The Rate and Risk Factors of Acute Kidney Injury among Cancer Patients’ Admissions in Palestine: A Single-Center Study

Introduction. Acute kidney injury (AKI) remains a critical issue for cancer patients despite recent treatment improvements. This study aimed to assess the incidence of AKI in cancer patients and its related risk factors. Methods. A Retrospective cohort study was conducted at tertiary hospitals in the period 2016–2018. A data abstraction sheet was used to collect related variables from patients’ records. During admission, the incidence of AKI was assessed using creatinine measurements. RIFLE criteria were used to classify it into five categories of severity: risk, injury, failure, loss, and end-stage renal disease. Results. Using RIFLE (Risk, Injury, Failure, Loss, and End-stage renal disease) criteria, 6.9% of admissions were complicated with AKI. The severity of these fell into the categories of risk, injury, and failure, 3.3%, 1.7%, and 1.9%, respectively. In the multivariate model, the odds for developing AKI was significantly higher for patients with congestive heart failure (AOR = 17.1, 95% CI 1.7–80.1), chronic kidney disease (adjusted OR = 6.8, 95% CI 1.4–32.2 ( P value 0.017)), sepsis (AOR = 4.4, 95% CI 1.9–10.1), hypercalcemia (AOR = 8.4, 95% CI 1.3–46.1), and admission to the ICU (AOR = 5.8, 95% CI 2.1–16.2). In addition, the mortality rate was nearly seven times higher for patients complicated by AKI (relative risk = 7.6, 95% CI 3.2–18.2). Conclusion. AKI was significantly associated with congestive heart failure, chronic kidney disease, sepsis, ICU admission, and hypercalcemia in cancer patients, resulting in poorer outcomes and higher mortality rates. AKI assessment for hospitalized cancer patients should be performed regularly, especially for patients at increased risk.

Comparison of Outcomes among Chronic Kidney Disease V Patients with COVID-19 at the National Kidney and Transplant Institute: A Retrospective Cohort Study

Background. There is very little published data on outcomes of COVID-19 among chronic kidney disease (CKD) patients. We compared the outcomes of COVID-19 in a tertiary care renal hospital among CKD V patients on hemodialysis (HD), peritoneal dialysis (PD), and dialysis initiation, in terms of duration of hospitalization, in-patient mortality, and 30-day mortality. Methods. A total of 436 CKD V patients, on either HD, PD, or dialysis initiation, with COVID-19 who were admitted at the National Kidney and Transplant Institute (NKTI) from March 13, 2020, to August 31, 2020, were included. Kaplan–Meier survival analysis was performed. Comparison of probability of mortality by group was performed using Log-Rank test. p values ≤0.05 were considered statistically significant. Results. Among 436 CKD V patients, 298 (68%) were on HD, 103 (24%) were on PD, and 35 (8%) required dialysis initiation. Overall in-hospital mortality was 34%; 38% were on HD, 20% on PD, and 37% on dialysis initiation. Total 30-day mortality was 27%; 32% were on HD, 26% on PD, and 16% on dialysis initiation. Median follow-up was 24 days. Among the 137 deaths recorded, total median time to death was 10 days; 8.5 days, 15.5 days, and 9 days for HD, PD, and dialysis initiation groups, respectively. Probability of mortality was significantly higher in HD patients versus PD patients ( p < 0.00001 ) and in the dialysis initiation group compared to PD patients ( p = 0.0234 ). Mortality probability, however, was not significantly different in HD patients versus the dialysis initiation group ( p = 0.63 ). Conclusion. Among CKD V patients diagnosed with COVID-19 at the NKTI, those on HD and on dialysis initiation had significantly higher in-hospital and 30-day mortality, compared to patients on PD.

Colistin-Induced Acute Kidney Injury and the Effect on Survival in Patients with Multidrug-Resistant Gram-Negative Infections: Significance of Drug Doses Adjusted to Ideal Body Weight

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.

Bevacizumab Increases Endothelin-1 Production via Forkhead Box Protein O1 in Human Glomerular Microvascular Endothelial Cells In Vitro

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.

Medicine Dose Adjustment Practice and Associated Factors among Renally Impaired Patients in Amhara Regional State, Ethiopia

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.

SARS-CoV-2 Antibodies in Hemodialysis Patients Six Months after Infection Compared to Healthcare Workers

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.

Pharmacological Treatment Options for Coronavirus Disease-19 in Renal Patients

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.

Anti-Factor H Antibodies in Egyptian Children with Hemolytic Uremic Syndrome

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 Implication of Dropping Race from the MDRD Equation to Estimate GFR in an African American-Only Cohort

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 MDRDrace removed and CKD-EPI and CKD-EPIrace 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 MDRDrace 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 MDRDrace 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.

Urinary Tract Infections in the First 6 Months after Renal Transplantation

Purpose. Urinary tract infections (UTIs) are common in the first 6 months after renal transplantation, and there are only limited data about UTIs after transplantation in Saudi Arabia in general. Methods. A retrospective study from January 2017 to May 2020 with 6-month follow-up. Results. 279 renal transplant recipients were included. Mean age was 43.4 ± 16.0 years, and114 (40.9%) were women. Urinary stents were inserted routinely during transplantation and were removed 35.3 ± 28 days postoperatively. Ninety-seven patients (35%) developed urinary tract infections (UTIs) in the first six months after renal transplantation. Of those who developed the first episode of UTI, the recurrence rates were 57%, 27%, and 14% for having one, two, or three recurrences, respectively. Late urinary stent removals, defined as more than 21 days postoperatively, tended to have more UTIs (OR: 1.43, P: 0.259, CI: 0.76–2.66). Age >40, female gender, history of neurogenic bladder, and transplantation abroad were statistically significant factors associated with UTIs and recurrence. Diabetes, level of immunosuppression, deceased donor renal transplantation, pretransplant residual urine volume, or history of vesicoureteral reflux (VUR) was not associated with a higher incidence of UTIs. UTIs were asymptomatic in 60% but complicated with bacteremia in 6% of the cases. Multidrug resistant organisms (MDROs) were the causative organisms in 42% of cases, and in-hospital treatment was required in about 50% of cases. Norfloxacin + Bactrim DD (160/800 mg) every other day was not associated with the lower risk of developing UTIs compared to the standard prophylaxis daily Bactrim SS (80/400 mg). Conclusion. UTIs and recurrence are common in the first 6 months after renal transplantation. Age >40, female gender, neurogenic bladder, and transplantation abroad are associated with the increased risk of UTIs and recurrence. MDROs are common causative organisms, and hospitalization is frequently required. Dual prophylactic antibiotics did not seem to be advantageous over the standard daily Bactrim.