Kidney Disease Research Articles

The experiences of people starting haemodialysis: A qualitative study.

Starting dialysis is a life-changing transition for people living with kidney disease. People feel overwhelmed with diet changes, medications and surgical interventions, and often experience high levels of anxiety, depression and hospital admissions. The objective of this study was to explore and describe the experiences and perspectives of people starting dialysis. Observational qualitative study using audio-recorded, individual, semi-structured interviews. We conducted 20 semi-structured interviews with English-speaking adults who were within 90 days of starting in-centre haemodialysis at centres of a nonprofit dialysis provider in Northern California. Trained qualitative researchers conducted interviews that were deidentified and transcribed verbatim before being inductively coded into codes, categories, and themes. Three overarching themes emerged from the interviews. Being overwhelmed when starting dialysis, realises the emotional unpreparedness of patients starting dialysis and how the centre's environment (waiting and treatment areas) and staff behaviour impact the dialysis start experience. Making sense of it all, covers how the patient's symptoms, behaviour, and dialysis-related experiences impact the dialysis start. Moving forward, describes how education informed optimal decision-making, and can provide hope for a longer and better life. Predominantly college-educated participants were recruited from a single dialysis organisation which may limit the transferability of results. Understanding the life-changing experiences that patients encounter when starting dialysis assist dialysis clinicians to help patients adjust and develop long-term coping strategies.

Integrin-linked kinase mRNA expression in circulating mononuclear cells as a biomarker of kidney and vascular damage in experimental chronic kidney disease

BackgroundTraditional biomarkers of chronic kidney disease (CKD) detect the disease in its late stages and hardly predict associated vascular damage. Integrin-linked kinase (ILK) is a scaffolding protein and a serine/threonine protein kinase that plays multiple roles in several pathophysiological processes during renal damage. However, the involvement of ILK as a biomarker of CKD and its associated vascular problems remains to be fully elucidated.MethodsCKD was induced by an adenine-rich diet for 6 weeks in mice. We used an inducible ILK knockdown mice (cKD-ILK) model to decrease ILK expression. ILK content in mice's peripheral blood mononuclear cells (PBMCs) was determined and correlated with renal function parameters and with the expression of ILK and fibrosis and inflammation markers in renal and aortic tissues. Also, the expression of five miRNAs that target ILK was analyzed in whole blood of mice.ResultsThe adenine diet increased ILK expression in PBMCs, renal cortex, and aortas, and creatinine and urea nitrogen concentrations in the plasma of WT mice, while these increases were not observed in cKD-ILK mice. Furthermore, ILK content in PBMCs directly correlated with renal function parameters and with the expression of renal and vascular ILK and fibrosis and inflammation markers. Finally, the expression of the five miRNAs increased in the whole blood of adenine-fed mice, although only four correlated with plasma urea nitrogen, and of those, three were downregulated in cKD-ILK mice.ConclusionsILK, in circulating mononuclear cells, could be a potential biomarker of CKD and CKD-associated renal and vascular damage.Graphical ILK content in circulating mononuclear cells reflects renal and vascular damage in a CKD experimental model.

Development of a kidney microphysiological system hardware platform for microgravity studies

Determining the physiological effects of microgravity on the human kidney is limited to relatively insensitive tests of biofluids (blood and urine) that do not return abnormal results until more than 50% of kidney function is lost. We have developed an “organ on chip” microphysiological model of the human kidney proximal tubule (PT-MPS) that can recapitulate many kidney functions and disease states and could play a critical role in determining mechanisms of early kidney dysfunction in microgravity. However, the ground-based PT-MPS system is incompatible with spaceflight as it requires a large pneumatic system coupled to a cell incubator for perfusion and intensive hand-on manipulation. Herein, we report the hardware engineering and performance of the Kidney Chip Perfusion Platform (KCPP), a small, advanced, semi-autonomous hardware platform to support kidney microphysiological model experiments in microgravity. The KCPP is composed of five components, the kidney MPS, the MPS housing and valve block, media cassettes, fixative cassettes, and the programable precision syringe pump. The system has been deployed twice to the ISSNL (aboard CRS-17 and CRS-22). From each set of ISSNL experiments and ground-based controls, we were able to recover PT-MPS effluent for biomarker analysis and RNA suitable for transcriptomics analysis demonstrating the usability and functionality of the KCPP.

