Canadian Journal of Kidney Health and Disease最新文献

Background: Neonatal acute kidney injury (nAKI) has been reported to be common among neonates admitted to the Neonatal Intensive Care Unit (NICU) and is associated with increased mortality and prolonged duration of hospital stay. However, data on this entity from sub-Saharan Africa are scanty.

Objectives: This study aimed to assess the burden, risk factors, and short-term outcomes of nAKI in neonates admitted to a low-resource NICU in Zambia.

Design: The design of the study is a prospective cohort study.

Setting: The setting of this study was the NICU at the Women and Newborn Hospital of the University Teaching Hospitals (WNBH-UTHs).

Patients: In total, 322 neonates who were admitted to the NICU between November 2021 and December 2022.

Methods: A serum creatinine was determined on all patients at admission (within 24 hours), at 72 hours and day 7. The modified neonatal Kidney Disease: Improving Global Outcome (KDIGO) Criteria were used to define nAKI. Data were extracted using a predesigned form and analyzed using SPSS. A P-value less than .05 was considered statistically significant.

Results: The prevalence of nAKI was 13.7% (44/322). On multivariable regression analysis, antepartum hemorrhage (adjusted odds ratio [AOR] 5.58; 95% confidence interval [CI]: [1.62-19.13], P = .007), vomiting in the neonate (AOR 5.76; 95% CI: [1.10-30.32], P = .04), history of use of unit second-line antibiotics, meropenem (AOR 4.37; 95% CI: [1.97-9.69], P < .001), and ciprofloxacin (AOR 4.53; 95% CI: [1.22-16.84], P = .02) were associated with increased risk of nAKI. Acute kidney injury (AKI) was significantly associated with longer length of hospital stay and higher mortality (P < .05).

Limitations: The study did not use the urine output criteria to define nAKI and this may have led to an underestimation of nAKI prevalence. Additionally, kidney, ureter, and bladder ultrasound was not performed on any of the study participants.

Conclusion: AKI is common in neonates admitted to the NICU at WNBH-UTHs, and it is associated with a higher risk of mortality and prolonged length of hospital stay. Further studies among the various NICU sub-populations are needed to better characterize risks and outcomes.

Background: Diabetic kidney disease (DKD) is the most common and deranging microvascular complication of diabetes mellitus (DM). Podocytopathy is a key component of glomerular damage in DKD. Micro RNA-21 (miRNA-21) is an epigenetic regulator that plays a role in podocyte damage; however, the results of previous studies have not resolved the controversy about the role of miRNA-21 in the pathogenesis of DKD.

Objective: The objective was to investigate the correlation between miRNA-21 levels and urinary nephrin, podocin, and urinary albumin-creatinine ratio (UACR) in patients with type 2 DM and albuminuria.

Design: This is a cross-sectional study.

Setting: This study was carried out in internal medicine outpatient clinic of Cipto Mangunkusumo Hospital Jakarta, Indonesia.

Patients: This study consisted of 42 adults with type 2 DM and albuminuria.

Measurements: The measurements include (1) Serum miRNA-21; (2) urinary podocin, nephrin, and albumin-creatinine ratio; and (3) serum miRNA-21 correlated to urinary podocin, nephrin, and albumin-creatinine ratio.

Methods: The Spearman bivariate analysis to assess the correlation of miRNA-21 with nephrin, podocin, and UACR.

Results: The mean relative expression of miRNA-21 was 0.069 (0.024), the median for nephrin, podocin, and UACR was 35.5 (15.75-51.25) ng/mL, 0.516 (0.442-0.545) ng/mL, and 150 (94.56-335.75) ng/mL, respectively. A correlation between miRNA-21 and nephrin was observed (r = 0.598; P < .0001). There was a correlation between miRNA-21 and UACR (r = 0.604; P < .0001). No correlation was found between miRNA-21 and podocin.

Limitations: A lack of non-DM and non-albuminuric control population and small sample size. We could not exclude concurrent disease, and all other potential confounding variables, particularly those related to inflammation.

Conclusions: The miRNA-21 can be considered an early biomarker for podocytopathy and albuminuria in DM, highlighting its potential for early diagnostic and therapeutic interventions. Further research is required to confirm these findings and explore their clinical applications, which could significantly alter management strategies for DKD.

