Slow Chronic Kidney Disease Progression Research Articles

Achieved clinic blood pressure level and chronic kidney disease progression in children: a report from the Chronic Kidney Disease in Children cohort.

Control of hypertension delays progression of pediatric chronic kidney disease (CKD), yet few data are available regarding what clinic blood pressure (BP) levels may slow progression. Longitudinal BP data from children in the Chronic Kidney Disease in Children cohort study who had hypertension or an auscultatory BP ≥ 90th percentile were studied. BP categories were defined as the maximum systolic or diastolic BP percentile (< 50th, 50th to 75th, 75th to 90th, and ≥ 90th percentile) with time-updated classifications corresponding to annual study visits. The primary outcome was time to kidney replacement therapy or a 30% decline in estimated glomerular filtration rate. Cox proportional hazard models described the effect of each BP category compared to BP ≥ 90th percentile. Seven hundred fifty-four participants (median age 9.9 years at study entry) met inclusion criteria; 65% were male and 26% had glomerular CKD. Any BP < 90th percentile was associated with a decreased risk of progression for those with glomerular CKD (hazard ratio (HR), 0.63; 95% CI, 0.28-1.39 (< 50th); HR, 0.59; 95% CI, 0.28-1.26 (50th-75th); HR, 0.40; 95% CI, 0.18-0.93 (75th-90th)). Similar results were found for those with non-glomerular CKD: any BP < 90th percentile was associated with decreased risk of progression (HR, 0.78; 90% CI, 0.49-1.25 (< 50th); HR, 0.53; 95% CI, 0.33-0.84 (50th-75th); HR, 0.71; 95% CI, 0.46-1.08 (75th-90th)). Achieved clinicBP < 90th percentile was associated with slower CKD progression in children with glomerular or non-glomerular CKD. These data provide guidance for management of children with CKD in the office setting. Graphical abstract.

Medical Nutrition Therapy Access in CKD: A Cross-sectional Survey of Patients and Providers

Rationale & ObjectiveNutrition management can slow the progression of chronic kidney disease (CKD) and help manage complications of CKD, but few individuals with CKD receive medical nutrition therapy before initiating dialysis. This study aimed to identify knowledge, attitudes, experiences, and practices regarding medical nutrition therapy and barriers and facilitators to medical nutrition therapy access for individuals with CKD stages G1-G5 from the perspective of patients and providers.Study DesignCross-sectional study composed of anonymous surveys.Setting & PopulationAdults with CKD stages G1-G5 and medical providers and registered dietitian nutritionists who regularly see patients with CKD stages G1-G5 were recruited by email using National Kidney Foundation and Academy of Nutrition and Dietetics databases and through the National Kidney Foundation 2019 Spring Clinical Meetings mobile app.Analytical ApproachDescriptive analyses and Fisher exact tests were conducted with Stata SE 16.ResultsRespondents included 348 patients, 66 registered dietitian nutritionists, and 30 medical providers. In general, patients and providers had positive perceptions of medical nutrition therapy and its potential to slow CKD progression and manage complications, and most patients reported interest in a medical nutrition therapy referral. However, there were feasibility concerns related to cost to the patient, lack of insurance coverage, and lack of renal registered dietitian nutritionists. There was low awareness of Medicare no-cost share coverage for medical nutrition therapy across patients and providers. About half the practices did not bill for medical nutrition therapy and those that did reported issues with being paid and low reimbursement rates.LimitationsResults may not be generalizable due to the small number of respondents and the potential for self-selection, nonresponse, and social desirability bias.ConclusionsMany patients with CKD stages G1-G5 are interested in medical nutrition therapy and confident that it can help with disease management, but there are feasibility concerns related to cost to the patient, insurance coverage, and reimbursement. There are significant opportunities to design and test interventions to facilitate medical nutrition therapy access for patients with CKD stages G1-G5.

A Model to Predict Risk of Hyperkalemia in Patients with Chronic Kidney Disease Using a Large Administrative Claims Database.