Contemporary Predictors of Major Adverse Cardiovascular Events following Percutaneous Coronary Intervention: A Nationally Representative US Sample

Background: Patient outcomes after percutaneous coronary intervention (PCI) have improved over the last 30 years due to better techniques, therapies, and care processes. This study evaluated contemporary predictors of post-PCI major adverse cardiovascular events (MACE) and summarized risk in a parsimonious risk prediction model. Methods: The Cardiovascular Patient-Level Analytical Platform (CLiPPeR) is an observational dataset of baseline variables and longitudinal outcomes from the American College of Cardiology’s CathPCI Registry® and national claims data. Cox regression was used to evaluate 2–6 years of patient follow-up (mean: 2.56 years), ending in December 2017, after index PCI between 2012 and 2015 (N = 1,450,787), to examine clinical and procedural predictors of MACE (first myocardial infarction, stroke, repeat PCI, coronary artery bypass grafting, and mortality). Cox analyses of post-PCI MACE were landmarked 28 days after index PCI. Results: Overall, 12.4% (n = 179,849) experienced MACE. All variables predicted MACE, with cardiogenic shock, cardiac arrest, four diseased coronary vessels, and chronic kidney disease having hazard ratios (HRs) ≥ 1.50. Other major predictors of MACE were in-hospital stroke, three-vessel disease, anemia, heart failure, and STEMI presentation. The index revascularization and discharge prescription of aspirin, P2Y12 inhibitor, and lipid-lowering medication had HR ≤ 0.67. The primary Cox model had c-statistic c = 0.761 for MACE versus c = 0.701 for the parsimonious model and c = 0.752 for the parsimonious model plus treatment variables. Conclusions: In a nationally representative US sample of post-PCI patients, predictors of longitudinal MACE risk were identified, and a parsimonious model efficiently encapsulated them. These findings may aid in assessing care processes to further improve care post-PCI outcomes.

Using eGFR and Albumin Creatinine Ratio as an Initial Screening Tool in Trinidadian Primary Care to Identify High-risk Population for CKD: A Cross-Sectional Study

Background: Chronic kidney disease (CKD) is a major public health burden and is often undiagnosed in the primary care setting. Untested and untreated, this often leads to renal failure and dialysis. Materials and Methods: This was a cross-sectional study of adults aged 20 years and over, diagnosed with type 2 diabetes mellitus and/or hypertension, with no previous history or record of CKD, and attending three chronic disease clinics in the Eastern Regional Health Authority (ERHA). Patients were screened for risk of CKD by using the albumin creatinine ratio. The eGFR was calculated based on serum creatinine by using the CKD Epidemiology Collaboration (EPI) 2009 equation. Results: In total, 430 patients agreed to participate with 61.2% of response rate. Of the 385 with complete data, 357 (92%) were detected as having a high risk for CKD; older patients (>66 years) and those with both diabetes and hypertension had high proportions of risk for CKD. There were significant associations between age, systolic hypertension, and the severity of risk for CKD. Conclusion: CKD is common at the primary care level among adults with NCDs in Trinidad, with many patients having been left out without being tested for CKD. Primary care physicians must take this into consideration in caring for NCD patients.

