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BMC Nephrology May 2024Protein carbamylation, a post-translational protein modification primarily driven by urea, independently associates with adverse clinical outcomes in patients with CKD.... (Comparative Study)
Comparative Study
BACKGROUND
Protein carbamylation, a post-translational protein modification primarily driven by urea, independently associates with adverse clinical outcomes in patients with CKD. Biomarkers used to quantify carbamylation burden have mainly included carbamylated albumin (C-Alb) and homocitrulline (HCit, carbamylated lysine). In this study, we aimed to compare the prognostic utility of these two markers in order to facilitate comparisons of existing studies employing either marker alone, and to inform future carbamylation studies.
METHODS
Both serum C-Alb and free HCit levels were assayed from the same timepoint in 1632 individuals with CKD stages 2-4 enrolled in the prospective Chronic Renal Insufficiency Cohort (CRIC) study. Adjusted Cox proportional hazard models were used to assess risks for the outcomes of death (primary) and end stage kidney disease (ESKD) using each marker. C-statistics, net reclassification improvement, and integrated discrimination improvement were used to compare the prognostic value of each marker.
RESULTS
Participant demographics included mean (SD) age 59 (11) years; 702 (43%) females; 700 (43%) white. C-Alb and HCit levels were positively correlated with one another (Pearson correlation coefficient 0.64). Higher C-Alb and HCit levels showed similar increased risk of death (e.g., the adjusted hazard ratio [HR] for death in the 4th carbamylation quartile compared to the 1st was 1.90 (95% confidence interval [CI] 1.35-2.66) for C-Alb, and 1.89 [1.27-2.81] for HCit; and on a continuous scale, the adjusted HR for death using C-Alb was 1.24 [1.11 to 1.39] per standard deviation increase, and 1.27 [1.10-1.46] using HCit). Both biomarkers also had similar HRs for ESKD. The C-statistics were similar when adding each carbamylation biomarker to base models (e.g., for mortality models, the C-statistic was 0.725 [0.707-0.743] with C-Alb and 0.725 [0.707-0.743] with HCit, both compared to a base model 0.723). Similarities were also observed for the net reclassification improvement and integrated discrimination improvement metrics.
CONCLUSIONS
C-Alb and HCit had similar performance across multiple prognostic assessments. The markers appear readily comparable in CKD epidemiological studies.
Topics: Humans; Female; Citrulline; Male; Protein Carbamylation; Biomarkers; Middle Aged; Renal Insufficiency, Chronic; Aged; Prospective Studies; Risk Assessment; Kidney Failure, Chronic; Prognosis; Proportional Hazards Models; Serum Albumin
PubMed: 38816682
DOI: 10.1186/s12882-024-03619-6 -
BMJ Open Diabetes Research & Care May 2024We compared the kidney outcomes between patients with diabetic kidney disease (DKD) aged ≥75 years initiating sodium-glucose cotransporter 2 (SGLT2) inhibitors versus...
INTRODUCTION
We compared the kidney outcomes between patients with diabetic kidney disease (DKD) aged ≥75 years initiating sodium-glucose cotransporter 2 (SGLT2) inhibitors versus other glucose-lowering drugs, additionally presenting with or without proteinuria.
RESEARCH DESIGN AND METHODS
Using the Japan Chronic Kidney Disease Database, we developed propensity scores, implementing a 1:1 matching protocol. The primary outcome included the decline rate in estimated glomerular filtration rate (eGFR), and secondary outcomes incorporated a composite of a 40% reduction in eGFR or progression to end-stage kidney disease.
RESULTS
At baseline, the mean age at initiation of SGLT2 inhibitors (n=348) or other glucose-lowering medications (n=348) was 77.7 years. The mean eGFR was 59.3 mL/min/1.73m and proteinuria was 230 (33.0%) patients. Throughout the follow-up period, the mean annual rate of eGFR change was -0.80 mL/min/1.73 m/year (95% CI -1.05 to -0.54) among SGLT2 inhibitors group and -1.78 mL/min/1.73 m/year (95% CI -2.08 to -1.49) in other glucose-lowering drugs group (difference in the rate of eGFR decline between the groups was 0.99 mL/min/1.73 m/year (95% CI 0.5 to 1.38)), favoring SGLT2 inhibitors (p<0.001). Composite renal outcomes were observed 38 in the SGLT2 inhibitors group and 57 in the other glucose-lowering medications group (HR 0.64, 95% CI 0.42 to 0.97). There was no evidence of an interaction between SGLT2 inhibitors initiation and proteinuria.
