期刊,Nephron 2022年146卷5期_国家学术搜索

期刊信息/Journal information

Nephron

S. Karger

主办单位：S. Karger

国际刊号：0028-2766

Nephron/Journal NephronSCIISTP

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Stage at Diagnosis and Prognosis of Colorectal, Stomach, Lung, Liver, Kidney, and Bladder Cancers in Dialysis Patients: A Multicenter Retrospective Study Using Cancer Registry Data and Administrative Data

Nanami KidaToshitaka MorishimaYoshiharu TsubakiharaIsao Miyashiro...

10页

查看更多>>摘要：Background: Cancer is an important comorbidity that can affect survival in dialysis patients. However, it is unclear if dialysis patients who develop cancer are disadvantaged by later detection and poorer prognosis. This study comparatively examined the stage at diagnosis and prognosis of several common cancer types in dialysis and nondialysis patients. Methods: In this retrospective cohort study, cancer registry data were linked with administrative data to identify dialysis and nondialysis patients with any new diagnosis of cancer between 2010 and 2015 at 36 hospitals in Osaka Prefecture, Japan. In these patients, we identified the cancer stage at diagnosis for patients with colorectal, stomach, lung, liver, kidney, and bladder cancers. The association between dialysis and survival time (up to 3 years of follow-up) was examined for each cancer type using Cox proportional hazards models that adjusted for age, sex, and cancer stage. Results: We analyzed 2,161 dialysis patients and 158,964 nondialysis patients with cancer. Dialysis patients had a higher prevalence of colorectal, liver, and kidney cancers than nondialysis patients. Colorectal, stomach, lung, liver, and kidney cancers were diagnosed earlier in dialysis patients, whereas bladder cancer was diagnosed at an advanced stage. The Cox proportional hazards models revealed that mortality was significantly higher in dialysis patients with colorectal, stomach, lung, and bladder cancers than in nondialysis patients (all p < 0.05). Conclusions: Dialysis patients had higher mortality for several common cancers despite their earlier detection. This poorer prognosis may be influenced by the unavailability and complications of cancer treatment for these patients.

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Evolution of Quality of Life in Chronic Kidney Disease Stage 4-5 Patients Transitioning to Dialysis and Transplantation

Markus HakamakiMikko J. JarvisaloRoosa LankinenNiina Koivuviita...

10页

查看更多>>摘要：Introduction: Chronic kidney disease (CKD) has a profound effect on patients' health-related quality of life (QoL). Longitudinal studies on QoL in CKD are scarce and have explored selected patients on renal replacement therapy (RRT). We studied the evolution of QoL in patients with advanced CKD transitioning to dialysis and transplantation in a prospective follow-up study. Methods: A total of 100 participants of the Chronic Arterial Disease, Quality of Life, and Mortality in Chronic Kidney Injury (CADKID) study were enrolled in the study. Kidney Disease Quality of Life Short Form, biochemistry, and echocardiography were obtained at baseline and after a median interval of 33 (range 12-85) months. Results: At the time of the follow-up QoL assessment, 32 patients were not receiving RRT, 30 were on hemodialysis (HD), 19 on peritoneal dialysis (PD), and 19 had received a kidney transplant. Among kidney transplant recipients (KTRs), "Burden of Kidney Disease" and "General Health" domains improved compared to patients who initiated HD (p < 0.0001 andp = 0.007, respectively), PD (p = 0.0005 and p = 0.03, respectively), or remained in predialysis care (p = 0.009 and p = 0.003, respectively) while "Effects of Kidney Disease" improved compared to those who started HD (p = 0.004) or PD (p = 0.002). The change in Short Form-36 (SF-36) Physical Component Summary was not different between patients on different treatment modalities. Higher plasma albumin and cholesterol levels were associated with improved QoL in "Symptoms/ Problems" (r=0.28, p = 0.005, and r = 0.30, p = 0.004, respectively) and "Effects of Kidney Disease" (r=0.27,p = 0.008, and r= 0.24,p = 0.03, respectively). Conclusion: QoL improved in KTRs in kidney disease-specific domains compared to patients initiating dialysis or those without RRT. Plasma albumin and lipids were associated with QoL over time.

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Effects of Body Weight Change on Development of Chronic Kidney Disease in Obese Metabolic Phenotypes

AkikoTodaShigeko HaraHiroshiTsujiYasuji Arase...

