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Comorbid type 2 diabetes mellitus (T2D) and chronic kidney disease (CKD) is associated with poor health outcomes and a high economic burden. Management of these conditions remains a significant challenge for current healthcare systems. The objective of this article is to describe the experiences of patients living with T2D and CKD and their thoughts on how communication between patients and their clinicians could be improved despite the multiple comorbidities that need to be addressed. We present the individual perspectives of three patient authors, followed by relevant discussion around the management of CKD in patients with T2D by clinician authors.Audio abstract available for this article. Audio Abstract. In this audio introduction, the authors Patrick Gee (a patient author) and Eugene Wright (a clinician author) provide a brief overview and discuss the key findings of their article titled "Living with Chronic Kidney Disease and Type 2 Diabetes Mellitus: The Patient and Clinician Perspective".People living with type 2 diabetes mellitus (T2D for short) and chronic kidney disease (CKD for short) may have worse health over time. Managing long-term health conditions can be expensive for those living with the conditions and for healthcare systems. To optimize their quality of life, people with T2D and CKD need the necessary resources to better manage their conditions. Healthcare professionals desire the best outcomes for their patients. Currently, communication between healthcare professionals and their patients is suboptimal, and ineffective communication creates a barrier to effective optimal care. The aim of this article is to describe the experiences of three people living with T2D and CKD (patients), who are also authors of the article. They outline their thoughts on how communication between patients and healthcare professionals might be improved when managing multiple conditions. We also present responses from three healthcare professionals (clinicians), who are co-authors of this article, to the points made by the patients, as well as their views on how to manage these long-term conditions.

AimsContemporary patterns of care of patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D) and the adoption of finerenone are not known. The FINE-REAL study (NCT05348733) is a prospective observational study in patients with CKD and T2D to provide insights into the use of the nonsteroidal mineralocorticoid receptor antagonist (MRA) finerenone in clinical practice.MethodsFINE-REAL is an international, prospective, multicenter, single-arm study enrolling approximately 5500 adults with CKD and T2D in an estimated 200 sites across 22 countries. The study is anticipated to be ongoing until 2027.ResultsThe primary objective is to describe treatment patterns in patients with CKD and T2D treated with finerenone in routine clinical practice. Secondary objectives include assessment of safety with finerenone. Other endpoints include characterization of healthcare resource utilization and occurrence of newly diagnosed diabetic retinopathy or its progression from baseline in patients with existing disease. A biobank is being organized for future explorative analyses with inclusion of participants from the United States.ConclusionsFINE-REAL is the first prospective observational study with a nonsteroidal MRA in a population with CKD and T2D and is expected to provide meaningful insights into the treatment of CKD associated with T2D. FINE-REAL will inform decision-making with respect to initiation of finerenone in patients with CKD and T2D.

Epithelial-to-mesenchymal transition (EMT) is an important developmental process, participates in tissue repair, and occurs during pathologic processes of tumor invasiveness, metastasis, and tissue fibrosis. The molecular mechanisms leading to EMT are poorly understood. Although it is well documented that transforming growth factor (TGF)-β plays a central role in the induction of EMT, the targets of TGF-β signaling are poorly defined. We have shown earlier that Na,K-ATPase β1-subunit levels are highly reduced in poorly differentiated kidney carcinoma cells in culture and in patients' tumor samples. In this study, we provide evidence that Na,K-ATPase is a new target of TGF-β1–mediated EMT in renal epithelial cells, a model system used in studies of both cancer progression and fibrosis. We show that following treatment with TGF-β1, the surface expression of the β1-subunit of Na,K-ATPase is reduced, before well-characterized EMT markers, and is associated with the acquisition of a mesenchymal phenotype. RNAi-mediated knockdown confirmed the specific involvement of the Na,K-ATPase β1-subunit in the loss of the epithelial phenotype and exogenous overexpression of the Na,K-ATPase β1-subunit attenuated TGF-β1–mediated EMT. We further show that both Na,K-ATPase α- and β-subunit levels are highly reduced in renal fibrotic tissues. These findings reveal for the first time that Na,K-ATPase is a target of TGF-β1–mediated EMT and is associated with the progression of EMT in cancer and fibrosis. Mol Cancer Ther; 9(6); 1515–24. ©2010 AACR.