CONCLUSIONS
The benefits of SGLT2 inhibitors on renal outcomes are also applicable to older patients with DKD aged≥75 years.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Female; Male; Aged; Japan; Glomerular Filtration Rate; Diabetic Nephropathies; Databases, Factual; Renal Insufficiency, Chronic; Aged, 80 and over; Diabetes Mellitus, Type 2; Follow-Up Studies; Disease Progression; Hypoglycemic Agents; Prognosis; Treatment Outcome
PubMed: 38816204
DOI: 10.1136/bmjdrc-2024-004115 -
Kidney360 May 2024
Topics: Humans; Acute Kidney Injury; Sepsis; Oliguria; Male; Kidney; Recovery of Function; Middle Aged
PubMed: 38814758
DOI: 10.34067/KID.0000000000000444 -
Kidney360 May 2024
Topics: Humans; Pancreatitis, Chronic; Renal Insufficiency; Male; Aged; Disease Progression; Female
PubMed: 38814757
DOI: 10.34067/KID.0000000000000402 -
Deutsches Arzteblatt International Jul 2024Chronic renal insufficiency (CRI) is becoming more common and has an increasing impact on public health. In Germany, approximately one in ten adults has CRI. Its most... (Review)
Review
BACKGROUND
Chronic renal insufficiency (CRI) is becoming more common and has an increasing impact on public health. In Germany, approximately one in ten adults has CRI. Its most serious consequence is generally not the development of end-stage renal failure, but rather the markedly increased cardiovascular risk as kidney function declines.
METHODS
This review is based on the findings of a selective search in PubMed for literature about the treatment options for CRI, and on our overview of the existing guideline recommendations on diagnostic testing.
RESULTS
Patients with diabetes mellitus and arterial hypertension are at especially high risk of developing CRI. For these patients, some of the guidelines recommend regular testing for albuminuria and measurement of the glomerular filtration rate (GFR), though sometimes only when specific risk constellations are present. The treatment of CRI has evolved in recent years. At first, aside from general measures, only RAS inhibitors were available as a specific therapy for CRI. With the extension of the approval of SGLT-2 inhibitors to non-diabetic CRI patients, the options for treatment have become wider. Two randomized controlled trials have revealed the benefit of SGLT-2 inhibitors with respect to their respective primary endpoints: time to a specified eGFR reduction and renal/cardiovascular death (HR 0.61 [0.51; 0.72] and 0.72 [0.64; 0.82]). The potential side effects and contraindications of SGLT-2 inhibitors must be taken into account. A further treatment option for diabetics with CRI has become available with the approval of the non-steroidal mineralocorticoid receptor antagonist finerenone.
CONCLUSION
In patients with risk factors, renal function should be regularly tested.
PubMed: 38814568
DOI: 10.3238/arztebl.m2024.0072 -
The Turkish Journal of Pediatrics May 2024Hemolytic uremic syndrome (HUS) is a serious cause of acute kidney injury in children. There is a suggestion that coronavirus disease 2019 (COVID-19) may be a trigger...
BACKGROUND
Hemolytic uremic syndrome (HUS) is a serious cause of acute kidney injury in children. There is a suggestion that coronavirus disease 2019 (COVID-19) may be a trigger for HUS. In this study, we present a pediatric case diagnosed with HUS associated with COVID-19, which progressed to end-stage kidney disease.
CASE
A previously healthy 13-year-old girl with fever and vomiting was referred to our hospital. Laboratory investigations revealed direct Coombs-negative hemolytic anemia, thrombocytopenia and renal impairment accompanied by COVID-19 infection. Although anemia and thrombocytopenia showed improvement on the seventh day after admission, the renal impairment persisted. The histopathological findings of a renal biopsy were compatible with both HUS and COVID-19. One month later, the patient had a recurrence of HUS, again testing positive for COVID-19. Kidney function improved with plasma exchange therapy. Eculizumab treatment was recommenced after COVID-19 PCR became negative. Anemia and thrombocytopenia did not recur with eculizumab, while renal impairment persisted. Eculizumab was discontinued after three months when genetic analysis for HUS was negative. Subsequently, the patient was diagnosed with end-stage kidney disease.