8页

查看更多>>摘要：Introduction: Obesity is a risk factor for chronic kidney disease (CKD), but whether the reduction of body mass index (BMI) helps prevent CKD is controversial. Recently, obese metabolic phenotypes have raised considerable interest. We thus investigated the effect of BMI change on CKD development. Methods: We analyzed the data of 6,959 subjects who underwent annual health checkups in both 2013 and 2018. The subjects were categorized into five groups according to their BMI percentage change (ΔBMI) and classified into four obese metabolic phenotypes. By a multivariate logistic regression analysis, we investigated the association between BMI change and CKD development within the 5 years. Results: In total subjects, compared with the maintained BMI group (ΔBMI ≥0% but <2.5%), the odd ratios (ORs) and 95% confidence intervals (CIs) of CKD development were 0.70 (95% CI 0.54-0.91) for the severe BMI decrease group (ΔBMI <-2.5%), and 1.40 (95% CI 1.08-1.81) for the severe BMI increase group (ΔBMI ≥5%). In the metabolically healthy obese (MHO) phenotype, the risks of CKD development were significantly higher in the moderate BMI increase group (ΔBMI ≥2.5% but <5%) (OR 3.04,95% CI 1.19-7.78) and a severe BMI increase group (OR 2.88, 95% CI 1.13-7.35). Regarding the metabolically unhealthy nonobese (MUNO) phenotype, the risks of CKD development were significantly lower in the severe BMI decrease group (OR 0.43,95% CI 0.25-0.74) and the moderate BMI decrease group (ΔBMI ≥-2.5% but <0%) (OR 0.58, 95% CI 0.35-0.98). Conclusions: In the MHO phenotype, an increased BMI deteriorated CKD development, and a decreased BMI ameliorated CKD development in the MUNO phenotype.

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Association of Serum Triglycerides and Renal Outcomes among 1.6 Million US Veterans

Leila HashemiMelissa SoohooJui-Ting HsiungHamid Moradi...

12页

查看更多>>摘要：Background: Previous studies have suggested that metabolic syndrome (MetS) components are associated with renal outcomes, defined as a decline in kidney function or reaching end-stage renal disease (ESRD). Elevated triglycerides (TGs) are a component of MetS that have been reported to be associated with renal outcomes. However, the association of TGs with renal outcomes in chronic kidney disease (CKD) patients independent of the other components of the MetS remains understudied. Methods: We examined 1,657,387 patients with data on TGs and other components of MetS in 2004-2006 and followed up until 2014. Patients with ESRD on renal replacement therapy were excluded. We examined time to ESRD, estimated glomerular filtration rate (eGFR) slope (renal function decline), and time to incident CKD (eGFR <60 mL/min/1.73 m~2) among baseline normal kidney function (non-CKD) patients, using Cox or logistic regression, adjusted for clinical characteristics and MetS components. We also stratified analyses by the number of MetS components. Results: The cohort was on average 64 years old and comprised 5% females, 15% African Americans, and 24% with nondialysis-dependent CKD. Among non-CKD patients, the adjusted relationship of TGs with time to incident CKD was strong and linear. Compared to TGs 120-<160 mg/ dL, higher TGs were associated with a faster renal function decline across all CKD stages. Elevated TGs ≥240 mg/dL were associated with a faster time to ESRD among non-CKD and CKD stages 3A-3B, while the risk gradually declined to null or lower in CKD stages 4-5. Models were robust after MetS component adjustment and stratification. Conclusion: Independent of MetS components, high TGs levels were associated with a higher incidence of CKD and a faster renal function decline, yet showed no or inverse associations with time to ESRD in CKD stages 4-5. Examining the effects of TGs-low-ering interventions on incident CKD and kidney preserving therapy warrants further studies including clinical trials.

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Comparison of Outcomes of In-Centre Haemodialysis Patients between the 1st and 2nd COVID-19 Outbreak in England, Wales, and Northern Ireland: A UK Renal Registry Analysis

Bhakti S.S. OnggoKatharine M. EvansJames F. MedcalfDorothea Nitsch...

12页

查看更多>>摘要：Introduction: This retrospective cohort study compares in-centre haemodialysis (ICHD) patients' outcomes between the 1st and 2nd waves of the COVID-19 pandemic in England, Wales, and Northern Ireland. Methods: All people aged ≥18 years receiving ICHD at 31 December 2019, who were still alive and not in receipt of a kidney transplant at 1 March and who had a positive polymerase chain reaction test for SARS-CoV-2 between 1 March 2020 and 31 January 2021, were included. The COVID-19 infections were split into two "waves": wave 1 from March to August 2020 and wave 2 from September 2020 to January 2021. Cumulative incidence of COVID-19, multivariableCox models for risk of positivity, median, and 95% credible interval of reproduction number in dialysis units were calculated separately for wave 1 and wave 2. Survival and hazard ratios for mortality were described with age- and sex-adjusted Kaplan-Meier plots and multivariable Cox proportional models. Results: 4,408 ICHD patients had COVID-19 during the study period. Unadjusted survival at 28 days was similar in both waves (wave 1 75.6% [95% confidence interval [CI]: 73.7-77.5], wave 2 76.3% [95% CI 74.3-78.2]), but death occurred more rapidly after detected infection in wave 1. Long vintage treatment and not being on the transplant waiting list were associated with higher mortality in both waves. Conclusions: Risk of death of patients on ICHD treatment with COVID-19 remained unchanged between the first and second outbreaks.This highlights that this vulnerable patient group needs to be prioritized for interventions to prevent severe COVID-19, including vaccination, and the implementation of measures to reduce the risk of transmission alone is not sufficient.

