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While major depression is known to be associated with glomerular filtration rate (GFR) decline, there is a lack of data on the association of other mental illnesses like posttraumatic stress disorder (PTSD) with kidney disease. In 640 adult participants of the Heart and Soul Study (mean baseline age of 66.2 years) with a high prevalence cardiovascular disease, hypertension and diabetes, we examined the association of PTSD with GFR decline over a 5 year follow-up. We observed a significantly greater estimated (e) GFR decline over time in those with PTSD compared to those without (2.97 versus 2.11 ml/min/1.73m

ObjectiveHigh levels of psychological distress increase the risk of a wide range of medical diseases. In this study, we investigated the association between posttraumatic stress disorder (PTSD) and kidney disease.MethodsWorld Trade Center (WTC) responders were included if they had two or more measures of estimated glomerular filtration rate (eGFR). The PTSD Checklist (PCL) was used to define no PTSD (PCL < 40), "mild" PTSD (40 ≤ PCL

BackgroundAcute kidney injury (AKI) is associated with mortality in patients hospitalized with COVID-19, however, its incidence, geographic distribution, and temporal trends since the start of the pandemic are understudied.MethodsElectronic health record data were obtained from 53 health systems in the United States (US) in the National COVID Cohort Collaborative (N3C). We selected hospitalized adults diagnosed with COVID-19 between March 6th, 2020, and January 6th, 2022. AKI was determined with serum creatinine (SCr) and diagnosis codes. Time were divided into 16-weeks (P1-6) periods and geographical regions into Northeast, Midwest, South, and West. Multivariable models were used to analyze the risk factors for AKI or mortality.ResultsOut of a total cohort of 306,061, 126,478 (41.0 %) patients had AKI. Among these, 17.9% lacked a diagnosis code but had AKI based on the change in SCr. Similar to patients coded for AKI, these patients had higher mortality compared to those without AKI. The incidence of AKI was highest in P1 (49.3%), reduced in P2 (40.6%), and relatively stable thereafter. Compared to the Midwest, the Northeast, South, and West had higher adjusted AKI incidence in P1, subsequently, the South and West regions continued to have the highest relative incidence. In multivariable models, AKI defined by either SCr or diagnostic code, and the severity of AKI was associated with mortality.ConclusionsUncoded cases of COVID-19-associated AKI are common and associated with mortality. The incidence and distribution of COVID-19-associated AKI have changed since the first wave of the pandemic in the US.

Electronic-based health care delivery systems are gaining popularity among patients and clinicians because of convenience. Importantly, telemedicine, the delivery of health care and/or health information using electronic systems, can deliver primary and specialized health care to geographically isolated patients, who account for nearly 20% of the US population. In nephrology, where a growing discrepancy exists between the geographic location of nephrologists and patients with kidney disease, telenephrology can bridge distance and deliver renal care and education to the isolated. Large nationalized health care systems, for which incentives are aligned to innovate and implement new platforms to deliver cost-effective care, have been at the forefront of telenephrology. These systems include synchronous direct physician-patient care through clinical videoconferencing, and asynchronous modalities such as electronic consultation and video telehealth to educate internists about specialized clinical topics. Large health care organizations are adopting these platforms as standalone services; however, expansion into the private health care system has been limited by reimbursement, regulations, and other issues. Though telenephrology is patient centered, studies are needed to rigorously test its clinical efficacy and cost-effectiveness. Nonetheless, growing patient demand for patient-centric health care will continue to expand the telenephrology space.

Background Numerous publications describe the clinical manifestations of post-acute sequelae of SARS-CoV-2 (PASC or "long COVID"), but they are difficult to integrate because of heterogeneous methods and the lack of a standard for denoting the many phenotypic manifestations. Patient-led studies are of particular importance for understanding the natural history of COVID-19, but integration is hampered because they often use different terms to describe the same symptom or condition. This significant disparity in patient versus clinical characterization motivated the proposed ontological approach to specifying manifestations, which will improve capture and integration of future long COVID studies. Methods The Human Phenotype Ontology (HPO) is a widely used standard for exchange and analysis of phenotypic abnormalities in human disease but has not yet been applied to the analysis of COVID-19. Findings We identified 303 articles published before April 29, 2021, curated 59 relevant manuscripts that described clinical manifestations in 81 cohorts three weeks or more following acute COVID-19, and mapped 287 unique clinical findings to HPO terms. We present layperson synonyms and definitions that can be used to link patient self-report questionnaires to standard medical terminology. Long COVID clinical manifestations are not assessed consistently across studies, and most manifestations have been reported with a wide range of synonyms by different authors. Across at least 10 cohorts, authors reported 31 unique clinical features corresponding to HPO terms; the most commonly reported feature was Fatigue (median 45.1%) and the least commonly reported was Nausea (median 3.9%), but the reported percentages varied widely between studies. Interpretation Translating long COVID manifestations into computable HPO terms will improve analysis, data capture, and classification of long COVID patients. If researchers, clinicians, and patients share a common language, then studies can be compared/pooled more effectively. Furthermore, mapping lay terminology to HPO will help patients assist clinicians and researchers in creating phenotypic characterizations that are computationally accessible, thereby improving the stratification, diagnosis, and treatment of long COVID. Funding U24TR002306; UL1TR001439; P30AG024832; GBMF4552; R01HG010067; UL1TR002535; K23HL128909; UL1TR002389; K99GM145411 .