A Prospective Study of Incidence, Risk Factors, and Outcomes of Acute Kidney Injury in Coronavirus Disease 2019

Background: Acute kidney injury (AKI) is common after coronavirus 2 infection (COVID-19), leading to higher morbidity and mortality. There is little prospective data from India regarding the incidence, risk factors, and outcome of AKI in COVID-19. Materials and Methods: This study was conducted prospectively in adult patients between September and December 2020 in a tertiary care hospital in the national capital region of Delhi. A total of 856 patients with COVID-19 infection were enrolled in the study. Survivors were followed for 3 months after discharge. Results: Out of 856 patients, 207 (24%) developed AKI. AKI was significantly higher in those with severe disease as compared to mild-moderate disease (88% vs. 12%, P = 0.04). Out of all AKI, 3.4% had stage 1, 9.2% had stage 2, and the rest 87.4% had stage 3 AKI. 183/207 (88%) patients were on mechanical ventilators, 133 (64%) required inotropic support, and 137/207 (83.6%) patients required kidney replacement therapy. Out of 207 AKI patients, 74% (153) died as compared to 4% (27) in non-AKI group (P = 0.0001). After 3 months, chronic kidney disease (CKD) developed in 10/54 (18.5%) patients. On multivariable analysis, the presence of diabetes mellitus, severe COVID-19 disease, high levels of C reactive protein, lactate dehydrogenase, D-Dimer, and use of intravenous steroids, tocilizumab and remdesivir, were found to be significant predictors of AKI. Conclusion: AKI is common after COVID-19 infection and it is a significant risk factor for mortality in COVID-19. Patients with diabetes and high levels of inflammatory markers have higher mortality. CKD may develop in many patients after discharge.

PAG Masked Protective Physical Exercise-Induced High H2S Levels in 5/6 Nephrectomized Rats

Background: To investigate the mechanisms of exercise therapeutics in preclinical animal models of chronic kidney disease (CKD), PAG (D, L-propargylglycine), an inhibitor of hydrogen sulfide production, was used to examine the protective effects of physical activity on oxidative stress and inflammation levels during CKD. Methods: Male Wistar rats with CKD, induced by the 5/6 nephrectomy procedure and subjected to 8 weeks of exercise training, received injections of PAG, a cystathionine γ-lyase (CSE) inhibitor, at a dose of 19 mg/kg, i.p., twice a week during those 8 weeks. The systolic blood pressure (BP) and renal sympathetic nerve activity (RSNA) were assessed. Additionally, plasma creatinine, BUN, renal hydrogen sulfide (H2S) levels, oxidative stress, and inflammatory markers were evaluated. Results: In the PAG group, inhibition of H2S production significantly reversed the improvements in plasma creatinine, BUN, renal malondialdehyde (MDA) level, superoxide dismutase (SOD) activity, TNF-α, and IL-6 that were achieved by exercise. Additionally, high RSNA and high BP, which were also reversed in the PAG group, compared to the CKD group subjected to exercise training. Conclusions: The results suggest that the improvement in BP, oxidative stress, and inflammation status by exercise in CKD may be at least partially due to CSE/H2S signaling.

Sodium-Glucose Cotransporter-2 Inhibitors and Cardiovascular Protection Among Patients With Type 2 Diabetes Mellitus: A Systematic Review