Background: Cisplatin (Cis) is potent chemotherapy used to treating already many different types of cancer; however, it is found to correlate with nephrotoxicity and other adverse health consequences. Thymoquinone (TQ) is an antioxidant and anti-inflammatory molecule that may defend against the consequences of different chemotherapies. Thymoquinone uses, although, are negatively impacted by its weak solubility and inadequate biological availability.

Objectives: This investigation examined the efficacy of a new nanoparticle (NP) absorbing TQ in an Ehrlich Ascites Carcinoma (EAC) mice model to address its low solubility, enhance its bioavailability, and protect against Cis-induced nephrotoxicity.

Methods: Following 4 treatment groups were included in this research: (1) control, (2) EAC, (3) EAC + Cis + Thymoquinone nanoparticle (TQ-NP) treated, and (4) EAC + Cis-treated.

Results: The study revealed that TQ-NP was efficacious in avoiding Cis-induced kidney problems in EAC mice, as well as restoring kidney function and pathology. Thymoquinone nanoparticle considerably reduced Cis-induced oxidative damage in renal tissue by augmenting antioxidant levels. According to tumor weight and histological investigation results, TQ-NP did not impair Cis's anticancer efficacy.

Conclusion: Thymoquinone nanoparticle might be used as a potential drug along with Cis anticancer therapy to reduce nephrotoxicity and other side effects while maintaining Cis anticancer properties.

Background: While historical rate of decline in kidney function is informally used by clinicians to estimate risk of future adverse clinical outcomes especially kidney failure, in people with type 2 diabetes the epidemiology and independent association of historical eGFR slope on risk is not well described.

Objective: Determine the association of eGFR slope and risk of clinically important outcomes.

Design setting and patients: Observational population-based cohort with type 2 diabetes in Alberta.

Measurement and methods: An Alberta population-based cohort with type 2 diabetes was assembled, characterized, and observed over 1 year (2018) for clinical outcomes of ESKD, first myocardial infarction, first stroke, heart failure, and disease-specific and all-cause hospitalization and mortality. Kidney function was defined using KDIGO criteria using the most recent eGFR and albuminuria measured in the preceding 18 months; annual eGFR slope utilized measurements in the 3 years prior and was parameterized using three methods (percentiles, and linear term with and without missingness indicator). Demographics, laboratory results, medications, and comorbid conditions using validated definitions were described. In addition to descriptive analysis, odds ratios from fully adjusted logistic models regressing outcomes on eGFR slope are reported; the marginal risk of clinical outcomes was also determined.

Results: Among 336 376 participants with type 2 diabetes, the median annual eGFR slope was -0.41 mL/min/1.73 m² (IQR -1.67, 0.62). In fully adjusted models, eGFR slope was independently associated with many adverse clinical outcomes; among those with ≤10th percentile of slope (median -4.71 mL/min/1.73 m²) the OR of kidney failure was 2.22 (95% CI 1.75, 2.82), new stroke 1.23 (1.08, 1.40), heart failure 1.42 (1.27, 1.59), MI 0.98 (0.77, 1.23) all-cause hospitalization 1.31 (1.26, 1.36) and all-cause mortality 1.56 (1.44, 1.68). For every -1 mL/min/1.73 m² in eGFR slope, the OR of outcomes ranged from 1.01 (0.98, 1.05 for new MI) to 1.09 (1.08, 1.10 for all-cause mortality); findings were significant for 10 of the 13 outcomes considered.

Limitations: Causality cannot be established with this study design.

Conclusions: These findings support consideration of the rate of eGFR decline in risk stratification and may inform clinicians and policymakers to optimize treatment and inform health care system planning.

Background: There are several steps patients and their health care providers must navigate to access kidney transplantation in British Columbia (BC).

Objective: We explored perceptions and experiences with the pretransplant process across BC to determine where process improvements can be made to enhance access to transplantation.

Design: Anonymous surveys were sent online and via post to health care providers (including nephrologists, registered nurses, and coordinators) and patients across BC.

Setting: Kidney care clinics, transplant regional clinics, and provincial transplant centers in BC.

Measurements: Surveys included Likert scale questions on the current pretransplant process and transplant education available in BC. The health provider survey focused on understanding the pretransplant process, knowledge, roles, and communication while the patient survey focused on patient education and experience of the pretransplant processes.