Supplementary Data from Na,K-ATPase Subunits as Markers for Epithelial-Mesenchymal Transition in Cancer and Fibrosis

BackgroundPatients with early chronic kidney disease (CKD) or underlying risk factors are often unaware of their kidney test results, common causes of CKD, and ways to lower risk of disease onset/progression.ObjectiveTo test feasibility of a pharmacist-led intervention targeting patient education and risk factors in patients with early CKD and those at risk for CKD.Practice descriptionAmbulatory care pharmacists in community-based primary care clinics delivered kidney health education, ordered labs, and recommended medication adjustments.Practice innovationWe identified patients with a moderate rate of decline (≥2 mL/min/1.73 m2 per year) in estimated glomerular filtration (eGFR) at-risk for CKD or early stage CKD. An interactive workbook was designed to teach patients about kidney test results and self-management of risk factors including hypertension, type 2 diabetes, cigarette smoking, and chronic oral nonsteroidal anti-inflammatory drug use.Evaluation methodsOutcomes included visit uptake, completion of annual albuminuria screening, and initiation of guideline-directed medications for CKD. Patients were surveyed pre- and post-intervention for kidney health knowledge and perceptions regarding pharmacist-provided information.ResultsOur sample of 20 participants had a mean eGFR of 59 mL/min/1.73 m2 and the meaneGFR decline was-4.6 mL/min/1.73 m2 per year. There were 47 visits during the pilot period from February 2021 to October 2021. Thirteen patients were missing albuminuria screening within 12 months; 2 of 9 patients with resulting labs had new microalbuminuria and were started on renoprotective medications. Patients had improved understanding of their kidney function test results and most did not consider the information scary or confusing.ConclusionBarriers to enrollment included fewer participants with multiple risk factors for CKD. The pharmacists were able to engage patients in learning the importance of monitoring and self-management of kidney health. A collaborative practice agreement may enhance a similar intervention that includes initiation of renoprotective medications.

Chronic low-grade inflammation, now coined by the new paradigm as "metaflammation" or "metainflammation", has been linked to chronic kidney disease and its progression. In diabetes, altered metabolism denotes factors associated with the metabolic syndrome and hyperglycemia, among others. The interplay among hyperglycemia, oxidative stress, and inflammation in the pathogenesis of diabetic kidney disease (DKD) has been broadly explored. Identification of mediators of inflammatory processes involving macrophage infiltration, production of inflammasomes, release of cytokines, and activation of pertinent signaling pathways including mitogen-activated protein kinase, Jun N-terminal kinase, Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway (JAK/STAT), and apoptosis signal-regulating kinase 1 signaling mechanisms have enabled the development of therapeutic agents for DKD. This review describes the evidence supporting the contribution of the inflammatory response and fibrotic changes and focuses on selected, novel, promising drugs as well as repurposed drugs that have made it to phase 2, 3, or 4 of clinical trials in adults with type 2 diabetes mellitus and their potential to become an important part of our armamentarium to improve the management of DKD. Importantly, drugs that solely target inflammatory processes may be insufficient to fully optimize care of patients with DKD because of the complex nature of the disease.

In a retrospective analysis of over 62,000 Black and non-Black participants from eight United States cohorts, Gutiérrez etal.1 examined estimated glomerular filtration rate (eGFR) equations to assess racial differences in kidney failure requiring replacement therapy and in mortality across different equations.

Background: The metabolic syndrome (MetS) is associated with elevated urinary albumin (UA) excretion and C-reactive protein (CRP). However, potential differences in CRP levels on the association between individual components of the MetS and microalbuminuria (MA; 30–300 μg/mL) and/or UA (0–300 μg/mL) by race/ethnicity is unknown. Methods: We analyzed National Health and Nutrition Examination Surveys (NHANES) data, (1999–2010) for adults (≥20 years of age) with the MetS (N = 5700). The Sobel–Goodman mediation test examined the influence of CRP on the association between individual MetS components and both MA and UA by race/ethnicity. We applied machine learning models to predict UA. Results: CRP mediated the association between waist circumference (WC) and MA in Whites and Hispanics but not in Blacks. However, in general, the proportion of the total effect of MetS components on UA, mediated by CRP, was: 11% for high-density lipoprotein cholesterol (HDL-C) and 40% for WC (P

Background: 25-hydroxy vitamin D (Vit D)-deficiency is common among patients with chronic kidney disease (CKD) and contributes to cardiovascular disease (CVD). African Americans (AAs) suffer disproportionately from CKD and CVD, and 80% of AAs are Vit D-deficient. The impact of Vit D repletion on cardio-renal biomarkers in AAs is unknown. We examined Vit D repletion on full-length osteopontin (flOPN), c-terminal fibroblast growth factor-23 (FGF-23), and plasminogen activator inhibitor-1 (PAI-1), which are implicated in vascular and kidney pathology. Methods: We performed a randomized, placebo-controlled study of high-risk AAs with Vit D deficiency, treated with 100,000 IU Vit D3 (cholecalciferol; n = 65) or placebo (n = 65) every 4 weeks for 12 weeks. We measured kidney function (CKD-EPI eGFR), protein-to-creatinine ratio, vascular function (pulse wave velocity; PWV), augmentation index, waist circumference, sitting, and 24-h-ambulatory blood pressure (BP), intact parathyroid hormone (iPTH) and serum calcium at baseline and study end, and compared Vit D levels with laboratory variables. We quantified plasma FGF-23, PAI-1, and flOPN by enzyme-linked immunosorbent assay. Multiple regression analyzed the relationship between log flOPN, FGF-23, and PAI-1 with vascular and renal risk factors. Results: Compared to placebo, Vit D3 repletion increased Vit D3 2-fold (p < 0.0001), decreased iPTH by 12% (p < 0.01) and was significantly correlated with PWV (p < 0.009). Log flOPN decreased (p = 0.03), log FGF-23 increased (p = 0.04), but log PAI-1 did not change. Multiple regression indicated association between log flOPN and PWV (p = 0.04) and diastolic BP (p = 0.02), while log FGF-23 was associated with diastolic BP (p = 0.05), and a trend with eGFR (p = 0.06). Conclusion: Vit D3 repletion may reduce flOPN and improve vascular function in high risk AAs with Vit D deficiency.

