International Journal of Nephrology最新文献

Background: The SARS-CoV-2 virus caused the global COVID-19 pandemic, with waxing and waning course. This study was conducted to compare outcomes in the first two waves, in mechanically ventilated patients.

Methods: This retrospective observational study included all mechanically ventilated COVID-19 patients above 18 years of age, between March 2020 and January 2021. Patients were grouped into first wave from March 2020 to July 2020, and second wave from August 2020 to January 2021. Outcome measures were mortality, the development of acute kidney injury (AKI), and need for renal replacement therapy (RRT). Univariate and multivariate cox regression analysis were used to delineate risk factors for the outcome measures.

Results: A total of 426 patients, 285 in the first wave and 185 in the second wave, were included. The incidence of AKI was significantly lower in the second wave (72% vs. 63%; p=0.04). There was no significant difference in mortality (70% vs. 63%; p=0.16) and need for RRT (36% vs. 30%; p=0.1). Risk factors for mortality were increasing age and AKI in both waves, and chronic kidney disease (CKD) (adj. HR 1.7; 95% CI 1.02-2.68; p=0.04) in the second wave. Risk factors for AKI were CKD in both the waves, while it was diabetes (adj. HR 1.4; 95% CI 1.02-1.95; p=0.04) and increasing age in the first wave. Remdesivir (adj. HR 0.5; 95% CI 0.3-0.7; p < 0.01) decreased the risk of AKI, and convalescent plasma (adj. HR 0.5; 95% CI 0.3-0.9; p=0.02) decreased the risk of mortality in the first wave, however, such benefit was not observed in the second wave.

Conclusions: Our study shows a decrease in the incidence of AKI in critically ill patients, however, the reason for this decrease is still unknown. Studies comparing the waves of the pandemic would not only help in understanding disease evolution but also to develop tailored management strategies.

Introduction: Patients receiving in-center hemodialysis are extremely vulnerable to COVID-19. It is unclear if routine screening of asymptomatic hemodialysis patients is an effective strategy to prevent COVID-19 outbreaks within the dialysis unit.

Methods: We conducted a retrospective analysis of in-center hemodialysis patients who underwent bimonthly COVID-19 rapid antigen test screening from February 15^th to December 26^th, 2021. Nasal rapid antigen testing was performed in all asymptomatic patients. All rapid antigen-positive tests were confirmed by RT-PCR nasopharyngeal swab. Besides universal rapid antigen screening, RT-PCR testing was conducted in all symptomatic patients and contacts of COVID-19 subjects.

Results: Overall, 4079 rapid antigen tests were performed in 277 hemodialysis patients on chronic hemodialysis with a mean age of 68.4 ± 14.6 years. Thirty-eight (0.9%) rapid antigen tests resulted positive. Only five (13.8%) positive-rapid antigen tests were also positive by RT-PCR testing. During the same period, 219 patients regularly screened by rapid antigen tests bimonthly underwent 442 RT-PCR nasopharyngeal swabs for clinical reasons. RT-PCR testing yielded a positive result in 13 (5.9%) patients. The time elapsed between PCR and the negative-rapid antigen test was 7.7 ± 4.6 days (range 1.8-13.9 days). At the end of the follow-up, 6.4% of the population on in-center hemodialysis contracted COVID-19, and routine rapid antigen tests detected only 5 out of 18 (27.7%) COVID-19 cases. No outbreaks of COVID-19 were identified within the dialysis unit.

Conclusion: Bimonthly rapid antigen screening led to the early diagnosis of COVID-19 in less than one-third of cases. The short incubation period of the new SARS-CoV-2 variants makes bimonthly test screening inadequate for an early diagnosis of COVID-19. More frequent tests are probably necessary to improve the utility of COVID-19 nasal rapid antigen test in patients on hemodialysis.

Background: CKD patients are often asymptomatic in the early stages and referred late to nephrologists. Late referred patients carry a poor prognosis. There is a lack of data on outcomes associated with referral patterns in CKD patients from northern India.