BackgroundChronic kidney disease (CKD) is responsible for substantial clinical and economic burden. Drugs that inhibit the renin-angiotensin-aldosterone system inhibitors (RAASi) slow CKD progression in many common clinical scenarios. Guideline-directed medical therapy requires maximal recommended doses of RAASi, which clinicians are often reluctant to prescribe because of the associated risk of hyperkalemia (HK).ObjectiveThis study aims to develop and validate a model to identify individuals with CKD at elevated risk for developing HK over a 12-month period on the basis of lab, medical, and pharmacy claims.MethodsUsing claims from a large US healthcare payer, we developed a model to predict the probability of individuals identified with CKD but not HK in 2016 (baseline year [BY]) who developed HK in 2017 (prediction year [PY]). The study population was comprised of members continuously enrolled with medical and pharmacy benefits and CKD (BY). Members were excluded from the analysis if they had HK (by lab results or diagnosis code) or dialysis (BY). Prediction model performance measures included area under the receiver operating characteristic curve (AUROC), calibration, and gain and lift charts.ResultsOf 435,512 members identified with CKD but not HK (BY), 6235 (1.43%) showed incident HK (PY). Compared with individuals without incident HK (PY), these members had a higher comorbidity burden, use of RAASi, and healthcare utilization. The AUROC and calibration analyses showed good predictive accuracy (area under the curve [AUC]=0.843 and calibration). The top 2 HK-prediction deciles identified 75.94% of members who went on to develop HK (PY).ConclusionGuideline-recommended doses of RAASi therapy can be limited by the risk of HK. Novel potassium binders may permit more patients at risk to benefit from these maximal RAASi doses. This predictive model successfully identified the risk of developing HK up to 1 year in advance.

STX-0119, a novel STAT3 dimerization inhibitor, prevents fibrotic gene expression in a mouse model of kidney fibrosis by regulating Cxcr4 and Ccr1 expression.

Kidney fibrosis is a histological hallmark of chronic kidney disease (CKD) and is believed to be involved in the progression of CKD. Therefore, inhibition of kidney fibrosis is a potential strategy for slowing CKD progression. Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is activated by interleukin‐6 and is reported to be involved in fibrosis. Previously, S3I‐201, an inhibitor of STAT3 phosphorylation, was shown to inhibit renal fibrosis in a mouse model, but its mechanism was not clarified completely. In this study, we investigated whether STX‐0119, a new inhibitor of STAT3 dimerization, suppressed kidney fibrotic gene expression using a mouse model of kidney fibrosis and examined the underlying mechanisms. Kidney fibrosis was induced by unilateral ureteral obstruction (UUO), which was accompanied by upregulation of STAT3 target genes. STX‐0119 administration suppressed the expression of fibrotic genes in UUO kidneys without affecting STAT3 phosphorylation. STX‐0119 decreased Cxcr4 mRNA in cultured rat kidney fibroblasts and Ccr1 mRNA in blood cells from UUO mice, both of which are reported to be involved in the progression of kidney fibrosis. These results suggest that STX‐0119 inhibits fibrotic gene expression in kidney by suppressing Cxcr4 and Ccr1 expression. This is the first report to indicate a part of the mechanism of the antifibrotic effects of a STAT3 inhibitor and suggests that STX‐0119 may be a lead compound for the treatment of kidney fibrosis.

Plant-Dominant Low-Protein Diet for Conservative Management of Chronic Kidney Disease.