Diabetes and hypertension are the most common causes of chronic kidney disease (CKD) in the general population as well as in the Black and African American population, who also suffer from high rates of CKD and CKD progression compared to the White population. Progression of CKD can lead to kidney failure, and patients with progressive kidney disease have a high risk of premature mortality, particularly from cardiovascular disease. Screening for early detection of CKD is important as it facilitates the initiation of medications that have been shown to delay the progression of diabetes-related as well as non-diabetes-related CKD, and reduce rates of death from both kidney and cardiovascular disease. The potential adverse effects from use of some of the newer reno- and cardio-protective glucose-lowering medications, such as the sodium glucose cotransporter-2 inhibitors, may be effectively avoided with detailed patient education and monitoring by the healthcare provider. It is important to note that lifestyle modification including regular exercise, diet, and smoking cessation are first-line in the management of diabetes and hypertension. When CKD occurs, co-management by providers using a comprehensive strategy may avert early complications and facilitate appropriate early referral for nephrology specialty care.

Religion and related institutions have resources to help individuals cope with chronic conditions, such as chronic kidney disease (CKD). The purpose of this investigation is to examine the association between religious service attendance and mortality for adults with CKD. Data were drawn from NHANES III linked to the 2015 public use Mortality File to analyze a sample of adults (n = 3558) who had CKD as defined by a single value of estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and/or albumin-to-creatinine ratio ≥17 mg/g for males or ≥25 for females. All-cause mortality was the primary outcome and religious service attendance was the primary independent variable. Cox proportional hazards models were estimated to determine the association between religious service attendance and mortality. The mortality risks for participants who attended a service at least once per week were 21% lower than their peers with CKD who did not attend a religious service at all (HR 0.79; CI 0.64–0.98). The association between religious service attendance and mortality in adults with CKD suggest that prospective studies are needed to examine the influence of faith-related behaviors on clinical outcomes in patients with CKD.

Chronic kidney disease due to diabetes, or diabetic kidney disease (DKD), is a worldwide leading cause of chronic kidney disease and kidney failure and an increasingly important global public health issue. It is associated with poor quality of life, high burden of chronic diseases, and increased risk of premature death. Until recently, people with DKD had limited therapeutic options. Treatments have focused largely on glycemic and blood pressure control and renin-angiotensin system blockade, leaving patients with significant residual risk for progression of DKD. The availability of newer classes of glucose-lowering agents, namely, sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists, has changed the therapeutic landscape for these patients. These therapies have offered unprecedented opportunities to reduce the risk for progression of kidney disease and the risk of death that have led to recent updates to clinical guidelines. As such, the American Diabetes Association, the Kidney Disease: Improving Global Outcomes, and the European Association for the Study of Diabetes now recommend the use of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists for patients with DKD to provide both kidney and cardiovascular protective benefits. This review highlights the importance of early detection of DKD and summarizes the latest recommendations in the clinical guidelines on management of patients with DKD with hope of facilitating their uptake into everyday clinical practice. An integrated approach to patient care with a multidisciplinary focus can help achieve the necessary shift in clinical care of patients with DKD.

