behaviors; 14 of 15 "Strongly agreed" or "Agreed" that telemedicine technology contributed to their understanding of the topic; 12 of 15 "Strongly agreed" that the session improved their understanding of the psychosocial burdens of dialysis, quality of life, and human suffering, and increased their empathy toward patients; and 12 of 15 "Strongly agreed" or "Agreed" that the session encouraged reflective thinking and was an aid to improving their communication skills. Telemedicine can be an effective and feasible method to deliver an ethics curriculum with a patient-centered approach. Additionally, the cross-cultural experience exposes students to additional contextual features of medicine.

Hospitalizations following living donor nephrectomy in the United States.

BACKGROUND AND OBJECTIVES: Living donors represented 43% of United States kidney donors in 2012. Although research suggests minimal long-term consequences of donation, few comprehensive longitudinal studies for this population have been performed. The primary aims of this study were to examine the incidence, risk factors, and causes of rehospitalization following donation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: State Inpatient Databases (SID) compiled by the Agency for Healthcare Research and Quality were used to identify living donors in four different states between 2005 and 2010 (n=4524). Multivariable survival models were used to examine risks for rehospitalization, and patient characteristics were compared with data from the Scientific Registry of Transplant Recipients (SRTR). Outcomes among patients undergoing appendectomy (n=200,274), cholecystectomy (n=255,231), and nephrectomy for nonmetastatic carcinoma (n=1314) were contrasted. RESULTS: The study population was similar to United States donors (for SRTR and SID, respectively: mean age, 41 and 41 years; African Americans, 12% and 10%; women, 60% and 61%). The 3-year incidence of rehospitalization following donation was 11% for all causes and 9% excluding pregnancy-related hospitalizations. After censoring of models for pregnancy-related rehospitalizations, older age (adjusted hazard ratio [AHR], 1.02 per year; 95% confidence interval [95% CI], 1.01 to 1.03), African American race (AHR, 2.16; 95% CI, 1.54 to 3.03), depression (AHR, 1.88; 95% CI, 1.12 to 3.14), hypothyroidism (AHR, 1.63; 95% CI, 1.06 to 2.49), and longer initial length of stay were related to higher rehospitalization rates among donors. Compared with living donors, adjusted risks for rehospitalizations were greater among patients undergoing appendectomy (AHR, 1.58; 95% CI, 1.42 to 1.75), cholecystectomy (AHR, 2.25; 95% CI, 2.03 to 2.50), and nephrectomy for nonmetastatic carcinoma (AHR, 2.95; 95% CI, 2.58 to 3.37). Risks for rehospitalizations were higher among African Americans than whites in each of the surgical groups. CONCLUSIONS: The SID is a valuable source for evaluating characteristics and outcomes of living kidney donors that are not available in traditional transplant databases. Rehospitalizations following donor nephrectomy are less than seen with other comparable surgical procedures but are relatively higher among donors who are older, are African American, and have select comorbid conditions. The increased risks for rehospitalizations among African Americans are not unique to living donation.

Transient versus persistent BK viremia and long-term outcomes after kidney and kidney-pancreas transplantation.

BACKGROUND AND OBJECTIVES: The objective was to study the long-term impact of transient versus persistent BK viremia on kidney transplant outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In total, 609 recipients who underwent kidney transplant from 2007 to 2011 were screened at months 1-12 for the occurrence of polyomavirus BK viremia; 130 patients (21.7%) developed BK viremia during the first year post-transplant. BK viremia patients were classified according to duration of infection (more or less than 3 months), and BK viral loads (more or less than 10,000 copies/ml) were classified as transient low viremia (n=42), transient high viremia (n=18), persistent low viremia (n=23), and persistent high viremia (n=47). All patients were followed a median of 36 (3-66) months. The rates of BK polyomavirus-associated nephropathy, acute rejection, and 1-year graft function were compared with the polyomavirus BK-negative control group. RESULTS: Patient and graft survival were not significantly different among the groups. Graft function (creatinine; milligrams per deciliter) at 1 year was significantly worse in the persistent high viremia (1.75±0.6) and transient high viremia (1.85±0.7) groups compared with aviremic controls (1.47±0.4; P=0.01 and P=0.01, respectively). The incidence of BK polyomavirus-associated nephropathy was limited to the persistent high viremia group (1.3%, P<0.001). The transient high viremia (50%) and persistent high viremia (34%) groups showed significantly (P=0.01) increased incidence of acute rejection versus aviremic controls (21.5%), transient low viremia (19%), or persistent low viremia (17.3%) groups. CONCLUSION: Low viral load BK viremia, either transient or persistent, was not associated with long-term transplant outcomes. Persistent high viremia was associated with a greater risk for BK polyomavirus-associated nephropathy and subsequent graft dysfunction. Although transient high viremia was not associated with BK polyomavirus-associated nephropathy, it was associated with worse graft function. These data support the role of surveillance for BK viremia after transplant.