Chronic kidney disease (CKD) affects >10% of the adult population. Each year, approximately 120,000 Americans develop end-stage kidney disease and initiate dialysis, which is costly and associated with functional impairments, worse health-related quality of life, and high early-mortality rates, exceeding 20% in the first year. Recent declarations by the World Kidney Day and the U.S. Government Executive Order seek to implement strategies that reduce the burden of kidney failure by slowing CKD progression and controlling uremia without dialysis. Pragmatic dietary interventions may have a role in improving CKD outcomes and preventing or delaying dialysis initiation. Evidence suggests that a patient-centered plant-dominant low-protein diet (PLADO) of 0.6–0.8 g/kg/day composed of >50% plant-based sources, administered by dietitians trained in non-dialysis CKD care, is promising and consistent with the precision nutrition. The scientific premise of the PLADO stems from the observations that high protein diets with high meat intake not only result in higher cardiovascular disease risk but also higher CKD incidence and faster CKD progression due to increased intraglomerular pressure and glomerular hyperfiltration. Meat intake increases production of nitrogenous end-products, worsens uremia, and may increase the risk of constipation with resulting hyperkalemia from the typical low fiber intake. A plant-dominant, fiber-rich, low-protein diet may lead to favorable alterations in the gut microbiome, which can modulate uremic toxin generation and slow CKD progression, along with reducing cardiovascular risk. PLADO is a heart-healthy, safe, flexible, and feasible diet that could be the centerpiece of a conservative and preservative CKD-management strategy that challenges the prevailing dialysis-centered paradigm.

Plant-based diets to manage the risks and complications of chronic kidney disease.

Traditional dietary recommendations for patients with chronic kidney disease (CKD) focus on the quantity of nutrients consumed. Without appropriate dietary counselling, these restrictions can result in a low intake of fruits and vegetables and a lack of diversity in the diet. Plant nutrients and plant-based diets could have beneficial effects in patients with CKD: increased fibre intake shifts the gut microbiota towards reduced production of uraemic toxins; plant fats, particularly olive oil, have anti-atherogenic effects; plant anions might mitigate metabolic acidosis and slow CKD progression; and as plant phosphorus has a lower bioavailability than animal phosphorus, plant-based diets might enable better control of hyperphosphataemia. Current evidence suggests that promoting the adoption of plant-based diets has few risks but potential benefits for the primary prevention of CKD, as well as for delaying progression in patients with CKD G3-5. These diets might also help to manage and prevent some of the symptoms and metabolic complications of CKD. We suggest that restriction of plant foods as a strategy to prevent hyperkalaemia or undernutrition should be individualized to avoid depriving patients with CKD of these potential beneficial effects of plant-based diets. However, research is needed to address knowledge gaps, particularly regarding the relevance and extent of diet-induced hyperkalaemia in patients undergoing dialysis.