CONCLUSIONS
COVID-19 can be associated with HUS relapses, leading to chronic kidney disease. Further studies should investigate the mechanism of HUS associated with COVID-19.
Topics: Humans; COVID-19; Female; Adolescent; Hemolytic-Uremic Syndrome; Kidney Failure, Chronic; Disease Progression; SARS-CoV-2
PubMed: 38814305
DOI: 10.24953/turkjpediatr.2024.4524 -
Turkish Journal of Medical Sciences 2023There are over 60,000 hemodialysis (HD) patients in Türkiye, and the number of patients is increasing yearly. Dialysate flow rate (Qd) is a factor in HD adequacy....
BACKGROUND AND AIM
There are over 60,000 hemodialysis (HD) patients in Türkiye, and the number of patients is increasing yearly. Dialysate flow rate (Qd) is a factor in HD adequacy. Approximately 150 L of water are consumed per session to prepare the dialysate. We aimed to investigate whether HD effectiveness can be achieved at a low Qd in different patient groups for the purpose of saving water.
MATERIALS AND METHODS
This prospective study included 81 HD patients from 2 centers. The patients underwent an aggregate total of 486 HD sessions, including 3 sessions at a Qd of 500 mL/min and 3 sessions at a Qd of 300 mL/min for each patient. We used online Kt/V readings recorded at the end of each dialysis session to compare the effectiveness of these 2 types of HD session performed at a different Qd.
RESULTS
The online Kt/V readings were similar between the standard (500) and low (300) Qd HD (1.51 ± 0.41 and 1.49 ± 0.44, respectively, p = 0.069). In the subgroup analyses, men had higher online Kt/V values at the standard Qd compared to the low Qd (1.35 ± 0.30 and 1.30 ± 0.32, respectively, p = 0.019), but the Kt/V values were not different for women. While the low Qd did not reduce online Kt/V in patients using small surface area dialysis membranes (1.75 ± 0.35 for 300 Qd and 1.75 ± 0.32 for 500 Qd, p = 0.931), it was associated with reduced online Kt/V in patients using large surface area dialysis membranes (1.12 ± 0.25 for 300 Qd and 1.17 ± 0.24 for 500 Qd, p = 0.006). The low Qd did not result in differences in online Kt/V among low-weight patients. However, online Kt/V values were better with the standard Qd in patients weighing 65 kg and above.
CONCLUSION
In our study, dialysis adequacy at a reduced dialysate flow was not inferior for women, patients with low body weight, or patients using small surface area membranes. Individualized HD at a reduced Qd of 300 mL/min in eligible patients can save 48 L of water per HD session and an average of 7500 L of water per year.
Topics: Humans; Renal Dialysis; Female; Male; Prospective Studies; Middle Aged; Aged; Water; Adult; Dialysis Solutions; Kidney Failure, Chronic
PubMed: 38813487
DOI: 10.55730/1300-0144.5756 -
Clinical Case Reports Jun 2024We report an observation of a young patient presenting with severe type 1 cryoglobulinemic vasculitis revealing a monoclonal gammopathy of clinical significant....
KEY CLINICAL MESSAGE
We report an observation of a young patient presenting with severe type 1 cryoglobulinemic vasculitis revealing a monoclonal gammopathy of clinical significant. Treatment with Melphalan-Thalidomide Prednisone improved the symptoms. Early diagnosis would prevent serious tissue damage.