Background: Accumulating evidence has demonstrated the positive effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors in managing patients with type 2 diabetes mellitus (T2DM). SGLT2 inhibitors protect patients with T2DM from cardiovascular complications and are generally safe.Aim: The aim of this study is to assess the cardiovascular effects of SGLT2 inhibitors in patients with T2DM.Methods: A systematic review was conducted using published English literature in PubMed and Google Scholar databases.Results: Most of the studies showed significant positive cardiovascular effects of SGLT2 inhibitors in patients with and without established cardiovascular disease (CVD). Empagliflozin reduced the risk of cardiovascular death, hospitalization for heart failure (HHF), cardiovascular death or heart failure, and major adverse cardiovascular events (MACE) such as nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death regardless of the number of cardiovascular risk factors. The effects of empagliflozin on cardiovascular events and mortality in patients with coronary artery bypass graft (CABG) were assessed. Further, the efficacy of empagliflozin in three different phenotypic groups, namely, younger patients with shorter duration of T2DM and highest glomerular filtration rate, women without coronary artery disease, and older adults with advanced coronary artery disease plus several comorbidities, was also assessed. The effects of canagliflozin were evaluated in patients with and without a history of CVD and with different body weights, and in those with and without prior heart failure. Treatment with canagliflozin based on multivariable-predicted cardiovascular risk factors prevented heart failure events more than treatment based on glycated hemoglobin and albuminuria alone. The efficacy of dapagliflozin was evaluated in patients with or at risk of atherosclerotic cardiovascular disease (ASCVD), heart failure status, and left ventricular ejection fraction (LVEF), as well as the elderly population. A reduction in HHF or cardiovascular death and insignificant reduction in MACE were noted. Furthermore, significant reduction in the risk of cardiovascular death and all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF) was also observed. Sotagliflozin was studied for its cardiovascular outcomes in patients with chronic kidney disease with or without albuminuria and resulted in a reduction in cardiovascular-related deaths and HHF.Conclusion: SGLT2 inhibitors have beneficial cardiovascular effects in patients with T2DM and should be incorporated into their management.

Implications of Five Different Risk Models In Primary Prevention Guidelines.

A lack of consensus exists across guidelines as to which risk model should be used for the primary prevention of cardiovascular disease (CVD). Our objective was to determine potential improvements in the number needed to treat (NNT) and number of events prevented (NEP) using different risk models in patients eligible for risk stratification. A retrospective observational cohort was assembled from primary care patients in Ontario, Canada between January 1st, 2010, to December 31st, 2014 and followed for up to 5 years. Risk estimation was undertaken in patients 40-75 years of age, without CVD, diabetes, or chronic kidney disease using the Framingham Risk Score (FRS), Pooled Cohort Equations (PCEs), a recalibrated FRS (R-FRS), Systematic Coronary Risk Evaluation 2 (SCORE2), and the low-risk region recalibrated SCORE2 (LR-SCORE2). The cohort consisted of 47,399 patients (59% women, mean age 54). The NNT with statins was lowest for SCORE2 at 40, followed by LR-SCORE2 at 41, R-FRS at 43, PCEs at 55, and FRS at 65. Models that selected for individuals with a lower NNT recommended statins to fewer, but higher risk patients. For instance, SCORE2 recommended statins to 7.9% of patients (5-year CVD incidence 5.92%). The FRS, however, recommended statins to 34.6% of patients (5-year CVD incidence 4.01%). Accordingly, the NEP was highest for the FRS at 406 and lowest for SCORE2 at 156. Newer models such as SCORE2 may improve statin allocation to higher risk groups with a lower NNT but prevent fewer events at the population level.

Application of CD38 monoclonal antibody in kidney disease

CD38 antigen is a glycoprotein that found on the surface of several immune cells, and this property makes its monoclonal antibodies have the effect of targeted elimination of immune cells. Therefore, the CD38 monoclonal antibody (such as daratumumab, Isatuximab) becomes a new treatment option for membranous nephropathy, lupus nephritis, renal transplantation, and other refractory kidney diseases. This review summarizes the application of CD38 monoclonal antibodies in different kidney diseases and highlights future prospects.

Personalized nutritional management in the transition from non-dialysis dependent chronic kidney disease to dialysis.

Dialysis has been the dominant treatment regimen in end-stage kidney disease as a means to remove uremic waste products and to maintain electrolyte, acid base, and fluid balance. However, given that dialysis may not always provide a survival benefit nor improved quality of life in certain subpopulations, there is growing recognition of the need for conservative and preservative management as an alternative treatment strategy for advanced chronic kidney disease (CKD). Personalized nutritional management tailored to patient's sociodemographics, social needs, psychological status, health literacy level, and preferences is a key component of conservative and preservative care, as well as in the management of patients transitioning from non-dialysis dependent CKD to dialysis. In this review, we discuss the nutritional and metabolic alterations that ensue in CKD; the rationale for low-protein diets in the conservative and preservative management of advanced CKD; the role of plant-based diets in kidney health; emerging data on dietary potassium and sodium intake on CKD outcomes; and the practical implementation of dietary interventions in advanced kidney disease.