P0716RAAS INHIBITION MODULATES KYNURENINE LEVELS IN A CKD POPULATION WITH AND WITHOUT TYPE 2 DIABETES MELLITUS

Abstract Background and Aims Kynurenine pathway of tryptophan metabolism is involved in the pathophysiology of chronic kidney disease (CKD) and diabetes mellitus (DM), mainly through the inflammation-induced activity of indoleamine 2,3-dioxygenase (IDO). Renin-angiotensin-aldosterone system inhibitors (RAASis) [angiotensin converting enzyme inhibitors (ACEis) and angiotensin II receptor antagonists (ARBs)] are recommended in these conditions to decrease proteinuria, slow CKD progression and reduce cardiovascular risk. The interactions between RAAS and the kynurenine pathway and the potential effects of RAASis have been reported in few experimental models but whether these drugs influence kynurenine levels in humans is unknown. We performed a single-centre cross-sectional observational study to evaluate tryptophan and kynurenine serum levels and IDO activity in CKD patients with and without type 2 DM, their correlations with markers of renal dysfunction, and their relationship with RAAS-inhibiting therapy. Method We enrolled 72 consecutive adult patients with CKD, of which 38 had DM, who were admitted to the Unit of Nephrology and Dialysis of our Hospital. Of them, 55 were receiving RAASis whereas 17 were not. Tryptophan was assessed by HPLC (high-performance liquid chromatography) analysis with an UltiMateTM 3000 chromatograph (Thermo Fisher Scientific, 168 Third Avenue Waltham, MA, USA); kynurenine was measured using an enzyme-linked immunosorbent assay (ELISA) kit (Catalogue n. K 7728; Immundiagnostik AG, Bensheim, Germany); IDO activity was calculated with the formula (kynurenine/tryptophan) x 100. Results Patients receiving RAASis and patients not under therapy only differed for frequency of arterial hypertension (100% vs 76.47%; P=0.002) and kynurenine levels, the latter being significantly lower in the treated group compared to the untreated one (1.56 ± 0.79 vs 2.16 ± 1.51 µmol/l; P=0.0378). Kynurenine did not correlate with estimated glomerular filtration rate (eGFR), proteinuria or albuminuria in the whole study cohort. Conversely, in patients not receiving RAASis it was inversely related to eGFR (r=-0.4862; P=0.0478) and directly related to proteinuria (ρ=0.493; P=0.0444) and albuminuria (ρ=0.542; P=0.0247); moreover, it varied across classes of albuminuria, being lower in patients with normoalbuminuria (0.98 ± 0.55 µmol/l) and higher in those with micro- (2.63 ± 1.53 µmol/l) and macroalbuminuria (3.09 ± 1.61 µmol/l) at the ANOVA test (F=4.008; P=0.042). In the same group, the relationship between IDO activity and eGFR was significant (ρ=-0.554; P=0.0210) and IDO activity differed across classes of albuminuria (F=3.702; P=0.05). Moreover, IDO activity was higher in patients with history of cardiovascular disease compared to those with no such history [10.22 (8.39 to 22.92) vs 7.57 (4.76 to 8.09) %; P=0.0343] whereas tryptophan had an opposite behaviour (17.00 ± 2.06 vs 22.00 ± 3.78 µmol/l; P=0.0036). Conclusion We observed lower kynurenine levels in CKD patients treated with RAASis compared to untreated patients, independently of the presence of DM, and a significant association between kynurenine and markers of renal damage only in the group not receiving RAASis. We could hypothesize that kynurenine may play a role in the pathophysiology of renal damage, as already suggested, and that drugs interfering with RAAS activation may act also by reducing kynurenine levels, in addition to their already known effects at the renal level. Indeed, kynurenine synthesis results to be higher in states of inflammation and RAAS has pro-inflammatory and pro-fibrotic actions; accordingly, RAASis could reduce the enzymatic activity responsible for kynurenine increase and this could be one of the mechanisms mediating the beneficial effects of RAAS inhibition on CKD progression. This may be relevant because kynurenine has shown pro-thrombotic effects and is emerging as a potential new biomarker of CKD.

RAS inhibition modulates kynurenine levels in a CKD population with and without type 2 diabetes mellitus.

Kynurenine pathway of tryptophan metabolism is involved in the pathophysiology of chronic kidney disease (CKD) and diabetes mellitus, mainly through the inflammation-induced activity of indoleamine 2,3-dioxygenase (IDO), and few studies have investigated its potential link with proteinuria. Renin-angiotensin system inhibitors (RASis) are recommended in these patients to decrease proteinuria, slow CKD progression and reduce cardiovascular risk, but whether these drugs influence kynurenine levels in humans is unknown. We evaluated serum tryptophan and kynurenine in patients suffering from CKD with or without type 2 diabetes mellitus, their correlations with markers of reduced kidney function, and their relationship with RAS-inhibiting therapy. Of 72 adult patients enrolled, 55 were receiving RASis, whereas 17 were not. Tryptophan was assessed by HPLC (high-performance liquid chromatography); kynurenine was measured using an enzyme-linked immunosorbent assay kit; IDO activity (%) was calculated with the formula (kynurenine/tryptophan) × 100. Kynurenine levels were significantly lower in the group under RASis compared to the untreated group (1.56 ± 0.79 vs 2.16 ± 1.51µmol/l; P = 0.0378). In patients not receiving RASis, kynurenine was inversely related to estimated glomerular filtration rate (eGFR) (r = - 0.4862; P = 0.0478) and directly related to both proteinuria (ρ = 0.493; P = 0.0444) and albuminuria (ρ = 0.542; P = 0.0247). IDO activity was higher in patients with history of cardiovascular disease compared to patients with no such history, and it negatively correlated with eGFR (ρ = - 0.554; P = 0.0210) in the same group. These findings may contribute to explain the well-known beneficial effects of RAS inhibition in CKD population, especially considering that kynurenine is emerging as a potential new biomarker of CKD.