Hispanic/Latinos have been underrepresented in genome-wide association studies (GWAS) for anthropometric traits despite their notable anthropometric variability, ancestry proportions, and high burden of growth stunting and overweight/obesity. To address this knowledge gap, we analyzed densely imputed genetic data in a sample of Hispanic/Latino adults to identify and fine-map genetic variants associated with body mass index (BMI), height, and BMI-adjusted waist-to-hip ratio (WHRadjBMI). We conducted a GWAS of 18 studies/consortia as part of the Hispanic/Latino Anthropometry (HISLA) Consortium (stage 1, n = 59,771) and generalized our findings in 9 additional studies (stage 2, n = 10,538). We conducted a trans-ancestral GWAS with summary statistics from HISLA stage 1 and existing consortia of European and African ancestries. In our HISLA stage 1 + 2 analyses, we discovered one BMI locus, as well as two BMI signals and another height signal each within established anthropometric loci. In our trans-ancestral meta-analysis, we discovered three BMI loci, one height locus, and one WHRadjBMI locus. We also identified 3 secondary signals for BMI, 28 for height, and 2 for WHRadjBMI in established loci. We show that 336 known BMI, 1,177 known height, and 143 known WHRadjBMI (combined) SNPs demonstrated suggestive transferability (nominal significance and effect estimate directional consistency) in Hispanic/Latino adults. Of these, 36 BMI, 124 height, and 11 WHRadjBMI SNPs were significant after trait-specific Bonferroni correction. Trans-ancestral meta-analysis of the three ancestries showed a small-to-moderate impact of uncorrected population stratification on the resulting effect size estimates. Our findings demonstrate that future studies may also benefit from leveraging diverse ancestries and differences in linkage disequilibrium patterns to discover novel loci and additional signals with less residual population stratification.

Background: Podocyte foot process effacement is a key histologic finding in proteinuric kidney disease. We previously showed that 3-week old CD2AP-deficient mice have significant proteinuria, glomerular hypertrophy and mesangial expansion. The goal of this study is to use morphometry to establish the temporal sequence of podocyte foot process effacement, glomerular volume expansion and albuminuria in Cd2ap−/− mice by measuring these parameters at the 2-week time point.Methods: Wild-type mice age 14 ± 1 days with the Cd2ap gene (WT, N = 5) and mice deficient for Cd2ap (Cd2ap KO, N = 5) were generated. Kidneys were harvested and fixed in 2.5% glutaraldehyde and processed for examination by light and electron microscopy. An average of 415.2 (range 268–716) grid points were counted for all the glomeruli, and quantification of glomerular volume from each kidney. Urine was collected the day prior to sacrifice for urine albumin-to-creatinine ratio (ACR) measurements.Results: There was no difference in albuminuria [median (range) mg/g] between WT [212.2 (177.6–388.4) mg/g] vs. Cd2ap KO mice [203.3 (164.7–910.2) mg/g], P = 0.89; or glomerular volume 68,307[10,931] vs. 66,844[13,022] μm3, p = 0.92. The volume densities of glomerular components of the podocyte, capillary lumen and mesangium were not different for the two groups, P = 0.14, 0.14 and 0.17 respectively. However, foot process width was increased in Cd2ap KO 1128[286] vs. WT [374 ± 42] nm, P = 0.02.Conclusion: Here we show that while 2-week old WT and Cd2ap KO mice have similar levels of albuminuria, glomerular and mesangial volume, Cd2ap KO mice have more extensive podocyte foot process effacement. The data suggests that podocyte injury is the initiating event leading to mesangial expansion and albuminuria in this model.

Hispanic/Latinos have been underrepresented in genome-wide association studies (GWAS) for anthropometric traits despite notable anthropometric variability with ancestry proportions, and a high burden of growth stunting and overweight/obesity in Hispanic/Latino populations. This address this knowledge gap, we analyzed densely-imputed genetic data in a sample of Hispanic/Latino adults, to identify and fine-map common genetic variants associated with body mass index (BMI), height, and BMI-adjusted waist-to-hip ratio (WHRadjBMI). We conducted a GWAS of 18 studies/consortia as part of the Hispanic/Latino Anthropometry (HISLA) Consortium (Stage 1, n=59,769) and validated our findings in 9 additional studies (HISLA Stage 2, n=9,336). We conducted a trans-ethnic GWAS with summary statistics from HISLA Stage 1 and existing consortia of European and African ancestries. In our HISLA Stage 1+2 analyses, we discovered one novel BMI locus, as well two novel BMI signals and another novel height signal, each within established anthropometric loci. In our trans-ethnic meta- analysis, we identified three additional novel BMI loci, one novel height locus, and one novel WHRadjBMI locus. We also identified three secondary signals for BMI, 28 for height, and two for WHRadjBMI. We replicated >60 established anthropometric loci in Hispanic/Latino populations at genome-wide significance—representing up to 30% of previously-reported index SNP anthropometric associations. Trans-ethnic meta-analysis of the three ancestries showed a small-to-moderate impact of uncorrected population stratification on the resulting effect size estimates. Our novel findings demonstrate that future studies may also benefit from leveraging differences in linkage disequilibrium patterns to discover novel loci and additional signals with less residual population stratification.