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Renal Involvement in Transthyretin Amyloidosis: The Double Presentation of Transthyretin Amyloidosis Deposition Disease

Roberta FenoglioSimone BaldovinoAntonella BarrecaEmanuel Bottasso...

8页

查看更多>>摘要：Transthyretin (TTR) amyloidosis (ATTR) is either an inherited condition or a non hereditary disease due to misfolding of wild-type (WT) TTR. Amyloid deposits can be mainly detected in nerves in the inherited form and in myocardium in the acquired variant. Renal involvement has been described only in the Val30Met mutation of the familial form and is thought to be extremely rare in the WT TTR. However, ATTR is multi-organ disease, and even in the WT forms, apparently limited to the heart, carpal tunnel syndrome and lumbar or cervical spine amyloid deposition have been described. A series of 4 cases of biopsy-proven renaI TTR amyloid deposition is reported in the present paper. We describe 2 WT ATTR patients, 1 patient with c.424G>A (p.(Val142lle)) mutation of the TTR gene, and 1 patient with Val30Met mutation of the TTR gene. In all patients, the biopsy showed the presence of amyloid deposits with different distribution (#1 pericapsu-lar, #2-3 vessels, #4 vessels, interstitium of medulla and cortex, and tubular basement membrane). The use of immuno-histochemistry has enabled the identification of TTR, and identify the precursor protein. The possibility of kidney involvement in TTR amyloidosis should be taken into account in patients with renal impairment and unexplained cardio-myopathy and/or neuropathy.This is even of greater interest to the elderly for the possible confounding co-existence of plasma cell dyscrasia that could lead the clinician, in the presence of renal amyloid deposits, to misdiagnose AL amyloidosis and undertake inappropriate treatments.

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Hemolytic Uremic Syndrome Associated with Norovirus Gastroenteritis: Case Report and Literature Review

Neslihan YilmazSelcukYuksel

5页

查看更多>>摘要：A previously healthy 3-year-old girl was admitted with fever, nonbloody diarrhea, vomiting for 3 days, and oliguria. Physical examination showed fatigue, pale appearance, hypertension, and mild periorbital edema. Laboratory examinations revealed anemia, thrombocytopenia, acute kidney injury, high LDH,and low haptoglobin levels. Urinalysis showed proteinuria and hematuria. Schistocytes and helmet cells were detected in the peripheral blood smear. There were no electrolyte imbalance and hypocomplementemia. Direct Coombs and viral panel were negative. Blood, urine, throat, and stool cultures were negative. Norovirus Gil was positive in stool PCR, while other diarrheal agents were negative. The patient was diagnosed with norovirus gastroenteritis-induced hemolytic uremic syndrome (HUS). Furosemide was started for oliguria and hypertension, and blood pressure was controlled with oral nifedipine. On the 12th day of hos-pitalization, he was discharged with fully recover. To date, norovirus-associated HUS has been reported in 5 cases. Two of these are adult cases and the other three and our case are pediatric patients. In this case report and literature review, we observed that norovirus can cause HUS, especially in children, with a milder course than other types of HUS. The reason why it is more complicated in adult cases may be the presence of an additional underlying kidney disease. Since it was detected coincidentally in 1 case in the literature, it may be useful to screen for mutations in the complement pathway that may cause aHUS, if possible, in diarrhea-associated HUS caused by norovirus agents, but it was not present in our case.