ABSTRACT
Monoclonal gammopathy encompass diverse clinical forms. Only the cancerous form, multiple myeloma (MM), is treated based on specific diagnostic criteria. A new clinical entity, monoclonal gammopathy of clinical significance (MGCS), warrants special attention due to its need for specific treatment. It involves patients with signs of potentially severe organ involvement that do not meet MM criteria. We present the case of a 34-year-old Malagasy woman with severe type I cryoglobulinemic vasculitis associated with noncancerous monoclonal gammopathy, showing a favorable outcome after treatment with Thalidomide. Symptoms included toe necrosis, a severe ulcer on the left calf evolving for 3 months, and stocking-like dysesthesias. Investigations revealed monoclonal gammopathy at 30.1 g/L, proteinuria at 1 g/24 h, medullary plasma cell at 6%, and circulating cryoglobulin of Ig kappa type. CRAB criteria (anemia, hypercalcemia, renal insufficiency, and osteolysis) were absent. Treatment with Thalidomide, combined with corticosteroids and local care for 4 months, resulted in ulcer healing, disappearance of dysesthesias, and persistent normalization of gammaglobulin. Our case underscores the importance of specific treatment for MGCS.
PubMed: 38813450
DOI: 10.1002/ccr3.8897 -
Frontiers in Endocrinology 2024Chronic kidney disease (CKD) is a common complication among individuals with hypertension. We aimed to identify the prevalence of CKD and the sex and race disparities...
BACKGROUND
Chronic kidney disease (CKD) is a common complication among individuals with hypertension. We aimed to identify the prevalence of CKD and the sex and race disparities within the hypertensive population in the United States from 2001-2016.
METHODS
A total of 16,148 participants with hypertension were included, representing 561,909,480 individuals from the U.S. population between 2001 and 2016, as documented in the National Health and Nutrition Examination Survey. The prevalence of albuminuria and CKD stage were assessed using survey-weighted general linear regression analysis. Heterogeneity in the CKD stage among the hypertensive population, stratified by sex and race, was identified through survey-weighted logistic regression analysis.
RESULTS
Overall, the prevalence of albuminuria remained stable (p for trend = 0.3196), and changes in the CKD stage were minimal (p for trend > 0.05) from 2001-2016. In the analysis of CKD stage heterogeneity by sex and race, the prevalence of CKD was higher among women than men and higher among individuals of other races combined than non-Hispanic Whites, but the differences were not statistically significant.
CONCLUSION
The overall CKD stage within the hypertensive population plateaued between 2001 and 2016. Our findings highlight the importance of continuous monitoring and potential refinement of renoprotection strategies in individuals with hypertension to mitigate the persistent burden of CKD and address health disparities among different demographic groups.
Topics: Humans; Male; Female; Renal Insufficiency, Chronic; Hypertension; United States; Prevalence; Middle Aged; Adult; Nutrition Surveys; Aged; Sex Factors; Racial Groups; Health Status Disparities
PubMed: 38812816
DOI: 10.3389/fendo.2024.1378631 -
Frontiers in Bioscience (Landmark... May 2024Chronic kidney disease (CKD) is a disorder that causes changes in both the structure and function of the kidneys, causing complications such as hypertension, edema, and... (Review)
Review
Chronic kidney disease (CKD) is a disorder that causes changes in both the structure and function of the kidneys, causing complications such as hypertension, edema, and oliguria. Renal fibrosis is also a common pathological feature of CKD. Matrix metalloproteinases (MMPs) are endopeptidases that degrade extracellular matrix (ECM) proteins. The proteinase domain consists of a zinc ion in the active site, which contributes to its stabilization with another zinc and three calcium structural ions. Many cellular processes are controlled by MMPs, such as cell-cell interactions and various signaling pathways, while they are also involved in degrading substrates on cell surfaces. Tissue inhibitors of metalloproteinases (TIMPs) are key regulators of metalloproteinases, and both are involved in regulating cell turnover, the regulation, and the progression of fibrosis and apoptosis in the tissue. MMPs play a role in renal fibrosis, such as the tubular cell epithelial-mesenchymal transition (TEM), activation of resident fibroblasts, endothelial-mesenchymal transition (EndoMT), and pericyte-myofibroblast transdifferentiation. This review aims to show the mechanisms through which MMPs contribute to renal fibrosis, paying particular attention to MMP-9 and the epithelial-mesenchymal transition.
Topics: Humans; Fibrosis; Epithelial-Mesenchymal Transition; Matrix Metalloproteinases; Kidney; Animals; Renal Insufficiency, Chronic; Matrix Metalloproteinase 9; Kidney Diseases
PubMed: 38812325
DOI: 10.31083/j.fbl2905192