Symptom burden, fatigue, sleep quality and perceived social support in hemodialysis patients with musculoskeletal discomfort: a single center experience from Egypt.

BACKGROUND AND AIMS: Musculoskeletal disorders (MSDs) are commonly encountered in hemodialysis (HD) patients. However, the causes linked to these disorders are still partially defined. The aim of this study was to determine the frequency of MSDs and their relationship to a variety of clinico-social characteristics such as sleep quality, mood disorders, fatigue, and social support, in addition to the patients' clinical and therapeutic profile. METHOD: The study included 94 patients on maintenance HD. Clinical and Sociodemographic data was gathered. To investigate the prevalence and trends of MSDs, the Nordic Musculoskeletal Questionnaire (NMQ-E) was employed. Patients completed the modified Edmonton Symptom Assessment System, Pittsburgh Sleep Quality Index (PSQI), multidimensional Fatigue Inventory (MFI-20), and Perceived Social Support from Family Scales. Univariate and multivariate regression analysis were used to assess the determinants of MSDs. RESULTS: The patients' mean age was 49.73 and 59.6% were males. Seventy-two percent of patients were afflicted by MSDs. Knee pain (48.9%), low back pain (43.6%), shoulder pain (41.6%), hip/thigh pain (35.1%), and neck pains (35.1%) were the most reported MSD domains. Pain (p = 0.001), fatigue (p = 0.01), depression (p = 0.015), and anxiety (p = 0.003) scores were substantially higher in patients with MSDs. Furthermore, patients with MSDs engaged in less physical activity (p = 0.02) and perceived less social support (p = 0.029). Patients with MSDs had lower subjective sleep quality, daytime dysfunction domains, and global PSQI scores (p = 0.02, 0.031, 0.036, respectively). Female gender (p = 0.013), fatigue (p = 0.012), depression (p = 0.014), anxiety (p = 0.004), lower activity (p = 0.029), and PSQI score (0.027), use of erythropoiesis-stimulating agents (ESAs), antihypertensive drugs, calcium and Iron supplementation were all significantly associated with MSDs. At the multivariable regression model, administration of ESAs (p = 0.017) and pain score (p = 0.040) were the only independent variables associated with the outcome. CONCLUSION: MSDs are quite common among HD patients. Female gender, pain, fatigue, depression, anxiety, reduced activity, poor sleep quality, and use of ESAs are all significantly associated with MSDs in HD patients. Patients with MSD perceived less social support compared to the other group. Patients treated with antihypertensive drugs, calcium and iron supplements were more likely to suffer MSDs.

Access to Nephrology Care for Pregnancy-Related Acute Kidney Injury in Low- and Lower-Middle-Income Countries: A Perspective.

Pregnancy-related acute kidney injury (AKI) is a major public health problem with substantial maternal and fetal morbidity and mortality. Women with pregnancy-related AKI require immediate access to nephrology care to prevent deleterious kidney and health outcomes. Patients with pregnancy-related AKI in low-income and lower-middle-income countries experience disparities in access to comprehensive nephrology care for many reasons. In this perspective, we highlight the burden of pregnancy-related AKI and explore the challenges among different low-income and lower-middle-income countries. The lack of adequate nephrology workforce and infrastructure for kidney health care represents a fundamental component of the problem. A shortage of nephrologists hampers the care of patients with pregnancy-related AKI leading to poor outcomes. The lack of diagnostic tools and therapeutic options, including kidney replacement therapy, impedes the implementation of effective management strategies. International efforts are warranted to empower women to get the right services and support at the right time. Dedicated preventive and early care programs are urgently needed to decrease the magnitude of pregnancy-related AKI, a complication under-represented in the literature.

Urinary congophilia in pregnancy: a marker of kidney injury rather than preeclampsia.