The effect of renin–angiotensin–aldosterone system blockers on the progression of chronic kidney disease in hypertensive elderly patients without proteinuria: PROERCAN study. Rationale and design

IntroductionBlood pressure (BP) control is fundamental to the care of patients with chronic kidney disease (CKD), and is relevant at all stages of CKD. Renin–angiotensin–aldosterone system (RAAS) blockers have shown to be effective, not only in BP control but also in reducing proteinuria and slowing CKD progression. However, there is a lack of evidence for recommending RAAS blockers in elderly patients with CKD without proteinuria. The primary outcome of the present study is to evaluate the impact of RAAS blockers on CKD progression in elderly patients without proteinuria. Materials and methodsThe PROERCAN trial (trial registration, NCT03195023) is a multicentre open-label, randomized controlled clinical trial with 110 participants over 65 years-old with hypertension and CKD stages 3–4 without proteinuria. Patients will be randomized in a 1:1 ratio to either receive RAAS blockers or other antihypertensive drugs, and will be followed up for three years. Primary outcome is the estimated glomerular filtration rate (eGFR) decline at 3 years. Secondary outcomes include BP control, renal and cardiovascular events, and mortality. Results and conclusionsThe design of this trial is presented here. The results will show if antihypertensive treatment with RAAS blockers has an impact on CKD progression in elderly patients without proteinuria. Any differences in BP control, cardiovascular events, and mortality with each antihypertensive treatment will be also clarified.

Aldosterone and the mineralocorticoid receptor in renal injury: A potential therapeutic target in feline chronic kidney disease.

There is a growing body of experimental and clinical evidence supporting mineralocorticoid receptor (MR) activation as a powerful mediator of renal damage in laboratory animals and humans. Multiple pathophysiological mechanisms are proposed, with the strongest evidence supporting aldosterone‐induced vasculopathy, exacerbation of oxidative stress and inflammation, and increased growth factor signalling promoting fibroblast proliferation and deranged extracellular matrix homeostasis. Further involvement of the MR is supported by extensive animal model experiments where MR antagonists (such as spironolactone and eplerenone) abrogate renal injury, including ischaemia‐induced damage. Additionally, clinical trials have shown MR antagonists to be beneficial in human chronic kidney disease (CKD) in terms of reducing proteinuria and cardiovascular events, though current studies have not evaluated primary end points which allow conclusions to made about whether MR antagonists reduce mortality or slow CKD progression. Although differences between human and feline CKD exist, feline CKD shares many characteristics with human disease including tubulointerstitial fibrosis. This review evaluates the evidence for the role of the MR in renal injury and summarizes the literature concerning aldosterone in feline CKD. MR antagonists may represent a promising therapeutic strategy in feline CKD.

The authority of courage and compassion: Healthcare policy leadership in addressing the kidney disease public health epidemic.

Recent developments in US kidney‐related healthcare policy have made chronic kidney disease (CKD) a societal focus in the United States. In the biggest policy change since the 1972 Social Security Amendments that extended Medicare coverage to patients with kidney failure regardless of age, a 2019 presidential executive order pledged to reduce end‐stage kidney disease, slow CKD progression, increase kidney transplants, and focus on home dialysis care. This manuscript seeks to outline key factors that can enable this milestone moment to evolve a policy framework that improves the health of society while being economically sustainable. Understanding the sociohistorical context of healthcare policy and the related lessons learned demonstrates that policy must take a broader view of the societal and system wide factors that affect chronic illness. Addressing the full breadth of the CKD epidemic requires looking at factors from both inside and outside traditional medical‐pathophysiological environments, including social determinants of health. This more fulsome insight will enable policy to better align the broad range of people and organizations who are working to combat the disease. By creating patient‐centered policy that both evolves with the speed of innovation and addresses root causes of CKD instead of narrowly focusing on symptoms or comorbidities alone, leaders in the public square have an historic opportunity to thoughtfully create the common ground of a lasting policy legacy that improves society's health today and for generations to come.