Patients with chronic kidney disease (CKD) have elevated circulating levels of trimethylamine N-oxide (TMAO), a metabolite derived from gut microbes and associated with cardiovascular diseases. High circulating levels of TMAO and its dietary precursor, choline, predict increased risk for development of CKD in apparently healthy subjects, and studies in mice fed TMAO or choline suggest that TMAO can contribute to kidney impairment and renal fibrosis. Here we examined the interactions between TMAO, kidney disease, and cardiovascular disease in mouse models. We observed that while female hyperlipidemic apoE KO mice fed a 0.2% adenine diet for 14 weeks developed CKD with elevated plasma levels of TMAO, provision of a non-lethal inhibitor of gut microbial trimethylamine (TMA) production, iodomethylcholine (IMC), significantly reduced multiple markers of renal injury (plasma creatinine, cystatin C, FGF23, and TMAO), reduced histopathologic evidence of fibrosis, and markedly attenuated development of microalbuminuria. In addition, while the adenine-induced CKD model significantly increased heart weight, a surrogate marker for myocardial hypertrophy, this was largely prevented by IMC supplementation. Surprisingly, adenine feeding did not increase atherosclerosis and significantly decreased the expression of inflammatory genes in the aorta compared to the control groups, effects unrelated to TMAO levels. Our data demonstrate that inhibition of TMAO production attenuated CKD development and cardiac hypertrophy in mice, suggesting that TMAO reduction may be a novel strategy in treating CKD and its cardiovascular disease complications.

Longitudinal data are critical to inform prediction of transition to type 2 diabetes mellitus (T2DM) from prediabetes. This study aimed to ascertain T2DM incidence and risk factors, including chronic kidney disease (CKD), in patients with prediabetes. The CURE-CKD registry of electronic health record data includes >2.6 million patients with and at-risk for CKD (T2DM, hypertension, prediabetes). Adults with prediabetes were identified by established criteria for % A1C, random and fasting glycemia, and administrative codes. T2DM was defined by corresponding established criteria. CKD was defined by estimated glomerular filtration rate 30 mg/g based upon 2 or more measurements >90 days apart, and administrative codes. Cox proportional hazards regression was used to predict T2DM. From 2006 to 2017, there were 678,493 patients with prediabetes and baseline A1C 5.9±0.3% (mean±SD). Incident T2DM occurred in 185,770 (27%) at a mean of 3.6 years. At baseline, 134,240 (20%) had CKD. Adjusted for age, gender, race/ethnicity, and hypertension, hazard ratios for T2DM were greater in patients with CKD (1.44, 95%CI [1.42, 1.47]) and with increases in 1% A1C (4.59 95%CI [4.47, 4.72]). CKD was common in prediabetes and, along with higher A1C, demonstrated the greatest hazards for incident T2DM. Presence of CKD identifies patients with prediabetes who are high-risk for transition to T2DM. Disclosure K.A. Hennessey: None. R.Z. Alicic: None. K.B. Daratha: None. C. Jones: None. J.J. Neumiller: None. O. Duru: None. S. Nicholas: Speaker’s Bureau; Self; Janssen Pharmaceuticals, Inc. Other Relationship; Self; Centers for Disease Control and Prevention, George Institute for Global Health, Goldfinch Bio, Inc., National Institutes of Health. S.M. McPherson: None. K.C. Norris: None. K.R. Tuttle: Consultant; Self; AstraZeneca, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Gilead Sciences, Inc., Goldfinch Bio, Novo Nordisk Inc.

The magnitude of risk for chronic kidney disease (CKD) in prediabetes is unclear. The study aim was to determine CKD incidence and risk factors in patients with prediabetes from the CURE-CKD registry of electronic health record data from >2.6 million patients with or at-risk for CKD. Adults with prediabetes were identified by established criteria for %A1C, random and fasting blood glycemia, and administrative codes. CKD was defined by estimated glomerular filtration rate (eGFR) 30 mg/g based upon two or more measurements >90 days apart and administrative codes. Cox proportional hazards regression was used to predict incident CKD. From 2006 to 2017, there were 544,253 patients with prediabetes and no CKD. Baseline A1C was 5.9±0.3% (mean±SD) and eGFR was 90.7±16.8 mL/min/1.73 m2. Notable medication use was: NSAIDs n=110,964 (20%), PPIs n=49,916 (9%), and ACEi/ARB n=63,738 (12%). Incident CKD occurred (n=59,583) at a rate of 25.2/1,000 person-years with mean time to CKD of 2.9 years. Older age, female gender, Hispanic/Latinx, Black, Native Hawaiian and Other Pacific Islander race/ethnicity, lower eGFR, PPI and ACEi/ARB use were associated with higher hazards of CKD in prediabetes (Table 1). Incident CKD is common in prediabetes with risk factors similar to those in diabetes. CKD screening and detection with a focus on kidney protection may offer novel opportunities to reduce CKD risk in prediabetes. Disclosure K.A. Hennessey: None. K.B. Daratha: None. R.Z. Alicic: None. C. Jones: None. J.J. Neumiller: None. O. Duru: None. S. Nicholas: Speaker’s Bureau; Self; Janssen Pharmaceuticals, Inc. Other Relationship; Self; Centers for Disease Control and Prevention, George Institute for Global Health, Goldfinch Bio, Inc., National Institutes of Health. S.M. McPherson: None. K.C. Norris: None. K.R. Tuttle: Consultant; Self; AstraZeneca, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Gilead Sciences, Inc., Goldfinch Bio, Novo Nordisk Inc.

