Burden of chronic kidney diseases and underlying causes in Zambia: evidence from the global burden of disease study 2019.

INTRODUCTION: Chronic kidney disease (CKD) has been a global public health problem and a major source of suffering and poor quality of life for those afflicted. Using data from the global burden of disease (GBD) study 2019, we estimated the magnitude of the burden of CKD as well as the underlying causes of CKD in the Zambian population. METHOD: The data used for this study were extracted from the GBD 2019 study. The GBD 2019 provides estimates of several metrics of disease burden including the commonly used disability-adjusted life year (DALYs) for over 369 diseases and injuries, and 87 risk factors and combinations of these in 204 countries and territories from 1990 to 2019. We estimated the burden of CKD as the number and rates (per 100,000 population) of DALYs, disaggregated by year, sex, and age group. We examined the underlying causes of CKD by estimating the population attributable fraction as the percentage contributions of risk factors to CKD DALY. RESULTS: The number of DALYs for CKD was estimated as 76.03 million (95% UI: 61.01 to 93.36) in 2019 compared to 39.42 million (95% UI: 33.09 to 45.90) in 1990, representing 93% increase whereas the DALYs rate per 100,000 population was estimated as 416.89 (95% UI: 334.53 to 511.93) in 2019 compared to 496.38 (95% UI: 416.55 to 577.87) in 1990, representing 16% reduction. CKD due to hypertension accounted for 18.7% of CKD DALYs and CKD due to diabetes (types 1 and 2) accounted for 22.7%, while CKD from glomerulonephritis accounted for the most DALYs at 33%. The age group most impacted from CKD were adolescents and young adults. CONCLUSION: The burden of CKD remains high in the Zambian population with diabetes, high blood pressure, and glomerulonephritis as important causes. The results highlight the need to develop a comprehensive action plan to prevent and treat kidney disease. Increasing the awareness of CKD among the public as well as adaptation of guidelines for treating patients with end stage kidney disease are important considerations.

COVID-19 and CKD: Employment, Food Security and Healthcare in El Salvador.

Background: In Central America, the COVID-19 pandemic coexists with a devastating epidemic of chronic kidney disease of unknown origin. The consequences of these overlapping health crises remain largely unknown. Methods: We assessed vulnerability to and impact of the first wave of COVID-19 on participants in a cohort study of chronic kidney disease (CKD) in El Salvador (n = 229). Participants were contacted by phone during August and September 2020. We queried changes to employment, healthcare access, household income and food security due to the pandemic (from March 2020 until the time of the interview) and COVID-19-associated symptoms during that time. Findings: We reached 94% of the cohort (n = 215). Nearly 40% of participants reported an unexpected change in employment or work activities and 8.8% reported new unemployment due to the pandemic. Participants with CKD (n = 27) had higher odds of reporting new income insecurity, food insecurity, and reductions in medical care access due to the pandemic. COVID-19-associated symptoms (an approximation of disease) were reported in 7.0% (n = 15). Participants with CKD were more likely to report COVID-19-associated symptoms compared to those without CKD, although these differences were not statistically significant. Conclusions: Overall, participants with CKD suffered greater economic consequences as a result of the pandemic and may have experienced higher incidence of COVID-19 disease, although laboratory diagnostics would be required to draw this conclusion. Longitudinal analyses are required to comprehensively evaluate the implications of the pandemic for individuals with CKD in Central America.

[Risk factors of kidney injury in patients with COVID-19].