Background Cannabis is categorized as an illicit drug in most US states, but legalization for medical indications is increasing. Policies and guidance on cannabis use in transplant patients remain controversial. Methods We examined a database linking national kidney transplant records (n = 52 689) with Medicare claims to identify diagnoses of cannabis dependence or abuse (CDOA) and associations [adjusted hazard ratio (aHR) with 95% upper and lower confidence limits (CLs)] with graft, patient, and other clinical outcomes. Results CDOA was diagnosed in only 0.5% (n = 254) and 0.3% (n = 163) of kidney transplant recipients in the years before and after transplant, respectively. Patients with pretransplant CDOA were more likely to be 19 to 30 years of age and of black race, and less likely to be obese, college-educated, and employed. After multivariate and propensity adjustment, CDOA in the year before transplant was not associated with death or graft failure in the year after transplant, but was associated with posttransplant psychosocial problems such as alcohol abuse, other drug abuse, noncompliance, schizophrenia, and depression. Furthermore, CDOA in the first year posttransplant was associated with an approximately 2-fold increased risk of death-censored graft failure (aHR, 2.29; 95% CL, 1.59-3.32), all-cause graft loss (aHR, 2.09; 95% CL, 1.50-2.91), and death (aHR, 1.79; 95% CL, 1.06-3.04) in the subsequent 2 years. Posttransplant CDOA was also associated with cardiovascular, pulmonary, and psychosocial problems, and with events such as accidents and fractures. Conclusions Although associations likely, in part, reflect associated conditions or behaviors, clinical diagnosis of CDOA in the year after transplant appears to have prognostic implications for allograft and patient outcomes. Recipients with posttransplant CDOA warrant focused monitoring and support.

Since late 2019, the novel coronavirus SARS-CoV-2 has introduced a wide array of health challenges globally. In addition to a complex acute presentation that can affect multiple organ systems, increasing evidence points to long-term sequelae being common and impactful. The worldwide scientific community is forging ahead to characterize a wide range of outcomes associated with SARS-CoV-2 infection; however the underlying assumptions in these studies have varied so widely that the resulting data are difficult to compareFormal definitions are needed in order to design robust and consistent studies of Long COVID that consistently capture variation in long-term outcomes. Even the condition itself goes by three terms, most widely “Long COVID”, but also “COVID-19 syndrome (PACS)” or, “post-acute sequelae of SARS-CoV-2 infection (PASC)”. In the present study, we investigate the definitions used in the literature published to date and compare them against data available from electronic health records and patient-reported information collected via surveys. Long COVID holds the potential to produce a second public health crisis on the heels of the pandemic itself. Proactive efforts to identify the characteristics of this heterogeneous condition are imperative for a rigorous scientific effort to investigate and mitigate this threat.

Introduction: Acute kidney injury (AKI) is strongly associated with poor outcomes in hospitalized patients with coronavirus disease 2019 (COVID-19), but data on the association of proteinuria and hematuria are limited to non-US populations. In addition, admission and in-hospital measures for kidney abnormalities have not been studied separately. Methods: This retrospective cohort study aimed to analyze these associations in 321 patients sequentially admitted between March 7, 2020 and April 1, 2020 at Stony Brook University Medical Center, New York. We investigated the association of proteinuria, hematuria, and AKI with outcomes of inflammation, intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), and in-hospital death. We used ANOVA, t test, χ2 test, and Fisher’s exact test for bivariate analyses and logistic regression for multivariable analysis. Results: Three hundred patients met the inclusion criteria for the study cohort. Multivariable analysis demonstrated that admission proteinuria was significantly associated with risk of in-hospital AKI (OR 4.71, 95% CI 1.28–17.38), while admission hematuria was associated with ICU admission (OR 4.56, 95% CI 1.12–18.64), IMV (OR 8.79, 95% CI 2.08–37.00), and death (OR 18.03, 95% CI 2.84–114.57). During hospitalization, de novo proteinuria was significantly associated with increased risk of death (OR 8.94, 95% CI 1.19–114.4, p = 0.04). In-hospital AKI increased (OR 27.14, 95% CI 4.44–240.17) while recovery from in-hospital AKI decreased the risk of death (OR 0.001, 95% CI 0.001–0.06). Conclusion: Proteinuria and hematuria both at the time of admission and during hospitalization are associated with adverse clinical outcomes in hospitalized patients with COVID-19.

