Renal Autologous Cell Therapy in Type 2 Diabetes with Late Stage 4 Diabetes-Related Chronic Kidney Disease: Trial Design and Early Analysis.

INTRODUCTION: Cell-based therapies potentially delay the trajectory toward end-stage kidney disease (ESKD) in late stage 4 diabetic chronic kidney disease (DKD). We describe the trial design, baseline patient characteristics, and early results of an IRB-approved phase II multicenter clinical trial, utilizing Renal Autologous Cell Therapy (REACT) in adults with pre-ESKD due to type 2 DKD. The trial objectives were safety and tolerability of REACT by assessment of the procedure, product administration, and renal-specific adverse events in addition to evaluate the impact on renal function following injection. METHODS: Ten adults with an eGFR of 14-20 mL/min/1.73 m2 were enrolled in a single-arm open-label trial. Following a percutaneous kidney biopsy, an ex vivo expansion of selected renal cells that form the REACT was injected into the cortex of the biopsied kidney with CT image guidance. Each participant received two doses of the REACT product at 6-month intervals. A 6-month observation pre-trial was required to establish patients' "own" baseline and rate of DKD progression. RESULTS: Five men and 5 women underwent 19 REACT injections (1 participant received only one injection). Their baseline characteristics were as follows: 3 Hispanic/Latino, 7 non-Hispanic, 7 white; mean (SD) age: 58.9 years (5.22), BMI 35.8 (8.2), eGFR (sCR) 15.5 (2.72), eGFR (sCR + Cys-C) 17.7 (3.67) mL/min/1.73 m2, sCr 3.6 mg/mL (0.73), Cys-C 2.6 mg/mL (0.52), and log random UACR 7.9 mg/g (1.01). The pre- and post-injection eGFR slope was -6.5 mL/min/1.73 m2 and -3.9 mL/min/1.73 m2. No cell-related adverse events occurred, and two procedure-related hematomas required observation without transfusion or angiographic interventions. Dialysis was delayed a mean of 16 months (range 6-28 months). At 15 months, 2 patients (20%) have eGFR slope stability and have not commenced renal replacement therapy. CONCLUSION: Trials that include patients with an eGFR of <20 mL/min/1.73 m2 are uncommon, and none to date involve autologous homologous cell-based treatments. REACT has the potential to stabilize or delay dialysis in high-risk late stage 4 DKD.

Point of Care Ultrasound in Monitoring of Post-Renal Biopsy Bleeding.

A 32-year-old male presented with hypertensive emergency and features of thrombotic microangiopathy. He underwent a kidney biopsy after renal dysfunction persisted despite clinical improvement otherwise. The kidney biopsy was performed with direct ultrasound guidance. The procedure was complicated by hematoma formation and persistent turbulent flow on color Doppler concerning for ongoing bleeding. Serial point of care ultrasounds of the kidney with color flow Doppler were used to monitor the size of the hematoma and determine if there was evidence of ongoing bleeding. These serial ultrasounds showed stable hematoma size, resolution of biopsy-associated Doppler signal and prevented further invasive interventions.

Apolipoprotein-1 risk variants and associated kidney phenotypes in an adult HIV cohort in Nigeria.

HIV-positive adults are at risk for various kidney diseases, and apolipoprotein 1 (APOL1) high-risk genotypes increase this risk. This study aimed to determine the prevalence and ethnic distribution of APOL1 risk genotypes among a cohort of HIV-positive Nigerian adults and explore the relationship between APOL1 risk variant status with albuminuria and estimated glomerular filtration rate (eGFR). We conducted a cross-sectional study among 2 458 persons living with HIV who attended an HIV clinic in northern Nigeria and had received antiretroviral therapy for a minimum of six months. We collected two urine samples four-eight weeks apart to measure albumin excretion, and blood samples to measure eGFR and determine APOL1 genotype. The frequency of APOL1 high-risk genotype was 6.2%, which varied by ethnic group: Hausa/Fulani (2.1%), Igbo (49.1%), and Yoruba (14.5%). The prevalence of microalbuminuria (urine/albumin creatinine ratio 30- 300 mg/g) was 37%, and prevalence of macroalbuminuria (urine/albumin creatinine ratio over 300 mg/g) was 3%. The odds of microalbuminuria and macroalbuminuria were higher for participants with the APOL1 high-risk genotype compared to those carrying the low-risk genotype ([adjusted odds ratio 1.97, 95% confidence interval 1.37-2.82] and [3.96, 1.95-8.02] respectively). APOL1 high-risk genotype participants were at higher risk of having both an eGFR under 60 ml/min/1.73m2 and urine/albumin creatinine ratio over 300 mg/g (5.56, 1.57-19.69). Thus, we found a high proportion of HIV-positive, antiretroviral therapy-experienced, and largely virologically suppressed adults had microalbuminuria. Hence, although the high-risk APOL1 genotype was less prevalent than expected, it was strongly associated with some level of albuminuria.

The Nephrology Clinician Educator: Pathway and Future.

In the medical profession, teaching has always been a routine expectation for practicing physicians. While this remains true today, in recent years, we have seen the emergence of a well-defined career pathway for those practicing physicians who want to focus on education: the clinician educator. This is a physician who is highly active in the practice of teaching, science of learning, service as a role model for young physicians, and leading educational programs. In nephrology, one can have a fruitful and fulfilling career as a lifelong clinician educator. As career interest in our specialty wanes, the clinician educator is the professional well suited to reverse this trend. In this article, we will further define the clinician educator and map out a pathway of skills needed to thrive in this rewarding career. We also provide recommendations to both educators and leaders to ensure the clinician educator pathway continues to grow.

Effect of Intensive vs Standard Blood Pressure Treatment Upon Erectile Function in Hypertensive Men: Findings From the Systolic Blood Pressure Intervention Trial.

INTRODUCTION: The effect of intensive blood pressure control upon erectile function in men with hypertension, but without diabetes, is largely unknown. AIM: To examine the effects of intensive systolic blood pressure (SBP) lowering on erectile function in a multiethnic clinical trial of men with hypertension. METHODS: We performed subgroup analyses from the Systolic Blood Pressure Intervention Trial ([SPRINT]; ClinicalTrials.gov: NCT120602, in a sample of 1255 men aged 50 years or older with hypertension and increased cardiovascular disease risk. Participants were randomly assigned to an intensive treatment group (SBP goal of <120 mmHg) or a standard treatment group (SBP goal of <140 mmHg). MAIN OUTCOME MEASURE: The main outcome measure was change in erectile function from baseline, using the 5-item International Index of Erectile Function (IIEF-5) total score, and erectile dysfunction ([ED]; defined as IIEF-5 score ≤21) after a median follow-up of 3 years. RESULTS: At baseline, roughly two-thirds (66.1%) of the sample had self-reported ED. At 48 months after randomization, we determined that the effects of more intensive blood pressure lowering were significantly moderated by race-ethnicity (p for interaction = 0.0016), prompting separate analyses stratified by race-ethnicity. In non-Hispanic whites, participants in the intensive treatment group reported slightly, but significantly better change in the IIEF-5 score than those in the standard treatment group (mean difference = 0.67; 95% CI = 0.03, 1.32; P = 0.041). In non-Hispanic blacks, participants in the intensive group reported slightly worse change in the IIEF-5 score than those in the standard group (mean difference = -1.17; 95% CI = -1.92, -0.41; P = 0.0025). However, in non-Hispanic whites and non-Hispanic blacks, further adjustment for the baseline IIEF-5 score resulted in nonsignificant differences (P > 0.05) according to the treatment group. In Hispanic/other participants, there were no significant differences in change in the IIEF-5 score between the two treatment groups (P = 0.40). In a subgroup of 280 participants who did not report ED at baseline, the incidence of ED did not differ in the two treatment groups (P = 0.53) and was without interaction by race-ethnicity. CLINICAL IMPLICATIONS: The effect of intensive treatment of blood pressure on erectile function was very small overall and likely not of great clinical magnitude. STRENGTH & LIMITATIONS: Although this study included a validated measure of erectile function, testosterone, other androgen, and estrogen levels were not assessed. CONCLUSION: In a sample of male patients at high risk for cardiovascular events but without diabetes, targeting a SBP of less than 120 mm Hg, as compared with less than 140 mm Hg, resulted in statistically significant effects on erectile function that differed in accordance with race-ethnicity, although the clinical importance of the differences may be of small magnitude. Foy CG, Newman JC, Russell GB, et al. Effect of Intensive vs Standard Blood Pressure Treatment Upon Erectile Function in Hypertensive Men: Findings From the Systolic Blood Pressure Intervention Trial. J Sex Med 2020;17:238-248.

Women's Reproductive Health for the Nephrologist.

Women with chronic kidney disease (CKD) are faced with complex decisions and significant challenges during their reproductive years. Contraceptive choices have a variety of side effects that can disproportionately affect women with CKD, limiting choice. CKD itself and the therapies needed to treat severe disease can affect future fertility. When conception is desired, young women with CKD must plan meticulously because an ill-timed pregnancy can result in disease progression or flare and exposure of an unborn child to potentially teratogenic medications. Among women with CKD, pregnancy risks are substantial, with up to 10-fold higher risk for preeclampsia and 6-fold higher risk for preterm delivery. These pregnancy complications associated with inadequate placentation also increase maternal and newborn risks for cardiovascular morbidity and mortality and progression to kidney failure later in life. As such, it is the obligation of every nephrologist caring for women of reproductive age to provide guidance in the choice of methods to prevent unplanned pregnancies, to choose treatments that preserve fertility, and to participate in shared decision making that optimizes pregnancy timing and outcomes. In this perspective, we review the many challenges associated with reproductive counseling in women with CKD.

How Low Do We Go (in the Post-SPRINT Era)?

Hypertension is frequently both a cause and complication of CKD. The optimal blood pressure target in CKD has been of hot debate over the decades with little data to inform the goals. Here, we review the data from the Systolic Blood Pressure Intervention Trial (SPRINT), Modification of Diet in Renal Disease (MDRD), African American Study of Kidney Disease and Hypertension (AASK), Ramipril Efficacy in Nephropathy-2 (REIN-2), and Action to Control Cardiovascular Risk in Diabetes (ACCORD) trials to use the available evidence to better inform what blood pressure goal should be recommended in patients with CKD and to answer the question "How low should we go?".

Bridging the gap for future clinician-educators.

BACKGROUND: In contrast to the training required in the UK, opportunities for medical education training in the USA are limited. Resident-as-teacher programmes are typically insufficient to prepare trainees to be successful clinician-educators, but few pursue formal education degrees. We sought to assess the need for, and feasibility of, a training pathway for subspecialty fellows in a large Department of Medicine that would prepare our trainees to become effective educators. METHODS: Quantitative and qualitative methods were used. Previous fellowship applicants and current programme directors were surveyed to determine the potential benefits of the programme. A pilot programme was conducted with fellows interested in education to determine the feasibility of the programme. Pilot participants were interviewed regarding the benefits that they gained from the pilot and the logistical challenges that they experienced. In contrast to the training required in the UK, opportunities for medical education training in the USA are limited RESULTS: Five highly ranked fellows would have scored our programmes higher if we offered this training pathway. Pilot participants and fellowship programme directors agreed that there is a compelling need for such a training pathway. A number of themes arose from the interviews that enabled us to build the framework for a strong programme. DISCUSSION: Our findings suggest that a clinician-educator training pathway that draws from multiple subspecialties has the potential to improve recruitment, provide needed career counselling and skills development to trainees, and to build a community of educators that will benefit the institution. Important insights from pilot participant interviews will inform the programme design, in order to keep trainees engaged and overcome logistical challenges.

The association between insulin resistance and atrial fibrillation: A cross-sectional analysis from SPRINT (Systolic Blood Pressure Intervention Trial).

It is unclear whether metabolic syndrome (MetS) is associated with atrial fibrillation (AF) in an older population with greater cardiovascular risk, including those with chronic kidney disease. The authors investigated the association between MetS and AF in participants in SPRINT (Systolic Blood Pressure Intervention Trial). MetS was defined based on the Modified Third National Cholesterol Education Program. The baseline prevalence rate for MetS was 55%, while 8.2% of the participants had AF. In multivariate regression analyses, AF was not associated with presence of MetS in either chronic kidney disease or non-chronic kidney disease subgroups. Age, race, history of cardiovascular diseases, decreased triglycerides, decreased pulse pressure, and albuminuria remained significantly associated with AF risk. In contrast to the general population, MetS was not associated with AF in the older population with increased cardiovascular risk studied in SPRINT.

Discharging Mrs. Fox: A Team-Based Interprofessional Collaborative Standardized Patient Encounter.

INTRODUCTION: In 2003, the Institute of Medicine recommended that interprofessional education be incorporated into the training programs of health care professionals. However, many logistical challenges hinder formal interprofessional learning in health care profession programs. METHODS: This resource is a 3-hour interprofessional small-group session designed for health professions student teams to engage in a standardized patient encounter, each team member contributing a profession-specific perspective to create a collaborative care plan across five discharge decisions. The activity includes a simulated standardized patient encounter and debrief session wherein students discuss the role of bias and communication and create a collaborative care plan. RESULTS: Following the activity, participants were surveyed about the value of the educational experience. Over 12 months, 106 students (81 medicine, nine nursing, 16 pharmacy) participated in the interprofessional activity. Eighty-four students responded to the postevent survey (79% response rate). Students were confident that the experience helped them integrate profession-specific knowledge, create a shared care plan, and understand how interprofessional collaboration contributes to quality care. The debriefing session and interprofessional interaction were an integral component of the experience. DISCUSSION: This resource is a feasible interprofessional small-group activity that has been implemented without excessive faculty time or institutional resources. It is adaptable to institutional needs, local resources, level of trainee, and professions. The session provides interprofessional students the opportunity to engage with one another and with the patient in a collaborative decision-making activity focused around a critical transition of care.