BACKGROUND: The differentiation between preeclampsia and similarly presenting kidney disease in pregnancy is a diagnostic challenge. Although some laboratory tests have been utilized, globally validated tools are yet needed, particularly in resource-limited settings. Congophilic proteins are abundantly detected in the urine of pregnant women who develop preeclampsia that is thought to be a marker of disease process. The present study aimed to assess the diagnostic and predictive utility of urinary congophilia in pregnant women with hypertensive disorders of pregnancy as well as kidney diseases. METHODS: This cohort study included 157 pregnant women, classified as healthy controls ( n  = 38), preeclampsia/eclampsia ( n  = 45), gestational hypertension ( n  = 9), chronic hypertension ( n  = 8), chronic kidney disease (CKD) ( n  = 27), and pregnancy-related acute kidney injury (PR-AKI) ( n  = 30). Urinary congophilia was assessed by Congo Red Dot Blot assay. RESULTS: Congo red retention (CRR) values were significantly higher in women with preeclampsia/eclampsia ( P  ≤ 0.001), chronic hypertension ( P  = 0.029), gestational hypertension ( P  = 0.017), CKD ( P  ≤ 0.001), PR-AKI secondary to preeclampsia ( P  ≤ 0.001), and PR-AKI secondary to other causes ( P  = 0.001), compared with healthy controls. Women with preeclampsia, CKD, and PR-AKI (non-preeclampsia related) exhibited the highest levels of CRR. CRR positively correlated to proteinuria ( P  = 0.006) and serum creatinine ( P  = 0.027). CRR did not significantly vary between women who presented antepartum and those presented postpartum after removal of the placenta ( P  = 0.707). CRR at a cut-off point of at least 1.272 had 91% specificity and 61.1% sensitivity in predicting renal recovery in PR-AKI patients. CRR had a poor specificity in discriminating preeclampsia from the other clinical presentations. CONCLUSION: Urinary congophilia could not discriminate preeclampsia from similarly presenting kidney diseases in pregnancy. Further studies are needed to improve differentiation of these conditions.

Angiotensin converting enzyme 2 gene expression and markers of oxidative stress are correlated with disease severity in patients with COVID-19.

BACKGROUND: Oxidative stress is thought to play a significant role in the pathogenesis and severity of COVID-19. Additionally, angiotensin converting enzyme 2 (ACE2) expression may predict the severity and clinical course of COVID-19. Accordingly, the aim of the present study was to evaluate the association of oxidative stress and ACE2 expression with the clinical severity in patients with COVID-19. METHODS AND RESULTS: The present study comprised 40 patients with COVID-19 and 40 matched healthy controls, recruited between September 2021 and March 2022. ACE 2 expression levels were measured using Hera plus SYBR Green qPCR kits with GAPDH used as an internal control. Serum melatonin (MLT) levels, serum malondialdehyde (MDA) levels, and total antioxidant capacity (TAC) were estimated using ELISA. The correlations between the levels of the studied markers and clinical indicators of disease severity were evaluated. Significantly, lower expression of ACE2 was observed in COVID-19 patients compared to controls. Patients with COVID-19 had lower serum levels of TAC and MLT but higher serum levels of MDA compared to normal controls. Serum MDA levels were correlated with diastolic blood pressure (DBP), Glasgow coma scale (GCS) scores, and serum potassium levels. Serum MLT levels were positively correlated with DBP, mean arterial pressure (MAP), respiratory rate, and serum potassium levels. TAC was correlated with GCS, mean platelet volume, and serum creatinine levels. Serum MLT levels were significantly lower in patients treated with remdesivir and inotropes. Receiver operating characteristic curve analysis demonstrates that all markers had utility in discriminating COVID-19 patients from healthy controls. CONCLUSIONS: Increased oxidative stress and increased ACE2 expression were correlated with disease severity and poor outcomes in hospitalized patients with COVID-19 in the present study. Melatonin supplementation may provide a utility as an adjuvant therapy in decreasing disease severity and death in COVID-19 patients.

Revisiting maintenance immunosuppression in patients with renal transplant failure: early weaning of immunosuppression versus prolonged maintenance-systematic review and meta-analysis.

INTRODUCTION: Prolonged immunosuppression after dialysis start has been assumed to reduce sensitization, need for graft nephrectomy, and to favor re-transplantation. In contrast, immunosuppression is considered to increase the risk of mortality, infection, and malignancy. We aimed to assess the evidence regarding superiority of early or late withdrawal of maintenance immunosuppression post renal transplant failure. METHODS: A literature search of the PubMed, WOS, Ovid, and Scopus databases was conducted. Combined relative risks, (RRs), mean differences, and 95% confidence intervals (CIs) were calculated by using a random-effect model. RESULTS: Ten studies involving 1187 patients with kidney transplant failure were included. No difference could be detected between patients with early withdrawal of  immunosuppressive drugs (≤ 3 months) or prolonged immunosuppressive treatment (> 3 months) regarding mortality (95% CI 0.91-2.28), panel reactive antibodies (PRAs) (95% CI - 0.75-30.10), re-transplantation rate (95% CI 0.55-1.35), infectious episodes (95% CI 0.67, 1.17), cancer (95% CI 0.26-1.54), and graft nephrectomy (95% CI 0.82-1.63). Similarly, no difference was found between immunosuppressive drug withdrawal over < 6 or ≥ 6 months regarding mortality (95% CI 0.16, 2.89), re-transplantation rate (95% CI 0.85-1.55), cancer (95% CI 0.37-1.63), and allograft nephrectomy (95% CI 0.87-4.33). CONCLUSION: Prolonged maintenance immunosuppression post kidney transplant failure is not associated with increased risk of mortality, infection, or malignancy, or reduced risk of sensitization or allograft nephrectomy compared with early withdrawal.