Background and Aims Glomerular filtrate rate (GFR) is a key index of kidney function, and directly measured GFR (mGFR) is the gold standard, but it is invasive and costly. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations have been widely used to estimate GFR with high accuracy. However, the comparative accuracy of estimated GFR (eGFR) using creatinine and cystatin C in CKD-EPI equations remains unclear. This study aimed to systematically assess the bias and accuracy of eGFR using equations of CKD-EPIcrea, CKD-EPIcys, and CKD-EPIcrea/cys in adult populations relevant to primary health care. Method Pubmed, Web of Science, EMBASE, and the Cochrane Library were searched from inception until December 2019 for studies comparing mGFR with simultaneous eGFR using CKD-EPI calculated from standardized serum creatinine and cystatin C. We pooled data on bias (difference between mGFR and eGFR), accuracy (P30; proportion of eGFR within 30% of mGFR), and correlation coefficient (R; between mGFR and eGFR), using random-effects models. Results A total of 35 studies with 23,667 participants, which reported the data on the bias, and/or P30, and/or R were included (Figure 1). The difference in the bias of eGFR using CKD-EPIcys was 4.84 mL/min/1.73 m2 (95% CI, 1.88∼7.80) lower than using CKD-EPIcrea, and 1.50 mL/min/1.73 m2 (95% CI, 0.05∼2.95) lower than using CKD-EPIcrea/cys. These gaps increased in subgroups of low mGFR ( Conclusion CKD-EPIcrea/cys and CKD-EPIcys equations gave less bias and more accurate estimates of mGFR than CKD-EPIcrea equation. Our findings validated and strengthened the use of cystatin C alone or in combination with creatinine in CKD-EPI equations. More variables and coefficients could be added in CKD-EPI equations to achieve less bias and more accuracy in future research.

Background: The directly measured glomerular filtrate rate (mGFR) is the gold standard for kidney function, but it is invasive and costly. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations have been widely used to estimate GFR, however, the comparative accuracy of estimated GFR (eGFR) using creatinine and cystatin C in CKD-EPI equations remains unclear. We performed this meta-analysis to assess the bias and accuracy of eGFR using equations of CKD-EPIcrea, CKD-EPIcys, and CKD-EPIcrea/cys in adult populations relevant to primary health care. Methods: Pubmed, Web of Science, EMBASE, and the Cochrane Library were searched from inception until December 2019 for related studies. Results: A total of 35 studies with 23,667 participants, which reported the data on the bias, and/or P30, and/or R were included. The difference in the bias of eGFR using CKD-EPIcys was 4.84 mL/min/1.73 m2 (95% CI, 1.88~7.80) lower than using CKD-EPIcrea, and 1.50 mL/min/1.73 m2 (95% CI, 0.05~2.95) lower than using CKD-EPIcrea/cys. These gaps increased in subgroups of low mGFR ( Conclusions: CKD-EPIcrea/cys and CKD-EPIcys gave less bias and more accurate estimates of mGFR than CKD-EPIcrea. More variables and coefficients could be added in CKD-EPI equations to achieve less bias and more accuracy in future research.

End-stage renal disease (ESRD) is one of the starkest examples of racial/ethnic disparities in health. Racial/ethnic minorities are 1.5 to nearly 4 times more likely than their non-Hispanic White counterparts to require renal replacement therapy (RRT), with African Americans suffering from the highest rates of ESRD. Despite improvements over the last 25 years, substantial racial differences are persistent in dialysis quality measures such as RRT modality options, dialysis adequacy, anemia, mineral and bone disease, vascular access, and pre-ESRD care. This report will outline the current status of racial disparities in key ESRD quality measures and explore the impact of race. While the term race represents a social construct, its association with health is more complex. Multiple individual and community level social determinants of health are defined by the social positioning of race in the U.S., while biologic differences may reflect distinct epigenetic changes and linkages to ancestral geographic origins. Together, these factors conspire to influence dialysis outcomes among African Americans with ESRD.

Author(s): Harding, Kimberly; Mersha, Tesfaye B; Pham, Phuong-Thu; Waterman, Amy D; Webb, Fern A; Vassalotti, Joseph A; Nicholas, Susanne B | Abstract: BackgroundThe persistent challenges of bridging healthcare disparities for African Americans (AAs) in need of kidney transplantation continue to be unresolved at the national level. This healthcare disparity is multifactorial: stemming from limited kidney donors suitable for AAs; inconsistent care coordination and suboptimal risk factor control; social determinants, low socioeconomic status, reduced access to care; and mistrust of clinicians and the healthcare system.SummaryThere are numerous opportunities to significantly lessen the disparities in kidney transplantation for AAs through the following measures: the adoption of new care and patient engagement models that include education, enhanced practice-level cultural sensitivity, and timely referral as well as increased research on the impact of the environment on genetic risk, and implementation of new transplantation-related policies. Key Messages: This systematic review describes pretransplant concerns related to access to kidney transplantation, posttransplant complications, and policy interventions to address the challenging issues associated with kidney transplantation in AAs.

Key Points Question What are the clinical characteristics of and major risk factors for chronic kidney disease among patients in 2 large US health care systems? Findings In this cohort study of the Center for Kidney Research, Education, and Hope (CURE-CKD) registry, more than 2.6 million adults and children had chronic kidney disease or were at risk. Albuminuria or proteinuria was tested in approximately one-eighth of adults with chronic kidney disease, renin-angiotensin system inhibitors were prescribed to one-fifth, and nonsteroidal anti-inflammatory agents or proton pump inhibitors were prescribed to more than one-third. Meaning Despite common occurrence of chronic kidney disease, rates of identification and use of kidney protective agents were low, while use of potential nephrotoxins was widespread., This cohort study examines the clinical features of, prevalence of, major risk factors for, and care for chronic kidney disease among adults and children treated in 2 large US health care systems., Importance Chronic kidney disease (CKD) is serious and common, yet recognition and public health responses are limited. Objective To describe clinical features of, prevalence of, major risk factors for, and care for CKD among patients treated in 2 large US health care systems. Design, Setting, and Participants This cohort study collected data from the Center for Kidney Disease Research, Education, and Hope (CURE-CKD) registry, an electronic health record–based registry jointly curated and sponsored by Providence St Joseph Health and the University of California, Los Angeles. Patients were adults and children with CKD (excluding end-stage kidney disease) and adults at risk of CKD (ie, with diabetes, hypertension, or prediabetes) identified by laboratory values, vital signs, prescriptions, and administrative codes. Data were collected from January 2006 through December 2017, with analyses performed from March 2019 through November 2019. Exposures Diabetes, hypertension, and prediabetes. Main Outcomes and Measures Clinical and demographic characteristics, prevalence, and prescribed medications. Results Of 2 625 963 adults and children in the sample, 606 064 adults (23.1%) with CKD had a median (interquartile range [IQR]) age of 70 (59-81) years, with 338 785 women (55.9%) and 434 474 non-Latino white individuals (71.7%). A total of 12 591 children (0.4%) with CKD had a median (IQR) age of 6 (1-13) years, with 7079 girls (56.2%) and 6653 non-Latino white children (52.8%). Median (IQR) estimated glomerular filtration rate was 53 (41-61) mL/min/1.73 m2 among adults and 70 (50-95) mL/min/1.73 m2 in children. Prevalence rates for CKD in adults were 4.8% overall (606 064 of 12 669 700) with 1.6% (93 644 of 6 011 129) during 2006 to 2009, 5.7% (393 455 of 6 903 084) during 2010 to 2013, and 8.4% (683 574 of 8 179 860) during 2014 to 2017 (P

Background Chronic kidney disease (CKD) is a global public health problem, exhibiting sharp increases in incidence, prevalence, and attributable morbidity and mortality. There is a critical need to better understand the demographics, clinical characteristics, and key risk factors for CKD; and to develop platforms for testing novel interventions to improve modifiable risk factors, particularly for the CKD patients with a rapid decline in kidney function. Methods We describe a novel collaboration between two large healthcare systems (Providence St. Joseph Health and University of California, Los Angeles Health) supported by leadership from both institutions, which was created to develop harmonized cohorts of patients with CKD or those at increased risk for CKD (hypertension/HTN, diabetes/DM, pre-diabetes) from electronic health record data. Results The combined repository of candidate records included more than 3.3 million patients with at least a single qualifying measure for CKD and/or at-risk for CKD. The CURE-CKD registry includes over 2.6 million patients with and/or at-risk for CKD identified by stricter guide-line based criteria using a combination of administrative encounter codes, physical examinations, laboratory values and medication use. Notably, data based on race/ethnicity and geography in part, will enable robust analyses to study traditionally disadvantaged or marginalized patients not typically included in clinical trials. Discussion CURE-CKD project is a unique multidisciplinary collaboration between nephrologists, endocrinologists, primary care physicians with health services research skills, health economists, and those with expertise in statistics, bio-informatics and machine learning. The CURE-CKD registry uses curated observations from real-world settings across two large healthcare systems and has great potential to provide important contributions for healthcare and for improving clinical outcomes in patients with and at-risk for CKD.

PURPOSE OF REVIEW: We summarize the evidence for and against a target systolic blood pressure (SBP)

Author(s): Tuttle, Katherine; Alicic, Radica Z; Duru, O Kenrik; Jones, Cami R; Daratha, Kenn B; Nicholas, Susanne B; McPherson, Sterling M; Neumiller, Joshua J; Bell, Douglas S; Mangione, Carol M; Norris, Keith C

© 2016 by the American Society of Nephrology.FSGS is the most common primary glomerular disease underlying ESRD in the United States and is increasing in incidence globally. FSGS results from podocyte injury, yet the mechanistic details of disease pathogenesis remain unclear. This has resulted in an unmet clinical need for cell-specific therapy in the treatment of FSGS and other proteinuric kidney diseases.We previously identified Yes-associated protein (YAP) as a prosurvival signaling molecule, the in vitro silencing of which increases podocyte susceptibility to apoptotic stimulus. YAP is a potent oncogene that is a prominent target for chemotherapeutic drug development. In this study, we tested the hypothesis that podocyte-specific deletion of Yap leads to proteinuric kidney disease through increased podocyte apoptosis. Yap was selectively silenced in podocytes using Cre-mediated recombination controlled by the podocin promoter. Yap silencing in podocytes resulted in podocyte apoptosis, podocyte depletion, proteinuria, and an increase in serum creatinine. Histologically, features characteristic of FSGS, including mesangial sclerosis, podocyte foot process effacement, tubular atrophy, interstitial fibrosis, and casts, were observed. In human primary FSGS, we noted reduced glomerular expression of YAP. Taken together, these results suggest a role for YAP as a physiologic antagonist of podocyte apoptosis, the signaling of which is essential for maintaining the integrity of the glomerular filtration barrier. These data suggest potential nephrotoxicity with strategies directed toward inhibition of YAP function. Further studies should evaluate the role of YAP in proteinuric glomerular disease pathogenesis and its potential utility as a therapeutic target.

OBJECTIVE African Americans (AA) suffer disproportionately from diabetic nephropathy (DN). C-reactive protein (CRP) has been associated with prevalent DN, but its association with incident DN in AA is unknown. We examined hs-CRP and incident DN in AA. RESEARCH DESIGN AND METHODS We conducted a longitudinal analysis of data from exams 1, 2, and 3 in 4,043 eligible Jackson Heart Study (JHS) participants. Participants with DN or without hs-CRP at exam 1 were excluded. Incident DN was defined as urinary albumin-to-creatinine ratio (ACR) >30 mg/g or self-reported dialysis/transplantation and type 2 diabetes mellitus (DM) or HbA1c >6.5% by exam 2 or 3 among participants free of DN at exam 1. Kaplan-Meier curves examined DN event-free survival probability by hs-CRP. With Cox proportional hazards regression we estimated hazard ratios (HRs) and 95% CI for DN by hs-CRP tertiles, adjusting for demographics and clinical and laboratory data. RESULTS During 7.8 years of median follow-up time, participants who developed DN had significantly higher baseline hs-CRP, age, fasting glucose, triglycerides, ACR, systolic blood pressure, waist circumference, and duration of DM (P < 0.05). The overall incident rate of DN was 7.9%. The mean time to incident DN was shorter for participants with hs-CRP in the high tertile (>4.24 mg/L) than in the low tertile ( CONCLUSIONS Inflammation, as measured by hs-CRP levels, may be associated with incident DN in AA. Further studies are warranted to replicate and elucidate the basis for this association.

Renal artery dissections (RADs) are lesions that disrupt vessels that primarily occur in patients with a known history of hypertension and caused by stenosis or enlargement of the renal artery typically due to underlying connective tissue disorders. However, RADs may occur spontaneously from trauma and no previous history of hypertension. Here, we report a rare case of bilateral isolated spontaneous RADs that characteristically occurs in healthy males. A 52-year-old male presented with left lower quadrant abdominal pain and renal insufficiency. Two years prior, he had experienced a similar episode of pain on the contralateral side, which was due to an infarct of the right kidney. On this admission, a computed tomography angiogram confirmed a new infarct of the left kidney, with dissection of a branch of the renal artery supplying the upper lobe. Work-up for cardiovascular, hematologic, radiographic or connective tissue causes was negative. We postulate that both RADs were potentially associated with the rapid twisting and turning of the abdominal area on a daily basis required for his occupation as an air traffic controller. The patient was treated with a renin angiotensin system inhibitor. After one year, both RADs had significantly improved and his renal function increased by ~23%. Isolated RAD may be associated with consistent or long-term activities that require rapid twisting and turning of the abdominal area. If left untreated, this may result in malignant hypertension, bilateral dissections, or renal ischemia. To avoid misdiagnosis; we provide a comprehensive review of the typical presentation and necessary assessment and management.