Methods: In this observational cohort study, all CKD patients who visited the nephrology OPD of the institute between Nov 1, 2018, and Dec 31, 2020, were classified as early referral (ER) if their first encounter with a nephrologist occurred more than one year before initiation of dialysis and education about dialysis (from a nurse or nephrologist). The remaining others were considered late referrals (LRs). The outcomes impact of early and late referrals was analyzed.

Results: A total of 992 (male 656) CKD patients (ER, n = 475 and LR, n = 517) were enrolled. Patients referred early were older and diabetic and had higher BMI, better education, occupation, and socioeconomic status as compared to those referred late. The mean eGFR at first contact with the nephrologist was (25.4 ± 11.5 ml/min) in ER and 9.6 ± 5.7 ml/min in the LR group and had a higher comorbidity score. The CKD-MBD parameters, hemoglobin, and nutritional parameters were worse in LR. Only a few patients had AVF, and the majority required emergency dialysis in the LR group. A total of 91 (9.2%) patients died, 17 (1.7% ER and 74 (7.5%) patients in the LR group patients. There was significantly lower survival at 6 months (ER 97.1% vs. LR 89.7%), 12 months (ER 96.4% vs. LR 85.7%), 18 months (ER 96.4% vs. LR 85.7%), and 24 months (ER 96.4% vs. LR 85.7%) in late referral group as compared to early referral group (P=0.005).

Conclusions: LR to nephrologists has the risk of the emergency start of dialysis with temporary vascular access and had a higher risk of mortality. The timely referral to the nephrologist in the predialysis stage is associated with better survival and reduced mortality.

Background: Colistin is a lifesaving treatment for multidrug-resistant Gram-negative bacterial (MDR-GNB) infections along with its well-known nephrotoxicity. The controversy of colistin-induced acute kidney injury (AKI) on mortality is noted. This study aimed to determine the risk factors and impact of AKI on the survival and significance of colistin dosage.

Methods: A retrospective cohort study was performed in adult patients who received intravenous colistin for MDR-GNB treatment between June 2015 and June 2017. Factors influencing colistin-induced AKI and survival were evaluated by Cox regression analysis. Cut-off levels of the colistin dose per ideal body weight (IBW) that significantly affected clinical outcomes were assessed with linearity trends and receiver operating characteristic analyses.

Results: AKI occurred in 68.5% of 412 enrolled patients with an incidence rate of 10.6 per 100 patients-days and a median time was 6 (3-13) days. Stages I-III of AKI were 38.3, 24.5, and 37.2%. Factors associated with colistin-induced AKI were advanced age, high serum bilirubin, AKI presented before colistin administration, increased daily colistin doses per IBW, and concomitant use of nephrotoxic drugs. Colistin-induced AKI was related to mortality (HR 1.74, 95% CI 1.06-2.86, p=0.028). In the non-AKI before colistin usage subgroup, the total dose and total dose/IBW were >1,500-2,000 mg and 30-35 mg/kg to benefit mortality reduction but were <2,500-3,000 mg and 45-50 mg/kg for risk reduction of AKI. A daily colistin dose/IBW >4.5 mg/kg/day also increased the risk of AKI. In the AKI developed before colistin subgroup, the cut-off values of total colistin dose >1250-1350 mg and total dose/IBW >23.5-24 mg/kg demonstrated significant risks of AKI.

Conclusion: The incidence of AKI after colistin administration was high and impacted mortality. Prevention and early correction of these related factors are mandatory. Careful use of colistin was also both beneficial in mortality and AKI reductions.