The diagnostic and prognostic utility of serum cystatin C and angiopoietin 2 in patients with liver cirrhosis complicated by acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) frequently affects patients with liver cirrhosis, diagnosed by changes in serum creatinine and urine output. This study aimed to evaluate the diagnostic and prognostic utility of serum cystatin C (Cys C) and angiopoietin 2 (Ang 2) in patients with liver cirrhosis complicated by AKI. METHODS: A total of 81 cirrhotic patients with AKI were included. AKI was diagnosed according to Kidney Disease Improving Global Outcomes criteria. All patients were assessed clinically and biochemically. Baseline serum Cys C and Ang 2 were assessed, and patients were prospectively followed-up to assess patients' and renal survival. RESULTS: Cys C significantly predicted AKI (p < 0.001). Ang 2 (≤179.7 pg/ml) was an independent predictor of mortality in multivariate analysis. Marked ascites and partial pressure of carbon dioxide ≤ 29 were significant predictors of nonrenal recovery. CONCLUSION: Cys C showed validity AKI diagnosis in cirrhotic patients while Ang 2 was an independent predictor of mortality.

Characterization of regulatory T cells in SARS-CoV-2 infected hemodialysis patients: relation to clinical and radiological severity.

BACKGROUND: Disordered Treg counts and function have been observed in patients with SARS-Cov-2 and are thought to contribute to disease severity. In hemodialysis patients, scarce data are available on the Treg response to SARS-CoV-2 or its relation to the clinical presentation. METHODS: A cross-sectional study included one hundred patients divided into three groups, thirty SARS-CoV-2-infected hemodialysis patients (COV-HD), and thirty confirmed SARSCoV-2 infected patients (COV), and forty non-infected hemodialysis patients (HD). Flow cytometric analysis of CD4, CD25, FoxP3, and CD39+ Tregs was done for all patients and tested for correlation to in-hospital mortality, clinical, radiological severity indices. RESULTS: COV-HD and COV patients had significantly lower Treg cell count than HD patients (Median value of 0.016 cell/ µl vs 0.28 cell/ µl, respectively- P: 0.001). COV-HD patients had higher CD39+ Tregs (median value of 0.006 cell/ µl vs 0.002 cell/ µl, respectively- P: 0.04). COV-HD patients had significantly lower hospital stay (median value of 3 vs 13 days, P:0.001), ICU admission rates (26.5% vs 46.7%, P:0.005) and in-hospital mortality (20.7% versus 43.3%, P:0.003) than COV patients. Treg and CD39 expressing Treg counts were not correlated to severity indices in both groups. A high neutrophil to lymphocyte ratio is strongly correlated to disease severity in COV-HD patients. CONCLUSIONS: This study provides evidence of T-cell, particularly T-regulatory cell decline in SARS-CoV-2 and suggests that hemodialysis per se does not distinctively impact the T-cell response. COV-HD patients exhibited a higher CD39+ Treg count and a better clinical profile, however, larger studies are needed to extrapolate on these findings.

Is Adynamic Bone Always a Disease? Lessons from Patients with Chronic Kidney Disease.

Renal osteodystrophy (ROD) is a common complication of end-stage kidney disease that often starts early with loss of kidney function, and it is considered an integral part in management of patients with chronic kidney disease (CKD). Adynamic bone (ADB) is characterized by suppressed bone formation, low cellularity, and thin osteoid seams. There is accumulating evidence supporting increasing prevalence of ADB, particularly in early CKD. Contemporarily, it is not very clear whether it represents a true disease, an adaptive mechanism to prevent bone resorption, or just a transitional stage. Several co-players are incriminated in its pathogenesis, such as age, diabetes mellitus, malnutrition, uremic milieu, and iatrogenic factors. In the present review, we will discuss the up-to-date knowledge of the ADB and focus on its impact on bone health, fracture risk, vascular calcification, and long-term survival. Moreover, we will emphasize the proper preventive and management strategies of ADB that are pivotal issues in managing patients with CKD. It is still unclear whether ADB is always a pathologic condition or whether it can represent an adaptive process to suppress bone resorption and further bone loss. In this article, we tried to discuss this hard topic based on the available limited information in patients with CKD. More studies are needed to be able to clearly address this frequent ROD finding.