Novel dietary and pharmacologic approaches for acid-base modulation to preserve kidney function and manage uremia.

We review mechanisms for chronic kidney disease (CKD) progression that might be addressed with nonpharmacologic and novel pharmacologic interventions as strategies by which to slow or even prevent CKD progression. Evolving data support the contribution of the broad spectrum of disorders of acid (H) accumulation, which we refer to as 'H stress', to CKD progression. Recent studies support that amelioration of H stress, including spectra of H accumulation that are insufficient to cause metabolic acidosis, is kidney-protective. In addition, gut-derived toxins appear to contribute to CKD progression and to the well described increased cardiovascular disease (CVD) risk in patients with CKD. Dietary and novel pharmacologic interventions hold promise as strategies to slow CKD progression through reducing levels of these gut-derived toxins. In addition, oxidative stress appears to mediate CKD progression and contributing factors like diet and cigarette smoking can exacerbate oxidative stress. Dietary changes and smoking cessation hold promise to favorably affect CKD progression by reducing kidney oxidative stress. The urgent need to add to the traditional armamentarium of blood pressure control and antiangiotensin II pharmacologic therapy for kidney protection has led to investigations into additional kidney-protective strategies. Acid stress, a disordered gut microbiome, and oxidative stress each appear to contribute to CKD progression and can be potentially addressed by nonpharmacologic and novel pharmacologic interventions.

The Effect of Crizanlizumab Plus Standard of Care (SoC) Versus Soc Alone on Renal Function in Patients with Sickle Cell Disease and Chronic Kidney Disease: A Randomized, Multicenter, Open-Label, Phase II Study (STEADFAST)

The Effect of Crizanlizumab Plus Standard of Care (SoC) Versus Soc Alone on Renal Function in Patients with Sickle Cell Disease and Chronic Kidney Disease: A Randomized, Multicenter, Open-Label, Phase II Study (STEADFAST)

Association between Sodium Intake and Urinary Fractional Albumin and Immunoglobulin G Excretion in Chronic Nondialytic Renal Disease: A Prospective Longitudinal Study

Background/Aims: Previous studies reported that fractional clearance of urinary proteins is better than total proteinuria in predicting chronic kidney disease (CKD) progression. However, the role of sodium in the fractional excretion of proteins has not been established. We aimed to evaluate the association between sodium intake and fractional albumin and immunoglobulin G (IgG) excretion in nondialytic CKD. Methods: We did a longitudinal, observational, and prospective study that included CKD patients aged 18–80. Included patients performed basal routine laboratory evaluations, urinary sodium excretion, and fractional albumin and IgG excretion that were repeated after 6-month of follow-up. Results: We evaluated 84 patients, mean age 55 ± 15.6 years, 40 women, and 74 whites. The change of estimated sodium intake had an association with the change of fractional albumin (R = 0.54; p < 0.001) and IgG (R = 0.56; p < 0.001) excretion in univariate analysis (increases in sodium intake were paralleled by increases in albumin and IgG excretion fractions). This association was maintained in a multiple generalized linear model even after adjusting for age and for changes in blood pressure, urinary potassium, protein intake, and blood glucose. Conclusion: In CKD patients, changes in estimated sodium intake were associated with changes in the fractional albumin and IgG excretion regardless of confounding factors. Findings of this study support the idea that reducing salt intake, and consequently, albumin and IgG fractional excretions could help to slow CKD progression. This hypothesis must be tested in long-term interventional studies.

Vegetable-Based Diets for Chronic Kidney Disease? It Is Time to Reconsider.