Results: A total of 100 health care providers and 146 patients responded. Seventy-six percent of health care providers understood their role and responsibility in the pretransplant process, while only 47% understood others' roles in the process. Fifty-nine percent of health care respondents felt adequately supported by the provincial donor and transplant teams. Seventy-one percent of registered nurses and 92% of nephrologists understood transplant eligibility. About 68% and 77% of nurses and nephrologists, respectively, reported having enough knowledge to discuss living donation with patients. Fifty percent of patients had received transplant education, of which 60% had a good grasp of the pretransplant clinical processes. Sixty-three percent felt their respective kidney teams had provided enough advice and tools to support them in finding a living donor. Fifty percent of patients reported feeling up to date with their status in the evaluation process.

Limitations: This analysis was conducted between December 2021 and June 2022 and may need to account for practice changes that occurred during the COVID-19 pandemic. Responses are from a selection of health care providers, thus acknowledging a risk of selection bias. Furthermore, we are not able to verify patients who reported receiving formal transplant education from their health care providers.

Conclusions: Exploring these themes suggests communication with regional clinics and transplant centers can be improved. In addition, patient and staff education can benefit from education on kidney transplantation and the pretransplant clinical processes. Our findings provide opportunities to develop strategies to actively address modifiable barriers in a patient's kidney transplantation journey.

Background: It is unclear whether the use of higher dialysate bicarbonate concentrations is associated with clinically relevant changes in the pre-dialysis serum bicarbonate concentration.

Objective: The objective is to examine the association between the dialysate bicarbonate prescription and the pre-dialysis serum bicarbonate concentration.

Design: This is a retrospective cohort study.

Setting: The study was performed using linked administrative health care databases in Ontario, Canada.

Patients: Prevalent adults receiving maintenance in-center hemodialysis as of April 1, 2020 (n = 5414) were included.

Measurements: Patients were grouped into the following dialysate bicarbonate categories at the dialysis center-level: individualized (adjustment based on pre-dialysis serum bicarbonate concentration) or standardized (>90% of patients received the same dialysate bicarbonate concentration). The standardized category was stratified by concentration: 35, 36 to 37, and ≥38 mmol/L. The primary outcome was the mean outpatient pre-dialysis serum bicarbonate concentration at the patient level.

Methods: We examined the association between dialysate bicarbonate category and pre-dialysis serum bicarbonate using an adjusted linear mixed model.

Results: All dialysate bicarbonate categories had a mean pre-dialysis serum bicarbonate concentration within the normal range. In the individualized category, 91% achieved a pre-dialysis serum bicarbonate ≥22 mmol/L, compared to 87% in the standardized category. Patients in the standardized category tended to have a serum bicarbonate that was 0.25 (95% confidence interval [CI] = -0.93, 0.43) mmol/L lower than patients in the individualized category. Relative to patients in the 35 mmol/L category, patients in the 36 to 37 and ≥38 mmol/L categories tended to have a serum bicarbonate that was 0.70 (95% CI = -0.30, 1.70) mmol/L and 0.87 (95% CI = 0.14, 1.60) mmol/L higher, respectively. There was no effect modification by age, sex, or history of chronic lung disease.

Limitations: We could not directly confirm that all laboratory measurements were pre-dialysis. Data on prescribed dialysate bicarbonate concentrations for individual dialysis sessions were not available, which may have led to some misclassification, and adherence to a practice of individualization could not be measured. Residual confounding is possible.

Conclusions: We found no significant difference in the pre-dialysis serum bicarbonate concentration irrespective of whether an individualized or standardized dialysate bicarbonate was used. Dialysate bicarbonate concentrations ≥38 mmol/L (vs 35 mmol/L) may increase the pre-dialysis serum bicarbonate concentration by 0.9 mmol/L.

Introduction: There is little evidence on the ideal frequency of routine blood work in maintenance dialysis patients to manage complications, including anemia, mineral bone disease (MBD), and hyperkalemia. Recent quality improvement studies from Ontario showed no negative impacts when decreasing the frequency from monthly to every 6 weeks in conventional in-center hemodialysis (ICHD) patients. In December 2020, Alberta Kidney Care-South (AKC-S) reduced the frequency of routine blood work from every 6 weeks to every 8 weeks for ICHD patients.

Objective: We aimed to assess the impact of reducing blood work frequency on patient outcomes.