AIM: To determine the incidence and risk factors of acute kidney injury (AKI) in Russian cohort of patients with COVID-19. MATERIALS AND METHODS: We included 315 patients, who were hospitalized with COVID-19 from October 2020 till February 2021. The diagnosis was established on the basis of the positive SARS-CoV-2 swab test and/or typical radiologic findings on CT scans. RESULTS: AKI complicated the clinical course in 92 (29.21%) cases. The independent risk factors of AKI were female sex, underline chronic kidney disease and the highest level of C-reactive protein during hospitalization. In the general group of patients were 41 (13%) lethal cases, in the group with AKI 32 (34.8%). Compared with those without AKI, patients with AKI had 4.065 (95% confidence interval 2.154 to 7.671) times the odds of death. Respiratory support, the highest serum creatinine and glucose levels appeared to be the risk factors of death among patients with AKI in the multivariable Cox regression. CONCLUSION: The clinical course of COVID-19 was complicated by AKI in 29% cases. The independent risk factors of AKI in patients with COVID-19 are underline chronic kidney disease, circulatory disorder and the highest level of C-reactive protein during hospitalization.

Kidney Injury in COVID-19: Epidemiology, Molecular Mechanisms and Potential Therapeutic Targets.

As of December 2021, SARS-CoV-2 had caused over 250 million infections and 5 million deaths worldwide. Furthermore, despite the development of highly effective vaccines, novel variants of SARS-CoV-2 continue to sustain the pandemic, and the search for effective therapies for COVID-19 remains as urgent as ever. Though the primary manifestation of COVID-19 is pneumonia, the disease can affect multiple organs, including the kidneys, with acute kidney injury (AKI) being among the most common extrapulmonary manifestations of severe COVID-19. In this article, we start by reflecting on the epidemiology of kidney disease in COVID-19, which overwhelmingly demonstrates that AKI is common in COVID-19 and is strongly associated with poor outcomes. We also present emerging data showing that COVID-19 may result in long-term renal impairment and delve into the ongoing debate about whether AKI in COVID-19 is mediated by direct viral injury. Next, we focus on the molecular pathogenesis of SARS-CoV-2 infection by both reviewing previously published data and presenting some novel data on the mechanisms of cellular viral entry. Finally, we relate these molecular mechanisms to a series of therapies currently under investigation and propose additional novel therapeutic targets for COVID-19.

Acute kidney injury in paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) is not associated with progression to chronic kidney disease.

BACKGROUND: Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) is a rare complication of SARS-CoV-2 associated with single or multiorgan dysfunction. OBJECTIVE: We aimed to evaluate the incidence of acute kidney injury (AKI) and risk factors for kidney dysfunction in PIMS-TS, with reporting of 6-month renal follow-up data. We also evaluated renal involvement between first and second waves of the SARS-CoV-2 pandemic in the UK, the latter attributed to the Alpha variant. DESIGN: A single-centre observational study was conducted through patient chart analysis. SETTING: Data were collected from patients admitted to Great Ormond Street Hospital, London, UK, between April 2020 and March 2021. PATIENTS: 110 patients <18 years of age. MAIN OUTCOME MEASURE: AKI during hospitalisation. AKI classification was based on upper limit of reference interval (ULRI) serum creatinine (sCr) values. RESULTS: AKI occurred in 33 (30%) patients. Hypotension/hypoperfusion was associated with almost all cases. In univariate analysis, the AKI cohort had higher peak levels of triglycerides (OR, 1.27 (95% CI, 1.05 to 1.6) per 1 mmol/L increase) and C reactive protein (OR, 1.06 (95% CI, 1.02 to 1.12) per 10 mg/L increase), with higher requirement for mechanical ventilation (OR, 3.8 (95% CI, 1.46 to 10.4)) and inotropic support (OR, 15.4 (95% CI, 3.02 to 2.81)). In multivariate analysis, triglycerides were independently associated with AKI stages 2-3 (adjusted OR, 1.26 (95% CI, 1.04 to 1.6)). At follow-up, none had macroalbuminuria and all had sCr values

Mesenchymal Stem Cell-Derived Extracellular Vesicles to the Rescue of Renal Injury.