Oral delivery of nanomedicine for genetic kidney disease

Abstract Chronic and genetic kidney diseases such as autosomal dominant polycystic kidney disease (ADPKD) have few therapeutic options, and clinical trials testing small molecule drugs have been unfavorable due to low kidney bioavailability and adverse side effects. Although nanoparticles can be designed to deliver drugs directly to the diseased site, there are no kidney-targeted nanomedicines clinically available, and most FDA-approved nanoparticles are administered intravenously which is not ideal for chronic diseases. To meet these challenges of chronic diseases, we developed a biomaterials-based strategy using chitosan particles (CP) for oral delivery of therapeutic, kidney-targeting peptide amphiphile micelles (KMs). We hypothesized that encapsuling KMs into CP would enhance the bioavailability of KMs upon oral administration given the high stability of chitosan in acidic conditions and mucoadhesive properties enabling absorption within the intestines. To test this, we evaluated the mechanism of KM access to the kidneys via intravital imaging and investigated the KM biodistribution in a porcine model. Next, we loaded KMs carrying the ADPKD drug metformin into CP (KM-CP-met) and measured in vitro therapeutic effect. Upon oral administration in vivo, KM-CP-met showed significantly greater bioavailability and accumulation in the kidneys as compared to KM only or free drug. As such, KM-CP-met treatment in ADPKD mice (Pkd1fl/fl; Pax8-rtTA; Tet-O-Cre which develops the disease over 120 days and mimics the slow development of ADPKD) showed enhanced therapeutic efficacy without affecting safety despite repeated treatment. Herein, we demonstrate the potential of KM-CP as a nanomedicine strategy for oral delivery for the long-term treatment of chronic kidney diseases.

Prevalence of hypertension and diabetes mellitus in Peruvian patients with chronic kidney disease: a systematic review and meta-analysis

BackgroundChronic Kidney Disease (CKD) represents a major challenge for public health, with hypertension and diabetes being the main causes of its occurrence. Therefore, this study aims to determine the prevalence of hypertension (HTN) and diabetes mellitus (DM) in Peruvian patients with CKD.MethodsA systematic search for studies about CKD in Peru was carried out in PubMed, Scopus, Embase, Web of Science, ScienceDirect, Google Scholar, Virtual Health Library (VHL), and Scielo from 2011 to December 2023. The protocol of this research was registered in the international registry of systematic reviews, the Prospective International Registry of Systematic Reviews (PROSPERO), with registration number CRD42023425118. Study selection, quality assessment, and data extraction were performed independently by two authors. Study quality was assessed using the Joanna Briggs Institute Statistical Meta-Analysis Assessment and Review Instrument. A random-effects model with inverse variance weighting was used to estimate the combined prevalence of HTN and DM in Peruvian patients with CKD. To analyze data heterogeneity, the I2 statistical test was used. Statistical analysis was performed with R version 4.2.3.ResultsA total of 1425 studies were retrieved, of which 23 were included in the final meta-analysis. A total of 43,321 patients with CKD were evaluated, of whom 52.22% were male and 47.78% were female. The combined prevalence of HTN in Peruvian patients with CKD was 38% (95% CI: 30–46%; 41,131 participants; 21 studies, I2 = 99%, p = 0), while the combined prevalence of DM in Peruvian patients with CKD was 33% (95% CI: 26–40%; 43,321 participants; 23 studies, I2 = 99%, p = 0).ConclusionApproximately one-third of Peruvian patients with CKD have HTN and DM. These findings highlight the importance of implementing prevention and control measures for these chronic noncommunicable diseases in the Peruvian population, such as promoting healthy lifestyles, encouraging early detection and proper management of hypertension and diabetes, and improving access to medical care and health services.