Pregnancy-related acute kidney injury in the African continent: where do we stand? A systematic review.

BACKGROUND: Pregnancy-Related Acute kidney injury (PR-AKI) is a global health problem with substantial maternal and fetal morbidity and mortality. However, little is known about the current situation in the developing world including African countries. Africa is the poorest continent per capita, and women from Sub-Saharan Africa alone account for 66% of the estimated global maternal deaths from preventable obstetric causes. METHODS: OBJECTIVE: To review the literature on the clinical profile, maternal and renal outcomes of women with PR-AKI in the African continent. SEARCH STRATEGY: Medline, ISI Web of Science, Scopus, and Cochrane library were searched in February 2022, using the MeSH terms and text key words: "pregnancy", "pregnant", "acute kidney injury", "acute renal insufficiency", "acute renal injury", "acute renal failure", and "Africa". SELECTION CRITERIA AND DATA COLLECTION: Studies from African countries which reported maternal and renal outcomes in women with PR-AKI during pregnancy or postpartum were included. Editorials, short communications, and case reports were excluded. The study quality was assessed using the NHLBI tool. Data extraction was done using predefined data fields. RESULTS: A total of 167 studies were evaluated, of which 14 studies from seven African countries met the inclusion criteria. Preeclampsia, obstetric hemorrhage, and sepsis represented the main causes of PR-AKI. Maternal mortality ranged between 0 and 34.4%. Although the majority of women needed ICU admission and hemodialysis, renal recovery occurred in 53.1-90% of patients. Perinatal mortality has been reported to be 1.5-60.5% in the included studies. AUTHORS' CONCLUSIONS: PR-AKI in Africa represents the second leading cause of AKI. Limited access to obstetric care, late referral, and late diagnosis of women with risks for PR-AKI hinder the curtailment of the problem. Provision of health care facilities with adequately trained personnel and implementation of preventive strategies will be of great value in decreasing the magnitude of the problem.

Amenorrhea, premenstrual tension syndrome, and dysmenorrhea among women of reproductive age on hemodialysis: A national study in Egypt.

BACKGROUND AND AIM: The current literature concerning the reproductive health of end stage renal disease (ESRD) females is scarce, outdated, and largely unknown in women living in developing countries. This study aims to estimate the prevalence of menstrual abnormalities and their associated factors among ESRD women in reproductive age undergoing chronic hemodialysis (HD) in Egypt. METHODS: Thirty-five dialysis centers were selected by simple random sampling to represent the different regions of Egypt. Non-pregnant women in the reproductive age (15-50 years) receiving dialysis at the participating centers completed a questionnaire about their menstrual health during a routine hemodialysis session. Their responses were verified by reviewing the medical records and assessing their clinical data. RESULTS: Out of the 472 women, 32.6% had amenorrhea. Menstrual irregularities were reported in 37% of the menstruating women. Premenstrual tension syndrome (PMS) was reported in 70% while dysmenorrhea in 58%. Amenorrhea was more prevalent in non-working women who started hemodialysis after the age of 30. PMS was more encountered in women with hypertension or in those with obstructive uropathy or autoimmune disease as a cause of ESRD. Dysmenorrhea was more prevalent among patients with autoimmune disease or chronic hepatitis C virus and those who started dialysis after the age of 30. CONCLUSION: Secondary amenorrhea, dysmenorrhea, and PMS are common among premenopausal women with ESRD on dialysis. Several factors including socio-economic factors, cause of ESRD, and hypertension contribute to these disorders. Future studies are needed to understand the underlying pathophysiologic mechanisms and management of these abnormalities.

Kidneys in SARS-CoV-2 era: A challenge of multiple faces.