Molecular mechanisms underlying the nephrotoxicity associated with bevacizumab are unclear. Endothelin-1 (ET-1) is involved in podocyte injury and proteinuria, and its level increases in most cases of kidney disorders. Forkhead box protein O1 (FoxO1), a transcription factor, is a major determinant of ET-1 promoter activation and is regulated by protein kinase B (Akt) phosphorylation-dependent nuclear exclusion. We evaluated the effect of bevacizumab on ET-1 production in human glomerular microvascular endothelial cells (hGECs). We analyzed the changes in the mRNA and protein levels of ET-1 in hGECs treated with bevacizumab using real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. Changes in the protein levels and phosphorylation status of Akt and FoxO1 in hGECs treated with bevacizumab were analyzed by western blotting. After cell lysis, FoxO1 protein was isolated from the cytoplasmic and nuclear fractions. We also investigated the effects of AS1842856 (a FoxO1 inhibitor) on bevacizumab-induced ET-1 production. Bevacizumab significantly and dose-dependently increased the mRNA and protein levels of ET-1 in hGECs (p < 0.05). Bevacizumab treatment also led to a decrease in phosphorylated Akt protein levels. Inhibition of Akt activity by LY294002 promoted ET-1 production. Bevacizumab also induced an increase in FoxO1 protein levels in the nucleus. Inhibition of FoxO1 activity by AS1842856 resulted in decreased ET-1 levels in bevacizumab-treated hGECs. ET-1 axis activation, Akt inactivation, and FoxO1 nuclear localization are the molecular mechanisms underlying bevacizumab-induced nephrotoxicity. Therefore, inhibition of renal ET-1 production could be a promising approach to protect against or treat bevacizumab-induced nephrotoxicity.

Background: The humoral response to SARS-CoV-2 infection in hemodialysis patients needs to be clarified.

Methods: In this retrospective study performed in two dialysis facilities, we measured the circulating levels of SARS-CoV-2 antibodies in patients who were on maintenance hemodialysis during the first wave of the epidemic in March and April 2020 and were still alive 6 months later. We also investigated associations between the patients diagnosed as infected during the first wave and several clinical, biological, and radiological parameters of COVID-19. Finally, we compared these circulating levels of SARS-CoV-2 antibodies with those of a control group of healthcare workers infected during the same period.

Results: Of the 299 hemodialysis patients who recovered from the first wave of the epidemic 6 months before, 59 had a positive SARS-CoV-2 antibody whereas only 45 patients were diagnosed as infected during the first wave of the epidemic. All infected hemodialysis patients developed circulating antibodies. Using a clustering method, a significant correlation was identified between the cluster with the lowest circulating levels of SARS-CoV-2 antibodies and the severity of COVID-19 based on several parameters including CRP, BNP, lymphocyte count, neutrophil-lymphocyte ratio, and oxygen requirements, as well as pulmonary involvement on chest scan. Moreover, the circulating levels of the SARS-CoV-2 antibodies in surviving hemodialysis patients (n = 59) were similar to those of the control group (n = 17).

Conclusion: The main finding of this study is that all of the surviving hemodialysis patients who were diagnosed with SARS-CoV-2 infection from March to April 2020 developed a persistent humoral response with significant circulating levels of SARS-CoV-2 antibodies, 6 months later. Another important finding is that surviving hemodialysis patients who had more severe disease had lower circulating levels of SARS-CoV-2 antibodies. Finally, circulating levels of SARS-CoV-2 antibodies were similar in surviving hemodialysis patients and healthcare workers without kidney disease.

Background: Kidney disease affects absorption, distribution, metabolism, and excretion of medicines and their metabolites. Therefore, when prescribing medicines for patients with kidney disease, dose adjustment is an accepted standard of practice.

Objective: This study aimed to assess medicine dose adjustment practice and associated factors among adult patients with renal impairment admitted to medical wards at Amhara region referral hospitals.

Method: Multicenter, institution-based, cross-sectional study was conducted from March 28, 2020, to August 30, 2020. The data was collected by using a pretested interviewer-administered structured questionnaire. Data were entered into Epi-Data version 4.6 and transferred into SPSS version 25 for further data processing and analysis. Descriptive statistics such as frequencies and percentages were computed. Both bivariable and multivariable binary logistic regression analyses were fitted to identify factors associated with dose adjustment practice. A 95% confidence interval and a p value less than 0.05 were used to declare statistical significance.

Result: Among 815 medicines' prescriptions that needed dose adjustment, 417 (51.2%) of them were dosed inappropriately. Number of medicines, number of comorbidities, and being unemployed were significantly associated with inappropriate dose adjustment.

Conclusion: Our study revealed that there was a considerable rate of inappropriate dose adjustment in patients with renal impairment. Training for health care providers, use of guidelines, and communication with clinical pharmacists should be encouraged for good prescription practice.

Patients with chronic kidney disease (CKD), including dialysis and transplant patients, are at greater risk of contracting SARS-CoV-2 due to kidney dysfunction and preexisting comorbidities. To date, a specific guideline on managing these high-risk patients infected with COVID-19 has not been established. As the current management of COVID-19 comprises mainly experimental drugs, the authors aim to provide information on dosing adjustments at different stages of kidney dysfunction and notable renal side effects. We performed a nonsystematical review of currently available COVID-19 drugs exploring several different clinical trial databases and search browsers. Several antivirals and monoclonal antibodies used in COVID-19 treatment require dosage adjustments in kidney dysfunction. In a global pandemic setting, nephrologists need to consider the appropriate dosage according to the renal function and closely monitor the side effects of different drug combinations to obtain the optimum therapeutic effect while avoiding further renal damage. Further studies are required to determine the safety and efficacy of these drugs in renal patients.

Background: Atypical hemolytic uremic syndrome (aHUS) is an important cause of acute kidney injury in children. It is primarily caused by dysregulation of the complement alternative pathway due to genetic mutations, mainly in complement factor H genes, or due to anti-factor H autoantibodies (anti-FH), leading to uncontrolled overactivation of the complement system. Early diagnosis and treatment of autoimmune HUS (AI-HUS) is essential and leads to a favorable outcome.

Methods: Fifty pediatric HUS patients and 50 age- and sex-matched controls were included in the study. Patients were subjected to full history taking, clinical examination, and laboratory testing. All candidates were subjected to an assessment of anti-FH in serum by a homemade enzyme-linked immunosorbent assay technique.

Results: A high frequency of serum anti-FH was detected in our aHUS patients. The disease onset of AI-HUS was mainly observed in March and April, with significantly higher rates in school-aged males. All patients who started immunosuppressives early together with plasmapheresis upon detection of their anti-FH had complete renal function recovery.

Conclusion: The high frequency of AI-HUS revealed in Egyptian HUS children in our study highlights the importance of implementing anti-FH testing in Egypt to provide early recognition for immediate proper management, including early immunosuppressive therapy, and hence improving patient outcomes.

The widely used Modification of Diet in Renal Disease (MDRD) formula adapts a 1.212 multiplier for individuals who are identified as African Americans (AAs) or Blacks, which leads to a higher GFR estimation. As it stands, AAs have a lower prevalence of chronic kidney disease (CKD) but higher incidence of end-stage renal disease (ESRD) compared with Whites. Many hypotheses have been postulated to explain this paradox, but the imprecision of the GFR estimation with race-adaptation could be contributory. We performed a single-center, longitudinal, retrospective study on a cohort of outpatient AA patients using the MDRD and MDRD_{race removed} and CKD-EPI and CKD-EPI_{race removed} and their progression to CKD G5 (eGFR <15 ml/min/1.73 m²). 327 patients were analyzed. Median follow-up was 88.1 months (interquartile range, 34.4-129.1). When race was removed from MDRD, 39.9% of patients in CKD G1/2 were reclassified to CKD G3a, 72.6% of patients in CKD G3a would be reclassified to CKD G3b, and 54.1% and 36.4% of patients would be reclassified from CKD 3b to CKD G4 and CKD G4 to CKD G5, respectively (p < 0.0001). Comparing the CKD-EPI formula against the MDRD in our cohort, we found that 8.2%, 18.8%, and 11.4% of patients were reclassified from CKD G1/2 to CKD G3a, CKD G3a to G3b, and CKD G3b to CKD G4 respectively. Overall median time to progression to CKD G5 was 137.4 (131.9-142.8) months in patients who were not reclassified and 133.6 (127.6-139.6) months for patients who were reclassified by MDRD_{race removed}(p < 0.288). Concerns of inequitable access to healthcare have elicited calls to review race-corrected eGFR equations. A substantial number of individuals would have their CKD stage reclassified should have the MDRD_{race removed} equation be adopted en masse on an AA-only population. The discrepancy is highest at the 45-59 and >60 ml/min/1.72 min² ranges. This will have tremendous impact on our center's approach to pharmacological dosing, referral system, best practices, and outcome surveillance. Comprehensive review of the current "race-corrected" eGFR will require a multifaceted approach and adjunctive use of noncreatinine-based approach.