Five-Year Cumulative Cardiovascular Health and Clinical Events in Patients With Chronic Kidney Disease: The CRIC Study.

Higher cardiovascular health (CVH) score is associated with lower risks of cardiovascular disease (CVD) and mortality in the general population. However, it is unclear whether cumulative CVH is associated with CVD, end-stage kidney disease (ESKD), and death in patients with chronic kidney disease. Among individuals from the prospective CRIC (Chronic Renal Insufficiency Cohort) Study, we used the percentage of the maximum possible CVH score attained from baseline to the year 5 visit to calculate cumulative CVH score. Multivariable-adjusted Cox proportional hazards regression was used to investigate the associations of cumulative CVH with risks of adjudicated CVD (myocardial infarction, stroke, and heart failure), ESKD, and all-cause mortality. A total of 3939 participants (mean age, 57.7 years; 54.9% men) were included. The mean (SD) cumulative CVH score attained during 5 years was 55.5% (12.3%). Over a subsequent median 10.2-year follow-up, 597 participants developed CVD, 656 had ESKD, and 1324 died. A higher cumulative CVH score was significantly associated with lower risks of CVD, ESKD, and mortality, independent of the CVH score at year 5. Multivariable-adjusted hazard ratios and 95% CIs per 10% higher cumulative CVH score during 5 years were 0.81 (0.69-0.95) for CVD, 0.82 (0.70-0.97) for ESKD, and 0.80 (0.72-0.89) for mortality. Among patients with chronic kidney disease stages 2 to 4, a better CVH status maintained throughout 5 years is associated with lower risks of CVD, ESKD, and all-cause mortality. The findings support the need for interventions to maintain ideal CVH status for prevention of adverse outcomes in the population with chronic kidney disease.

Kidney Measurement and Glomerular Filtration Rate Evolution in Children with Polycystic Kidney Disease

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder characterized by renal tubular cystic dilatations. The cysts can develop anywhere along the nephron, and over time the cystic dilatation leads to kidney enlargement. On the other hand, the cysts begin to reduce the number of functional nephrons as a consequence of cystic expansion that further contributes to the decline in renal function over the years. The pressure exerted by the dilated cysts leads to compensatory mechanisms that further contribute to the decline in renal function. These structural changes are responsible of glomerular hyperfiltration states, albuminuria, proteinuria, and hematuria. However, the presentation of ADPKD varies in children, from a completely asymptomatic child with incidental ultrasound detection of cysts to a rapidly progressive disease. There have been reports of early onset ADPKD in children younger than 2 years that showed a more rapid decline in renal function. ADPKD is caused by a mutation in PKD1 and PKD2 genes. Today, the PKD1 gene mutation seems to account for up to 85% of the cases worldwide, and it is associated with worse renal outcomes. Individuals with PKD2 gene mutation seem to present a milder form of the disease, with a more delayed onset of end-stage kidney disease. The cardinal sign of ADPKD is the presence of renal cysts during renal ultrasound. The current guidelines provide clinicians the recommendations for genetic testing in children with a positive family history. Given that the vast majority of children with ADPKD present with normal or supra-normal kidney function, we explored the glomerular filtration rates dynamics and the renal ultrasound-adjusted percentiles. In total, 14 out of 16 patients had kidney percentiles over 90%. The gene mutations were equally distributed among our cohort. In addition, we compared the modified Schwartz formula to the quadratic equation after adjusting the serum creatinine measurements. It seems that even though children with ADPKD have enlarged kidneys, the renal function is more likely normal or near normal when the quadratic estimation of glomerular filtration rate is used (qGFR tended to be lower, 111.95 ± 12.43 mL/min/1.73 m2 when compared to Schwartz eGFR 126.28 ± 33.07 mL/min/1.73 m2, p = 0.14). Also, when the quadratic equation was employed, not even a single patient reached the glomerular hyperfiltration threshold. The quadratic formula showed that glomerular filtration rates are linear or slightly decreasing after 1 year of follow-up (quadratic ΔeGFR = −0.32 ± 5.78 mL/min/1.73 m2), as opposed to the Schwartz formula that can falsely classify children in a hyperfiltration state (ΔeGFR = 7.51 ± 19.46 mL/min/1.73 m2), p = 0.019.