INTRODUCTION: With the evolution of SARS-CoV-2 pandemic, it was believed to be a direct respiratory virus. But, its deleterious effects were observed on different body systems, including kidneys. AIM OF WORK: In this review, we tried as much as we can to summarize what has been discussed in the literature about the relation between SARS-CoV-2 infection and kidneys since December, 2019. METHODS: Each part of the review was assigned to one or two authors to search for relevant articles in three databases (Pubmed, Scopus, and Google scholar) and collected data were summarized and revised by two independent researchers. CONCLUSION: The complexity of COVID-19 pandemic and kidney could be attributed to the direct effect of SARS-CoV-2 infection on the kidneys, different clinical presentation, difficulties confronting dialysis patients, restrictions of the organ transplant programs, poor outcomes and bad prognosis in patients with known history of kidney diseases who got infected with SARS-CoV-2.

The Relation of Serum Dehydroepiandrosterone Sulfate Level to Protein Energy Wasting in Hemodialysis Patients.

Protein-energy wasting (PEW) is a major risk for morbidity and mortality in hemodialysis (HD) patients. The change in the concentration of dehydroepiandrosterone sulfate (DHEA-S) may play a role in PEW. The aim of this work was to study the possible relationship between serum DHEA-S levels and various nutritional and inflammatory parameters in a cohort of HD patients. In total, 78 HD patients (47 males and 31 females) were included in this crosssectional observational study. In addition to taking their history, clinical examinations, and routine laboratory investigations, the nutritional status was assessed, and their serum DHEA-S was measured. Nutritional status was assessed by anthropometric measures, bioelectrical impedance analysis, malnutrition inflammation scores, and subjective global assessments. A diagnosis of malnutrition was made based on the recommendations of the International Society of Renal Nutrition and Metabolism. The relationship between DHEA-S and various nutritional parameters was analyzed. Eighteen patients (23.1%) suffered from PEW. Those with PEW had a longer duration of HD (P = 0.04), and lower serum levels of creatinine (P = 0.003), hemoglobin (P = 0.01), albumin (P <0.0001), cholesterol (P = 0.02), and DHEA-S (P = 0.01). Among the variables, serum DHEA-S levels were significant predictors of PEW in this cohort (odds ratio: 0.976; 95% confidence interval: 0.954-1.0; P = 0.04). PEW is frequently encountered in HD patients. Decreased serum DHEA-S levels were associated with PEW in male HD patients. Further studies are needed to assess the effect of hormone supplementation on this serious disorder in HD patients.

Angiogenic markers predict kidney injury and obstetric complications in women with preeclampsia and pregnancy-related acute kidney injury.

Pregnancy-related acute kidney injury (PRAKI) particularly on top of preeclampsia (PE) represents a major cause of maternal and fetal morbidity and mortality. Reliable diagnostic tools are needed to further evaluate the diagnosis and prognosis of PRAKI. Our objective was to study the diagnostic and prognostic value of angiogenic markers (e.g., stromal cell-derived factor 1 (SDF-1), vascular endothelial growth factor (VEGF), alarmins as uric acid) in women with PE and PRAKI. This prospective study included three groups; PRAKI, PE patients, and healthy controls that were compared regarding serum levels of the studied markers correlated to renal, maternal, and fetal outcomes. SDF-1, VEGF, and uric acid levels were significantly different between the three included groups and predicted PRAKI diagnosis. Patients with hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome exhibited the highest titers of SDF-1 and VEGF. A positive correlation was found between SDF-1 and renal recovery. Conclusively, serum assays of SDF-1, VEGF, and uric acid may add a diagnostic value in PRAKI and PE.

Renal replacement therapy for critically ill patients with COVID-19-associated acute kidney injury: A review of current knowledge.

The outbreak of coronavirus disease 2019 (COVID-19) has rapidly evolved into a global pandemic. A significant proportion of COVID-19 patients develops severe symptoms, which may include acute respiratory distress syndrome and acute kidney injury as manifestations of multi-organ failure. Acute kidney injury (AKI) necessitating renal replacement therapy (RRT) is increasingly prevalent among critically ill patients with COVID-19. However, few studies have focused on AKI treated with RRT. Many questions are awaiting answers as regards AKI in the setting of COVID-19; whether patients with COVID-19 commonly develop AKI, what are the underlying pathophysiologic mechanisms? What is the best evidence regarding treatment approaches? Identification of the potential indications and the preferred modalities of RRT in this context, is based mainly on clinical experience. Here, we review the current approaches of RRT, required for management of critically ill patients with COVID-19 complicated by severe AKI as well as the precautions that should be adopted by health care providers in dealing with these cases. Electronic search was conducted in MEDLINE, PubMed, ISI Web of Science, and Scopus scientific databases. We searched the terms relevant to this review to identify the relevant studies. We also searched the conference proceedings and ClinicalTrials.gov database.