Active surveillance for renal angiomyolipoma: outcomes and factors predictive of delayed intervention.

OBJECTIVE: To present the outcomes of active surveillance (AS) for renal angiomyolipomas (AMLs) and to assess the clinical features predicting delayed intervention of this treatment option. PATIENTS AND METHODS: We retrospectively reviewed the outcomes of patients diagnosed with AMLs on computed tomography (CT) who were managed with AS at our institution. The AS protocol consisted of 6- and 12-month, then annual follow-up visits, each one including a physical examination and CT imaging. Discontinuation of AS was defined as the need or decision for an active procedure during the follow-up period. Causes of delayed intervention, as well as the type of active treatment (AT), were recorded. Clinical features at presentation of patients failing AS were compared with those who remained under AS at the time of the last follow-up. Predictive factors of delayed intervention were analysed using univariate and multivariate Cox regression models. RESULTS: Overall, 130 patients were included in the analysis, of whom 102 (78.5%) were incidentally diagnosed, while 15 (11.5%) and 13 patients (10%) presented with flank pain and haematuria, respectively. After a mean (sd) follow-up of 49 (40) months, 17 patients (13%) discontinued AS and underwent AT. Patients who underwent delayed intervention were more likely to present with a higher body mass index, larger tumours and symptomatic disease. Angioembolization represented the first-line AT after AS (64.7%), whereas partial nephrectomy was adopted in 29.4% of patients. On the univariate analysis, risk factors for delayed intervention included tumour size ≥4 cm, symptoms at diagnosis, and history of concomitant or contralateral kidney disease. On the multivariate analysis, only tumour size and symptoms remained independently associated with discontinuation of AS. CONCLUSIONS: Tumour size and symptoms at initial presentation were highly predictive of discontinuation of AS in the management of AMLs. Selective angioembolization was the first-line option used for AT after AS was discontinued.

Comorbidity burden and perioperative complications for living kidney donors in the United States.

BACKGROUND AND OBJECTIVES: Since 1998, 35% of kidney transplants in the United States have been derived from living donors. Research suggests minimal long-term health consequences after donation, but comprehensive studies are limited. The primary objective was to evaluate trends in comorbidity burden and complications among living donors. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The National Inpatient Sample (NIS) was used to identify donors from 1998 to 2010 (n=69,117). Comorbid conditions, complications, and length of stay during hospitalization were evaluated. Outcomes among cohorts undergoing appendectomies, cholecystectomies and nephrectomy for nonmetastatic carcinoma were compared, and sample characteristics were validated with the Scientific Registry of Transplant Recipients (SRTR). Survey regression models were used to identify risk factors for outcomes. RESULTS: The NIS captured 89% (69,117 of 77,702) of living donors in the United States. Donor characteristics were relatively concordant with those noted in SRTR (mean age, 40.1 versus 40.3 years [P=0.18]; female donors, 59.0% versus 59.1% [P=0.13]; white donors, 68.4% versus 69.8% [P<0.001] for NIS versus SRTR). Incidence of perioperative complications was 7.9% and decreased from 1998 to 2010 (from 10.1% to 7.6%). Men (adjusted odds ratio [AOR], 1.37; 95% confidence interval [CI], 1.20 to 1.56) and donors with hypertension (AOR, 3.35; 95% CI, 2.24 to 5.01) were more likely to have perioperative complications. Median length of stay declined over time (from 3.7 days to 2.5 days), with longer length of stay associated with obesity, depression, hypertension, and pulmonary disorders. Presence of depression (AOR, 1.08; 95% CI, 1.04 to 1.12), hypothyroidism (AOR, 1.07; 95% CI, 1.04 to 1.11), hypertension (AOR, 1.38; 95% CI, 1.27 to 1.49), and obesity (AOR, 1.07; 95% CI, 1.03 to 1.11) increased over time. Complication rates and length of stay were similar for patients undergoing appendectomies and cholecystectomies but were less than those with nephrectomies for carcinoma. CONCLUSIONS: The NIS is a representative sample of living donors. Complications and length of stay after donation have declined over time, while presence of documented comorbid conditions has increased. Patients undergoing appendectomy and cholecystectomy have similar outcomes during hospitalization. Monitoring the health of living donors remains critically important.

CMV Viremia is associated with a decreased incidence of BKV reactivation after kidney and kidney-pancreas transplantation.

BACKGROUND: Cytomegalovirus (CMV) and BK virus (BKV) infections can cause significant morbidity after kidney and kidney-pancreas transplant. There are limited data on the epidemiology and interactions between these two viral pathogens. METHODS: We prospectively screened 609 kidney or kidney-pancreas transplant recipients from January 2007 to June 2011 for BKV and/or CMV viremia. This included 7453 quantitative BKV polymerase chain reaction and 15,496 quantitative CMV polymerase chain reaction tests. We evaluated risk factors and timing of these infections and the impact of treatment of one infection on the other. RESULTS: Among 609 recipients, 108 (17.7%) developed CMV viremia, of which 95 (88%) were asymptomatic, 5 (5%) had CMV syndrome, and 8 (7%) developed CMV tissue invasive disease at a median of 5.6 months after transplantation. Risk factors for CMV infection using multivariable analysis were D+R- serogroup (P≤0.0001), donor age >50 years (P=0.013), and higher mean tacrolimus (P=0.0009) and mycophenolate mofetil (P=0.01) blood levels. The incidence of BKV infection in the total population was 163 of 609 (26.7%), of which 150 (92%) occurred in patents without antecedent CMV viremia. Such patients demonstrated a higher rate of subsequent BKV viremia than patients with antecedent CMV viremia (P=0.003; hazard ratio, 2.05; 95% confidence interval, 1.2-3.4). Moreover, we found that only symptomatic CMV viremia had a significant negative impact on graft survival when compared with asymptomatic CMV viremia and those without CMV viremia (relative risk, 3.5; 95% confidence interval, 1.06-8.9; P=0.04). CONCLUSION: CMV viremia may indirectly protect against subsequent BK viremia possibly due to a reduction of intensity of immunosuppression after diagnosis of CMV viremia.

The impact of surveillance and rapid reduction in immunosuppression to control BK virus-related graft injury in kidney transplantation.

We prospectively screened 609 consecutive kidney (538) and kidney-pancreas (71) transplant recipients for BK viremia over a 4-year interval using polymerase chain reaction viral load detection and protocol kidney biopsies. We found that BK viremia is common at our center: total cases 26.7%, cases during first year 21.3% (mean 4 months), and recipients with ≥ 10 000 copies/ml 12.3%. We found few predictive clinical or demographic risk factors for any BK viremia or viral loads ≥ 10,000 copies/ml, other than prior treatment of biopsy confirmed acute rejection and/or higher immunosuppressive blood levels of tacrolimus (P = 0.001) or mycophenolate mofetil (P = 0.007). Viral loads at diagnosis (<10 000 copies/ml) demonstrated little impact on graft function or survival. However, rising copy numbers demand early reductions in immunosuppressive drug doses of at least 30-50%. Viral loads >185 000 copies/ml at diagnosis were predictive of BK virus-associated nephropathy (BKVAN; OR: 113.25, 95% CI: 17.22-744.6, P < 0.001). Surveillance for BK viremia and rapid reduction of immunosuppression limited the incidence of BKVAN to 1.3%. The addition of leflunomide or ciprofloxacin to immunosuppressive dose reduction did not result in greater rates of viral clearance. These data support the role of early surveillance for BK viremia to limit the impact on transplant outcome, although the most effective schedule for screening awaits further investigation.