Association of the systemic immune-inflammation index with anemia: a population-based study

BackgroundInflammation has been reported to be related to anemia. As a novel inflammatory marker, Systemic immune-inflammation index (SII) has not been studied with Anemia. The aim of this study was to investigate the possible relationship between SII and anemia.MethodsThis retrospective cross-sectional survey was conducted using data from the 2005–2018 National Health and Nutrition Examination Survey (NHANES) population. In total, 19851 American adults aged ≥18 years were included. SII was calculated as the platelet count×neutrophil count/lymphocyte count. Anemia was defined as hemoglobin (Hgb) levels of < 13 g/dL in males and < 12 g/dL in females. Logistic regression analyses, subgroup analyses and sensitivity analyses were performed to investigate the relationship between SII and anemia.ResultsOur study included a total of 19851 patients, of which 1501 (7.6%) had anemia. After adjusting for all covariates, the multivariate logistic regression analysis showed that a higher SII (In-transform) level was associated with increased likelihood of anemia (OR=1.51, 95% CI: 1.36–1.68, P<0.001). The association between SII and anemia exhibited a nonlinear manner. The positive correlation between SII and anemia was related to the severity of anemia. Subgroup analysis showed that there was no significant dependence on age, family income, body mass index, hypertension, kidney disease and cancer except gender on this positive association. Furthermore, sensitivity analyses confirmed the robustness of our results.ConclusionOur study demonstrated that SII was positively associated with anemia especially among female participants. And this positive correlation was related to the severity of anemia. Further large-scale prospective studies are still needed to analyze the role of SII in anemia.

Pharmacological action of epoetin beta in the treatment of anemia in patients with kidney diseases

Pharmacological action of epoetin beta in the treatment of anemia in patients with kidney diseases

First episode of febrile urinary tractinfection in children, detection and risk factors of kidney scarring: Aprospective cohort study.

This prospective study aimed to evaluate the characteristics and findings of children who presented with acute pyelonephritis (APN) and to determine the independent risk factors for kidney scarring. Patients who satisfied the following criteria were enrolled in the study: first known episode of APN; at least two of the following findings: fever ≥ 38.5 °C, white blood cell count ≥ 10,000/mm3, erythrocyte sedimentation rate ≥ 20 mm/h, C-reactive protein ≥ 20 mg/dL; absence of congenital abnormalities or other kidney and systemic diseases, except vesicoureteral reflux (VUR); no APN relapses until the time of kidney scar detection. 99mTc-Dimercaptosuccinic acid kidney scintigraphy (99mTc-DMSA) was performed at admission, along with a kidney ultrasound. Follow-up 99mTc-DMSA took place after 6 months. Radiographic cystourethrography for VUR detection and grading was performed 1 month after the acute infection. We enrolled 70 children in the study. The kidney ultrasound failed to diagnose more than half of the cases of APN. VUR was found in 21.5% of children. 75% had findings of APN in the acute phase through 99mTc-DMSA, while in the second 99mTc-DMSA, there was a complete remission in 68% of them. Scars were observed more frequently in older children, children with VUR grade ≥ III, and children not on antibiotic prophylaxis. VUR did not appear to be associated with the first episode of APN, and children older than 1 year of age had a higher risk of scarring. Antibiotic prophylaxis may prevent kidney scarring due to host immunomodulatory effects, but more studies are needed so that conclusions can be drawn.

Metabolic Acidosis in CKD: Pathogenesis, Adverse Effects, and Treatment Effects

Metabolic acidosis is a frequent complication of chronic kidney disease and is associated with a number of adverse outcomes, including worsening kidney function, poor musculoskeletal health, cardiovascular events, and death. Mechanisms that prevent metabolic acidosis detrimentally promote further kidney damage, creating a cycle between acid accumulation and acid-mediated kidney injury. Disrupting this cycle through the provision of alkali, most commonly using sodium bicarbonate, is hypothesized to preserve kidney function while also mitigating adverse effects of excess acid on bone and muscle. However, results from clinical trials have been conflicting. There is also significant interest to determine whether sodium bicarbonate might improve patient outcomes for those who do not have overt metabolic acidosis. Such individuals are hypothesized to be experiencing acid-mediated organ damage despite having a normal serum bicarbonate concentration, a state often referred to as subclinical metabolic acidosis. Results from small- to medium-sized trials in individuals with subclinical metabolic acidosis have also been inconclusive. Well-powered clinical trials to determine the efficacy and safety of sodium bicarbonate are necessary to determine if this intervention improves patient outcomes.

The atypical chemokine receptor 2 reduces T cell expansion and tertiary lymphoid tissue but does not limit autoimmune organ injury in lupus-prone B6lpr mice

IntroductionThe atypical chemokine receptor 2 (ACKR2) is a chemokine scavenger receptor, which limits inflammation and organ damage in several experimental disease models including kidney diseases. However, potential roles of ACKR2 in reducing inflammation and tissue injury in autoimmune disorders like systemic lupus erythematosus (SLE) and lupus nephritis are unknown, as well as its effects on systemic autoimmunity. MethodsTo characterize functional roles of ACKR2 in SLE, genetic Ackr2 deficiency was introduced into lupus-prone C57BL/6lpr (Ackr2-/- B6lpr) mice. ResultsUpon inflammatory stimulation in vitro, secreted chemokine levels increased in Ackr2 deficient tubulointerstitial tissue but not glomeruli. Moreover, Ackr2 expression was induced in kidneys and lungs of female C57BL/6lpr mice developing SLE. However, female Ackr2-/- B6lpr mice at 28 weeks of age showed similar renal functional parameters as wildtype (WT)-B6lpr mice. Consistently, assessment of activity and chronicity indices for lupus nephritis revealed comparable renal injury. Interestingly, Ackr2-/- B6lpr mice showed significantly increased renal infiltrates of CD3+ T and B cells, but not neutrophils, macrophages or dendritic cells, with T cells predominantly accumulating in the tubulointerstitial compartment of Ackr2-/- B6lpr mice. In addition, histology demonstrated significantly increased peribronchial lung infiltrates of CD3+ T cells in Ackr2-/- B6lpr mice. Despite this, protein levels of pro-inflammatory chemokines and mRNA expression of inflammatory mediators were not different in kidneys and lungs of WT- and Ackr2-/- B6lpr mice. This data suggests compensatory mechanisms for sufficient chemokine clearance in Ackr2-deficient B6lpr mice in vivo. Analysis of systemic autoimmune responses revealed comparable levels of circulating lupus-associated autoantibodies and glomerular immunoglobulin deposition in the two genotypes. Interestingly, similar to kidney and lung CD4+ T cell numbers and activation were significantly increased in spleens of Ackr2-deficient B6lpr mice. In lymph nodes of Ackr2-/- B6lpr mice abundance of activated dendritic cells decreased, but CD4+ T cell numbers were comparable to WT. Moreover, increased plasma levels of CCL2 were present in Ackr2-/- B6lpr mice, which may facilitate T cell mobilization into spleens and peripheral organs. DiscussionIn summary, we show that ACKR2 prevents expansion of T cells and formation of tertiary lymphoid tissue, but is not essential to limit autoimmune tissue injury in lupus-prone B6lpr mice.