Acute kidney injury (AKI) and chronic kidney disease (CKD) are rising in global prevalence and cause significant morbidity for patients. Current treatments are limited to slowing instead of stabilising or reversing disease progression. In this review, we describe mesenchymal stem cells (MSCs) and their constituents, extracellular vesicles (EVs) as being a novel therapeutic for CKD. MSC-derived EVs (MSC-EVs) are membrane-enclosed particles, including exosomes, which carry genetic information that mimics the phenotype of their cell of origin. MSC-EVs deliver their cargo of mRNA, miRNA, cytokines, and growth factors to target cells as a form of paracrine communication. This genetically reprograms pathophysiological pathways, which are upregulated in renal failure. Since the method of exosome preparation significantly affects the quality and function of MSC-exosomes, this review compares the methodologies for isolating exosomes from MSCs and their role in tissue regeneration. More specifically, it summarises the therapeutic efficacy of MSC-EVs in 60 preclinical animal models of AKI and CKD and the cargo of biomolecules they deliver. MSC-EVs promote tubular proliferation and angiogenesis, and inhibit apoptosis, oxidative stress, inflammation, the epithelial-to-mesenchymal transition, and fibrosis, to alleviate AKI and CKD. By reprogramming these pathophysiological pathways, MSC-EVs can slow or even reverse the progression of AKI to CKD, and therefore offer potential to transform clinical practice.

Prevalence of Chronic Kidney Disease, Its Risk Factors and Outcome in Nepal: A Systematic Review and Meta-analysis.

BACKGROUND: Hypertension, diabetes, glomerulonephritis, obesity, and family history of kidney diseases are major risk factors for chronic kidney disease. Due to the paucity of data on a national level regarding the prevalence, risk factors, and complications of chronic kidney disease, we performed this meta-analysis. METHODS: We searched online databases from January 2000 till October 2020. Two reviewers screened articles using Covidence software. Comprehensive Meta-Analysis Software version 3 was used for data analysis. RESULTS: Among chronic kidney disease patients, 35.96% were found to have high LDL, 34.22% had hypercholesterolemia, 39.18% had hypertriglyceridemia, and 42.23% had low HDL. Pigmentary changes were reported in 37.71%, pruritus in 30.96%; and xerosis in 48.55%. Among the reported nail problems, the brown nail was reported in 7.19%, half and half nail in 6.07%, and white nail in 20.65%. CONCLUSIONS: The prevalence of chronic kidney disease among high-risk cohorts in Nepal was significant among risk group with hypertension and diabetes being the most common risk factors. The most common stage of chronic kidney disease was Stage V, and the common complications were skin problems and dyslipidemia.

Diagnostic role of urine specific gravity to detect kidney impairment on heat-exposed workers in a shoe factory in Indonesia: a cross-sectional study.

OBJECTIVES: Globally, there are increasing cases of chronic kidney disease of unknown origin among heat-exposed workers. We aimed to see the kidney damages of indoor heat-exposed workers and whether urine specific gravity can predict any kidney damages. DESIGN: A cross-sectional study. SETTING: A shoe-making factory in West Java, Indonesia. PARTICIPANTS: 119 subjects were included. Minimum total sample size was 62. Subjects were indoor heat-exposed workers who were exposed to occupational wet-bulb globe temperature (WBGT) of 28°C-30°C for 8 hours daily with 1 hour break, 5 days a week. The inclusion criterion was healthy subjects according to the result from annual medical check-up in 2019. The exclusion criteria were subjects who were taking vitamins and/or supplements that might cause disturbance in urine specific gravity and/or hydration status, pregnant and fasting. PRIMARY AND SECONDARY OUTCOME MEASURES: Area under the curve (AUC), sensitivity and specificity of urine specific gravity for the detection of urinary nephrin and urinary kidney injury molecule-1 (KIM-1) were analysed. Estimated glomerular filtration rate (eGFR) and quantitative albuminuria were also measured. RESULTS: WBGT in the work area of the subject was 28°C-30°C. There were 15 (12.6%) subjects who had eGFR <90 mL/min, but ≥60 mL/min. High serum vasopressin levels were found in 79 subjects with a mean of 6.54 (95% CI 5.94 to 7.14) ng/mL. Most subjects had nephrinuria (87.4%) with preserved renal function (87.4%). Several subjects had elevated urinary KIM-1 (10.9%) and albuminuria (7.6%). AUC of urine specific gravity for increased urinary nephrin was 81.7% (95% CI 68.8% to 94.6%) and statistically significant (p<0.001). Cut-off value of ≥1.018 for urine specific gravity has sensitivity of 71.2% and specificity of 80% for detecting elevation of urinary nephrin levels. CONCLUSION: Urine specific gravity with a cut-off value of ≥1.018 could be used to detect nephrinuria among heat-exposed workers.

Divergence between serum creatine and cystatin C in estimating glomerular filtration rate of critically ill COVID-19 patients.

BACKGROUND: The clinical use of serum creatine (sCr) and cystatin C (CysC) in kidney function evaluation of critically ill patients has been in continuous discussion. The difference between estimated glomerular filtration rate calculated by sCr (eGFRcr) and CysC (eGFRcysc) of critically ill COVID-19 patients were investigated in this study. METHODS: This is a retrospective, single-center study of critically ill patients with COVID-19 admitted in intensive care unit (ICU) at Wuhan, China. Control cases were moderate COVID-19 patients matched in age and sex at a ratio of 1:1. The eGFRcr and eGFRcysc were compared. The association between eGFR and death were analyzed in critically ill cases. The potential factors influencing the divergence between eGFRcr and eGFRcysc were explored. RESULTS: A total of 76 critically ill COVID-19 patients were concluded. The mean age was 64.5 ± 9.3 years. The eGFRcr (85.45 (IQR 60.58-99.23) ml/min/1.73m2) were much higher than eGFRcysc (60.6 (IQR 34.75-79.06) ml/min/1.73m2) at ICU admission. About 50 % of them showed eGFRcysc < 60 ml/min/1.73 m2 while 25% showed eGFRcr < 60 ml/min/1.73 m2 (χ2 = 10.133, p = 0.001). This divergence was not observed in moderate group. The potential factors influencing the divergence included serum interleukin-6 (IL-6), tumor necrosis factor (TNF-α) level as well as APACHEII, SOFA scores. Reduced eGFRcr (<60 mL/min/1.73 m2) was associated with death (HR = 1.939, 95%CI 1.078-3.489, p = 0.027). CONCLUSIONS: The eGFRcr was generally higher than eGFRcysc in critically ill COVID-19 cases with severe inflammatory state. The divergence might be affected by inflammatory condition and illness severity. Reduced eGFRcr predicted in-hospital death. In these patients, we advocate for caution when using eGFRcysc.

COVID-19 and the kidney: A retrospective analysis of 37 critically ill patients using machine learning.

INTRODUCTION: There is evidence that SARS-CoV2 has a particular affinity for kidney tissue and is often associated with kidney failure. METHODS: We assessed whether proteinuria can be predictive of kidney failure, the development of chronic kidney disease, and mortality in 37 critically ill COVID-19 patients. We used machine learning (ML) methods as decision trees and cut-off points created by the OneR package to add new aspects, even in smaller cohorts. RESULTS: Among a total of 37 patients, 24 suffered higher-grade renal failure, 20 of whom required kidney replacement therapy. More than 40% of patients remained on hemodialysis after intensive care unit discharge or died (27%). Due to frequent anuria proteinuria measured in two-thirds of the patients, it was not predictive for the investigated endpoints; albuminuria was higher in patients with AKI 3, but the difference was not significant. ML found cut-off points of >31.4 kg/m2 for BMI and >69 years for age, constructed decision trees with great accuracy, and identified highly predictive variables for outcome and remaining chronic kidney disease. CONCLUSIONS: Different ML methods and their clinical application, especially decision trees, can provide valuable support for clinical decisions. Presence of proteinuria was not predictive of CKD or AKI and should be confirmed in a larger cohort.