Traditional dietary recommendations to renal patients limited the intake of fruits and vegetables because of their high potassium content. However, this paradigm is rapidly changing due to the multiple benefits derived from a fundamentally vegetarian diet such as, improvement in gut dysbiosis, reducing the number of pathobionts and protein-fermenting species leading to a decreased production of the most harmful uremic toxins, while the high fiber content of these diets enhances intestinal motility and short-chain fatty acid production. Metabolic acidosis in chronic kidney disease (CKD) is aggravated by the high consumption of meat and refined cereals, increasing the dietary acid load, while the intake of fruit and vegetables is able to neutralize the acidosis and its deleterious consequences. Phosphorus absorption and bioavailability is also lower in a vegetarian diet, reducing hyperphosphatemia, a known cause of cardiovascular mortality in CKD. The richness of multiple plants in magnesium and vitamin K avoids their deficiency, which is common in these patients. These beneficial effects, together with the reduction of inflammation and oxidative stress observed with these diets, may explain the reduction in renal patients’ complications and mortality, and may slow CKD progression. Finally, although hyperkalemia is the main concern of these diets, the use of adequate cooking techniques can minimize the amount absorbed.

Direct-acting antiviral therapy slows kidney function decline in patients with Hepatitis C virus infection and chronic kidney disease

Hepatitis C virus (HCV) infection is common and can accelerate chronic kidney disease (CKD) progression. Direct-acting antiviral (DAA) therapies against hepatitis C have consistently shown rates of sustained viral remission. However, the effect on kidney function is unknown. In a retrospective observational cohort study of HCV-infected patients receiving DAA therapies from 2013 to 2017, the slopes of estimated glomerular filtration rate (eGFR) decline were compared in the three years before DAA therapy to the slope after therapy. Pre- and post-treatment albuminuria values were also compared. In all, 1,178 patients were included; mean age of 56, 64% male, 71% white, 21% were diabetic, and 42% with cirrhosis. In patients with eGFR less than 60ml/min per 1.73m2, the annual decline in eGFR in the three years prior to treatment was -5.98 ml/min per year (95% confidence interval -7.30 to -4.67) and improved to -1.32 ml/min per year (95% confidence interval -4.50 to 1.88) after DAA therapy. In patients with eGFR greater than 60ml/min per 1.73m2 the annual decline in eGFR in the three years prior to treatment was -1.43 ml/min per year (95% confidence interval -1.78 to -1.08) and after DAA therapy was -2.32 ml/min per year (95% confidence interval -3.36 to -1.03). Albuminuria improved significantly in patients without diabetes, but not in those with diabetes. Predictors of eGFR improvement included having CKD at baseline and being non-diabetic. Events of acute kidney injury were rare, occurring in 29 patients, and unrelated to antiviral therapy in 76% of cases. Thus, DAA therapy for HCVs infection may slow CKD progression.

Gap acidosis except lactic acidosis develops and progresses during chronic kidney disease stage G5.

Gap acidosis, a type of metabolic acidosis caused by titratable acid accumulation, participates in CKD progression. It was found at all the stages of chronic kidney disease (CKD), whereas the kidney was believed to preserve its ability to excrete titratable acid until renal function is impaired severely. Serum concentrations of lactate (Lac) and the other usually unmeasured anions (OUA) were separately examined using 420 records of blood gas analysis performed simultaneously with serum chemistry at a general hospital. Between the records grouped by the CKD stage, Lac was generally higher in the early stages than the late stages (2.2 ± 1.1, 1.9 ± 1.7, 1.5 ± 1.3, and 1.2 ± 0.6mmol/L in G1-2, G3, G4, and G5, respectively). While OUA was not significantly different between G1-2, G3, and G4 (1.3 ± 2.0, 2.5 ± 2.7, and 2.6 ± 2.2mEq/L, respectively), it was higher in G5 (4.7 ± 2.3mEq/L) than in G1-4 (P < 0.001). In G5, OUA generally increased as eGFR decreased, and OUA was 6.6 ± 1.9, 4.7 ± 2.1 and 3.6 ± 2.0mEq/L in subgroups of eGFR < 5, 5-10, and 10-15mL/min/1.73 m2, respectively (P ≤ 0.001). Gap acidosis except lactic acidosis developed and progressed during the CKD stage G5, while lactic acidosis developed in the CKD stages G1-4. Prevention of lactic acidosis by preserving peripheral perfusion in the early CKD stages could slow CKD progression.