Background Retrospective studies on the use of Renin-Angiotensin-Aldosterone System blockade in patients with Coronavirus Disease 2019 (COVID-19) have been informative but conflicting, and prospective studies are required to demonstrate the safety, tolerability, and outcomes of initiating these agents in hospitalized patients with COVID-19 and hypertension. Methods and findings This is a single center feasibility study encompassing two cohorts: (1) prospective cohort (April 21, 2020 to May 29, 2020) and (2) retrospective cohort (March 7, 2020 to April 1, 2020) of hospitalized patients with real-time polymerase chain reaction (PCR) positive SARS-CoV-2 by nasopharyngeal swab. Key inclusion criteria include BP > 130/80 and a requirement of supplemental oxygen with FiO2 of 25% or higher to maintain SpO2 > 92%. Key exclusion criteria included hyperkalemia and acute kidney injury (AKI) at the time of enrollment. Prospective cohort consisted of de novo initiation of losartan and continuation for a minimum of 7 days and assessed for adverse events (AKI, hyperkalemia, transaminitis, hypotension) and clinical outcomes (change in SpO2/FiO2 and inflammatory markers, need for ICU admission and mechanical ventilation). Retrospective cohort consisted of continuation of losartan (prior-to-hospitalization) and assessment of similar outcomes. In the prospective cohort, a total of 250 hospitalized patients were screened and inclusion/exclusion criteria were met in 16/250 patients and in the retrospective cohort, a total of 317 hospitalized patients were screened and inclusion/exclusion criteria were met in 14/317 patients. Most common adverse event was hypotension, leading to discontinuation in 3/16 (19%) and 2/14 (14%) patients in the prospective and retrospective cohort. No patients developed AKI in the prospective cohort as compared to 1/14 (7%) patients in the retrospective cohort, requiring discontinuation of losartan. Hyperkalemia occurred in 1/16 (6%) and 0/14 patients in the prospective and retrospective cohorts, respectively. In the prospective cohort, 3/16 (19%) and 2/16 (13%) patients required ICU admission and mechanical ventilation. In comparison, 3/14 (21%) required ICU admission and mechanical ventilation in the retrospective cohort. A majority of patients in both cohorts (14/16 (88%) and 13/14 (93%) patients from the prospective and retrospective cohort) were discharged alive from the hospital. A total of 9/16 (prospective) and 5/14 (retrospective) patients completed a minimum 7 days of losartan. In these 9 patients in the prospective cohort, a significant improvement in SpO2/FiO2 ratio was observed from day 1 to 7. No significant changes in inflammatory markers (initiation, peak, and day 7) were observed in either cohort. Conclusion In this pilot study we demonstrate that losartan was well-tolerated among hospitalized patients with COVID-19 and hypertension. We also demonstrate the feasibility of patient recruitment and the appropriate parameters to assess the outcomes and safety of losartan initiation or continuation, which provides a framework for future randomized clinical trials.

Hypertension guidelines recommend calcium channel blockers (CCBs), thiazide diuretics, and angiotensin-converting-enzyme inhibitors/angiotensin receptor blockers (ACEi/ARBs) as first-line agents to treat hypertension. Hypertension is common among kidney transplant (KTx) recipients, but data are limited regarding patterns of antihypertensive medication (AHM) use in this population. We examined a novel database that links national registry data for adult KTx recipients (age > 18 years) with AHM fill records from a pharmaceutical claims warehouse (2007-2016) to describe use and correlates of AHM use during months 7-12 post-transplant. For patients filling AHMs, individual agents used included: dihydropyridine (DHP) CCBs, 55.6%; beta-blockers (BBs), 52.8%; diuretics, 30.0%; ACEi/ARBs, 21.1%; non-DHP CCBs, 3.0%; and others, 20.1%. Both BB and ACEi/ARB use were significantly lower in the time period following the 2014 Eighth Joint National Committee (JNC-8) guidelines (2014-2016), compared with an earlier period (2007-2013). The median odds ratios generated from case-factor adjusted models supported variation in use of ACEi/ARBs (1.51) and BBs (1.55) across transplant centers. Contrary to hypertension guidelines for the general population, KTx recipients are prescribed relatively more BBs and fewer ACEi/ARBs. The clinical impact of this AHM prescribing pattern warrants further study.

Fast glomerular filtration rate (GFR) decline is associated with adverse outcomes, but the associated risk factors among patients without chronic kidney disease (CKD) are not well defined. From a primary care registry of 37,796, we identified 2219 (6%) adults with at least three estimated (e)GFR values and a baseline eGFR between 60 and 119 ml/min/1.73 m2 during an observation period of 8 years. We defined fast GFR decline as > 5 ml/min/1.73 m2 per year. The outcome measure was incident CKD (eGFR

Living donor kidney transplantation is the preferred treatment option for ESRD. However, recent data suggest a small increase in the long-term risk of kidney failure in living kidney donors when compared to healthy nondonors. These data have led to a need for reconsideration of how donor candidates are evaluated and selected for donation. A Kidney Disease: Improving Global Outcomes (KDIGO) work group completed a comprehensive clinical practice guideline for evaluation of living kidney donor candidates in 2017, based on systematic evidence review, de novo evidence generation, and expert opinion. Central to the evaluation framework is assessment of glomerular filtration rate (GFR), which is used to screen for kidney disease and aid the prediction of long-term kidney failure risk after donation. Accurate estimation of the level of GFR and risk of kidney failure, and communication of estimated risks, can support evidence-based donor selection and shared decision-making. In this review, we discuss approaches to optimal GFR estimation in the donor evaluation process, long-term risk projection, and risk communication to donor candidates, integrating recommendations from the new KDIGO guideline, other recent literature, and experience from our own research and practice. We conclude by highlighting topics for further research in this important area of transplant medicine.

Data outside of clinical trials with direct-acting antiviral regimens with or without ribavirin as treatment of chronic hepatitis C virus in solid organ transplant recipients are limited. Liver transplant (LT), kidney transplant (KT), and dual liver kidney (DLK) transplant recipients from the Hepatitis C Therapeutic Registry and Research Network database, a multicenter, longitudinal clinical care treatment cohort, treated with direct-acting antiviral regimens between January 1, 2014, and February 15, 2016, were included to assess safety and efficacy. Included were 443 posttransplant patients (KT = 60, LT = 347, DLK = 36); 42% had cirrhosis, and 54% had failed prior antiviral therapy. Most had genotype (GT) 1 (87% with 52% GT1a, 27% GT1b, and 8% GT1 no subtype) and were treated with sofosbuvir (SOF)/ledipasvir ± ribavirin (85%) followed by SOF + daclatasvir ± ribavirin (9%) and ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (6%). Rates of sustained virologic response (SVR) at 12 weeks were available on 412 patients, and 395 patients (95.9%) achieved SVR at 12 weeks: 96.6%, 94.5%, and 90.9% among LT, KT, and DLK transplant recipients, respectively. Ribavirin did not influence SVR rates and was more often used in those with higher BMI, higher estimated glomerular filtration rate and lower creatinine. Female gender, baseline albumin ≥3.5 g/dL, baseline total bilirubin ≤1.2 mg/dL, absence of cirrhosis, and hepatic decompensation predicted SVR at 12 weeks. Six episodes of acute rejection (n = 2 KT, 4 LT) occurred, during hepatitis C virus treatment in 4 and after cessation of treatment in 2. Conclusion In a large prospective observational cohort study, direct-acting antiviral therapy with SOF/ledipasvir, ombitasvir/paritaprevir/ritonavir + dasabuvir, and SOF plus daclatasvir was efficacious and safe in LT, KT, and DLK transplant recipients; ribavirin did not influence SVR, and graft rejection was rare. (Hepatology 2017;66:1090-1101).

Dietary supplements are widely used for their perceived health benefits without side effects and hence have minimal regulation. However, they have been associated with various toxicities including kidney disease. We report a 65-year-old male who had very heavy daily intake of dietary supplements for 3 years. He presented with acute kidney injury and nephrotic-range proteinuria. The renal biopsy showed acute tubular necrosis with vacuolization, acute interstitial nephritis, and secondary membranous nephropathy, consistent with an non-steroidal anti-inflammatory drug (NSAID)-like nephropathy. This was postulated to be related to the cyclooxygenase (COX) inhibitors (anthocyanins) in cherry extract that was a significant part of the patient's dietary supplement use. His proteinuria completely resolved and serum creatinine stabilized after discontinuation of all dietary supplements and a prolonged (5 months) course of prednisone. Clinicians are advised to specifically inquire about dietary supplements, especially cherry extract, as a potential cause of new-onset renal failure and proteinuria. .

We examined a novel linkage of national U.S. donor registry data with records from a pharmacy claims warehouse (2007–2016) to examine associations (adjusted hazard ratio, (LCL) aHR (UCL)) of postdonation fills of antidiabetic medications (ADM, insulin or non-insulin agents) with body mass index (BMI) at donation and other demographic and clinical factors. In 28,515 living kidney donors (LKDs), incidence of ADM use at 9 years rose in a graded manner with higher baseline BMI: underweight, 0.9%; normal weight, 2.1%; overweight, 3.5%; obese, 8.5%. Obesity was associated with higher risk of ADM use compared to normal BMI (aHR, (3.36)4.59(6.27)). Metformin was the most commonly used ADM and was filled more often by obese than by normal weight donors (9-year incidence, 6.87% vs. 1.85%, aHR, (3.55)5.00(7.04)). Insulin use was uncommon and did not differ significantly by BMI. Among a subgroup with BMI data at the 1-year post-donation anniversary (n=19,528), compared with stable BMI, BMI increase >0.5 kg/m(2) by year 1 was associated with increased risk of subsequent ADM use (aHR, (1.03)1.48 (2.14,) P=0.036). While this study did not assess the impact of donation on the development of obesity, these data support that among LKD, obesity is a strong correlate of ADM use.

PURPOSE OF REVIEW: Research over the past few decades points to the importance of frailty, or the lack of physiologic reserve, in the natural history of chronic diseases and in modifying the impact of potential interventions. End-stage kidney disease (ESKD) and the intervention of kidney transplantation are no exception. We review the recent epidemiologic and cohort-based evidence on the association between frailty and kidney transplant outcomes and provide a framework of questions with which to approach future research endeavors and clinical practice. RECENT FINDINGS: Frailty in kidney transplant candidates can be measured in numerous ways, including descriptive phenotype, description scores, functional testing, and surrogate measures. Regardless of the metric, the presence of frailty is strongly associated with inferior pre- and posttransplant outcomes compared to the absence of frailty. However, some frail patients with ESKD can benefit from transplant over chronic dialysis. Evidence-based approaches for identifying frail ESKD patients who can benefit from transplant over dialysis, with acceptable posttransplant outcomes, are lacking. Interventional trials to improve frailty and physical function before transplant (prehabilitation) and after transplant (rehabilitation) are also lacking. CONCLUSION: Frailty is increasingly recognized as highly relevant to peritransplant outcomes, but more work is needed to: 1) tailor management to the unique needs of frail patients, both pre- and posttransplant; 2) define phenotypes of frail patients who are expected to benefit from transplant over dialysis; and 3) develop interventions to reverse frailty, both pre- and post-transplant.

Background & aimsRenal clearance is the major elimination pathway for sofosbuvir (SOF). We assessed the safety and efficacy of SOF-containing regimens in patients with varying baseline estimated glomerular filtration rate (eGFR).MethodsHCV-TARGET database is a multicentre, longitudinal 'real-world' treatment cohort.ResultsA total of 1789 patients [genotypes 1 (72%), 2 (17%) 3 (9%), 4-6 (2%)] had baseline eGFR determination: 73 with eGFR≤45 (18 with eGFR≤30, 5 on dialysis) were compared to 1716 with eGFR>45 ml/min/1.73 m(2) . Patients with baseline eGFR≤45 vs. >45 differed in being female (55% vs. 36%), age ≥65 years (24% vs. 16%), Black race (22% vs. 12%), having cirrhosis with decompensation (73% vs. 24%) and being post-transplant (49% vs. 10%), all P < 0.05. All patients with eGFR≤45 were treated with SOF 400 mg/day (including those on haemodialysis) and had median starting ribavirin (RBV) dose of 800 mg (IQR: 400-1200). Sustained virologic response (SVR) frequencies were similar across eGFR groups, ranging from 82-83%. Patients with eGFR ≤45 more frequently experienced anaemia, worsening renal function and serious AEs (all P < 0.05), and these associations persisted when limiting analysis to RBV-free regimens. Patients with baseline eGFR≤30 and eGFR 31-45 had similar frequencies of efficacy and safety outcomes.ConclusionsSustained viral clearance was achieved in 83% of patients with renal impairment (eGFR ≤45 ml/min/1.73 m(2) ) treated with SOF-containing regimens. However, these patients had higher rates of anaemia, worsening renal dysfunction and serious adverse events regardless of use of RBV. Patient with renal impairment require close monitoring and should be treated by providers extensively experienced with SOF-containing regimens.

Background Chronic kidney disease (CKD) is associated with increased all-cause mortality. How non-traditional risk factors modify the mortality risk associated with CKD has not been studied. We approached this question using elevated monocyte count, which is associated with increased risk of death in the general population; however, there is very limited data in CKD. Materials and methods A national cohort of 1,706,589 U.S. veterans without end-stage renal disease (ESRD) was followed over a median of 9.16 years. Estimated glomerular filtration rate (eGFR; mL/min/1.73m2) was divided into 6 categories: 15 - 30, 30 - 45, 45 - 60, 60 - 90, 90 - 105 (reference), and > 105. Monocyte count (k/cmm) was grouped into quartiles: 0.00 - 0.40 (reference), 0.40 - 0.56, 0.56 - 0.70, and > 0.70. Multinomial logistic regression, Cox proportional hazard regression, and formal interaction analyses on both the multiplicative and additive scales were undertaken. Results Monocyte count > 0.56 k/cmm was associated with increased risk of death overall (hazard ratio (HR) 1.40, confidence interval (CI) 1.38, 1.41 in monocyte quartile 4) and across each eGFR category. Very high (> 105 mL/min/1.73m2) and low (15 - 30 mL/min/1.73m2) eGFR categories were associated with increased mortality risk (HR 1.40, CI 1.38, 1.42 and HR 2.07, CI 2.03, 2.11, respectively). The mortality risk associated with high monocyte count and low eGFR exhibited a strong negative interaction (p Conclusion While low and very high eGFR were both associated with increased mortality risk, a monocyte count > 0.56 k/cmm only modified the risk associated with low eGFR. This suggests a shared underlying mechanism of death between CKD and high monocyte count. .

While guidelines support metformin as a therapeutic option for diabetic patients with mild-to-moderate renal insufficiency, the frequency and outcomes of metformin use in kidney transplant recipients are not well described. We integrated national U.S. transplant registry data with records from a large pharmaceutical claims clearinghouse (2008-2015). Associations (adjusted hazard ratio, 95% LCL aHR95% UCL ) of diabetes regimens (with and excluding metformin) in the first year post-transplant with patient and graft survival over the subsequent year were quantified by multivariate Cox regression, adjusted for recipient, donor, and transplant factors and propensity for metformin use. Among 14 144 recipients with pretransplant type 2 diabetes mellitus, 4.7% filled metformin in the first year post-transplant; most also received diabetes comedications. Compared to those who received insulin-based regimens without metformin, patients who received metformin were more likely to be female, have higher estimated glomerular filtration rates, and have undergone transplant more recently. Metformin-based regimens were associated with significantly lower adjusted all-cause (aHR 0.18 0.410.91 ), malignancy-related (aHR 0.45 0.450.99 ), and infection-related (aHR 0.12 0.320.85 ) mortality, and nonsignificant trends toward lower cardiovascular mortality, graft failure, and acute rejection. No evidence of increased adverse graft or patient outcomes was noted. Use of metformin-based diabetes treatment regimens may be safe in carefully selected kidney transplant recipients.

Introduction Late nephrology referral is associated with adverse outcomes especially among minorities. Research on the association of the rate of chronic kidney disease (CKD) progression with nephrology referral in white versus black patients is lacking. Objectives Compute the odds of nephrology referral in primary care and their associations with race and the rate of CKD progression. Methods Electronic health record data were obtained from 2170 patients in primary care clinics in the Saint Louis metropolitan area with at least two estimated glomerular filtration rate (eGFR) values over a 7-year observation period. Fast CKD progression was defined as a decline in eGFR of ≥5 ml/min/1.73 m2/year. Logistic regression models were computed to measure the associations between eGFR progression, race and nephrology referral before and after adjusting for potential confounding factors. Results Nephrology referrals were significantly more prevalent among those with fast compared to slow progression (5.6 versus 2.0%, P < 0.0001), however, a majority of fast progressors were not referred. Fast CKD progression and black race were associated with increased odds of nephrology referral (OR = 2.74; 95% CI: 1.60-4.72 and OR = 2.42; 95% CI: 1.28-4.56, respectively). The interaction of race and eGFR progression in nephrology referral was found to be non-significant. Conclusion Nephrology referrals are more common in fast CKD progression, but referrals are underutilized. Nephrology referral is more common among blacks but its' association with rate of decline does not differ by race. Further studies are required to investigate the benefit of early referral of patients at risk of fast CKD progression.

Background: Medullary sponge kidney (MSK) is characterized by malformation of the terminal collecting ducts and is associated with an increased risk of nephrolithiasis, nephrocalcinosis, urinary tract infections, renal acidification defects, and reduced bone density. It has been historically diagnosed with intravenous pyelography (IVP), which is falling out of favor as an imaging modality. CT urography (CTU) performed with multidetector CT (MDCT) has been shown to create images of the renal collecting system with similar detail as IVP; however, its utility in diagnosing MSK has not been defined. Case Report: We present the first 15 patients with recurrent symptomatic nephrolithiasis who were evaluated in our renal stone clinic with CTU. Four patients were diagnosed with MSK after visualization of the characteristic radiologic findings. Discussion: CTU effectively demonstrates the characteristic radiologic findings of MSK including collecting tubule dilatation, medullary nephrocalcinosis, nephrolithiasis, and medullary cysts. Dose reduction protocols can reduce radiation exposure below that associated with conventional IVP. We propose CTU be considered for the diagnosis of MSK.

Introduction: 5-aminosalicylic acid (5-ASA) compounds have been used in the management of ulcerative colitis for decades. Nephrotoxicity has been previously described in patients treated with 5-ASA compounds and usually manifests as interstitial nephritis, however a few cases of nephrotic syndrome have been reported. Balsalazide is a pro-drug composed of 5-ASA linked to an inert carrier. Case Presentation: Here we report the case of a 74-year-old man with a history of ulcerative proctosigmoiditis treated with balsalazide who presented to our clinic with bilateral lower extremity edema three months after initiation of balsalazide. Laboratory workup showed nephrotic range proteinuria without an apparent secondary etiology. Given worsening proteinuria and renal function despite cessation of balsalazide, the patient underwent renal biopsy that revealed minimal change disease. High dose steroids were started and complete remission of proteinuria was achieved one month into therapy which was slowly tapered over the next five months. Eventual resolution of edema and return of creatinine back to patient’s baseline level was achieved. Conclusion: To our knowledge, this is the first report of nephrotic syndrome manifesting soon after initiation of balsalazide therapy. Our work highlights the importance of maintaining a high clinical suspicion for nephrotoxicity when using balsalazide.

The original version of this article did not include the authors’ National Institutes of Health grant in the Funding and Acknowledgements. The following should appear in the Funding and Conflict of Interest sections of the paper.

Background Inflammation is known to be associated with posttraumatic stress disorder. It is not known if total white blood cell count, a routinely checked inflammatory marker, is associated with posttraumatic stress disorder symptom trajectories using medical record data. Methods We used latent class growth analysis to identify three-year posttraumatic stress disorder symptom trajectories using posttraumatic stress disorder (PTSD) Checklist (PCL) scores. The outcome for each patient was maximum white blood cell count from index posttraumatic stress disorder diagnosis to last PCL . Using linear regression analysis, we then calculated and compared the average white blood cell count for each trajectory before and after controlling for age, gender, race, obesity, smoking, diabetes, hypertension, cardiovascular disease, depression, and other comorbid inflammatory conditions. Results Patients were 40.2 (SD ± 13.5) years of age, 83.7% males and 67.9% white. We identified three PCL trajectory groups based on symptom severity over time: “moderate-large decrease,” “moderate-severe-slight decrease,” and “severe-persistent.” In adjusted analyses, “severe-persistent” versus “moderate-large decrease” had significantly higher white blood cell count (B = 0.64; 95%CI = 0.18, 1.09; p = .006). Although non-significant, “moderate-severe-slight decrease” versus “moderate-large decrease” also had a higher white blood cell count (B = 0.42; 95% CI: −0.02, 0.86; p = .061). Conclusion Persistently severe posttraumatic stress disorder is associated with a higher white blood cell count than improving posttraumatic stress disorder. White blood cell appears to have utility for measuring the association between psychiatric disorders and inflammation in retrospective cohort studies involving large administrative medical record data bases.

Biomedical research often requires primary cultures of specific cell types, which are challenging to obtain at high purity in a reproducible manner. Here we engineered the murine Rosa26 locus by introducing the diphtheria toxin receptor flanked by loxP sites. The resultant strain was nicknamed the Terminator mouse. This approach results in diphtheria toxin–receptor expression in all non-Cre expressing cell types, making these cells susceptible to diphtheria toxin exposure. In primary cultures of kidney cells derived from the Terminator mouse, over 99.99% of cells were dead within 72h of diphtheria toxin treatment. After crossing the Terminator with the podocin-Cre (podocyte specific) mouse or the Ggt-Cre (proximal tubule specific) mouse, diphtheria toxin treatment killed non-Cre expressing cells but spared podocytes and proximal tubule cells, respectively, enriching the primary cultures to over 99% purity, based on both western blotting and immunostaining of marker proteins. Thus, the Terminator mouse can be a useful tool to selectively and reproducibly obtain even low-abundant cell types at high quantity and purity.

D-penicillamine, used to treat cystinuria, is known to cause impaired collagen deposition and dysfunction in elastic fibers. D-penicillamine also has been associated with glomerular abnormalities, typically membranous glomerulonephritis. We describe a patient with severe bilateral cystic kidney disease that developed after long-term D-penicillamine use for treatment of cystinuria. The cysts in the kidneys were noted during an evaluation for acute kidney injury. The patient had no evidence of cysts on prior renal imaging at a time when his kidney function was normal. Simultaneously, he presented with multiorgan manifestations of D-penicillamine toxicity, including the skin findings of cutix laxa and elastosis perforans serpiginosa. Consequently, D-penicillamine treatment was discontinued, after which the progression of cystic kidney disease gradually ceased, along with the other systemic manifestations of toxicity. To our knowledge, this is the first report of cystic kidney disease associated with and perhaps caused by long-term d-penicillamine therapy. The proposed mechanism of cyst formation is the malfunction of the extracellular matrix of the kidney by d-penicillamine that leads to an impaired repair process after kidney injury.

Polycystic kidney disease (PKD) exhibits an inflammatory component, but the contribution of inflammation to cyst progression is unknown. Macrophages promote the proliferation of tubular cells following ischemic injury, suggesting that they may have a role in cystogenesis. Furthermore, cultured Pkd1-deficient cells express the macrophage chemoattractants Mcp1 and Cxcl16 and stimulate macrophage migration. Here, in orthologous models of both PKD1 and PKD2, abnormally large numbers of alternatively activated macrophages surrounded the cysts. To determine whether pericystic macrophages contribute to the proliferation of cyst-lining cells, we depleted phagocytic cells from Pkd1(fl/fl);Pkhd1-Cre mice by treating with liposomal clodronate from postnatal day 10 until day 24. Compared with vehicle-treated controls, macrophage-depleted mice had a significantly lower cystic index, reduced proliferation of cyst-lining cells, better-preserved renal parenchyma, and improved renal function. In conclusion, these data suggest that macrophages home to cystic areas and contribute to cyst growth. Interruption of these homing and proliferative signals could have therapeutic potential for PKD.

While Wnt and Hgf signaling pathways are known to regulate epithelial cell responses during injury and repair, whether they exhibit functional cross-talk is not well defined. Canonical Wnt signaling is initiated by the phosphorylation of the Lrp5/6 co-receptors. In the current study we demonstrate that Hgf stimulates Met and Gsk3-dependent and Wnt-independent phosphorylation of Lrp5/6 at three separate activation motifs in subconfluent, de-differentiated renal epithelial cells. Hgf treatment stimulates the selective association of active Gsk3 with Lrp5/6. In contrast, Akt-phosphorylated inactive Gsk3 is excluded from this association. Hgf stimulates β-catenin stabilization and nuclear accumulation and protects against epithelial cell apoptosis in an Lrp5/6-dependent fashion. In vivo, the increase in Lrp5/6 phosphorylation and β-catenin stabilization in the first 6–24 h after renal ischemic injury was significantly reduced in mice lacking Met receptor in the renal proximal tubule. Our results thus identify Hgf as an important transactivator of canonical Wnt signaling that is mediated by Met-stimulated, Gsk3-dependent Lrp5/6 phosphorylation.

Commentary on: McBrien K, Rabi DM, Campbell N, et al. Intensive and standard blood pressure targets in patients with type 2 diabetes mellitus: systematic review and meta-analysis. Arch Intern Med 2012;172:1296–303.[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Although lowering blood pressure (BP) to the standard target of 140/90 mm Hg improves cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM), the benefits of more intensive lowering to

LP08 SAFETY AND EFFICACY OF SOFOSBUVIR-CONTAINING REGIMENS IN HEPATITIS C INFECTED PATIENTS WITH REDUCED RENAL FUNCTION: REAL-WORLD EXPERIENCE FROM HCV-TARGET V. Saxena, F.M. Koraishy, M. Sise, J.K. Lim, R.T. Chung, A. Liapakis, D.R. Nelson, M. Schmidt, M.W. Fried, N. Terrault, and HCV-TARGET. University of California San Francisco, San Francisco, Saint Louis University School of Medicine, St. Louis, Massachusetts General Hospital, Boston, Yale University School of Medicine, New Haven, University of Florida, Gainesville, University of North Carolina, Chapel Hill, United States E-mail: varun.saxena@ucsf.edu