Methods: We compared prevalent AKC-S ICHD patients in 2 cohorts: (1) retrospective control (October 31, 2019-October 31, 2020) and (2) prospective intervention (December 1, 2020-December 1, 2021). Primary outcomes were true frequency of routine blood work, odds of patients being within target for anemia and MBD, and proportion of lab values of hyperkalemia. Furthermore, we compared hospitalizations and mortality.

Results: A total of 972 patients in Calgary's ICHD program were included, 787 in each period (with 602 patients overlapping both cohorts). The frequency of routine blood work decreased from every 39.5 days in the control period to every 54.2 days in the intervention period (P < .01). There was a reduction in the odds of phosphate values in targets (P = .02), and an increase in the odds of labs with hyperkalemia (>6.0 mmol/L) during the intervention period (P = .01). There was no significant change in the odds of being within the accepted targets during the intervention period compared with the control period for hemoglobin, Tsat, calcium, or parathyroid hormone (PTH). Fewer patients were hospitalized during the intervention period and the risk of death decreased as well, although additional factors such as the COVID-19 pandemic may have affected this. A cost-savings of $32 962 occurred from the reduced anemia and MBD blood work during the intervention period.

Conclusions: When ICHD units in Calgary reduced routine blood work frequency from every 6 weeks to 8 weeks, there were no negative impacts on hospitalizations or deaths. A slightly lower proportion of phosphate values were within target, and a 0.7% increase in potassium values greater than 6 mmol/L was demonstrated. Our study suggests that blood work frequency in ICHD dialysis patients may be further reduced to every 8 weeks safely. Ultimately, additional pragmatic trials are needed to identify the optimal frequency of routine blood work.

Rationale: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease characterized by excessive immune activation. It is more commonly seen in children but increasingly recognized in adults. Primary HLH relies on a genetic predisposition, whereas secondary HLH develops in the context of infections, malignancies, or autoimmune diseases. Hemophagocytic lymphohistiocytosis has been rarely described in patients on immunosuppressive therapy after kidney transplant. Here, we describe a case of HLH in a patient with a remote history of kidney transplant, triggered by a viral infection.

Presenting concerns: A 45-year-old female, with a kidney transplant in 2009 for IgA nephropathy, presented with fever, vomiting, and back pain of 1-week duration. She was on triple immunosuppression consisting of daily doses of prednisone 5 mg, azathioprine 100 mg, and tacrolimus extended release 1 mg, and a baseline creatinine of 130 µmol/L.

Diagnosis: Initial investigations showed anemia, leukopenia, elevated serum creatinine, transaminitis, and markedly increased ferritin of 67 600 µg/L which prompted a bone marrow biopsy to rule out HLH. The bone marrow showed an increased proportion of CD68+ cells (macrophages) with more than 5 in 1000 hemophagocytic macrophages. Her soluble IL-2 receptor (CD25) level was 3406 pg/mL (606-2299 pg/mL) which was mildly elevated. She fulfilled 4 of the 8 criteria for HLH and with an H score was 223 which suggested a diagnosis of HLH with 96.9% probability. An extensive secondary workup for possible triggers for HLH led to a swab from genital ulcers that was positive for herpes simplex virus (HSV) type 2. The polymerase chain reaction (PCR) in the blood for HSV type 2 was also positive.

Interventions: Given the diagnosis of HSV type 2 as the putative trigger for HLH, she was started on parenteral acyclovir for 2 weeks followed by oral valacyclovir for 2 more weeks. In the context of infection, the azathioprine was stopped while low-dose steroid and tacrolimus were continued.

Outcomes: With the initiation of treatment for HSV infection, leukopenia, creatinine, and transaminases improved along with ferritin levels. At her 6-month follow-up, her blood counts and liver enzymes had normalized, and ferritin was 566 µg/L.

Teaching points: Hemophagocytic lymphohistiocytosis is a rare disease in kidney transplant recipients with a high mortality rate. It can occur even in remote kidney transplant recipients so a high degree of suspicion is necessary to lead to a prompt diagnosis. Infections are common triggers for secondary HLH. Early identification and treatment of the triggering infection may improve outcomes.

Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions worldwide are diagnosed, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because in the early stages, it is often silent. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary-care level. Many systematic barriers exist, ranging from patient to clinician to health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay.