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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

Background The factors associated with estimated glomerular filtrate rate (eGFR) decline in low risk adults remain relatively unknown. We hypothesized that a polygenic risk score (PRS) will be associated with eGFR decline. Methods We analyzed genetic data from 1,601 adult participants with European ancestry in the World Trade Center Health Program (baseline age 49.68 ± 8.79 years, 93% male, 23% hypertensive, 7% diabetic and 1% with cardiovascular disease) with ≥ three serial measures of serum creatinine. PRSs were calculated from an aggregation of single nucleotide polymorphisms (SNPs) from a recent, large-scale genome-wide association study (GWAS) of rapid eGFR decline. Generalized linear models were used to evaluate the association of PRS with renal outcomes: baseline eGFR and CKD stage, rate of change in eGFR, stable versus declining eGFR over a 3–5-year observation period. eGFR decline was defined in separate analyses as “clinical” (> -1.0 ml/min/1.73 m2/year) or “empirical” (lower most quartile of eGFR slopes). Results The mean baseline eGFR was ~ 86 ml/min/1.73 m2. Subjects with decline in eGFR were more likely to be diabetic. PRS was significantly associated with lower baseline eGFR (B = -0.96, p = 0.002), higher CKD stage (OR = 1.17, p = 0.010), decline in eGFR (OR = 1.14, p = 0.036) relative to stable eGFR, and the lower quartile of eGFR slopes (OR = 1.21, p = 0.008), after adjusting for established risk factors for CKD. Conclusion Common genetic variants are associated with eGFR decline in middle-aged adults with relatively low comorbidity burdens.

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.

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.

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.

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. .

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 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. .

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.

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.