Urinary citrate: helpful to predict acid retention in CKD patients?

Acid retention occurs early during the course of chronic kidney disease (CKD). Studies conducted in patients with CKD suggest that alkali supplementation may slow CKD progression. However, the diagnosis of acid retention is challenging when plasma bicarbonate concentration is still normal. In this issue, Goraya etal. suggest that urinary citrate may predict acid retention in eubicarbonatemic patients with stages 1 and 2 CKD . Although interesting, this claim yet requires confirmation by further studies.

Predictors of Net Acid Excretion in the Chronic Renal Insufficiency Cohort (CRIC) Study

Higher urine net acid excretion (NAE) is associated with slower chronic kidney disease progression, particularly in patients with diabetes mellitus. To better understand potential mechanisms and assess modifiable components, we explored independent predictors of NAE in the CRIC (Chronic Renal Insufficiency Cohort) Study. Cross-sectional. A randomly selected subcohort of adults with chronic kidney disease enrolled in the CRIC Study with NAE measurements. A comprehensive set of variables across prespecified domains including demographics, comorbid conditions, medications, laboratory values, diet, physical activity, and body composition. 24-hour urine NAE. NAE was defined as the sum of urine ammonium and calculated titratable acidity in a subset of CRIC participants. 22 individuals were excluded for urine pH< 4 (n= 1) or≥7.4 (n= 19) or extreme outliers of NAE values (n= 2). From an analytic sample of 978, we identified the association of individual variables with NAE in the selected domains using linear regression. We estimated the percent variance explained by each domain using the adjusted R2 from a domain-specific model. Mean NAE was 33.2 ± 17.4 (SD) mEq/d. Multiple variables were associated with NAE in models adjusted for age, sex, estimated glomerular filtration rate (eGFR), race/ethnicity, and body surface area, including insulin resistance, dietary potential renal acid load, and a variety of metabolically active medications (eg, metformin, allopurinol, and nonstatin lipid agents). Body size, as indicated by body surface area, body mass index, or fat-free mass; race/ethnicity; and eGFR also were independently associated with NAE. Bydomains, more variance was explained bydemographics, body composition, and laboratory values, which included eGFR and serum bicarbonate level. Cross-sectional; use of stored biological samples. NAE relates to several clinical domains including body composition, kidney function, and diet, but also to metabolic factors such as insulin resistance and the use of metabolically active medications.

Mechanisms of Injury in APOL1-associated Kidney Disease.

An improved understanding of the pathogenesis in apolipoprotein L1 (APOL1) gene-associated chronic kidney disease (CKD) arose from observations in kidney transplantation. APOL1 genotyping could soon improve the safety of living kidney donation in individuals with recent African ancestry and alter the allocation of deceased donor kidneys. This article reviews the potential mechanisms that underlie development of APOL1-associated nephropathy. Roles for circulating APOL1 protein versus intrinsic renal expression of APOL1 are discussed, as well as the requirement for modifying genetic and/or environmental factors. Abundant evidence supports local kidney production of APOL1 renal-risk variant protein in the development of nephropathy; this is true in both native kidney disease and after renal transplantation. Only a minority of kidneys from individuals with APOL1 high-risk genotypes will develop CKD or manifest shorter renal allograft survival after transplantation. Therefore, modifying factors that explain why only a subset of kidneys develops nephropathy remain critical to identify. It appears likely that environmental exposures, as opposed to major APOL1-second gene interactions, will prove to be stronger modifiers of the risk for nephropathy. The evolving understanding of the pathogenesis in APOL1-associated nephropathy will identify biomarkers predicting nephropathy in individuals at high genetic risk and lead to novel therapies to prevent or slow native CKD progression and prolong survival of transplanted kidneys. In the interim, the National Institutes of Health-sponsored "APOL1 Long-term Kidney Transplantation Outcomes" Network will determine whether APOL1 genotyping in individuals with recent African ancestry improves outcomes and safety in kidney transplantation.