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The Proximal Tubule as the Pathogenic and Therapeutic Target in Acute Kidney Injury

Kwok M.HoDavid J.R.Morgan

9页

查看更多>>摘要：Background: In 2004, the term acute kidney injury (AKI) was introduced with the intention of broadening our understanding of rapid declines in renal function and to replace the historical terms of acute renal failure and acute tubular necrosis (ATN). Despite this evolution in terminology, the mechanisms of AKI have stayed largely elusive with the pathophysiological concepts of ATN remaining the mainstay in our understanding of AKI. Summary: The proximal tubule (PT), having the highest mitochondrial content in the kidney and relying heavily on oxidative phosphorylation to generate ATP, is vulnerable to ischaemic insults and mitochondrial dysfunction. Histologically, pathological changes in the PT are more consistent than changes to the glomeruli or the loop of Henle in AKI. Physiologically, activation of tubuloglo-merular feedback due to PT dysfunction leads to an increase in preglomerular afferent arteriole resistance and a reduction in glomerular filtration. Pharmacologically, frusemide -a drug commonly used in the setting of oliguric AKI - is actively secreted by the PT and its diuretic effect is compromised by its failure to be secreted into the urine and thus be delivered to its site of action at the loop of Henle in AKI. Increases in the urinary, but not plasma biomarkers, of PT injury within 1 h of shock suggest that the PT as the initiation pathogenic target of AKI. Key Message: Therapeutic agents targeting specifically the PT epithelial cells, in particular its mitochondria - including amino acid ergothioneine and su-peroxide scavenger MitoTEMPO - show great promises in ameliorating AKI.

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Drug Testing for Chronic Kidney Disease and Diabetes in Animals versus Humans: A Comparative Analysis of Study Designs and Reporting Qualities

Valentin KonnManga MotrapuMonika Katarzyna SwiderskaHans-Joachim Anders...

11页

查看更多>>摘要：Introduction: Diabetes is a highly prevalent accelerator or even cause of chronic kidney disease imposing a large unmet medical need at the global scale. Massive research activities continue to be in search of a cure but the yield of the classical bench-to-bedside research approach has been low. We speculated that a significant mismatch in design and quality of animal and clinical studies in this domain is a hurdle for translation. Methods: We performed a meta-analysis of matched pairs of animal and human studies that tested the efficacy of distinctdrug interventionsfordiabetic kidney disease (DKD). We reviewed study designs and reporting quality of such studies over the last decade according to the standards listed in the CONSORT and ARRIVE recommendations, respectively. Results: We noted a wide diversity in the study designs of animal studies in terms of diabetes induction. Major mismatches with the respective human studies referred to age and sex distribution, comorbidities, stage of the kidney disease, and selection of primary endpoints. Usually, treatment was initiated before onset of kidney disease without any standard of care as a background therapy. The reporting quality of animal studies was poor for randomization procedures, blinding, sample size calculation for a pre-specified primary endpoint or the safety analysis. Reporting quality of clinical studies had deficits in trial design-, recruitment-, allocation-, and outcome-related aspects. Conclusion: Bench-to-bedside translation in the domain of DKD suffers from major deficits in the design of experimental studies in view of the projected clinical trials as well as from significant deficits in the reporting quality in preclinical and Clinical Studies.

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Propofol Disrupts Clear Cell Renal Cell Carcinoma Tumorigenesis by Regulating circFBXW7/miR-942 Axis

Yunfeng HuangYuanbo WuShengqiang Lu

14页

查看更多>>摘要：Background: Propofol is a commonly used intravenous anesthetic and has been found to perform anticancer effects in many cancers. However, the effects and mechanisms of propofol in clear cell renal cell carcinoma (ccRCC) remain largely undefined. Methods: The expression of circular RNA FBXW7 (circFBXW7) and miR-942 was detected by qRT-PCR. Cell proliferation, apoptosis, migration, and invasion capacities were analyzed using cell counting kit-8, colony formation, flow cytometry, and transwell assays, respectively. Western blot was used to detect the expression levels of PCNA, Cleaved-caspase 3 and MMP protein. The bindings between miR-942 and circFBXW7 were verified using RNA pull-down, dual-luciferase reporter, and RIP assays. Xeno-graft tumor analysis was employed to detect tumorigenesis in vivo. Results: Propofol alleviated cell proliferation, migration, invasion, and induced apoptosis in vitro and impeded tumor growth in vivo in ccRCC. Propofol elevated the level of circFBXW7, which knockdown reversed the anticancer effects of propofol on ccRCC cell tumorigenesis. CircFBXW7 directly bound to miR-942, and suppressed ccRCC cell malignant biological behaviors via targeting miR-942. Besides that, propofol decreased miR-942 expression, and miR-942 overexpression attenuated the effects of propofol on ccRCC cells. Moreover, propofol could regulate miR-942 expression through circFBXW7. Conclusion: Propofol suppressed the growth, migration, and invasion of ccRCC cells by regulating circFBXW7/miR-942 axis, suggesting a potential therapeutic strategy for the intervention of human ccRCC development.

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